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Objective: Studies exploring the relationship between neonatal abstinence syndrome (NAS) and congenital anomalies (CA) in the United States are limited given the small sample size or data prior to the opioid epidemic. We aimed to determine if there is an association between NAS and CA in a nationally representative cohort of newborn hospitalization in the United States., Study Design: This was a cross-sectional analysis of NAS-related hospitalizations within the 2016 Kids Inpatient Database. International Classification of Diseases (ICD-10-CM) diagnostic codes were used to identify NAS hospitalizations and those with and without CA. The primary outcome was the odds of CAs in NAS hospitalizations. Multivariate survey logistic regression was used to analyze the relationship between NAS and CA., Results: Among 3.7 million newborn hospitalizations, 25,394 had NAS (6.7 per 1,000). The prevalence of any CA was higher in those with NAS when compared with non-NAS hospitalizations (10.3 vs. 4.9%; odds ratio = 2.27; 95% confidence interval [CI]: 2.13-2.43). Adjusted analysis showed similar results (adjusted odds ratio: = 1.83, CI: 1.71-1.95). NAS hospitalizations with CA had a higher mortality rate (0.6 vs 0.04%, p  < 0.0001) and higher resource use., Conclusion: This nationwide study shows that NAS may be associated with increased odds of CAs, suggesting that NAS may be a risk factor for increased morbidity in the newborn period., Key Points: · 1 in 10 newborns with NAS had at least one congenital anomaly.. · NAS hospitalization with congenital anomalies had higher resource use and mortality.. · Pediatricians caring for newborns with NAS should have a high index of suspicion for birth defects.., Competing Interests: None declared., (Thieme. All rights reserved.)

Expanding β cell mass is a critical goal in the fight against diabetes. CDK4, an extensively characterized cell cycle activator, is required to establish and maintain β cell number. β cell failure in the IRS2-deletion mouse type 2 diabetes model is, in part, due to loss of CDK4 regulator cyclin D2. We set out to determine whether replacement of endogenous CDK4 with the inhibitor-resistant mutant CDK4-R24C rescued the loss of β cell mass in IRS2-deficient mice. Surprisingly, not only β cell mass but also β cell dedifferentiation was effectively rescued, despite no improvement in whole body insulin sensitivity. Ex vivo studies in primary islet cells revealed a mechanism in which CDK4 intervened downstream in the insulin signaling pathway to prevent FOXO1-mediated transcriptional repression of critical β cell transcription factor Pdx1. FOXO1 inhibition was not related to E2F1 activity, to FOXO1 phosphorylation, or even to FOXO1 subcellular localization, but rather was related to deacetylation and reduced FOXO1 abundance. Taken together, these results demonstrate a differentiation-promoting activity of the classical cell cycle activator CDK4 and support the concept that β cell mass can be expanded without compromising function.

The purpose of this paper is to explore how social influence (SI), which is disaggregated into subjective norms (SN), social image (SIM), and social identity (SID), predicts perceived usefulness (PU), perceived pleasure (PP), and continuance intention (CI) toward sports and fitness applications. The underlying context is the socialization and gamification of exercise during the Covid-19 pandemic. Based on the theory of SI and the technology acceptance model, a theoretical framework was built where PU and PP mediate the influence of SI on CI, and proposed hypotheses were tested. The responses of 296 Keep users (a popular sports and fitness application in China) to a questionnaire survey were analyzed. SN and SIM were found to have significant positive effects on SID; SID has significant positive effects on PU and PP; both PU and PP have significant positive effects on the CI of users; SID and PU positively and significantly mediate the relationship between SN/SIM and CI; PU positively and significantly mediates the SID-CI relationship. However, the role of PP in mediating the influence of SI on CI is non-significant. This paper deepens the current understanding of the mechanisms that influence the relationship between SI and CI under the context of socialization and gamification services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Du, Wang and Oteng-Darko.)

Aging is associated with loss of proliferation of the insulin-secreting β-cell, a possible contributing factor to the increased prevalence of type 2 diabetes in the elderly. Our group previously discovered that moderate endoplasmic reticulum (ER) stress occurring during glucose exposure increases the adaptive β-cell proliferation response. Specifically, the ATF6α arm of the tripartite Unfolded Protein Response (UPR) promotes β-cell replication in glucose excess conditions. We hypothesized that β-cells from older mice have reduced proliferation due to aberrant UPR signaling or an impaired proliferative response to ER stress or ATF6α activation. To investigate, young and old mouse islet cells were exposed to high glucose with low-dose thapsigargin or activation of overexpressed ATF6α, and β-cell proliferation was quantified by BrdU incorporation. UPR pathway activation was compared by qPCR of target genes and semi-quantitative Xbp1 splicing assay. Intriguingly, although old β-cells had reduced proliferation in high glucose compared to young β-cells, UPR activation and induction of proliferation in response to low-dose thapsigargin or ATF6α activation in high glucose were largely similar between young and old. These results suggest that loss of UPR-led adaptive proliferation does not explain the reduced cell cycle entry in old β-cells, and raise the exciting possibility that future therapies that engage adaptive UPR could increase β-cell number through proliferation even in older individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Snyder, Darko, Sharma and Alonso.)

Success or failure of pancreatic beta cell adaptation to ER stress is a determinant of diabetes susceptibility. The ATF6 and IRE1/XBP1 pathways are separate ER stress-response effectors important to beta cell health and function. ATF6α. and XBP1 direct overlapping transcriptional responses in some cell types. However, the signaling dynamics and interdependence of ATF6α and XBP1 in pancreatic beta cells have not been explored. To assess pathway-specific signal onset, we performed timed exposures of primary mouse islet cells to ER stressors and measured the early transcriptional response. Comparing the time course of induction of ATF6 and XBP1 targets suggested that the two pathways have similar response dynamics. The role of ATF6α in target induction was assessed by acute knockdown using islet cells from Atf6 α flox/flox mice transduced with adenovirus expressing Cre recombinase. Surprisingly, given the mild impact of chronic deletion in mice, acute ATF6α knockdown markedly reduced ATF6-pathway target gene expression under both basal and stressed conditions. Intriguingly, although ATF6α knockdown did not alter Xbp1 splicing dynamics or intensity, it did reduce induction of XBP1 targets. Inhibition of Xbp1 splicing did not decrease induction of ATF6α targets. Taken together, these data suggest that the XBP1 and ATF6 pathways are simultaneously activated in islet cells in response to acute stress and that ATF6α is required for full activation of XBP1 targets, but XBP1 is not required for activation of ATF6α targets. These observations improve understanding of the ER stress transcriptional response in pancreatic islets., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Sharma et al.)

Pancreatic β-cell regeneration, the therapeutic expansion of β-cell number to reverse diabetes, is an important goal. Replication of differentiated insulin-producing cells is the major source of new β-cells in adult mice and juvenile humans. Nucleoside analogs such as BrdU, which are incorporated into DNA during S-phase, have been widely used to quantify β-cell proliferation. However, reports of β-cell nuclei labeling with both BrdU and γ-phosphorylated H2A histone family member X (γH2AX), a DNA damage marker, have raised questions about the fidelity of BrdU to label S-phase, especially during conditions when DNA damage is present. We performed experiments to clarify the causes of BrdU-γH2AX double labeling in mouse and human β-cells. BrdU-γH2AX colabeling is neither an age-related phenomenon nor limited to human β-cells. DNA damage suppressed BrdU labeling and BrdU-γH2AX colabeling. In dispersed islet cells, but not in intact islets or in vivo, pro-proliferative conditions promoted both BrdU and γH2AX labeling, which could indicate DNA damage, DNA replication stress, or cell cycle-related intrinsic H2AX phosphorylation. Strategies to increase β-cell number must not only tackle the difficult challenge of enticing a quiescent cell to enter the cell cycle, but also achieve safe completion of the cell division process., (© 2019 by the American Diabetes Association.)

This study reports on aflatoxin production and peanut (Bailey's variety) quality, for four peanut pre-storage treatments; [(Raw clean (Raw-Cl), Raw inoculated with Aspergillus flavus NRRL 3357 (Raw-Inf), inoculated partially roasted but not-blanched (PRN-blanch); and inoculated partially roasted, blanched with discolored nuts sorted out (PR-blanched)]. All four treated samples were packaged in four different packaging systems [polypropylene woven sacks (PS), hermetic packs (HP), hermetic packs with oxygen absorbers (HPO), and vacuumed hermetic packs (HPV)] and stored under controlled conditions at a temperature of 30 ± 1 °C and water activity of 0.85 ± 0.02, for 14 weeks. Raw-Inf samples in PS had a higher fungal growth with a mean value of 8.01 × 10 4  CFU/g, compared to the mean values of samples in hermetic packs: 1.07 × 10 3  CFU/g for HP, 14.55 CFU/g for HPO, and 57.82 CFU/g for HPV. Similarly, the hermetic bags were able to reduce aflatoxin level of the Raw-Inf samples by 50.6% (HP), 63.0% (HPV), and 66.8% (HPO). Partial roasting and blanching in PS also reduced aflatoxin level by about 74.6%. Quality maintenance was the best for peanuts in HPO, recording peroxide value (PV) of 10.16 meq/kg and p -Anisidine ( p -Av) of 3.95 meq/kg compared to samples in polypropylene woven sacks which had PV of 19.25 meq/kg and p -Av of 6.48 meq/kg. These results indicate that using zero-oxygen hermetic packaging, instead of the conventional polypropylene woven sacks, helped to suppress aflatoxin production and quality deterioration. Also, partially roasted, blanched and sorted peanuts showed a potential for reducing aflatoxin presence during storage.

In the past decade, several Bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. One strain was indistinguishable from B. cereus G9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. The finding that B. cereus G9241 pathogenesis in mice is dependent on pagA1-derived protective antigen (PA) synthesis suggests that an anthrax toxin-based vaccine may be effective against this toxin-encoding B. cereus strain. Dunkin Hartley guinea pigs were immunized with protein- and DNA-based anthrax toxin-based vaccines, immune responses were evaluated and survival rates were calculated after lethal aerosol exposure with B. cereus G9241 spores. Each vaccine induced seroconversion with the protein immunization regimen eliciting significantly higher serum levels of antigen-specific antibodies at the prechallenge time-point compared with the DNA-protein prime-boost immunization schedule. Complete protection against lethal challenge was observed in all groups with a detectable prechallenge serum titer of toxin neutralizing antibodies. For the first time, we demonstrated that the efficacy of fully defined anthrax toxin-based vaccines was protective against lethal B. cereus G9241 aerosol challenge in the guinea pig animal model., (Published 2014. This article is a US Government work and is in the public domain in the USA.)