The Development and Integration of a Safety Officer Role to Facilitate Prevention of COVID-19 Virus Transmission in an Adult Inpatient Rehabilitation Setting Using Collaborative Change Leadership Methodology.

Background: With the onset of the COVID-19 pandemic, a large urban academic hospital responded by creating the temporary role of a "Safety Officer (SO)." The key task of the SO role was to supervise staff donning and doffing personal protective equipment (PPE) and provide real-time feedback on their performance. The support for safe donning and doffing would contribute to staff well-being by reducing their fear of infection transmission.

Family-Reflections.com: Creating a parent-to-parent web-based tool regarding pediatric home ventilation.

Background: The decision to initiate pediatric mechanical ventilation via tracheostomy ("home ventilation") is complex and parents often desire information from other parents who have faced this decision. However, parent-to-parent communication is challenging as it is difficult to connect new families to experienced families in ways that optimize informed, balanced decision-making.

Objective: Create a parent-to-parent web-based tool to support decision-making about pediatric home ventilation.

Discovery of small molecules that target a tertiary-structured RNA.

There is growing interest in therapeutic intervention that targets disease-relevant RNAs using small molecules. While there have been some successes in RNA-targeted small-molecule discovery, a deeper understanding of structure-activity relationships in pursuing these targets has remained elusive. One of the best-studied tertiary-structured RNAs is the theophylline aptamer, which binds theophylline with high affinity and selectivity.

Antitarget Selectivity and Tolerability of Novel Pyrrolo[2,3-]pyrimidine RET Inhibitors.

The selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-]pyrimidine scaffold. The optimization of this pyrrolo[2,3-]pyrimidine core resulted in compound , which demonstrated potent RET kinase inhibition and robust efficacy in RET-driven tumor xenografts upon multiday dosing in mice.

The cognitive augmented mobility program (CAMP): feasibility and preliminary efficacy.

Background: Best evidence suggests incorporating task-specific training, aerobics, and strengthening to improve mobility and gait in persons with stroke (PWS). Related research suggests incorporating cognitive problem-solving strategy training may lead to better skill maintenance and transfer. The present study examined the feasibility and preliminary outcomes of an evidence-based cognitive augmented mobility program (CAMP) for PWS.

Efficacy and Tolerability of Pyrazolo[1,5-]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma.

RET (REarranged during Transfection) kinase gain-of-function aberrancies have been identified as potential oncogenic drivers in lung adenocarcinoma, along with several other cancer types, prompting the discovery and assessment of selective inhibitors. Internal mining and analysis of relevant kinase data informed the decision to investigate a pyrazolo[1,5-]pyrimidine scaffold, where subsequent optimization led to the identification of compound WF-47-JS03 (), a potent RET kinase inhibitor with >500-fold selectivity against KDR (Kinase insert Domain Receptor) in cellular assays. In subsequent mouse studies, compound demonstrated effective brain penetration and was found to induce strong regression of RET-driven tumor xenografts at a well-tolerated dose (10 mg/kg, po, qd).

A theory-based multi-component intervention to increase reactive balance measurement by physiotherapists in three rehabilitation hospitals: an uncontrolled single group study.

Background: Most implementation interventions in rehabilitation, including physiotherapy, have used passive, non-theoretical approaches without demonstrated effectiveness. The goal of this study was to improve an important domain of physiotherapy practice - reactive balance measurement - with a targeted theory-based multi-component intervention developed using the Theoretical Domains Framework. The primary objective was to determine documented reactive balance measure use in a 12-month baseline, during, and for three months post- intervention.

Development of a Theory-Based Intervention to Increase Clinical Measurement of Reactive Balance in Adults at Risk of Falls.

Background: Effective balance reactions are essential for avoiding falls, but are not regularly measured by physical therapists. Physical therapists report wanting to improve reactive balance assessment, and theory-based approaches are recommended as the foundation for the development of interventions. This article describes how a behavior change theory for health care providers, the theoretical domains framework (TDF), was used to develop an intervention to increase reactive balance measurement among physical therapists who work in rehabilitation settings and treat adults who are at risk of falls.

A pattern-based approach to bowel obstruction in the newborn.

Intestinal obstruction is common in newborns, and the radiologist plays a critical role in the care of these children. Diagnosing and managing the potentially obstructed newborn can be challenging, especially given the myriad underlying pathologies that range from benign to acutely life-threatening. A familiarity with the most common diagnoses is essential, but equally important to the radiologist is a systematic approach to management of the child in this setting.

Predicting cognitive decline in subjects at risk for Alzheimer disease by using combined cerebrospinal fluid, MR imaging, and PET biomarkers.

Purpose: To assess the extent to which multiple Alzheimer disease (AD) biomarkers improve the ability to predict future decline in subjects with mild cognitive impairment (MCI) compared with predictions based on clinical parameters alone.

Materials And Methods: All protocols were approved by the institutional review board at each site, and written informed consent was obtained from all subjects. The study was HIPAA compliant.

Use of Nintendo Wii Fit™ in the rehabilitation of outpatients following total knee replacement: a preliminary randomised controlled trial.

Objectives: To determine whether Nintendo Wii Fit™ is an acceptable adjunct to physiotherapy treatment in the rehabilitation of balance, lower extremity movement, strength and function in outpatients following total knee replacement.

Design: Preliminary randomised controlled trial.

Setting: Outpatient department of a rehabilitation hospital.

Limited utility of exercise-stress testing to prevent T-wave oversensing in pediatric internal cardioverter defibrillator recipients.

Background: Inappropriate internal cardioverter defibrillator (ICD) therapies may result from T-wave oversensing (TWOS) during exertion in children. The aim of this study was to evaluate the utility of an exercise treadmill test to predict inappropriate ICD therapies secondary to TWOS.

Methods: Eligible pediatric ICD recipients underwent exercise-stress testing with concomitant evaluation of all intracardiac electrograms.

Easy access to firearms: juveniles' risks for violent offending and violent victimization.

Keeping firearms at home may increase personal safety but it may also increase the risk of injury. This study uses data from three waves of the National Longitudinal Study of Adolescent Health to assess the extent to which adolescents' easy access to firearms at home increases the risk of violent offending and violent victimization. Access to firearms was higher for males, Whites, and adolescents having two parents, especially fathers.

The utility of a video game system in rehabilitation of burn and nonburn patients: a survey among occupational therapy and physiotherapy practitioners.

The objective of this study was to investigate perceptions of occupational therapists and physiotherapists on the use of Nintendo Wii™ (Nintendo of America Inc., Redmond, WA) in rehabilitation. Occupational therapists and physiotherapists in a rehabilitation hospital trialed four Wii games that addressed physical movement, balance, coordination, and cognitive performance.

Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation.

A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.

The SH2 domain of the C-terminal Src kinase [Csk] contains a unique disulfide bond that is not present in other known SH2 domains. To investigate whether this unusual disulfide bond serves a novel function, the effects of disulfide bond formation on catalytic activity of the full-length protein and on the structure of the SH2 domain were investigated. The kinase activity of full-length Csk decreases by an order of magnitude upon formation of the disulfide bond in the distal SH2 domain.

SRC tail phosphorylation is limited by structural changes in the regulatory tyrosine kinase Csk.

Src family tyrosine kinases are down-regulated through phosphorylation of a single C-terminal tyrosine by the nonreceptor tyrosine kinase Csk. Despite the fundamental role of Csk in controlling cell growth and differentiation, it is unclear what limits this key signaling reaction and controls the production of catalytically repressed Src. To investigate this issue, stopped-flow fluorescence experiments were performed to determine which steps modulate catalysis.

The role of victim-related factors in victim restitution: a multi-method analysis of restitution in Pennsylvania.

Mandatory statutes do not always produce change, but a 1995 Pennsylvania statutory change making restitution mandatory dramatically increased the proportion of cases in which restitution was imposed. There are three possible reasons for this generally successful implementation: (a) judges agreed with the victim-centered goals of the statute, (b) there were mechanisms in place to implement the goals of assisting victims, and (c) there was a context supportive of victims that made it easier to follow the law. Two studies investigated these possible explanations.

Dynamic coupling between the SH2 domain and active site of the COOH terminal Src kinase, Csk.

The SH2 domain is required for high catalytic activity in the COOH-terminal Src kinase (Csk). Previous solution studies suggest that a short peptide sequence, the SH2-kinase linker, provides a functional connection between the active site and the distal SH2 domain that could underlie this catalytic phenomenon. Substitutions in Phe183 (tyrosine, alanine, and glycine), a critical hydrophobic residue in the linker, result in large decreases in substrate turnover and large increases in the K(m) for ATP.

Efficient gene delivery and gene expression in zebrafish using the Sleeping Beauty transposon.

We used the Tc1/mariner family transposable element Sleeping Beauty (SB) for transgenesis and long-term expression studies in the zebrafish (Danio rerio), a popular organism for clinical disease, vertebrate patterning, and cell biology applications. SB transposase enhanced the transgenesis and expression rate sixfold (from 5 to 31%) and more than doubled the total number of tagged chromosomes over standard, plasmid injection-based transgenesis methods. Molecular analysis of these loci demonstrated a precise integration of these elements into recipient chromosomes with genetic footprints diagnostic of transposition.

Novel destabilization of nucleotide binding by the gamma phosphate of ATP in the yeast SR protein kinase Sky1p.

SR protein kinases (SRPKs) regulate the temporal and cell-specific selection of alternative splice sites. These enzymes are highly unique members of the protein kinase family. SRPKs contain a large domain insert (approximately 200 residues) within the kinase core, do not require phosphorylation for regulation, have an extended helix insert near the nucleotide pocket, and possess unusual substrate specificity determinants.