Generation of two homozygous SHOX2 knock-out human induced pluripotent stem cell lines using CRISPR/Cas9.

SHOX2 is a homeobox transcription factor associated with atrial fibrillation (AF) and sinus node dysfunction. Here, we generated two homozygous SHOX2 knock-out hiPSC lines from a healthy control line and a corrected AF patient line (disease-specific SHOX2 mutation corrected to WT) using CRISPR/Cas9. These cell lines maintained pluripotency, an ability to differentiate into all three germlayers and a normal karyotype, presenting a valuable tool to investigate the impact of a full SHOX2 knock-out with respect to arrhythmogenic diseases on a cellular level.

Uniparental isodisomy as a cause of recessive Mendelian disease: a diagnostic pitfall with a quick and easy solution in medium/large NGS analyses.

Complete uniparental isodisomy (iUPD)-the presence of two identical chromosomes in an individual that originate from only a single parental homolog-is an underestimated cause of recessive Mendelian disease in humans. Correctly identifying iUPD in an index patient is of enormous consequence to correctly counseling the family/couple, as the recurrence risk for siblings is reduced from 25% to usually <1%. In medium/large-scale NGS analyses, we found that complete iUPD can be rapidly and straightforwardly inferred from a singleton dataset (index patient only) through a simple chromosome- and genotype-filtering step in <1 min.

Effect of Wheelchair Stroke Pattern on Upper Extremity Muscle Fatigue.

Background: Shoulder dysfunction is common in persons with spinal cord injury (SCI) with an incidence of up to 63%. Dysfunction is a result of muscle imbalances, specifically denervated rotator cuff muscles that are repetitively used during manual wheelchair propulsion.

Objective: To determine which arm stroke technique, pump (P) or semicircular (SC), is most energy efficient for long periods of propulsion.

Choice of dopaminergic therapy among early, mild Parkinson disease subjects in North America.

The choice of dopaminergic therapy in early Parkinson disease (PD) is an important clinical decision, yet factors influencing this decision have not been extensively studied. We sought to investigate the factors that may be associated with the choice of dopaminergic therapy at the NINDS Exploratory Trials in PD (NET-PD) Long-Term Study-1 (LS1). NET-PD LS1 was a clinical trial of creatine versus placebo in participants with early, mild PD on stable doses of dopaminergic therapy.

Acute and chronic psychostimulant treatment modulates the diurnal rhythm activity pattern of WKY female adolescent rats.

The psychostimulants considered the gold standard in the treatment of attention deficit hyperactivity disorder, one of the most common childhood disorders, are also finding their way into the hands of healthy young adults as brain augmentation to improve cognitive performance. The possible long-term effects of psychostimulant exposure in adolescence are considered controversial, and thus, the objective of this study was to investigate whether the chronic exposure to the psychostimulant amphetamine affects the behavioral diurnal rhythm activity patterns of female adolescent Wistar-Kyoto (WKY) rat. The hypothesis of this study is that change in diurnal rhythm activity pattern is an indicator for the long-term effect of the treatment.

Adult female rats' altered diurnal locomotor activity pattern following chronic methylphenidate treatment.

Methylphenidate (MPD) is one of the most prescribed pharmacological agents, which is also used for cognitive enhancement and recreational purposes. The objective of this study was to investigate the repetitive dose-response effects of MPD on circadian rhythm of locomotor activity pattern of female WKY rats. The hypothesis is that a change in the circadian activity pattern indicates a long-lasting effect of the drug.

A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury.

A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days.

Potential gains in life expectancy from reducing heart disease, cancer, Alzheimer's disease, kidney disease or HIV/AIDS as major causes of death in the USA.

Objectives: Potential gains in life expectancy (PGLEs) that give proper consideration to competing risks are an effective indicator for measuring the impact of multiple causes of death on a defined population. This study aimed to assess PGLE by hypothetically reducing the major causes of death in the USA from 2001 to 2008.

Study Design: PGLEs due to the reduction and elimination of heart disease, cancer, Alzheimer's disease, kidney disease or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) were calculated by age, gender and race.

Behavioral daily rhythmic activity pattern of adolescent female rat is modulated by acute and chronic cocaine.

Cocaine is one of well-known drugs of abuse, and many children experience early exposure to cocaine. Because of an immature neuronal system in adolescents, they may react differently to repeated cocaine administration compared to adults. Most of the published papers report the effect of cocaine on adult male rats and this paper focused on the effects of cocaine on the 24 h locomotor activity rhythm patterns activity of adolescent Sprague Dawley (SD) female rats.

Physical activity guideline in Mexican-Americans: does the built environment play a role?

Given disproportionate burden of physical inactivity among US Hispanics and emerging interests in the potential role of the built environment on physical activity, we tested the hypothesis that residing in a more walkable block group is associated with increased physical activity in a cohort of Mexican-American adults. 10,183 Mexican-American adults from Houston, TX, USA were studied. Physical activity was assessed through self-report.

Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.

In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation.

Incidence and severity of acute complications after spinal cord injury.

Object: The aim of this multicenter, prospective study was to determine the spectrum, incidence, and severity of complications during the initial hospitalization of patients with spinal cord injury.

Methods: The study was conducted at 9 university-affiliated hospitals that comprise the clinical centers of the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The study population comprised 315 patients admitted to NACTN clinical centers between June 25, 2005, and November 2, 2010, who had American Spinal Injury Association (ASIA) Impairment Scale grades of A-D and were 18 years of age or older.

Predictors of pulmonary complications in blunt traumatic spinal cord injury.

Object: Pulmonary complications are the most common acute systemic adverse events following spinal cord injury (SCI), and contribute to morbidity, mortality, and increased length of hospital stay (LOS). Identification of factors associated with pulmonary complications would be of value in prevention and acute care management. Predictors of pulmonary complications after SCI and their effect on neurological recovery were prospectively studied between 2005 and 2009 at the 9 hospitals in the North American Clinical Trials Network (NACTN).

North American Clinical Trials Network for the Treatment of Spinal Cord Injury: goals and progress.

The North American Clinical Trials Network (NACTN) for the Treatment of Spinal Cord Injury is a consortium of 10 neurosurgery departments, a data management center, and a pharmacological center. The NACTN was established with the goal of bringing recent molecular and cell-based discoveries in neuroprotection and regeneration from the laboratory into clinical trials that optimize meaningful data outcomes and maximum safety to patients. The requirements of planning and executing clinical trials in spinal cord injury (SCI) and the steps that the NACTN has taken to address these requirements are discussed and illustrated in articles in this issue of the Journal of Neurosurgery: Spine.

Safety climate and verbal abuse among public hospital-based workers in Costa Rica.

Objective: Low levels of safety climate and training have been associated with higher occurrence of occupational-related health outcomes; workplace violence and verbal abuse could be considered an early indicator of escalating psychological workplace violence. We examined whether low level of safety factors were associated with a higher prevalence of verbal abuse at the workplace.

Methods: We used data from a cross-sectional survey administered among a stratified random sample of 1,000 employees from 10 of the 29 public hospitals in Costa Rica.

Spatial analysis of county-level breast cancer mortality in Texas.

Objective: The objectives of the study were to detect high-risk areas and to examine how racial and ethnic status affect the geographic distribution of female breast cancer mortality in Texas. Analyses were based on county-level data for the years from 2000 to 2008.

Materials And Methods: Breast cancer mortality data were obtained from the Texas Cancer Registry, and the Spatial Scan Statistics method was used to run Purely Spatial Analyses using the Discrete Poisson, Bernoulli, and Multinomial models.

A randomized recruitment intervention trial in Parkinson's disease to increase participant diversity: early stopping for lack of efficacy.

Background: Failure to include participants of diverse race and ethnicity (i.e. those other than European Caucasian, non-Hispanic) in clinical trials impedes the safe development of new therapies given the potential for racial/ethnicity-related variations in treatment response.

Morphine administration and abrupt cessation alter the behavioral diurnal activity pattern.

In mammals, there is an underlying mechanism that dictates the organism's biological functions and daily activity schedule, known as circadian rhythms, which play a major role in maintaining steady metabolism, homeostasis, and immunity. Limited research has been done investigating the effects of continuous opiate administration on the circadian rhythm activity pattern. A change in circadian activity pattern is suggested as an experimental model to demonstrate long-term effect of the drug.

Adolescent rat circadian activity is modulated by psychostimulants.

Circadian pattern of activity regulates many aspects of mammalian physiology and behavior to particular times of the day by entraining the circadian clocks to external environmental signals. Since circadian rhythms are sensitive to many pharmacological agents, it is important to understand if the repetitive use of psychostimulants such as amphetamine will alter the circadian rhythm behavioral activity pattern. The present study uses male Sprague-Dawley rats to study the long-term effects of amphetamine on the locomotor circadian rhythm activity pattern.

Repetitive methylphenidate administration modulates the diurnal behavioral activity pattern of adult female SD rats.

Diurnal rhythms influence many of the physiological processes that act to maintain homeostasis of the body in response to different environmental changes. Thus, disturbances in diurnal rhythms can lead to various physiological complications. Repeated exposure to psychostimulants may cause long-term effects by disturbing diurnal rhythms.

Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998-2005.

To determine the risk of cardiotoxicities in association with trastuzumab with/without anthracycline-containing chemotherapy in a large nationwide population-based cohort of patients with breast cancer. We studied 47,806 women with breast cancer ages ≥ 65 in 1998-2005 from 16 cancer registries in the Surveillance, Epidemiology and End Results (SEER)-Medicare data and 16,092 cases matched with equal number of controls on the propensity of receiving chemotherapy or trastuzumab. Cumulative incidence of congestive heart failure in year-1 was 5.

Alcohol usage and abrupt cessation modulate diurnal activity.

Alcohol has many effects throughout the body. The effect on circadian rhythms and the correlation of these effects to withdrawal effects of alcohol present interesting findings. By measuring 3 planes of activity of female Sprague-Dawley rats during alcohol usage and continuing study through the first 2 days following withdrawal of alcohol allow for the observation of a drastic modulation of the circadian pattern of activity.

Repetitive ritalin treatment modulates the diurnal activity pattern of young SD male rats.

Attention Deficit Hyperactivity Disorder (ADHD) is a common behavioral disorder of children and is treated by psychostimulants. Psychostimulant exposure to children at the time of neuronal development can cause behavioral and physiological changes continuing during adulthood. Most of the studies on psychostimulants investigate the acute effects of the drug.

Serological differences in folate/vitamin B12 in pregnancies affected by neural tube defects.

Background: Laboratory evidence is presented of significant associations between reduced maternal serum folate and vitamin B12 levels and neural tube birth defects (NTD) compared to referents.

Methods: This was an incident case-control study. Cases of neural tube defects (including anencephaly and open spina bifida) diagnosed in residents within 100 miles of the US-Mexico border from January 1993 to October 2000 were eligible.