AbstractmAKAPβ is the scaffold for a multimolecular signaling complex in cardiac myocytes that is required for the induction of neonatal myocyte hypertrophy. We now show that the pro-hypertrophic phosphatase calcineurin binds directly to a single site on mAKAPβ that does not conform to any of the previously reported consensus binding sites. Calcineurin -mAKAPβ complex formation is increased in the presence of Ca 2+ /calmodulin and in norepinephrine-stimulated primary cardiac myocytes. This binding is of functional significance because myocytes exhibit diminished norepinephrine-stimulated hypertrophy when expressing a mAKAPβ mutant incapable of binding calcineurin. In addition to calcineurin, the transcription factor NFATc3 also associates with the mAKAPβ scaffold in myocytes. Calcineurin bound to mAKAPβ can dephosphorylate NFATc3 in myocytes, and expression of mAKAPβ is required for NFAT transcriptional activity. Taken together, our results reveal the importance of regulated calcineurin binding to mAKAPβ for the induction of cardiac myocyte hypertrophy. Furthermore, these data illustrate how scaffold proteins organizing localized signaling complexes provide the molecular architecture for signal transduction networks regulating key cellular processes.

The low rate of thromboembolic complications and the cost savings suggest that IPC might be used safely and effectively for thromboprophylaxis in trauma patients.

BackgroundMetabolic syndrome (MetS) is a constellation of symptoms used as a measure to identify patients at increased risk for cardiovascular disease, type 2 diabetes, and all-cause mortality. The results of prolonged life expectancy and cumulative toxic effects of antiretroviral therapy increase the chance that HIV can cause clinical abnormalities, including MetS.MethodsWe evaluated 89 people living with HIV (PLWH; mean age 48 ± 7 years; mean duration of HIV infection 17 ± 12 years; 47% men; 66% African-American, 22% Hispanic, and 10% non-Hispanic white; and 84% unemployed) enrolled in a community-based exercise training and nutrition education program targeting individuals of low socio-economic status (SES). The prevalence of MetS characteristics and the factors associated with the presence of MetS were analyzed.ResultsOne in three (33%; 12 men and 17 women) PLWH met ATPIII criteria for MetS. In our cohort, MetS was driven by high waist circumference and elevated blood pressure. In addition, higher use of protease inhibitors, elevated hemoglobin A1c (HbA1c), greater self-reported daily caloric intake and consumption of carbohydrates, sugar, added sugar, and higher glycemic load were found among the individuals with MetS, compared to those without it. Elevated HbA1c and high total sugar consumption were the strongest predictors and accounted for 30% of the occurrence of MetS.ConclusionsThe overall prevalence of MetS in our PLWH cohort receiving antiretroviral therapy is higher than previously reported in the general population and in other PLWH cohorts. Additional work is needed to determine whether MetS is a more disease dependent or lifestyle dependent condition in PLWH.

BackgroundType 2 diabetes mellitus is frequently unrecognized until complications appear. Diabetic autonomic neuropathy is one of the early complications of type 2 diabetes mellitus, resulting in autonomic nervous system (ANS) dysfunction. The purpose of this study was to determine the validity of ANS function indicators to screen for type 2 diabetes mellitus, as measured by the TM-Oxi and SudoPath system.MethodsAll enrolled participants completed a basic sociodemographic and medical history questionnaire including current medications. Healthy controls (n = 25) underwent a 2-hour oral glucose tolerance test (OGTT) to evaluate glucose, insulin, and insulin C-peptide. Patients with type 2 diabetes mellitus (n = 24) were assessed with fasting plasma glucose (FPG) and glycosylated hemoglobin. The TM-Oxi and SudoPath system evaluation was completed by all subjects. Data were analyzed using SPSS 22. Frequency and descriptive statistics were calculated on all variables. The criterion for statistical significance was α = 0.05.ResultsThe twenty-five healthy controls had a mean age of 37.0 years. The twenty-four type 2 diabetes mellitus patients currently undergoing standard treatment had a mean age of 48.9 years. Based on the American Diabetes Association guidelines, we detected pre-diabetes in 4 subjects and diabetes in 1 subject, while all other subjects had normal FPG values. At 120 minutes, the correlations between the OGTT and cardiometabolic risk score (CMRS) were: r = 0.56 (p = 0.004) for glucose and r = 0.53 (p = 0.006) for insulin. At 120 minutes, the correlations between the OGTT and photoplethysmography index (PTGi) were: r = -0.56 (p = 0.003) for glucose and r = -0.41 (p = 0.04) for insulin. The CMRS, PTGi, and plethysmography total power index (PTGVLFi) differed significantly between the diabetes patients and healthy participants. The specificity and sensitivity for the CMRS, PTGi, and PTVLFi comparing the diabetes patients with healthy controls were high.ConclusionThe TM-Oxi and SudoPath system shows promise as a valid, convenient, and non-invasive screening method for type 2 diabetes mellitus. The ANS function and CMR indicators measured by this system may be useful in guiding diabetes and cardiovascular health screening, treatment, and monitoring.

Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge.