The NLS-RYBP also interacted with both importin species (dissociation constant in the low micromolar range), at low or high ionic strength, as shown by intrinsic fluorescence and ITC. These findings indicate that the NLS region, which was mainly unfolded in isolation in solution, was essentially responsible for the binding of RYBP to each of the importin species. Furthermore, the molecular simulations predict that the anchoring of NLS-RYBP takes place in the major binding site for the NLS of cargo proteins bound to Impα3. Taken together, our findings pinpoint the theoretical predictions of the NLS region in RYBP and, more importantly, suggest that this IDP relies on an importin for its nuclear translocation.
  Pycnodysostosis is an autosomal recessive skeletal dysplasia with easily recognizable clinical features and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 25 Indian patients with pycnodysostosis from 20 families.
 
  Clinical information was collected on a predesigned clinical proforma. Sanger method was employed to sequence all the exons and exon/intron boundaries of the CTSK gene. Novel variants were systematically assessed by prediction softwares and protein modelling. The pathogenicity of variant was established based on ACMG-AMP criteria. An attempt was also made to establish a genotype-phenotype correlation and devise a diagnostic scoring system based on clinical and radiological findings.
 
  Consanguinity and positive family history were present in 65% (13/20) and 45% (9/20) of the families respectively. Short stature and fractures were the predominant presenting complaints and was evident in 96% (24/25) and 32% (8/25) of affected individuals respectiveystem which requires further validation.
 This study delineated the genotypic and phenotypic characterisation of Indian patients with pycnodysostosis with identification of 10 novel variants. We also attempted to develop a clinically useful diagnostic scoring system which requires further validation.Sedentary behavior increases the risk for multiple chronic diseases, early mortality, and accelerated cognitive decline in older adults. Interventions to reduce sedentary behavior among older adults are needed to improve health outcomes and reduce the burden on healthcare systems. We designed a randomized controlled trial that uses a self-affirmation manipulation and gain-framed health messaging to effectively reduce sedentary behavior in older adults. This message-based intervention lasts 6 weeks, recruiting 80 healthy but sedentary older adults from the community, between the ages of 60 and 95 years. Participants are randomly assigned to one of two groups 1) an intervention group, which receives self-affirmation followed by gain-framed health messages daily or 2) a control group, which receives daily loss-framed health messages only. Objective physical activity engagement is measured by accelerometers. Accelerometers are deployed a week before, during, and the last week of intervention to examine potential changes in sedentary time and physical activity engagement. Participants undertake structural and functional (resting and task-based) MRI scans, neuropsychological tests, computerized behavioral measures, and neurobehavioral inventories at baseline and after the intervention. A 3-month follow-up assesses the long-term maintenance of any engendered behaviors from the intervention period. This study will assess the effectiveness of a novel behavioral intervention at reducing sedentarism in older adults and examine the neurobehavioral mechanisms underlying any such changes.
  To determine if providing firearm storage devices with training during clinical care improves safe storage practices in household members of children who present to a pediatric hospital with an emergent mental health complaint.
 
  Prospective, pre-post study. Enrollment occurred in the emergency department or the inpatient psychiatric unit.  https://www.selleckchem.com/products/gdc-0084.html  Participants in the observation phase received usual care. Participants in the intervention phase were randomized to be offered a firearm storage device at either no or low ($5) cost and trained in its use. We surveyed participants at enrollment, 7, & 30 days post visit. Our primary outcome was triple-safe storage (TSS) - storing firearms unloaded, locked, and with ammunition stored and locked separately.
 
  About 256 participants enrolled. In the observation phase TSS increased from 21% (95% confidence interval [CI] 14%-30%) at baseline to 31% (95% CI 21%-42%) at 7 and 31% (95% CI 21%-43%) at 30 days. In the intervention phase, TSS increased from 32% (95% CI 25%-39%) at baseline to 56% (95% CI 48%-64%) at 7 and 56% (95% CI 47%-64%) at 30 days. Among those not practicing TSS at baseline, 7-day TSS was higher in the intervention (38%) versus the observation phase (14%, P=.001).
 
  Distribution and training in the use of firearm storage devices increased TSS in the study population, improves pediatric safety and should be part of the routine care of these high-risk patients.
 Distribution and training in the use of firearm storage devices increased TSS in the study population, improves pediatric safety and should be part of the routine care of these high-risk patients.
  Pediatric residents must demonstrate competence prior to graduation in Accreditation Council for Graduate Medical Education (ACGME) required procedures. Recent literature shows general pediatricians (GPeds) infrequently perform these procedures yet believe them important to learn. The purpose of this study was to determine why GPeds believe learning procedures was important, what barriers prevent them from developing and maintaining procedural skills, and what procedures they believe should be included in training.
 
  Fifty-one GPeds from the American Board of Pediatrics General Examination Committee and the central Ohio region participated in 30-minute semistructured recorded phone interviews that probed their use of procedures across training and current practice. Participants represented urban, suburban, and rural geographic regions and practiced in a variety of settings. We conducted a thematic analysis of transcribed interviews.
 
  GPeds believed currently required ACGME procedures were crucial to learn for 5 reasons 1) adaptation to change in practice type or location, 2) emergency preparedness, 3) counseling patients and families, 4) distance from a tertiary care center and specialists, and 5) professional identity as a pediatrician.