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Large-scale impact assessments of soil-transmitted helminth (STH) programs are essential for determining the frequency of mass drug administration (MDA). In baseline surveys, the prevalence of STHs in the Indian States of Chhattisgarh and Himachal Pradesh was 80.2% in 2015 and 29.0% in 2016, respectively. In 2018, we estimated the prevalence and intensity of STHs after six rounds of biannual MDA in Chhattisgarh and annual MDA in Himachal Pradesh. We conducted multistage cluster sampling surveys in preschool-age children (PSAC), school-age children (SAC), and adolescent cohorts. Stool samples from 3,033 respondents (PSAC, n = 625; SAC, n = 1,363; adolescents, n = 1,045) in Chhattisgarh and 942 respondents (PSAC, n = 192; SAC, n = 388; adolescents, n = 362) in Himachal Pradesh were examined for presence of STH infection using the Kato-Katz method. The overall cluster-adjusted prevalence in Chhattisgarh was 11.6% among all age groups (95% CI, 5.6-22.4)-an 85.5% reduction in the prevalence since 2015. Prevalence was not significantly different across cohorts (PSAC, 11.0% [95% CI, 5.0-22.6]; SAC, 10.9% [95% CI, 5.2-21.6]; adolescents, 12.8% [95% CI, 6.2-24.5]). Ascaris lumbricoides was the most common helminth, with most infections of light intensity. In Himachal Pradesh, only three STH infections were detected in 2018, resulting in a cluster-adjusted prevalence of 0.3% (95% CI, 0.1-1.7)-a 99.0% reduction in prevalence since 2016. All infections were of light intensity. Both states showed substantial improvements in socioeconomic and water, sanitation, and hygiene (WASH) indicators since the baseline surveys. Extensive reductions in prevalence and intensity are linked to sustained, high deworming coverage, as well as socioeconomic WASH indicators.

Background: After a traumatic intracranial hemorrhage (tICH), patients often receive a platelet transfusion to reverse the effects of antiplatelet medication and to reduce neurologic complications. As platelet transfusions have their own risks, this study evaluated their effects on tICH progression, need for operations and mortality., Methods: In this retrospective study, we identified patients admitted to a level 1 trauma centre with a tICH from 2011 to 2015 who were taking acetylsalicylic acid (ASA) or clopidogrel, or both. We categorized patients into 2 groups: platelet transfusion recipients and nonrecipients. We collected data on demographic characteristics, changes in brain computed tomography findings, neurosurgical interventions, in-hospital death and intensive care unit (ICU) length of stay (LOS). We used multivariable logistic regression to compare outcomes between the 2 groups., Results: We identified 224 patients with tICH, 156 (69.6%) in the platelet transfusion group and 68 (30.4%) in the no transfusion group. There were no between-group differences in progression of bleeds or rates of neurosurgical interventions. In the transfusion recipients, there was a trend toward increased ICU LOS (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 0.74-3.40) and in-hospital death (adjusted OR 3.23, 95% CI 0.48-21.74)., Conclusion: There were no differences in outcomes between patients who received platelet transfusions and those who did not; however, the results suggest a worse clinical course, as indicated by greater ICU LOS and mortality, in the transfusion recipients. Routine platelet transfusion may not be warranted in patients taking ASA or clopidogrel who experience a tICH, as it may increase ICU LOS and mortality risk., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Thousands of nuclear and cytosolic proteins are modified with a single β-N-acetylglucosamine on serine and threonine residues in mammals, a modification termed O-GlcNAc. This modification is essential for normal development and plays important roles in virtually all intracellular processes. Additionally, O-GlcNAc is involved in many disease states, including cancer, diabetes, and X-linked intellectual disability. Given the myriad of functions of the O-GlcNAc modification, it is therefore somewhat surprising that O-GlcNAc cycling is mediated by only two enzymes: the O-GlcNAc transferase (OGT), which adds O-GlcNAc, and the O-GlcNAcase (OGA), which removes it. A significant outstanding question in the O-GlcNAc field is how do only two enzymes mediate such an abundant and dynamic modification. In this review, we explore the current understanding of mechanisms for substrate selection for the O-GlcNAc cycling enzymes. These mechanisms include direct substrate interaction with specific domains of OGT or OGA, selection of interactors via partner proteins, posttranslational modification of OGT or OGA, nutrient sensing, and localization alteration. Altogether, current research paints a picture of an exquisitely regulated and complex system by which OGT and OGA select substrates. We also make recommendations for future work, toward the goal of identifying interaction mechanisms for specific substrates that may be able to be exploited for various research and medical treatment goals., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although it has become increasingly common for hospitals to engage in development projects aimed at improving the social determinants of health in surrounding communities, scholarly literature examining the establishment of trust between hospitals and communities is sparse. Because of an extensive and complex history of abuse suffered by marginalized populations at the hands of medical institutions, trust building is critical to the pursuit of equitable health outcomes in these communities. A scoping review was conducted to assess the current base of knowledge for building trust between hospital systems and community members. The review identified only 13 relevant articles addressing this topic, centered on six key themes: with whom to form partnerships; how to form partnerships; conceptualizing and defining trust; questions about investment and hiring; effective communication with communities; and, understanding communities., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Greater Baltimore Medical Center.)

The O-GlcNAc transferase (OGT) modifies nuclear and cytoplasmic proteins with β- N -acetyl-glucosamine (O-GlcNAc). With thousands of O-GlcNAc-modified proteins but only one OGT encoded in the mammalian genome, a prevailing question is how OGT selects its substrates. Prior work has indicated that the tetratricopeptide repeat (TPR) domain of OGT is involved in substrate selection. Furthermore, several variants of OGT causal for X-linked intellectual disability (XLID) occur in the TPR domain. Therefore, we adapted the BioID labeling method to identify interactors of a TPR-BirA* fusion protein in HeLa cells. We identified 115 interactors representing known and novel O-GlcNAc-modified proteins and OGT interactors (raw data deposited in MassIVE, Dataset ID MSV000085626). The interactors are enriched in known OGT processes (e.g., chromatin remodeling) as well as processes in which OGT has yet to be implicated (e.g., pre-mRNA processing). Importantly, the identified TPR interactors are linked to several disease states but most notably are enriched in pathologies featuring intellectual disability that may underlie the mechanism by which mutations in OGT lead to XLID. This interactome for the TPR domain of OGT serves as a jumping-off point for future research exploring the role of OGT, the TPR domain, and its protein interactors in multiple cellular processes and disease mechanisms, including intellectual disability.

Intellectual disability (ID) is a neurodevelopmental condition that affects ~1% of the world population. In total 5-10% of ID cases are due to variants in genes located on the X chromosome. Recently, variants in OGT have been shown to co-segregate with X-linked intellectual disability (XLID) in multiple families. OGT encodes O-GlcNAc transferase (OGT), an essential enzyme that catalyses O-linked glycosylation with β-N-acetylglucosamine (O-GlcNAc) on serine/threonine residues of thousands of nuclear and cytosolic proteins. In this review, we compile the work from the last few years that clearly delineates a new syndromic form of ID, which we propose to classify as a novel Congenital Disorder of Glycosylation (OGT-CDG). We discuss potential hypotheses for the underpinning molecular mechanism(s) that provide impetus for future research studies geared towards informed interventions.

The endothelins and their receptors are best known for their regulation of the vascular system. Their widespread expression in epithelial cells and their overexpression in some tumors has prompted investigation into their ability to regulate cancer progression. In this study, we assessed the mRNA expression of the major endothelin B receptor gene (EDNRB) isoforms and found differences in both mRNA and protein expression in normal breast cells and breast cancer cell lines. Knocking down the EDNRB gene in breast cancer cells altered invasiveness toward endothelin 3 (ET3), and we observed EDNRB isoform-specific regulation of breast cancer cell invasion and cell signaling, as well as isoform- and subtype-specific differences in breast cancer patient survival. The results reported in this study emphasize the importance of the endothelin B receptor in breast cancer. To our knowledge, this study is the first to clarify the differential expression and roles of specific EDNRB isoforms in breast cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We have developed and validated a nested real-time PCR (NRT-PCR) for the genotyping of Chlamydia trachomatis and used it specifically for the typing of either eight genovars from D to K or three genovars of lymphogranuloma venereum (LGV). The 11 probes used in the NRT-PCR correctly identified the DNA from D to K and LGV reference strains and did not cross-react with the DNA from 26 strains representing the bacterial pathogens and commensals of the oropharynx, genital tract, and rectum. The NRT-PCR had a 95% probability of detection at four genome copies (confidence interval, three to six copies) of C. trachomatis per reaction. One hundred cervical and urethral swab specimens containing C. trachomatis DNA from 63 women and 37 men were used to validate the method. The results from the NRT-PCR and the DNA sequencing of amplicons generated from the omp1 gene showed 100% correlation for these samples. The assay also identified the LGV-II genotype in 24 of 48 rectal swab specimens containing C. trachomatis DNA that were obtained from men having sex with men. The Sexually Transmitted Bacteria Reference Laboratory, London, independently confirmed these results using group-specific LGV real-time PCR and restriction fragment length polymorphism analysis. Compared with the NRT-PCR, non-NRT-PCR was found to be less sensitive: it typed C. trachomatis DNA in only 80% of the genital samples and 90% of the rectal swab samples. This is the first successful demonstration of the use of real-time PCR for the genotype-specific typing of C. trachomatis strains that cause sexually transmitted diseases.

This study investigated the comparative performance of the Amplicor assay and an in-house semi-automated, multiplex real-time PCR for the diagnosis of genital chlamydial infection. Four different assays, the COBAS Amplicor CT test (Amplicor PCR), in-house real-time PCR (IHRT-PCR), in-house nested cryptic plasmid PCR and in-house nested major outer membrane protein PCR, were performed on genital swabs from 1000 consecutive patients attending a genitourinary medicine clinic. The samples were designated true positive if Chlamydia trachomatis DNA was detected by at least two of the four above-mentioned assays while a sample was defined as true negative if C. trachomatis DNA was detected in only one or none of the assays. By this criterion, there were 129 true positive and 871 true negative samples for C. trachomatis DNA in this cohort. Amplicor PCR designated 144 samples positive: 128 (89%) of 144 samples were true positive and 16 (11%) were false positive. IHRT-PCR detected 126 of 129 true positive samples and did not generate any false positive results. The sensitivity of IHRT-PCR was comparable with, and specificity was higher than, Amplicor PCR for the diagnosis of genital chlamydial infection.

A multitarget real-time PCR (MRT-PCR) for detection of Chlamydia trachomatis DNA was developed and validated. There were three targets for amplification in a single reaction: the cryptic plasmid (CP), the major outer membrane protein (MOMP) gene, and an internal control. The assay had the following characteristics: (i) detection and confirmation of the presence of C. trachomatis DNA in a single reaction, (ii) detection of all genovars of C. trachomatis without any cross-reactivity with pathogenic bacteria or commensal organisms of the oropharynx and genital tract, (iii) a 95% probability of detection with three copies of MOMP and one copy of CP per reaction mixture, (iv) identification of the inhibition of amplification, (v) a quantitative dynamic range of 25 to 250,000 genome copies per reaction mixture, (vi) high intra- and interassay reproducibilities, and (vii) correct identification of all samples in the validation panel. There were 146 COBAS Amplicor PCR (Amplicor PCR)-positive samples and 122 Amplicor PCR-negative samples in the panel. MRT-PCR detected CP DNA alone in 6 (4%) Amplicor PCR-positive samples and both CP and MOMP DNAs in 140 (96%) of 146 Amplicor PCR-positive samples. The quantity of MOMP DNA in 95 (68%) of 140 samples was within the dynamic range of the assay. The median C. trachomatis load in these samples was 321 genome copies per reaction mixture (range, 26 to 40,137 genome copies per reaction mixture). Due to the inclusion of two different C. trachomatis-specific targets, the assay confirmed 259 (97%) of 268 results in a single reaction. This assay could be used in the qualitative format for the routine detection of C. trachomatis and in the quantitative format for study of the pathogenesis of C. trachomatis-associated diseases. The assay demonstrated the potential to eliminate the need for confirmatory testing in almost all samples, thus reducing the turnaround time and the workload.