Lineage tracing studies have revealed that transcription factors play a cardinal role in pancreatic development, differentiation and function. Three transitions define pancreatic organogenesis, differentiation and maturation. In the primary transition, when pancreatic organogenesis is initiated, there is active proliferation of pancreatic progenitor cells. During the secondary transition, defined by differentiation, there is growth, branching, differentiation and pancreatic cell lineage allocation. The tertiary transition is characterized by differentiated pancreatic cells that undergo further remodeling, including apoptosis, replication and neogenesis thereby establishing a mature organ. Transcription factors function at multiple levels and may regulate one another and auto-regulate. The interaction between extrinsic signals from non-pancreatic tissues and intrinsic transcription factors form a complex gene regulatory network ultimately culminating in the different cell lineages and tissue types in the developing pancreas. Mutations in these transcription factors clinically manifest as subtypes of diabetes mellitus. Current treatment for diabetes is not curative and thus, developmental biologists and stem cell researchers are utilizing knowledge of normal pancreatic development to explore novel therapeutic alternatives. This review summarizes current knowledge of transcription factors involved in pancreatic development and β-cell differentiation in rodents.

Background: Hospital settings are at increased risk of spreading Coronavirus Disease 2019 (COVID-19) infections, hence non-pharmaceutical prevention interventions (NPPIs) and prioritized vaccination of healthcare workers and resident patients are critical. The status of COVID-19 hospital acquired infections (HAIs) in low-income settings is unclear. We aimed to identify and summarize the existing evidence on COVID-19 HAIs amongst patients, prior to the rollout of vaccines in countries worldwide. Methods: We conducted a scoping review of English peer-reviewed literature in PubMed, Web of Science and Scopus using a combination of selected search terms. Full texts articles presenting results on COVID-19 HAIs in hospitalised patients before the rollout of vaccines in countries worldwide were eligible. Data extracted from eligible articles included estimates of COVID-19 HAIs, country, and type of hospital setting, and was summarized narratively. Quality assessment of included articles was not possible. Results: Literature searches generated a total of 5920 articles, and 45 were eligible for analysis. Eligible articles were from Europe, North America, Asia, and Brazil and none were from low-income countries. The proportion of COVID-19 HAIs ranged from 0% when strict NPPIs were applied, to 65% otherwise. The estimates of COVID-19 HAIs did not differ by country but were lower in studies conducted after implementation of NPPIs and in specialized hospital settings for operative surgery. Studies conducted before the implementation of NPPIs or in long-term care and psychiatric wards often reported high estimates of HAI. Although there was no clear trend in general wards, those situated in academic hospitals managed to reduce HAI rates under strict NPPI protocols. Operative surgery settings, unlike psychiatric settings, effectively prevented COVID-19 HAI using tailored NPPIs. Conclusion: The available evidence shows a high risk of COVID-19 HAIs, the feasibility of preventing HAIs in different healthcare settings and the importance of appropriately tailored NPPIs. There were no data from low-income settings, therefore, it is unclear whether the reported NPPI approaches could be equally effective elsewhere. We recommend routine monitoring of COVID-19 HAIs in countries with low vaccination coverage, to identify and close gaps in NPPIs and understand gains made from vaccinating healthcare workers and hospitalized patients.

South Africa has the highest burden of human immunodeficiency virus (HIV) infections in the world with significant geographical variations. We identified the predictors of HIV infections and their sub-geographical-level contributions to the epidemic using a decade long data (2002–2012) from 6484 South African women. Generalized additive models were used to uncover the most significant features of these estimates across the region. In the overall analysis, younger age, not married or cohabiting with a partner, partner has another partner(s) and null/prim parity, using injectable contraceptives and presence of other sexually transmitted infections (STIs) were identified as independent predictors of HIV seroconversions. Overall, the top three highest contributors to infections were women’s marital status (PAR% = 73%, 95% CI: 68%, 77%), parity (PAR% = 47%, 95% CI: 42%, 53%) and partnership factors (PAR% = 37%, 95% CI: 30%, 44%). However, their contributions varied remarkably at sub-geographical level. This was mainly due to the substantial localized variations in their prevalence and hazard ratios across the region. Our results will guide policy makers to develop tailored prevention strategies in order to allocate scarce resources by targeting the most significant contributors of HIV infection at sub-geographical level.

Women enrolled in human immunodeficiency virus (HIV) prevention efficacy trials receive counseling on prevention of HIV, sexually transmitted infections (STIs), and pregnancy during every visit. Incident pregnancy has an impact on efficacy outcomes. Incidence rates of pregnancy and HIV/STIs among women who became pregnant and associated risk factors were assessed. Data from 9165 women participating in HIV prevention trials in KwaZulu-Natal, South Africa from 2002–2012 were combined. Demographic and behavioral predictors of incidence pregnancy and incidence HIV and STIs were determined using Cox regression models. Overall pregnancy incidence was 9.6 per 100 person-year (py) (95% confidence interval [Cl], 9.1–10.3). Human immunodeficiency virus incidence among pregnant women was 5.93 per 100 py (95% Cl, 4.73–7.44). Incidence of STIs among pregnant women for Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and Treponema pallidum (syphilis) were 10.87, 7.42, 3.92, and 1.43 per 100 py, respectively. In the adjusted analyses, we observed overlapping risk factors for HIV acquisition during pregnancy, ie, young age, not married/not cohabitating, and low parity. The risk of pregnancy and HIV acquisition is more than 3 times higher among young women (<20 years of age). We identified overlapping risk factors for pregnancy and HIV incidence, suggesting an urgent need for appropriate, targeted, individual-centred counseling for women participating in HIV prevention trials.

South Africa has the highest burden of human immunodeficiency virus (HIV) infections in the world. There is also growing evidence that an individual’s risk of contracting HIV is increased by the presence of other sexually transmitted infections (STIs). The primary objective of this study was to examine the association between the prevalence of STIs in a cohort of South African women who enrolled in HIV prevention trials (2002–2012). The current study linked the individual factors with the community-level characteristics using geo-referencing. These multi-level data were analyzed in generalized additive mixed models settings. In the multivariate logistic regression model, younger age (odds ratio [OR] 4.30, 95% CI 3.20, 5.77 and OR 2.72, 95% CI 2.02, 3.66 for age < 25 and 25–29, respectively); being single/not cohabiting (OR 4.57, 95% CI 3.18, 6.53), two + sex partners (OR 1.46, 95% CI 1.18,1.80); parity < 2 (OR 2.04, 95% CI 1.53, 2.72), parity = 2 (OR 1.85, 95% CI 1.37, 2.48), and using injectables (contraceptive) (OR 1.53, 95% CI 1.13, 2.06) were all significantly associated with increased prevalence of STIs. Women who resided in the communities with high proportions of female headed-households were also significantly at higher risk for STIs (OR 1.20, p = .0025). Because these factors may reflect characteristics of the larger groups who share similar cultural norms and social environments, they can provide considerable insight into the spread of STIs. Prevention strategies based on individual and community-level drivers of STIs are likely to be the most effective means of targeting and reaching those at greatest risk of infection. This strategy has the potential to play a significant role in the epidemic’s trajectory.

Background: In low- and middle-income countries (LMICs) such as South Africa, there is paucity of data on SARS-CoV-2 infections among children attending school, including seroprevalence and transmission dynamics. Objective: This pilot study aims to assess (1) the prevalence of self-reported or confirmed SARS-CoV-2 prior infections, COVID-19 symptoms (including long COVID), seroprevalence of SARS-CoV-2 antibodies, and general/mental health, (2) longitudinal changes in SARS-CoV-2 seroprevalence, and (3) SARS-CoV-2 acute infections, immune responses, transmission dynamics, and symptomatic versus asymptomatic contacts in a unique cohort of unvaccinated primary school learners, their parents, teachers, and close contacts in semirural primary school settings. Methods: Learners (grades 1-7) from primary schools in KwaZulu-Natal, South Africa, their parents, and teachers will be invited to enroll into the COVID kids school study (CoKiDSS). CoKiDSS comprises 3 parts: a cross-sectional survey (N=640), a follow-up survey (n=300), and a nested case-cohort substudy. Finger-prick blood and saliva samples will be collected for serological and future testing, respectively, in the cross-sectional (451 learners:147 parents:42 teachers) and follow-up (210 learners:70 parents:20 teachers) surveys. The nested case-cohort substudy will include cases from the cross-sectional survey with confirmed current SARS-CoV-2 infection (n=30) and their close contacts (n=up to 10 per infected participant). Finger-prick blood (from all substudy participants), venous blood (from cases), and nasal swabs (from cases and contacts) will be collected for serological testing, immunological testing, and viral genome sequencing, respectively. Questionnaires covering sociodemographic and general and mental health information, prior and current SARS-CoV-2 symptoms and testing information, vaccination status, preventative behavior, and lifestyle will be administered. Statistical methods will include generalized linear mixed models, intracluster correlation, descriptive analysis, and graphical techniques. Results: A total of 645 participants were enrolled into the cross-sectional survey between May and August 2023. A subset of 300 participants were followed up in the follow-up survey in October 2023. Screening of the participants into the nested case-cohort substudy is planned between November 2023 and September 2024. Data cleanup and analysis for the cross-sectional survey is complete, while those for the follow-up survey and nested case substudy will be completed by the third quarter of 2024. The dissemination and publication of results is anticipated for the fourth quarter of 2024. Conclusions: This study provides data from an LMIC setting on the impact of SARS-CoV-2 on school-attending learners, their parents, and teachers 3 years after the SARS-CoV-2 pandemic was declared and 21-24 months after resumption of normal school attendance. In particular, this study will provide data on the prevalence of self-reported or confirmed SARS-CoV-2 prior infection, prior and current symptoms, seroprevalence, changes in seroprevalence, SARS-CoV-2 transmission, SARS-CoV-2 adaptive immune responses, and symptoms of long COVID and mental health among a triad of learners, their parents, and teachers. International Registered Report Identifier (IRRID): DERR1-10.2196/52713