Telemedicine-guided education on secondary stroke and fall prevention following inpatient rehabilitation for Texas patients with stroke and their caregivers: a feasibility pilot study.

INTRODUCTION: The aftermath of stroke leaves many consequences including cognitive deficits and falls due to imbalance. Stroke survivors and families struggle to navigate the complex healthcare system with little assistance posthospital discharge, often leading to early hospital readmission and worse stroke outcomes. Telemedicine Guided Education on Secondary Stroke and Fall Prevention Following Inpatient Rehabilitation feasibility study examines whether stroke survivors and their caregivers find value in telerehabilitation (TR) home visits that provide individualised care and education by a multidisciplinary team after discharge from inpatient rehabilitation. METHODS AND ANALYSIS: A prospective, single arm, pilot study is designed to evaluate the feasibility of weekly TR home visits initiated postdischarge from inpatient rehabilitation. Newly diagnosed patients with stroke are recruited from a Houston-based comprehensive stroke centre inpatient rehabilitation unit, loaned an iPad with data plan and trained to use information technology security-approved videoconferencing application. After hospital discharge, six weekly TR home visits are led by rotating specialists (pharmacist, physical/occupational therapist, speech therapist, rehabilitation physician, social worker, geriatrician specialised in fracture prevention) followed by satisfaction survey on week 7. Specialists visually assess patients in real time, educate them on secondary stroke and fall prevention and suggest ways to improve function including direct medical interventions when indicated. Primary outcomes are proportion of eligible patients consenting to the study, participation rate in all six TR home visits and satisfaction score. The study started 31 December 2015 with plan to enrol up to 50 patients over 24 months. Feasibility study results will inform us as to whether a randomised controlled trial is warranted to determine efficacy of TR home visit intervention in improving stroke outcomes. ETHICS AND DISSEMINATION: Ethics approval obtained by the Institutional Review Board (IRB), Committee for the Protection of Human Subjects, IRB number: HSC-MS-14-0994. Study results will be submitted for publication in a peer-reviewed journal.

Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression.

This report provides a global view of how gene expression is affected by DNA replication. We analyzed synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression. We use a higher-order singular value decomposition to integrate the global mRNA expression measured in the multiple time courses, detect and remove experimental artifacts and identify significant combinations of patterns of expression variation across the genes, time points and conditions. We find that, first, approximately 88% of the global mRNA expression is independent of DNA replication. Second, the requirement of DNA replication for efficient histone gene expression is independent of conditions that elicit DNA damage checkpoint responses. Third, origin licensing decreases the expression of genes with origins near their 3' ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation.

Antipsychotics produce locomotor impairment in larval zebrafish.

Zebrafish has been a favored vertebrate genetic model organism for studying developmental processes. It also holds a great potential for understanding the genetic basis of behavior and associated behavioral disorders. Despite such potential, their use in the study of behavior is greatly under-explored. It is well known that multiple classes of drugs used to treat psychiatric diseases produce extrapyramidal side (EPS) effects and consequent movement disorders in humans. The underlying molecular causes of these drug-induced movement disorders are poorly understood. Here we report that zebrafish treated with the antipsychotics fluphenazine and haloperidol (both of which can induce severe EPS in humans) develop movement defects. In contrast, another antipsychotic olanzapine, which produces mild to little EPS in humans, leads to minimal movement defects in zebrafish. These results establish a rapid assay system in which the effects of EPS-inducing agents can be assessed. Thus, future genetic screening in zebrafish shall identify genes and pathways that elucidate drug-induced movement disorder in human as well as provide insights into the brain control of locomotor activity. Future chemical screening in zebrafish may act as a preclinical test for the EPS effect of certain drugs, as well as a test used to researching drugs made to counteract the effects of EPS.

Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening.

Larval zebrafish are used extensively for developmental genetic studies due to their salient features, such as small size, external development, optical transparency, and accessibility in large numbers. However, their use for the study of drug and alcohol abuse has not been explored. Here we investigated the response of larval zebrafish to acute treatment of alcohol. Our analyses showed that like adults, the larval zebrafish exhibited a dose-dependent locomotor response to ethanol: intermediate doses led to hyperactivity, whereas high doses have a neurodepressive effect resulting in hypoactivity and sedation. Alcohol also induced morphological changes of melanocytes, providing a visible cellular measure of the biological effects of alcohol in vivo. In addition, alcohol induced thigmotaxis behavior (preference for the edge of a compartment). In the behaviors we analyzed, genetic background influenced the locomotor responses to alcohol. The present study demonstrates that larval zebrafish exert a response to the acute treatment of alcohol, which is genetically modifiable. Therefore, the larval zebrafish represent a tractable vertebrate model system for a large-scale genetic analysis of the biological effects of alcohol.

Humanized mice as a model for rheumatoid arthritis.

Genetic susceptibility to rheumatoid arthritis (RA), a common autoimmune disease, is associated with certain HLA-DR4 alleles. Treatments are rarely curative and are often tied to major side effects. We describe the development of a humanized mouse model wherein new, less toxic, vaccine-like treatments for RA might be pretested. This model includes four separate transgenes: HLA-DR*0401 and human CD4 molecules, a RA-related human autoantigenic protein (HCgp-39), and a T-cell receptor (TCRalphabeta) transgene specific for an important HCgp-39 epitope, eliciting strong Th1 responses in the context of HLA-DR*0401.