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Mucosal pH abnormalities are associated with anastomotic dehiscence, ischemia, and malignancy. We postulated that intraluminal pH influences intestinal epithelial motility, proliferation, and differentiation and studied extracellular pHo (7.0-8.5) effects on human (Caco-2) intestinal epithelial motility, proliferation, and differentiation. Mucosal healing was modeled by sheet migration and differentiation by alkaline phosphatase and dipeptidyl dipeptidase specific activity. In parallel differentiation and motility studies, we inhibited proliferation with mitomycin to dissociate indirect mitogenic effects. Intracellular pHi was quantitated using BCECF/AM at varying extracellular pHo and in migrating cells. Motility was maximal at pHo 7.6 and proliferation at 7.2. Each decreased with acidity and alkalinity. By contrast, brush border enzyme activity was lowest at pHo 7.0 and highest at pHo 8.5. pHi was highest at pHo 8.5. Migrating cell pHi was higher than static cell pHi. Thus, extracellular pHo deviations perturb Caco-2 pHi homeostasis and motility. Alkalinity promotes differentiation while acidity induces proliferation and limits differentiation. [ABSTRACT FROM AUTHOR]

See also the commentary by Sitek in this issue. Supplemental material is available for this article.

Objectives: To determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia., Design: A systematic, postmortem prevalence study., Setting: A busy, inner-city morgue in Lusaka., Participants: We sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies., Interventions: Not applicable-this was an observational study., Primary Outcomes: Prevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time., Secondary Outcomes: Shifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates., Results: From 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed 'probably due to COVID-19', and weakest among children, with an age-dependent increase in PCR signal intensity., Conclusions: COVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Patient identification in low- to middle-income countries is one of the most pressing public health challenges of our day. Given the ubiquity of mobile phones, their use for health-care coupled with a biometric identification method, present a unique opportunity to address this challenge. Our research proposes an Android-based solution of an ear biometric tool for reliable identification. Unlike many popular biometric approaches (e.g., fingerprints, irises, facial recognition), ears are noninvasive and easily accessible on individuals across a lifespan. Our ear biometric tool uses a combination of hardware and software to identify a person using an image of their ear. The hardware supports an image capturing process that reduces undesired variability. The software uses a pattern recognition algorithm to transform an image of the ear into a unique identifier. We created three cross-sectional datasets of ear images, each increasing in complexity, with the final dataset representing our target use-case population of Zambian infants (N=224, aged 6days-6months). Using these datasets, we conducted a series of validation experiments, which informed iterative improvements to the system. Results of the improved system, which yielded high recognition rates across the three datasets, demonstrate the feasibility of an Android ear biometric tool as a solution to the persisting patient identification challenge., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Etter L et al.)

Conventional markets can underprovide ecosystem services. Deliberate creation of a market for ecosystem services [e.g., a payments for ecosystem services (PES) scheme] can close the gap. The new ecosystem service market alters behaviors and quantities of ecosystem service provided and reveals prices for the ecosystems service: a market-clearing equilibrium. Assessing the potential for PES programs, which often act as ecological infrastructure investment mechanisms, requires forecasting the market-clearing equilibrium. Forecasting the equilibrium is complicated, especially at relevant social and ecological scales. It requires greater disciplinary integration than valuing ecosystem services or computing the marginal cost of making a land-use change to produce a service. We conduct an ex ante benefit-cost assessment and forecast market-clearing prices and quantities for ecological infrastructure investment contracts in the Panama Canal Watershed. The Panama Canal Authority could offer contracts to private farmers to change land use to increase dry-season water flow and reduce sedimentation. A feasible voluntary contracting system yields a small program of about 1,840 ha of land conversion in a 279,000-ha watershed and generates a 4.9 benefit-cost ratio. Physical and social constraints limit market supply and scalability. Service delays, caused by lags between the time payments must be made and the time services stemming from ecosystem change are realized, hinder program feasibility. Targeting opportunities raise the benefit-cost ratio but reduce the hectares likely to be converted. We compare and contrast our results with prior state-of-the-art assessments on this system., Competing Interests: The authors declare no conflict of interest.

In the developing atrioventricular (AV) valve, limb bud, and somites, cartilage cell lineage differentiation is regulated by bone morphogenetic protein (BMP), while fibroblast growth factor (FGF) controls tendon cell fate. We observed aggrecan and sox9, characteristic of cartilage cell types, and scleraxis and tenascin, characteristic of tendon cell types, in developing avian semilunar valves. Addition of BMP4 to outflow tract (OFT) precursor cells of young (E4.5) but not older (E6) chick embryos activated Smad1/5/8 and induced sox9 and aggrecan expression, while FGF4 treatment increased phosphorylated MAPK (dpERK) signaling and promoted expression of scleraxis and tenascin. These results identify BMP and FGF pathways that promote expression of cartilage- or tendon-like characteristics in semilunar valve precursor cells. In contrast to AV valve precursor cells, which diversify into leaflets (cartilage-like) or chordae tendineae (tendon-like), semilunar valve cells exhibit both cartilage- and tendon-like characteristics in the developing and mature valve cusp.

We report the case of a 43-year-old woman with basal cell carcinoma (BCC) of the umbilicus. Although BCC is a common skin tumor, only 2 cases of BCC arising within the umbilicus have been reported previously. Our review of the literature shows that truncal BCCs frequently develop in younger patients, often grow larger, and are associated with an increased risk for developing multiple nonmelanoma skin cancers. Therefore, we advocate a low threshold for performing biopsies on umbilical lesions that are atypical in appearance, course, or response to therapy.

Pruritus is the most common symptom of skin disease. Even in the absence of primary cutaneous findings, severe and extensive pruritus often is associated with systemic disease. This review considers briefly the physiology of pruritus and discusses the various systemic diseases often accompanied by this bothersome symptom. In addition to exploring the possible mechanisms and potential therapies of itching in selected disorders, this review presents general recommendations for evaluating patients with unexplained pruritus and management guidelines for alleviating their discomfort.