Impaired response of mature adipocytes of diabetic mice to hypoxia.

Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

Just-in-Time Electronic Health Record Retraining to Support Clinician Redeployment during the COVID-19 Surge.

BACKGROUND: In response to surges in demand for intensive care unit (ICU) care related to the COVID-19 pandemic, health care systems have had to increase hospital capacity. One institution redeployed certified registered nurse anesthetists (CRNAs) as ICU clinicians, which necessitated training in ICU-specific electronic health record (EHR) workflows prior to redeployment. Under time- and resource-constrained settings, clinical informatics (CI) fellows could effectively be lead instructors for such training. OBJECTIVE: This study aimed to deploy CI fellows as lead EHR instructional trainers for clinician redeployment as part of an organization's response to disaster management. METHODS: CI fellows led a multidisciplinary team alongside subject matter experts to develop and deploy a tailored EHR curriculum comprising in-person classes and online video modules, leveraging high-fidelity simulated patient cases. The participants completed surveys immediately after the in-person training session and after deployment. RESULTS: Eighteen CRNAs participated, with 15 completing the postactivity survey (83%). All felt the training was useful and improved their EHR skills with a Net Promoter score of +87. Most (93%) respondents indicated the pace of the session was "just right," and 100% felt the clarity of instruction was "just right" or "extremely easy" to understand. Twelve participants (67%) completed the postdeployment survey. The training increased comfort in the ICU for all respondents, and 91% felt the training prepared them to work in the ICU with minimal guidance. All stated that the concepts learned would be useful in their anesthesia role. Fifty-eight percent viewed the online video library. CONCLUSION: This case report demonstrates that CI fellows with dual domain expertise in their clinical specialty and informatics are uniquely poised to deliver clinician redeployment EHR training in response to operational crises. Such opportunities can achieve fellowship educational goals while conserving physician resources which can be a strategic option as organizations plan for disaster management.

The TallyHo polygenic mouse model of diabetes: implications in wound healing.

BACKGROUND: Impairments in wound healing represent a significant source of morbidity and mortality in patients with diabetes. To help uncover the derangements associated with diabetic wound healing, murine animal models have been extensively used. In this article, the authors present results, and the accompanying wound healing implications, from experiments across three validated wound healing models using a newer polygenic strain of diabetes. METHODS: The authors investigated the wound healing impairments of the TallyHo/JnJ diabetic mouse strain, using three validated wound healing models: an incisional model, a splinted excisional model, and a cutaneous ischemia-reperfusion injury model. Appropriate control strain mice were used for comparison. Wounds were analyzed using gross, histologic, and molecular techniques. RESULTS: TallyHo mice displayed deficits across all three wound healing models. There was a reduced resistance/response to oxidative stress and a global decrease in the initial inflammatory response to healing. In addition, there was a global decrease in the stimulus for angiogenesis and collagen formation, ultimately leading to reduced reepithelialization, granulation tissue formation, wound contraction, and wound tensile strength. Gross and histologic findings were corroborated with molecular data, which revealed a significant down-regulation of important cytokines, including vascular endothelial growth factor, neutrophilic attractant protein-2, monocyte chemoattractant protien-1, heme oxygenase-1, interleukin-1ß, and interleukin-6, when normalized to the control strain (p<0.05). CONCLUSIONS: The TallyHo polygenic mouse model of diabetes demonstrates predictable and clinically relevant wound healing impairments that offer important implications into the derangements of diabetic wound healing observed clinically. Therapeutics targeting these specific derangements could provide improvements in the care of diabetic wounds.