Evaluating a bedside tool for neuroanatomical localization with extended-matching questions.

Neuroanatomical localization (NL) is a key skill in neurology, but learners often have difficulty with it. This study aims to evaluate a concise NL tool (NLT) developed to help teach and learn NL. To evaluate the NLT, an extended-matching questions (EMQ) test to assess NL was designed and validated. The EMQ was validated with fourth-year medical students and internal medicine and neurology residents. The NLT's usability was evaluated with third- and fourth-year students, and the effectiveness was evaluated with an experimental study of second-year students, using the EMQ as the outcome measure. Students were taught how to use both the NLT and textbook algorithms (control) to perform NL, then randomized into either group, and only allowed to use their assigned tool to complete the EMQ. Primary outcome was the difference in mean EMQ scores expressed as a percentage of total score. For EMQ validation, students (n = 56) scored lower than residents (n = 50) (76.7% ± 1.7 vs. 83.0% ± 1.6; mean ± standard error of mean, P < 0.009). The EMQ demonstrated good reliability (Cronbach's α 0.85) and generalizability (G-coefficient 0.85). Third- (n = 77) and fourth-year (n = 42) students found the NLT user-friendly and helpful in their learning of NL. In the experimental study, scores were significantly higher for NLT group (n = 94) than for controls (n = 101) (42.5 vs. 37.0%, P = 0.014); the effect size (Cohen's d) was 0.36. The EMQ is validated to reliably assess NL and is generalizable, feasible, practical, and of low cost. The concise and user-friendly NLT for NL was effective in aiding medical student performance of NL. Anat Sci Educ 11: 262-269. © 2017 American Association of Anatomists.

Does influenza A infection increase oxidative damage?

Considerable data implicate oxidative damage in influenza pathogenesis. We examined temporal changes in oxidative damage using accurate biomarkers in an adult cohort with acute influenza infection and their relationships with clinical parameters. Clinical information and blood samples were collected during their acute illness and 3 months later. A fatigue questionnaire was administered 3 months following influenza infection. Thirty-five patients (mean age, 34 years) with polymerase chain reaction-confirmed influenza A infection were included; all patients returned for follow-up assessments. Adjusted levels of plasma F2-isoprostanes, total hydroxyeicosatetraenoic products (HETEs), 7ß-hydroxycholesterol and 7-ketocholesterol, serum gamma-glutamyltransferase, and high-sensitivity C-reactive protein (hsCRP) were increased during the acute illness compared with age-matched controls. Despite clinical recovery, levels of these biomarkers remained higher at month 3 compared with controls. A proportion of patients had persistent symptoms such as fatigue (23%), myalgia (14%), and arthralgia (11%) at month 3. Patients with significant fatigue had higher baseline levels of plasma F2-isoprostanes, F4-neuroprostanes, and total HETEs compared to those without fatigue. By contrast, patients with persistent arthralgia and myalgia had higher baseline levels of serum hsCRP compared to those without these symptoms. Our observations lead to the hypothesis that oxidative damage participates in the pathogenesis of influenza infection and postinfectious fatigue.

Does high-dose coenzyme Q10 improve oxidative damage and clinical outcomes in Parkinson's disease?

Evidence on the efficacy of high-dose coenzyme Q10 (CoQ10) in Parkinson's disease (PD) is conflicting. An open-label dose-escalation study was performed to examine the effects of CoQ10 on biomarkers of oxidative damage and clinical outcomes in 16 subjects with early idiopathic PD. Each dose (400, 800, 1200, and 2400 mg/day) was consumed daily for 2 weeks. High-dose CoQ10 was well tolerated and improvements in the total Unified Parkinson's Disease Rating Scale (median, 37 vs. 27; p=0.048) were observed following study completion. Plasma F2-isoprostanes (adjusted for arachidonate) were significantly reduced in the 400-1200 mg/day dose range, but increased at 2400 mg/day dosage. A similar pattern of change was observed with serum phospholipase A2 activities. Levels of plasma all trans-retinol, plasma total tocopherol, serum uric acid, and serum total cholesterol were unchanged despite an increase in the CoQ10 dosage. Subjects with symptomatic benefits from CoQ10 (decrease in total UPDRS >10 points) had lower baseline plasma ubiquinol (p=0.07, Mann-Whitney U test) and decreased F2-isoprostanes per unit arachidonate (p=0.04, Wilcoxon Signed-Ranks test). These results lead to the hypothesis that the therapeutic response to CoQ10 depends on baseline levels of ubiquinol and whether the dosage of CoQ10 used can ameliorate the burden of oxidative damage.

Cyclooxygenase-1 mediated platelet reactivity in young male smokers.

BACKGROUND: The purpose of this study is to investigate the acute and chronic effects of cigarette smoking on cyclooxygenase- 1(COX-1)-mediated platelet reactivity among cigarette smokers. METHODS: The levels of collagen-induced platelet aggregation, platelet COX-1 activity, and expressions were compared between smokers and age-matched nonsmokers. In smokers, the acute effects of cigarette smoking were assessed by repeating these measurements an hour after smoking. RESULTS: Twenty-five smokers and age-matched nonsmokers (all men; mean age, 29 years) were studied. Collagen-induced platelet aggregation and plasma/urinary thromboxane B2 (TXB2) and 11-dehydroxythromboxane B2 levels were higher in cigarette smokers compared to nonsmokers. Greater expression of platelet COX-1 was observed in smokers than in nonsmokers. Among smokers, collagen-induced platelet aggregation correlated positively with platelet volume and circulating nicotine and cotinine concentrations. The levels of plasma/urinary TXB2 were significantly increased an hour after cigarette smoking. CONCLUSION: Cigarette smoking aggravates COX-1-mediated platelet reactivity in young, otherwise healthy, smoking men.

Neurophobia in medical students and junior doctors--blame the GIK.

INTRODUCTION: We aimed to create a definition of neurophobia, and determine its prevalence and educational risk factors amongst medical students and junior doctors in Singapore. MATERIALS AND METHODS: We surveyed medical students and junior doctors in a general hospital using electronic and paper questionnaires. We asked about knowledge, interest, perceived difficulty in neurology, and confidence in managing neurology patients compared to 7 other internal medicine specialties; quality and quantity of undergraduate and postgraduate neuroscience teaching, clinical neurology exposure, and postgraduate qualifications. Neurophobia was defined as ≤4 composite score of difficulty and confidence with neurology. RESULTS: One hundred and fifty-eight medical students (63.5%) and 131 junior doctors (73.2%) responded to the questionnaire. Neurophobia prevalence was 47.5% in medical students, highest amongst all medical subspecialties, and 36.6% in junior doctors. Multivariate analysis revealed that for medical students, female gender (OR 3.0, 95% CI, 1.3 to 6.7), low interest (OR 2.5, 95% CI, 1.0 to 6.2), low knowledge (OR 10.1, 95% CI, 4.5 to 22.8), and lack of clinical teaching by a neurologist (OR 2.8, 95% CI, 1.2 to 6.6) independently increased the risk of neurophobia. For doctors, low interest (OR 3.0, 95% CI, 1.3 to 7.0) and low knowledge (OR 2.7, 95% CI, 1.2 to 6.2) independently increased the risk of neurophobia, and female gender was of borderline significance (OR 2.0, 95% CI, 0.9 to 4.6). CONCLUSION: Neurophobia is highly prevalent amongst Singapore medical students and junior doctors. Low interest and knowledge are independent risk factors shared by both groups; female gender may also be a shared risk factor. The mnemonic GIK (Gender, Interest, Knowledge) identifies the risk factors to mitigate when planning teaching strategies to reduce neurophobia.

Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection.

BACKGROUND: Leukotriene B4, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B4 and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age-matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils. RESULTS: Plasma leukotriene B4 was elevated during the febrile stages of dengue infection compared to levels during convalescence and in study controls. Plasma leukotriene B4 also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B4; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Pre-incubation of either live or heat-inactivated DENV-2 resulted in reduced leukotriene B4 release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B4 was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5-lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B4 production. CONCLUSION: These findings provide important clinical and mechanistic data on the involvement of 5-lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings.

Biomarkers of oxidative damage are elevated among individuals with high cardiovascular risk: refining subject selection strategies for antioxidant trials.

The purpose of this study was to evaluate the use of Framingham risk scores (FRRs) to identify high-risk individuals with biochemical evidence of increased oxidative damage, who may benefit from antioxidant therapies. A bimodal change in plasma F2-isoprostane levels was observed with cardiovascular risk categories, while plasma neuroprostanes, 7α-hydroxycholesterol, and serum γ-glutamyltransferase levels were higher among individuals at high risk of cardiovascular events (Framingham score, > 36). Total plasma hydroxyeicosatetraenoic acid products (HETEs) and serum high-sensitivity CRP (hsCRP) levels were consistently higher across Framingham risk categories. Multivariable analysis identified plasma 7α-hydroxycholesterol (odds ratio (OR), 1.06; 95% confidence interval (CI), 1.03-1.10) and γ-glutamyltransferase (OR, 1.02; 95% CI, 1.01-1.03) as significant predictors of high cardiovascular risk (Framingham score, > 36), accounting for approximately 21% of its variation. Cardiovascular risk scores are useful to identify individuals with high burden of oxidative damage who may benefit from antioxidant therapy.

Acute effects of cigarette smoking on insulin resistance and arterial stiffness in young adults.

BACKGROUND: It is unclear whether changes in insulin sensitivity or arterial stiffness in cigarette smokers could explain the link between cigarette smoking and diabetes mellitus. The purpose of the study was to evaluate the acute effects of cigarette smoking on insulin resistance and arterial stiffness in a cohort of young healthy adults. METHODS: Metabolic risk components, hemodynamic parameters, plasma nitrite/nitrate and high-sensitivity C-reactive protein (hsCRP) levels, were compared between smokers and age- and gender-matched controls (non-smokers). In smokers, these levels were determined 8-h following cigarette abstinence and an hour after smoking. RESULTS: One hundred nineteen smokers and age-matched non-smokers (mean age, 32 years; 83% men) were included in this study. Compared with non-smokers, smokers had a significantly higher number of abnormal metabolic risk components, HOMA-IR index and total nitrite/nitrate levels. There were no differences in brachial/central blood pressure, augmentation index and hsCRP between smokers and non-smokers. An hour after smoking, smokers had significantly higher levels of HOMA-IR, total nitrite/nitrate, hsCRP and heart rate compared with baseline levels. By contrast, brachial/central blood pressure and augmentation index were unchanged after cigarette smoking. Baseline vascular and insulin resistance status predicted the extent of rise in the HOMA-IR and augmentation indices acutely after cigarette smoking (adjusted R(2) 0.358 and 0.124, p < 0.001 respectively). CONCLUSIONS: Individuals with more advanced vascular damage and insulin resistance are vulnerable to the acute effects of cigarette smoking.

Accurate targeting of botulinum toxin injections: how to and why.

Botulinum toxin (BTX), the exotoxin of the obligate anaerobe, Clostridium botulinum, is used to ameliorate pain and treat conditions associated with glandular, smooth and skeletal muscle overactivity. The benefits derived from the injection of BTX may be negated by unintended weakness of uninjected muscles. Performance of BTX injections may be facile, requiring only surface marking or clinical-localisation techniques but may be more technically demanding, necessitating the use of equipment, such as electromyography (EMG) or ultrasonography (U/S). Less often, endoscopic, fluoroscopic or computed tomographic (CT) guidance may be required. Despite evidence to support the efficacy of BTX injections in treating many conditions, there is no evidence to support the superiority of any one injection technique over needle localisation using surface anatomy. This is possibly due to the lack of well-designed controlled studies, that is, current studies are hampered by small patient numbers, lack of consistency of injection technique and the application of different rating scales. Intuitively, certain injection techniques are more suited to injection of specific muscles or conditions, for example, U/S or passive-monitoring EMG should be used to treat cervical dystonia, active-monitoring EMG applied for strabismus injections, whereas either active-monitoring EMG or endoscopy is indicated when giving BTX for spasmodic dysphonia. Finally, electrical-stimulation EMG or U/S (or a combination of both) would be most suitable when injecting the forearm muscles for spasticity or writer's cramps.

Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels.

OBJECTIVE: There is considerable controversy about what constitutes optimal zinc intakes in patients with type 2 diabetes mellitus. Several studies suggest that higher zinc intakes improve vascular function and decrease oxidative damage. We aimed to assess the effects of zinc supplementation using a range of reliable biomarkers of oxidative damage and vascular function in patients with type 2 diabetes. METHODS: Forty male type 2 diabetic patients were supplemented either with 240 mg/day of zinc as zinc gluconate (n=20) or with placebo (n=20) for 3 months. Blood and spot urine samples were taken at baseline, days 3 and 7, months 1, 2 and 3 during supplementation and 1 month after cessation. Serum zinc, reliable biomarkers of oxidative damage (F(2)-isoprostanes, neuroprostanes, cholesterol oxidation products, allantoin) as well as hydroxyeicosatetraenoic acid products and vascular-related indices (augmentation index, pulse wave velocity and aortic pressure) were measured. RESULTS: Despite significantly higher levels of serum zinc in the treatment group, markers of oxidative damage, levels of hydroxyeicosatetraenoic acid products and vascular indices were unchanged by zinc supplementation during the four-month study period. CONCLUSION: Improving the zinc status in patients with type 2 diabetes with normal zinc levels did not have any impact on oxidative damage and vascular function, and such supplementation may not be generally beneficial in these individuals.

Oxidative damage in ischemic stroke revealed using multiple biomarkers.

BACKGROUND AND PURPOSE: We investigated changes in oxidative damage after ischemic stroke using multiple biomarkers. METHODS: Serial blood and urine samples of ischemic stroke subjects and age-matched control subjects were assayed for F2-isoprostanes, hydroxyeicosatetraenoic acid products, F4-neuroprostanes, 24-hydroxycholesterol, allantoin, and urate. RESULTS: Sixty-six stroke subjects (mean age, 65 years; median National Institutes of Health Stroke Scale 17) and 132 control subjects were recruited. A bimodal pattern of change was observed in plasma and urinary F2-isoprostanes and plasma 24-hydroxycholesterol. The rise in plasma hydroxyeicosatetraenoic acid products, F4-neuroprostanes, and allantoin was highest 6 to 12 hours after stroke onset, whereas plasma urate was significantly lower than controls on Days 1 to 3. After adjusting for age and baseline National Institutes of Health Stroke Scale, baseline plasma esterified hydroxyeicosatetraenoic acid products (OR, 1.01; 95% CI, 1.01 to 1.02), plasma urate (1.01; 1.00 to 1.01), and plasma free F4-neuroprostanes (2.73; 1.76 to 3.93) were associated with 90-day good functional recovery (modified Rankin Scale ≤1). CONCLUSIONS: Multiple markers of oxidative damage are increased immediately after stroke and remain elevated for several days. Recognition of these temporal changes may help design better antioxidant treatment trials for acute ischemic stroke.

Biomarkers of oxidative damage in cigarette smokers: which biomarkers might reflect acute versus chronic oxidative stress?

Cigarette smoking predisposes to the development of multiple diseases involving oxidative damage. We measured a range of oxidative damage biomarkers to understand which differ between smokers and nonsmokers and if the levels of these biomarkers change further during the act of smoking itself. Despite overnight abstinence from smoking, smokers had higher levels of plasma total and esterified F(2)-isoprostanes, hydroxyeicosatetraenoic acid products (HETEs), F(4)-neuroprostanes, 7-ketocholesterol, and 24- and 27-hydroxycholesterol. Levels of urinary F(2)-isoprostanes, HETEs, and 8-hydroxy-2'-deoxyguanosine were also increased compared with age-matched nonsmokers. Several biomarkers (plasma free F(2)-isoprostanes, allantoin, and 7ß-hydroxycholesterol and urinary F(2)-isoprostane metabolites) were not elevated. The smokers were then asked to smoke a cigarette; this acute smoking elevated plasma and urinary F(2)-isoprostanes, plasma allantoin, and certain cholesterol oxidation products compared to presmoking levels, but not plasma HETEs or urinary 8-hydroxy-2'-deoxyguanosine. Smokers showed differences in plasma fatty acid composition. Our findings confirm that certain oxidative damage biomarkers are elevated in smokers even after a period of abstinence from smoking, whereas these plus some others are elevated after acute smoking. Thus, different biomarkers do not measure identical aspects of oxidative stress.

Use of botulinum toxin in the neurology clinic.

Botulinum neurotoxin (BoNT) is an effective treatment for conditions associated with overactivity of glandular, smooth or skeletal muscle, and this toxin can also ameliorate certain painful conditions. Electromyography, endoscopy and imaging techniques such as ultrasonography and fluoroscopy have been used to increase the accuracy of BoNT injections. This Review assesses the mechanisms of action of BoNT, and examines the use of BoNT injections in numerous neurological conditions, including dystonia, spasticity, headaches and other painful disorders, hemifacial spasm, essential tremor, motor tics, hyperhidrosis, and sialorrhea and drooling. Important practical aspects, such as the reconstitution of BoNT, dosing, and methods of administration, are also addressed.

Acceptability of medical students by patients from private and public family practices and specialist outpatient clinics.

INTRODUCTION: Previous studies on patient acceptance of medical student teaching were from Western populations and in one setting only. However, there has been no prospective study comparing patient acceptability before and after an actual experience. We studied patient acceptability of medical student teaching in private and public family practices and public hospital specialist outpatient clinics in Singapore, and before and after an actual medical student teaching consultation. MATERIALS AND METHODS: We conducted an anonymous cross-sectional survey from March through October 2007 of Singaporean or permanent resident patients attending 76 teaching private family practices, 9 teaching public family practices and 8 specialty clinics in a teaching public hospital. We used pre-consultation cross-sectional patient surveys in all three settings. For private family practice setting only, post-consultation patient survey was conducted after an actual experience with medical student presence. RESULTS: Out of 5123 patients, 4142 participated in the cross-sectional survey (80.9%) and 1235 of 1519 patients in the prospective cohort study (81.3%). Eighty percent were comfortable with medical students present, 79% being interviewed and 60% being examined. Regarding being examined by medical students, parents of children were least comfortable while patients between 41 to 60 years were most comfortable (adjusted OR = 1.99 [1.55-2.57]). Females were less comfortable with medical student teaching than males. Chinese patients were the least comfortable about being interviewed or examined by medical students among the ethnic groups. Indians were most comfortable with being interviewed by medical students (adjusted OR = 1.38 [1.02-1.86]) but Malays were the most comfortable being examined by them (adjusted OR = 1.32 [1.07-1.62]). Family practice patients were more receptive to medical student teaching than the hospital's specialist outpatients. Common barriers to patient acceptance were lack of assurance of patient privacy, dignity and confidentiality. Actual exposure to medical student teaching did not change levels of patient acceptance. CONCLUSIONS: Compared to similar studies from Western countries, Asian patients appear to be less receptive to medical student teaching than Western patients. Family practice settings offer medical students a more receptive learning environment.