A community health worker-led program to improve access to gestational diabetes screening in urban slums of Pune, India: Results from a mixed methods study.

The World Health Organization recommends all pregnant women receive screening for gestational diabetes (GDM) with a fasting oral glucose tolerance test (OGTT). However, very few women receive recommended screening in resource-limited countries like India. We implemented a community health worker (CHW)-delivered program to evaluate if home-based, CHW-delivered OGTT would increase GDM screening in a low-resource setting. We conducted a mixed methods study in two urban slum communities in Pune, India. CHWs were trained to deliver home-based, point-of-care fasting OGTT to women in their third trimester of pregnancy. The primary outcome was uptake of CHW-delivered OGTT. Secondary outcomes included GDM prevalence and linkage to GDM care. Individual interviews were conducted with purposively sampled pregnant women, CHWs, and local clinicians to assess barriers and facilitators of this approach. From October 2021-June 2022, 248 eligible pregnant women were identified. Of these, 223 (90%) accepted CHW-delivered OGTT and 31 (14%) were diagnosed with GDM. Thirty (97%) women diagnosed with GDM subsequently sought GDM care; only 10 (33%) received lifestyle counseling or pharmacologic therapy. Qualitative interviews indicated that CHW-delivered testing was considered highly acceptable as home-based testing saved time and was more convenient than clinic-based testing. Inconsistent clinical management of GDM was attributed to providers' lack of time to deliver counseling, and perceptions that low-income populations are not at risk for GDM. Convenience and trust in a CHW-delivered GDM screening program resulted in high access to gold-standard OGTT screening and identification of a high GDM prevalence among pregnant women in two urban slum communities. Appropriate linkage to care was limited by clinician time constraints and misperceptions of GDM risk. CHW-delivered GDM screening and counseling may improve health education and access to preventive healthcare, offloading busy public clinics in high-need, low-resource settings.

Perspectives of Muslim Religious Leaders to Shape an Educational Intervention About Family Planning in Rural Tanzania: A Qualitative Study.

INTRODUCTION: Uptake of effective contraceptive methods can be hindered by poor understanding and uncertainty about its compatibility with religious beliefs. We sought to understand the perspectives of Muslim religious leaders in rural Tanzania on family planning (FP) and acceptable strategies for providing FP education to leaders and their communities. METHODS: We conducted in-depth interviews with Muslim leaders from 4 communities in northwest Tanzania. Open-ended questions explored leaders' views on FP in relation to their communities, Muslim texts and teaching, and their experience as leaders. We also investigated how FP education could be provided in their communities and asked practical questions regarding seminar implementation. Interviews were conducted in Kiswahili and transcribed and translated into English. Data were coded independently by 2 investigators using NVivo 1.5.1 and analyzed thematically. RESULTS: We interviewed 17 male and 15 female Muslim leaders. All leaders supported FP as a concept in which births are spaced, interpreting this as espoused by the Qur'an and a basic right of children raised in Islam. Leaders uniformly endorsed the use of breastfeeding and the calendar method to space births but had divergent and sometimes opposing views on other methods, including condom use, oral contraceptives, and intrauterine devices. All leaders acknowledged the need for FP education among their congregants and were in favor of helping to teach an FP seminar in their communities. CONCLUSION: Our data reveal insights into how education for Muslim leaders may equip them to promote birth spacing and enhance understanding of FP in their communities in ways that are concordant with Islamic teaching. Our findings will guide the design and pilot-testing of an educational intervention for Muslim religious leaders to promote knowledge and uptake of FP in rural Tanzania.

Schistosoma mansoni Infection Is Associated With Increased Monocytes and Fewer Natural Killer T Cells in the Female Genital Tract.

Schistosoma mansoni infection may impair genital mucosal antiviral immunity, but immune cell populations have not been well characterized. We characterized mononuclear cells from cervical brushings of women with and without S mansoni infection. We observed lower frequencies of natural killer T cells and higher frequencies of CD14+ monocytes in infected women.

Sex-Related Differences in Clinical Presentation and Risk Factors for Mortality in Patients Hospitalized With Coronavirus Disease 2019 in New York City.

We evaluated sex-related differences in symptoms and risk factors for mortality in 4798 patients hospitalized with coronavirus disease 2019 in New York City. When adjusted for age and comorbidities, being male was an independent predictor of death with mortality significantly higher than females, even with low severe acute respiratory syndrome coronavirus 2 viral load at admission.

Effects of schistosomes on host anti-viral immune response and the acquisition, virulence, and prevention of viral infections: A systematic review.

Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections.

Extensive Epitranscriptomic Methylation of A and C Residues on Murine Leukemia Virus Transcripts Enhances Viral Gene Expression.

While it has been known for several years that viral RNAs are subject to the addition of several distinct covalent modifications to individual nucleotides, collectively referred to as epitranscriptomic modifications, the effect of these editing events on viral gene expression has been controversial. Here, we report the purification of murine leukemia virus (MLV) genomic RNA to homogeneity and show that this viral RNA contains levels of N6-methyladenosine (m6A), 5-methylcytosine (m5C), and 2'O-methylated (Nm) ribonucleotides that are an order of magnitude higher than detected on bulk cellular mRNAs. Mapping of m6A and m5C residues on MLV transcripts identified multiple discrete editing sites and allowed the construction of MLV variants bearing silent mutations that removed a subset of these sites. Analysis of the replication potential of these mutants revealed a modest but significant attenuation in viral replication in 3T3 cells in culture. Consistent with a positive role for m6A and m5C in viral replication, we also demonstrate that overexpression of the key m6A reader protein YTHDF2 enhances MLV replication, while downregulation of the m5C writer NSUN2 inhibits MLV replication.IMPORTANCE The data presented in the present study demonstrate that MLV RNAs bear an exceptionally high level of the epitranscriptomic modifications m6A, m5C, and Nm, suggesting that these each facilitate some aspect of the viral replication cycle. Consistent with this hypothesis, we demonstrate that mutational removal of a subset of these m6A or m5C modifications from MLV transcripts inhibits MLV replication in cis, and a similar result was also observed upon manipulation of the level of expression of key cellular epitranscriptomic cofactors in trans Together, these results argue that the addition of several different epitranscriptomic modifications to viral transcripts stimulates viral gene expression and suggest that MLV has therefore evolved to maximize the level of these modifications that are added to viral RNAs.

Acute Lengthening of Progenitor Mitosis Influences Progeny Fate during Cortical Development in vivo.

BACKGROUND/AIMS: Prenatal microcephaly is posited to arise from aberrant mitosis of neural progenitors, which disrupts both neuronal production and survival. Although microcephaly has both a genetic and environmental etiology, the mechanisms by which dysregulation of mitosis causes microcephaly are poorly understood. We previously discovered that prolonged mitosis of mouse neural progenitors, either ex vivo or in vitro, directly alters progeny cell fate, -resulting in precocious differentiation and apoptosis. This raises questions as to whether prolonged progenitor mitosis affects cell fate and neurogenesis in vivo, and what are the underlying mechanisms? METHODS/RESULTS: Towards addressing these knowledge gaps, we developed an in vivo model of mitotic delay. This uses pharmacological inhibition to acutely and reversibly prolong mitosis during cortical development, and fluorescent dyes to label direct progeny. Using this model, we discovered that a causal relationship between mitotic delay of neural progenitors and altered progeny cell fate is evident in vivo. Using transcriptome analyses to investigate the state of delayed cells and their progeny, we uncovered potential molecular mechanisms by which prolonged mitosis induces altered cell fates, including DNA damage and p53 signaling. We then extended our studies to human neural progenitors, demonstrating that lengthened mitosis duration also directly alters neuronal cell fate. CONCLUSIONS: This study establishes a valuable new experimental paradigm towards understanding mechanisms whereby lengthened mitosis duration may explain some cases of microcephaly.