Metabotropic Glutamate Receptor 2 Expression Is Chronically Elevated in Male Rats With Post-Traumatic Stress Disorder Related Behavioral Traits Following Repetitive Low-Level Blast Exposure.

Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits. In this report, we explored mGluR2/3 expression following blast exposure in male rats. Western blotting revealed that mGluR2 protein (but not mGluR3) was increased in all brain regions studied (anterior cortex, hippocampus, and amygdala) at 43 or 52 weeks after blast exposure but not at 2 weeks or 6 weeks. mGluR2 RNA was elevated at 52 weeks while mGluR3 was not. Immunohistochemical staining revealed no changes in the principally presynaptic localization of mGluR2 by blast exposure. Administering the mGluR2/3 antagonist LY341495 after behavioral traits had emerged rapidly reversed blast-induced effects on novel object recognition and cued fear responses 10 months following blast exposure. These studies support alterations in mGluR2 receptors as a key pathophysiological event following blast exposure and provide further support for group II metabotropic receptors as therapeutic targets in the neurobehavioral effects that follow blast injury.

Diabetes status and postoperative complications for patients receiving open rotator cuff repair.

Background: Diabetic patients are known to have poor wound healing and worse outcomes following surgeries. The purpose of this study is to evaluate diabetes status and complications for patients receiving open rotator cuff repair. Methods: Patients undergoing open rotator cuff repair from 2006 to 2018 were identified in a national database. Patients were stratified into 3 cohorts: no diabetes mellitus, non-insulin dependent diabetes mellitus (NIDDM), and insulin dependent diabetes mellitus (IDDM). Differences in demographics, comorbidities, and complications were assessed with the use of bivariate and multivariate analyses. Results: Of 7678 total patients undergoing open rotator cuff repair, 6256 patients (81.5%) had no diabetes, 975 (12.7%) had NIDDM, and 447 (5.8%) had IDDM. Bivariate analyses revealed that IDDM patients had increased risk of mortality, extended length of stay, and readmission compared to non-diabetic patients (p < 0.05 for all). IDDM patients had higher risks of major complications and readmission relative to NIDDM patients (p < 0.05 for both). On multivariate analysis, there were no differences in any postoperative complications between the non-diabetic, NIDDM, and IDDM groups. Discussion: Diabetes does not affect postoperative complications following open rotator cuff repairs. Physicians should be aware of this finding and counsel their patients appropriately.Level of Evidence: III.

Weight Loss Outcomes With Telemedicine During COVID-19.

Background: Amidst the COVID-19 pandemic, telemedicine was rapidly implemented to maintain patient care during quarantine. However, there is little data on how this transition may have impacted weight loss outcomes and interventions among patients with overweight or obesity. Methods: This was a retrospective observational study of adults who established care for medically managed obesity at the Weill Cornell Comprehensive Weight Control Center during September-November 2019 and May-July 2020 and who completed 6 months of follow-up. Weight loss outcomes and weight management interventions were explored and stratified by patient-provider interaction: in-person visits only, in-person and video visits, and video visits only. Results: Of 499 charts eligible for review, 245 (49%) returned for their 6-month follow-up visit and were included for analysis. Of 245 patients, 69 had in-person visits only ("in-person"), 85 started in-person and later switched to video visits ("hybrid"), and 91 had video visits only ("video"). All cohorts were predominantly white and female. Median ages were 56, 49, and 49 years; baseline median weights were 98.9, 96.8, and 93.0 kg; and baseline median BMIs were 35.3, 34.4, and 34.0 kg/m2 for in-person, hybrid, and video cohorts, respectively. The median percent weight changes over 6 months were not significantly different among cohorts: -4.3% [-8.5, -1.5] in the in-person cohort, -5.6% [-8.7, -2.2] in the hybrid group, and -5.8% [-9.7, -2.4] in the video cohort. The percent of patients who achieved ≥5% weight loss were also similar: 46.4%, 55.3%, and 59.3%, respectively. The median number of visits in the video cohort was more than in the in-person or hybrid groups (5 vs. 4). Median number of anti-obesity medications (AOMs) prescribed was similar among groups. The most common AOMs were metformin (all cohorts) followed by semaglutide 1.0 mg (in-person and video) or topiramate (hybrid). Conclusion: Patients on anti-obesity medications who were followed for 6 months via video or video plus in-person visits (hybrid) experienced clinically significant weight loss. Median number of AOMs were similar among groups, and the most common AOMs were metformin, semaglutide 1.0 mg, and topiramate. More investigation is required to compare telemedicine models with in-person care.

Cyfip1 Regulates SynGAP1 at Hippocampal Synapses.

In humans, copy number variations in CYFIP1 appear to have sweeping physiological and structural consequences in the brain, either producing or altering the severity of intellectual disability, autism, and schizophrenia. Independently, SynGAP1 haploinsufficiency produces intellectual disability and, frequently, autism. Cyfip1 inhibits protein translation and promotes actin polymerization, and SynGAP1 is a synaptically localized Ras/Rap GAP. While these proteins are clearly distinct, studies investigating their functions in mice have shown that each regulates the maturation of synapses in the hippocampus and haploinsufficiency for either produces an exaggerated form of mGluR-dependent long-term depression, suggesting that some signaling pathways converge. In this study, we examined how Cyfip1 haploinsufficiency impacts SynGAP1 levels and localization, as well as potential sites for mechanistic interaction in mouse hippocampus. The data show that synaptic, but not total, levels of SynGAP1 in Cyfip1 +/- mice were abnormally low during early postnatal development and in adults. This may be in response to a shift in the balance of kinases that activate SynGAP1 as levels of Cdk5 were reduced and those of activated CaMKII were maintained in Cyfip1 +/- mice compared to wild-type mice. Alternatively, this could reflect altered actin dynamics as Rac1 activity in Cyfip1 +/- hippocampus was boosted significantly compared to wild-type mice, and levels of synaptic F-actin were generally enhanced due in part to an increase in the activity of the WAVE regulatory complex. Decreased synaptic SynGAP1 coupled with a CaMKII-mediated bias toward Rap1 inactivation at synapses is also consistent with increased levels of synaptic GluA2, increased AMPA receptor-mediated responses to stimulation, and increased levels of synaptic mGluR1/5 compared to wild-type mice. Collectively, our data suggest that Cyfip1 regulates SynGAP1 and the two proteins work coordinately at synapses to appropriately direct actin polymerization and GAP activity.