FEED Validator

for Atom and RSS and KML

Congratulations!

This is a valid RSS feed.

Recommendations

This feed is valid, but interoperability with the widest range of feed readers could be improved by implementing the following recommendations.

line 7, column 285: Self reference doesn't match document location [help]

... e462414&amp;utm_medium=rss" rel="self"/>
                                             ^

line 18, column 0: content:encoded should not contain xmlns:xlink attribute (94 occurrences) [help]
```
      <content:encoded><![CDATA[<div>Elife. 2024  ...
```
line 18, column 0: content:encoded should not contain xmlns:mml attribute (94 occurrences) [help]
```
      <content:encoded><![CDATA[<div>Elife. 2024  ...
```
line 18, column 0: content:encoded should not contain xmlns:p1 attribute (94 occurrences) [help]
```
      <content:encoded><![CDATA[<div>Elife. 2024  ...
```
line 28, column 6: An item should not include both pubDate and dc:date (50 occurrences) [help]
```
      <dc:date>2024-04-19</dc:date>
      ^
```

line 109, column 162: title should not contain HTML: em (3 occurrences) [help]

... eotide phosphodiesterases ENPP1 and CdnP</title>
                                             ^

Source: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB

<?xml version='1.0' encoding='UTF-8'?>
<rss xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:atom="http://www.w3.org/2005/Atom" xmlns:content="http://purl.org/rss/1.0/modules/content/" version="2.0">
<channel>
<title>tuberculosis and AND (bishai OR grosset OR manabe)</title>
<link>https://pubmed.ncbi.nlm.nih.gov/rss-feed/?feed_id=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&utm_source=Feedvalidator&ff=20240507201515&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&v=2.18.0.post9+e462414&utm_medium=rss</link>
<description>tuberculosis and AND (bishai OR grosset OR manabe): Latest results from PubMed</description>
<atom:link href="https://pubmed.ncbi.nlm.nih.gov/rss-feed/?feed_id=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&utm_source=Feedvalidator&ff=20240507201515&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&v=2.18.0.post9+e462414&utm_medium=rss" rel="self"/>
<docs>http://www.rssboard.org/rss-specification</docs>
<generator>PubMed RSS feeds (2.18.0.post9+e462414)</generator>
<language>en</language>
<lastBuildDate>Wed, 08 May 2024 00:15:20 +0000</lastBuildDate>
<pubDate>Fri, 19 Apr 2024 06:00:00 -0400</pubDate>
<ttl>120</ttl>
<item>
<title>A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice</title>
<link>https://pubmed.ncbi.nlm.nih.gov/38639995/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria,...</description>
<content:encoded><![CDATA[<div>Elife. 2024 Apr 19;13:e89157. doi: 10.7554/eLife.89157. Online ahead of print.ABSTRACTMechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking ability and to potentially improve efficacy of the BCG vaccine, we used CRISPRi to inhibit expression of the essential enzyme pair, MurT-GatD, implicated in amidation of peptidoglycan side-chains. We demonstrate that depletion of these enzymes results in reduced growth, cell wall defects, increased susceptibility to antibiotics, altered spatial localization of new peptidoglycan and increased NOD-1 expression in macrophages. In cell culture experiments, training of a human monocyte cell line with this recombinant BCG yielded improved control of Mtb growth. In the murine model of TB infection, we demonstrate that depletion of MurT-GatD in BCG, which is expected to unmask the D-glutamate diaminopimelate (iE-DAP) NOD-1 ligand, yields superior prevention of TB disease compared to the standard BCG vaccine. In vitro and in vivo experiments in this study demonstrate the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/38639995/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">38639995</a> | DOI:<a href=https://doi.org/10.7554/eLife.89157>10.7554/eLife.89157</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:38639995</guid>
<pubDate>Fri, 19 Apr 2024 06:00:00 -0400</pubDate>
<dc:creator>Moagi Tube Shaku</dc:creator>
<dc:creator>Peter K Um</dc:creator>
<dc:creator>Karl L Ocius</dc:creator>
<dc:creator>Alexis J Apostolos</dc:creator>
<dc:creator>Marcos M Pires</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Bavesh D Kana</dc:creator>
<dc:date>2024-04-19</dc:date>
<dc:source>eLife</dc:source>
<dc:title>A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice</dc:title>
<dc:identifier>pmid:38639995</dc:identifier>
<dc:identifier>doi:10.7554/eLife.89157</dc:identifier>
</item>
<item>
<title>Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021</title>
<link>https://pubmed.ncbi.nlm.nih.gov/38582094/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>BACKGROUND: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons...</description>
<content:encoded><![CDATA[<div>Lancet. 2024 Apr 3:S0140-6736(24)00367-2. doi: 10.1016/S0140-6736(24)00367-2. Online ahead of print.ABSTRACTBACKGROUND: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds.FINDINGS: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles.INTERPRETATION: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere.FUNDING: Bill & Melinda Gates Foundation.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/38582094/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">38582094</a> | DOI:<a href=https://doi.org/10.1016/S0140-6736(24)00367-2>10.1016/S0140-6736(24)00367-2</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:38582094</guid>
<pubDate>Sat, 06 Apr 2024 06:00:00 -0400</pubDate>
<dc:creator>GBD 2021 Causes of Death Collaborators</dc:creator>
<dc:date>2024-04-06</dc:date>
<dc:source>Lancet (London, England)</dc:source>
<dc:title>Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021</dc:title>
<dc:identifier>pmid:38582094</dc:identifier>
<dc:identifier>doi:10.1016/S0140-6736(24)00367-2</dc:identifier>
</item>
<item>
<title>Myc Dysregulation in Activated Macrophages Initiates Iron-Mediated Lipid Peroxidation that Fuels Type I Interferon and Compromises TB Resistance</title>
<link>https://pubmed.ncbi.nlm.nih.gov/38496444/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop clinical, mostly pulmonary, TB. To dissect mechanisms of susceptibility in immunocompetent individuals, we developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining feature of human TB: development of necrotic lung lesions after infection with virulent Mtb. In this study, we explored the connectivity of the sst1-regulated pathways during...</description>
<content:encoded><![CDATA[<div>bioRxiv [Preprint]. 2024 Mar 10:2024.03.05.583602. doi: 10.1101/2024.03.05.583602.ABSTRACTA quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop clinical, mostly pulmonary, TB. To dissect mechanisms of susceptibility in immunocompetent individuals, we developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining feature of human TB: development of necrotic lung lesions after infection with virulent Mtb. In this study, we explored the connectivity of the sst1-regulated pathways during prolonged macrophage activation with TNF. We determined that the aberrant response of the sst1-susceptible macrophages to TNF was primarily driven by conflicting Myc and antioxidant response pathways that resulted in a coordinated failure to properly sequester intracellular iron and activate ferroptosis inhibitor enzymes. Consequently, iron-mediated lipid peroxidation fueled IFNβ superinduction and sustained the Type I Interferon (IFN-I) pathway hyperactivity that locked the sst1-susceptible macrophages in a state of unresolving stress and compromised their resistance to Mtb. The accumulation of the aberrantly activated, stressed, macrophages within granuloma microenvironment led to the local failure of anti-tuberculosis immunity and tissue necrosis. Our findings suggest a novel link between metabolic dysregulation in macrophages and susceptibility to TB, offering insights into potential therapeutic targets aimed at modulating macrophage function and improving TB control.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/38496444/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">38496444</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10942339/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10942339</a> | DOI:<a href=https://doi.org/10.1101/2024.03.05.583602>10.1101/2024.03.05.583602</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:38496444</guid>
<pubDate>Mon, 18 Mar 2024 06:00:00 -0400</pubDate>
<dc:creator>Shivraj M Yabaji</dc:creator>
<dc:creator>Vadim Zhernovkov</dc:creator>
<dc:creator>Prasanna Babu Araveti</dc:creator>
<dc:creator>Suruchi Lata</dc:creator>
<dc:creator>Oleksii S Rukhlenko</dc:creator>
<dc:creator>Salam Al Abdullatif</dc:creator>
<dc:creator>Yuriy Alekseev</dc:creator>
<dc:creator>Qicheng Ma</dc:creator>
<dc:creator>Gargi Dayama</dc:creator>
<dc:creator>Nelson C Lau</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Nicholas A Crossland</dc:creator>
<dc:creator>Joshua D Campbell</dc:creator>
<dc:creator>Boris N Kholodenko</dc:creator>
<dc:creator>Alexander A Gimelbrant</dc:creator>
<dc:creator>Lester Kobzik</dc:creator>
<dc:creator>Igor Kramnik</dc:creator>
<dc:date>2024-03-18</dc:date>
<dc:source>bioRxiv : the preprint server for biology</dc:source>
<dc:title>Myc Dysregulation in Activated Macrophages Initiates Iron-Mediated Lipid Peroxidation that Fuels Type I Interferon and Compromises TB Resistance</dc:title>
<dc:identifier>pmid:38496444</dc:identifier>
<dc:identifier>pmc:PMC10942339</dc:identifier>
<dc:identifier>doi:10.1101/2024.03.05.583602</dc:identifier>
</item>
<item>
<title>Improved bladder cancer antitumor efficacy with a recombinant BCG that releases a STING agonist</title>
<link>https://pubmed.ncbi.nlm.nih.gov/38168333/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Despite the introduction of several new agents for the treatment of bladder cancer (BC), intravesical BCG remains a first line agent for the management of non-muscle invasive bladder cancer. In this study we evaluated the antitumor efficacy in animal models of BC of a recombinant BCG known as BCG-disA-OE that releases the small molecule STING agonist c-di-AMP. We found that compared to wild-type BCG (BCG-WT), in both the orthotopic, carcinogen-induced rat MNU model and the heterotopic syngeneic...</description>
<content:encoded><![CDATA[<div>bioRxiv [Preprint]. 2023 Dec 15:2023.12.15.571740. doi: 10.1101/2023.12.15.571740.ABSTRACTDespite the introduction of several new agents for the treatment of bladder cancer (BC), intravesical BCG remains a first line agent for the management of non-muscle invasive bladder cancer. In this study we evaluated the antitumor efficacy in animal models of BC of a recombinant BCG known as BCG-disA-OE that releases the small molecule STING agonist c-di-AMP. We found that compared to wild-type BCG (BCG-WT), in both the orthotopic, carcinogen-induced rat MNU model and the heterotopic syngeneic mouse MB-49 model BCG-disA-OE afforded improved antitumor efficacy. A mouse safety evaluation further revealed that BCG-disA-OE proliferated to lesser degree than BCG-WT in BALB/c mice and displayed reduced lethality in SCID mice. To probe the mechanisms that may underlie these effects, we found that BCG-disA-OE was more potent than BCG-WT in eliciting IFN-β release by exposed macrophages, in reprogramming myeloid cell subsets towards an M1-like proinflammatory phenotypes, inducing epigenetic activation marks in proinflammatory cytokine promoters, and in shifting monocyte metabolomic profiles towards glycolysis. Many of the parameters elevated in cells exposed to BCG-disA-OE are associated with BCG-mediated trained innate immunity suggesting that STING agonist overexpression may enhance trained immunity. These results indicate that modifying BCG to release high levels of proinflammatory PAMP molecules such as the STING agonist c-di-AMP can enhance antitumor efficacy in bladder cancer.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/38168333/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">38168333</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10760079/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10760079</a> | DOI:<a href=https://doi.org/10.1101/2023.12.15.571740>10.1101/2023.12.15.571740</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:38168333</guid>
<pubDate>Wed, 03 Jan 2024 06:00:00 -0500</pubDate>
<dc:creator>Peter K Um</dc:creator>
<dc:creator>Monali Praharaj</dc:creator>
<dc:creator>Kara A Lombardo</dc:creator>
<dc:creator>Takahiro Yoshida</dc:creator>
<dc:creator>Andres Matoso</dc:creator>
<dc:creator>Alex S Baras</dc:creator>
<dc:creator>Liang Zhao</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Joy Huang</dc:creator>
<dc:creator>Pankaj Prasad</dc:creator>
<dc:creator>Max Kates</dc:creator>
<dc:creator>David McConkey</dc:creator>
<dc:creator>Drew M Pardoll</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Trinity J Bivalacqua</dc:creator>
<dc:date>2024-01-03</dc:date>
<dc:source>bioRxiv : the preprint server for biology</dc:source>
<dc:title>Improved bladder cancer antitumor efficacy with a recombinant BCG that releases a STING agonist</dc:title>
<dc:identifier>pmid:38168333</dc:identifier>
<dc:identifier>pmc:PMC10760079</dc:identifier>
<dc:identifier>doi:10.1101/2023.12.15.571740</dc:identifier>
</item>
<item>
<title>Structure-based virtual screening and in vitro validation of inhibitors of cyclic dinucleotide phosphodiesterases ENPP1 and CdnP</title>
<link>https://pubmed.ncbi.nlm.nih.gov/38095464/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>In this paper, we describe novel inhibitors of cyclic dinucleotide phosphodiesterase enzymes from Mycobacterium tuberculosis (M.tb) (CdnP) and mammals (ENPP1). The phosphodiesterase enzymes hydrolyze cyclic dinucleotides, such as 2',3'-cyclic GMP-AMP and c-di-AMP, which are stimulator of interferon gene (STING) agonists. By blocking the hydrolysis of STING agonists, the cyclic GMP-AMP synthase (cGAS)-STING-IRF3 pathway is potentiated. There is strong evidence in tuberculosis and in cancer...</description>
<content:encoded><![CDATA[<div>Microbiol Spectr. 2024 Jan 11;12(1):e0201223. doi: 10.1128/spectrum.02012-23. Epub 2023 Dec 14.ABSTRACTIn this paper, we describe novel inhibitors of cyclic dinucleotide phosphodiesterase enzymes from Mycobacterium tuberculosis (M.tb) (CdnP) and mammals (ENPP1). The phosphodiesterase enzymes hydrolyze cyclic dinucleotides, such as 2',3'-cyclic GMP-AMP and c-di-AMP, which are stimulator of interferon gene (STING) agonists. By blocking the hydrolysis of STING agonists, the cyclic GMP-AMP synthase (cGAS)-STING-IRF3 pathway is potentiated. There is strong evidence in tuberculosis and in cancer biology that potentiation of the cGAS-STING-IRF3 pathway leads to improved M.tb clearance and also improved antitumor responses in cancer. In addition to the identification of novel inhibitors and their biochemical characterization, we provide proof-of-concept evidence that our E-3 inhibitor potentiates the cGAS-STING-IRF3 pathway in both macrophage cell lines and also in primary human monocyte-derived macrophages.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/38095464/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">38095464</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10783014/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10783014</a> | DOI:<a href=https://doi.org/10.1128/spectrum.02012-23>10.1128/spectrum.02012-23</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:38095464</guid>
<pubDate>Thu, 14 Dec 2023 06:00:00 -0500</pubDate>
<dc:creator>Akshay Rohilla</dc:creator>
<dc:creator>Alok Kumar Singh</dc:creator>
<dc:creator>Benjamin Koleske</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-12-14</dc:date>
<dc:source>Microbiology spectrum</dc:source>
<dc:title>Structure-based virtual screening and in vitro validation of inhibitors of cyclic dinucleotide phosphodiesterases ENPP1 and CdnP</dc:title>
<dc:identifier>pmid:38095464</dc:identifier>
<dc:identifier>pmc:PMC10783014</dc:identifier>
<dc:identifier>doi:10.1128/spectrum.02012-23</dc:identifier>
</item>
<item>
<title>Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide</title>
<link>https://pubmed.ncbi.nlm.nih.gov/38071218/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>The antibiotic pyrazinamide (PZA) is a cornerstone of tuberculosis (TB) therapy that shortens treatment durations by several months despite being only weakly bactericidal. Intriguingly, PZA is also an anti-inflammatory molecule shown to specifically reduce inflammatory cytokine signaling and lesion activity in TB patients. However, the target and clinical importance of PZA's host-directed activity during TB therapy remain unclear. Here, we identify the host enzyme Poly(ADP-ribose) Polymerase 1...</description>
<content:encoded><![CDATA[<div>Nat Commun. 2023 Dec 9;14(1):8161. doi: 10.1038/s41467-023-43937-1.ABSTRACTThe antibiotic pyrazinamide (PZA) is a cornerstone of tuberculosis (TB) therapy that shortens treatment durations by several months despite being only weakly bactericidal. Intriguingly, PZA is also an anti-inflammatory molecule shown to specifically reduce inflammatory cytokine signaling and lesion activity in TB patients. However, the target and clinical importance of PZA's host-directed activity during TB therapy remain unclear. Here, we identify the host enzyme Poly(ADP-ribose) Polymerase 1 (PARP1), a pro-inflammatory master regulator strongly activated in TB, as a functionally relevant host target of PZA. We show that PZA inhibits PARP1 enzymatic activity in macrophages and in mice where it reverses TB-induced PARP1 activity in lungs to uninfected levels. Utilizing a PZA-resistant mutant, we demonstrate that PZA's immune-modulatory effects are PARP1-dependent but independent of its bactericidal activity. Importantly, PZA's bactericidal efficacy is impaired in PARP1-deficient mice, suggesting that immune modulation may be an integral component of PZA's antitubercular activity. In addition, adjunctive PARP1 inhibition dramatically reduces inflammation and lesion size in mice and may be a means to reduce lung damage and shorten TB treatment duration. Together, these findings provide insight into PZA's mechanism of action and the therapeutic potential of PARP1 inhibition in the treatment of TB.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/38071218/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">38071218</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10710439/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10710439</a> | DOI:<a href=https://doi.org/10.1038/s41467-023-43937-1>10.1038/s41467-023-43937-1</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:38071218</guid>
<pubDate>Sat, 09 Dec 2023 06:00:00 -0500</pubDate>
<dc:creator>Stefanie Krug</dc:creator>
<dc:creator>Manish Gupta</dc:creator>
<dc:creator>Pankaj Kumar</dc:creator>
<dc:creator>Laine Feller</dc:creator>
<dc:creator>Elizabeth A Ihms</dc:creator>
<dc:creator>Bong Gu Kang</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Ted M Dawson</dc:creator>
<dc:creator>Valina L Dawson</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-12-09</dc:date>
<dc:source>Nature communications</dc:source>
<dc:title>Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide</dc:title>
<dc:identifier>pmid:38071218</dc:identifier>
<dc:identifier>pmc:PMC10710439</dc:identifier>
<dc:identifier>doi:10.1038/s41467-023-43937-1</dc:identifier>
</item>
<item>
<title>Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37973991/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>As one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days...</description>
<content:encoded><![CDATA[<div>Nat Commun. 2023 Nov 16;14(1):7427. doi: 10.1038/s41467-023-43304-0.ABSTRACTAs one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomic analysis of lungs from JHU083-treated Mtb-infected mice reveals citrulline accumulation, suggesting elevated nitric oxide (NO) synthesis, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. JHU083-treated macrophages also produce more NO potentiating their antibacterial activity. When tested in an immunocompromised mouse model of Mtb infection, JHU083 loses its therapeutic efficacy suggesting the drug's host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37973991/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37973991</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10654700/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10654700</a> | DOI:<a href=https://doi.org/10.1038/s41467-023-43304-0>10.1038/s41467-023-43304-0</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37973991</guid>
<pubDate>Fri, 17 Nov 2023 06:00:00 -0500</pubDate>
<dc:creator>Sadiya Parveen</dc:creator>
<dc:creator>Jessica Shen</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Liang Zhao</dc:creator>
<dc:creator>Jesse Alt</dc:creator>
<dc:creator>Benjamin Koleske</dc:creator>
<dc:creator>Robert D Leone</dc:creator>
<dc:creator>Rana Rais</dc:creator>
<dc:creator>Jonathan D Powell</dc:creator>
<dc:creator>John R Murphy</dc:creator>
<dc:creator>Barbara S Slusher</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-11-17</dc:date>
<dc:source>Nature communications</dc:source>
<dc:title>Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis</dc:title>
<dc:identifier>pmid:37973991</dc:identifier>
<dc:identifier>pmc:PMC10654700</dc:identifier>
<dc:identifier>doi:10.1038/s41467-023-43304-0</dc:identifier>
</item>
<item>
<title>Comprehensive analysis of long COVID in a Japanese nationwide prospective cohort study</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37783167/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSIONS: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan.</description>
<content:encoded><![CDATA[<div>Respir Investig. 2023 Nov;61(6):802-814. doi: 10.1016/j.resinv.2023.08.008. Epub 2023 Sep 30.ABSTRACTBACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID.METHODS: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications.RESULTS: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID.CONCLUSIONS: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37783167/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37783167</a> | DOI:<a href=https://doi.org/10.1016/j.resinv.2023.08.008>10.1016/j.resinv.2023.08.008</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37783167</guid>
<pubDate>Mon, 02 Oct 2023 06:00:00 -0400</pubDate>
<dc:creator>Hideki Terai</dc:creator>
<dc:creator>Makoto Ishii</dc:creator>
<dc:creator>Ryo Takemura</dc:creator>
<dc:creator>Ho Namkoong</dc:creator>
<dc:creator>Kyoko Shimamoto</dc:creator>
<dc:creator>Katsunori Masaki</dc:creator>
<dc:creator>Takae Tanosaki</dc:creator>
<dc:creator>Shotaro Chubachi</dc:creator>
<dc:creator>Emiko Matsuyama</dc:creator>
<dc:creator>Reina Hayashi</dc:creator>
<dc:creator>Takashi Shimada</dc:creator>
<dc:creator>Lisa Shigematsu</dc:creator>
<dc:creator>Fumimaro Ito</dc:creator>
<dc:creator>Masanori Kaji</dc:creator>
<dc:creator>Hatsuyo Takaoka</dc:creator>
<dc:creator>Momoko Kurihara</dc:creator>
<dc:creator>Kensuke Nakagawara</dc:creator>
<dc:creator>Saki Tomiyasu</dc:creator>
<dc:creator>Kotaro Sasahara</dc:creator>
<dc:creator>Ayaka Saito</dc:creator>
<dc:creator>Shiro Otake</dc:creator>
<dc:creator>Shuhei Azekawa</dc:creator>
<dc:creator>Masahiko Okada</dc:creator>
<dc:creator>Takahiro Fukushima</dc:creator>
<dc:creator>Atsuho Morita</dc:creator>
<dc:creator>Hiromu Tanaka</dc:creator>
<dc:creator>Keeya Sunata</dc:creator>
<dc:creator>Masato Asaoka</dc:creator>
<dc:creator>Miyuki Nishie</dc:creator>
<dc:creator>Taro Shinozaki</dc:creator>
<dc:creator>Toshiki Ebisudani</dc:creator>
<dc:creator>Yuto Akiyama</dc:creator>
<dc:creator>Akifumi Mitsuishi</dc:creator>
<dc:creator>Shingo Nakayama</dc:creator>
<dc:creator>Takunori Ogawa</dc:creator>
<dc:creator>Kaori Sakurai</dc:creator>
<dc:creator>Misato Irie</dc:creator>
<dc:creator>Kazuma Yagi</dc:creator>
<dc:creator>Keiko Ohgino</dc:creator>
<dc:creator>Jun Miyata</dc:creator>
<dc:creator>Hiroki Kabata</dc:creator>
<dc:creator>Shinnosuke Ikemura</dc:creator>
<dc:creator>Hirofumi Kamata</dc:creator>
<dc:creator>Hiroyuki Yasuda</dc:creator>
<dc:creator>Ichiro Kawada</dc:creator>
<dc:creator>Ryusei Kimura</dc:creator>
<dc:creator>Masahiro Kondo</dc:creator>
<dc:creator>Toshiki Iwasaki</dc:creator>
<dc:creator>Noriyuki Ishida</dc:creator>
<dc:creator>Gaku Hiruma</dc:creator>
<dc:creator>Naoki Miyazaki</dc:creator>
<dc:creator>Yoshiki Ishibashi</dc:creator>
<dc:creator>Sei Harada</dc:creator>
<dc:creator>Takanori Fujita</dc:creator>
<dc:creator>Daisuke Ito</dc:creator>
<dc:creator>Shogyoku Bun</dc:creator>
<dc:creator>Hajime Tabuchi</dc:creator>
<dc:creator>Sho Kanzaki</dc:creator>
<dc:creator>Eisuke Shimizu</dc:creator>
<dc:creator>Keitaro Fukuda</dc:creator>
<dc:creator>Jun Yamagami</dc:creator>
<dc:creator>Keigo Kobayashi</dc:creator>
<dc:creator>Toshiyuki Hirano</dc:creator>
<dc:creator>Takashi Inoue</dc:creator>
<dc:creator>Mizuha Haraguchi</dc:creator>
<dc:creator>Junko Kagyo</dc:creator>
<dc:creator>Tetsuya Shiomi</dc:creator>
<dc:creator>Ho Lee</dc:creator>
<dc:creator>Kai Sugihara</dc:creator>
<dc:creator>Nao Omori</dc:creator>
<dc:creator>Koichi Sayama</dc:creator>
<dc:creator>Kengo Otsuka</dc:creator>
<dc:creator>Naoki Miyao</dc:creator>
<dc:creator>Toshio Odani</dc:creator>
<dc:creator>Mayuko Watase</dc:creator>
<dc:creator>Takao Mochimaru</dc:creator>
<dc:creator>Ryosuke Satomi</dc:creator>
<dc:creator>Yoshitaka Oyamada</dc:creator>
<dc:creator>Keita Masuzawa</dc:creator>
<dc:creator>Takanori Asakura</dc:creator>
<dc:creator>Sohei Nakayama</dc:creator>
<dc:creator>Yusuke Suzuki</dc:creator>
<dc:creator>Rie Baba</dc:creator>
<dc:creator>Satoshi Okamori</dc:creator>
<dc:creator>Daisuke Arai</dc:creator>
<dc:creator>Ichiro Nakachi</dc:creator>
<dc:creator>Naota Kuwahara</dc:creator>
<dc:creator>Akiko Fujiwara</dc:creator>
<dc:creator>Takenori Oakada</dc:creator>
<dc:creator>Takashi Ishiguro</dc:creator>
<dc:creator>Taisuke Isosno</dc:creator>
<dc:creator>Yasushi Makino</dc:creator>
<dc:creator>Shuko Mashimo</dc:creator>
<dc:creator>Tatsuya Kaido</dc:creator>
<dc:creator>Naoto Minematsu</dc:creator>
<dc:creator>Soichiro Ueda</dc:creator>
<dc:creator>Kazuhiro Minami</dc:creator>
<dc:creator>Rie Hagiwara</dc:creator>
<dc:creator>Tadashi Manabe</dc:creator>
<dc:creator>Takahiro Fukui</dc:creator>
<dc:creator>Yohei Funatsu</dc:creator>
<dc:creator>Hidefumi Koh</dc:creator>
<dc:creator>Takashi Yoshiyama</dc:creator>
<dc:creator>Hiroyuki Kokuto</dc:creator>
<dc:creator>Tatsuya Kusumoto</dc:creator>
<dc:creator>Ayano Oashi</dc:creator>
<dc:creator>Masayoshi Miyawaki</dc:creator>
<dc:creator>Fumitake Saito</dc:creator>
<dc:creator>Tetsuo Tani</dc:creator>
<dc:creator>Kota Ishioka</dc:creator>
<dc:creator>Saeko Takahashi</dc:creator>
<dc:creator>Morio Nakamura</dc:creator>
<dc:creator>Norihiro Harada</dc:creator>
<dc:creator>Hitoshi Sasano</dc:creator>
<dc:creator>Ai Goto</dc:creator>
<dc:creator>Yu Kusaka</dc:creator>
<dc:creator>Takehiko Ohba</dc:creator>
<dc:creator>Yasushi Nakano</dc:creator>
<dc:creator>Kazumi Nishio</dc:creator>
<dc:creator>Yukiko Nakajima</dc:creator>
<dc:creator>Shoji Suzuki</dc:creator>
<dc:creator>Shuichi Yoshida</dc:creator>
<dc:creator>Hiroki Tateno</dc:creator>
<dc:creator>Nobuhiro Kodama</dc:creator>
<dc:creator>Maeda Shunsuke</dc:creator>
<dc:creator>Satoshi Sakamoto</dc:creator>
<dc:creator>Masaki Okamoto</dc:creator>
<dc:creator>Yoji Nagasaki</dc:creator>
<dc:creator>Akira Umeda</dc:creator>
<dc:creator>Kazuya Miyagawa</dc:creator>
<dc:creator>Hisato Shimada</dc:creator>
<dc:creator>Kazuto Hagimura</dc:creator>
<dc:creator>Kengo Nagashima</dc:creator>
<dc:creator>Toshiro Sato</dc:creator>
<dc:creator>Yasunori Sato</dc:creator>
<dc:creator>Naoki Hasegawa</dc:creator>
<dc:creator>Toru Takebayashi</dc:creator>
<dc:creator>Jin Nakahara</dc:creator>
<dc:creator>Masaru Mimura</dc:creator>
<dc:creator>Kaoru Ogawa</dc:creator>
<dc:creator>Shigeto Shimmura</dc:creator>
<dc:creator>Kazuno Negishi</dc:creator>
<dc:creator>Kazuo Tsubota</dc:creator>
<dc:creator>Masayuki Amagai</dc:creator>
<dc:creator>Rei Goto</dc:creator>
<dc:creator>Yoko Ibuka</dc:creator>
<dc:creator>Yuko Kitagawa</dc:creator>
<dc:creator>Takanori Kanai</dc:creator>
<dc:creator>Koichi Fukunaga</dc:creator>
<dc:date>2023-10-02</dc:date>
<dc:source>Respiratory investigation</dc:source>
<dc:title>Comprehensive analysis of long COVID in a Japanese nationwide prospective cohort study</dc:title>
<dc:identifier>pmid:37783167</dc:identifier>
<dc:identifier>doi:10.1016/j.resinv.2023.08.008</dc:identifier>
</item>
<item>
<title>The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37781921/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>First achieved in 1998 by Cole et al., the complete genome sequence of Mycobacterium tuberculosis continues to provide an invaluable resource to understand tuberculosis (TB), the leading cause of global infectious disease mortality. At the 25-year anniversary of this accomplishment, we describe how insights gleaned from the M. tuberculosis genome have led to vital tools for TB research, epidemiology, and clinical practice. The increasing accessibility of whole-genome sequencing across research...</description>
<content:encoded><![CDATA[<div>J Clin Invest. 2023 Oct 2;133(19):e173156. doi: 10.1172/JCI173156.ABSTRACTFirst achieved in 1998 by Cole et al., the complete genome sequence of Mycobacterium tuberculosis continues to provide an invaluable resource to understand tuberculosis (TB), the leading cause of global infectious disease mortality. At the 25-year anniversary of this accomplishment, we describe how insights gleaned from the M. tuberculosis genome have led to vital tools for TB research, epidemiology, and clinical practice. The increasing accessibility of whole-genome sequencing across research and clinical settings has improved our ability to predict antibacterial susceptibility, to track epidemics at the level of individual outbreaks and wider historical trends, to query the efficacy of the bacille Calmette-Guérin (BCG) vaccine, and to uncover targets for novel antitubercular therapeutics. Likewise, we discuss several recent efforts to extract further discoveries from this powerful resource.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37781921/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37781921</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10541200/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10541200</a> | DOI:<a href=https://doi.org/10.1172/JCI173156>10.1172/JCI173156</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37781921</guid>
<pubDate>Mon, 02 Oct 2023 06:00:00 -0400</pubDate>
<dc:creator>Benjamin N Koleske</dc:creator>
<dc:creator>William R Jacobs</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-10-02</dc:date>
<dc:source>The Journal of clinical investigation</dc:source>
<dc:title>The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions</dc:title>
<dc:identifier>pmid:37781921</dc:identifier>
<dc:identifier>pmc:PMC10541200</dc:identifier>
<dc:identifier>doi:10.1172/JCI173156</dc:identifier>
</item>
<item>
<title>MDA5 RNA-sensing pathway activation by Mycobacterium tuberculosis promotes innate immune subversion and pathogen survival</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37725440/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Host cytosolic sensing of Mycobacterium tuberculosis (M. tuberculosis) RNA by the RIG-I-like receptor (RLR) family perturbs innate immune control within macrophages; however, a distinct role of MDA5, a member of the RLR family, in M. tuberculosis pathogenesis has yet to be fully elucidated. To further define the role of MDA5 in M. tuberculosis pathogenesis, we evaluated M. tuberculosis intracellular growth and innate immune responses in WT and Mda5-/- macrophages. Transfection of M. tuberculosis...</description>
<content:encoded><![CDATA[<div>JCI Insight. 2023 Oct 23;8(20):e166242. doi: 10.1172/jci.insight.166242.ABSTRACTHost cytosolic sensing of Mycobacterium tuberculosis (M. tuberculosis) RNA by the RIG-I-like receptor (RLR) family perturbs innate immune control within macrophages; however, a distinct role of MDA5, a member of the RLR family, in M. tuberculosis pathogenesis has yet to be fully elucidated. To further define the role of MDA5 in M. tuberculosis pathogenesis, we evaluated M. tuberculosis intracellular growth and innate immune responses in WT and Mda5-/- macrophages. Transfection of M. tuberculosis RNA strongly induced proinflammatory cytokine production in WT macrophages, which was abrogated in Mda5-/- macrophages. M. tuberculosis infection in macrophages induced MDA5 protein expression, accompanied by an increase in MDA5 activation as assessed by multimer formation. IFN-γ-primed Mda5-/- macrophages effectively contained intracellular M. tuberculosis proliferation to a markedly greater degree than WT macrophages. Further comparisons of WT versus Mda5-/- macrophages revealed that during M. tuberculosis infection MDA5 contributed to IL-1β production and inflammasome activation and that loss of MDA5 led to a substantial increase in autophagy. In the mouse TB model, loss of MDA5 conferred host survival benefits with a concomitant reduction in M. tuberculosis bacillary burden. These data reveal that loss of MDA5 is host protective during M. tuberculosis infection in vitro and in vivo, suggesting that M. tuberculosis exploits MDA5 to subvert immune containment.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37725440/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37725440</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10619499/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10619499</a> | DOI:<a href=https://doi.org/10.1172/jci.insight.166242>10.1172/jci.insight.166242</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37725440</guid>
<pubDate>Tue, 19 Sep 2023 06:00:00 -0400</pubDate>
<dc:creator>C Korin Bullen</dc:creator>
<dc:creator>Alok K Singh</dc:creator>
<dc:creator>Stefanie Krug</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Preeti Thakur</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-09-19</dc:date>
<dc:source>JCI insight</dc:source>
<dc:title>MDA5 RNA-sensing pathway activation by Mycobacterium tuberculosis promotes innate immune subversion and pathogen survival</dc:title>
<dc:identifier>pmid:37725440</dc:identifier>
<dc:identifier>pmc:PMC10619499</dc:identifier>
<dc:identifier>doi:10.1172/jci.insight.166242</dc:identifier>
</item>
<item>
<title>Sex and Gender Differences in Tuberculosis Pathogenesis and Treatment Outcomes</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37695428/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Tuberculosis remains a daunting public health concern in many countries of the world. A consistent observation in the global epidemiology of tuberculosis is an excess of cases of active pulmonary tuberculosis among males compared with females. Data from both humans and animals also suggest that males are more susceptible than females to develop active pulmonary disease. Similarly, male sex has been associated with poor treatment outcomes. Despite this growing body of evidence, little is known...</description>
<content:encoded><![CDATA[<div>Curr Top Microbiol Immunol. 2023;441:139-183. doi: 10.1007/978-3-031-35139-6_6.ABSTRACTTuberculosis remains a daunting public health concern in many countries of the world. A consistent observation in the global epidemiology of tuberculosis is an excess of cases of active pulmonary tuberculosis among males compared with females. Data from both humans and animals also suggest that males are more susceptible than females to develop active pulmonary disease. Similarly, male sex has been associated with poor treatment outcomes. Despite this growing body of evidence, little is known about the mechanisms driving sex bias in tuberculosis disease. Two dominant hypotheses have been proposed to explain the predominance of active pulmonary tuberculosis among males. The first is based on the contribution of biological factors, such as sex hormones and genetic factors, on host immunity during tuberculosis. The second is focused on non-biological factors such as smoking, professional exposure, and health-seeking behaviors, known to be influenced by gender. In this chapter, we review the literature regarding these two prevailing hypotheses by presenting human but also experimental animal studies. In addition, we presented studies aiming at examining the impact of sex and gender on other clinical forms of tuberculosis such as latent tuberculosis infection and extrapulmonary tuberculosis, which both appear to have their own specificities in relation to sex. We also highlighted potential intersections between sex and gender in the context of tuberculosis and shared future directions that could guide in elucidating mechanisms of sex-based differences in tuberculosis pathogenesis and treatment outcomes.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37695428/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37695428</a> | DOI:<a href=https://doi.org/10.1007/978-3-031-35139-6_6>10.1007/978-3-031-35139-6_6</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37695428</guid>
<pubDate>Mon, 11 Sep 2023 06:00:00 -0400</pubDate>
<dc:creator>Djeneba Dabitao</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-09-11</dc:date>
<dc:source>Current topics in microbiology and immunology</dc:source>
<dc:title>Sex and Gender Differences in Tuberculosis Pathogenesis and Treatment Outcomes</dc:title>
<dc:identifier>pmid:37695428</dc:identifier>
<dc:identifier>doi:10.1007/978-3-031-35139-6_6</dc:identifier>
</item>
<item>
<title>Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37674985/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited...</description>
<content:encoded><![CDATA[<div>iScience. 2023 Aug 24;26(10):107733. doi: 10.1016/j.isci.2023.107733. eCollection 2023 Oct 20.ABSTRACTBacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, with a transcriptional shift away from exhaustion markers and toward antigen presentation and repair. Similarly, BCG enhanced recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, that show reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37674985/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37674985</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10477068/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10477068</a> | DOI:<a href=https://doi.org/10.1016/j.isci.2023.107733>10.1016/j.isci.2023.107733</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37674985</guid>
<pubDate>Thu, 07 Sep 2023 06:00:00 -0400</pubDate>
<dc:creator>Alok K Singh</dc:creator>
<dc:creator>Rulin Wang</dc:creator>
<dc:creator>Kara A Lombardo</dc:creator>
<dc:creator>Monali Praharaj</dc:creator>
<dc:creator>C Korin Bullen</dc:creator>
<dc:creator>Peter Um</dc:creator>
<dc:creator>Manish Gupta</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Stephanie Davis</dc:creator>
<dc:creator>Oliver Komm</dc:creator>
<dc:creator>Peter B Illei</dc:creator>
<dc:creator>Alvaro A Ordonez</dc:creator>
<dc:creator>Melissa Bahr</dc:creator>
<dc:creator>Joy Huang</dc:creator>
<dc:creator>Anuj Gupta</dc:creator>
<dc:creator>Kevin J Psoter</dc:creator>
<dc:creator>Patrick S Creisher</dc:creator>
<dc:creator>Maggie Li</dc:creator>
<dc:creator>Andrew Pekosz</dc:creator>
<dc:creator>Sabra L Klein</dc:creator>
<dc:creator>Sanjay K Jain</dc:creator>
<dc:creator>Trinity J Bivalacqua</dc:creator>
<dc:creator>Srinivasan Yegnasubramanian</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-09-07</dc:date>
<dc:source>iScience</dc:source>
<dc:title>Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells</dc:title>
<dc:identifier>pmid:37674985</dc:identifier>
<dc:identifier>pmc:PMC10477068</dc:identifier>
<dc:identifier>doi:10.1016/j.isci.2023.107733</dc:identifier>
</item>
<item>
<title>Relationship between patient sex and anatomical sites of extrapulmonary tuberculosis in Mali</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37637324/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis.</description>
<content:encoded><![CDATA[<div>J Clin Tuberc Other Mycobact Dis. 2023 Aug 9;33:100389. doi: 10.1016/j.jctube.2023.100389. eCollection 2023 Dec.ABSTRACTBACKGROUND: Contribution of host factors in mediating susceptibility to extrapulmonary tuberculosis is not well understood.OBJECTIVE: To examine the influence of patient sex on anatomical localization of extrapulmonary tuberculosis.METHODS: We conducted a retrospective cross-sectional study in Mali, West Africa. Hospital records of 1,304 suspected cases of extrapulmonary tuberculosis, available in TB Registry of a tertiary tuberculosis referral center from 2019 to 2021, were examined.RESULTS: A total of 1,012 (77.6%) were confirmed to have extrapulmonary tuberculosis with a male to female ratio of 1.59:1. Four clinical forms of EPTB predominated, namely pleural (40.4%), osteoarticular (29.8%), lymph node (12.5%), and abdominal TB (10.3%). We found sex-based differences in anatomical localization of extrapulmonary tuberculosis, with males more likely than females to have pleural TB (OR: 1.51; 95% CI [1.16 to 1.98]). Conversely, being male was associated with 43% and 41% lower odds of having lymph node and abdominal TB, respectively (OR: 0.57 and 0.59).CONCLUSION: Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37637324/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37637324</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10448223/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10448223</a> | DOI:<a href=https://doi.org/10.1016/j.jctube.2023.100389>10.1016/j.jctube.2023.100389</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37637324</guid>
<pubDate>Mon, 28 Aug 2023 06:00:00 -0400</pubDate>
<dc:creator>Bocar Baya</dc:creator>
<dc:creator>Ibrahim Sanogo</dc:creator>
<dc:creator>Mahamadou Kone</dc:creator>
<dc:creator>Dianguina Soumare</dc:creator>
<dc:creator>Kadidia Ouattara</dc:creator>
<dc:creator>Amadou Somboro</dc:creator>
<dc:creator>Mamadou Wague</dc:creator>
<dc:creator>Nadie Coulibaly</dc:creator>
<dc:creator>Isaac Koloma</dc:creator>
<dc:creator>Mariam Coulibaly</dc:creator>
<dc:creator>Mohamed Nantoume</dc:creator>
<dc:creator>Mamadou Perou</dc:creator>
<dc:creator>Kadidia Kone</dc:creator>
<dc:creator>Djeneba Coulibaly</dc:creator>
<dc:creator>Hawa Boukary Diarra</dc:creator>
<dc:creator>Bourahima Kone</dc:creator>
<dc:creator>Ayouba Diarra</dc:creator>
<dc:creator>Mamadou D Coulibaly</dc:creator>
<dc:creator>Moumine Sanogo</dc:creator>
<dc:creator>Bassirou Diarra</dc:creator>
<dc:creator>Mahamadou Diakite</dc:creator>
<dc:creator>Chad J Achenbach</dc:creator>
<dc:creator>Seydou Doumbia</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Sabra L Klein</dc:creator>
<dc:creator>Jane L Holl</dc:creator>
<dc:creator>Souleymane Diallo</dc:creator>
<dc:creator>Robert L Murphy</dc:creator>
<dc:creator>Yacouba Toloba</dc:creator>
<dc:creator>Djeneba Dabitao</dc:creator>
<dc:date>2023-08-28</dc:date>
<dc:source>Journal of clinical tuberculosis and other mycobacterial diseases</dc:source>
<dc:title>Relationship between patient sex and anatomical sites of extrapulmonary tuberculosis in Mali</dc:title>
<dc:identifier>pmid:37637324</dc:identifier>
<dc:identifier>pmc:PMC10448223</dc:identifier>
<dc:identifier>doi:10.1016/j.jctube.2023.100389</dc:identifier>
</item>
<item>
<title>Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37287871/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>BACKGROUND: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT).</description>
<content:encoded><![CDATA[<div>EClinicalMedicine. 2023 Jun 2;60:102030. doi: 10.1016/j.eclinm.2023.102030. eCollection 2023 Jun.ABSTRACTBACKGROUND: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT).METHODS: This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50 cells/μL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes.FINDINGS: Of all 269 participants, 76.2% (n = 205) were anaemic, and 31.2% (n = 84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32-9.76, p = 0.012) and death (aOR: 3.63, 95% CI: 1.07-12.33, p = 0.039).INTERPRETATION: Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes.FUNDING: National Institutes of Health.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37287871/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37287871</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10242630/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10242630</a> | DOI:<a href=https://doi.org/10.1016/j.eclinm.2023.102030>10.1016/j.eclinm.2023.102030</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37287871</guid>
<pubDate>Thu, 08 Jun 2023 06:00:00 -0400</pubDate>
<dc:creator>Mariana Araújo-Pereira</dc:creator>
<dc:creator>Sonya Krishnan</dc:creator>
<dc:creator>Padmini Salgame</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Mina C Hosseinipour</dc:creator>
<dc:creator>Gregory Bisson</dc:creator>
<dc:creator>Damocles Patrice Severe</dc:creator>
<dc:creator>Vanessa Rouzier</dc:creator>
<dc:creator>Samantha Leong</dc:creator>
<dc:creator>Vidya Mave</dc:creator>
<dc:creator>Fredrick Kipyego Sawe</dc:creator>
<dc:creator>Abraham M Siika</dc:creator>
<dc:creator>Cecilia Kanyama</dc:creator>
<dc:creator>Sufia S Dadabhai</dc:creator>
<dc:creator>Javier R Lama</dc:creator>
<dc:creator>Javier Valencia-Huamani</dc:creator>
<dc:creator>Sharlaa Badal-Faesen</dc:creator>
<dc:creator>Umesh Gangaram Lalloo</dc:creator>
<dc:creator>Kogieleum Naidoo</dc:creator>
<dc:creator>Lerato Mohapi</dc:creator>
<dc:creator>Cissy Kityo</dc:creator>
<dc:creator>Bruno B Andrade</dc:creator>
<dc:creator>Amita Gupta</dc:creator>
<dc:date>2023-06-08</dc:date>
<dc:source>EClinicalMedicine</dc:source>
<dc:title>Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial</dc:title>
<dc:identifier>pmid:37287871</dc:identifier>
<dc:identifier>pmc:PMC10242630</dc:identifier>
<dc:identifier>doi:10.1016/j.eclinm.2023.102030</dc:identifier>
</item>
<item>
<title>A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37205421/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan sidechains. As the current BCG vaccine is derived from pathogenic mycobacteria,...</description>
<content:encoded><![CDATA[<div>bioRxiv [Preprint]. 2023 May 3:2023.05.03.539199. doi: 10.1101/2023.05.03.539199.ABSTRACTMechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan sidechains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking ability and to potentially improve efficacy of the BCG vaccine, we used CRISPRi to inhibit expression of the essential enzyme pair, MurT-GatD, implicated in amidation of peptidoglycan sidechains. We demonstrate that depletion of these enzymes results in reduced growth, cell wall defects, increased susceptibility to antibiotics and altered spatial localization of new peptidoglycan. In cell culture experiments, training of monocytes with this recombinant BCG yielded improved control of Mtb growth. In the murine model of TB infection, we demonstrate that depletion of MurT-GatD in BCG, resulting in unmasking of the D-glutamate diaminopimelate (iE-DAP) NOD-1 ligand, yields superior prevention of TB disease compared to the standard BCG vaccine. This work demonstrates the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37205421/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37205421</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10187164/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10187164</a> | DOI:<a href=https://doi.org/10.1101/2023.05.03.539199>10.1101/2023.05.03.539199</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37205421</guid>
<pubDate>Fri, 19 May 2023 06:00:00 -0400</pubDate>
<dc:creator>Moagi T Shaku</dc:creator>
<dc:creator>Peter Um</dc:creator>
<dc:creator>Karl L Ocius</dc:creator>
<dc:creator>Alexis J Apostolos</dc:creator>
<dc:creator>Marcos M Pires</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Bavesh D Kana</dc:creator>
<dc:date>2023-05-19</dc:date>
<dc:source>bioRxiv : the preprint server for biology</dc:source>
<dc:title>A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice</dc:title>
<dc:identifier>pmid:37205421</dc:identifier>
<dc:identifier>pmc:PMC10187164</dc:identifier>
<dc:identifier>doi:10.1101/2023.05.03.539199</dc:identifier>
</item>
<item>
<title>Mycobacterium tuberculosis disease associates with higher HIV-1-specific antibody responses</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37168567/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Mycobacterium tuberculosis (Mtb) is the most common infection among people with HIV (PWH). Mtb disease-associated inflammation could affect HIV-directed immune responses in PWH. We show that HIV antibodies are broader and more potent in PWH in the presence as compared to the absence of Mtb disease. With co-existing Mtb disease, the virus in PWH also encounters unique antibody selection pressure. The Mtb-linked HIV antibody enhancement associates with specific mediators important for B cell and...</description>
<content:encoded><![CDATA[<div>iScience. 2023 Apr 10;26(5):106631. doi: 10.1016/j.isci.2023.106631. eCollection 2023 May 19.ABSTRACTMycobacterium tuberculosis (Mtb) is the most common infection among people with HIV (PWH). Mtb disease-associated inflammation could affect HIV-directed immune responses in PWH. We show that HIV antibodies are broader and more potent in PWH in the presence as compared to the absence of Mtb disease. With co-existing Mtb disease, the virus in PWH also encounters unique antibody selection pressure. The Mtb-linked HIV antibody enhancement associates with specific mediators important for B cell and antibody development. This Mtb humoral augmentation does not occur due to cross-reactivity, a generalized increase in all antibodies, or differences in duration or amount of antigen exposure. We speculate that the co-localization of Mtb and HIV in lymphatic tissues leads to the emergence of potent HIV antibodies. PWH's Mtb disease status has implications for the future use of HIV broadly neutralizing antibodies as prophylaxis or treatment and the induction of better humoral immunity.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37168567/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37168567</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10165194/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10165194</a> | DOI:<a href=https://doi.org/10.1016/j.isci.2023.106631>10.1016/j.isci.2023.106631</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37168567</guid>
<pubDate>Thu, 11 May 2023 06:00:00 -0400</pubDate>
<dc:creator>Bukola Adeoye</dc:creator>
<dc:creator>Lydia Nakiyingi</dc:creator>
<dc:creator>Yvetane Moreau</dc:creator>
<dc:creator>Ethel Nankya</dc:creator>
<dc:creator>Alex J Olson</dc:creator>
<dc:creator>Mo Zhang</dc:creator>
<dc:creator>Karen R Jacobson</dc:creator>
<dc:creator>Amita Gupta</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Mina C Hosseinipour</dc:creator>
<dc:creator>Johnstone Kumwenda</dc:creator>
<dc:creator>Manish Sagar</dc:creator>
<dc:creator>AIDS Clinical Trials Group A5274 (REMEMBER) Study Team</dc:creator>
<dc:date>2023-05-11</dc:date>
<dc:source>iScience</dc:source>
<dc:title>Mycobacterium tuberculosis disease associates with higher HIV-1-specific antibody responses</dc:title>
<dc:identifier>pmid:37168567</dc:identifier>
<dc:identifier>pmc:PMC10165194</dc:identifier>
<dc:identifier>doi:10.1016/j.isci.2023.106631</dc:identifier>
</item>
<item>
<title>CRISPR Correction of the GBA Mutation in Human-Induced Pluripotent Stem Cells Restores Normal Function to Gaucher Macrophages and Increases Their Susceptibility to Mycobacterium tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37159513/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase (GCase) GBA gene, which result in macrophage dysfunction. CRISPR (clustered regularly interspaced short palindromic repeats) editing of the homozygous L444P (1448T→C) GBA mutation in type 2 GD (GBA-/-) human-induced pluripotent stem cells (hiPSCs) yielded both heterozygous (GBA+/-) and homozygous (GBA+/+) isogenic lines. Macrophages derived from GBA-/-, GBA+/- and GBA+/+...</description>
<content:encoded><![CDATA[<div>J Infect Dis. 2023 Sep 15;228(6):777-782. doi: 10.1093/infdis/jiad141.ABSTRACTGaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase (GCase) GBA gene, which result in macrophage dysfunction. CRISPR (clustered regularly interspaced short palindromic repeats) editing of the homozygous L444P (1448T→C) GBA mutation in type 2 GD (GBA-/-) human-induced pluripotent stem cells (hiPSCs) yielded both heterozygous (GBA+/-) and homozygous (GBA+/+) isogenic lines. Macrophages derived from GBA-/-, GBA+/- and GBA+/+ hiPSCs showed that GBA mutation correction restores normal macrophage functions: GCase activity, motility, and phagocytosis. Furthermore, infection of GBA-/-, GBA+/- and GBA+/+ macrophages with the Mycobacterium tuberculosis H37Rv strain showed that impaired mobility and phagocytic activity were correlated with reduced levels of bacterial engulfment and replication suggesting that GD may be protective against tuberculosis.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37159513/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37159513</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10686692/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10686692</a> | DOI:<a href=https://doi.org/10.1093/infdis/jiad141>10.1093/infdis/jiad141</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37159513</guid>
<pubDate>Tue, 09 May 2023 06:00:00 -0400</pubDate>
<dc:creator>Sivaprakash Ramalingam</dc:creator>
<dc:creator>Amit Kumar</dc:creator>
<dc:creator>Stefanie Krug</dc:creator>
<dc:creator>Harikrishnan Mohan</dc:creator>
<dc:creator>Desirazu N Rao</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Srinivasan Chandrasegaran</dc:creator>
<dc:date>2023-05-09</dc:date>
<dc:source>The Journal of infectious diseases</dc:source>
<dc:title>CRISPR Correction of the GBA Mutation in Human-Induced Pluripotent Stem Cells Restores Normal Function to Gaucher Macrophages and Increases Their Susceptibility to Mycobacterium tuberculosis</dc:title>
<dc:identifier>pmid:37159513</dc:identifier>
<dc:identifier>pmc:PMC10686692</dc:identifier>
<dc:identifier>doi:10.1093/infdis/jiad141</dc:identifier>
</item>
<item>
<title>Structure-directed identification of pyridine-2-methylamine derivatives as MmpL3 inhibitors for use as antitubercular agents</title>
<link>https://pubmed.ncbi.nlm.nih.gov/37116266/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Mycobacterial membrane protein Large 3 (MmpL3), an inner membrane protein, plays a crucial role in the transport of mycolic acids that are essential for the viability of M. tuberculosis and has been a promising therapeutic target for new anti-TB agents. Herein, we report the discovery of pyridine-2-methylamine antitubercular compounds using a structure-based drug design strategy. Compound 62 stands out as the most potent compound with high activity against M. tb strain H37Rv (MIC = 0.016 μg/mL)...</description>
<content:encoded><![CDATA[<div>Eur J Med Chem. 2023 Jul 5;255:115351. doi: 10.1016/j.ejmech.2023.115351. Epub 2023 Apr 21.ABSTRACTMycobacterial membrane protein Large 3 (MmpL3), an inner membrane protein, plays a crucial role in the transport of mycolic acids that are essential for the viability of M. tuberculosis and has been a promising therapeutic target for new anti-TB agents. Herein, we report the discovery of pyridine-2-methylamine antitubercular compounds using a structure-based drug design strategy. Compound 62 stands out as the most potent compound with high activity against M. tb strain H37Rv (MIC = 0.016 μg/mL) as well as the clinically isolated strains of MDR/XDR-TB (MIC = 0.0039-0.0625 μg/mL), low Vero cell toxicity (IC50 ≥ 16 μg/mL), and moderate liver microsomal stability (CLint = 28 μL/min/mg). Furthermore, the resistant mutant of S288T due to single nucleotide polymorphism in mmpL3 was resistant to pyridine-2-methylamine 62, demonstrating compound 62 is likely target to MmpL3.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/37116266/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">37116266</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10239758/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10239758</a> | DOI:<a href=https://doi.org/10.1016/j.ejmech.2023.115351>10.1016/j.ejmech.2023.115351</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:37116266</guid>
<pubDate>Fri, 28 Apr 2023 06:00:00 -0400</pubDate>
<dc:creator>Yu Wen</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Yuxue Jiao</dc:creator>
<dc:creator>Wei Zhang</dc:creator>
<dc:creator>Ting Liu</dc:creator>
<dc:creator>Fan Yang</dc:creator>
<dc:creator>Jie Tang</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Li-Fang Yu</dc:creator>
<dc:date>2023-04-28</dc:date>
<dc:source>European journal of medicinal chemistry</dc:source>
<dc:title>Structure-directed identification of pyridine-2-methylamine derivatives as MmpL3 inhibitors for use as antitubercular agents</dc:title>
<dc:identifier>pmid:37116266</dc:identifier>
<dc:identifier>pmc:PMC10239758</dc:identifier>
<dc:identifier>doi:10.1016/j.ejmech.2023.115351</dc:identifier>
</item>
<item>
<title>The Mycobacterium tuberculosis mycothiol S-transferase is divalent metal-dependent for mycothiol binding and transfer</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36970142/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Mycothiol S-transferase (MST) (encoded by the rv0443 gene) was previously identified as the enzyme responsible for the transfer of Mycothiol (MSH) to xenobiotic acceptors in Mycobacterium tuberculosis (M.tb) during xenobiotic stress. To further characterize the functionality of MST in vitro and the possible roles in vivo, X-ray crystallographic, metal-dependent enzyme kinetics, thermal denaturation studies, and antibiotic MIC determination in rv0433 knockout strain were performed. The binding of...</description>
<content:encoded><![CDATA[<div>RSC Med Chem. 2023 Jan 26;14(3):491-500. doi: 10.1039/d2md00401a. eCollection 2023 Mar 22.ABSTRACTMycothiol S-transferase (MST) (encoded by the rv0443 gene) was previously identified as the enzyme responsible for the transfer of Mycothiol (MSH) to xenobiotic acceptors in Mycobacterium tuberculosis (M.tb) during xenobiotic stress. To further characterize the functionality of MST in vitro and the possible roles in vivo, X-ray crystallographic, metal-dependent enzyme kinetics, thermal denaturation studies, and antibiotic MIC determination in rv0433 knockout strain were performed. The binding of MSH and Zn2+ increases the melting temperature by 12.9 °C as a consequence of the cooperative stabilization of MST by both MSH and metal. The co-crystal structure of MST in complex with MSH and Zn2+ to 1.45 Å resolution supports the specific utilization of MSH as a substrate as well as affording insights into the structural requirements of MSH binding and the metal-assisted catalytic mechanism of MST. Contrary to the well-defined role of MSH in mycobacterial xenobiotic responses and the ability of MST to bind MSH, cell-based studies with an M.tb rv0443 knockout strain failed to provide evidence for a role of MST in processing of rifampicin or isoniazid. These studies suggest the necessity of a new direction to identify acceptors of the enzyme and better define the biological role of MST in mycobacteria.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36970142/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36970142</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10034076/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10034076</a> | DOI:<a href=https://doi.org/10.1039/d2md00401a>10.1039/d2md00401a</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36970142</guid>
<pubDate>Mon, 27 Mar 2023 06:00:00 -0400</pubDate>
<dc:creator>Yahani P Jayasinghe</dc:creator>
<dc:creator>Michael T Banco</dc:creator>
<dc:creator>Jared J Lindenberger</dc:creator>
<dc:creator>Lorenza Favrot</dc:creator>
<dc:creator>Zuzana Palčeková</dc:creator>
<dc:creator>Mary Jackson</dc:creator>
<dc:creator>Shino Manabe</dc:creator>
<dc:creator>Donald R Ronning</dc:creator>
<dc:date>2023-03-27</dc:date>
<dc:source>RSC medicinal chemistry</dc:source>
<dc:title>The Mycobacterium tuberculosis mycothiol S-transferase is divalent metal-dependent for mycothiol binding and transfer</dc:title>
<dc:identifier>pmid:36970142</dc:identifier>
<dc:identifier>pmc:PMC10034076</dc:identifier>
<dc:identifier>doi:10.1039/d2md00401a</dc:identifier>
</item>
<item>
<title>Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36873289/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>BACKGROUND: Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda.</description>
<content:encoded><![CDATA[<div>Afr J Lab Med. 2023 Feb 7;12(1):1956. doi: 10.4102/ajlm.v12i1.1956. eCollection 2023.ABSTRACTBACKGROUND: Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda.INTERVENTION: Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care.LESSONS LEARNT: Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda.RECOMMENDATIONS: Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36873289/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36873289</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9982508/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9982508</a> | DOI:<a href=https://doi.org/10.4102/ajlm.v12i1.1956>10.4102/ajlm.v12i1.1956</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36873289</guid>
<pubDate>Mon, 06 Mar 2023 06:00:00 -0500</pubDate>
<dc:creator>Denis Omali</dc:creator>
<dc:creator>Allan Buzibye</dc:creator>
<dc:creator>Richard Kwizera</dc:creator>
<dc:creator>Pauline Byakika-Kibwika</dc:creator>
<dc:creator>Rhoda Namakula</dc:creator>
<dc:creator>Joshua Matovu</dc:creator>
<dc:creator>Olive Mbabazi</dc:creator>
<dc:creator>Emmanuel Mande</dc:creator>
<dc:creator>Christine Sekaggya-Wiltshire</dc:creator>
<dc:creator>Damalie Nakanjako</dc:creator>
<dc:creator>Ursula Gutteck</dc:creator>
<dc:creator>Keith McAdam</dc:creator>
<dc:creator>Philippa Easterbrook</dc:creator>
<dc:creator>Andrew Kambugu</dc:creator>
<dc:creator>Jan Fehr</dc:creator>
<dc:creator>Barbara Castelnuovo</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Mohammed Lamorde</dc:creator>
<dc:creator>Daniel Mueller</dc:creator>
<dc:creator>Concepta Merry</dc:creator>
<dc:date>2023-03-06</dc:date>
<dc:source>African journal of laboratory medicine</dc:source>
<dc:title>Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda</dc:title>
<dc:identifier>pmid:36873289</dc:identifier>
<dc:identifier>pmc:PMC9982508</dc:identifier>
<dc:identifier>doi:10.4102/ajlm.v12i1.1956</dc:identifier>
</item>
<item>
<title>Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36865287/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>As one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a novel glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35...</description>
<content:encoded><![CDATA[<div>bioRxiv [Preprint]. 2023 Feb 23:2023.02.23.529704. doi: 10.1101/2023.02.23.529704.ABSTRACTAs one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a novel glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomics analysis of lungs from JHU083-treated Mtb-infected mice revealed reduced glutamine levels, citrulline accumulation suggesting elevated NOS activity, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. When tested in an immunocompromised mouse model of Mtb infection, JHU083 lost its therapeutic efficacy suggesting the drug's host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36865287/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36865287</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9980128/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9980128</a> | DOI:<a href=https://doi.org/10.1101/2023.02.23.529704>10.1101/2023.02.23.529704</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36865287</guid>
<pubDate>Fri, 03 Mar 2023 06:00:00 -0500</pubDate>
<dc:creator>Sadiya Parveen</dc:creator>
<dc:creator>Jessica Shen</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Liang Zhao</dc:creator>
<dc:creator>Benjamin Koleske</dc:creator>
<dc:creator>Robert D Leone</dc:creator>
<dc:creator>Rana Rais</dc:creator>
<dc:creator>Jonathan D Powell</dc:creator>
<dc:creator>John R Murphy</dc:creator>
<dc:creator>Barbara S Slusher</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-03-03</dc:date>
<dc:source>bioRxiv : the preprint server for biology</dc:source>
<dc:title>Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis</dc:title>
<dc:identifier>pmid:36865287</dc:identifier>
<dc:identifier>pmc:PMC9980128</dc:identifier>
<dc:identifier>doi:10.1101/2023.02.23.529704</dc:identifier>
</item>
<item>
<title>Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36853048/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Despite numerous advances in tuberculosis (TB) drug development, long treatment durations have led to the emergence of multidrug resistance, which poses a major hurdle to global TB control. Shortening treatment time therefore remains a top priority. Host-directed therapies that promote bacterial clearance and/or lung health may improve the efficacy and treatment duration of tuberculosis antibiotics. We recently discovered that inhibition of the integrated stress response, which is abnormally...</description>
<content:encoded><![CDATA[<div>mBio. 2023 Apr 25;14(2):e0349622. doi: 10.1128/mbio.03496-22. Epub 2023 Feb 28.ABSTRACTDespite numerous advances in tuberculosis (TB) drug development, long treatment durations have led to the emergence of multidrug resistance, which poses a major hurdle to global TB control. Shortening treatment time therefore remains a top priority. Host-directed therapies that promote bacterial clearance and/or lung health may improve the efficacy and treatment duration of tuberculosis antibiotics. We recently discovered that inhibition of the integrated stress response, which is abnormally activated in tuberculosis and associated with necrotic granuloma formation, reduced bacterial numbers and lung inflammation in mice. Here, we evaluated the impact of the integrated stress response (ISR) inhibitor ISRIB, administered as an adjunct to standard tuberculosis antibiotics, on bacterial clearance, relapse, and lung pathology in a mouse model of tuberculosis. Throughout the course of treatment, ISRIB robustly lowered bacterial burdens compared to the burdens with standard TB therapy alone and accelerated the time to sterility in mice, as demonstrated by significantly reduced relapse rates after 4 months of treatment. In addition, mice receiving adjunctive ISRIB tended to have reduced lung necrosis and inflammation. Together, our findings identify the ISR pathway as a promising therapeutic target with the potential to shorten TB treatment durations and improve lung health. IMPORTANCE Necrosis of lung lesions is a hallmark of tuberculosis (TB) that promotes bacterial growth, dissemination, and transmission. This process is driven by the persistent hyperactivation of the integrated stress response (ISR) pathway. Here, we show that adjunctive ISR inhibition during standard antibiotic therapy accelerates bacterial clearance and reduces immunopathology in a clinically relevant mouse model of TB, suggesting that host-directed therapies that de-escalate these pathological stress responses may shorten TB treatment durations. Our findings present an important conceptual advance toward overcoming the challenge of improving TB therapy and lowering the global burden of disease.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36853048/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36853048</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10128048/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10128048</a> | DOI:<a href=https://doi.org/10.1128/mbio.03496-22>10.1128/mbio.03496-22</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36853048</guid>
<pubDate>Tue, 28 Feb 2023 06:00:00 -0500</pubDate>
<dc:creator>Stefanie Krug</dc:creator>
<dc:creator>Pankaj Prasad</dc:creator>
<dc:creator>Shiqi Xiao</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Camilo A Ruiz-Bedoya</dc:creator>
<dc:creator>Mariah Klunk</dc:creator>
<dc:creator>Alvaro A Ordonez</dc:creator>
<dc:creator>Sanjay K Jain</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Igor Kramnik</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2023-02-28</dc:date>
<dc:source>mBio</dc:source>
<dc:title>Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice</dc:title>
<dc:identifier>pmid:36853048</dc:identifier>
<dc:identifier>pmc:PMC10128048</dc:identifier>
<dc:identifier>doi:10.1128/mbio.03496-22</dc:identifier>
</item>
<item>
<title>Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36821550/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Tuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at...</description>
<content:encoded><![CDATA[<div>PLoS One. 2023 Feb 23;18(2):e0268935. doi: 10.1371/journal.pone.0268935. eCollection 2023.ABSTRACTTuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda. HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda were retrospectively reviewed. Estimated trends of TPT (given as Isoniazid monotherapy) uptake and completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models. On average, a total of 39,774 PLHIV aged 15 years and above were eligible for TPT each calendar year at the six health facilities. Across all 4 years, more than 70% were females (range: 73.5% -74.6%) and the median age ranged from 33 to 34 years. From 2016 quarter one to 2019 quarter two, TPT uptake was consistently below 25%, but, as expected, the uptake significantly increased by about 3-folds from 22.1% to 61.2%, in 2019 quarter two (i.e. before the roll-out of the 100-day accelerated TPT intervention) and quarter three (i.e. after the roll-out of the 100-day accelerated TPT intervention) respectively. This increase remained highly significant even after adjusting for patients' baseline characteristics (adjusted prevalence ratio [aPR] = 2.58 [95%CI 2.45, 2.72], P-value<0.001). TPT completion was consistently high at above 70% at most of the time, but, it increased significantly among those initiated during 2018 quarter four and in the subsequent two quarters after the roll-out of the 100-day accelerated TPT intervention (i.e. TPT completion was: 83.2%, 95.3%, and 97.1% among individuals initiated during 2018 quarter4, and 2019 quarters 1 and 2, respectively). The increase in TPT completion during this period remained significant even after adjusting for patients' baseline characteristics (aPR [95%CI] = 1.09 [1.04, 1.14], P value<0.001, and 1.10 [1.05,1.15], P value<0.001, for individuals initiated during 2019 quarter 1, and 2, respectively compared to those initiated during 2018 quarter 4). Not on ART or newly started on ART compared to ART experienced, and pregnant at TPT initiation compared to not pregnant were associated with poor TPT completion, whereas older age (≥25 years versus 15-24 years) was associated with higher TPT completion. The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines. Future analysis with additional years of data post 100-days TPT intervention is required to evaluate the sustainability of the observed gains.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36821550/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36821550</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9949662/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9949662</a> | DOI:<a href=https://doi.org/10.1371/journal.pone.0268935>10.1371/journal.pone.0268935</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36821550</guid>
<pubDate>Thu, 23 Feb 2023 06:00:00 -0500</pubDate>
<dc:creator>Joseph Musaazi</dc:creator>
<dc:creator>Christine Sekaggya-Wiltshire</dc:creator>
<dc:creator>Stephen Okoboi</dc:creator>
<dc:creator>Stella Zawedde-Muyanja</dc:creator>
<dc:creator>Mbazi Senkoro</dc:creator>
<dc:creator>Nelson Kalema</dc:creator>
<dc:creator>Paul Kavuma</dc:creator>
<dc:creator>Proscovia M Namuwenge</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Barbara Castelnuovo</dc:creator>
<dc:creator>Agnes Kiragga</dc:creator>
<dc:date>2023-02-23</dc:date>
<dc:source>PloS one</dc:source>
<dc:title>Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda</dc:title>
<dc:identifier>pmid:36821550</dc:identifier>
<dc:identifier>pmc:PMC9949662</dc:identifier>
<dc:identifier>doi:10.1371/journal.pone.0268935</dc:identifier>
</item>
<item>
<title>Aetiology of hospitalized fever and risk of death at Arua and Mubende tertiary care hospitals in Uganda from August 2019 to August 2020</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36411415/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: In those with hospitalized fever, malaria and tuberculosis were common causes of febrile illness, but most deaths were non-malarial, and most HIV-negative participants did not have a positive diagnostic result. Those with respiratory failure had a high risk of death.</description>
<content:encoded><![CDATA[<div>BMC Infect Dis. 2022 Nov 21;22(1):869. doi: 10.1186/s12879-022-07877-3.ABSTRACTBACKGROUND: Epidemiology of febrile illness in Uganda is shifting due to increased HIV treatment access, emerging viruses, and increased surveillance. We investigated the aetiology and outcomes of acute febrile illness in adults presenting to hospital using a standardized testing algorithm of available assays in at Arua and Mubende tertiary care hospitals in Uganda.METHODS: We recruited adults with a ≥ 38.0 °C temperature or history of fever within 48 h of presentation from August 2019 to August 2020. Medical history, demographics, and vital signs were recorded. Testing performed included a complete blood count, renal and liver function, malaria smears, blood culture, and human immunodeficiency virus (HIV). When HIV positive, testing included cryptococcal antigen, CD4 count, and urine lateral flow lipoarabinomannan assay for tuberculosis. Participants were followed during hospitalization and at a 1-month visit. A Cox proportional hazard regression was performed to evaluate for baseline clinical features and risk of death.RESULTS: Of 132 participants, the median age was 33.5 years (IQR 24 to 46) and 58.3% (n = 77) were female. Overall, 73 (55.3%) of 132 had a positive microbiologic result. Among those living with HIV, 31 (68.9%) of 45 had at least one positive assay; 16 (35.6%) had malaria, 14 (31.1%) tuberculosis, and 4 (8.9%) cryptococcal antigenemia. The majority (65.9%) were HIV-negative; 42 (48.3%) of 87 had at least one diagnostic assay positive; 24 (27.6%) had positive malaria smears and 1 was Xpert MTB/RIF Ultra positive. Overall, 16 (12.1%) of 132 died; 9 (56.3%) of 16 were HIV-negative, 6 died after discharge. High respiratory rate (≥ 22 breaths per minute) (hazard ratio [HR] 8.05; 95% CI 1.81 to 35.69) and low (i.e., < 92%) oxygen saturation (HR 4.33; 95% CI 1.38 to 13.61) were identified to be associated with increased risk of death.CONCLUSION: In those with hospitalized fever, malaria and tuberculosis were common causes of febrile illness, but most deaths were non-malarial, and most HIV-negative participants did not have a positive diagnostic result. Those with respiratory failure had a high risk of death.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36411415/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36411415</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9680122/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9680122</a> | DOI:<a href=https://doi.org/10.1186/s12879-022-07877-3>10.1186/s12879-022-07877-3</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36411415</guid>
<pubDate>Mon, 21 Nov 2022 06:00:00 -0500</pubDate>
<dc:creator>Paul W Blair</dc:creator>
<dc:creator>Kenneth Kobba</dc:creator>
<dc:creator>Francis Kakooza</dc:creator>
<dc:creator>Matthew L Robinson</dc:creator>
<dc:creator>Emmanuel Candia</dc:creator>
<dc:creator>Jonathan Mayito</dc:creator>
<dc:creator>Edgar C Ndawula</dc:creator>
<dc:creator>Abraham J Kandathil</dc:creator>
<dc:creator>Alphonsus Matovu</dc:creator>
<dc:creator>Gilbert Aniku</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Mohammed Lamorde</dc:creator>
<dc:date>2022-11-21</dc:date>
<dc:source>BMC infectious diseases</dc:source>
<dc:title>Aetiology of hospitalized fever and risk of death at Arua and Mubende tertiary care hospitals in Uganda from August 2019 to August 2020</dc:title>
<dc:identifier>pmid:36411415</dc:identifier>
<dc:identifier>pmc:PMC9680122</dc:identifier>
<dc:identifier>doi:10.1186/s12879-022-07877-3</dc:identifier>
</item>
<item>
<title>Cerebral Tuberculoma Diagnosed by Nested Polymerase Chain Reaction of a Formalin-fixed Paraffin-embedded Brain Biopsy Sample</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36328574/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>A 38-year-old man was taken to hospital with generalized clonic seizure. Brain magnetic resonance imaging (MRI) showed multiple ring-enhancing lesions centered in the left frontoparietal lobe. A histopathological examination of a brain biopsy sample revealed granulomatous lesions with caseous necrosis. We extracted DNA from a formalin-fixed paraffin-embedded (FFPE) brain specimen, and nested polymerase chain reaction (PCR) of the DNA sample detected the Mycobacterium tuberculosis-specific...</description>
<content:encoded><![CDATA[<div>Intern Med. 2023 Jun 15;62(12):1827-1833. doi: 10.2169/internalmedicine.0356-22. Epub 2022 Nov 2.ABSTRACTA 38-year-old man was taken to hospital with generalized clonic seizure. Brain magnetic resonance imaging (MRI) showed multiple ring-enhancing lesions centered in the left frontoparietal lobe. A histopathological examination of a brain biopsy sample revealed granulomatous lesions with caseous necrosis. We extracted DNA from a formalin-fixed paraffin-embedded (FFPE) brain specimen, and nested polymerase chain reaction (PCR) of the DNA sample detected the Mycobacterium tuberculosis-specific insertion sequence IS6110. The lesions worsened after anti-tuberculosis drugs were administered, which we considered to be a paradoxical response and continued treatment. A genetic diagnosis of M. tuberculosis using FFPE specimens is useful for diagnosing tuberculoma.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36328574/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36328574</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10332954/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10332954</a> | DOI:<a href=https://doi.org/10.2169/internalmedicine.0356-22>10.2169/internalmedicine.0356-22</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36328574</guid>
<pubDate>Thu, 03 Nov 2022 06:00:00 -0400</pubDate>
<dc:creator>Morihiro Yamamoto</dc:creator>
<dc:creator>Tatsuo Manabe</dc:creator>
<dc:creator>Kazuki Yokokawa</dc:creator>
<dc:creator>Kazufumi Tsuzaka</dc:creator>
<dc:creator>Minoru Yamada</dc:creator>
<dc:creator>Rei Miyanaga</dc:creator>
<dc:creator>Taro Saito</dc:creator>
<dc:creator>Daisuke Yamamoto</dc:creator>
<dc:creator>Akihiro Matsumura</dc:creator>
<dc:creator>Syuuichirou Suzuki</dc:creator>
<dc:creator>Shin Hisahara</dc:creator>
<dc:date>2022-11-03</dc:date>
<dc:source>Internal medicine (Tokyo, Japan)</dc:source>
<dc:title>Cerebral Tuberculoma Diagnosed by Nested Polymerase Chain Reaction of a Formalin-fixed Paraffin-embedded Brain Biopsy Sample</dc:title>
<dc:identifier>pmid:36328574</dc:identifier>
<dc:identifier>pmc:PMC10332954</dc:identifier>
<dc:identifier>doi:10.2169/internalmedicine.0356-22</dc:identifier>
</item>
<item>
<title>Structure-Based Optimization of Coumestan Derivatives as Polyketide Synthase 13-Thioesterase(Pks13-TE) Inhibitors with Improved hERG Profiles for Mycobacterium tuberculosis Treatment</title>
<link>https://pubmed.ncbi.nlm.nih.gov/36174223/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Pks13 was identified as a key enzyme involved in the final step of mycolic acid biosynthesis. We previously identified antitubercular coumestans that targeted Pks13-TE, and these compounds exhibited high potency both in vitro and in vivo. However, lead compound 8 presented potential safety concerns because it inhibits the hERG potassium channel in electrophysiology patch-clamp assays (IC(50) = 0.52 μM). By comparing the Pks13-TE-compound 8 complex and the ligand-binding pocket of the hERG ion...</description>
<content:encoded><![CDATA[<div>J Med Chem. 2022 Oct 13;65(19):13240-13252. doi: 10.1021/acs.jmedchem.2c01064. Epub 2022 Sep 29.ABSTRACTPks13 was identified as a key enzyme involved in the final step of mycolic acid biosynthesis. We previously identified antitubercular coumestans that targeted Pks13-TE, and these compounds exhibited high potency both in vitro and in vivo. However, lead compound 8 presented potential safety concerns because it inhibits the hERG potassium channel in electrophysiology patch-clamp assays (IC50 = 0.52 μM). By comparing the Pks13-TE-compound 8 complex and the ligand-binding pocket of the hERG ion channel, fluoro-substituted and oxazine-containing coumestans were designed and synthesized. Fluoro-substituted compound 23 and oxazine-containing coumestan 32 showed excellent antitubercular activity against both drug-susceptible and drug-resistant Mtb strains (MIC = 0.0039-0.0078 μg/mL) and exhibited limited hERG inhibition (IC50 ≥ 25 μM). Moreover, 32 exhibited improved metabolic stability relative to parent compound 8 while showing favorable bioavailability in mouse models via serum inhibition titration assays.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/36174223/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">36174223</a> | DOI:<a href=https://doi.org/10.1021/acs.jmedchem.2c01064>10.1021/acs.jmedchem.2c01064</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:36174223</guid>
<pubDate>Thu, 29 Sep 2022 06:00:00 -0400</pubDate>
<dc:creator>Wei Zhang</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Shuang-Shuang Wang</dc:creator>
<dc:creator>Yan-Peng Cai</dc:creator>
<dc:creator>Fan Yang</dc:creator>
<dc:creator>Jie Tang</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Li-Fang Yu</dc:creator>
<dc:date>2022-09-29</dc:date>
<dc:source>Journal of medicinal chemistry</dc:source>
<dc:title>Structure-Based Optimization of Coumestan Derivatives as Polyketide Synthase 13-Thioesterase(Pks13-TE) Inhibitors with Improved hERG Profiles for Mycobacterium tuberculosis Treatment</dc:title>
<dc:identifier>pmid:36174223</dc:identifier>
<dc:identifier>doi:10.1021/acs.jmedchem.2c01064</dc:identifier>
</item>
<item>
<title>The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35995775/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases....</description>
<content:encoded><![CDATA[<div>Nat Commun. 2022 Aug 22;13(1):4830. doi: 10.1038/s41467-022-32276-2.ABSTRACTCoronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35995775/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35995775</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9395416/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9395416</a> | DOI:<a href=https://doi.org/10.1038/s41467-022-32276-2>10.1038/s41467-022-32276-2</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35995775</guid>
<pubDate>Mon, 22 Aug 2022 06:00:00 -0400</pubDate>
<dc:creator>Qingbo S Wang</dc:creator>
<dc:creator>Ryuya Edahiro</dc:creator>
<dc:creator>Ho Namkoong</dc:creator>
<dc:creator>Takanori Hasegawa</dc:creator>
<dc:creator>Yuya Shirai</dc:creator>
<dc:creator>Kyuto Sonehara</dc:creator>
<dc:creator>Hiromu Tanaka</dc:creator>
<dc:creator>Ho Lee</dc:creator>
<dc:creator>Ryunosuke Saiki</dc:creator>
<dc:creator>Takayoshi Hyugaji</dc:creator>
<dc:creator>Eigo Shimizu</dc:creator>
<dc:creator>Kotoe Katayama</dc:creator>
<dc:creator>Masahiro Kanai</dc:creator>
<dc:creator>Tatsuhiko Naito</dc:creator>
<dc:creator>Noah Sasa</dc:creator>
<dc:creator>Kenichi Yamamoto</dc:creator>
<dc:creator>Yasuhiro Kato</dc:creator>
<dc:creator>Takayoshi Morita</dc:creator>
<dc:creator>Kazuhisa Takahashi</dc:creator>
<dc:creator>Norihiro Harada</dc:creator>
<dc:creator>Toshio Naito</dc:creator>
<dc:creator>Makoto Hiki</dc:creator>
<dc:creator>Yasushi Matsushita</dc:creator>
<dc:creator>Haruhi Takagi</dc:creator>
<dc:creator>Masako Ichikawa</dc:creator>
<dc:creator>Ai Nakamura</dc:creator>
<dc:creator>Sonoko Harada</dc:creator>
<dc:creator>Yuuki Sandhu</dc:creator>
<dc:creator>Hiroki Kabata</dc:creator>
<dc:creator>Katsunori Masaki</dc:creator>
<dc:creator>Hirofumi Kamata</dc:creator>
<dc:creator>Shinnosuke Ikemura</dc:creator>
<dc:creator>Shotaro Chubachi</dc:creator>
<dc:creator>Satoshi Okamori</dc:creator>
<dc:creator>Hideki Terai</dc:creator>
<dc:creator>Atsuho Morita</dc:creator>
<dc:creator>Takanori Asakura</dc:creator>
<dc:creator>Junichi Sasaki</dc:creator>
<dc:creator>Hiroshi Morisaki</dc:creator>
<dc:creator>Yoshifumi Uwamino</dc:creator>
<dc:creator>Kosaku Nanki</dc:creator>
<dc:creator>Sho Uchida</dc:creator>
<dc:creator>Shunsuke Uno</dc:creator>
<dc:creator>Tomoyasu Nishimura</dc:creator>
<dc:creator>Takashri Ishiguro</dc:creator>
<dc:creator>Taisuke Isono</dc:creator>
<dc:creator>Shun Shibata</dc:creator>
<dc:creator>Yuma Matsui</dc:creator>
<dc:creator>Chiaki Hosoda</dc:creator>
<dc:creator>Kenji Takano</dc:creator>
<dc:creator>Takashi Nishida</dc:creator>
<dc:creator>Yoichi Kobayashi</dc:creator>
<dc:creator>Yotaro Takaku</dc:creator>
<dc:creator>Noboru Takayanagi</dc:creator>
<dc:creator>Soichiro Ueda</dc:creator>
<dc:creator>Ai Tada</dc:creator>
<dc:creator>Masayoshi Miyawaki</dc:creator>
<dc:creator>Masaomi Yamamoto</dc:creator>
<dc:creator>Eriko Yoshida</dc:creator>
<dc:creator>Reina Hayashi</dc:creator>
<dc:creator>Tomoki Nagasaka</dc:creator>
<dc:creator>Sawako Arai</dc:creator>
<dc:creator>Yutaro Kaneko</dc:creator>
<dc:creator>Kana Sasaki</dc:creator>
<dc:creator>Etsuko Tagaya</dc:creator>
<dc:creator>Masatoshi Kawana</dc:creator>
<dc:creator>Ken Arimura</dc:creator>
<dc:creator>Kunihiko Takahashi</dc:creator>
<dc:creator>Tatsuhiko Anzai</dc:creator>
<dc:creator>Satoshi Ito</dc:creator>
<dc:creator>Akifumi Endo</dc:creator>
<dc:creator>Yuji Uchimura</dc:creator>
<dc:creator>Yasunari Miyazaki</dc:creator>
<dc:creator>Takayuki Honda</dc:creator>
<dc:creator>Tomoya Tateishi</dc:creator>
<dc:creator>Shuji Tohda</dc:creator>
<dc:creator>Naoya Ichimura</dc:creator>
<dc:creator>Kazunari Sonobe</dc:creator>
<dc:creator>Chihiro Tani Sassa</dc:creator>
<dc:creator>Jun Nakajima</dc:creator>
<dc:creator>Yasushi Nakano</dc:creator>
<dc:creator>Yukiko Nakajima</dc:creator>
<dc:creator>Ryusuke Anan</dc:creator>
<dc:creator>Ryosuke Arai</dc:creator>
<dc:creator>Yuko Kurihara</dc:creator>
<dc:creator>Yuko Harada</dc:creator>
<dc:creator>Kazumi Nishio</dc:creator>
<dc:creator>Tetsuya Ueda</dc:creator>
<dc:creator>Masanori Azuma</dc:creator>
<dc:creator>Ryuichi Saito</dc:creator>
<dc:creator>Toshikatsu Sado</dc:creator>
<dc:creator>Yoshimune Miyazaki</dc:creator>
<dc:creator>Ryuichi Sato</dc:creator>
<dc:creator>Yuki Haruta</dc:creator>
<dc:creator>Tadao Nagasaki</dc:creator>
<dc:creator>Yoshinori Yasui</dc:creator>
<dc:creator>Yoshinori Hasegawa</dc:creator>
<dc:creator>Yoshikazu Mutoh</dc:creator>
<dc:creator>Tomoki Kimura</dc:creator>
<dc:creator>Tomonori Sato</dc:creator>
<dc:creator>Reoto Takei</dc:creator>
<dc:creator>Satoshi Hagimoto</dc:creator>
<dc:creator>Yoichiro Noguchi</dc:creator>
<dc:creator>Yasuhiko Yamano</dc:creator>
<dc:creator>Hajime Sasano</dc:creator>
<dc:creator>Sho Ota</dc:creator>
<dc:creator>Yasushi Nakamori</dc:creator>
<dc:creator>Kazuhisa Yoshiya</dc:creator>
<dc:creator>Fukuki Saito</dc:creator>
<dc:creator>Tomoyuki Yoshihara</dc:creator>
<dc:creator>Daiki Wada</dc:creator>
<dc:creator>Hiromu Iwamura</dc:creator>
<dc:creator>Syuji Kanayama</dc:creator>
<dc:creator>Shuhei Maruyama</dc:creator>
<dc:creator>Takashi Yoshiyama</dc:creator>
<dc:creator>Ken Ohta</dc:creator>
<dc:creator>Hiroyuki Kokuto</dc:creator>
<dc:creator>Hideo Ogata</dc:creator>
<dc:creator>Yoshiaki Tanaka</dc:creator>
<dc:creator>Kenichi Arakawa</dc:creator>
<dc:creator>Masafumi Shimoda</dc:creator>
<dc:creator>Takeshi Osawa</dc:creator>
<dc:creator>Hiroki Tateno</dc:creator>
<dc:creator>Isano Hase</dc:creator>
<dc:creator>Shuichi Yoshida</dc:creator>
<dc:creator>Shoji Suzuki</dc:creator>
<dc:creator>Miki Kawada</dc:creator>
<dc:creator>Hirohisa Horinouchi</dc:creator>
<dc:creator>Fumitake Saito</dc:creator>
<dc:creator>Keiko Mitamura</dc:creator>
<dc:creator>Masao Hagihara</dc:creator>
<dc:creator>Junichi Ochi</dc:creator>
<dc:creator>Tomoyuki Uchida</dc:creator>
<dc:creator>Rie Baba</dc:creator>
<dc:creator>Daisuke Arai</dc:creator>
<dc:creator>Takayuki Ogura</dc:creator>
<dc:creator>Hidenori Takahashi</dc:creator>
<dc:creator>Shigehiro Hagiwara</dc:creator>
<dc:creator>Genta Nagao</dc:creator>
<dc:creator>Shunichiro Konishi</dc:creator>
<dc:creator>Ichiro Nakachi</dc:creator>
<dc:creator>Koji Murakami</dc:creator>
<dc:creator>Mitsuhiro Yamada</dc:creator>
<dc:creator>Hisatoshi Sugiura</dc:creator>
<dc:creator>Hirohito Sano</dc:creator>
<dc:creator>Shuichiro Matsumoto</dc:creator>
<dc:creator>Nozomu Kimura</dc:creator>
<dc:creator>Yoshinao Ono</dc:creator>
<dc:creator>Hiroaki Baba</dc:creator>
<dc:creator>Yusuke Suzuki</dc:creator>
<dc:creator>Sohei Nakayama</dc:creator>
<dc:creator>Keita Masuzawa</dc:creator>
<dc:creator>Shinichi Namba</dc:creator>
<dc:creator>Takayuki Shiroyama</dc:creator>
<dc:creator>Yoshimi Noda</dc:creator>
<dc:creator>Takayuki Niitsu</dc:creator>
<dc:creator>Yuichi Adachi</dc:creator>
<dc:creator>Takatoshi Enomoto</dc:creator>
<dc:creator>Saori Amiya</dc:creator>
<dc:creator>Reina Hara</dc:creator>
<dc:creator>Yuta Yamaguchi</dc:creator>
<dc:creator>Teruaki Murakami</dc:creator>
<dc:creator>Tomoki Kuge</dc:creator>
<dc:creator>Kinnosuke Matsumoto</dc:creator>
<dc:creator>Yuji Yamamoto</dc:creator>
<dc:creator>Makoto Yamamoto</dc:creator>
<dc:creator>Midori Yoneda</dc:creator>
<dc:creator>Kazunori Tomono</dc:creator>
<dc:creator>Kazuto Kato</dc:creator>
<dc:creator>Haruhiko Hirata</dc:creator>
<dc:creator>Yoshito Takeda</dc:creator>
<dc:creator>Hidefumi Koh</dc:creator>
<dc:creator>Tadashi Manabe</dc:creator>
<dc:creator>Yohei Funatsu</dc:creator>
<dc:creator>Fumimaro Ito</dc:creator>
<dc:creator>Takahiro Fukui</dc:creator>
<dc:creator>Keisuke Shinozuka</dc:creator>
<dc:creator>Sumiko Kohashi</dc:creator>
<dc:creator>Masatoshi Miyazaki</dc:creator>
<dc:creator>Tomohisa Shoko</dc:creator>
<dc:creator>Mitsuaki Kojima</dc:creator>
<dc:creator>Tomohiro Adachi</dc:creator>
<dc:creator>Motonao Ishikawa</dc:creator>
<dc:creator>Kenichiro Takahashi</dc:creator>
<dc:creator>Takashi Inoue</dc:creator>
<dc:creator>Toshiyuki Hirano</dc:creator>
<dc:creator>Keigo Kobayashi</dc:creator>
<dc:creator>Hatsuyo Takaoka</dc:creator>
<dc:creator>Kazuyoshi Watanabe</dc:creator>
<dc:creator>Naoki Miyazawa</dc:creator>
<dc:creator>Yasuhiro Kimura</dc:creator>
<dc:creator>Reiko Sado</dc:creator>
<dc:creator>Hideyasu Sugimoto</dc:creator>
<dc:creator>Akane Kamiya</dc:creator>
<dc:creator>Naota Kuwahara</dc:creator>
<dc:creator>Akiko Fujiwara</dc:creator>
<dc:creator>Tomohiro Matsunaga</dc:creator>
<dc:creator>Yoko Sato</dc:creator>
<dc:creator>Takenori Okada</dc:creator>
<dc:creator>Yoshihiro Hirai</dc:creator>
<dc:creator>Hidetoshi Kawashima</dc:creator>
<dc:creator>Atsuya Narita</dc:creator>
<dc:creator>Kazuki Niwa</dc:creator>
<dc:creator>Yoshiyuki Sekikawa</dc:creator>
<dc:creator>Koichi Nishi</dc:creator>
<dc:creator>Masaru Nishitsuji</dc:creator>
<dc:creator>Mayuko Tani</dc:creator>
<dc:creator>Junya Suzuki</dc:creator>
<dc:creator>Hiroki Nakatsumi</dc:creator>
<dc:creator>Takashi Ogura</dc:creator>
<dc:creator>Hideya Kitamura</dc:creator>
<dc:creator>Eri Hagiwara</dc:creator>
<dc:creator>Kota Murohashi</dc:creator>
<dc:creator>Hiroko Okabayashi</dc:creator>
<dc:creator>Takao Mochimaru</dc:creator>
<dc:creator>Shigenari Nukaga</dc:creator>
<dc:creator>Ryosuke Satomi</dc:creator>
<dc:creator>Yoshitaka Oyamada</dc:creator>
<dc:creator>Nobuaki Mori</dc:creator>
<dc:creator>Tomoya Baba</dc:creator>
<dc:creator>Yasutaka Fukui</dc:creator>
<dc:creator>Mitsuru Odate</dc:creator>
<dc:creator>Shuko Mashimo</dc:creator>
<dc:creator>Yasushi Makino</dc:creator>
<dc:creator>Kazuma Yagi</dc:creator>
<dc:creator>Mizuha Hashiguchi</dc:creator>
<dc:creator>Junko Kagyo</dc:creator>
<dc:creator>Tetsuya Shiomi</dc:creator>
<dc:creator>Satoshi Fuke</dc:creator>
<dc:creator>Hiroshi Saito</dc:creator>
<dc:creator>Tomoya Tsuchida</dc:creator>
<dc:creator>Shigeki Fujitani</dc:creator>
<dc:creator>Mumon Takita</dc:creator>
<dc:creator>Daiki Morikawa</dc:creator>
<dc:creator>Toru Yoshida</dc:creator>
<dc:creator>Takehiro Izumo</dc:creator>
<dc:creator>Minoru Inomata</dc:creator>
<dc:creator>Naoyuki Kuse</dc:creator>
<dc:creator>Nobuyasu Awano</dc:creator>
<dc:creator>Mari Tone</dc:creator>
<dc:creator>Akihiro Ito</dc:creator>
<dc:creator>Yoshihiko Nakamura</dc:creator>
<dc:creator>Kota Hoshino</dc:creator>
<dc:creator>Junichi Maruyama</dc:creator>
<dc:creator>Hiroyasu Ishikura</dc:creator>
<dc:creator>Tohru Takata</dc:creator>
<dc:creator>Toshio Odani</dc:creator>
<dc:creator>Masaru Amishima</dc:creator>
<dc:creator>Takeshi Hattori</dc:creator>
<dc:creator>Yasuo Shichinohe</dc:creator>
<dc:creator>Takashi Kagaya</dc:creator>
<dc:creator>Toshiyuki Kita</dc:creator>
<dc:creator>Kazuhide Ohta</dc:creator>
<dc:creator>Satoru Sakagami</dc:creator>
<dc:creator>Kiyoshi Koshida</dc:creator>
<dc:creator>Kentaro Hayashi</dc:creator>
<dc:creator>Tetsuo Shimizu</dc:creator>
<dc:creator>Yutaka Kozu</dc:creator>
<dc:creator>Hisato Hiranuma</dc:creator>
<dc:creator>Yasuhiro Gon</dc:creator>
<dc:creator>Namiki Izumi</dc:creator>
<dc:creator>Kaoru Nagata</dc:creator>
<dc:creator>Ken Ueda</dc:creator>
<dc:creator>Reiko Taki</dc:creator>
<dc:creator>Satoko Hanada</dc:creator>
<dc:creator>Kodai Kawamura</dc:creator>
<dc:creator>Kazuya Ichikado</dc:creator>
<dc:creator>Kenta Nishiyama</dc:creator>
<dc:creator>Hiroyuki Muranaka</dc:creator>
<dc:creator>Kazunori Nakamura</dc:creator>
<dc:creator>Naozumi Hashimoto</dc:creator>
<dc:creator>Keiko Wakahara</dc:creator>
<dc:creator>Sakamoto Koji</dc:creator>
<dc:creator>Norihito Omote</dc:creator>
<dc:creator>Akira Ando</dc:creator>
<dc:creator>Nobuhiro Kodama</dc:creator>
<dc:creator>Yasunari Kaneyama</dc:creator>
<dc:creator>Shunsuke Maeda</dc:creator>
<dc:creator>Takashige Kuraki</dc:creator>
<dc:creator>Takemasa Matsumoto</dc:creator>
<dc:creator>Koutaro Yokote</dc:creator>
<dc:creator>Taka-Aki Nakada</dc:creator>
<dc:creator>Ryuzo Abe</dc:creator>
<dc:creator>Taku Oshima</dc:creator>
<dc:creator>Tadanaga Shimada</dc:creator>
<dc:creator>Masahiro Harada</dc:creator>
<dc:creator>Takeshi Takahashi</dc:creator>
<dc:creator>Hiroshi Ono</dc:creator>
<dc:creator>Toshihiro Sakurai</dc:creator>
<dc:creator>Takayuki Shibusawa</dc:creator>
<dc:creator>Yoshifumi Kimizuka</dc:creator>
<dc:creator>Akihiko Kawana</dc:creator>
<dc:creator>Tomoya Sano</dc:creator>
<dc:creator>Chie Watanabe</dc:creator>
<dc:creator>Ryohei Suematsu</dc:creator>
<dc:creator>Hisako Sageshima</dc:creator>
<dc:creator>Ayumi Yoshifuji</dc:creator>
<dc:creator>Kazuto Ito</dc:creator>
<dc:creator>Saeko Takahashi</dc:creator>
<dc:creator>Kota Ishioka</dc:creator>
<dc:creator>Morio Nakamura</dc:creator>
<dc:creator>Makoto Masuda</dc:creator>
<dc:creator>Aya Wakabayashi</dc:creator>
<dc:creator>Hiroki Watanabe</dc:creator>
<dc:creator>Suguru Ueda</dc:creator>
<dc:creator>Masanori Nishikawa</dc:creator>
<dc:creator>Yusuke Chihara</dc:creator>
<dc:creator>Mayumi Takeuchi</dc:creator>
<dc:creator>Keisuke Onoi</dc:creator>
<dc:creator>Jun Shinozuka</dc:creator>
<dc:creator>Atsushi Sueyoshi</dc:creator>
<dc:creator>Yoji Nagasaki</dc:creator>
<dc:creator>Masaki Okamoto</dc:creator>
<dc:creator>Sayoko Ishihara</dc:creator>
<dc:creator>Masatoshi Shimo</dc:creator>
<dc:creator>Yoshihisa Tokunaga</dc:creator>
<dc:creator>Yu Kusaka</dc:creator>
<dc:creator>Takehiko Ohba</dc:creator>
<dc:creator>Susumu Isogai</dc:creator>
<dc:creator>Aki Ogawa</dc:creator>
<dc:creator>Takuya Inoue</dc:creator>
<dc:creator>Satoru Fukuyama</dc:creator>
<dc:creator>Yoshihiro Eriguchi</dc:creator>
<dc:creator>Akiko Yonekawa</dc:creator>
<dc:creator>Keiko Kan-O</dc:creator>
<dc:creator>Koichiro Matsumoto</dc:creator>
<dc:creator>Kensuke Kanaoka</dc:creator>
<dc:creator>Shoichi Ihara</dc:creator>
<dc:creator>Kiyoshi Komuta</dc:creator>
<dc:creator>Yoshiaki Inoue</dc:creator>
<dc:creator>Shigeru Chiba</dc:creator>
<dc:creator>Kunihiro Yamagata</dc:creator>
<dc:creator>Yuji Hiramatsu</dc:creator>
<dc:creator>Hirayasu Kai</dc:creator>
<dc:creator>Koichiro Asano</dc:creator>
<dc:creator>Tsuyoshi Oguma</dc:creator>
<dc:creator>Yoko Ito</dc:creator>
<dc:creator>Satoru Hashimoto</dc:creator>
<dc:creator>Masaki Yamasaki</dc:creator>
<dc:creator>Yu Kasamatsu</dc:creator>
<dc:creator>Yuko Komase</dc:creator>
<dc:creator>Naoya Hida</dc:creator>
<dc:creator>Takahiro Tsuburai</dc:creator>
<dc:creator>Baku Oyama</dc:creator>
<dc:creator>Minoru Takada</dc:creator>
<dc:creator>Hidenori Kanda</dc:creator>
<dc:creator>Yuichiro Kitagawa</dc:creator>
<dc:creator>Tetsuya Fukuta</dc:creator>
<dc:creator>Takahito Miyake</dc:creator>
<dc:creator>Shozo Yoshida</dc:creator>
<dc:creator>Shinji Ogura</dc:creator>
<dc:creator>Shinji Abe</dc:creator>
<dc:creator>Yuta Kono</dc:creator>
<dc:creator>Yuki Togashi</dc:creator>
<dc:creator>Hiroyuki Takoi</dc:creator>
<dc:creator>Ryota Kikuchi</dc:creator>
<dc:creator>Shinichi Ogawa</dc:creator>
<dc:creator>Tomouki Ogata</dc:creator>
<dc:creator>Shoichiro Ishihara</dc:creator>
<dc:creator>Arihiko Kanehiro</dc:creator>
<dc:creator>Shinji Ozaki</dc:creator>
<dc:creator>Yasuko Fuchimoto</dc:creator>
<dc:creator>Sae Wada</dc:creator>
<dc:creator>Nobukazu Fujimoto</dc:creator>
<dc:creator>Kei Nishiyama</dc:creator>
<dc:creator>Mariko Terashima</dc:creator>
<dc:creator>Satoru Beppu</dc:creator>
<dc:creator>Kosuke Yoshida</dc:creator>
<dc:creator>Osamu Narumoto</dc:creator>
<dc:creator>Hideaki Nagai</dc:creator>
<dc:creator>Nobuharu Ooshima</dc:creator>
<dc:creator>Mitsuru Motegi</dc:creator>
<dc:creator>Akira Umeda</dc:creator>
<dc:creator>Kazuya Miyagawa</dc:creator>
<dc:creator>Hisato Shimada</dc:creator>
<dc:creator>Mayu Endo</dc:creator>
<dc:creator>Yoshiyuki Ohira</dc:creator>
<dc:creator>Masafumi Watanabe</dc:creator>
<dc:creator>Sumito Inoue</dc:creator>
<dc:creator>Akira Igarashi</dc:creator>
<dc:creator>Masamichi Sato</dc:creator>
<dc:creator>Hironori Sagara</dc:creator>
<dc:creator>Akihiko Tanaka</dc:creator>
<dc:creator>Shin Ohta</dc:creator>
<dc:creator>Tomoyuki Kimura</dc:creator>
<dc:creator>Yoko Shibata</dc:creator>
<dc:creator>Yoshinori Tanino</dc:creator>
<dc:creator>Takefumi Nikaido</dc:creator>
<dc:creator>Hiroyuki Minemura</dc:creator>
<dc:creator>Yuki Sato</dc:creator>
<dc:creator>Yuichiro Yamada</dc:creator>
<dc:creator>Takuya Hashino</dc:creator>
<dc:creator>Masato Shinoki</dc:creator>
<dc:creator>Hajime Iwagoe</dc:creator>
<dc:creator>Hiroshi Takahashi</dc:creator>
<dc:creator>Kazuhiko Fujii</dc:creator>
<dc:creator>Hiroto Kishi</dc:creator>
<dc:creator>Masayuki Kanai</dc:creator>
<dc:creator>Tomonori Imamura</dc:creator>
<dc:creator>Tatsuya Yamashita</dc:creator>
<dc:creator>Masakiyo Yatomi</dc:creator>
<dc:creator>Toshitaka Maeno</dc:creator>
<dc:creator>Shinichi Hayashi</dc:creator>
<dc:creator>Mai Takahashi</dc:creator>
<dc:creator>Mizuki Kuramochi</dc:creator>
<dc:creator>Isamu Kamimaki</dc:creator>
<dc:creator>Yoshiteru Tominaga</dc:creator>
<dc:creator>Tomoo Ishii</dc:creator>
<dc:creator>Mitsuyoshi Utsugi</dc:creator>
<dc:creator>Akihiro Ono</dc:creator>
<dc:creator>Toru Tanaka</dc:creator>
<dc:creator>Takeru Kashiwada</dc:creator>
<dc:creator>Kazue Fujita</dc:creator>
<dc:creator>Yoshinobu Saito</dc:creator>
<dc:creator>Masahiro Seike</dc:creator>
<dc:creator>Hiroko Watanabe</dc:creator>
<dc:creator>Hiroto Matsuse</dc:creator>
<dc:creator>Norio Kodaka</dc:creator>
<dc:creator>Chihiro Nakano</dc:creator>
<dc:creator>Takeshi Oshio</dc:creator>
<dc:creator>Takatomo Hirouchi</dc:creator>
<dc:creator>Shohei Makino</dc:creator>
<dc:creator>Moritoki Egi</dc:creator>
<dc:creator>Yosuke Omae</dc:creator>
<dc:creator>Yasuhito Nannya</dc:creator>
<dc:creator>Takafumi Ueno</dc:creator>
<dc:creator>Tomomi Takano</dc:creator>
<dc:creator>Kazuhiko Katayama</dc:creator>
<dc:creator>Masumi Ai</dc:creator>
<dc:creator>Atsushi Kumanogoh</dc:creator>
<dc:creator>Toshiro Sato</dc:creator>
<dc:creator>Naoki Hasegawa</dc:creator>
<dc:creator>Katsushi Tokunaga</dc:creator>
<dc:creator>Makoto Ishii</dc:creator>
<dc:creator>Ryuji Koike</dc:creator>
<dc:creator>Yuko Kitagawa</dc:creator>
<dc:creator>Akinori Kimura</dc:creator>
<dc:creator>Seiya Imoto</dc:creator>
<dc:creator>Satoru Miyano</dc:creator>
<dc:creator>Seishi Ogawa</dc:creator>
<dc:creator>Takanori Kanai</dc:creator>
<dc:creator>Koichi Fukunaga</dc:creator>
<dc:creator>Yukinori Okada</dc:creator>
<dc:date>2022-08-22</dc:date>
<dc:source>Nature communications</dc:source>
<dc:title>The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force</dc:title>
<dc:identifier>pmid:35995775</dc:identifier>
<dc:identifier>pmc:PMC9395416</dc:identifier>
<dc:identifier>doi:10.1038/s41467-022-32276-2</dc:identifier>
</item>
<item>
<title>Sex Differences in Active Pulmonary Tuberculosis Outcomes in Mali, West Africa</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35895582/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly...</description>
<content:encoded><![CDATA[<div>Am J Trop Med Hyg. 2022 Jun 13;107(2):433-440. doi: 10.4269/ajtmh.21-1141. Print 2022 Aug 17.ABSTRACTMen and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients' sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35895582/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35895582</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9393465/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9393465</a> | DOI:<a href=https://doi.org/10.4269/ajtmh.21-1141>10.4269/ajtmh.21-1141</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35895582</guid>
<pubDate>Wed, 27 Jul 2022 06:00:00 -0400</pubDate>
<dc:creator>Djeneba Dabitao</dc:creator>
<dc:creator>Amadou Somboro</dc:creator>
<dc:creator>Ibrahim Sanogo</dc:creator>
<dc:creator>Bassirou Diarra</dc:creator>
<dc:creator>Chad J Achenbach</dc:creator>
<dc:creator>Jane L Holl</dc:creator>
<dc:creator>Bocar Baya</dc:creator>
<dc:creator>Moumine Sanogo</dc:creator>
<dc:creator>Mamadou Wague</dc:creator>
<dc:creator>Nadie Coulibaly</dc:creator>
<dc:creator>Mahamadou Kone</dc:creator>
<dc:creator>Hawa Baye Drame</dc:creator>
<dc:creator>Mohamed Tolofoudie</dc:creator>
<dc:creator>Bourahima Kone</dc:creator>
<dc:creator>Ayouba Diarra</dc:creator>
<dc:creator>Mamadou D Coulibaly</dc:creator>
<dc:creator>Kathryn Saliba-Shaw</dc:creator>
<dc:creator>Yacouba Toloba</dc:creator>
<dc:creator>Mahamadou Diakite</dc:creator>
<dc:creator>Seydou Doumbia</dc:creator>
<dc:creator>Sabra L Klein</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Souleymane Diallo</dc:creator>
<dc:creator>Robert L Murphy</dc:creator>
<dc:date>2022-07-27</dc:date>
<dc:source>The American journal of tropical medicine and hygiene</dc:source>
<dc:title>Sex Differences in Active Pulmonary Tuberculosis Outcomes in Mali, West Africa</dc:title>
<dc:identifier>pmid:35895582</dc:identifier>
<dc:identifier>pmc:PMC9393465</dc:identifier>
<dc:identifier>doi:10.4269/ajtmh.21-1141</dc:identifier>
</item>
<item>
<title>The contribution of late HIV diagnosis on the occurrence of HIV-associated tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35848588/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry.</description>
<content:encoded><![CDATA[<div>AIDS. 2022 Nov 15;36(14):2005-2013. doi: 10.1097/QAD.0000000000003321. Epub 2022 Jul 15.ABSTRACTOBJECTIVES: To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials.DESIGN: We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk.METHODS: People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy. The risk of TB was compared in LP (accessing care with CD4 + cell count ≤350 cells/μl) vs. nonlate presentation using survival curves and a weighted Cox regression. We emulated two strategies: initiating ART with CD4 + cell count less than 350 cells/μl vs. CD4 + cell count at least 350 cells/μl (late initiation). We estimated TB attributable risk and population attributable fraction up to 5 years from the emulated date of randomization.RESULTS: Twenty thousand one hundred and twelve patients and 1936 TB cases were recorded. Over 50% of TB cases were diagnosed at presentation for HIV care. More than 50% of the incident cases of TB after ART initiation were attributable to late presentation; nearly 70% of TB cases during the first year of follow-up could be attributed to late presentation and more than 50%, 5 years after first attending HIV care.CONCLUSION: Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35848588/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35848588</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC10421563/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC10421563</a> | DOI:<a href=https://doi.org/10.1097/QAD.0000000000003321>10.1097/QAD.0000000000003321</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35848588</guid>
<pubDate>Mon, 18 Jul 2022 06:00:00 -0400</pubDate>
<dc:creator>Enrico Girardi</dc:creator>
<dc:creator>Yanink Caro-Vega</dc:creator>
<dc:creator>Alessandro Cozzi-Lepri</dc:creator>
<dc:creator>Joseph Musaazi</dc:creator>
<dc:creator>Gabriela Carriquiry</dc:creator>
<dc:creator>Barbara Castelnuovo</dc:creator>
<dc:creator>Andrea Gori</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>José Eduardo Gotuzzo</dc:creator>
<dc:creator>Antonella D'arminio Monforte</dc:creator>
<dc:creator>Brenda Crabtree-Ramírez</dc:creator>
<dc:creator>Cristina Mussini</dc:creator>
<dc:date>2022-07-18</dc:date>
<dc:source>AIDS (London, England)</dc:source>
<dc:title>The contribution of late HIV diagnosis on the occurrence of HIV-associated tuberculosis</dc:title>
<dc:identifier>pmid:35848588</dc:identifier>
<dc:identifier>pmc:PMC10421563</dc:identifier>
<dc:identifier>doi:10.1097/QAD.0000000000003321</dc:identifier>
</item>
<item>
<title>Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35842266/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune...</description>
<content:encoded><![CDATA[<div>Trends Immunol. 2022 Aug;43(8):640-656. doi: 10.1016/j.it.2022.06.004. Epub 2022 Jul 13.ABSTRACTTuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35842266/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35842266</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9344469/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9344469</a> | DOI:<a href=https://doi.org/10.1016/j.it.2022.06.004>10.1016/j.it.2022.06.004</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35842266</guid>
<pubDate>Sat, 16 Jul 2022 06:00:00 -0400</pubDate>
<dc:creator>Manish Gupta</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Sabra L Klein</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2022-07-16</dc:date>
<dc:source>Trends in immunology</dc:source>
<dc:title>Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis</dc:title>
<dc:identifier>pmid:35842266</dc:identifier>
<dc:identifier>pmc:PMC9344469</dc:identifier>
<dc:identifier>doi:10.1016/j.it.2022.06.004</dc:identifier>
</item>
<item>
<title>Patient and health system level barriers to and facilitators for tuberculosis treatment initiation in Uganda: a qualitative study</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35764982/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: We found that barriers to treatment initiation existed at both the patient and health facility-level across all levels of the (Capability, Opportunity and Motivation) model. The intervention functions identified here should be tested for feasibility.</description>
<content:encoded><![CDATA[<div>BMC Health Serv Res. 2022 Jun 28;22(1):831. doi: 10.1186/s12913-022-08213-w.ABSTRACTBACKGROUND: The WHO END TB strategy targets to place at least 90% of all patients diagnosed with Tuberculosis (TB) on appropriate treatment. In Uganda, approximately 20% of patients diagnosed with TB are not initiated on TB treatment. We sought to identify the patient and health system level barriers to and facilitators for TB treatment initiation in Uganda.METHODS: We conducted the study at ten public health facilities (three primary care, four district and three tertiary referral hospitals). We carried out in-depth interviews with patients diagnosed with TB and key informant interviews with health managers. In addition, we held focus group discussions with healthcare workers involved in TB care. Data collection and thematic analysis of transcripts was informed by the Capability, Opportunity, Motivation and Behavior (COM-B) model. We identified relevant intervention functions using the Behavior Change Wheel.RESULTS: We interviewed 79 respondents (31 patients, 10 health managers and 38 healthcare workers). Common barriers at the health facility level included; lack of knowledge about the proportion of patients not initiated on TB treatment (psychological capability); difficulty accessing sputum results from the laboratory as well as difficulty tracing patients due to inadequate recording of patient addresses (physical opportunity). At the patient level, notable barriers included long turnaround time for sputum results and lack of transport funds to return to health facilities (physical opportunity); limited TB knowledge (psychological capability) and stigma (social opportunity). The most important facilitators identified were quick access to sputum test results either on the date of first visit (same-day diagnosis) or on the date of first return and availability of TB treatment (physical opportunity). We identified education, restructuring of the service environment to improve sputum results turnaround time and enablement to improve communication of test results as relevant intervention functions to alleviate these barriers to and enhance facilitators for TB treatment initiation.CONCLUSION: We found that barriers to treatment initiation existed at both the patient and health facility-level across all levels of the (Capability, Opportunity and Motivation) model. The intervention functions identified here should be tested for feasibility.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35764982/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35764982</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9513807/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9513807</a> | DOI:<a href=https://doi.org/10.1186/s12913-022-08213-w>10.1186/s12913-022-08213-w</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35764982</guid>
<pubDate>Tue, 28 Jun 2022 06:00:00 -0400</pubDate>
<dc:creator>Stella Zawedde-Muyanja</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Adithya Cattamanchi</dc:creator>
<dc:creator>Barbara Castelnuovo</dc:creator>
<dc:creator>Achilles Katamba</dc:creator>
<dc:date>2022-06-28</dc:date>
<dc:source>BMC health services research</dc:source>
<dc:title>Patient and health system level barriers to and facilitators for tuberculosis treatment initiation in Uganda: a qualitative study</dc:title>
<dc:identifier>pmid:35764982</dc:identifier>
<dc:identifier>pmc:PMC9513807</dc:identifier>
<dc:identifier>doi:10.1186/s12913-022-08213-w</dc:identifier>
</item>
<item>
<title>Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35714072/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: The multifaceted intervention was feasible and resulted in a higher proportion of patients initiating TB treatment within two weeks of diagnosis.</description>
<content:encoded><![CDATA[<div>PLoS One. 2022 Jun 17;17(6):e0265035. doi: 10.1371/journal.pone.0265035. eCollection 2022.ABSTRACTBACKGROUND: One in five patients diagnosed with TB in Uganda are not initiated on TB treatment within two weeks of diagnosis. We evaluated a multifaceted intervention for improving TB treatment initiation among patients diagnosed with TB using Xpert® MTB/RIF testing in Uganda.METHODS: This was a pre-post interventional study at one tertiary referral hospital. The intervention was informed by the COM-B model and included; i) medical education sessions to improve healthcare worker knowledge about the magnitude and consequences of pretreatment loss to follow-up; ii) modified laboratory request forms to improve recording of patient contact information; and iii) re-designed workflow processes to improve timeliness of sputum testing and results dissemination. TB diagnostic process and outcome data were collected and compared from the period before (June to August 2019) and after (October to December 2019) intervention initiation.RESULTS: In September 2019, four CME sessions were held at the hospital and were attended by 58 healthcare workers. During the study period, 1242 patients were evaluated by Xpert® MTB/RIF testing at the hospital (679 pre and 557 post intervention). Median turnaround time for sputum test results improved from 12 hours (IQR 4-46) in the pre-intervention period to 4 hours (IQR 3-6) in the post-intervention period. The proportion of patients started on treatment within two weeks of diagnosis improved from 59% (40/68) to 89% (49/55) (difference 30%, 95% CI 14%-43%, p<0.01) while the proportion of patients receiving a same-day diagnosis increased from 7.4% (5/68) to 25% (14/55) (difference 17.6%, 95% CI 3.9%-32.7%, p<0.01).CONCLUSION: The multifaceted intervention was feasible and resulted in a higher proportion of patients initiating TB treatment within two weeks of diagnosis.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35714072/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35714072</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9491700/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9491700</a> | DOI:<a href=https://doi.org/10.1371/journal.pone.0265035>10.1371/journal.pone.0265035</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35714072</guid>
<pubDate>Fri, 17 Jun 2022 06:00:00 -0400</pubDate>
<dc:creator>Stella Zawedde-Muyanja</dc:creator>
<dc:creator>Joseph Musaazi</dc:creator>
<dc:creator>Barbara Castelnuovo</dc:creator>
<dc:creator>Adithya Cattamanchi</dc:creator>
<dc:creator>Achilles Katamba</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:date>2022-06-17</dc:date>
<dc:source>PloS one</dc:source>
<dc:title>Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda</dc:title>
<dc:identifier>pmid:35714072</dc:identifier>
<dc:identifier>pmc:PMC9491700</dc:identifier>
<dc:identifier>doi:10.1371/journal.pone.0265035</dc:identifier>
</item>
<item>
<title>Design, Synthesis and Biological Evaluation of N-phenylindole Derivatives as Pks13 Inhibitors againstMycobacterium tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35566191/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Polyketide synthase 13 (Pks13), an essential enzyme for the survival of Mycobacterium tuberculosis (Mtb), is an attractive target for new anti-TB agents. In our previous work, we have identified 2-phenylindole derivatives against Mtb. The crystallography studies demonstrated that the two-position phenol was solvent-exposed in the Pks13-TE crystal structure and a crucial hydrogen bond was lost while introducing bulkier hydrophobic groups at indole N moieties. Thirty-six N-phenylindole derivatives...</description>
<content:encoded><![CDATA[<div>Molecules. 2022 Apr 29;27(9):2844. doi: 10.3390/molecules27092844.ABSTRACTPolyketide synthase 13 (Pks13), an essential enzyme for the survival of Mycobacterium tuberculosis (Mtb), is an attractive target for new anti-TB agents. In our previous work, we have identified 2-phenylindole derivatives against Mtb. The crystallography studies demonstrated that the two-position phenol was solvent-exposed in the Pks13-TE crystal structure and a crucial hydrogen bond was lost while introducing bulkier hydrophobic groups at indole N moieties. Thirty-six N-phenylindole derivatives were synthesized and evaluated for antitubercular activity using a structure-guided approach. The structure-activity relationship (SAR) studies resulted in the discovery of the potent Compounds 45 and 58 against Mtb H37Rv, with an MIC value of 0.0625 μg/mL and 0.125 μg/mL, respectively. The thermal stability analysis showed that they bind with high affinity to the Pks13-TE domain. Preliminary ADME evaluation showed that Compound 58 displayed modest human microsomal stability. This report further validates that targeting Pks13 is a valid strategy for the inhibition of Mtb and provides a novel scaffold for developing leading anti-TB compounds.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35566191/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35566191</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9106008/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9106008</a> | DOI:<a href=https://doi.org/10.3390/molecules27092844>10.3390/molecules27092844</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35566191</guid>
<pubDate>Sat, 14 May 2022 06:00:00 -0400</pubDate>
<dc:creator>Yanpeng Cai</dc:creator>
<dc:creator>Wei Zhang</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Tongtong Zhu</dc:creator>
<dc:creator>Weijun Xu</dc:creator>
<dc:creator>Fan Yang</dc:creator>
<dc:creator>Jie Tang</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Lifang Yu</dc:creator>
<dc:date>2022-05-14</dc:date>
<dc:source>Molecules (Basel, Switzerland)</dc:source>
<dc:title>Design, Synthesis and Biological Evaluation of N-phenylindole Derivatives as Pks13 Inhibitors againstMycobacterium tuberculosis</dc:title>
<dc:identifier>pmid:35566191</dc:identifier>
<dc:identifier>pmc:PMC9106008</dc:identifier>
<dc:identifier>doi:10.3390/molecules27092844</dc:identifier>
</item>
<item>
<title>District-level religious composition and child health in India</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35550656/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSIONS: Households residing where there are higher levels of religious minorities in India experience worse child survival. These effects are not mediated by the household's own religious affiliation. There is evidence that health system performance and quality is systematically worse in communities with higher proportions of religious minorities. Our study can help policymakers identify communities where children may be at higher risk based on community heterogeneity and the potential for...</description>
<content:encoded><![CDATA[<div>J Health Popul Nutr. 2022 May 12;41(1):19. doi: 10.1186/s41043-022-00298-7.ABSTRACTBACKGROUND: Community characteristics are a significant social determinant of child health. Little is known about the effects of social heterogeneity as a specific factor that might impact health. This paper aims to fill the void in research on the health effects of India's district-level religious heterogeneity.METHODS: Weighted state fixed effects multivariate logistic regression was applied to India's Third District Level Household Survey (2007-2008). The dependent variables were death of a child under five and indicators of healthcare utilization. The key independent variables were the proportions in the district who were Hindu, Muslim, Christian, Buddhist, and Sikh. The analysis controlled for generic community diversity, household religion, and socioeconomic status. Separate, sub-group analysis focused on Muslims only, Christians only, and Buddhists only.RESULTS: Multivariate fixed effects models show that a 1% point increase in the proportion of Muslim, Christian, or Buddhist households in a community is associated with respective odds ratios of child death of 1.008, 1.009, and 1.012 of experiencing the death of a child. The impact of a household's own religious affiliation is statistically insignificant in these models. Higher proportions of Muslims and Christians in a community lower the odds of BCG (a vaccine for childhood tuberculosis) receipt and child healthcare-seeking.CONCLUSIONS: Households residing where there are higher levels of religious minorities in India experience worse child survival. These effects are not mediated by the household's own religious affiliation. There is evidence that health system performance and quality is systematically worse in communities with higher proportions of religious minorities. Our study can help policymakers identify communities where children may be at higher risk based on community heterogeneity and the potential for insufficient collective action. Policymakers might consider flagging these communities for special attention, because social heterogeneity is likely to be of long duration.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35550656/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35550656</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9102242/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9102242</a> | DOI:<a href=https://doi.org/10.1186/s41043-022-00298-7>10.1186/s41043-022-00298-7</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35550656</guid>
<pubDate>Fri, 13 May 2022 06:00:00 -0400</pubDate>
<dc:creator>Bailey Richards</dc:creator>
<dc:creator>Krishna Rao</dc:creator>
<dc:creator>David Bishai</dc:creator>
<dc:date>2022-05-13</dc:date>
<dc:source>Journal of health, population, and nutrition</dc:source>
<dc:title>District-level religious composition and child health in India</dc:title>
<dc:identifier>pmid:35550656</dc:identifier>
<dc:identifier>pmc:PMC9102242</dc:identifier>
<dc:identifier>doi:10.1186/s41043-022-00298-7</dc:identifier>
</item>
<item>
<title>Design, synthesis and evaluation of novel indole-2-carboxamides for growth inhibition of Mycobacterium tuberculosis and paediatric brain tumour cells</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35481189/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>The omnipresent threat of tuberculosis (TB) and the scant treatment options thereof necessitate the development of new antitubercular agents, preferably working via a novel mechanism of action distinct from the current drugs. Various studies identified the mycobacterial membrane protein large 3 transporter (MmpL3) as the target of several classes of compounds, including the indole-2-caboxamides. Herein, several indoleamide analogues were rationally designed, synthesised, and evaluated for their...</description>
<content:encoded><![CDATA[<div>RSC Adv. 2021 Apr 26;11(26):15497-15511. doi: 10.1039/d0ra10728j. eCollection 2021 Apr 26.ABSTRACTThe omnipresent threat of tuberculosis (TB) and the scant treatment options thereof necessitate the development of new antitubercular agents, preferably working via a novel mechanism of action distinct from the current drugs. Various studies identified the mycobacterial membrane protein large 3 transporter (MmpL3) as the target of several classes of compounds, including the indole-2-caboxamides. Herein, several indoleamide analogues were rationally designed, synthesised, and evaluated for their antitubercular and antitumour activities. Compound 8g displayed the highest activity (MIC = 0.32 μM) against the drug-sensitive (DS) Mycobacterium tuberculosis (M. tb) H37Rv strain. This compound also exhibited high selective activity towards M. tb over mammalian cells [IC50 (Vero cells) = 40.9 μM, SI = 128], suggesting its minimal cytotoxicity. In addition, when docked into the MmpL3 active site, 8g adopted a binding profile similar to the indoleamide ligand ICA38. A related compound 8f showed dual antitubercular (MIC = 0.62 μM) and cytotoxic activities against paediatric glioblastoma multiforme (GBM) cell line KNS42 [IC50 (viability) = 0.84 μM]. Compound 8f also showed poor cytotoxic activity against healthy Vero cells (IC50 = 39.9 μM). Compounds 9a and 15, which were inactive against M. tb, showed potent cytotoxic (IC50 = 8.25 and 5.04 μM, respectively) and antiproliferative activities (IC50 = 9.85 and 6.62 μM, respectively) against KNS42 cells. Transcriptional analysis of KNS42 cells treated with compound 15 revealed a significant downregulation in the expression of the carbonic anhydrase 9 (CA9) and the spleen tyrosine kinase (SYK) genes. The expression levels of these genes in GBM tumours were previously shown to contribute to tumour progression, suggesting their involvement in our observed antitumour activities. Compounds 9a and 15 were selected for further evaluations against three different paediatric brain tumour cell lines (BT12, BT16 and DAOY) and non-neoplastic human fibroblast cells HFF1. Compound 9a showed remarkable cytotoxic (IC50 = 0.89 and 1.81 μM, respectively) and antiproliferative activities (IC50 = 7.44 and 6.06 μM, respectively) against the two tested atypical teratoid/rhabdoid tumour (AT/RT) cells BT12 and BT16. Interestingly, compound 9a was not cytotoxic when tested against non-neoplastic HFF1 cells [IC50 (viability) = 119 μM]. This suggests that an indoleamide scaffold can be fine-tuned to confer a set of derivatives with selective antitubercular and/or antitumour activities.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35481189/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35481189</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9029315/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9029315</a> | DOI:<a href=https://doi.org/10.1039/d0ra10728j>10.1039/d0ra10728j</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35481189</guid>
<pubDate>Thu, 28 Apr 2022 06:00:00 -0400</pubDate>
<dc:creator>Shahinda S R Alsayed</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Anders W Bailey</dc:creator>
<dc:creator>Amreena Suri</dc:creator>
<dc:creator>Chiang-Ching Huang</dc:creator>
<dc:creator>Mauro Mocerino</dc:creator>
<dc:creator>Alan Payne</dc:creator>
<dc:creator>Simone Treiger Sredni</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Hendra Gunosewoyo</dc:creator>
<dc:date>2022-04-28</dc:date>
<dc:source>RSC advances</dc:source>
<dc:title>Design, synthesis and evaluation of novel indole-2-carboxamides for growth inhibition of Mycobacterium tuberculosis and paediatric brain tumour cells</dc:title>
<dc:identifier>pmid:35481189</dc:identifier>
<dc:identifier>pmc:PMC9029315</dc:identifier>
<dc:identifier>doi:10.1039/d0ra10728j</dc:identifier>
</item>
<item>
<title>Allosteric cooperation in β-lactam binding to a non-classical transpeptidase</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35475970/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>L,D-transpeptidase function predominates in atypical 3 → 3 transpeptide networking of peptidoglycan (PG) layer in Mycobacterium tuberculosis. Prior studies of L,D-transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or β-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by β-lactams. Here, we report identification of an allosteric site at a distance of 21 Å from the catalytic site that binds the...</description>
<content:encoded><![CDATA[<div>Elife. 2022 Apr 27;11:e73055. doi: 10.7554/eLife.73055.ABSTRACTL,D-transpeptidase function predominates in atypical 3 → 3 transpeptide networking of peptidoglycan (PG) layer in Mycobacterium tuberculosis. Prior studies of L,D-transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or β-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by β-lactams. Here, we report identification of an allosteric site at a distance of 21 Å from the catalytic site that binds the sugar moiety of PG substrates (hereafter referred to as the S-pocket). This site also binds a second β-lactam molecule and influences binding at the catalytic site. We provide evidence that two β-lactam molecules bind co-operatively to this enzyme, one non-covalently at the S-pocket and one covalently at the catalytic site. This dual β-lactam-binding phenomenon is previously unknown and is an observation that may offer novel approaches for the structure-based design of new drugs against M. tuberculosis.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35475970/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35475970</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9094749/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9094749</a> | DOI:<a href=https://doi.org/10.7554/eLife.73055>10.7554/eLife.73055</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35475970</guid>
<pubDate>Wed, 27 Apr 2022 06:00:00 -0400</pubDate>
<dc:creator>Nazia Ahmad</dc:creator>
<dc:creator>Sanmati Dugad</dc:creator>
<dc:creator>Varsha Chauhan</dc:creator>
<dc:creator>Shubbir Ahmed</dc:creator>
<dc:creator>Kunal Sharma</dc:creator>
<dc:creator>Sangita Kachhap</dc:creator>
<dc:creator>Rana Zaidi</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Gyanu Lamichhane</dc:creator>
<dc:creator>Pankaj Kumar</dc:creator>
<dc:date>2022-04-27</dc:date>
<dc:source>eLife</dc:source>
<dc:title>Allosteric cooperation in β-lactam binding to a non-classical transpeptidase</dc:title>
<dc:identifier>pmid:35475970</dc:identifier>
<dc:identifier>pmc:PMC9094749</dc:identifier>
<dc:identifier>doi:10.7554/eLife.73055</dc:identifier>
</item>
<item>
<title>Mycobacterium tuberculosis: A Pathogen That Can Hold Its Breath a Long Time</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35442854/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>No abstract</description>
<content:encoded><![CDATA[<div>Am J Respir Crit Care Med. 2022 Jul 1;206(1):10-12. doi: 10.1164/rccm.202203-0432ED.NO ABSTRACTPMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35442854/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35442854</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC9954324/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC9954324</a> | DOI:<a href=https://doi.org/10.1164/rccm.202203-0432ED>10.1164/rccm.202203-0432ED</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35442854</guid>
<pubDate>Wed, 20 Apr 2022 06:00:00 -0400</pubDate>
<dc:creator>Moagi T Shaku</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2022-04-20</dc:date>
<dc:source>American journal of respiratory and critical care medicine</dc:source>
<dc:title>Mycobacterium tuberculosis: A Pathogen That Can Hold Its Breath a Long Time</dc:title>
<dc:identifier>pmid:35442854</dc:identifier>
<dc:identifier>pmc:PMC9954324</dc:identifier>
<dc:identifier>doi:10.1164/rccm.202203-0432ED</dc:identifier>
</item>
<item>
<title>Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35313583/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>COVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guérin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG reduced both lung...</description>
<content:encoded><![CDATA[<div>bioRxiv [Preprint]. 2022 Mar 15:2022.03.15.484018. doi: 10.1101/2022.03.15.484018.ABSTRACTCOVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guérin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG reduced both lung SCV2 viral load and bronchopneumonia. This was accompanied by an increase in lung alveolar macrophages, a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. Single cell transcriptome profiling showed that BCG uniquely recruits immunoglobulin-producing plasma cells to the lung suggesting accelerated antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, and differentially expressed gene (DEG) analysis showed a transcriptional shift away from exhaustion markers and towards antigen presentation and repair. Similarly, BCG enhanced lung recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, with both cell-types also showing reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35313583/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35313583</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8936112/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8936112</a> | DOI:<a href=https://doi.org/10.1101/2022.03.15.484018>10.1101/2022.03.15.484018</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35313583</guid>
<pubDate>Tue, 22 Mar 2022 06:00:00 -0400</pubDate>
<dc:creator>Alok K Singh</dc:creator>
<dc:creator>Rulin Wang</dc:creator>
<dc:creator>Kara A Lombardo</dc:creator>
<dc:creator>Monali Praharaj</dc:creator>
<dc:creator>C Korin Bullen</dc:creator>
<dc:creator>Peter Um</dc:creator>
<dc:creator>Stephanie Davis</dc:creator>
<dc:creator>Oliver Komm</dc:creator>
<dc:creator>Peter B Illei</dc:creator>
<dc:creator>Alvaro A Ordonez</dc:creator>
<dc:creator>Melissa Bahr</dc:creator>
<dc:creator>Joy Huang</dc:creator>
<dc:creator>Anuj Gupta</dc:creator>
<dc:creator>Kevin J Psoter</dc:creator>
<dc:creator>Sanjay K Jain</dc:creator>
<dc:creator>Trinity J Bivalacqua</dc:creator>
<dc:creator>Srinivasan Yegnasubramanian</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2022-03-22</dc:date>
<dc:source>bioRxiv : the preprint server for biology</dc:source>
<dc:title>Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation</dc:title>
<dc:identifier>pmid:35313583</dc:identifier>
<dc:identifier>pmc:PMC8936112</dc:identifier>
<dc:identifier>doi:10.1101/2022.03.15.484018</dc:identifier>
</item>
<item>
<title>Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35169141/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>In addition to its role as a TB vaccine, BCG has been shown to elicit heterologous protection against many other pathogens including viruses through a process termed trained immunity. Despite its potential as a broadly protective vaccine, little has been done to determine if BCG-mediated trained immunity levels can be optimized. Here we re-engineer BCG to express high levels of c-di-AMP, a PAMP recognized by stimulator of interferon genes (STING). We find that BCG overexpressing c-di-AMP elicits...</description>
<content:encoded><![CDATA[<div>Nat Commun. 2022 Feb 15;13(1):878. doi: 10.1038/s41467-022-28509-z.ABSTRACTIn addition to its role as a TB vaccine, BCG has been shown to elicit heterologous protection against many other pathogens including viruses through a process termed trained immunity. Despite its potential as a broadly protective vaccine, little has been done to determine if BCG-mediated trained immunity levels can be optimized. Here we re-engineer BCG to express high levels of c-di-AMP, a PAMP recognized by stimulator of interferon genes (STING). We find that BCG overexpressing c-di-AMP elicits more potent signatures of trained immunity including higher pro-inflammatory cytokine responses, greater myeloid cell reprogramming toward inflammatory and activated states, and enhances epigenetic and metabolomic changes. In a model of bladder cancer, we also show that re-engineered BCG induces trained immunity and improved functionality. These results indicate that trained immunity levels and antitumor efficacy may be increased by modifying BCG to express higher levels of key PAMP molecules.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35169141/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35169141</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8847416/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8847416</a> | DOI:<a href=https://doi.org/10.1038/s41467-022-28509-z>10.1038/s41467-022-28509-z</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35169141</guid>
<pubDate>Wed, 16 Feb 2022 06:00:00 -0500</pubDate>
<dc:creator>Alok Kumar Singh</dc:creator>
<dc:creator>Monali Praharaj</dc:creator>
<dc:creator>Kara A Lombardo</dc:creator>
<dc:creator>Takahiro Yoshida</dc:creator>
<dc:creator>Andres Matoso</dc:creator>
<dc:creator>Alex S Baras</dc:creator>
<dc:creator>Liang Zhao</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Joy Huang</dc:creator>
<dc:creator>Pankaj Prasad</dc:creator>
<dc:creator>Jonathan D Powell</dc:creator>
<dc:creator>Max Kates</dc:creator>
<dc:creator>David McConkey</dc:creator>
<dc:creator>Drew M Pardoll</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Trinity J Bivalacqua</dc:creator>
<dc:date>2022-02-16</dc:date>
<dc:source>Nature communications</dc:source>
<dc:title>Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer</dc:title>
<dc:identifier>pmid:35169141</dc:identifier>
<dc:identifier>pmc:PMC8847416</dc:identifier>
<dc:identifier>doi:10.1038/s41467-022-28509-z</dc:identifier>
</item>
<item>
<title>Augmentation of the Riboflavin-Biosynthetic Pathway Enhances Mucosa-Associated Invariant T (MAIT) Cell Activation and Diminishes Mycobacterium tuberculosis Virulence</title>
<link>https://pubmed.ncbi.nlm.nih.gov/35164552/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Mucosa-associated invariant T (MAIT) cells play a critical role in antimicrobial defense. Despite increased understanding of their mycobacterial ligands and the clinical association of MAIT cells with tuberculosis (TB), their function in protection against Mycobacterium tuberculosis infection remains unclear. Here, we show that overexpressing key genes of the riboflavin-biosynthetic pathway potentiates MAIT cell activation and results in attenuation of M. tuberculosis virulence in vivo. Further,...</description>
<content:encoded><![CDATA[<div>mBio. 2021 Feb 22;13(1):e0386521. doi: 10.1128/mbio.03865-21. Epub 2022 Feb 15.ABSTRACTMucosa-associated invariant T (MAIT) cells play a critical role in antimicrobial defense. Despite increased understanding of their mycobacterial ligands and the clinical association of MAIT cells with tuberculosis (TB), their function in protection against Mycobacterium tuberculosis infection remains unclear. Here, we show that overexpressing key genes of the riboflavin-biosynthetic pathway potentiates MAIT cell activation and results in attenuation of M. tuberculosis virulence in vivo. Further, we observed greater control of M. tuberculosis infection in MAIThi CAST/EiJ mice than in MAITlo C57BL/6J mice, highlighting the protective role of MAIT cells against TB. We also endogenously adjuvanted Mycobacterium bovis BCG with MR1 ligands via overexpression of the lumazine synthase gene ribH and evaluated its protective efficacy in the mouse model of M. tuberculosis infection. Altogether, our findings demonstrate that MAIT cells confer host protection against TB and that overexpression of genes in the riboflavin-biosynthetic pathway attenuates M. tuberculosis virulence. Enhancing MAIT cell-mediated immunity may also offer a novel approach toward improved vaccines against TB. IMPORTANCE Mucosa-associated invariant T (MAIT) cells are an important subset of innate lymphocytes that recognize microbial ligands derived from the riboflavin biosynthesis pathway and mediate antimicrobial immune responses. Modulated MAIT cell responses have been noted in different forms of tuberculosis. However, it has been unclear if increased MAIT cell abundance is protective against TB disease. In this study, we show that augmentation of the mycobacterial MAIT cell ligands leads to higher MAIT cell activation with reduced M. tuberculosis virulence and that elevated MAIT cell abundance confers greater control of M. tuberculosis infection. Our study also highlights the potential of endogenously adjuvanting the traditional BCG vaccine with MR1 ligands to augment MAIT cell activation. This study increases current knowledge on the roles of the riboflavin-biosynthetic pathway and MAIT cell activation in M. tuberculosis virulence and host immunity against TB.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/35164552/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">35164552</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8844931/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8844931</a> | DOI:<a href=https://doi.org/10.1128/mbio.03865-21>10.1128/mbio.03865-21</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:35164552</guid>
<pubDate>Tue, 15 Feb 2022 06:00:00 -0500</pubDate>
<dc:creator>Ruchi Jain Dey</dc:creator>
<dc:creator>Bappaditya Dey</dc:creator>
<dc:creator>Melanie Harriff</dc:creator>
<dc:creator>Elizabeth T Canfield</dc:creator>
<dc:creator>David M Lewinsohn</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2022-02-15</dc:date>
<dc:source>mBio</dc:source>
<dc:title>Augmentation of the Riboflavin-Biosynthetic Pathway Enhances Mucosa-Associated Invariant T (MAIT) Cell Activation and Diminishes Mycobacterium tuberculosis Virulence</dc:title>
<dc:identifier>pmid:35164552</dc:identifier>
<dc:identifier>pmc:PMC8844931</dc:identifier>
<dc:identifier>doi:10.1128/mbio.03865-21</dc:identifier>
</item>
<item>
<title>Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: study protocol</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34836924/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>INTRODUCTION: The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by...</description>
<content:encoded><![CDATA[<div>BMJ Open Respir Res. 2021 Nov;8(1):e001015. doi: 10.1136/bmjresp-2021-001015.ABSTRACTINTRODUCTION: The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale.METHODS AND ANALYSIS: In this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives.ETHICS AND DISSEMINATION: This trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34836924/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34836924</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8628335/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8628335</a> | DOI:<a href=https://doi.org/10.1136/bmjresp-2021-001015>10.1136/bmjresp-2021-001015</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34836924</guid>
<pubDate>Sat, 27 Nov 2021 06:00:00 -0500</pubDate>
<dc:creator>Kensuke Nakagawara</dc:creator>
<dc:creator>Ho Namkoong</dc:creator>
<dc:creator>Hideki Terai</dc:creator>
<dc:creator>Katsunori Masaki</dc:creator>
<dc:creator>Takae Tanosaki</dc:creator>
<dc:creator>Kyoko Shimamoto</dc:creator>
<dc:creator>Ho Lee</dc:creator>
<dc:creator>Hiromu Tanaka</dc:creator>
<dc:creator>Satoshi Okamori</dc:creator>
<dc:creator>Hiroki Kabata</dc:creator>
<dc:creator>Shotaro Chubachi</dc:creator>
<dc:creator>Shinnosuke Ikemura</dc:creator>
<dc:creator>Hirofumi Kamata</dc:creator>
<dc:creator>Hiroyuki Yasuda</dc:creator>
<dc:creator>Ichiro Kawada</dc:creator>
<dc:creator>Makoto Ishii</dc:creator>
<dc:creator>Yoshiki Ishibashi</dc:creator>
<dc:creator>Sei Harada</dc:creator>
<dc:creator>Takanori Fujita</dc:creator>
<dc:creator>Daisuke Ito</dc:creator>
<dc:creator>Shogyoku Bun</dc:creator>
<dc:creator>Hajime Tabuchi</dc:creator>
<dc:creator>Sho Kanzaki</dc:creator>
<dc:creator>Eisuke Shimizu</dc:creator>
<dc:creator>Keitaro Fukuda</dc:creator>
<dc:creator>Jun Yamagami</dc:creator>
<dc:creator>Keigo Kobayashi</dc:creator>
<dc:creator>Toshiyuki Hirano</dc:creator>
<dc:creator>Takashi Inoue</dc:creator>
<dc:creator>Junko Kagyo</dc:creator>
<dc:creator>Tetsuya Shiomi</dc:creator>
<dc:creator>Keiko Ohgino</dc:creator>
<dc:creator>Koichi Sayama</dc:creator>
<dc:creator>Kengo Otsuka</dc:creator>
<dc:creator>Naoki Miyao</dc:creator>
<dc:creator>Toshio Odani</dc:creator>
<dc:creator>Yoshitaka Oyamada</dc:creator>
<dc:creator>Keita Masuzawa</dc:creator>
<dc:creator>Sohei Nakayama</dc:creator>
<dc:creator>Yusuke Suzuki</dc:creator>
<dc:creator>Rie Baba</dc:creator>
<dc:creator>Ichiro Nakachi</dc:creator>
<dc:creator>Naota Kuwahara</dc:creator>
<dc:creator>Takashi Ishiguro</dc:creator>
<dc:creator>Shuko Mashimo</dc:creator>
<dc:creator>Naoto Minematsu</dc:creator>
<dc:creator>Soichiro Ueda</dc:creator>
<dc:creator>Tadashi Manabe</dc:creator>
<dc:creator>Yohei Funatsu</dc:creator>
<dc:creator>Hidefumi Koh</dc:creator>
<dc:creator>Takashi Yoshiyama</dc:creator>
<dc:creator>Fumitake Saito</dc:creator>
<dc:creator>Kota Ishioka</dc:creator>
<dc:creator>Saeko Takahashi</dc:creator>
<dc:creator>Morio Nakamura</dc:creator>
<dc:creator>Ai Goto</dc:creator>
<dc:creator>Norihiro Harada</dc:creator>
<dc:creator>Yu Kusaka</dc:creator>
<dc:creator>Yasushi Nakano</dc:creator>
<dc:creator>Kazumi Nishio</dc:creator>
<dc:creator>Hiroki Tateno</dc:creator>
<dc:creator>Ryuya Edahiro</dc:creator>
<dc:creator>Yoshito Takeda</dc:creator>
<dc:creator>Atsushi Kumanogoh</dc:creator>
<dc:creator>Nobuhiro Kodama</dc:creator>
<dc:creator>Masaki Okamoto</dc:creator>
<dc:creator>Akira Umeda</dc:creator>
<dc:creator>Kazuto Hagimura</dc:creator>
<dc:creator>Toshiro Sato</dc:creator>
<dc:creator>Naoki Miyazaki</dc:creator>
<dc:creator>Ryo Takemura</dc:creator>
<dc:creator>Yasunori Sato</dc:creator>
<dc:creator>Toru Takebayashi</dc:creator>
<dc:creator>Jin Nakahara</dc:creator>
<dc:creator>Masaru Mimura</dc:creator>
<dc:creator>Kaoru Ogawa</dc:creator>
<dc:creator>Shigeto Shimmura</dc:creator>
<dc:creator>Kazuno Negishi</dc:creator>
<dc:creator>Kazuo Tsubota</dc:creator>
<dc:creator>Masayuki Amagai</dc:creator>
<dc:creator>Rei Goto</dc:creator>
<dc:creator>Yoko Ibuka</dc:creator>
<dc:creator>Naoki Hasegawa</dc:creator>
<dc:creator>Yuko Kitagawa</dc:creator>
<dc:creator>Takanori Kanai</dc:creator>
<dc:creator>Koichi Fukunaga</dc:creator>
<dc:date>2021-11-27</dc:date>
<dc:source>BMJ open respiratory research</dc:source>
<dc:title>Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: study protocol</dc:title>
<dc:identifier>pmid:34836924</dc:identifier>
<dc:identifier>pmc:PMC8628335</dc:identifier>
<dc:identifier>doi:10.1136/bmjresp-2021-001015</dc:identifier>
</item>
<item>
<title>BCG invokes superior STING-mediated innate immune response over radiotherapy in a carcinogen murine model of urothelial cancer</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34731491/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Radiation and bacillus Calmette-Guérin (BCG) instillations are used clinically for treatment of urothelial carcinoma, but the precise mechanisms by which they activate an immune response remain elusive. The role of the cGAS-STING pathway has been implicated in both BCG and radiation-induced immune response; however, comparison of STING pathway molecules and the immune landscape following treatment in urothelial carcinoma has not been performed. We therefore comprehensively analyzed the local...</description>
<content:encoded><![CDATA[<div>J Pathol. 2022 Feb;256(2):223-234. doi: 10.1002/path.5830. Epub 2021 Dec 10.ABSTRACTRadiation and bacillus Calmette-Guérin (BCG) instillations are used clinically for treatment of urothelial carcinoma, but the precise mechanisms by which they activate an immune response remain elusive. The role of the cGAS-STING pathway has been implicated in both BCG and radiation-induced immune response; however, comparison of STING pathway molecules and the immune landscape following treatment in urothelial carcinoma has not been performed. We therefore comprehensively analyzed the local immune response in the bladder tumor microenvironment following radiotherapy and BCG instillations in a well-established spontaneous murine model of urothelial carcinoma to provide insight into activation of STING-mediated immune response. Mice were exposed to the oral carcinogen, BBN, for 12 weeks prior to treatment with a single 15 Gy dose of radiation or three intravesical instillations of BCG (1 × 108 CFU). At sacrifice, tumors were staged by a urologic pathologist and effects of therapy on the immune microenvironment were measured using the NanoString Myeloid Innate Immunity Panel and immunohistochemistry. Clinical relevance was established by measuring immune biomarker expression of cGAS and STING on a human tissue microarray consisting of BCG-treated non-muscle-invasive urothelial carcinomas. BCG instillations in the murine model elevated STING and downstream STING-induced interferon and pro-inflammatory molecules, intratumoral M1 macrophage and T-cell accumulation, and complete tumor eradication. In contrast, radiotherapy caused no changes in STING pathway or innate immune gene expression; rather, it induced M2 macrophage accumulation and elevated FoxP3 expression characteristic of immunosuppression. In human non-muscle-invasive bladder cancer, STING protein expression was elevated at baseline in patients who responded to BCG therapy and increased further after BCG therapy. Overall, these results show that STING pathway activation plays a key role in effective BCG-induced immune response and strongly indicate that the effects of BCG on the bladder cancer immune microenvironment are more beneficial than those induced by radiation. © 2021 The Pathological Society of Great Britain and Ireland.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34731491/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34731491</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8738146/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8738146</a> | DOI:<a href=https://doi.org/10.1002/path.5830>10.1002/path.5830</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34731491</guid>
<pubDate>Wed, 03 Nov 2021 06:00:00 -0400</pubDate>
<dc:creator>Kara A Lombardo</dc:creator>
<dc:creator>Aleksandar Obradovic</dc:creator>
<dc:creator>Alok Kumar Singh</dc:creator>
<dc:creator>James L Liu</dc:creator>
<dc:creator>Gregory Joice</dc:creator>
<dc:creator>Max Kates</dc:creator>
<dc:creator>William Bishai</dc:creator>
<dc:creator>David McConkey</dc:creator>
<dc:creator>Alcides Chaux</dc:creator>
<dc:creator>Marie-Lisa Eich</dc:creator>
<dc:creator>M Katayoon Rezaei</dc:creator>
<dc:creator>George J Netto</dc:creator>
<dc:creator>Charles G Drake</dc:creator>
<dc:creator>Phuoc Tran</dc:creator>
<dc:creator>Andres Matoso</dc:creator>
<dc:creator>Trinity J Bivalacqua</dc:creator>
<dc:date>2021-11-03</dc:date>
<dc:source>The Journal of pathology</dc:source>
<dc:title>BCG invokes superior STING-mediated innate immune response over radiotherapy in a carcinogen murine model of urothelial cancer</dc:title>
<dc:identifier>pmid:34731491</dc:identifier>
<dc:identifier>pmc:PMC8738146</dc:identifier>
<dc:identifier>doi:10.1002/path.5830</dc:identifier>
</item>
<item>
<title>Recombinant BCGs for tuberculosis and bladder cancer</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34593271/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Bacillus Calmette-Guérin (BCG) vaccine is an attenuated live strain of Mycobacterium bovis. It may be the most widely used vaccine in human history and is the only licensed human tuberculosis (TB) vaccine available. Despite its excellent safety history, a century of use in global vaccination programs, and its significant contribution to reducing TB mortality among children, the efficacy of BCG continues to be disputed due to its incomplete protection against pulmonary TB in adults. Still...</description>
<content:encoded><![CDATA[<div>Vaccine. 2021 Dec 8;39(50):7321-7331. doi: 10.1016/j.vaccine.2021.09.040. Epub 2021 Sep 27.ABSTRACTBacillus Calmette-Guérin (BCG) vaccine is an attenuated live strain of Mycobacterium bovis. It may be the most widely used vaccine in human history and is the only licensed human tuberculosis (TB) vaccine available. Despite its excellent safety history, a century of use in global vaccination programs, and its significant contribution to reducing TB mortality among children, the efficacy of BCG continues to be disputed due to its incomplete protection against pulmonary TB in adults. Still vaccines offer the best chance to contain the ongoing spread of multi-drug resistance TB and disease dissemination. The development of improved vaccines against TB therefore remains a high global priority. Interestingly, recent studies indicate that genetically modified BCG, or administration of existing BCG through alternate routes, or revaccination, offers improved protection, suggesting that BCG is well poised to make a comeback. Intravesical BCG is also the only approved microbial immunotherapy for any form of cancer, and is the first-line therapy for treatment-naïve non-muscle invasive bladder cancer (NMBIC), which represents a majority of the new bladder cancer cases diagnosed. However, almost a third of patients with NMIBC are either BCG unresponsive or have tumor recurrence, leading to a higher risk of disease progression. With very few advances in intravesical therapy over the past two decades for early-stage disease, and a limited pipeline of therapeutics in Phase 3 or late Phase 2 development, there is a major unmet need for improved intravesical therapies for NMIBC. Indeed, genetically modified candidate BCG vaccines engineered to express molecules that confer stronger protection against pulmonary TB or induce potent anti-tumor immunity in NMIBC have shown promise in both pre-clinical and clinical settings. This review discusses the development of second generation, genetically modified BCG candidates as TB vaccines and as anti-tumor adjuvant therapy for NMIBC.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34593271/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34593271</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8648981/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8648981</a> | DOI:<a href=https://doi.org/10.1016/j.vaccine.2021.09.040>10.1016/j.vaccine.2021.09.040</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34593271</guid>
<pubDate>Fri, 01 Oct 2021 06:00:00 -0400</pubDate>
<dc:creator>Alok K Singh</dc:creator>
<dc:creator>Geetha Srikrishna</dc:creator>
<dc:creator>Trinity J Bivalacqua</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2021-10-01</dc:date>
<dc:source>Vaccine</dc:source>
<dc:title>Recombinant BCGs for tuberculosis and bladder cancer</dc:title>
<dc:identifier>pmid:34593271</dc:identifier>
<dc:identifier>pmc:PMC8648981</dc:identifier>
<dc:identifier>doi:10.1016/j.vaccine.2021.09.040</dc:identifier>
</item>
<item>
<title>124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34424479/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: ^(124)I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, ^(124)I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19.</description>
<content:encoded><![CDATA[<div>Mol Imaging Biol. 2022 Feb;24(1):135-143. doi: 10.1007/s11307-021-01638-5. Epub 2021 Aug 23.ABSTRACTPURPOSE: Molecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by lung injury that we sought to model. Activated macrophages/phagocytes have an important role in lung injury, which is responsible for subsequent respiratory failure and death. We performed pulmonary PET/CT with 124I-iodo-DPA-713, a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by activated macrophages cells, to evaluate the local immune response in a hamster model of SARS-CoV-2 infection.PROCEDURES: Pulmonary 124I-iodo-DPA-713 PET/CT was performed in SARS-CoV-2-infected golden Syrian hamsters. CT images were quantified using a custom-built lung segmentation tool. Studies with DPA-713-IRDye680LT and a fluorescent analog of DPA-713 as well as histopathology and flow cytometry were performed on post-mortem tissues.RESULTS: Infected hamsters were imaged at the peak of inflammatory lung disease (7 days post-infection). Quantitative CT analysis was successful for all scans and demonstrated worse pulmonary disease in male versus female animals (P < 0.01). Increased 124I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary 124I-iodo-DPA-713 PET activity was noted in male versus female hamsters (P = 0.02). DPA-713-IRDye680LT also localized to the pneumonic lesions. Flow cytometry demonstrated a higher percentage of myeloid and CD11b + cells (macrophages, phagocytes) in male versus female lung tissues (P = 0.02).CONCLUSION: 124I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, 124I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34424479/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34424479</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8381721/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8381721</a> | DOI:<a href=https://doi.org/10.1007/s11307-021-01638-5>10.1007/s11307-021-01638-5</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34424479</guid>
<pubDate>Mon, 23 Aug 2021 06:00:00 -0400</pubDate>
<dc:creator>Camilo A Ruiz-Bedoya</dc:creator>
<dc:creator>Filipa Mota</dc:creator>
<dc:creator>Alvaro A Ordonez</dc:creator>
<dc:creator>Catherine A Foss</dc:creator>
<dc:creator>Alok K Singh</dc:creator>
<dc:creator>Monali Praharaj</dc:creator>
<dc:creator>Farina J Mahmud</dc:creator>
<dc:creator>Ali Ghayoor</dc:creator>
<dc:creator>Kelly Flavahan</dc:creator>
<dc:creator>Patricia De Jesus</dc:creator>
<dc:creator>Melissa Bahr</dc:creator>
<dc:creator>Santosh Dhakal</dc:creator>
<dc:creator>Ruifeng Zhou</dc:creator>
<dc:creator>Clarisse V Solis</dc:creator>
<dc:creator>Kathleen R Mulka</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:creator>Andrew Pekosz</dc:creator>
<dc:creator>Joseph L Mankowski</dc:creator>
<dc:creator>Jason Villano</dc:creator>
<dc:creator>Sabra L Klein</dc:creator>
<dc:creator>Sanjay K Jain</dc:creator>
<dc:date>2021-08-23</dc:date>
<dc:source>Molecular imaging and biology</dc:source>
<dc:title>124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection</dc:title>
<dc:identifier>pmid:34424479</dc:identifier>
<dc:identifier>pmc:PMC8381721</dc:identifier>
<dc:identifier>doi:10.1007/s11307-021-01638-5</dc:identifier>
</item>
<item>
<title>Urine Lipoarabinomannan Testing in Adults With Advanced Human Immunodeficiency Virus in a Trial of Empiric Tuberculosis Therapy</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34398958/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSIONS: Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.</description>
<content:encoded><![CDATA[<div>Clin Infect Dis. 2021 Aug 16;73(4):e870-e877. doi: 10.1093/cid/ciab179.ABSTRACTBACKGROUND: The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear.METHODS: The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen-negative HIV-positive adults initiating antiretroviral therapy with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method.RESULTS: A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9-32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04).CONCLUSIONS: Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34398958/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34398958</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8366821/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8366821</a> | DOI:<a href=https://doi.org/10.1093/cid/ciab179>10.1093/cid/ciab179</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34398958</guid>
<pubDate>Mon, 16 Aug 2021 06:00:00 -0400</pubDate>
<dc:creator>Mitch M Matoga</dc:creator>
<dc:creator>Gregory P Bisson</dc:creator>
<dc:creator>Amita Gupta</dc:creator>
<dc:creator>Sachiko Miyahara</dc:creator>
<dc:creator>Xin Sun</dc:creator>
<dc:creator>Carrie Fry</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Johnstone Kumwenda</dc:creator>
<dc:creator>Kanyama Cecilia</dc:creator>
<dc:creator>Mulinda Nyirenda</dc:creator>
<dc:creator>McNeil Ngongondo</dc:creator>
<dc:creator>Abineli Mbewe</dc:creator>
<dc:creator>David Lagat</dc:creator>
<dc:creator>Carole Wallis</dc:creator>
<dc:creator>Henry Mugerwa</dc:creator>
<dc:creator>Mina C Hosseinipour</dc:creator>
<dc:date>2021-08-16</dc:date>
<dc:source>Clinical infectious diseases : an official publication of the Infectious Diseases Society of America</dc:source>
<dc:title>Urine Lipoarabinomannan Testing in Adults With Advanced Human Immunodeficiency Virus in a Trial of Empiric Tuberculosis Therapy</dc:title>
<dc:identifier>pmid:34398958</dc:identifier>
<dc:identifier>pmc:PMC8366821</dc:identifier>
<dc:identifier>doi:10.1093/cid/ciab179</dc:identifier>
</item>
<item>
<title>P1 gene of Mycoplasma pneumoniae isolated from 2016 to 2019 and relationship between genotyping and macrolide resistance in Hokkaido, Japan</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34165424/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>We characterized 515 Mycoplasma pneumoniae specimens in Hokkaido. In 2013 and 2014, the p1 gene type 1 strain, mostly macrolide-resistant, was dominant and the prevalence of macrolide resistance was over 50 %. After 2017, the p1 gene type 2 lineage, mostly macrolide-sensitive, increased and the prevalence of macrolide resistance became 31.0 % in 2017, 5.3 % in 2018 and 16.3 % in 2019.</description>
<content:encoded><![CDATA[<div>J Med Microbiol. 2021 Jun;70(6). doi: 10.1099/jmm.0.001365.ABSTRACTWe characterized 515 Mycoplasma pneumoniae specimens in Hokkaido. In 2013 and 2014, the p1 gene type 1 strain, mostly macrolide-resistant, was dominant and the prevalence of macrolide resistance was over 50 %. After 2017, the p1 gene type 2 lineage, mostly macrolide-sensitive, increased and the prevalence of macrolide resistance became 31.0 % in 2017, 5.3 % in 2018 and 16.3 % in 2019.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34165424/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34165424</a> | DOI:<a href=https://doi.org/10.1099/jmm.0.001365>10.1099/jmm.0.001365</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34165424</guid>
<pubDate>Thu, 24 Jun 2021 06:00:00 -0400</pubDate>
<dc:creator>Nobuhisa Ishiguro</dc:creator>
<dc:creator>Rikako Sato</dc:creator>
<dc:creator>Hideaki Kikuta</dc:creator>
<dc:creator>Masanori Nakanishi</dc:creator>
<dc:creator>Hayato Aoyagi</dc:creator>
<dc:creator>Toshihiko Mori</dc:creator>
<dc:creator>Naoko Nagano</dc:creator>
<dc:creator>Yuichi Tabata</dc:creator>
<dc:creator>Kyosuke Hazama</dc:creator>
<dc:creator>Mutsuko Konno</dc:creator>
<dc:creator>Tatsuru Yamanaka</dc:creator>
<dc:creator>Katsumi Azuma</dc:creator>
<dc:creator>Hiroshi Tanaka</dc:creator>
<dc:creator>Mitsuo Narita</dc:creator>
<dc:creator>Keisuke Morita</dc:creator>
<dc:creator>Yasuhisa Odagawa</dc:creator>
<dc:creator>Akihito Ishizaka</dc:creator>
<dc:creator>Akira Tsuchida</dc:creator>
<dc:creator>Satoshi Sasaki</dc:creator>
<dc:creator>Atsuko Horino</dc:creator>
<dc:creator>Tsuyoshi Kenri</dc:creator>
<dc:creator>Takehiro Togashi</dc:creator>
<dc:creator>Atsushi Manabe</dc:creator>
<dc:date>2021-06-24</dc:date>
<dc:source>Journal of medical microbiology</dc:source>
<dc:title>P1 gene of Mycoplasma pneumoniae isolated from 2016 to 2019 and relationship between genotyping and macrolide resistance in Hokkaido, Japan</dc:title>
<dc:identifier>pmid:34165424</dc:identifier>
<dc:identifier>doi:10.1099/jmm.0.001365</dc:identifier>
</item>
<item>
<title>Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34074248/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>CONCLUSION: Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.</description>
<content:encoded><![CDATA[<div>BMC Infect Dis. 2021 Jun 1;21(1):513. doi: 10.1186/s12879-021-06220-6.ABSTRACTBACKGROUND: In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB.METHODS: A subset of 138 PLHIV from the 'SOUTH' study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity.RESULTS: A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient's colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8.CONCLUSION: Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34074248/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34074248</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8170957/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8170957</a> | DOI:<a href=https://doi.org/10.1186/s12879-021-06220-6>10.1186/s12879-021-06220-6</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34074248</guid>
<pubDate>Wed, 02 Jun 2021 06:00:00 -0400</pubDate>
<dc:creator>Juliet Namugenyi</dc:creator>
<dc:creator>Joseph Musaazi</dc:creator>
<dc:creator>Achilles Katamba</dc:creator>
<dc:creator>Joan Kalyango</dc:creator>
<dc:creator>Emmanuel Sendaula</dc:creator>
<dc:creator>Andrew Kambugu</dc:creator>
<dc:creator>Jan Fehr</dc:creator>
<dc:creator>Barbara Castelnouvo</dc:creator>
<dc:creator>Yukari C Manabe</dc:creator>
<dc:creator>Willy Ssengooba</dc:creator>
<dc:creator>Christine Sekaggya-Wiltshire</dc:creator>
<dc:date>2021-06-02</dc:date>
<dc:source>BMC infectious diseases</dc:source>
<dc:title>Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study</dc:title>
<dc:identifier>pmid:34074248</dc:identifier>
<dc:identifier>pmc:PMC8170957</dc:identifier>
<dc:identifier>doi:10.1186/s12879-021-06220-6</dc:identifier>
</item>
<item>
<title>BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases</title>
<link>https://pubmed.ncbi.nlm.nih.gov/34060492/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>First administered to a human subject as a tuberculosis (TB) vaccine on July 18, 1921, Bacillus Calmette-Guérin (BCG) has a long history of use for the prevention of TB and later the immunotherapy of bladder cancer. For TB prevention, BCG is given to infants born globally across over 180 countries and has been in use since the late 1920s. With about 352 million BCG doses procured annually and tens of billions of doses having been administered over the past century, it is estimated to be the most...</description>
<content:encoded><![CDATA[<div>J Clin Invest. 2021 Jun 1;131(11):e148291. doi: 10.1172/JCI148291.ABSTRACTFirst administered to a human subject as a tuberculosis (TB) vaccine on July 18, 1921, Bacillus Calmette-Guérin (BCG) has a long history of use for the prevention of TB and later the immunotherapy of bladder cancer. For TB prevention, BCG is given to infants born globally across over 180 countries and has been in use since the late 1920s. With about 352 million BCG doses procured annually and tens of billions of doses having been administered over the past century, it is estimated to be the most widely used vaccine in human history. While its roles for TB prevention and bladder cancer immunotherapy are widely appreciated, over the past century, BCG has been also studied for nontraditional purposes, which include (a) prevention of viral infections and nontuberculous mycobacterial infections, (b) cancer immunotherapy aside from bladder cancer, and (c) immunologic diseases, including multiple sclerosis, type 1 diabetes, and atopic diseases. The basis for these heterologous effects lies in the ability of BCG to alter immunologic set points via heterologous T cell immunity, as well as epigenetic and metabolomic changes in innate immune cells, a process called "trained immunity." In this Review, we provide an overview of what is known regarding the trained immunity mechanism of heterologous protection, and we describe the current knowledge base for these nontraditional uses of BCG.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/34060492/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">34060492</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8159679/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8159679</a> | DOI:<a href=https://doi.org/10.1172/JCI148291>10.1172/JCI148291</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:34060492</guid>
<pubDate>Tue, 01 Jun 2021 06:00:00 -0400</pubDate>
<dc:creator>Alok K Singh</dc:creator>
<dc:creator>Mihai G Netea</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2021-06-01</dc:date>
<dc:source>The Journal of clinical investigation</dc:source>
<dc:title>BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases</dc:title>
<dc:identifier>pmid:34060492</dc:identifier>
<dc:identifier>pmc:PMC8159679</dc:identifier>
<dc:identifier>doi:10.1172/JCI148291</dc:identifier>
</item>
<item>
<title>Effective Host-Directed Therapy for Tuberculosis by Depletion of Myeloid-Derived Suppressor Cells and Related Cells Using a Diphtheria Toxin Fusion Protein</title>
<link>https://pubmed.ncbi.nlm.nih.gov/33955457/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Myeloid-derived suppressor cells (MDSCs) are present in elevated numbers in tuberculosis patients and have been found to be permissive for Mycobacterium tuberculosis proliferation. To determine whether depletion of MDSCs may improve host control of tuberculosis, we used a novel diphtheria toxin-based fusion protein DABIL-4 that targets and depletes interleukin 4 (IL-4) receptor-positive cells. We show that DABIL-4 depletes both polymorphonuclear MDSCs and monocytic MDSCs, increases interferon-γ...</description>
<content:encoded><![CDATA[<div>J Infect Dis. 2021 Dec 1;224(11):1962-1972. doi: 10.1093/infdis/jiab235.ABSTRACTMyeloid-derived suppressor cells (MDSCs) are present in elevated numbers in tuberculosis patients and have been found to be permissive for Mycobacterium tuberculosis proliferation. To determine whether depletion of MDSCs may improve host control of tuberculosis, we used a novel diphtheria toxin-based fusion protein DABIL-4 that targets and depletes interleukin 4 (IL-4) receptor-positive cells. We show that DABIL-4 depletes both polymorphonuclear MDSCs and monocytic MDSCs, increases interferon-γ + T cells, and reduces the lung bacillary burden in a mouse tuberculosis model. These results indicate that MDSC-depleting therapies targeting the IL-4 receptor are beneficial in tuberculosis and offer an avenue towards host-directed tuberculosis therapy.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/33955457/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">33955457</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8643419/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8643419</a> | DOI:<a href=https://doi.org/10.1093/infdis/jiab235>10.1093/infdis/jiab235</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:33955457</guid>
<pubDate>Thu, 06 May 2021 06:00:00 -0400</pubDate>
<dc:creator>Sadiya Parveen</dc:creator>
<dc:creator>Shichun Lun</dc:creator>
<dc:creator>Michael E Urbanowski</dc:creator>
<dc:creator>Mitchell Cardin</dc:creator>
<dc:creator>Jessica Shen</dc:creator>
<dc:creator>John R Murphy</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2021-05-06</dc:date>
<dc:source>The Journal of infectious diseases</dc:source>
<dc:title>Effective Host-Directed Therapy for Tuberculosis by Depletion of Myeloid-Derived Suppressor Cells and Related Cells Using a Diphtheria Toxin Fusion Protein</dc:title>
<dc:identifier>pmid:33955457</dc:identifier>
<dc:identifier>pmc:PMC8643419</dc:identifier>
<dc:identifier>doi:10.1093/infdis/jiab235</dc:identifier>
</item>
<item>
<title>Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis</title>
<link>https://pubmed.ncbi.nlm.nih.gov/33953722/?utm_source=Feedvalidator&utm_medium=rss&utm_campaign=None&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&fc=None&ff=20240507201515&v=2.18.0.post9+e462414</link>
<description>Following infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may...</description>
<content:encoded><![CDATA[<div>Front Immunol. 2021 Apr 19;12:660916. doi: 10.3389/fimmu.2021.660916. eCollection 2021.ABSTRACTFollowing infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may prolong the TB treatment duration and permanently diminish the lung function of TB survivors. The host also expresses certain anti-inflammatory mediators which may play either beneficial or detrimental roles depending on the timing of their deployment. The balance between the timing and expression levels of pro- and anti-inflammatory responses plays an important role in the fate of infection. Interestingly, M. tuberculosis appears to manipulate both sides of the human immune response to remodel the host environment for its own benefit. Consequently, therapies which modulate either end of this spectrum of immune responses at the appropriate time may have the potential to improve the treatment of TB or to reduce the formation of permanent lung damage after microbiological cure. Here, we highlight host-directed TB therapies targeting pro- or anti-inflammatory processes that have been evaluated in pre-clinical models. The repurposing of already available drugs known to modulate these responses may improve the future of TB therapy.PMID:<a href="https://pubmed.ncbi.nlm.nih.gov/33953722/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">33953722</a> | PMC:<a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8089478/?utm_source=Feedvalidator&utm_medium=rss&utm_content=0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB&ff=20240507201515&v=2.18.0.post9+e462414">PMC8089478</a> | DOI:<a href=https://doi.org/10.3389/fimmu.2021.660916>10.3389/fimmu.2021.660916</a></div>]]></content:encoded>
<guid isPermaLink="false">pubmed:33953722</guid>
<pubDate>Thu, 06 May 2021 06:00:00 -0400</pubDate>
<dc:creator>Stefanie Krug</dc:creator>
<dc:creator>Sadiya Parveen</dc:creator>
<dc:creator>William R Bishai</dc:creator>
<dc:date>2021-05-06</dc:date>
<dc:source>Frontiers in immunology</dc:source>
<dc:title>Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis</dc:title>
<dc:identifier>pmid:33953722</dc:identifier>
<dc:identifier>pmc:PMC8089478</dc:identifier>
<dc:identifier>doi:10.3389/fimmu.2021.660916</dc:identifier>
</item>
</channel>
</rss>

If you would like to create a banner that links to this page (i.e. this validation result), do the following:

Download the "valid RSS" banner.
Upload the image to your own server. (This step is important. Please do not link directly to the image on this server.)
Add this HTML to your page (change the image src attribute if necessary):

<a href="http://www.feedvalidator.org/check.cgi?url=http%3A//eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi%3Frss_guid%3D0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB"><img src="valid-rss-rogers.png" alt="[Valid RSS]" title="Validate my RSS feed" /></a>

If you would like to create a text link instead, here is the URL you can use:

http://www.feedvalidator.org/check.cgi?url=http%3A//eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi%3Frss_guid%3D0PH-BzJj8av-LCmCX9QLPGfPfYrq14hnVxB4KcMLZqB

Home · About · News · Docs · Terms