Chromogranin A-positive hormone-negative endocrine cells in pancreas in human pregnancy.

Introduction: We sought to determine whether chromogranin A-positive hormone-negative (CPHN) endocrine cells are increased in the pancreas of pregnant women, offering potential evidence in support of neogenesis. Methods: Autopsy pancreata from pregnant women (n = 14) and age-matched non-pregnant control women (n = 9) were obtained. Staining of pancreatic sections for chromogranin A, insulin and a cocktail of glucagon, somatostatin, pancreatic polypeptide and ghrelin was undertaken, with subsequent evaluation for CPHN cell frequency. Results: The frequency of clustered ß-cells was increased in pregnant compared to non-pregnant subjects (46.6 ± 5.0 vs. 31.8 ± 5.0% clustered ß-cells of total clustered endocrine cells, pregnant vs. non-pregnant, p < .05). Frequency of endocrine cocktail cells was lower in pregnant women than non-pregnant women (36.2 ± 4.0 vs. 57.0 ± 6.8% clustered endocrine cocktail cells of total clustered endocrine cells, pregnant vs. non-pregnant, p < .01). No difference in frequency of CPHN cells was found in islets, nor in clustered or single cells scattered throughout the exocrine pancreas, between pregnant and non-pregnant women. The frequency of CPHN cells in pregnancy was independent of the number of pregnancies (gravidity). Conclusions: Our findings of no increase in CPHN cell frequency in pancreas of pregnant women suggest that this potential ß-cell regenerative mechanism is not that by which the increased ß-cell mass of pregnancy is achieved. However, an increase in the percentage of clustered ß-cells was found in pregnancy, with decreased frequency of other endocrine cells in clusters, suggesting a compensatory shift from other pancreatic endocrine cell types to ß-cells as a mechanism to meet the increased insulin demands of pregnancy.

The Use of Digital Tools to Mitigate the COVID-19 Pandemic: Comparative Retrospective Study of Six Countries.

BACKGROUND: Since the COVID-19 outbreak began in Wuhan, China, countries worldwide have been forced to take unprecedented measures to combat it. While some countries are still grappling with the COVID-19 pandemic, others have fared better and have re-established relative normalcy quickly. The rapid transmission rate of the virus has shown a greater need for efficient and technologically modern containment measures. The use of digital tools to facilitate strict containment measures in countries that have fared well against the COVID-19 pandemic has sparked both interest and controversy. OBJECTIVE: In this study, we compare the precautions taken against the spread of COVID-19 in the United States, Spain, and Italy, with Taiwan, South Korea, and Singapore, particularly related to the use of digital tools for contact tracing, and propose policies that could be used in the United States for future COVID-19 waves or pandemics. METHODS: COVID-19 death rate data were obtained from the European Center for Disease Prevention and Control (ECDC), accessed through the Our World in Data database, and were evaluated based on population size per 100,000 people from December 31, 2019, to September 6, 2020. All policies and measures enacted were obtained from their respective governmental websites. RESULTS: We found a strong association between lower death rates per capita and countries that implemented early mask use and strict border control measures that included mandatory quarantine using digital tools. There is a significant difference in the number of deaths per 100,000 when comparing Taiwan, South Korea, and Singapore with the United States, Spain, and Italy. CONCLUSIONS: Based on our research, it is evident that early intervention with the use of digital tools had a strong correlation with the successful containment of COVID-19. Infection rates and subsequent deaths in Italy, Spain, and the United States could have been much lower with early mask use and, more importantly, timely border control measures using modern digital tools. Thus, we propose that the United States execute the following national policies should a public health emergency be declared: (1) immediately establish a National Command responsible for enacting strict mandatory guidelines enforced by federal and state governments, including national mask use; (2) mandate civilian cooperation with health officials in contact tracing and quarantine orders; and (3) require incoming travelers to the United States and those quarantined to download a contact tracing app. We acknowledge the countries we studied differ in their cultures, political systems, and reporting criteria for COVID-19 deaths. Further research may need to be conducted to address these limitations; however, we believe that the proposed policies could protect the American public.

Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas.

Context: Previously, we identified chromograninA positive hormone-negative (CPHN) cells in high frequency in human fetal and neonatal pancreas, likely representing nascent endocrine precursor cells. Here, we characterize the putative endocrine fate and replicative status of these newly formed cells. Objective: To establish the replicative frequency and transcriptional identity of CPHN cells, extending our observation on CPHN cell frequency to a larger cohort of fetal and infant pancreas. Design, Setting, and Participants: 8 fetal, 19 infant autopsy pancreata were evaluated for CPHN cell frequency; 12 fetal, 24 infant/child pancreata were evaluated for CPHN replication and identity. Results: CPHN cell frequency decreased 84% (islets) and 42% (clusters) from fetal to infant life. Unlike the beta-cells at this stage, CPHN cells were rarely observed to replicate (0.2 ± 0.1 vs. 4.7 ± 1.0%, CPHN vs. islet hormone positive cell replication, p < 0.001), indicated by the lack of Ki67 expression in CPHN cells whether located in the islets or in small clusters, and with no detectable difference between fetal and infant groups. While the majority of CPHN cells express (in overall compartments of pancreas) the pan-endocrine transcription factor NKX2.2 and beta-cell specific NKX6.1 in comparable frequency in fetal and infant/child cases (81.9 ± 6.3 vs. 82.8 ± 3.8% NKX6.1+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.9; 88.0 ± 4.7 vs. 82.1 ± 5.3% NKX2.2+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.4), the frequency of clustered CPHN cells expressing NKX6.1 or NKX2.2 is lower in infant/child vs. fetal cases (1.2 ± 0.3 vs. 16.7 ± 4.7 clustered NKX6.1+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01; 2.7 ± 1.0 vs. 16.0 ± 4.0 clustered NKX2.2+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01). Conclusions: The frequency of CPHN cells declines steeply from fetal to infant life, presumably as they differentiate to hormone-expressing cells. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells. Precis : CPHN cell frequency declines steeply from fetal to infant life, as they mature to hormone expression. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells.

ß-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of ß-Cell Dedifferentiation and Degranulation.

CONTEXT: Type 2 diabetes is characterized by a ß-cell deficit and a progressive defect in ß-cell function. It has been proposed that the deficit in ß-cells may be due to ß-cell degranulation and transdifferentiation to other endocrine cell types. OBJECTIVE: The objective of the study was to establish the potential impact of ß-cell dedifferentiation and transdifferentiation on ß-cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated. DESIGN, SETTING, AND PARTICIPANTS: Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases. RESULTS: Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 ± 0.03 cells/islet vs 0.03 ± 0.01 cells/islet, P < .01), the impact on the ß-cell deficit would be minimal. Furthermore, we established that the deficit in ß-cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells. CONCLUSIONS: Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in ß-cells in type 2 diabetes but may reflect, in part, attempted ß-cell regeneration.