Omega 3 Fatty Acid Inhibition of Inflammatory Cytokine-Mediated Connexin43 Regulation in the Heart

Background: The proinflammatory cytokine $Interleukin-1\beta$ $(IL-1\beta)$, which increases in the heart post myocardial infarction (MI), has been shown to cause loss of Connexin43 (Cx43) function, an event known to underlie formation of the arrhythmogenic substrate. Omega 3 Fatty acids exhibit antiarrhythmic properties and impact $IL-1\beta$ signaling. We hypothesize that Omega-3 fatty acids prevent arrhythmias in part, by inhibiting $IL-1\beta$ signaling thus maintaining functional Cx43 channels. Methods: Rat neonatal myocytes or Madin-Darby Canine Kidney Epithelial (MDCK) cells grown in media in the absence (Ctr) or presence of $30 \mu M$ docosahexaenoic acid (DHA, an Omega-3 Fatty acid) were treated with $0.1 \mu M$ activated $IL-1\beta$. We determined Cx43 channel function using a dye spread assay. Western blot and immunostaining were used to examine Cx43 levels/localization and downstream effectors of $IL-1\beta$. In addition we used a murine model of MI for 24 h to determine the impact of an Omega-3 fatty acid enriched diet on Cx43 levels/localization post MI. Results: $IL-1\beta$ significantly inhibited Cx43 function in Ctr cells $(200.9 \pm 17.7 \mu m [Ctr] vs. 112.8 \pm 14.9 \mu m [0.1 \mu M IL-1\beta], p<0.05)$. However, DHA-treated cells remained highly coupled in the presence of $IL-1\beta$ $[167.9 \pm 21.9 \mu m [DHA] vs. 164.4 \pm 22.3 \mu m [DHA + 0.1 \ muM IL-1\beta], p<0.05, n = 4]$. Additionally, western blot showed that $IL-1\beta$ treatment caused a 38.5% downregulation of Cx43 $[1.00 au [Ctr] vs. 0.615 au (0.1 \mu M IL-1\beta)$ which was completely abolished in DHA-treated cells $(0.935 au [DHA] vs. 1.02 au [DHA + 0.1 \mu M IL-1\beta), p < 0.05, n = 3]$. Examination of the downstream modulator of $IL-1\beta$, $NF\kappa \beta$ showed that while hypoxia caused translocation of $NF\kappa \beta$ to the nucleus, this was inhibited by DHA. Additionally we found that a diet enriched in Omega-3 Fatty acids inhibited lateralization of Cx43 in the post-MI murine heart as well as limited activation of fibroblasts which would lead to decreased fibrosis overall. Conclusions: Omega 3 Fatty acid treatment inhibited $IL-1\beta$-stimulated loss of Cx43 protein, and more importantly, inhibited loss of Cx43 function by inhibiting translocation of $NF\kappa \beta$. In the intact heart a diet enriched in Omega 3 Fatty Acids limited loss of Cx43 at the intercalated disk in the heart following MI. These data suggest that one of cardio-protective mechanisms by which Omega 3 Fatty acids work includes prevention of the pro-arrhythmic loss of Cx43 post MI and the attenuation of cardiac fibrosis after injury

Complete Genome Sequences of Mycobacterium smegmatis Phages Chewbacca, Reptar3000, and Riparian, Isolated in Las Vegas, Nevada

Here, we present the complete genome sequences of Mycobacterium smegmatis phages Chewbacca, Reptar3000, and Riparian, isolated from soil in Las Vegas, NV. The phages were isolated and annotated by undergraduate students enrolled in the Phage Discovery course offered by the School of Life Sciences at the University of Nevada, Las Vega

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Comparison of a Novel Insulin Bolus-Patch with Pen/Syringe Injection to Deliver Mealtime Insulin for Efficacy, Preference, and Quality of Life in Adults with Diabetes: A Randomized, Crossover, Multicenter Study

Objective: This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. Research Design and Methods: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). Results: Using bolus-patch, MDBG (mean•SE) was equivalent to that using pen/syringe (8.61+/-0.28 vs. 9.02+/-0.26-mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18+/-0.18 vs. 3.63+/-0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2+/-1.7 vs. 40.3+/-1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). Conclusions: Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90477/1/dia-2E2011-2E0047.pd

Pediatric Rapid Response Team Quality Improvement Initiative – Preliminary Findings

Background: Rapid Response Teams are activated in non-critical care settings to provide or expedite access to escalated care before patient condition rapidly deteriorates. Patients who undergo cardiopulmonary arrest may experience emergency “Code Blue” activation. However, in clinical situations where a patient’s condition is concerning but not yet deteriorating, an intermediary Rapid Response Team (RRT) may be activated to facilitate early detection and management of at-risk patients. Pediatric Rapid response team implementation is associated with “reduction in hospital-wide mortality rate and code rate outside of the pediatric ICU”. UC Davis Medical Center has had preexisting RRTs, but prior to Fall 2020 did not have a pediatricspecific RRT for its Children’s Hospital. UCDMC is unique in that it is one of few major academic medical centers that does not have structural separation between the children- and adult-side of the hospital, and are instead housed within the same medical center. The Pediatric Rapid Response Team at UC Davis Children’s Hospital was implemented September 2020

Communication-constrained distributed quantile regression with optimal statistical guarantees

We address the problem of how to achieve optimal inference in distributed quantile regression without stringent scaling conditions. This is challenging due to the non-smooth nature of the quantile regression (QR) loss function, which invalidates the use of existing methodology. The difficulties are resolved through a double-smoothing approach that is applied to the local (at each data source) and global objective functions. Despite the reliance on a delicate combination of local and global smoothing parameters, the quantile regression model is fully parametric, thereby facilitating interpretation. In the low-dimensional regime, we establish a finite-sample theoretical framework for the sequentially defined distributed QR estimators. This reveals a trade-off between the communication cost and statistical error. We further discuss and compare several alternative confidence set constructions, based on inversion of Wald and score-type tests and resampling techniques, detailing an improvement that is effective for more extreme quantile coefficients. In high dimensions, a sparse framework is adopted, where the proposed doubly-smoothed objective function is complemented with an ℓ1-penalty. We show that the corresponding distributed penalized QR estimator achieves the global convergence rate after a near-constant number of communication rounds. A thorough simulation study further elucidates our findings

Pediatric Rapid Response Team Implementation and Outcomes in a Children’s Hospital within a Mixed Academic Health Center

Rapid Response Teams (RRTs) are teamsof healthcare providers called to patient bedside for unexpected or sudden changes inpatient conditions. Such teams are intended to intervene before patients experience Sudden Adverse Events (SAEs) or require ‘code blue’ activation. Markers such as abnormal vital signs raise concern for providers and patient families as these acute changes may precedecardiopulmonary arrest (CPA).2 A mechanismof activation to urgently introduce additional providers to bedside allows for patients to be seen before patient deterioration. A systematic review noted that “rapid response systems were associated with a reduction in hospital mortality and cardiopulmonary arrest.

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts