Duplication (dup7q11.23) and deletion (Williams syndrome) of chromosomal region 7q11.23 cause neurodevelopmental disorders with contrasting anxiety phenotypes. We found that 30% of 4- to 12-year-olds with dup7q11.23 but fewer than 5% of children with WS or in the general population met diagnostic criteria for a separation-anxiety disorder. To address the role of one commonly duplicated or deleted gene in separation anxiety, we compared mice that had varying numbers of Gtf2i copies. Relative to mouse pups with one or two Gtf2i copies, pups with additional Gtf2i copies showed significantly increased maternal separation-induced anxiety as measured by ultrasonic vocalizations. This study links the copy number of a single gene from 7q11.23 to separation anxiety in both mice and humans, highlighting the utility of mouse models in dissecting specific gene functions for genomic disorders that span many genes. This study also offers insight into molecular separation-anxiety pathways that might enable the development of targeted therapeutics.
Rationale: Ventilator-induced lung injury (VILI) significantly contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury. Understanding the molecular basis for response to cyclic stretch (CS) and its derangement during high-volume ventilation is of high priority. Objectives: To identify specific molecular regulators involved in the development of VILI. Methods: We undertook a comparative examination of cis-regulatory sequences involved in the coordinated expression of CS-responsive genes using microarray analysis. Analysis of stretched versus nonstretched cells identified significant enrichment for genes containing putative binding sites for the transcription factor activating transcription factor 3 (ATF3). To determine the role of ATF3 in vivo, we compared the response of ATF3 gene-deficient mice to wild-type mice in an in vivo model of VILI. Measurements and Main Results: ATF3 protein expression and nuclear translocation is increased in the lung after mechanical ventilation in wild-type mice. ATF3-deficient mice have greater sensitivity to mechanical ventilation alone or in conjunction with inhaled endotoxin, as demonstrated by increased cell infiltration and proinflammatory cytokines in the lung and bronchoalveolar lavage, and increased pulmonary edema and indices of tissue injury. The expression of stretch-responsive genes containing putative ATF3 cisregulatory regions was significantly altered in ATF3-deficient mice. Conclusions: ATF3 deficiency confers increased sensitivity to mechanical ventilation alone or in combination with inhaled endotoxin. We propose ATF3 acts to counterbalance CS and high volume-induced inflammation, dampening its ability to cause injury and consequently protecting animals from injurious CS.
Heterogeneous interventions and poor study design limit the strength of biofeedback evidence. A thoughtful biofeedback paradigm and standardized outcome toolbox can strengthen the confidence in the effect of biofeedback interventions for improving motor rehabilitation for people with CP. Implications for Rehabilitation Biofeedback can improve motor outcomes for people with Cerebral Palsy. If given too frequently, biofeedback may prevent the client from learning autonomously. Use consistent and concurrent feedback to improve simple/specific motor activities. Use terminal feedback and client-directed feedback to improve more complex/general motor activities.
Performance and durability of conductive yarns are essential factors to consider in the development of smart garments for textile computing applications. Conductive yarns and materials are used in various consumer and industrial products, however, their performance after washing, which is present with smart garments, is an unconventional, yet important consideration. This study investigates the impact of domestic washing on conductive silver-plated nylon and carbon-containing nylon yarns knitted into different patterns, simulating the incorporation of the conductive yarns into smart textiles. Various factors such as conductive yarn materials, types of knitting machine, and conductive feature patterns were considered. The resistance of silver-based textile electrodes increased by 100−300% over 50 wash cycles. Sulfidation and mechanical abrasion are the two main reasons for silver yarn degradation. The resistance of carbon-based textile electrodes stabilized after about five laundry cycles, showing little to no change afterward. Finally, the best performing silver and carbon electrodes were compared with gold-standard hydrogel electrodes for skin-electrode impedance and electrocardiogram measurement before and after 35 times of laundering. The results obtained demonstrated that both of the textile electrodes performed comparably to hydrogel electrodes and can be considered for continuous monitoring of biopotential signals from the human body.
Background Cardiac troponin (cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are increasingly used clinically to evaluate and prognosticate acute myocardial infarction and heart failure, respectively. Pediatric reference intervals and cut-offs have not been established for Roche’s Elecsys Troponin T hs (high sensitive) assay. Although pediatric reference intervals exist for NT-proBNP, cut-off values do not exist. In this study, we report reference intervals and 99th percentile cut-offs in a large, healthy Canadian pediatric population using the CALIPER cohort. Methods Blood samples from 484 healthy children and adolescents between 0 and <19 years old were recruited from hospital outpatient clinics and community settings. Serum samples were analyzed using Roche’s Cobas e411 and evaluated for high-sensitivity cTnT (hs-cTnT) and NT-proBNP concentrations. 95% reference intervals and 99th percentile cut-off values were established. Results Three hs-cTnT age partitions were established (0 to <6 months, 6 months to <1 year, and 1 to <19 years) with highest concentrations observed in children under 1 year. Two NT-proBNP age partitions were established (0 to <1 year, and 1 to <19 years), also with higher concentrations in infants under 1 year of age. For each of these age partitions, the 99th percentile cut-off, 95% reference interval, and proportion of detectable concentrations were determined. Conclusions This is the first study to examine hs-cTnT and NT-proBNP reference values together in a healthy pediatric cohort without other clinical indications. We present 99th percentile cut-offs, which will allow clinicians to appropriately evaluate cardiovascular disease in children and adolescents.
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