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BackgroundAutomatically tracking mental well-being could facilitate personalization of treatments for mood disorders such as depression and bipolar disorder. Smartphones present a novel and ubiquitous opportunity to track individuals' behavior and may be useful for inferring and automatically monitoring mental well-being.ObjectiveThe aim of this study was to assess the extent to which activity and sleep tracking with a smartphone can be used for monitoring individuals' mental well-being.MethodsA cohort of 106 individuals was recruited to install an app on their smartphone that would track their well-being with daily surveys and track their behavior with activity inferences from their phone's accelerometer data. Of the participants recruited, 53 had sufficient data to infer activity and sleep measures. For this subset of individuals, we related measures of activity and sleep to the individuals' well-being and used these measures to predict their well-being.ResultsWe found that smartphone-measured approximations for daily physical activity were positively correlated with both mood (P=.004) and perceived energy level (P

Chromosome 15q11.2–q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. Chromosomal multiplication of the UBE3A gene is presumed to be the primary driver of Dup15q pathophysiology, given that UBE3A exhibits maternal monoallelic expression in neurons and that maternal duplications typically yield far more severe neurodevelopmental outcomes than paternal duplications. However, studies into the pathogenic effects of UBE3A overexpression in mice have yielded conflicting results. Here, we investigated the neurodevelopmental impact of Ube3a gene overdosage using bacterial artificial chromosome–based transgenic mouse models (Ube3aOE) that recapitulate the increases in Ube3a copy number most often observed in Dup15q. In contrast to previously published Ube3a overexpression models, Ube3aOE mice were indistinguishable from wild-type controls on a number of molecular and behavioral measures, despite suffering increased mortality when challenged with seizures, a phenotype reminiscent of sudden unexpected death in epilepsy. Collectively, our data support a model wherein pathogenic synergy between UBE3A and other overexpressed 15q11.2–q13.1 genes is required for full penetrance of Dup15q syndrome phenotypes.

Abstract Background The use of antipsychotic medication and psychotropic polypharmacy has increased in the United States over the last two decades especially for children from low-income families and those in foster care. Although attention has been paid to providing greater insight, prescribing patterns remain concerning since there is a lack of evidence related to safety and efficacy. High-level psychotropic polypharmacy has not been described. We aim to compare the use of HLPP for children receiving Medicaid services and those in foster care and identify factors associated with the duration of use of high-level psychotropic polypharmacy. Additionally, we will examine the frequency of laboratory metabolic screening and emergency department, inpatient, and outpatient visits. Methods A cross-sectional, secondary analysis of statewide data describes trends in high-level psychotropic polypharmacy from 2012 to 2017 and the prevalence and predictors of high-level psychotropic polypharmacy duration and resource use in 2017 for all children on Medicaid and those in foster care. High-level psychotropic polypharmacy included concurrent use, at least four classes of medications including an antipsychotic, and at least 30 days duration. Results High-level psychotropic polypharmacy increased from 2012 to 2014 for both groups but stabilized in 2015–2016. Children in foster care showed a slight increase compared to their peers in 2017. There was no association between duration and demographic characteristics or foster care status. Diagnoses predicted duration. Neither group received metabolic monitoring at an acceptable rate. Conclusions Concerning patterns of high-level psychotropic polypharmacy and metabolic monitoring were identified. Cautious use of high-level psychotropic polypharmacy and greater oversight to ensure that these children are receiving comprehensive services like behavioral health, primary care, and primary prevention.

Background: Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased microbial translocation and systemic inflammation in the development of liver injury in patients with T2DM. Methods: Patients with T2DM (n = 17) and non-diabetic controls (NDC; n = 11) aged 25–80 yrs. participated in this study. Serum levels of endotoxin, calprotectin, soluble CD14 and CD163, and several inflammatory cytokines were measured. In addition to standard liver injury markers, ALT and AST, novel serum markers of liver injury, keratin 18 (K-18) M30 (apoptosis-associated caspase-cleaved keratin 18), and M65 (soluble keratin 18) were evaluated. Statistical analyses were performed using the Mann–Whitney test to assess differences between study groups. Pearson's correlation analysis was performed to determine the strength of association between two variables using GraphPad Prism 9.5.0 software. Results: Patients with T2DM had significantly higher levels of sCD14 in comparison to NDC, suggesting an increase in gut permeability, microbial translocation, and monocyte/macrophage activation. Importantly, relevant to the ensuing inflammatory responses, the increase in sCD14 in patients with T2DM was accompanied by a significant increase in sCD163, a marker of hepatic Kupffer cell activation and inflammation. Further, a positive correlation was observed between sCD163 and endotoxin and sCD14 in T2DM patients but not in NDC. In association with these changes, keratin 18 (K-18)-based serum markers (M65 and M30) that reflect hepatocyte death were significantly higher in the T2DM group indicating ongoing liver injury. Notably, both M65 and M30 levels correlated with sCD14 and sCD163, suggesting that immune cell activation and hepatic inflammation may be linked to the development of liver injury in T2DM. Conclusions: These findings suggest that the pathogenic changes in the gut–liver axis, marked by increased microbial translocation, may be a major component in the etiology of hepatocyte inflammation and injury in patients with T2DM. However, larger longitudinal studies, including histological evidence, are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

BACKGROUND: We hypothesized that tumor- and hospital-level factors, compared with surgeon characteristics, are associated with the majority of variation in the 12 or more lymph nodes (LNs) examined quality standard for resected colon cancer. STUDY DESIGN: A dataset containing an anonymized surgeon identifier was obtained from the National Cancer Database for stage I to III colon cancers from 2010 to 2017. Multilevel logistic regression models were built to assign a proportion of variance in achievement of the 12 LNs standard among the following: (1) tumor factors (demographic and pathologic characteristics), (2) surgeon factors (volume, approach, and margin status), and (3) facility factors (volume and facility type). RESULTS: There were 283,192 unique patient records with 15,358 unique surgeons across 1,258 facilities in our cohort. Achievement of the 12 LNs standard was high (90.3%). Achievement of the 12 LNs standard by surgeon volume was 88.1% and 90.7% in the lowest and highest quartiles, and 86.8% and 91.6% at the facility level for high and low annual volume quartiles, respectively. In multivariate analysis, the following tumor factors were associated with meeting the 12 LNs standard: age, sex, primary tumor site, tumor grade, T stage, and comorbidities (all p < 0.001). Tumor factors were responsible for 71% of the variation in 12 LNs yield, whereas surgeon and facility characteristics contributed 17% and 12%, respectively. CONCLUSIONS: Twenty-nine percent of the variation in the 12 LNs standard is linked to modifiable factors. The majority of variation in this quality metric is associated with non-modifiable tumor-level factors. [ABSTRACT FROM AUTHOR]

Abstract Objective: To describe pediatric outpatient visits and antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic. Design: An observational, retrospective control study from January 2019 to October 2021. Setting: Outpatient clinics, including 27 family medicine clinics, 27 pediatric clinics, and 26 urgent or prompt care clinics. Patients: Children aged 0–19 years receiving care in an outpatient setting. Methods: Data were extracted from the electronic health record. The COVID-19 era was defined as April 1, 2020, to October 31, 2021. Virtual visits were identified by coded encounter or visit type variables. Visit diagnoses were assigned using a 3-tier classification system based on appropriateness of antibiotic prescribing and a subanalysis of respiratory visits was performed to compare changes in the COVID-19 era compared to baseline. Results: Through October 2021, we detected an overall sustained reduction of 18.2% in antibiotic prescribing to children. Disproportionate changes occurred in the percentages of antibiotic visits in respiratory visits for children by age, race or ethnicity, practice setting, and prescriber type. Virtual visits were minimal during the study period but did not result in higher rates of antibiotic visits or in-person follow-up visits. Conclusions: These findings suggest that reductions in antibiotic prescribing have been sustained despite increases in outpatient visits. However, additional studies are warranted to better understand disproportionate rates of antibiotic visits.

This essay seeks to restore stagnation as a category of analysis to understand late-Soviet socialism. It argues that the conservative politics of the Brezhnev period and its tepid economic growth were the results of a choice by Soviet elites to prioritise political stability over a consumerist reconfiguration of the Soviet growth model. This choice was undertaken in the context of the Kosygin reforms, measures aimed at arresting the looming stagflation of the late Khrushchev era. The defeat of the reforms marked a political caesura at which stagnation became an acceptable risk for the party elite. [ABSTRACT FROM AUTHOR]

Intestinal epithelial barrier is critical for the maintenance of normal gut homeostasis and disruption of this barrier may trigger or exaggerate mucosal inflammation. The actin cytoskeleton is a key regulator of barrier structure and function, controlling the assembly and permeability of epithelial adherens and tight junctions. Epithelial cells express two actin isoforms: a β-cytoplasmic actin and γ-cytoplasmic actin. Our previous in vitro studies demonstrated that these actin isoforms play distinctive roles in establishing the intestinal epithelial barrier, by controlling the organization of different junctional complexes. It remains unknown, whether β-actin and γ-actin have unique or redundant functions in regulating the gut barrier in vivo. To address this question, we selectively knocked out β-actin expression in mouse intestinal epithelium. Mice with intestinal epithelial knockout of β-actin do not display gastrointestinal abnormalities or gross alterations of colonic mucosal architecture. This could be due to compensatory upregulation of γ-actin expression. Despite such compensation, β-actin knockout mice demonstrate increased intestinal permeability. Furthermore, these animals show more severe clinical symptoms during dextran sodium sulfate induced colitis, compared to control littermates. Such exaggerated colitis is associated with the higher expression of inflammatory cytokines, increased macrophage infiltration in the gut, and accelerated mucosal cell death. Consistently, intestinal organoids generated from β-actin knockout mice are more sensitive to tumor necrosis factor induced cell death, ex vivo. Overall, our data suggests that β-actin functions as an essential regulator of gut barrier integrity in vivo, and plays a tissue protective role during mucosal injury and inflammation.

Current integration processes, develop actively on the territory of Eurasian Economic Union (EEU). A single labour market has been created. Building a model of social interaction between the State Parties of EEU is crucial for the development of longterm strategy of the EEU. The Treaty on the Eurasian Economic Union (2014) provides identifying factors, threats and potential areas of cooperation between the EEU countries in the sphere of pension services. This identification requires systematizing the key indicators of EEU national pension systems. There is a necessity to improve not only the pension system of every country individually but also to search the possibilities for their coordination in the future. From the beginning of 1990th, in all EEU countries, the pension systems have been establishing and developing. The authors present the brief review and comparative analysis of these systems. We identify their similarities and differences according to set criteria and determine possible areas for integration of pension systems in EEU. We consider both the socio-economic parameters (including retirement age, amount of pension payments, pension payment procedures and pattern of pension payments) and the demographic features of the EEU countries. The paper systematizes the macroeconomic and population indicators. On their basis, we reveal the opportunities and risks for the EEU countries cooperation in the sphere of pension system. To investigate the pension systems of EEU countries, we applied the methods of logical, comparative and statistical analysis. The results of this study indicate that the coordination of the pension systems of EEU countries needs cooperation in four directions. First of all, it is necessary to elaborate the single principles of social guarantees for retirees. Secondly, there is a need to ensure guaranteed retirement income. Thirdly, single basic approaches for the regulation of investment activities of pension funds should be elaborated. Last, single data bank for pension provision can be created.

BACKGROUND: Endotracheal intubation is a common procedure associated with adverse events, including severe desaturation. Many patients receive noninvasive respiratory support to reduce the need for intubation. There are minimal data about the association between noninvasive respiratory support and the risk of a severe desaturation event during intubation. We aim to differentiate patients based on the level of noninvasive respiratory support, analyze the severe desaturation event by groups, and identify modifiable risk factors. METHODS: Oral intubations, excluding tube exchanges or re-intubation after unplanned extubation, from October 2018 through July 2020, at the study site were reviewed. A severe desaturation event was defined as SpO2 < 70% or a >15% decrease from baseline in cyanotic heart disease. We analyzed outcomes by 4 groups: room air/nasal cannula (≤0.5 L/kg/min), high-flow nasal cannula (HFNC) (0.5-2 L/kg/min), high HFNC (62 L/kg/min), and noninvasive ventilation (NIV). RESULTS: Of 243 subjects who were intubated, 31% were receiving room air/nasal cannula, 25% were receiving HFNC, 18% were receiving high HFNC, and 26% were receiving NIV. Twelve percent of all the subjects had a severe desaturation event. In a univariate analysis, the incidence of a severe desaturation event was similar among all levels of respiratory support (P = .14). A severe desaturation event was more likely in those subjects who were receiving FIO2 6 0.6 at the time of the decision to intubate (19.6%) versus FIO2 < 0.6 (8.1%) (P = .02). The duration of non-invasive respiratory support was longer (5 vs 1 h; P = .02) among those with a severe desaturation event. In a regression analysis, when adjusting for 62 intubation attempts pre-intubation, NIV use was independently associated with increased odds of severe desaturation events (odds ratio 3.14, CI 1.08-10.5). CONCLUSIONS: Results of our study suggest that FIO2 > 0.60, the duration of noninvasive respiratory support, and exposure to NIV before an intubation are risk factors of severe desatu- ration events during intubation. [ABSTRACT FROM AUTHOR]