Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression

Teaching the Harlem Renaissance in the 21st Century

Designed for teachers and community educators, this resource presents student-centered curricula for grades 6-12. Each of the nine modules uses critical inquiry approaches to encourage students’ examination of the materiality of different texts and media as the means for exploring and synthesizing content to arrive at their own new understandings of the Harlem Renaissance. Teaching the Harlem Renaissance in the 21st Century accompanied the Wallach Art Gallery exhibition, Uptown Triennial 2020 (on view September 24, 2020–February 28, 2021). The resource is the result of a partnership with the Wallach Art Gallery, the Double Discovery Center, and Institute for Urban and Minority Education at Columbia University

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Effectiveness of iPad apps on visual-motor skills among children with special needs between 4y0m–7y11m

<p><b>Aims:</b> The aim of this randomized controlled trial was to assess the effectiveness of interventions using iPad applications compared to traditional occupational therapy on visual-motor integration (VMI) in school-aged children with poor VMI skills.</p> <p><b>Methods:</b> Twenty children aged 4y0m to 7y11m with poor VMI skills were randomly assigned to the experimental group (interventions using iPad apps targeting VMI skills) or control group (traditional occupational therapy intervention sessions targeting VMI skills). The intervention phase consisted of two 40-min sessions per week, over a period of 10 weeks. Participants were required to attend a minimum of 8 and a maximum of 12 sessions. The subjects were tested using the Beery-VMI and the visual-motor subscale of the M-FUN, at baseline and follow-up.</p> <p><b>Results:</b> Results from a 2-way mixed design ANOVA yielded significant results for the main effect of time for the M-FUN total raw score, as well as in the subscales Amazing Mazes, Hidden Forks, Go Fishing and VM Behavior. However, gains did not differ between intervention types over time. No significant results were found for the Beery-VMI.</p> <p><b>Conclusions:</b> This study supports the need for further research into the use of iPads for the development of VMI skills in the pediatric population.Implications for Rehabilitation</p><p>This is the first study to look at the use of iPads with school-aged children with poor visual-motor skills.</p><p>There is limited literature related to the use of iPads in pediatric occupational therapy, while they are increasingly being used in practice.</p><p>When compared to the traditional occupational therapy interventions, participants in the iPad intervention appeared to be more interested, engaged and motivated to participate in the therapy sessions.</p><p>Using iPad apps as an adjunct to therapy in intervention could be effective in improving VMI skills over time.</p><p></p> <p>This is the first study to look at the use of iPads with school-aged children with poor visual-motor skills.</p> <p>There is limited literature related to the use of iPads in pediatric occupational therapy, while they are increasingly being used in practice.</p> <p>When compared to the traditional occupational therapy interventions, participants in the iPad intervention appeared to be more interested, engaged and motivated to participate in the therapy sessions.</p> <p>Using iPad apps as an adjunct to therapy in intervention could be effective in improving VMI skills over time.</p

Hematopoietic Fas Deficiency Does Not Affect Experimental Atherosclerotic Lesion Formation despite Inducing a Proatherogenic State

The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr−/−). Bone marrow from Fas−/− mice was used to reconstitute irradiated Ldlr−/− mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr−/− mice reconstituted with Fas−/− hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas−/− bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr−/− mice

Cortisol Levels and Risk for Psychosis: Initial Findings from the North American Prodrome Longitudinal Study

BACKGROUND: Studies of biomarkers of hypothalamic-pituitary-adrenal (HPA) activity indicate that psychotic disorders are associated with elevated cortisol. This study examined cortisol levels in healthy controls and individuals who meet clinical high risk (CHR) criteria for psychosis. It was hypothesized that cortisol levels would be; a) elevated in the CHR group relative to controls, b) positively correlated with symptom severity, and c) most elevated in CHR patients who transition to psychotic level severity. METHODS: Baseline assessments were conducted at eight centers in the North American Prodrome Longitudinal Study (NAPLS). The present CHR sample included 256 individuals meeting Structured Interview for Prodromal Syndromes (SIPS) criteria, and 141 controls, all of whom underwent baseline assessment and measurement of salivary cortisol. RESULTS: Consistent with previous reports, there was an effect of age on cortisol, with increases through the adolescent/early adult years. Analysis of covariance (ANCOVA) showed a main effect of diagnostic group, with the CHR group showing higher cortisol. There were modest, positive correlations of cortisol with baseline symptom severity, and ANCOVA revealed higher baseline cortisol in those who transitioned to psychotic level symptoms when compared to healthy controls and CHR subjects who remitted. CONCLUSIONS: The present findings add to accumulating evidence of heightened cortisol secretion in CHR individuals. The findings also indicate nonspecific associations between cortisol levels and symptom severity, as well as symptom progression. The role of HPA activity in prediction of conversion to psychosis, and its relation with other biomarkers of risk, should receive attention in future research