Complete genome sequence of an isolate of leek yellow stripe virus from garlic in India

Not AvailableThe complete genome sequence of leek yellow stripe virus (LYSV) isolate AC-50 from garlic in India was determined and the predicted amino acid (aa) sequence was analyzed. The LYSV RNA genome is 10,131 nucleotides (nt) long excluding the poly(A) tail (KP168261) and has a large open reading frame (ORF) encoding a putative polyprotein of 3152 aa with conserved motifs typical of members of the genus Potyvirus in the family Potyviridae. The pretty interesting Potyviridae ORF (PIPO) coding region was identified in the P3 coding region. LYSV isolate AC-50 shares maximum nt and aa sequence identity of 79.9% and 87.2% with a LYSV isolate from Australia (HQ258895) at the full genome and polyprotein level, respectively, and clusters with clade II isolates from China, Mexico, Australia, Brazil and Spain. The P1 coding region of isolate AC-50 was highly variable with an identity range of 48.9- 70.9% with other LYSV isolates and a deletion of 204 nt compared to Japanese and Australian isolates. The ratio of nonsynonymous (dN) and synonymous (dS) polymorphic sites suggested that purifying selection dominates in the evolution of LYSV and the mean dN/dS ratio was highest for P1, confirming that this coding region is under less evolutionary constraints

Covid-19 and Tobacco Cessation:Lessons from India

OBJECTIVES: The Government of India prohibited the sale of tobacco products during the COVID-19 lockdown to prevent spread of the SARS-CoV-2 virus. This study assessed the tobacco cessation behaviour and its predictors among adult tobacco users during the initial COVID-19 lockdown period in India. STUDY DESIGN: : Cross-sectional study. METHODS: A cross-sectional study was conducted with 801 adult tobacco users (both smoking and smokeless tobacco) in two urban metropolitan cities of India over a 2-month period (July–August 2020). The study assessed complete tobacco cessation and quit attempts during the lockdown period. Logistic and negative binomial regression models were used to study correlates of tobacco cessation and quit attempts, respectively. RESULTS: In total, 90 (11.3%) tobacco users reported that they had quit using tobacco after the COVID-19 lockdown period. Overall, a median of two quit attempts (interquartile range [IQR] 0–6) were made by tobacco users. Participants with good knowledge on the harmful effects of tobacco use and COVID-19 were significantly more likely to quit tobacco use (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.2–4.0) and reported more quit attempts (incidence risk ratio [IRR] 5.7; 95% CI 2.8-11.8] compared with those with poor knowledge. Participants who had access to tobacco products were less likely to quit tobacco use compared with those who had no access (OR 0.3; 95% CI 0.2–0.5]. CONCLUSIONS: Access restrictions and correct knowledge on the harmful effects of tobacco use and COVID-19 can play an important role in creating a conducive environment for tobacco cessation among users

Do U.S. Environmental Protection Agency water quality guidelines for recreational waters prevent gastrointestinal illness? A systematic review and meta-analysis.

Despite numerous studies, uncertainty remains about how water quality indicators can best be used in the regulation of recreational water. We conducted a systematic review of this topic with the goal of quantifying the association between microbial indicators of recreational water quality and gastrointestinal (GI) illness. A secondary goal was to evaluate the potential for GI illness below current guidelines. We screened 976 potentially relevant studies and from these identified 27 studies. From the latter, we determined summary relative risks for GI illness in relation to water quality indicator density. Our results support the use of enterococci in marine water at U.S. Environmental Protection Agency guideline levels. In fresh water, (Italic)Escherichia(/Italic) coli was a more consistent predictor of GI illness than are enterococci and other bacterial indicators. A log (base 10) unit increase in enterococci was associated with a 1.34 [95% confidence intervals (CI), 1.00-1.75] increase in relative risk in marine waters, and a log (base 10) unit increase in E. coli was associated with a 2.12 (95% CI, 0.925-4.85) increase in relative risk in fresh water. Indicators of viral contamination were strong predictors of GI illness in both fresh and marine environments. Significant heterogeneity was noted among the studies. In our analysis of heterogeneity, studies that used a nonswimming control group, studies that focused on children, and studies of athletic or other recreational events found elevated relative risks. Future studies should focus on the ability of new, more rapid and specific microbial methods to predict health effects, and estimating the risks of recreational water exposure among susceptible persons

Impact of Round-the-Clock, Rapid Oral Fluid HIV Testing of Women in Labor in Rural India

Nitika Pant Pai and colleagues report the results of offering a round-the-clock rapid HIV testing program in a rural labor ward setting in India

The Impact of Antiretroviral Therapy in a Cohort of HIV Infected Patients Going in and out of the San Francisco County Jail

BackgroundJails are an important venue of HIV care and a place for identification, treatment and referral for care. HIV infected inmates in the San Francisco County jail are offered antiretroviral treatment (ART), which many take only while in jail. We evaluated the effect of ART administration in a cohort of jail inmates going in and out of jail over a nine year period.Methodology/Principal FindingsIn this retrospective study, we examined inmates with HIV going in and out of jail. Inmates were categorized by patterns of ART use: continuous ART - ART both in and out of jail, [...] more likely to have higher VL than inmates on continuous ART. Furthermore, Inmates on intermittent ART and never-on ART lost 1.60; 95%CI (1.06, 2.13) and 1.97; 95%CI (0.96, 3.00) more CD4 cells per month, respectively, compared to continuously treated inmates. The continuous ART inmates gained 0.67CD4 cells/month.Conclusions/SignificanceContinuous ART therapy in jail inmate's benefits CD4 cell counts and control of VL especially compared to those who never took ART. Although jail inmates on intermittent ART were more likely to lose CD4 cells and experience higher VL over time than those on continuous ART, CD4 cell loss was slower in these inmates as compared to inmates never on ART. Further studies are needed to evaluate whether or not intermittent ART provides some benefit in outcome if continuous ART is not possible or likely

Social Stigma and Knowledge of Tuberculosis and HIV among Patients with Both Diseases in Thailand

INTRODUCTION: Disease-related stigma and knowledge are believed to be associated with patients' willingness to seek treatment and adherence to treatment. HIV-associated tuberculosis (TB) presents unique challenges, because TB and HIV are both medically complex and stigmatizing diseases. In Thailand, we assessed knowledge and beliefs about these diseases among HIV-infected TB patients. METHODS: We prospectively interviewed and examined HIV-infected TB patients from three provinces and one national referral hospital in Thailand from 2005-2006. At the beginning of TB treatment, we asked patients standardized questions about TB stigma, TB knowledge, and HIV knowledge. Responses were grouped into scores; scores equal to or greater than the median score of study population were considered high. Multiple logistic regression analysis was used to identify factors associated with scores. RESULTS: Of 769 patients enrolled, 500 (65%) reported high TB stigma, 177 (23%) low TB knowledge, and 379 (49%) low HIV knowledge. Patients reporting high TB stigma were more likely to have taken antibiotics before TB treatment, to have first visited a traditional healer or private provider, to not know that monogamy can reduce the risk of acquiring HIV infection, and to have been hospitalized at enrollment. Patients with low TB knowledge were more likely to have severe TB disease, to be hospitalized at enrollment, to be treated at the national infectious diseases referral hospital, and to have low HIV knowledge. Patients with low HIV knowledge were more likely to know a TB patient and to have low TB knowledge. DISCUSSION: We found that stigma and low disease-specific knowledge were common among HIV-infected TB patients and associated with similar factors. Further research is needed to determine whether reducing stigma and increasing TB and HIV knowledge among the general community and patients reduces diagnostic delay and improves patient outcomes

Synthesis and Biological Evaluation of 2-Methyl-4,5-Disubstituted Oxazoles as a Novel Class of Highly Potent Antitubulin Agents

Antimitotic agents that interfere with microtubule formation are one of the major classes of cytotoxic drugs for cancer treatment. Multiple 2-methyl-4-(3′,4′,5′-trimethoxyphenyl)-5-substituted oxazoles and their related 4-substituted-5-(3′,4′,5′-trimethoxyphenyl) regioisomeric derivatives designed as cis-constrained combretastatin A-4 (CA-4) analogues were synthesized and evaluated for their antiproliferative activity in vitro against a panel of cancer cell lines and, for selected highly active compounds, interaction with tubulin, cell cycle effects and in vivo potency. Both these series of compounds were characterized by the presence of a common 3′,4′,5′-trimethoxyphenyl ring at either the C-4 or C-5 position of the 2-methyloxazole ring. Compounds 4g and 4i, bearing a m-fluoro-p-methoxyphenyl or p-ethoxyphenyl moiety at the 5-position of 2-methyloxazole nucleus, respectively, exhibited the greatest antiproliferative activity, with IC50 values of 0.35-4.6 nM (4g) and 0.5–20.2 nM (4i), which are similar to those obtained with CA-4. These compounds bound to the colchicine site of tubulin and inhibited tubulin polymerization at submicromolar concentrations. Furthermore, 4i strongly induced apoptosis that follows the mitochondrial pathway. In vivo, 4i in a mouse syngeneic model demonstrated high antitumor activity which significantly reduced the tumor mass at doses ten times lower than that required for CA-4P, suggesting that 4i warrants further evaluation as a potential anticancer drug

Viral Load Levels Measured at Set-Point Have Risen Over the Last Decade of the HIV Epidemic in the Netherlands

HIV-1 RNA plasma concentration at viral set-point is associated not only with disease outcome but also with the transmission dynamics of HIV-1. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands.We selected 906 therapy-naïve patients with at least one plasma HIV-1 RNA concentration measured 9 to 27 months after estimated seroconversion. Changes in HIV-1 RNA and CD4 cell count at viral set-point over time were analysed using linear regression models. The ATHENA national observational cohort contributed all patients who seroconverted in or after 1996; the Amsterdam Cohort Studies (ACS) contributed seroconverters before 1996. The mean of the first HIV-1 RNA concentration measured 9-27 months after seroconversion was 4.30 log(10) copies/ml (95% CI 4.17-4.42) for seroconverters from 1984 through 1995 (n = 163); 4.27 (4.16-4.37) for seroconverters 1996-2002 (n = 232), and 4.59 (4.52-4.66) for seroconverters 2003-2007 (n = 511). Compared to patients seroconverting between 2003-2007, the adjusted mean HIV-1 RNA concentration at set-point was 0.28 log(10) copies/ml (95% CI 0.16-0.40; p<0.0001) and 0.26 (0.11-0.41; p = 0.0006) lower for those seroconverting between 1996-2002 and 1984-1995, respectively. Results were robust regardless of type of HIV-1 RNA assay, HIV-1 subtype, and interval between measurement and seroconversion. CD4 cell count at viral set-point declined over calendar time at approximately 5 cells/mm(3)/year.The HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands. This is accompanied by a decreasing CD4 cell count over the period 1984-2007 and may have implications for both the course of the HIV infection and the epidemic

Fitting the HIV Epidemic in Zambia: A Two-Sex Micro-Simulation Model

BACKGROUND: In describing and understanding how the HIV epidemic spreads in African countries, previous studies have not taken into account the detailed periods at risk. This study is based on a micro-simulation model (individual-based) of the spread of the HIV epidemic in the population of Zambia, where women tend to marry early and where divorces are not frequent. The main target of the model was to fit the HIV seroprevalence profiles by age and sex observed at the Demographic and Health Survey conducted in 2001. METHODS AND FINDINGS: A two-sex micro-simulation model of HIV transmission was developed. Particular attention was paid to precise age-specific estimates of exposure to risk through the modelling of the formation and dissolution of relationships: marriage (stable union), casual partnership, and commercial sex. HIV transmission was exclusively heterosexual for adults or vertical (mother-to-child) for children. Three stages of HIV infection were taken into account. All parameters were derived from empirical population-based data. Results show that basic parameters could not explain the dynamics of the HIV epidemic in Zambia. In order to fit the age and sex patterns, several assumptions were made: differential susceptibility of young women to HIV infection, differential susceptibility or larger number of encounters for male clients of commercial sex workers, and higher transmission rate. The model allowed to quantify the role of each type of relationship in HIV transmission, the proportion of infections occurring at each stage of disease progression, and the net reproduction rate of the epidemic (R(0) = 1.95). CONCLUSIONS: The simulation model reproduced the dynamics of the HIV epidemic in Zambia, and fitted the age and sex pattern of HIV seroprevalence in 2001. The same model could be used to measure the effect of changing behaviour in the future

Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe

Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions1-7. How local chromatin interactions govern higher-order folding of chromatin fibers and the function of cohesin in this process remain poorly understood. Here we perform genome-wide chromatin conformation capture (Hi-C) analysis8 to explore the high-resolution organization of the Schizosaccharomyces pombe genome, which despite its small size exhibits fundamental features found in other eukaryotes9. Our analyses of wild type and mutant strains reveal key elements of chromosome architecture and genome organization. On chromosome arms, small regions of chromatin locally interact to form “globules”. This feature requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structures and global chromosome territories. By contrast, heterochromatin, which loads cohesin at specific sites including pericentromeric and subtelomeric domains9-11, is dispensable for globule formation but nevertheless affects genome organization. We show that heterochromatin mediates chromatin fiber compaction at centromeres and promotes prominent interarm interactions within centromere-proximal regions, providing structural constraints crucial for proper genome organization. Loss of heterochromatin relaxes constraints on chromosomes, causing an increase in intra- and inter-chromosomal interactions. Together, our analyses uncover fundamental genome folding principles that drive higher-order chromosome organization crucial for coordinating nuclear functions