Notes

Chemical substance removal of thrombospondin-1 and also -2 produces a skeletal phenotype not necessarily expected by the individual gene knockouts.
Most PRSS were unstandardized and broadly described, involving linkage to treatment (91.7%) or follow-up support (91.7%). MOUD initiation was reported the most often (66.7%), followed by PRSS engagement (33.3%) and opioid use (25.0%). No studies reported findings for MOUD retention or remission. Findings for available outcomes were inconsistent and difficult to compare due to the heterogeneity of PRSS interventions and methodological limitations.

Effectiveness of PRSS interventions on stages of the OUD treatment cascade remain inconclusive. Additional research is necessary before supporting the implementation of PRSS on a broad scale.
Effectiveness of PRSS interventions on stages of the OUD treatment cascade remain inconclusive. Additional research is necessary before supporting the implementation of PRSS on a broad scale.Longitudinal studies are essential to understand healthy and pathological neurocognitive aging such as Alzheimer's Disease, but longitudinal designs are rare in both humans and non-human primate models of aging because of the difficulty of tracking cognitive change in long-lived primates. Common marmosets (Callithrix jacchus) are uniquely suited for aging studies due to their naturally short lifespan (10-12 years), sophisticated cognitive and social abilities and Alzheimer Disease-like neuropathology. We report the first longitudinal study of cognitive aging in marmosets (N = 28) as they transitioned from middle- (∼5 years) to old age (∼9 years). We characterized aging trajectories using reversal learning with different stimuli each year. Marmosets initially improved on cognitive performance due to practice, but worsened in the final year, suggesting the onset of age-related decline. Cognitive impairment emerged earlier in females than males and was more prominent for discrimination than for reversal learning. Sex differences in cognitive aging could not be explained by differences in motivation or motor abilities, which improved or remained stable across aging. Likewise, males and females did not differ in aging trajectories of overall behavior or reactivity to a social stressor, with the exception of a progressive decline in the initiation of social behavior in females. Patterns of cognitive aging were highly variable across marmosets of both sexes, suggesting the potential for pathological aging for some individuals. selleck inhibitor Future work will link individual cognitive trajectories to neuropathology in order to better understand the relationships between neuropathologic burden and vulnerability to age-related cognitive decline in each sex.Ulotaront (SEP-363856) is a novel non-D2-receptor-binding agent under development for the treatment of patients with schizophrenia. A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with lower limit of quantitation of 0.0200 ng/mL (i.e. 20.0 pg/mL) was successfully developed and validated for the simultaneous quantitation of ulotaront and its N-desmethyl metabolite (M11A) in human plasma. Plasma samples were extracted by solid phase extraction with Oasis MCX 96-well plate, followed by a reversed phase LC separation coupled with MS/MS detection in positive mode (m/z 184.1 → 135.0 for ulotaront and 170.1 → 135.0 for M11A). Stable isotope-labeled compounds SEP-363856-d3 and M11A-d4 were used as internal standards (IS) for corresponding analytes. The validated calibration curve range was 0.0200-20.0 ng/mL for both analytes using a 0.200 mL plasma. Extraction recoveries were found to be 75.7% and 75.1% for ulotaront and IS1, and 82.7% and 83.9% for M11A and IS2, respectively. Frozen plasma samples were confirmed to be stable for up to 730 days at both -20 °C and -70 °C. The validated method has been successfully used to evaluate the pharmacokinetics (PK) of ulotaront and M11A in clinical studies. The application to the first-in-human PK study (single ascending dose) presented in this work demonstrated that ulotaront exhibited near dose proportionality for both Cmax (maximum concentration) and AUC (area under the curve) over the dose range from 5 to 125 mg. M11A was found as a minor metabolite with an exposure of about 2-3% of the parent compound.We investigate how the decline in home prices over the Great Recession in the U.S. impacted drinking behavior. We match data on actual and shadow home prices (from Zillow Research) to individuals' drinking behavior from the Behavioral Risk Factor Surveillance System (BRFSS) by county of residence and year/month of the interview. We improve upon the existing literature by using new measures of exogenous macroeconomic shocks captured by fluctuations in home prices and finding heterogeneous impacts of the downturn based on homeownership. We find that decline in home prices is commonly associated with increases in alcohol consumption, both on extensive and intensive margins. Additionally, we find that the effects are more consistent among homeowners compared to renters. Given that alcohol consumption is one of the leading causes of death in the U.S. and that the COVID-19 pandemic has triggered an economic crisis in many societies, the results have important public health implications.Advances in our understanding of risk and resilience factors in adolescent brain health and development increasingly demand a broad set of assessment tools that consider a youth's peer, family, school, neighborhood, and cultural contexts in addition to neurobiological, genetic, and biomedical information. The Culture and Environment (CE) Workgroup (WG) of the Adolescent Brain Cognitive Development (ABCD) Study curates these important components of the protocol throughout ten years of planned data collection. In this report, the CE WG presents an update on the evolution of the ABCD Study® CE protocol since study inception (Zucker et al., 2018), as well as emerging findings that include CE measures. Background and measurement characteristics of instruments present in the study since baseline have already been described in our 2018 report, and therefore are only briefly described here. New measures introduced since baseline are described in more detail. Descriptive statistics on all measures are presented based on a total sample of 11,000+ youth and their caregivers assessed at baseline and the following two years. Psychometric properties of the measures, including longitudinal aspects of the data, are reported, along with considerations for future measurement waves. The CE WG ABCD® components are an essential part of the overall protocol that permits characterization of the unique cultural and social environment within which each developing brain is transactionally embedded.Children from low-socioeconomic status (SES) households on average exhibit lower academic achievement than their higher-SES peers. We investigated a novel hypothesis that differences in early-developing sensory networks-specifically the ventral visual stream (VVS), which is involved in processing visual stimuli-contribute to SES-related disparities in executive functions (EF) and academic outcomes. We used fMRI to investigate SES-related differences in neural function in children (6-8 years, n = 62) during two attentional tasks involving attention to visual information cued attention and memory-guided attention. Recruitment of VVS during both tasks was associated with EF and academic achievement, and SES-related differences in VVS activation during cued attention were marginally explained by differences in cognitive stimulation. VVS activation during cued attention mediated SES-related differences in academic achievement. Finally, the link between VVS activation during both tasks and academic achievement was mediated by differences in EF. We extend previous work by highlighting that (i) early-developing visual processing regions play a role in supporting complex attentional processes, (ii) childhood SES is associated with VVS function, which is explained in part by SES-related differences in cognitive stimulation and (iii) provide preliminary evidence that individual differences in VVS function may play a role in the emergence of the income-achievement gap.Behavioural difficulties are seen as hallmarks of many neurodevelopmental conditions. Differences in functional brain organisation have been observed in these conditions, but little is known about how they are related to a child's profile of behavioural difficulties. We investigated whether behavioural difficulties are associated with how the brain is functionally organised in an intentionally heterogeneous and transdiagnostic sample of 957 children aged 5-15. We used consensus community detection to derive data-driven profiles of behavioural difficulties and constructed functional connectomes from a subset of 238 children with resting-state functional Magnetic Resonance Imaging (fMRI) data. We identified three distinct profiles of behaviour that were characterised by principal difficulties with hot executive function, cool executive function, and learning. Global organisation of the functional connectome did not differ between the groups, but multivariate patterns of connectivity at the level of Intrinsic Connectivity Networks (ICNs), nodes, and hubs significantly predicted group membership in held-out data. Fronto-parietal connector hubs were under-connected in all groups relative to a comparison sample and children with hot vs cool executive function difficulties were distinguished by connectivity in ICNs associated with cognitive control, emotion processing, and social cognition. This demonstrates both general and specific neurodevelopmental risk factors in the functional connectome.
The use of telehealth interventions, such as the remote monitoring of patient clinical data (e.g. blood pressure, blood glucose, heart rate, medication use), has been proposed as a strategy to better manage chronic conditions and to reduce the impact on patients and healthcare systems. The use of algorithms for data acquisition, analysis, transmission, communication and visualisation are now common in remote patient monitoring. However, their use and impact on chronic disease management has not been systematically investigated.

To investigate the use, impact, and performance of remote monitoring algorithms across various types of chronic conditions.

A literature search of MEDLINE complete, CINHAL complete, and EMBASE was performed using search terms relating to the concepts of remote monitoring, chronic conditions, and data processing algorithms. Comparable outcomes from studies describing the impact on process measures and clinical and patient-reported outcomes were pooled for a summary effect and metas to exist minimal testing in experimental studies, with only two included impact studies citing a performance study as support for the intervention algorithm used. Because of the disconnect between performance and impact studies, there is currently limited evidence of the effect of integrating advanced inference algorithms in remote monitoring interventions. If the field of remote patient monitoring is to progress, future impact studies should address this disconnect by evaluating high performance validated algorithms in robust clinical trials.
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