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Morphology is a defining feature of neuronal identity. Like neurons, glia display diverse morphologies, both across and within glial classes, but are also known to be morphologically plastic. Here, we explored the relationship between glial morphology and transcriptional signature using the Drosophila central nervous system (CNS), where glia are categorised into 5 main classes (outer and inner surface glia, cortex glia, ensheathing glia, and astrocytes), which show within-class morphological diversity. We analysed and validated single-cell RNA sequencing data of Drosophila glia in 2 well-characterised tissues from distinct developmental stages, containing distinct circuit types: the embryonic ventral nerve cord (VNC) (motor) and the adult optic lobes (sensory). Our analysis identified a new morphologically and transcriptionally distinct surface glial population in the VNC. However, many glial morphological categories could not be distinguished transcriptionally, and indeed, embryonic and adult astrocytes were transcriptionally analogous despite differences in developmental stage and circuit type. While we did detect extensive within-class transcriptomic diversity for optic lobe glia, this could be explained entirely by glial residence in the most superficial neuropil (lamina) and an associated enrichment for immune-related gene expression. In summary, we generated a single-cell transcriptomic atlas of glia in Drosophila, and our extensive in vivo validation revealed that glia exhibit more diversity at the morphological level than was detectable at the transcriptional level. This atlas will serve as a resource for the community to probe glial diversity and function.

Introduction: Obesity, a known risk factor for atrial fibrillation (AF), is potentially reversible through lifestyle changes, including diet and physical activity. However, lack of compliance is a major obstacle in attaining sustained weight loss. We investigated the impact of patient engagement using a digital monitoring system on compliance for lifestyle-change measures and subsequent outcome. Methods: A total of 105 consecutive patients with coexistent AF and obesity (body mass index ≥28) were classified into 2 groups based on the monitoring method: group 1, use of digital platform (n = 20); group 2, conventional method (n = 85). Group 1 used the RFMx digital monitoring platform (smartphone app) that sets weekly goals for exercise and weight loss, tracks patient compliance data continuously, and sends regular text reminders. Conventional method included monitoring patients’ adherence to diet and change in weight during in-person clinic visits or monthly phone calls from staff. Results: Baseline characteristics of groups 1 and 2 were comparable. At 6 months of follow-up, 12 (60%) and 28 (33%) from group 1 and 2, respectively, were compliant with the physician instructions regarding diet and exercise (P = .025). Weight loss was observed in 9 of 12 (75%) from group 1 and 11 of 28 (39%) from group 2 (P = .038) and mean reduction in weight was 9.9 ± 8.9 lb and 4.0 ± 2.1 lb (P = .042). Conclusion: In this series, continuous digital monitoring was seen to be associated with significant improvement in compliance through better patient engagement, resulting in more weight loss compared to the conventional method.

ObjectivesAdolescents with a homicidal tendency is a growing concern in the United States. Studies in the past have showcased the relationship between homicidal ideation (HI) and psychiatric illnesses, but very limited information is available on the adolescent and inpatient population. We aim to evaluate the prevalence of demographic characteristics and psychiatric disorders in adolescents with and without HI.Materials and methodsAdolescent (age 12–17) population admitted to the hospital with the diagnosis of homicidal ideation was identified from the 2016–2018 National Inpatient Sample Dataset (NISD). Patients without HI were defined as the control group. The prevalence of psychiatric comorbidities between the groups was compared by applying the Rao-Scott adjusted chi-square test. We used multivariable logistic regression to generate odds ratio (OR) of homicidal ideation as an outcome; we adjusted age, sex, race, socioeconomic status, substance use disorders, alcohol use disorders, and psychiatric comorbidities.ResultsA total of 18,935 patients (mean age: 14.5) with HI diagnosis were identified in this study. Majority of the patients were male subjects in the HI group compared to the control group (58.7 vs. 41.2%, p < 0.001). Racially, HI was more prevalent in white race (56.0 vs. 52.6%, p < 0.001) and black race (22.3 vs. 17.8%, p < 0.001), compared to Hispanic race (14.9 vs. 21.3%, p < 0.001). Major depression (Odds ratio [OR]: 2.66, p < 0.001), bipolar disorder (OR: 3.52, p < 0.001), anxiety disorder (OR: 1.85, p < 0.001), ADHD, and other conduct disorders (OR: 4.01, p < 0.001), schizophrenia (OR: 4.35, p < 0.001) are strong predictors of HI. Suicidality was prevalent in 66.9% of patients with HI.ConclusionWe found a higher prevalence of psychiatric illnesses such as depression, anxiety, and bipolar disorder in adolescents with homicidal ideation in the inpatient setting. White and black races were more prevalent in patients with homicidal ideation. Further large-scale longitudinal research studies are warranted to establish the correlation between psychiatric disorders and homicidal ideation among adolescents.

IntroductionSecond-generation antipsychotics are associated with significant weight gain. The aim of this systematic review and meta-analysis was to determine the efficacy and safety of metformin for the treatment of weight gain in children and young adults treated with second-generation antipsychotics.MethodsWe followed PRISMA guidelines to evaluated studies published before March 2020 in Medline, Google Scholar, PubMed, Cochrane library database, annual scientific sessions of the American Psychiatric Association, American Academy of Child and Adolescent, Psychiatry, and American Society of Clinical Psychopharmacology. Studies included compared metformin with the placebo for management of weight gain in children and adolescents taking atypical antipsychotics. Non-randomized studies, animal experiment studies, editorials, and review studies were excluded. Multiple parameters, including change in anthropometric-biochemical parameters, drug discontinuation rate, and side effects among the groups were assessed. The random-effects method was used for meta-analysis.ResultsFour studies with were included in the final analysis (213 patients; metformin: 106; control: 107). After pooled analysis, 12–16 weeks of metformin therapy was associated with a significant reduction in weight [(mean difference (MD): −4.53 lbs, confidence interval (CI): −6.19 to −2.87, p-value < 0.001)], and BMI z score [MD, −0.09, CI: −0.16, −0.03, p-value: 0.004] compared to control. Metformin was also associated with a significant reduction in insulin resistance [MD: −1.38, CI: −2.26 to −0.51, p-value: 0.002]. There were higher odds of nausea-vomiting [OR: 4.07, CI: 1.32–12.54, p-value: 0.02] and diarrhea [OR: 2.93, CI: 1.50–5.71, p-value: 0.002] in the metformin group. However, there was no difference in drug discontinuation rate [OR: 1.45, CI: 0.41–5.06, p-value: 0.56].ConclusionMetformin may prove beneficial in the treatment of weight gain in children treated with second-generation antipsychotics. The pooled treatment effect showed a significant reduction in BMI Z-score and weight in just 12–16 weeks. The limitations include small sample size, variation in metformin dose, and duration of treatment. This meta-analysis should be interpreted as promising, and further larger studies are warranted before drawing a conclusion.

Manganese neurotoxicity is a hallmark of hypermanganesemia with dystonia 2, an inherited manganese transporter defect caused by mutations in SLC39A14. To identify novel potential targets of manganese neurotoxicity, we performed transcriptome analysis of slc39a14−/− mutant zebrafish that were exposed to MnCl2. Differentially expressed genes mapped to the central nervous system and eye, and pathway analysis suggested that Ca2+ dyshomeostasis and activation of the unfolded protein response are key features of manganese neurotoxicity. Consistent with this interpretation, MnCl2 exposure led to decreased whole-animal Ca2+ levels, locomotor defects and changes in neuronal activity within the telencephalon and optic tectum. In accordance with reduced tectal activity, slc39a14−/− zebrafish showed changes in visual phototransduction gene expression, absence of visual background adaptation and a diminished optokinetic reflex. Finally, numerous differentially expressed genes in mutant larvae normalised upon MnCl2 treatment indicating that, in addition to neurotoxicity, manganese deficiency is present either subcellularly or in specific cells or tissues. Overall, we assembled a comprehensive set of genes that mediate manganese-systemic responses and found a highly correlated and modulated network associated with Ca2+ dyshomeostasis and cellular stress. This article has an associated First Person interview with the first author of the paper.

Background We evaluated long‐term outcome of isolation of pulmonary veins, left atrial posterior wall, and superior vena cava, including time to recurrence and prevalent triggering foci at repeat ablation in patients with paroxysmal atrial fibrillation with or without cardiovascular comorbidities. Methods and Results A total of 1633 consecutive patients with paroxysmal atrial fibrillation that were arrhythmia‐free for 2 years following the index ablation were classified into: group 1 (without comorbidities); n=692 and group 2 (with comorbidities); n=941. We excluded patients with documented ablation of areas other than pulmonary veins, the left atrial posterior wall, and the superior vena cava at the index procedure. At 10 years after an average of 1.2 procedures, 215 (31%) and 480 (51%) patients had recurrence with median time to recurrence being 7.4 (interquartile interval [IQI] 4.3–8.5) and 5.6 (IQI 3.8–8.3) years in group 1 and 2, respectively. A total of 201 (93.5%) and 456 (95%) patients from group 1 and 2 underwent redo ablation; 147/201 and 414/456 received left atrial appendage and coronary sinus isolation and 54/201 and 42/456 had left atrial lines and flutter ablation. At 2 years after the redo, 134 (91.1%) and 391 (94.4%) patients from group 1 and 2 receiving left atrial appendage/coronary sinus isolation remained arrhythmia‐free whereas sinus rhythm was maintained in 4 (7.4%) and 3 (7.1%) patients in respective groups undergoing empirical lines and flutter ablation (P

Background We compared the cognitive status and quality of life in patients with atrial fibrillation undergoing left atrial appendage occlusion (LAAO) or remaining on oral anticoagulation (OAC) after atrial fibrillation ablation. Methods and Results Cognition was assessed by the Montreal Cognitive Assessment (MoCA) survey at baseline and follow‐up. Consecutive patients receiving LAAO or OAC after atrial fibrillation ablation were screened, and patients with a score of ≤17 were excluded from the study. Quality of life was measured at baseline and 1 year using the Atrial Fibrillation Effect on Quality of Life survey. A total of 50 patients (CHA2DS2‐VASc [congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65–74 years, sex category] score: 3.30±1.43) in the LAAO group and 48 (CHA2DS2‐VASc score 2.73±1.25) in the OAC group were included in this prospective study. Mean baseline MoCA score was 26.18 and 26.08 in the LAAO and OAC groups, respectively (P=0.846). At 1 year, scores were 26.94 and 23.38 in the respective groups. MoCA score decreased by an estimated −2.74 (95% CI, −3.61 to −1.87; P

Introduction. Insomnia is an important symptom associated with major depressive disorder (MDD). In addition, it is one of the risk factors for suicide. Studies have shown the relationship be-tween insomnia and suicidal behavior in patients with MDD. However, this association has not been evaluated in a large sample of hospitalized patients. Objectives. To evaluate the suicidal be-havior in MDD patients with insomnia compared to those without insomnia. Methods. From the National Inpatient Sample (NIS 2006–2015) database using the ICD-9 code, patients’ data were obtained with the primary diagnosis of MDD and comorbid diagnosis of insomnia disorders (MDD+I). These patients were compared with MDD patients without insomnia disorders (MDD–I) by performing a 1:2 match for the primary diagnosis code. Suicidal ideation/attempt da-ta were compared between the groups by multivariate logistic regression analysis. Results. After the diagnostic code matching, 139061 patients were included in the MDD+I group and 276496 patients in the MDD–I group. MDD+I patients were older (47 years vs. 45 years, p < 0.001) com-pared to the MDD–I group. The rate of suicidal ideation/attempt was 56.0% in the MDD+I group and 42.0% in the MDD–I group (p < 0.001). After adjusting for age, sex, race, borderline personal-ity disorders, anxiety disorders, and substance use disorders, ‘insomnia’ was associated with 1.71 times higher odds of suicidal behavior among MDD patients admitted to the hospital. (Odds ratio: 1.71, 95% confidence interval 1.60–1.82, p < 0.001). Conclusions. Insomnia among MDD patients is significantly associated with the risk of suicide. MDD patients with insomnia need to be closely monitored for suicidal behavior.

Although pharmacological rhythm control of AF in patients with heart failure with reduced ejection fraction (HFrEF) does not seem to provide any benefit over rate control, catheter ablation of AF has been shown to improve clinical outcomes. These results can be explained with higher success rates of catheter ablation in restoring and maintaining sinus rhythm compared with antiarrhythmic drugs. In addition, pharmacotherapy is not void of side-effects, which are thought to offset its potential antiarrhythmic benefits. Therefore, efforts should be made towards optimisation of ablation techniques for AF in patients with HFrEF.

Background: Atrial fibrillation (AF) is a common complication after cardiac surgery. Ranolazine is a Food and Drug Administration approved anti-ischemic drug, which also has anti-arrhythmic properties. Recent studies have demonstrated the benefit of ranolazine in preventing post-operative AF (POAF) in patients undergoing cardiac surgery. Hence, we performed a meta-analysis of published studies comparing ranolazine plus standard therapy versus standard therapy for POAF prevention in patients undergoing cardiac surgery. Methods: We performed a comprehensive search of Medline, Google Scholar, PubMed, abstracts from annual scientific sessions, and Cochrane library database for studies that assessed the effectiveness of ranolazine plus standard therapy by comparing it with standard therapy alone in preventing POAF in patients undergoing cardiac surgery. From all the studies, data on POAF events among groups were collected, and the random-effects (DerSimonian and Laird) method was used for meta-analysis. Results: Four studies with 663 patients were included in the final analysis, with 300 and 363 patients in the ranolazine plus standard therapy and standard therapy groups, respectively. The types of cardiac surgeries were coronary artery bypass grafting (CABG), valve surgery or combination of CABG, and valve surgeries. After pooled analysis, ranolazine plus standard therapy was associated with a significant reduction in POAF events compared to standard therapy alone (risk ratio=0.44 [0.25, 0.78], p-value=0.005). There was no difference in adverse events between the two therapies. However, in one study, more patients in the ranolazine group had transient symptomatic hypotension after the surgery. Conclusions: Ranolazine may prove beneficial in POAF prevention following cardiac surgeries. Although the pooled treatment effect is quite impressive with a reduction of more than 50% of risk of developing POAF, small number of studies and variation in ranolazine dose regimen in each study make our results inconclusive, but worthy of further investigation. That is why this result has to be interpreted as only hypothesis generating, rather than conclusion drawing.

A recent surveillance analysis indicates that cardiac arrest/death occurs in ≈1:50,000 professional or semi-professional athletes, and the most common cause is attributable to life-threatening ventricular arrhythmias (VAs). It is critically important to diagnose any inherited/acquired cardiac disease, including coronary artery disease, since it frequently represents the arrhythmogenic substrate in a substantial part of the athletes presenting with major VAs. New insights indicate that athletes develop a specific electro-anatomical remodeling, with peculiar anatomic distribution and VAs patterns. However, because of the scarcity of clinical data concerning the natural history of VAs in sports performers, there are no dedicated recommendations for VA ablation. The treatment remains at the mercy of several individual factors, including the type of VA, the athlete’s age, and the operator’s expertise. With the present review, we aimed to illustrate the prevalence, electrocardiographic (ECG) features, and imaging correlations of the most common VAs in athletes, focusing on etiology, outcomes, and sports eligibility after catheter ablation.