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Obesity is a multifactorial metabolic disorder associated with endothelial dysfunction and increased risk of cardiovascular disease. Adipose capillary adipose endothelial cells (CaECs) plays a crucial role in lipid transport and storage. Here, we investigated the mechanisms underlying CaEC-adipocyte interaction and its impact on metabolic function. Single-cell RNA sequencing (scRNAseq) revealed an enrichment of fatty acid handling machinery in CaECs from high fat diet (HFD) mice, suggesting their specialized role in lipid metabolism. Transmission electron microscopy (TEM) confirmed direct heterocellular contact between CaECs and adipocytes. To model this, we created an in vitro co-culture transwell system to model the heterocellular contact observed with TEM. Contact between ECs and adipocytes in vitro led to upregulation of fatty acid binding protein 4 in response to lipid stimulation, hinting intercellular signaling may be important between ECs and adipocytes. We mined our and others scRNAseq datasets to examine which connexins may be present in adipose capillaries and adipocytes and consistently identified connexin 43 (Cx43) in mouse and humans. Genetic deletion of endothelial Cx43 resulted in increased epididymal fat pad (eWAT) adiposity and dyslipidemia in HFD mice. Consistent with this observation, phosphorylation of Cx43 at serine 368, which closes gap junctions, was increased in HFD mice and lipid-treated ECs. Mice resistant to this post-translational modification, Cx43S368A, were placed on an HFD and were found to have reduced eWAT adiposity and improved lipid profiles. These findings suggest Cx43-mediated heterocellular communication as a possible regulatory mechanism of adipose tissue function., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Physiological Society.)

In the vasculature, nitric oxide (NO) is produced in the endothelium by endothelial nitric oxide synthase (eNOS) and is critical for the regulation of blood flow and blood pressure. Blood flow may also be regulated by the formation of nitrite-derived NO catalyzed by hemoproteins under hypoxic conditions. We sought to investigate whether nitrite administration may affect tissue perfusion and systemic hemodynamics in WT and eNOS knockout mice. We found that global eNOS KO mice show decreased tissue perfusion compared to WT mice by using laser speckle contrast imaging. To study both the acute and long-term effects of sodium nitrite (0, 0.1, 1, and 10 mg/kg) on peripheral blood flow and systemic blood pressure, a bolus of nitrite was delivered intraperitoneally every 24 h over 4 consecutive days. We found that nitrite administration resulted in a dose-dependent and acute increase in peripheral blood flow in eNOS KO mice but had no effects in WT mice. The nitrite induced changes in tissue perfusion were transient, as determined by intraindividual comparisons of tissue perfusion 24-h after injection. Accordingly, 10 mg/kg sodium nitrite acutely decreased blood pressure in eNOS KO mice but not in WT mice as determined by invasive Millar catheterization. Interestingly, we found the vasodilatory effects of nitrite to be inversely correlated to baseline tissue perfusion. These results demonstrate the nitrite acutely recovers hypoperfusion and hypertension in global eNOS KO mice and suggest the vasodilatory actions of nitrite are dependent upon tissue hypoperfusion., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Endothelial cells (ECs) adapt to the unique needs of their resident tissue and metabolic perturbations, such as obesity. We sought to understand how obesity affects EC metabolic phenotypes, specifically mitochondrial gene expression. We investigated the mesenteric and adipose endothelium because these vascular beds have distinct roles in lipid homeostasis. Initially, we performed bulk RNA sequencing on ECs from mouse adipose and mesenteric vasculatures after a normal chow (NC) diet or high-fat diet (HFD) and found higher mitochondrial gene expression in adipose ECs compared with mesenteric ECs in both NC and HFD mice. Next, we performed single-cell RNA sequencing and categorized ECs as arterial, capillary, venous, or lymphatic. We found mitochondrial genes to be enriched in adipose compared with mesentery under NC conditions in artery and capillary ECs. After HFD, these genes were decreased in adipose ECs, becoming like mesenteric ECs. Transcription factor analysis revealed that peroxisome proliferator-activated receptor-γ (PPAR-γ) had high specificity in NC adipose artery and capillary ECs. These findings were recapitulated in single-nuclei RNA-sequencing data from human visceral adipose. The sum of these findings suggests that mesenteric and adipose arterial ECs metabolize lipids differently, and the transcriptional phenotype of the vascular beds converges in obesity due to downregulation of PPAR-γ in adipose artery and capillary ECs. NEW & NOTEWORTHY Using bulk and single-cell RNA sequencing on endothelial cells from adipose and mesentery, we found that an obesogenic diet induces a reduction in adipose endothelial oxidative phosphorylation gene expression, resulting in a phenotypic convergence of mesenteric and adipose endothelial cells. Furthermore, we found evidence that PPAR-γ drives this phenotypic shift. Mining of human data sets segregated based on body mass index supported these findings. These data point to novel mechanisms by which obesity induces endothelial dysfunction.

Purpose: Guidelines regarding parental leave in oral and maxillofacial surgery do not exist. This inconsistency may contribute to gender disparities and an increase in resident burnout. The purpose of this study was to examine perceptions and attitudes of oral and maxillofacial surgery residents toward parental leave., Materials and Methods: This was a cross-sectional study in which an anonymous 26-item questionnaire was electronically mailed to all current oral and maxillofacial surgery residents in the United States during August 2020. The survey consisted of 5 sections: 1) resident information, 2) residency program information, 3) parental policy information, 4) attitudes regarding parental leave, and 5) attitudes regarding early parenthood., Results: Surveys were sent to 860 oral and maxillofacial surgery residents; 220 completed the questionnaire (25.6%). Majority of respondents were male between the ages of 26 and 30. Half of the respondents did not know whether their oral and maxillofacial surgery program had a formal parental leave policy. Almost a third of residents reported that their program did not have a policy regarding parental leave. Only some programs had a policy regarding parental leave. Most programs allotted 2 days to 2 weeks for parental leave. Parenthood did not prevent pursuit of fellowship training. The majority of co-residents indicated that parenthood had a neutral impact on the performance of their colleagues. Lactation facilities and/or childcare services were not present in all programs., Conclusions: Most oral and maxillofacial surgery residents support parental leave despite the lack of a formal policy in their residency program. Residents who had a child during residency received up to 2 weeks as parental leave. Residents felt that their programs were supportive of parental leave. Parenthood did not prevent the pursuit of fellowship training., (Published by Elsevier Inc.)

Introduction: Compared with the older pediatric population, neonates have greater perioperative morbidity and mortality. Difficulty with glucose regulation may be a contributing modifiable risk factor during perioperative anesthetic management. To mitigate the risk of hyperglycemia in neonates, some providers empirically halve the preoperative rate of dextrose-containing infusions during surgery., Aim: To assess the association between halving the preoperative maintenance dextrose rate and postoperative euglycemia in neonatal intensive care unit patients undergoing exploratory laparotomies., Methods: Neonatal intensive care unit patients who underwent exploratory laparotomy under general anesthesia from 1/1/2014 to 11/21/2019 were included in this analysis. Hyperglycemia and hypoglycemia were defined as >150 mg/dL and <46 mg/dL. A calculated dextrose ratio was utilized to categorize patients into full and half intraoperative dextrose rate cohorts. Univariate analyses were performed with Fisher's exact test, the Wilcoxon rank sum test, or Spearman's correlation. Multivariable analyses with regression models were conducted after graphical evaluation of a predetermined set of independent variables., Results: 107 patients were included in the full dextrose rate cohort and 96 patients in the half dextrose rate cohort with postoperative hyperglycemia occurring in 47 and 28 patients, respectively. On univariate analysis, halving the preoperative dextrose rate was associated with decreased postoperative hyperglycemia (odds ratio: 0.53; 95% CI: 0.28-0.98, P = 0.041). This association continued in the regression model (adjusted odds ratio: 0.49; 95% CI: 0.25-0.80, P = 0.008) after controlling for preoperative dextrose rate, preoperative serum glucose, preoperative pH, surgical duration, postmenstrual age at surgery, and the presence of necrotizing enterocolitis. Only one patient was hypoglycemic postoperatively, and they were in the full dextrose cohort., Conclusion: Halving of preoperative dextrose rates intraoperatively during exploratory laparotomy in neonatal intensive care unit patients was associated with a decreased risk of postoperative hyperglycemia without substantially increasing the occurrence of postoperative hypoglycemia. The practice of halving preoperative dextrose rates may be an effective empirical approach for intraoperative glucose management in the high-risk neonatal population when blood glucose monitoring is challenging., (© 2020 John Wiley & Sons Ltd.)

Background: Depression is common among older patients yet is often inadequately treated. Patient beliefs about antidepressants are known to affect treatment initiation and adherence, but are often not expressed in clinical settings., Objective: To explore attitudes toward antidepressants in a sample of depressed, community-dwelling elders who were offered treatment. DESIGN. Cross-sectional, qualitative study utilizing semi-structured interviews., Participants: Primary care patients age 60 years and over with depression, from academic and community primary care practices of the University of Pennsylvania Health System and the Philadelphia Department of Veterans Affairs. Patients participated in either the Prevention of Suicide in Primary Care Elderly: Collaborative Trial or the Primary Care Research in Substance Abuse and Mental Health for the Elderly Trial. Sixty-eight patients were interviewed and responses from 42 participants with negative attitudes toward medication for depression were analyzed., Measurements: Interviews were audiotaped, transcribed, and entered into a qualitative software program for coding and analysis. A multidisciplinary team of investigators coded the transcripts and identified key features of narratives expressing aversion to antidepressants., Results: Four themes characterized resistance to antidepressants: (1) fear of dependence; (2) resistance to viewing depressive symptoms as a medical illness; (3) concern that antidepressants will prevent natural sadness; (4) prior negative experiences with medications for depression., Conclusions: Many elders resisted the use of antidepressants. Patients expressed concerns that seem to reflect their concept of depression as well as their specific concerns regarding antidepressants. These findings may enhance patient-provider communication about depression treatment in elders.