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Purpose: Although asthma is common in children with sleep-disordered breathing (SDB), it is unclear whether and to what extent asthma is associated with SDB-related outcomes. Our objectives are to describe risk factors for asthma among children with mild SDB (mSDB) and assess the association between asthma and the severity of sleep-related outcomes., Methods: Cross-sectional analyses were conducted for children aged 3-12.9 years with mSDB enrolled in Pediatric Adenotonsillectomy for Snoring Children Study. Sleep-related outcomes included SDB symptoms (Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder scale (PSQ-SRBD)), SDB-specific quality of life (OSA-18), sleepiness (modified Epworth Sleepiness Score) and polysomnographic and actigraphic measures. Asthma was defined by caregiver-reported diagnosis with current asthma symptoms and medication use, or a Composite Asthma Severity Index (CASI) score ≥ 4. Asthma was further categorized into mild (CASI < 4) and moderate-to-severe (CASI ≥ 4). Regression analyses were conducted to identify asthma risk factors and estimate the associations between mild and moderate-to-severe asthma with sleep-related outcomes., Results: The sample included 425 children (20.3%-Black, 17.4%-Hispanic; 51.7%-female). The prevalence of asthma was 19.1% (7.1% moderate-to-severe, 12.0% mild). Environmental tobacco smoke exposure and markers of atopy were associated with asthma in multivariable-adjusted analyses. Moderate-to-severe asthma was associated with increased OSA symptoms measured by PSQ-SRBD (adjusted effect estimate for moderate-to-severe vs. no asthma ( β ^ adj ; 95%CI): 0.08; 0.01, 0.15)) and decreased quality of life measured by OSA-18 ( β ^ adj ; 95%CI: 7.5; 1.20, 13.82)), and a small increase in the arousal index ( β ^ adj ; 95%CI: 0.80; 0.09, 1.51))., Conclusion: Moderate-to-severe asthma was associated with worse QoL and greater SDB symptoms among children with mSDB. The co-occurrence of common risk factors for mSDB and asthma and worse symptoms and quality of life in children with both conditions support coordinated strategies for prevention and co-management of both disorders., Clinical Trial: Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040, https://clinicaltrials.gov/study/NCT02562040., Competing Interests: Declarations. Human and animal rights and informed consent: All procedures performed in studies involving human participants were in accordance with the ethical standards of each site participating in PATS and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the institutional review board at each site. Written informed consent was obtained from caregivers and assent from children older than 7 or 8 years (according to each site’s local requirements). Conflict of interest: Dr. Redline reports consulting fees from Apnimed Inc, Eli Lilly and Jazz Pharma, unrelated to this study., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

There is a pressing need to develop measures that are sensitive to the earliest subtle cognitive changes of Alzheimer's disease (AD) to improve early detection and track disease progression. The Loewenstein-Acevedo Scales of Semantic Interference (LASSI-L) has been shown to successfully discriminate between cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (MCI) and to correlate with total and regional brain amyloid load. The present study investigated how the LASSI-L scores change over time among three distinct diagnostic groups. Eighty-six community-dwelling older adults underwent a baseline evaluation including: a clinical interview, a neuropsychological evaluation, Magnetic Resonance Imaging (MRI), and amyloid Positron Emission Tomography (PET). A follow up evaluation was conducted 12 months later. Initial mean values were calculated using one-way ANOVAs and chi-square analyses. Post-hoc comparisons were conducted using Tukey's Honestly Significant Difference (HSD). A 3 × 2 repeated measures analysis was utilized to examine differences in LASSI-L performance over time. The MCI amyloid positive group demonstrated a significantly greater decline in LASSI-L performance than the MCI amyloid negative and CU groups respectively. The scales that best differentiated the three groups included the Cued A2, which taps into maximum learning capacity, and Cued B2, which assesses the failure to recover from proactive semantic interference. Our findings further support the LASSI-L's discriminative validity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Difficulties in inhibition and self-monitoring are early features of incipient Alzheimer's disease and may manifest as susceptibility to proactive semantic interference. However, due to limitations of traditional memory assessment paradigms, recovery from interference effects following repeated learning opportunities has not been explored., Objective: This study employed a novel computerized list learning test consisting of repeated learning trials to assess recovery from proactive and retroactive semantic interference., Design: The design was cross-sectional., Setting: Participants were recruited from the community as part of a longitudinal study on normal and abnormal aging., Participants: The sample consisted of 46 cognitively normal individuals and 30 participants with amnestic mild cognitive impairment., Measurements: Participants were administered the Cognitive Stress Test and traditional neuropsychological measures. Step-wise logistic regression was applied to determine which Cognitive Stress Test measures best discriminated between diagnostic groups. This was followed by receiver operating characteristic analyses., Results: Cued A3 recall, Cued B3 recall and Cued B2 intrusions were all independent predictors of diagnostic status. The overall predictive utility of the model yielded 75.9% sensitivity, 91.1% specificity, and an overall correct classification rate of 85.1%. When these variables were jointly entered into receiver operating characteristic analyses, the area under the curve was .923 (p<.001)., Conclusions: This novel paradigm's use of repeated learning trials offers a unique opportunity to assess recovery from proactive and retroactive semantic interference. Participants with mild cognitive impairment exhibited a continued failure to recover from proactive interference that could not be explained by mere learning deficits., Competing Interests: This study was. supported by the National Institute on Aging (NIA). The CST measure was developed by and is intellectual property held by Drs. Loewenstein and Curiel at the University of Miami.

Environmental pollution is a threat to humans and wildlife species. Of particular concern are endocrine disrupting chemicals (EDCs). An important target of EDCs is nuclear receptors (NRs) that control endocrine and metabolic responses through transcriptional regulation. Owing in part to structural differences of NRs, adverse effects of EDCs vary significantly among species. Here, we describe a multiplexed reporter assay (the Ecotox FACTORIAL) enabling parallel assessment of compounds' effects on estrogen, androgen, thyroid, and PPARγ receptors of representative mammals, birds, reptiles, amphibians, and fish. The Ecotox FACTORIAL is a single-well assay comprising a set of species-specific, one-hybrid GAL4-NR reporter constructs transiently transfected into test cells. To harmonize cross-species assessments, we used a combination of two approaches. First, we used the same type of test cells for all reporters; second, we implemented a parallel detection of reporter RNAs. The assay demonstrated excellent quality, reproducibility, and insignificant intra-assay variability. Importantly, the EC50 values for NR ligands were consistent with those reported for conventional assays. Using the assay allowed ranking the hazard potential of environmental pollutants (e.g., bisphenols, polycyclic aromatic hydrocarbons, and synthetic progestins) across species. Furthermore, the assay permitted detecting taxa-specific effects of surface water samples. Therefore, the Ecotox FACTORIAL enables harmonized assessment of the endocrine and metabolic disrupting activity of chemicals and surface water in humans as well as in wildlife species.

Essentials Many mediators increase tissue factor (TF) expression in a wide variety of cell types. The only known example of TF downregulation is by pericytes during wound healing angiogenesis. Downregulation of TF mRNA and protein in cultured pericytes is Protein Kinase C (PKC) dependent. Pericyte TF regulation is unique, since PKC mediates increased TF in all other cell types tested. SUMMARY: Background Embryonic and tumor-associated angiogenesis are linked to elevated expression of the procoagulant transmembrane receptor tissue factor (TF). In contrast, we have reported that high baseline TF expression by perivascular cells (pericytes) is dramatically reduced during angiogenesis at sites of wound healing. This is the only setting in which active TF downregulation has been reported, thus revealing a novel mechanism of TF regulation. Objectives To define the mechanisms underlying the unique pattern of TF expression in pericytes. Methods TF expression in primary cultures of human pericytes is not altered by angiogenic cytokines or growth factors, but is actively downregulated by phorbol 12-myristate 13-acetate (PMA). We characterized TF transcription, protein stability and trafficking in response to PMA. Results Exposure to PMA reduced TF mRNA synthesis and shortened the half-life of TF protein from 11 h to 4.5 h. Addition of PMA rapidly triggered endocytosis of cell surface TF, followed by degradation in lysosomes. Cell surface TF coagulant activity was maintained until internal stores were depleted. Reduction of TF transcription, TF endocytosis and enhanced degradation of TF protein were all blocked by broad-spectrum inhibitors of protein kinase C (PKC). This was a surprising finding, because PKC activation increases TF expression in other cell types that have been tested. Conclusions The unique PKC-dependent pathway of TF downregulation in pericytes suggests that TF downregulation may play a functional role in angiogenesis. Distinct pathways regulating pathological and physiological TF expression could be utilized to modulate TF expression for therapeutic purposes., (© 2019 International Society on Thrombosis and Haemostasis.)

Background: Behavior in response to distressful events during outpatient pediatric surgery can contribute to postoperative maladaptive behaviors, such as temper tantrums, nightmares, bed-wetting, and attention seeking. Currently available perioperative behavioral assessment tools have limited utility in guiding interventions to ameliorate maladaptive behaviors because they cannot be used in real time, are only intended to be used during 1 phase of the experience (e.g., perioperative), or provide only a static assessment of the child (e.g., level of anxiety). A simple, reliable, real-time tool is needed to appropriately identify children and parents whose behaviors in response to distressful events at any point in the perioperative continuum could benefit from timely behavioral intervention. Our specific aims were to (1) refine the Perioperative Adult Child Behavioral Interaction Scale (PACBIS) to improve its reliability in identifying perioperative behaviors and (2) validate the refined PACBIS against several established instruments., Methods: The PACBIS was used to assess the perioperative behaviors of 89 children aged 3 to 12 years presenting for adenotonsillectomy and their parents. Assessments using the PACBIS were made during perioperative events likely to prove distressing to children and/or parents (perioperative measurement of blood pressure, induction of anesthesia, and removal of the IV catheter before discharge). Static measurements of perioperative anxiety and behavioral compliance during anesthetic induction were made using the modified Yale Preoperative Anxiety Scale and the Induction Compliance Checklist (ICC). Each event was videotaped for later scoring using the Child-Adult Medical Procedure Interaction Scale-Short Form (CAMPIS-SF) and Observational Scale of Behavioral Distress (OSBD). Interrater reliability using linear weighted kappa (kappa(w)) and multiple validations using Spearman correlation coefficients were analyzed., Results: The PACBIS demonstrated good to excellent interrater reliability, with kappa(w) ranging from 0.62 to 0.94. The Child Coping and Child Distress subscores of the PACBIS demonstrated strong concurrent correlations with the modified Yale Preoperative Anxiety Scale, ICC, CAMPIS-SF, and OSBD. The Parent Positive subscore of the PACBIS correlated strongly with the CAMPIS-SF and OSBD, whereas the Parent Negative subscore showed significant correlation with the ICC. The PACBIS has strong construct and predictive validities., Conclusions: The PACBIS is a simple, easy to use, real-time instrument to evaluate perioperative behaviors of both children and parents. It has good to excellent interrater reliability and strong concurrent validity against currently accepted scales. The PACBIS offers a means to identify maladaptive child or parental behaviors in real time, making it possible to intervene to modify such behaviors in a timely fashion.