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. Twenty-four rats were divided into two groups, control (N = 12) and experimental (N = 12), and kept in a 12:12-h light/dark cycle in an open-field cage. After 5-7 days of acclimation, 11 days of consecutive non-stop behavioral recordings began. On experimental day 1 (ED1), all groups were given an injection of saline. On ED2 to ED7, the experimental group was injected with 0.6 mg/kg amphetamine followed by 3 days of washout from ED8 to ED10, and amphetamine re-challenge on ED11 similar to ED2. The locomotor movements were counted by the computerized animal activity monitoring system, and the cosinor statistical test analysis was used to fit a 24-h curve of the control recording to the activity pattern after treatment. The horizontal activity, total distance, number of stereotypy, vertical activity, and stereotypical movements were analyzed to find out whether the diurnal rhythm activity patterns were altered. Data obtained using these locomotor indices of diurnal rhythm activity pattern suggest that amphetamine treatment significantly modulates the locomotor diurnal rhythm activity pattern of female WKY adolescent rats.

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. Changes in the locomotor activity rhythm patterns could indicate that cocaine elicits long-term changes in the clock genes of the body that regulate different physiological processes. The objective of this study was to investigate whether cocaine in adolescent female rats modulated their daily activity pattern. Animals were divided into control (saline), 3.0, 7.5, 15.0 mg/kg cocaine groups. On experimental day 1 (ED 1), all groups were given saline injection. From ED 2 to ED 7, either saline or cocaine (3.0, 7.5, or 15.0 mg/kg) was given daily. ED 8 to ED 10 were the washout days, where no injection was given. On ED 11, the animals were injected with saline or with the same dose of cocaine as they were treated on ED 2 to ED 7. Each animal's locomotor activities was recorded nonstop following saline or cocaine injection for 11 consecutive days using the open field assay. In conclusion, it was observed that all three groups receiving repeated cocaine administration (3.0, 7.5, and 15.0 mg/kg) displayed significantly altered locomotor activity rhythm patterns.

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. The aim of the present study is to use the open field assay to determine whether repeated exposure to the psychostimulant methylphenidate (MPD) changes diurnal locomotor activity patterns of female adult Sprague-Dawley (SD) rats. As much as 31 female adult SD rats were divided into four groups. On experimental day (ED) 1, all groups were given an injection of saline. On ED 2-7, animals were injected once a day with either saline, or 0.6 mg/kg MPD, or 2.5 mg/kg MPD, or 10 mg/kg MPD depending on the group. On ED 8-10, no injections were given (washout period). On ED 11, animals were treated as they were on ED 2-7. Locomotor movements were recorded using a computerized animal activity monitoring system. The horizontal activity (HA), total distance traveled (TDT), and number of stereotypies (NOS) were analyzed by cosine curve statistical analysis (CCSA) test. The HA and TDT diurnal rhythm activity patterns of ED 2, 7, 8, and 11 were significantly different (p < 0.05) from the control recording of ED 1 according to the CCSA test. The observation obtained in this study suggests that repeated administration of MPD (all doses tested) is able to change diurnal locomotor patterns, which indicates that chronic MPD treatment exerts long-term effects.

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. Most cases were diagnosed in utero upon visits to clinics, obstetrical or genetic expert offices. Cases identified upon hospital admission or at delivery were also eligible. Cases identified after discharge were not. Controls were matched on geographic region, maternal age, race/ethnicity, gestational age, and type of health insurance (including none). RESULTS: Three hundred eighty-two border area residents (107 cases and 275 individually matched controls) provided biological specimens. Median folate concentrations for case mothers were 36% lower than controls (9.8 ng/mL vs. 15 ng/mL). Maternal serum folate concentrations in quartiles above 9.5 ng/mL indicated significantly reduced risk (OR = 0.4, OR = 0.3, and OR = 0.2). Likewise, the risk for NTD decreased (OR = 0.4, OR = 0.3, and OR = 0.2) in quartiles of sera B12 concentrations above 246 pg/mL. CONCLUSIONS: Physician attention is invited to significantly lower concentrations of serum folate and vitamin B12 in women with NTD-affected pregnancies. This study assayed sera samples from women while still pregnant or immediately after delivery. The confounding effect of reduced folate and B12 levels with other biological and chemical exposures will be addressed in subsequent communications.

Prolonged methylphenidate treatment alters the behavioral diurnal activity pattern of adult male Sprague-Dawley rats.

Methylphenidate (MPD) is becoming a drug of abuse among adult professionals and students, alike. Yet, few studies have investigated its long-term effects on the adult population. We hypothesized that prolonged administration of MPD leads to changes in the diurnal horizontal activity (HA) pattern, an effect persisting beyond acute drug effects. Four groups of adult male Sprague-Dawley rats (N=32) were divided into a saline/control, 0.6, 2.5, or 10.0 mg/kg MPD group. Each group was treated with saline on experimental day 1, followed by six consecutive days of designated treatment (days 2-7), then, after three consecutive days of washout (days 8-10), each group was re-challenged with its respective treatment (day 11). Activity was monitored continuously throughout the 11 experimental days. There was a dose-dependent increase in HA in the first hour post-injection. The 0.6 mg/kg MPD group exhibited changes in diurnal activity pattern only during the wash-out period. The 2.5 mg/kg MPD group exhibited the most profound changes in HA after 6 days of continuous injection, washout, and MPD re-challenge (p<0.05, p=0.001, p<0.001) respectively, and the 10.0 mg/kg MPD group exhibited changes during the washout and re-challenge periods (p<0.01, p<0.001), respectively. In conclusion, prolonged administration of MPD modulated the diurnal HA pattern in a dose-dependent manner.

Factors contributing to elevated indoor radon in the Paso Del Norte region of the Texas-Mexico border: information for physicians.

BACKGROUND: We collected sample data on radon concentrations concurrently in the air, water, and soil in the northern part of the Texas-Mexico border (both sides) popularly known as Paso Del Norte. METHODS: These field data were used to statistically correlate relative contributions of yard soil, tap water, location, and house features to concentrations of radon indoors. RESULTS: Indoor air radon concentrations in some homes were up to nine-fold the limit recommended by the US Environmental Protection Agency (USEPA). Concentrations of radon in tap water were up to nearly three-fold the recommended limit. Apartments and manufactured homes had generally greater concentrations of indoor radon. Statistically significant associations were indicated between indoor radon air levels and radon in the soil (P < 0.001); radon in the water and radium in water (P = 0.016); radon air levels and apartment living (P = 0.010); and mobile homes vs. wood, brick, and stucco construction (P = 0.016). CONCLUSION: Radon soil gas, apartment living, and the aluminum plank wall environment of mobile homes were associated with elevated indoor radon in the homes studied. Physician's attention is invited to the potential nontrivial risk from radon, as it becomes trapped inside enclosed structures. This article is intended to serve as a resource for primary care physicians who want to better understand the distribution and contributing factors for indoor radon. The Surgeon General recommends every US home be tested for radon as of January 13, 2005.

Severe back pain among farmworker high school students from Starr County, Texas: baseline results.

PURPOSE: This cohort study is among the first to estimate the prevalence of and examine potential risk factors for severe back pain (resulting in medical care, 4+ hours of time lost, or pain lasting 1+ weeks) among adolescent farmworkers. These youth often perform tasks requiring bent/stooped postures and heavy lifting. METHODS: Of 2536 students who participated (response rate across the three public high schools, 61.2% to 83.9%), 410 students were farmworkers (largely Hispanic and migrant). Students completed a self-administered Web-based survey including farm work/nonfarm work and back-pain items relating to a 9-month period. RESULTS: The prevalence of severe back pain was 15.7% among farmworkers and 12.4% among nonworkers. The prevalence increased to 19.1% among farm workers (n = 131) who also did nonfarm work. A multiple logistic regression for farmworkers showed that significantly increased adjusted odds ratios for severe back pain were female sex (4.59); prior accident/back injury (9.04); feeling tense, stressed, or anxious sometimes/often (4.11); lifting/carrying heavy objects not at work (2.98); current tobacco use (2.79); 6+ years involved in migrant farm work (5.02); working with/around knives (3.87); and working on corn crops (3.40). CONCLUSIONS: Areas for further research include ergonomic exposure assessments and examining the effects of doing farm work and nonfarm work simultaneously.

Recent change in the annual pattern of sexually transmitted diseases in the United States.

This study analyzed the 1999 to 2003 database of the Center for Disease Control and Prevention (CDC) for seasonal and longer-term time trends in the sexually transmitted diseases (STDs) of chlamydia, gonorrhea, and syphilis in the United States. Linear regression was used to ascertain time trends, and a linear mixed auto-regression model was applied to determine the statistical significance of the major peaks relative to the annualized time series mean. A statistically significant increasing trend during the 5 yr span was documented only in the incidence of chlamydia. No clear annual periodicity was detected in any of the STDs; instead, significant three-month cycles were documented in all the STDs, with prominent peaks evident in March, May, August, and November. The March and May peaks could be associated with the sexual activities of young adults during spring break, which for different colleges and universities, commences as early as mid- to late-February and concludes as late as early- to mid-April, when huge numbers of sexually active youth congregate at beach resort settings. We propose the August peak is representative of summer sexual activity, in particular, of youths during school recess when adult supervision is poor. Finally, the autumn peak seems to be an expression of an endogenous annual rhythm in human reproductive biology, exemplified by elevated levels of testosterone in young males and sexual activity at this time of the year.

Seasonality of primarily childhood and young adult infectious diseases in the United States.

The Center for Disease Control (CDC) in the United States collects and maintains records of communicable (so-called notifiable) infectious diseases that cause significant morbidity and mortality and impact the national economy. This investigation focused on seasonal patterns in the primarily childhood and young adult infectious diseases of meningococcal meningitis, mumps, pertussis, typhoid fever, streptococcal toxic shock syndrome (1990 to 2003 CDC database), and varicella (1993 to 2003 CDC database). Linear regression was performed to ascertain the trend in the incidence of each disease, and multi-component cosinor analysis was applied to determine and describe periodicities. Significant decreasing trends in incidence were detected in meningococcal meningitis, mumps, typhoid fever, and streptococcal toxic shock syndrome, and increasing trends were found in pertussis and varicella. Significant annual patterns were documented in meningococcal meningitis (January peak), mumps (April peak), pertussis (August peak), varicella (April peak), typhoid fever (August peak), and in the hospital-acquired streptococcal toxic shock syndrome (February peak). Such seasonal patterns and long-term trends in infectious diseases are of practical public health significance in indicating which can benefit from timely prevention interventions.

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. Baseline data from 1616 out of the 1741 participants were evaluated using univariable and multivariable logistic or generalized logit regression analyses for available factors associated with the choice of dopaminergic therapy. The dopaminergic therapy choice was determined as: (i) therapy that subjects recalled taking 180days before the study; (ii) therapy at baseline; and (iii) the longest duration of therapy reported by participants. Younger age, higher education level, longer length of time since PD diagnosis and use of an adjunctive, non-dopaminergic or monoamine oxidase inhibitor medication were associated with more frequent use of dopamine agonist compared to levodopa or combination therapy.

Bladder cancer screening program for a petrochemical cohort with potential exposure to beta-napthylamine.

Approximately 1800 workers in pipe manufacturing plants in the United States may have been exposed to beta-napthlyamnine between 1970 and 1996. Once the chemical was detected, the contaminated additive in the resin was identified and discontinued. A bladder cancer-screening program was initiated in 1999. An annual two-stage screening program was developed to test for microscopic hematuria (stage one) and cytology (stage two), with a urology referral of positive or suspicious cytology. This paper presents the program methodology, cohort enumeration, recruitment, and enrollment strategies, and screening protocol. Enrollment data from the first 3 years are presented. Annual screening of a cohort of current and former employees is feasible. Original personnel records are often incomplete, making cohort identification important. Personal contact and follow-up are key elements of successful recruitment and retention.

Worker safety training in public hospitals in Costa Rica.

To develop a worker safety training program for its public hospital system, the Costa Rican Social Security System entered into a collaborative agreement with the University of Texas School of Public Health. A national survey to assess safety in the public hospitals revealed high rates of injury and under-reporting of injuries, as well a lack of worker safety training. A program developed based on the results of the survey was implemented using a training-of-trainers model. The program created opportunities for human resource development in occupational health in the hospital system, allowed for the sustainability of the training effort, and reduced dependency on external funding. Over 3700 workers were trained in its first three years, and 57 trainers were established in local hospitals and clinics.

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. Geographical information systems were used to create a "walkability index" (WI). We examined the relationship between WI and physical activity using regression models. Findings for the entire study population suggested a direct association between neighborhood walkability and physical activity that approached statistical significance (High WI vs. Low WI: OR = 1.16; 95% CI 0.95-1.40). Furthermore, participants who lived in a higher WI neighborhood were more likely to meet physical activity guidelines in 2 groups: (1) men whose recreational physical activity included walking (High WI vs. Low WI: OR = 5.43; 95% CI 1.30-22.73) and (2) men whose only recreational physical activity was (High WI vs. Low WI: OR = 9.54; 95% CI 1.84-49.60). Our findings suggest gender differences in the association between the built environment and physical activity in Mexican-American adults. Attempts to encourage walking among Mexican-American adults may be easier in high-walkability neighborhoods than in low-walkability neighborhoods.

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. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14-70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.

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. RESULTS AND CONCLUSIONS: Highest rates of female breast cancer mortality in Texas have shifted over time from southeastern areas towards northern and eastern areas, and breast cancer mortality at the county level is distributed heterogeneously based on racial/ethnic status. Non-Hispanic blacks were at highest risk in the northeastern region and lowest risk in the southern region, while Hispanics were at highest risk in the southern region along the border with Mexico and lowest risk in the northeastern region.

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. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using survey logistic regression models to estimate the association between safety factors and verbal abuse from the following sources: administrators, supervisors, patients, patients' relatives and coworkers. RESULTS: There was a high prevalence of verbal abuse among the healthcare workforce from both external (i.e., patients and patients' relatives) and internal workplace sources (i.e., coworkers, supervisors and administrators). A low level of safety climate was associated with verbal abuse from all sources with associations ranging from verbal abuse from administrators (OR=6.07; 95%CI: 2.05-17.92) to verbal abuse from patients (OR=2.24; 95%CI: 1.23-4.09). CONCLUSION: These results highlight the need to address organizational characteristics of the workplace that may increase the risk of verbal abuse for the future development of prevention interventions in this setting.

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. The progress that the NACTN has made in meeting these goals can be summarized as organizing a network of hospitals capable of enrolling a sufficient number of patients for conducting Phase I and II trials; creating a Data Management Center and a database of the natural history of recovery after SCI (at the time of this writing 485 patients were enrolled in the database); creating a database of the incidence and severity of complications that occur during acute and subacute treatment after SCI; developing a Pharmacological Center capable of performing pharmacokinetic and pharmacodynamic studies of therapeutic drugs; completing enrollment of 36 patients in NACTN's first clinical trial, a Phase I study of riluzole, a neuroprotective drug; and performing pharmacokinetic and pharmacodynamic studies of riluzole in acute SCI.

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. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.

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). METHODS: The authors sought to address 2 specific aims: 1) define and analyze the predictors of moderate and severe pulmonary complications following SCI; and 2) investigate whether pulmonary complications negatively affected the American Spinal Injury Association (ASIA) Impairment Scale conversion rate of patients with SCI. The NACTN registry of the demographic data, neurological findings, imaging studies, and acute hospitalization duration of patients with SCI was used to analyze the incidence and severity of pulmonary complications in 109 patients with early MR imaging and long-term follow-up (mean 9.5 months). Univariate and Bayesian logistic regression analyses were used to analyze the data. RESULTS: In this study, 86 patients were male, and the mean age was 43 years. The causes of injury were motor vehicle accidents and falls in 80 patients. The SCI segmental level was in the cervical, thoracic, and conus medullaris regions in 87, 14, and 8 patients, respectively. Sixty-four patients were neurologically motor complete at the time of admission. The authors encountered 87 complications in 51 patients: ventilator-dependent respiratory failure (26); pneumonia (25); pleural effusion (17); acute lung injury (6); lobar collapse (4); pneumothorax (4); pulmonary embolism (2); hemothorax (2), and mucus plug (1). Univariate analysis indicated associations between pulmonary complications and younger age, sports injuries, ASIA Impairment Scale grade, ascending neurological level, and lesion length on the MRI studies at admission. Bayesian logistic regression indicated a significant relationship between pulmonary complications and ASIA Impairment Scale Grades A (p = 0.0002) and B (p = 0.04) at admission. Pulmonary complications did not affect long-term conversion of ASIA Impairment Scale grades. CONCLUSIONS: The ASIA Impairment Scale grade was the fundamental clinical entity predicting pulmonary complications. Although pulmonary complications significantly increased LOS, they did not increase mortality rates and did not adversely affect the rate of conversion to a better ASIA Impairment Scale grade in patients with SCI. Maximum canal compromise, maximum spinal cord compression, and Acute Physiology and Chronic Health Evaluation-II score had no relationship to pulmonary complications.