Organophosphate Poisoning–Induced Intermediate Syndrome: Can Electrophysiological Changes Help Predict Outcome?

Cynthia Aaron discusses the possible clinical implications of a new study evaluating electrophysiological changes in a cohort of patients with organophosphate poisoning

Evaluating a web-based computer-tailored physical activity intervention for those living with and beyond lung cancer (ExerciseGuide UK): protocol for a single group feasibility and acceptability study

Background: Lung cancer is the leading cause of cancer-related death globally. Physical activity and exercise provide unequivocal benefits to those living with and beyond lung cancer. However, few of those living with and beyond cancer meet the national physical activity guidelines. Various barriers exist for this population’s engagement in physical activity and exercise, such as the lack of knowledge and lack of tailored information, little access to exercise specialists, fatigue, and mobility challenges. Digitally delivered programmes have the potential to address several of these barriers, with techniques like “computer-tailoring” available to enable the delivery of tailored content at a time and place that is convenient. However, evaluation of such programmes is needed prior to implementation. This protocol describes a single group study that will examine the feasibility and acceptability of an online tool (ExerciseGuide UK) that provides those living with and beyond lung cancer web-based computer-tailored physical activity prescription and modules underpinned by behaviour change theories. Methods: Thirty-five individuals diagnosed with lung cancer, or cancer affecting the lung (e.g. pleural mesothelioma), will be recruited into a single-intervention arm. The platform will provide tailored resources and a personalised physical activity programme using IF-THEN algorithms. Exercise prescription will be tailored on factors such as self-reported specific pain location, exercise history, and current physical fitness. In addition, modules grounded in behaviour change will supplement the physical activity programme and will focus on topics such as exercise benefits, safety, goal setting, and tracking. The primary outcome will be assessed using pre-established criteria on feasibility and mixed-methods approach for acceptability. Secondary outcomes will explore changes in the physical activity, quality of life, anxiety, and depression. Discussion: This manuscript describes the protocol for a study examining the feasibility and acceptability of a web-based computer-tailored physical activity intervention for those living with and beyond lung cancer. The publication of this protocol aims to increase the transparency of the methods, report pre-determined criteria, and aid replication of the study and associated materials. If feasible and acceptable, this intervention will inform future studies of digital-based interventions. Trail registration: ClinicalTrails.gov, NCT05121259. Registered on November 16, 2021

Regulation of Simulation Use in United States Prelicensure Nursing Programs

Background Simulation usage has proliferated throughout nursing education. Although nursing programs have sought integration of simulation to substitute traditional clinical learning hours, the variability of regulations between states raises questions about consistency of learner outcomes. Methods The Boards of Nursing (BONs) of the United States and the District of Columbia were queried by internet, phone, and email to discover regulations and guidelines for the use of simulation in nursing education. Results More than half of the BONs reported regulations for simulation use, but they varied greatly. Some had regulations defining a percentage of traditional clinical hours that could be replaced with simulation. A few BONs specified an equivalent ratio of hours between simulation and clinical, but most did not. Some BONs described requirements for simulation instructors, but few provided specific criteria. Conclusions This search revealed great variability in how BONs are defining and regulating the use of simulation in prelicensure nursing education including the amount of traditional clinical hours that can be replaced with simulation. Because a description of measured learning that occurs during traditional clinical learning hours is lacking, inconsistency in regulation will persist

Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart

Noncellular differentiation effects have emerged as important mechanisms mediating therapeutic effects of stem or progenitor cell transplantation. Here, we investigated the expression patterns and sources of humoral factors and their regional and systemic biological effects after bone marrow (BM)-derived endothelial progenitor cell (EPC) transplantation into ischemic myocardium. Although most of the transplanted EPCs disappeared within a week, up-regulation of multiple humoral factors was sustained for longer than two weeks, which correlated well with the recovery of cardiac function. To determine the source of the humoral factors, we injected human EPCs into immunodeficient mice. Whereas the expression of human EPC (donor)-derived cytokines rapidly decreased to a nondetectable level within a week, up-regulation of mouse (recipient)-derived cytokines, including factors that could mobilize BM cells, was sustained. Histologically, we observed higher capillary density, a higher proliferation of myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size. Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were increased in the peripheral circulation and incorporated into the site of neovascularization and myocardial repair. These data indicate that myocardial EPC transplantation induces humoral effects, which are sustained by host tissues and play a crucial role in repairing myocardial injury

The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients

Carpenter syndrome (CRPTS) is a rare autosomal recessive condition caused by biallelic variants in genes that encode negative regulators of hedgehog signalling (RAB23 [CRPT1] or, more rarely, MEGF8 [CRPT2]), and is characterised by craniosynostosis, polysyndactyly, and other congenital abnormalities. We describe a further six families comprising eight individuals with MEGF8-associated CRPT2, increasing the total number of reported cases to fifteen, and refine the phenotype of CRPT2 compared to CRPT1. The core features of craniosynostosis, polysyndactyly and (in males) cryptorchidism are almost universal in both CRPT1 and CRPT2. However, laterality defects are present in nearly half of those with MEGF8-associated CRPT2, but are rare in RAB23-associated CRPT1. Craniosynostosis in CRPT2 commonly involves a single midline suture in comparison to the multi-suture craniosynostosis characteristic of CRPT1. No patient to date has carried two MEGF8 gene alterations that are both predicted to lead to complete loss-of-function, suggesting that a variable degree of residual MEGF8 activity may be essential for viability and potentially contributing to variable phenotypic severity. These data refine the phenotypic spectrum of CRPT2 in comparison to CRPT1 and more than double the number of likely pathogenic MEGF8 variants in this rare disorder

Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization

The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs

Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2

SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (ΔSAS) have been described in the literature. We describe 17 additional individuals with ΔSAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 ± 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non-ΔSAS). Individuals in the ΔSAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = −2.3 to −1.1, p \u3c 0.0001) and height (95% CI = −2.3 to −1.0, p \u3c 0.0001) Z-score means from birth to last available measurement. ΔSAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of ΔSAS individuals generated by automated image analysis was distinct as compared to matched controls and non-ΔSAS individuals. We also present additional genotype–phenotype correlations for individuals in the ΔSAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with ΔSAS variants

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd