The physiological role of the TGR5 receptor in the pancreas is not fully understood. We previously showed that activation of TGR5 in pancreatic ␤ cells by bile acids induces insulin secretion. Glucagon released from pancreatic ␣ cells and glucagonlike peptide 1 (GLP-1) released from intestinal L cells regulate insulin secretion. Both glucagon and GLP-1 are derived from alternate splicing of a common precursor, proglucagon by PC2 and PC1, respectively. We investigated whether TGR5 activation in pancreatic ␣ cells enhances hyperglycemia-induced PC1 expression thereby releasing GLP-1, which in turn increases ␤ cell mass and function in a paracrine manner. (11,12). Recently, TGR5 receptors have been identified on both pancreatic islet ␣ and ␤ cells (13,14). We have previously demonstrated that TGR5 activation on ␤ cells can increase insulin secretion (14). However, the function and physiological role of TGR5 in ␣ cells remain obscure.Glucagon and GLP-1 are produced from a common precursor proglucagon by alternate splicing mediated by proconvertase-2 (PC2) and PC1, respectively (15,16). Whereas the L cells express PC1 only, the pancreatic islet ␣ cells express both PC1 and PC2 (17). Under euglycemic conditions, PC2 activity predominates, and ␣ cells secrete mainly glucagon (18). We hypothesized that TGR5 activation by bile acids under hyperglycemia would activate PC1 as seen in L cells and switch the ␣ cell secretory phenotype from glucagon to GLP-1, which would have a trophic effect on adjacent ␤ cells in a paracrine manner. A combination of decreased systemic glucagon secretion and increased local GLP-1 production would be expected to improve insulin resistance and maintain islet ␤ cell mass. Indeed, several mouse models of diabetes such as streptozotocin-induced diabetes, prediabetic NOD mice, and both ob/ob and db/db mice are associated with increased ␣ cell PC1 and GLP-1 expression, although the mechanisms are not fully understood (19,20).

Melanins are ubiquitous complex polymers that are commonly known in humans to cause pigmentation of our skin. Melanins are also present in bacteria, fungi, and helminths. In this review, we will describe the diverse interactions of fungal melanin with the mammalian immune system. We will particularly focus on Cryptococcus neoformans and also discuss other major melanotic pathogenic fungi. Melanin interacts with the immune system through diverse pathways, reducing the effectiveness of phagocytic cells, binding effector molecules and antifungals, and modifying complement and antibody responses.

BACKGROUND: Corticosteroids may be beneficial in a subset of patients with coronavirus disease 2019 (COVID-19), but predictors of therapeutic response remain unknown. C-reactive protein (CRP) is a routinely measured biomarker, and reduction in its levels after initiation of therapy may predict inpatient mortality. METHODS: In this retrospective cohort study, the charts of patients who were admitted to Montefiore Medical Center between March 10, 2020, and May 2, 2020 for the management of COVID-19 were examined. Of all patients who met inclusion criteria, patients who received corticosteroid treatment were categorized as CRP responders (≥50% CRP level reduction) and CRP nonresponders (<50% CRP level reduction) based on change in CRP within 72 hours of corticosteroid treatment initiation. The outcomes of interest were two-fold: (1) CRP response after treatment with corticosteroid, and (2) differences in mortality among patients with CRP response compared those without. RESULTS: Of 2,707 patients admitted during the study period, 324 received corticosteroid treatment. Of patients who received corticosteroid treatment, CRP responders had reduced risk of death compared with risk among CRP nonresponders (25.2% vs 47.8%; unadjusted odds ratio [OR], 0.37; 95% CI, 0.21-0.65; P < .001). This effect remained strong and significant after adjustment for potential confounders (adjusted OR, 0.27; 95% CI, 0.14-0.54; P < .001). CONCLUSION: Reduction in CRP by 50% or more within 72 hours of initiating corticosteroid therapy potentially predicts inpatient mortality. This may serve as an early biomarker of response to corticosteroid therapy in patients with COVID-19.

Multiparameter continuous physiological monitoring (MCPM) technologies are critical in the clinical management of high-risk neonates; yet, these technologies are frequently unavailable in many African healthcare facilities. We conducted a prospective clinical feasibility study of EarlySense’s novel under-mattress MCPM technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of EarlySense’s technology to Masimo’s Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR) and respiratory rate (RR) measurements using up-time, clinical event detection performance, and accuracy. Between September 15 and December 15, 2020, we collected and analyzed 470 hours of EarlySense data from 109 enrolled neonates. EarlySense’s technology’s up-time per neonate was 2.9 (range 0.8, 5.3) hours for HR and 2.1 (range 0.9, 4.0) hours for RR. The difference compared to the reference was a median of 0.6 (range 0.1, 3.1) hours for HR and 0.8 (range 0.1, 2.9) hours for RR. EarlySense’s technology identified high HR and RR events with high sensitivity (HR 81%; RR 83%) and specificity (HR 99%; RR 83%), but was less sensitive for low HR and RR (HR 0%; RR 14%) although maintained specificity (HR 100%; RR 95%). There was a greater number of false negative and false positive RR events than false negative and false positive HR events. The normalized spread of limits of agreement was 9.6% for HR and 28.6% for RR, which met the a priori-identified limit of 30%. EarlySense’s MCPM technology was clinically feasible as demonstrated by high percentage of up-time, strong clinical event detection performance, and agreement of HR and RR measurements compared to the reference technology. Studies in critically ill neonates, assessing barriers and facilitators to adoption, and costing analyses will be key to the technology’s development and potential uptake and scale-up.