Active Learning: Action Potential and Clinical Applications in Neuroscience Medical Education.

Active learning in medical education engages adult learners and increases collaborative opportunities for consolidation of concepts. An innovative learning activity was used to engage medical students in an activity about action potentials and its clinical applications, resulting in increased understanding, application, and retention of the clinical relevance of the topic.

Feed Intake as an Estimation of Attractability in Pacific White Shrimp Litopenaeus vannamei.

A simple bioassay that quantifies feed intake as an estimation of relative attractability of feeds containing different ingredients in the Pacific white shrimp Litopenaeus vannamei is described. Fish meal (FM), fish protein hydrolysate (FPH), squid meal (SqM) and casein (CN) were assessed at the same dietary level for their relative influence on feed intake rates of Litopenaeus vannamei. A bland diet containing 92% whole wheat grain meal, 6% diatomaceous earth and 2% alginate with a known low attractability was used as the standard control or base diet. Ingredients were added to the bland base control diet at a level of 3% as fed. Shrimp were stocked into 80 L glass tanks (n= 20 per tank) in a recirculating aquaculture system. Tanks were randomly assigned to one of five diet treatments (3tanks/treatment). Experiments measuring the attractability of each feed were conducted twice daily at 0900 hours and 1330 hours over a five day period. For each experiment, 40 feed pellets (ca. 1 g) corresponding to the assigned treatment were provided to each tank. To calculate the rate of feed intake, pellets remaining in each tank were counted at six minute intervals for a seventy-two minute period. Differences in rate of feed intake among diets were evaluated using Cox Regression Analysis. This attractability assay required only small amounts of ingredients and incorporated ingredients into a bland feed, which significantly reduces the influence from other ingredients or compound in the pellets. All of the test protein ingredients, especially SqM, in the feeds significantly increased the feed consumption rate. The diet containing SqM was consumed at a significantly higher rate than those containing casein and FM but not FPH. FPH and CN containing diets were not significantly different but consumed at a higher rate than the diet containing FM. Results of these trials indicate that the presence of certain ingredients can increase feed intake, thereby increasing nutrient availability of the diets. This reported method to determine consumption of diets containing certain ingredients can be considered as a valid method to estimate attractability.

Obesity in African-Americans: The role of physiology.

The disproportionate obesity in African American (AA) women has a physiologic basis and can be explained by the interactive effects of insulin secretion, insulin clearance, insulin sensitivity and the glycaemic load of the diet. This review will present data supporting a physiologic basis for obesity propensity in obesity-prone AA women that resides in their unique metabolic/endocrine phenotype: high beta-cell responsiveness, low hepatic insulin extraction and relatively high insulin sensitivity, which together result in a high exposure of tissues and organs to insulin. When combined with a high-glycaemic (HG) diet (that stimulates insulin secretion), this underlying propensity to obesity becomes manifest, as ingested calories are diverted from energy production to storage. Our data indicate that both weight loss and weight loss maintenance are optimized with low-glycaemic (LG) vs HG diet in AA. Whether greater obesity in AA is mechanistically related to their greater prevalence of type 2 diabetes is debatable. This review provides data indicating that obesity is not strongly related to insulin resistance in AA. Rather, insulin resistance in AA is associated with relatively low adipose tissue in the leg, consistent with a genetic predisposition to impaired lipid storage. Greater bioenergetic efficiency has been reported in AA and, via resultant oxidative damage, could plausibly contribute to insulin resistance. In summary, it is proposed here that a subset of AA women are predisposed to obesity due to a specific metabolic/endocrine phenotype. However, greater diabetes risk in AA has an independent aetiology based on impaired lipid storage and mitochondrial efficiency/oxidative stress.

The Impact of Meeting Patients with Neurological Disorders on Medical Student Empathy.

PURPOSE: Empathy tends to decline during medical education, typically beginning in the third year of medical school and often continuing throughout residency and the physician's medical career. The purpose of this study was to determine if first year medical student empathy is affected by small group interactions with patients with neurological disorders, and to investigate if changes in empathy persisted over time. MATERIALS AND METHODS: Eighty first year medical students participating in a Neuroscience Module interacted with a variety of neurological patients in a small group informational session. Prior to the experience, participants completed the Jefferson Scale of Physician Empathy-Student (JSPE-S) version. After the experience, students completed a post-test JSPE-S questionnaire, and a final post-post-test JSPE-S questionnaire was completed 5 weeks later. Empathy scores were compared with a repeated measures MANOVA. The relationship between gender and empathy, and the effect of the age of the neurological patients on empathy scores were also examined. RESULTS: Empathy scores for seventy-one students who completed the JSPE-S questionnaires were analyzed. Students had significantly higher empathy immediately after the patient interaction experience, and the change in empathy was sustained over the course of 5 weeks (p = 0.015). The age of the neurological patients had a significant effect on empathy scores. There was no significant difference between empathy scores and gender. CONCLUSIONS: This study supports the incorporation of a group patient interaction experience into the medical school curriculum as an inexpensive and practical method of enhancing medical student empathy in a non-clinical setting.

Influence of Commercial and Laboratory Diets on Growth, Body Composition, and Reproduction in the Zebrafish Danio rerio.

The value of the zebrafish (Danio rerio) as a model organism continues to expand. In developing the model, current feeding practice in zebrafish laboratories includes the use of commercially available diets. In this study, we compared outcomes in growth, body composition, and reproduction among zebrafish fed five highly utilized commercial diets and one formulated chemically defined reference diet. Wild-type zebrafish larvae were raised on live feed until 21 days postfertilization and then fed diets for 16 weeks. All fish received a daily ration of >5% of body weight (adjusted biweekly). Growth varied among diets throughout the feeding trial, and at study termination (week 16), significant differences among diets were observed for terminal weight gain, body condition index, body fat deposition, and reproductive outcomes. In addition, the proportion of viable embryos produced from females fed the formulated reference diet was high relative to the commercial diets. These data suggest that metabolic profiles, most likely reflecting nutrient/energy availability, utilization, and allocation, vary relative to diet in zebrafish. Undefined differences in metabolic profiles could result in erroneous predictions of health outcomes and make comparisons among laboratories more challenging. We recommend that dietary standards should be defined for zebrafish to support their common utility in biomedical research.

Environmental and Human Health Impacts of Spreading Oil and Gas Wastewater on Roads.

Thirteen states in the United States allow the spreading of O&G wastewaters on roads for deicing or dust suppression. In this study, the potential environmental and human health impacts of this practice are evaluated. Analyses of O&G wastewaters spread on roads in the northeastern, U.S. show that these wastewaters have salt, radioactivity, and organic contaminant concentrations often many times above drinking water standards. Bioassays also indicated that these wastewaters contain organic micropollutants that affected signaling pathways consistent with xenobiotic metabolism and caused toxicity to aquatic organisms like Daphnia magna. The potential toxicity of these wastewaters is a concern as lab experiments demonstrated that nearly all of the metals from these wastewaters leach from roads after rain events, likely reaching ground and surface water. Release of a known carcinogen (e.g., radium) from roads treated with O&G wastewaters has been largely ignored. In Pennsylvania from 2008 to 2014, spreading O&G wastewater on roads released over 4 times more radium to the environment (320 millicuries) than O&G wastewater treatment facilities and 200 times more radium than spill events. Currently, state-by-state regulations do not require radium analyses prior to treating roads with O&G wastewaters. Methods for reducing the potential impacts of spreading O&G wastewaters on roads are discussed.

Posaconazole Pharmacokinetics in Healthy Cats after Oral and Intravenous Administration.

BACKGROUND: Posaconazole is the most active available azole antifungal drug, but absorption and pharmacokinetics are not available to guide dosing regimens in cats. OBJECTIVE: To determine the pharmacokinetics of posaconazole in cats given an IV solution and PO suspension. ANIMALS: Six healthy, adult research cats. METHODS: After a 12-hour fast, each cat received 15 mg/kg of posaconazole PO suspension with food. Four cats also received 3 mg/kg IV posaconazole after a 7-day washout period. Plasma was collected at predetermined intervals for analysis using high-pressure liquid chromatography (HPLC). Concentration data were analyzed using a 2-compartment pharmacokinetic analysis for IV administration data and a 1-compartment analysis with first-order input for PO administration data using Phoenix® software. RESULTS: After IV dosing, volume of distribution (VSS ) was 1.9 (0.3) L/kg (mean, standard deviation), terminal half-life (T½ ) was 57.7 (28.4) hours, and clearance was 28.1 (17.3) mL/kg/h. After PO dosing, peak concentration (CMAX ) was 1.2 (0.5) µg/mL and T½ was 38.1 (15.0) hours. Bioavailability of PO suspension was 15.9% (8.6). No adverse effects were observed with either route of administration. CONCLUSION AND CLINICAL IMPORTANCE: Despite low PO absorption, these data allow for simulation of PO dosage regimens that could be explored in clinical studies. Two regimens can be considered to maintain targeted trough concentrations of 0.5-0.7 µg/mL as extrapolated from studies in humans: (1) 30 mg/kg PO loading dose followed by 15 mg/kg q48h, or (2) 15 mg/kg PO loading dose followed by 7.5 mg/kg q24h.

In Vivo Determination of Body Composition in Zebrafish (Danio rerio) by Quantitative Magnetic Resonance.

Zebrafish (Danio rerio) as a model research organism continues to expand its relevance and role in multiple research disciplines, with recent work directed toward models of metabolism, nutrition, and energetics. Multiple technologies exist to assess body composition in animal research models at various levels of detail (tissues/organs, body regions, and whole organism). The development and/or validation of body composition assessment tools can open new areas of research questions for a given organism. Using fish from a comparative nutrition study, quantitative magnetic resonance (QMR) assessment of whole body fat and fat-free mass (FFM) in live fish was performed. QMR measures from two cohorts (n = 26 and n = 27) were compared with chemical carcass analysis (CCA) of FM and FFM. QMR was significantly correlated with chemical carcass values (fat, p < 0.001; lean, p = 0.002), although QMR significantly overestimated fat mass (FM) (0.011 g; p < 0.0001) and underestimated FFM (-0.024 g; p < 0.0001) relative to CCA. In a separate cross-validation group of fish, prediction equations corrected carcass values for FM (p = 0.121) and FFM (p = 0.753). These results support the utilization of QMR-a nonlethal nondestructive method-for cross-sectional or longitudinal body composition assessment outcomes in zebrafish.

Pharmacokinetics of ceftiofur sodium and ceftiofur crystalline free acid in neonatal foals.

Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharmacokinetic parameters for i.v. and s.c. ceftiofur sodium were: AUC(0→∝) (86.4 ± 8.5 and 91 ± 22 h·µg/mL for i.v. and s.c., respectively), terminal elimination half-life (5.82 ± 1.00 and 5.55 ± 0.81 h for i.v. and s.c., respectively), C(max(obs)) (13 ± 1.9 µg/mL s.c.), T(max(obs)) (0.75 ± 0.4 h for s.c.). Mean (± SD) noncompartmental pharmacokinetic parameters for s.c. ceftiofur crystalline free acid were: AUC(0→∝) (139.53 ± 22.63 h·µg/mL), terminal elimination half-life (39.7 ± 14.7), C(max(obs)) (2.52 ± 0.35 µg/mL) and t(max(obs)) (11.33 ± 1.63 h). No adverse effects attributed to drug administration were observed in any foal. Ceftiofur- and desfuroylceftiofur-related metabolites reached sufficient plasma concentrations to effectively treat common bacterial pathogens isolated from septicemic foals.

Profile of neurocognitive impairments associated with female in-patients with anorexia nervosa.

BACKGROUND: Although many studies have reported impairments of neurocognitive performance in patients with anorexia nervosa (AN), these have involved a wide range of assessment methods and some findings are inconsistent. METHOD: Twenty-five female in-patients with a DSM-IV diagnosis of AN, identified from three units specializing in the treatment of eating disorders, volunteered for the study. Twenty-five non-clinical control subjects were recruited, matched for age, gender and estimated IQ. Subjects were assessed with a range of computer-administered neurocognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), which has been validated in many studies of neuropsychiatric disorders. RESULTS: The patient group showed significant but moderate impairments (i.e. less than one standard deviation below the mean performance of the control group) on tests of spatial recognition memory, a planning task and rapid visual information processing, while a subgroup of patients (n = 14) showed greater degrees of impairments on at least one of these tests. The degrees of impairments did not correlate with body mass index (BMI). No impairments were observed on tests of spatial span, pattern recognition memory, spatial working memory, matching-to-sample, paired associates learning and set-shifting. CONCLUSIONS: The findings, in relation to a mean BMI of 15.3, are compatible with, in general, subtle impairments in neurocognition in AN. However, in those patients with relatively severe degrees of impairments, these may have adverse effects on complex tasks of social and occupational functioning. Further research is needed on the nature of relevant causal mechanisms, including the effects of potentially confounding variables.

Prevalence of untreated asthma in a population sample of 6000 older adults in Bristol, UK.

BACKGROUND: A study was undertaken to estimate the prevalence of untreated asthma in older adults. METHODS: A cross sectional population based survey of 6000 men and women aged 65 years and over was performed in 21 general practices in north Bristol, south west England. The main outcome measure was untreated asthma as defined by a two stage process comprising a respiratory questionnaire (symptoms suggestive of asthma or doctor diagnosed asthma not receiving respiratory treatment) followed by lung function tests (significant reversibility following bronchodilators or corticosteroids and/or significant within day variability in peak expiratory flow). RESULTS: 4792 of the 6000 participants (80%) completed the respiratory questionnaire and, of those not receiving respiratory treatment, 55 reported a previous doctor diagnosis of asthma and a further 696 had symptoms suggestive of asthma. Lung function testing in 280 of 501 randomly selected individuals from these groups resulted in 38 being defined as having asthma and an estimated population prevalence for untreated asthma of 2.4% (95% CI 1.6% to 3.6%) in men and 1.2% (95% CI 0.7% to 2.1%) in women. Most subjects (84%) with untreated asthma had moderate or severe disease. Untreated asthma was most common in individuals with doctor diagnosed asthma (21%) and those with breathlessness or wheeze (13-20%). CONCLUSION: Untreated asthma in the elderly is a common and important problem. Opportunistic use of appropriate lung function tests in older people with a history of doctor diagnosed asthma or wheeze or breathlessness at rest could identify untreated asthmatics who might benefit from treatment.

Regulatory role of nitric oxide over hippocampal 5-HT release in vivo.

Previous work has shown that N-methyl-D-aspartate (NMDA) receptor activation decreases 5-hydroxytryptamine (5-HT) release in the hippocampus of freely moving rats. Given the association between NMDA receptor function and nitric oxide (NO) production with the regulation of 5-HT release in other brain regions, we have studied this in rat hippocampus. NMDA (100 microM) decreased hippocampal 5-HT release by approximately 70% and this was reversed by the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 10 microM). The NO donor S-nitroso-N-acetylpenicillamine (SNAP) had an inverse concentration-dependent effect on 5-HT release. At 500 microM, SNAP elevated dialysate 5-HT by 55% over basal, while at 5 mM a 70% decrease was seen. The non-selective nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) at 1 mM increased extracellular 5-HT, although a return to basal levels occurred despite the continued presence of the drug. At 1 mM L-NAME prevented the decrease in 5-HT elicited by NMDA (100 microM) infusion. 7-Nitroindazole (7-NI), a relatively selective neuronal NOS (nNOS) inhibitor, decreased extracellular 5-HT at 100 microM and 1 mM. When 100 microM 7-NI was infused for 60 min prior to NMDA, 5-HT levels were transiently increased above basal before returning to control levels. Following combined application of the two drugs, no decrease in dialysate 5-HT was seen. Our data support a role for NO in modulating both basal and NMDA-evoked changes in 5-HT release in the hippocampus, however, the association appears to be complex. It may be that the recorded changes in 5-HT release are secondary to changes in the release of amino acid transmitters which we have previously found to be dependent on the prevailing extracellular NO concentration.

Fite stain positivity in Rhodococcus equi: yet another acid-fast organism in respiratory cytology--a case report.

Rhodococcus equi is an aerobic Gram-positive and acid-fast coccobacillus that may cause cavitary pneumonia in immunocompromised hosts such as HIV-infected patients. Numerous Grocott's methenamine silver (GMS)-positive organisms were initially noted on the direct smear; a minor number of acid-fast organisms were seen in the Thin-Prep slide. Since the abundant mucous material with the attached organisms seen in conventional smears may be lost in liquid-based preparations, more sensitive stains such as Fite, as well as a more diligent search for organisms, is needed. This case illustrates the importance of careful selection and evaluation of special stains in sputum specimens.

Nitric oxide-mediated regulation of dopamine release in the hippocampus in vivo.

Infusion of N-methyl-D-aspartate (NMDA) into the hippocampus of freely moving rats produced a concentration-dependent decrease in the extracellular levels of dopamine, an effect which was reversed by D-2-amino-5-phosphonovaleric acid (D-AP5). To determine the involvement of nitric oxide (NO) in this response, two nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), were examined for their ability to modify both basal and NMDA-inhibited dopamine release. When infused alone both NOS inhibitors elicited an increase in extracellular dopamine concentration, moreover, when administered prior to the application of NMDA, the agonist failed to elicit a decrease in dopamine levels. Infusion of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) over a 30 min period caused either an increase or a decrease in dopamine release depending upon the concentration used. At the lower concentration (0.5 mM) SNAP promoted dopamine release whilst at the higher concentration (5 mM), the donor elicited a long lasting reduction in basal dopamine levels. The effect of the lower concentration of SNAP was reversed by the prior application of D-AP5, but that of the higher concentration was unaffected by the antagonist.

An epidemiological survey of methicillin-resistant Staphylococcus aureus in a tertiary referral hospital.

Over a 30-month period from July 1995 to December 1997, new detections of methicillin-resistant Staphylococcus aureus (MRSA) were prospectively studied in a tertiary referral hospital. The aims of the study were to determine the incidence of colonization of patients admitted to each of the hospital's 39 clinical units and ascertain where each patient had become colonized. Epidemiological information (time to detection, ward movement, admission to other hospitals, data on MRSA isolations in hospital wards) and phage typing were used by the hospital's infection control unit to make this determination. Routine containment procedures included cohorting, flagging and triclosan body washes. Surveillance cultures were collected infrequently. Patients known to be colonized with MRSA were excluded from orthopaedic and haematology wards. During the study period, 995 patients were found to be newly colonized. The incidence of colonization varied from nil to 72 per 1000 admissions, being highest in the main intensive care unit and in services which frequently used that unit. The incidence of colonization in elective orthopaedic surgery (< 1 per 1000) and haematology (3 per 1000) was very low. Determining the place where patients acquired MRSA was made difficult by the high frequency of endemic phage types and frequent patient transfer between wards. Epidemiological data suggested that the main intensive care unit and surgical wards nursing patients with colorectal, urological and vascular diseases were the places where most patients became colonized. MRSA was never acquired by patients nursed in wards which practised an exclusion policy towards patients known to be colonized with MRSA. Our data suggest that in tertiary referral hospitals, where MRSA is not only endemic but frequently imported from other hospitals, it is possible to establish areas where MRSA is never acquired.

Respiratory symptoms in older people and use of domestic gas appliances.

BACKGROUND: Studies in children and young women have indicated an increased risk of respiratory illness in association with the use of domestic gas appliances, possibly caused by oxides of nitrogen generated when gas is burned. It is not known whether risks are similarly increased in older subjects. METHODS: A questionnaire about respiratory symptoms in the past year and potential risk factors for respiratory disease was mailed to 6000 men and women aged 65 years and older who were selected at random from the lists of general practices in North Bristol, UK. Associations between symptoms and the use of gas appliances were examined by logistic regression with adjustment for age, sex, social class, and smoking habits. RESULTS: Questionnaires were completed by 4792 (80%) of those mailed. The most common symptoms were exercise induced breathlessness, wheeze, or chest tightness (51%); wheeze (27%); morning phlegm (20%); and daytime breathlessness at rest (19%). In an analysis that included all subjects only weak associations were found with use of gas appliances, odds ratios all being 1.2 or less. The risks associated with use of a gas hob tended to be higher in women, with odds ratios of 1.36 (95% CI 1.01 to 1.83) for wheeze and 1.33 (95% CI 0.56 to 3.17) for morning chest tightness, but were lower than had been reported previously in younger women. CONCLUSION: The absence of stronger associations cannot readily be explained by bias or confounding. Gas cookers and fires are unlikely to be an important cause of respiratory illness in the elderly. If they do cause such illness, the largest risks are likely to be in women who use gas hobs.