Attention-deficit/hyperactivity disorder (ADHD) comorbid with sleep disturbances can produce profound disruption in daily life and negatively impact quality of life of both the child and the family. ...However, the temporal relationship between ADHD and sleep impairment is unclear, as are underlying common brain mechanisms.
This study used data from the Quebec Longitudinal Study of Child Development (n = 1601, 52% female) and the Adolescent Brain Cognitive Development Study (n = 3515, 48% female). Longitudinal relationships between symptoms were examined using cross-lagged panel models. Gray matter volume neural correlates were identified using linear regression. The transcriptomic signature of the identified brain-ADHD-sleep relationship was characterized by gene enrichment analysis. Confounding factors, such as stimulant drugs for ADHD and socioeconomic status, were controlled for.
ADHD symptoms contributed to sleep disturbances at one or more subsequent time points in both cohorts. Lower gray matter volumes in the middle frontal gyrus and inferior frontal gyrus, amygdala, striatum, and insula were associated with both ADHD symptoms and sleep disturbances. ADHD symptoms significantly mediated the link between these structural brain abnormalities and sleep dysregulation, and genes were differentially expressed in the implicated brain regions, including those involved in neurotransmission and circadian entrainment.
This study indicates that ADHD symptoms and sleep disturbances have common neural correlates, including structural changes of the ventral attention system and frontostriatal circuitry. Leveraging data from large datasets, these results offer new mechanistic insights into this clinically important relationship between ADHD and sleep impairment, with potential implications for neurobiological models and future therapeutic directions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
No global positioning system (GPS) technology study has been conducted among a sample of young gay, bisexual, and other men who have sex with men (YMSM). As such, the purpose of this study was to ...evaluate the feasibility and acceptability of using GPS methods to understand the spatial context of substance use and sexual risk behaviors among a sample of YMSM in New York City, a high-risk population.
Data came from a subsample of the ongoing P18 Cohort Study (n = 75). GPS feasibility and acceptability among participants was measured with: 1) a pre- and post-survey and 2) adherence to the GPS protocol which included returning the GPS device, self-report of charging and carrying the GPS device as well as objective data analyzed from the GPS devices. Analyses of the feasibility surveys were treated as repeated measures as each participant had a pre- and post-feasibility survey. When comparing the similar GPS survey items asked at baseline and at follow-up, we present percentages and associated p-values based on chi-square statistics.
Participants reported high ratings of pre-GPS acceptability, ease of use, and low levels of wear-related concerns in addition to few concerns related to safety, loss, or appearance, which were maintained after baseline GPS feasibility data collection. The GPS return rate was 100%. Most participants charged and carried the GPS device on most days. Of the total of 75 participants with GPS data, 75 (100%) have at least one hour of GPS data for one day and 63 (84%) had at least one hour on all 7 days.
Results from this pilot study demonstrate that utilizing GPS methods among YMSM is feasible and acceptable. GPS devices may be used in spatial epidemiology research in YMSM populations to understand place-based determinants of health such as substance use and sexual risk behaviors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oral mucositis (OM) is a treatment-limiting adverse side effect of radiation and chemotherapy. Approximately 80% of patients undergoing radiotherapy (RT) for head and neck cancers (HNC) develop OM, ...representing a major unmet medical condition. Our understanding of the immunopathogenesis of OM is limited, due in part to the surprising paucity of information regarding healing mechanisms in the oral mucosa. RNAseq of oral tissue in a murine model that closely mimics human OM, showed elevated expression of IL-17 and related immune pathways in response to head and neck irradiation (HNI). Strikingly, mice lacking the IL-17 receptor (IL-17RA) exhibited markedly more severe OM. Restoration of the oral mucosa was compromised in
mice and components associated with healing, including matrix metalloproteinase 3, 10 and IL-24 were diminished. IL-17 is typically associated with recruitment of neutrophils to mucosal sites following oral infections. Unexpectedly, in OM the absence of IL-17RA resulted in excessive neutrophil recruitment and immunopathology. Instead, neutrophil activation was IL-1R-driven in
mice. Blockade of IL-1R and depletion of neutrophils lessened the severity of damage in these mice. Overall, we show IL-17 is protective in OM through multiple mechanisms including restoration of the damaged epithelia and control of the neutrophil response. We also present a clinically relevant murine model of human OM to improve mechanistic understanding and develop rational translational therapeutics.
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•PM10 induced neurodevelopmental toxicity in zebrafish embryos and larvae.•PM10 exposure inhibited the locomotor behavior and growth of dopaminergic neurons.•PM10 exposure induced the ...neurovasculature defects and cerebral haemorrhage.•PM10 altered the expression of genes associated with embryonic brain development including those of dopaminergic pathway.
Particulate matter with 10 μm or less in diameter (PM10) exposure is a major threat to health and environment around the world. Even though a number of clinical and experimental studies have focused on the cardiopulmonary effects of PM10, its impact on neurovascular development and the underlying toxicity is relatively less studied. The present study is therefore undertaken to evaluate the potential toxic effects of PM10 on neurodevelopment and the associated gene expression profiles in the zebrafish embryo/larvae. During 2017–2018, PM10 samples (24 h sampling, 180 sampling days) were collected in an urban downtown site of Jinan, Shandong province, China. To delineate the potential toxic effects of PM10 during neurodevelopment, zebrafish embryos/larvae were exposed to different concentrations viz., 25, 50, 100, 200, and 400 μg/mL of PM10 solution for 24–120 h post-fertilization (hpf) and the effects on the mortality, morphology, swimming behavior, electroencephalogram discharges, growth of dopaminergic neurons, neurovasculature development and gene expression profiles of dopaminergic and neurodevelopment-related genes using qRT-PCR were studied.
A significant increase in the mortality rate and morphological abnormalities were observed in 200 μg/mL of the PM10 treated group at 120 hpf. High concentrations (≥100 μg/mL) of PM10 exposure reduced locomotor behavior, caused abnormal electroencephalogram discharges, degeneration of dopaminergic neurons, inhibition of neurovascular development, cerebral hemorrhage, and significant changes in the expression pattern of genes involved in dopaminergic pathway and neurodevelopment such as (th1, dat, drd1, drd2a, drd3, drd4b, syn2a, gap43, α1-tubulin, gfap, map2, elavl3, eno2, neurog1, sox2, shha, and mbp). Taken together, all these parameters collectively imply developmental neurotoxicity and dysfunction of the dopaminergic neurons which provides the first evidence of PM10-induced neurodevelopmental toxicity in the zebrafish embryo/larvae.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The extensive heterogeneity of biological data poses challenges to analysis and interpretation. Construction of a large-scale mechanistic model of
enabled us to integrate and cross-evaluate a ...massive, heterogeneous dataset based on measurements reported by various groups over decades. We identified inconsistencies with functional consequences across the data, including that the total output of the ribosomes and RNA polymerases described by data are not sufficient for a cell to reproduce measured doubling times, that measured metabolic parameters are neither fully compatible with each other nor with overall growth, and that essential proteins are absent during the cell cycle-and the cell is robust to this absence. Finally, considering these data as a whole leads to successful predictions of new experimental outcomes, in this case protein half-lives.
We report a mechanistic investigation of calcium bistriflimide-mediated sulfur(VI)–fluoride exchange (SuFEx) between sulfonyl fluorides and amines. We determine the likely pre-activation resting ...statea calcium bistriflimide complex with ligated aminesthus allowing for corroborated calculation of the SuFEx activation barrier at ∼21 kcal/mol, compared to 21.5 ± 0.14 kcal/mol derived via kinetics experiments. Transition state analysis revealed: (1) a two-point calcium-substrate contact that activates the sulfur(VI) center and stabilizes the leaving fluoride and (2) a 1,4-diazabicyclo2.2.2octane additive that provides Brønsted-base activation of the nucleophilic amine. Stable Ca–F complexes upon sulfonamide formation are likely contributors to inhibited catalytic turnover, and a proof-of-principle redesign provided evidence that sulfonamide formation is feasible with 10 mol % calcium bistriflimide.
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IJS, KILJ, NUK, PNG, UL, UM
Body-focused repetitive behaviors (BFRBs), such as trichotillomania and skin picking disorder, are psychiatric disorders characterized by repetitive grooming that result in hair loss or excoriations. ...Questions remain as to whether there are racial/ethnic differences in the clinical presentation of BFRBs.
We recruited 539 adults with DSM-5 trichotillomania or skin picking disorder. Of these, 76 (14.1%) self-identified as Black, Asian, or Minority Ethnic (BAME), while 463 (85.9%) self-identified as white Caucasian (hereafter referred to as non-BAME). BAME and non-BAME participants were compared on demographics, symptom severity, comorbid conditions and psychosocial impairment.
Groups did not differ in terms of age, sex, or education levels. BAME individuals reported significantly more time spent picking or hair pulling per day compared to non-BAME individuals, and were less likely to have received treatment for their BFRB symptoms. Some differences were also found with respect to where on the body people pull and pick from.
In general, the clinical profiles of BFRBs appeared similar between those from BAME versus non-BAME backgrounds. However, differences were found in terms of treatments received and an aspect of symptom severity. The findings highlight the need to better understand the heterogeneity of BFRBs including potential health inequalities.
•Few studies have examined associations of race/ethnicity on body focused repetitive behaviors.•This study found that ethnic minorities experienced greater severity of picking and pulling.•Ethnic minorities were less likely to have received treatment for trichotillomania or skin picking disorder.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•PUI is associated with eating disorder psychopathology and body dissatisfaction.•PUI is associated with bulimia symptoms, restrained eating and drive for thinness.•Multiple facets of online use are ...influencing factors for eating disorder symptoms.•Males with eating disorder symptoms are similarly affected in those domains by PUI.•Small but significant PUI ∼ ED effects may have accumulative influence over time.
Eating disorders are widespread illnesses with significant impact. There is growing concern about how those at risk of eating disorders overuse online resources to their detriment. We conducted a pre-registered systematic review and meta-analysis of studies examining Problematic Usage of the Internet (PUI) and eating disorder and related psychopathology. The meta-analysis comprised n = 32,295 participants, in which PUI was correlated with significant eating disorder general psychopathology Pearson r = 0.22 (s.e. = 0.04, p < 0.001), body dissatisfaction r = 0.16 (s.e. = 0.02, p < 0.001), drive-for-thinness r = 0.16 (s.e. = 0.04, p < 0.001) and dietary restraint r = 0.18 (s.e. = 0.03). Effects were not moderated by gender, PUI facet or study quality. Results are in support of PUI impacting on eating disorder symptoms; males may be equally vulnerable to these potential effects. Prospective and experimental studies in the field suggest that small but significant effects exist and may have accumulative influence over time and across all age groups. Those findings are important to expand our understanding of PUI as a multifaceted concept and its impact on multiple levels of ascertainment of eating disorder and related psychopathology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose Secondary prevention has an important role in urinary stone disease. The core of secondary prevention is the identification of modifiable risk factors by a 24-hour urine collection, which ...then directs selective medical therapy. While this decreases the recurrence rate, little is known about the frequency with which 24-hour urine collections are obtained. Materials and Methods Using medical claims from 2002 to 2006 we identified adults with incident urinary stone episodes. With appropriate diagnosis codes we determined those at high risk for recurrence. Of these patients we determined the proportion in whom a 24-hour urine collection was done within 6 months of diagnosis. Finally, we fitted regression models to measure associations between patient and provider level factors, and obtaining a 24-hour urine collection. Results We identified 28,836 patients at high risk for recurrence. The prevalence of 24-hour urine testing increased from 7.0% in 2003 to 7.9% in 2006 (p = 0.011), although the overall prevalence was exceedingly low at 7.4%. Multivariable regression revealed that region of residence and level of comorbid illness were independently associated with 24-hour urine collection, as was the type of physician who performed the followup. For instance, the odds of metabolic evaluation were 2.9 times higher when a patient was seen by a nephrologist (OR 2.92, 95% CI 2.32–3.67), and more than threefold higher when seen by a urologist (OR 3.87, 95% CI 3.48–4.30). Conclusions Obtaining 24-hour urine collections in stone formers at high risk is uncommon, raising a quality of care concern.
Purpose of Review
The 22q11.2 deletion syndrome (22q11DS) is associated with a broad spectrum of neurodevelopmental phenotypes and is the strongest known single genetic risk factor for schizophrenia. ...Compared to other rare structural pathogenic genetic variants, 22q11DS is relatively common and one of the most extensively studied. This review provides a state-of-the-art overview of current insights regarding associated neurodevelopmental phenotypes and potential implications for 22q11DS and beyond.
Recent Findings
We will first discuss recent findings with respect to neurodevelopmental phenotypic expression associated with 22q11DS, including psychotic disorders, intellectual functioning, autism spectrum disorders, as well as their interactions. Second, we will address considerations that are important in interpreting these data and propose potential implications for both the clinical care for and the empirical study of individuals with 22q11DS. Third, we will highlight variable penetrance and pleiotropy with respect to neurodevelopmental phenotypes in 22q11DS. We will discuss how these phenomena are consistently observed in the context of virtually all rare pathogenic variants and that they pose substantial challenges from both a clinical and a research perspective.
Summary
We outline how 22q11DS could be viewed as a genetic model for studying neurodevelopmental phenotypes. In addition, we propose that 22q11DS research can help elucidate mechanisms underlying variable expression and pleiotropy of neurodevelopmental phenotypes, insights that are likely relevant for 22q11DS and beyond, including for individuals with other rare pathogenic genetic variants and for individuals with idiopathic neurodevelopmental conditions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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