Knowledge Attainment and Engagement Among Medical Students: A Comparison of Three Forms of Online Learning.

Objective: This study compared knowledge attainment and student enjoyment and engagement between clinical case vignette, patient-testimony videos and mixed reality (MR) teaching via the Microsoft HoloLens 2, all delivered remotely to third year medical students. The feasibility of conducting MR teaching on a large scale was also assessed. Setting & Participants: Medical students in Year 3 at Imperial College London participated in three online teaching sessions, one in each format. All students were expected to attend these scheduled teaching sessions and to complete the formative assessment. Inclusion of their data used as part of the research trial was optional. Primary and Secondary Outcome Measures: The primary outcome measure was performance on a formative assessment, which served to compare knowledge attainment between three forms of online learning. Moreover, we aimed to explore student engagement with each form of learning via a questionnaire, and also feasibility of applying MR as a teaching tool on a large scale. Comparisons between performances on the formative assessment between the three groups were investigated using a repeated measures two-way ANOVA. Engagement and enjoyment were also analysed in the same manner. Results: A total of 252 students participated in the study. Knowledge attainment of students using MR was comparable with the other two methods. Participants reported higher enjoyment and engagement (p<0.001) for the case vignette method, compared with MR and video-based teaching. There was no difference in enjoyment or engagement ratings between MR and the video-based methods. Conclusion: This study demonstrated that the implementation of MR is an effective, acceptable, and feasible way of teaching clinical medicine to undergraduate students on a large scale. However, case-based tutorials were found to be favoured most by students. Future work could further explore the best uses for MR teaching within the medical curriculum.

Development of a Novel Tool To Demystify Drug Distribution at Tissue-Blood Barriers.

Tissue endothelial cells express ABC-transporter enzymes that change the concentration of small molecules within different tissue compartments. These "blood-tissue barriers" have been shown to directly affect the efficacy and toxicity of anticancer, antimicrobial, psychiatric, and anti-epileptic drugs. Currently this phenomenon is best studied for the blood-brain barrier, but remains enigmatic for most other tissues. In addition, canonical pharmacokinetic theory specifically assumes an equal concentration of free drug within all tissue compartments. Inspired by Lipinski's "rule of 5," we here clarify current knowledge on drug-tissue distribution by: 1) curating the in-vivo literature on 73 drugs across 23 tissues and 2) developing two graphical web-based applications to visually describe and interpret data. These curated in-vivo dataset and visualization tools enabled us to achieve new insights into the logic of the barrier-tissue organization and showed remarkable correspondence to whole-body imaging of radiolabeled molecules.

Corrigendum to "Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent".

[This corrects the article DOI: 10.1155/2015/924387.].

Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent.

Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P = 0.005), irrespective of site, gender, and central obesity (P ≤ 0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P < 0.001). Diabetes was less in those with low ferritin (<20 mg/mL), P < 0.008, and risk estimate = 0.35 (95% CI 0.15-0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P = 0.001) and age (P < 0.001). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors.

CD36 expression and lipid metabolism following an oral glucose challenge in South Asians.

AIM: To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians. METHODS: An observational study of South Asians whom as an ethnic group have - a higher risk of developing diabetes. The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-, and macro-vascular complications. Twenty-nine healthy South Asian participants [mean age 34.6 (8.9) years, 76.2% male, mean body-mass index 25.0 (5.2) kg/m(2)] were recruited from an urban residential area of central Birmingham (United Kingdom). The main outcomes measured were post prandial (30 min) and post absorptive (120 min) changes from fasting (0 min) in circulating lipoproteins, lipds and hormones, and monocyte expression of CD36 post injection of a 75 g oral glucose challenge. The inducements of variations of monocyte CD36 expression were analysed. RESULTS: Our results showed evident changes in monocyte CD36 expression following the glucose challenge (P < 0.001). Non-esterified fatty acids (NEFA) levels decreased progressively during the challenge (P < 0.001), in contrast to increased cholesterol (but not triglyceride) concentrations within very low density lipoprotein (VLDL) and low density lipoprotein subfractions (P < 0.01). Levels of, glucose, serum triglycerides and high density lipoprotein cholesterol remained largely unchanged. Variations of monocyte CD36 were negatively (r = -0.47, P = 0.04) associated to fat from the diet and positively to carbohydrate from the diet (r = 0.65, P < 0.001). CONCLUSION: These data suggest that the initiation of VLDL genesis follows the consumption of glucose within this population, inferring that the sequestration of NEFA from these particles happens due to the increased availability of CD36 receptors. While these are preliminary results, it would appear that lifestyle exposures have a role in moderating the expression of CD36.

A combination of mild hypothermia and sevoflurane affords long-term protection in a modified neonatal mouse model of cerebral hypoxia-ischemia.

BACKGROUND: Infant brain injury from hypoxia-ischemia (HI) can lead to life-long impairment, but protective strategies are lacking. Short-term but not long-term protection has been demonstrated in the Rice-Vannucci neonatal brain ischemia model (RVM) by volatile anesthetic administration before HI, while exposure during HI has not been tested. In the current study, we evaluated a combination of sevoflurane and mild hypothermia as a protective approach during HI, both short- and long-term, by introducing intubation and mechanical ventilation to the RVM. METHODS: The right common carotid artery was ligated in 10-day-old mice during brief sevoflurane anesthesia, followed by a 2-hour recovery with the dam. Littermates were then randomized to either: HI spontaneously breathing 10% oxygen for 60 minutes (the classical RVM); HI-Protect mild hypothermia and orotracheal intubation and mechanical ventilation with 3.5% sevoflurane in 10% oxygen for 60 minutes; or Room Air spontaneously breathing room air for 60 minutes. In a nonsurviving cohort, cerebral oxygenation was monitored in the area at risk and the contralateral hemisphere during HI or HI-Protect using visible-light spectroscopy (Spectros Corp). Mean arterial blood pressure and heart rate were measured. Arterial blood gases were obtained. Right/left brain hemispheric weight ratios and brain damage scores were determined 1 week after HI. In another group, learning and behavior were assessed in young adulthood (9 weeks) using spontaneous locomotion, Morris water maze, and apomorphine injection. RESULTS: During HI, ipsilateral and contralateral brain oxygenation, arterial blood pressures, blood gases, and glucose levels were similar in both ischemic groups, while heart rate was slower in the HI-Protect group. One week after ischemia, brain hemispheric weight ratios and injury scores in several brain regions were significantly worse after HI, compared with HI-Protect. Nine weeks after HI, Morris water maze hidden platform and reversal platform escape latencies, measures of spatial memory function, were superior after HI-Protect, compared with HI (P < 0.0001). HI-Protect animals demonstrated significantly less circling behavior after an apomorphine challenge (P < 0.0001), a measure of striatal integrity. CONCLUSIONS: To test the neuroprotective effects of volatile anesthetics during neonatal brain ischemia, we developed a modification of the RVM. By using mechanical ventilation and endotracheal intubation, sevoflurane administration during HI was survivable. The combination of sevoflurane administration and mild hypothermia during HI conferred not only short-term structural, but also long-term functional protection, compared with littermates treated according to the RVM. These findings warrant further studies to improve neurological outcome in critically ill infants.

Cardiovascular Risk Profiles amongst Women in a Multiethnic Population in Inner City Britain: A Potential Impact of Anaemia.

The risk of diabetes is markedly reduced in men with iron deficiency anaemia (IDA). The nature of this relationship in women is not clear, nor is there information about the influence of ethnicity, given the increased susceptibility of diabetes amongst South Asians and Afro-Caribbeans. We reviewed 3563 patients with a diagnosis of anaemia from 2000 to 2007. The age-adjusted prevalence of vitamin B12 deficiency and IDA was calculated, together with cardiovascular comorbidities amongst Caucasians, South Asians, and Afro-Caribbeans. The prevalence of vitamin B12 deficiency (women only) or IDA was markedly higher in South Asians compared to Caucasians and Afro-Caribbeans. Among women with IDA, diabetes was more prevalent among South Asians (45%, 95% CI 39.0-51.0) compared to Caucasians (3.0%, 2.1-4.0); P < 0.001. Among South Asian women with vitamin B12 deficiency, the prevalence of diabetes was reduced 8.5% (5.2-12.0). South Asian women with vitamin B12 deficiency had a higher prevalence of myocardial infarction (MI) and ischemic heart disease (IHD), but this relationship was reversed in IDA. IDA is associated with a greater prevalence of diabetes in South Asian women, but it is not coordinated by a greater risk of macrovascular complications. Given the cardiovascular impact of diabetes in South Asians, this association merits further study in relation to its pathophysiological implication.

Characterization and quantification of isoflurane-induced developmental apoptotic cell death in mouse cerebral cortex.

BACKGROUND: Accumulating evidence indicates that isoflurane and other, similarly acting anesthetics exert neurotoxic effects in neonatal animals. However, neither the identity of dying cortical cells nor the extent of cortical cell loss has been sufficiently characterized. We conducted the present study to immunohistochemically identify the dying cells and to quantify the fraction of cells undergoing apoptotic death in neonatal mouse cortex, a substantially affected brain region. METHODS: Seven-day-old littermates (n = 36) were randomly assigned to a 6-hour exposure to either 1.5% isoflurane or fasting in room air. Animals were euthanized immediately after exposure and brain sections were double-stained for activated caspase 3 and one of the following cellular markers: Neuronal Nuclei (NeuN) for neurons, glutamic acid decarboxylase (GAD)65 and GAD67 for GABAergic cells, as well as GFAP (glial fibrillary acidic protein) and S100ß for astrocytes. RESULTS: In 7-day-old mice, isoflurane exposure led to widespread increases in apoptotic cell death relative to controls, as measured by activated caspase 3 immunolabeling. Confocal analyses of caspase 3-labeled cells in cortical layers II and III revealed that the overwhelming majority of cells were postmitotic neurons, but some were astrocytes. We then quantified isoflurane-induced neuronal apoptosis in visual cortex, an area of substantial injury. In unanesthetized control animals, 0.08% ± 0.001% of NeuN-positive layer II/III cortical neurons were immunoreactive for caspase 3. By contrast, the rate of apoptotic NeuN-positive neurons increased at least 11-fold (lower end of the 95% confidence interval [CI]) to 2.0% ± 0.004% of neurons immediately after isoflurane exposure (P = 0.0017 isoflurane versus control). In isoflurane-treated animals, 2.9% ± 0.02% of all caspase 3-positive neurons in superficial cortex also coexpressed GAD67, indicating that inhibitory neurons may also be affected. Analysis of GABAergic neurons, however, proved unexpectedly complex. In addition to inducing apoptosis among some GAD67-immunoreactive neurons, anesthesia also coincided with a dramatic decrease in both GAD67 (0.98 vs 1.84 ng/mg protein, P < 0.00001, anesthesia versus control) and GAD65 (2.25 ± 0.74 vs 23.03 ± 8.47 ng/mg protein, P = 0.0008, anesthesia versus control) protein levels. CONCLUSIONS: Prolonged exposure to isoflurane increased neuronal apoptotic cell death in 7-day-old mice, eliminating approximately 2% of cortical neurons, of which some were identified as GABAergic interneurons. Moreover, isoflurane exposure interfered with the inhibitory nervous system by downregulating the central enzymes GAD65 and GAD67. Conversely, at this age, only a minority of degenerating cells were identified as astrocytes. The clinical relevance of these findings in animals remains to be determined.

Cell age-specific vulnerability of neurons to anesthetic toxicity.

OBJECTIVE: Anesthetics have been linked to widespread neuronal cell death in neonatal animals. Epidemiological human studies have associated early childhood anesthesia with long-term neurobehavioral abnormalities, raising substantial concerns that anesthetics may cause similar cell death in young children. However, key aspects of the phenomenon remain unclear, such as why certain neurons die, whereas immediately adjacent neurons are seemingly unaffected, and why the immature brain is exquisitely vulnerable, whereas the mature brain seems resistant. Elucidating these questions is critical for assessing the phenomenon's applicability to humans, defining the susceptible age, predicting vulnerable neuronal populations, and devising mitigating strategies. METHODS: This study examines the effects of anesthetic exposure on late- and adult-generated neurons in newborn, juvenile, and adult mice, and characterizes vulnerable cells using birth-dating and immunohistochemical techniques. RESULTS: We identify a critical period of cellular developmental during which neurons are susceptible to anesthesia-induced apoptosis. Importantly, we demonstrate that anesthetic neurotoxicity can extend into adulthood in brain regions with ongoing neurogenesis, such as dentate gyrus and olfactory bulb. INTERPRETATION: Our findings suggest that anesthetic vulnerability reflects the age of the neuron, not the age of the organism, and therefore may potentially not only be relevant to children but also to adults undergoing anesthesia. This observation further predicts differential heightened regional vulnerability to anesthetic neuroapoptosis to closely follow the distinct regional peaks in neurogenesis. This knowledge may help guide neurocognitive testing of specific neurological domains in humans following exposure to anesthesia, dependent on the individual's age during exposure.

Vitamin D deficiency amongst minority ethnic groups in the UK: a cross sectional study.

BACKGROUND: Vitamin D deficiency is common amongst minority groups in Britain but its magnitude amongst South Asian (SA) and Black African-Caribbean (AC) groups is not well defined. The steroidal, endocrine nature of vitamin D provides it with a putative link with cardiovascular disease (CVD), and we hypothesised that aberrant levels of this hormone would reflect a heightened risk of CVD in these ethnic groups. METHODS: SA (n=1105, 57% male) and AC (n=748, 51% male) were recruited as part of a community heart failure study from 20 primary care practices, Birmingham, UK. Vitamin D2/D3 levels were measured to determine rates of total vitamin D status, which were age/sex adjusted. RESULTS: The majority of SAs had severe vitamin D deficiency (42.2%, 95% CI: 39.2-45.1), which was more frequent than in AC (12.5%, 10.2-14.9, p<0.001. Vitamin status in SA and AC was unrelated to the presence of osteoporosis, and on multivariate analysis of SA, vitamin D levels were independently associated with age (ß=0.18, p<0.001), haemoglobin (ß=0.12, p=0.002), and negatively with alkaline phosphatase (a marker of bone mineralisation, ß=-0.11, p=0.022). Amongst AC, vitamin D was independently associated with having ever smoked (ß=-0.13, p=0.006) and systolic blood pressure (ß=0.10, p=0.038). CONCLUSIONS: Vitamin D deficiency is a frequent biochemical observation amongst minority groups in Britain but the clinical significance is unclear, and ethnically specific. A proportionate susceptibility to bone disease is not apparent in either minority group.

Is the higher risk of cardiovascular disease amongst South Asian populations linked to abnormalities of haemoglobin? A preliminary case control study.

The elevated burden of cardiovascular disease (CVD) amongst South Asian populations is a complex and multi-factorial phenomenon. South Asians evolved from environments where malaria was endemic, and while haemoglobin disorders frequent this group, a link to CVD has not been described. Using a case-control feasibility study, haemoglobin abnormalities identified by mass spectrometry were compared between South Asian patients with CVD (n = 72) and non-CVD controls (n = 84). Carotid-artery intima media thickness (CIMT) was used as a marker of vascular damage. Ultracentrifugation was used to separate lipoprotein subfractions, which were analysed for iron. Haemoglobin anomalies were more frequent for CVD patients than controls (34.7% vs. 14.3%, P < 0.001), as were subfractionated lipoprotein concentrations of iron (P < 0.001). Patients with haemoglobin disorders had greater CIMT (0.75 vs. 0.65 mm, P = 0.008), and lower HDL cholesterol (0.78 vs. 1.03 mmol/l, P = 0.003). These preliminary data suggest that haemoglobin disorders contribute to atherosclerotic disease in South Asians and further research is warranted.

Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial.

BACKGROUND: Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk. METHODS/DESIGN: The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner. DISCUSSION: It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities. Trial registration Current Controlled Trials ISRCTN02839188.

Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice.

BACKGROUND: Volatile anesthetics facilitate surgical procedures and imaging studies in millions of children every year. Neuronal cell death after prolonged exposure to isoflurane in developing animals has raised serious concerns regarding its safe use in children. Although sevoflurane and desflurane are becoming more popular for pediatric anesthesia, their cytotoxic effects have not been compared with those of isoflurane. Accordingly, using newborn mice, the current study established the respective potencies of desflurane, isoflurane, and sevoflurane and then compared equipotent doses of these anesthetics regarding their effects on cortical neuroapoptosis. METHODS: Minimum alveolar concentrations were determined in littermates (aged 7-8 days, n = 42) using tail-clamp stimulation in a bracketing study design. By using equipotent doses of approximately 0.6 minimum alveolar concentration, another group of littermates was randomly assigned to receive desflurane, isoflurane, or sevoflurane or to fast in room air for 6 h. After exposure, animals (n = 47) were euthanized, neocortical apoptotic neuronal cell death was quantified, and caspase 3 activity was compared between the four groups. RESULTS: The minimum alveolar concentration was determined to be 12.2% for desflurane, 2.7% for isoflurane, and 5.4% for sevoflurane. After a 6-h exposure to approximately 0.6 minimum alveolar concentration of desflurane, isoflurane, or sevoflurane, neuronal cell death and apoptotic activity were significantly increased, irrespective of the specific anesthetic used. CONCLUSIONS: In neonatal mice, equipotent doses of the three commonly used inhaled anesthetics demonstrated similar neurotoxic profiles, suggesting that developmental neurotoxicity is a common feature of all three drugs and cannot be avoided by switching to newer agents.

Apolipoproteins in the discrimination of atherosclerotic burden and cardiac function in patients with stable coronary artery disease.

AIMS: To compare the performance of apolipoproteins (Apo) and oxidized LDL against routine clinical lipid profiles in the discrimination of atherosclerotic burden and cardiac function in stable coronary artery disease (CAD) patients. METHODS AND RESULTS: Using a cross-sectional approach, we measured oxidized LDL, Apo AI and B in 199 patients (34-81 years) with stable symptomatic CAD. The discrimination of (i) atherosclerotic burden (coronary atheroma scores, the number of diseased coronary vessels), and (ii) cardiac function [NYHA classification, left-ventricular systolic dysfunction (LVSD)] were judged using receiver operating characteristic (ROC) curves. The ratio of Apo AI to B was correlated to oxidized LDL (Spearman, r = 0.37, P < 0.001); however, oxidized LDL was unrelated to measures of cardiac function or CAD severity. Concentrations of Apo AI decreased from 1.38 to 1.20 g/L with increasing atheroma scores (P = 0.02), while triglyceride levels increased from 1.50 to 2.23 mmol/L (P = 0.016). High-density lipoprotein (HDL) cholesterol and Apo AI levels were higher among those with heart failure (P = 0.002), and increased ordinally with NYHA class (P = 0.005). On ROC analysis, reduced levels of Apo AI and HDL cholesterol were discriminators for patients in the upper quartile for atheroma score (P < 0.004). Raised indices of HDL were associated with heart failure (P < 0.002). CONCLUSION: Apo AI levels are a consistent discriminator of atherosclerotic burden among patients with stable CAD. However, heart failure presents an element of confounding in the diagnostic and prognostic utility of Apo monitoring among these patients.

Omega-3 polyunsaturated fatty acids: a necessity for a comprehensive secondary prevention strategy.

Long-chain omega-3 polyunsaturated fatty acid (PUFA) supplementation has been used for the secondary prevention of fatal and nonfatal myocardial infarction (MI). However, the benefit of this therapy is frequently confused with other established treatments in the therapeutic strategy among such patients. We review the data on omega-3 PUFA use in secondary care and consider indications for its use which include post-MI and raised triglycerides. We suggest that the available evidence supports the use of omega-3 supplementation as part of the comprehensive secondary care package for post-MI patients.

Glycemic status underlies increased arterial stiffness and impaired endothelial function in migrant South Asian stroke survivors compared to European Caucasians: pathophysiological insights from the West Birmingham Stroke Project.

BACKGROUND: The pathophysiology of an increased risk of cerebrovascular disease mortality among South Asians (SA) remains unclear. Indices of arterial stiffness and endothelial dysfunction are independent markers of vascular disease, having both prognostic and diagnostic implications. We hypothesized that there are ethnic variations in indices of arterial stiffness and endothelial dysfunction between SA and European Caucasian (EC) stroke patients, which may underline a poorer prognosis in the former, and further investigated promoters of vessel wall abnormalities. METHODS: Using a cross-sectional approach, a total of 100 SA stroke survivors were prospectively recruited from the ongoing West Birmingham Stroke Project. Indices of vessel wall characteristics (arterial stiffness and endothelial function [change in reflective index]) were measured noninvasively using the digital volume pulse analysis technique in a temperature-controlled environment, using a direct standardized approach. SA stroke subjects were compared to 60 EC stroke survivors, 60 SA with risk factors, and 73 healthy controls. RESULTS: Among stroke patients, both ethnic groups were comparable for cardiovascular risk profile, except for more diabetes mellitus in SA (P=0.007) subjects and a higher prevalence of atrial fibrillation in EC (P=0.04) subjects. According to the TOAST and Bamford classifications, SA subjects had more small vessel (P=0.04) and lacunar infarctions (P=0.01). SA subjects had higher measurements of arterial stiffness (P<0.001) and impaired endothelial-dependent vascular function (change in reflective index %; P<0.001). On univariate analysis, endothelial function was negatively correlated with fasting plasma glucose (r=-0.4; P<0.001) and total cholesterol level (r=-0.2; P<0.001). On multivariate analysis, glycemic status was independently associated with impaired endothelial function (P=0.008) and increased arterial stiffness (P<0.001) among SA subjects. CONCLUSIONS: SA stroke survivors had more small vessel disease-related cerebrovascular events compared to EC subjects. Underlying glycemic status in SA subjects had an adverse impact on the vascular system, leading to abnormal vessel wall characteristics.

Ischemic stroke in South Asians: a review of the epidemiology, pathophysiology, and ethnicity-related clinical features.

BACKGROUND AND PURPOSE: Within the United Kingdom, mortality from stroke is higher among South Asians compared to European whites. The reasons for this excess cerebrovascular risk in South Asians remain unclear. The aim of this review is to present a comprehensive and systematic overview of the available literature relating to ischemic stroke among South Asian populations identifying distinct features of stroke epidemiology in this group. SUMMARY OF REVIEW: A high frequency of lacunar strokes is a familiar pattern among South Asians, which suggests a greater prevalence of small-vessel disease in South Asians. This may be a consequence of abnormal metabolic and glycemic processes. In addition, stroke mortality among South Asians appears to be explained by glycemic status, which is an independent predictor of long-term stroke mortality. Within India, there is a perceptible rural-urban gradient in stroke prevalence, underlying the dangers of the rapid transition in socioeconomic circumstances seen across the Indian subcontinent. CONCLUSIONS: This review emphasizes the importance of further research into ischemic stroke for South Asians given their higher cardiovascular disease burden and necessity for targeted healthcare approaches.

Circulating levels of adiponectin, leptin, and tumour necrosis factor alpha in hypertension.

BACKGROUND: Abnormal adipocyte function is implicated in the coalition of multiple cardiovascular risk factors, where aberrant circulating levels of the adipose-derived hormones adiponectin, leptin, and tumour necrosis factor (TNF) alpha may provide the putative link between hypertension and increased cardiovascular risk. The pragmatic utility of these 'adipocytokines' in the clinical setting of hypertension is unclear, and we hypothesized a relationship of circulating adipocytokines to hypertension, and associated cardiovascular morbidity. METHOD: Using a cross-sectional approach, we measured plasma adipocytokines in 278 'high-risk' treated hypertensive participants of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study (mean (SD) age 62.9 (7.7) years), who were compared to 54 newly diagnosed untreated hypertensives (61.3 (10.9) years) and 55 healthy controls (48.3 (12.3) years). RESULTS: Levels of all three adipocytokines were lower amongst treated hypertensives compared to newly diagnosed hypertensives and healthy controls (P<0.001 for leptin and adiponectin), and varied with gender, co-morbidities (e.g. diabetes, cardiovascular disease (CVD), left ventricular hypertrophy) and by treatments (e.g. statins and beta-blockade). Levels of adiponectin (P<0.001) and leptin (P=0.02) rose in an ordinal fashion with increasing hypertension severity (grade). Levels of leptin were associated with diastolic blood pressure in a positive fashion (P<0.001). CONCLUSIONS: While hypertension affects adipocytokine levels, the clinical interpretation of circulating levels in hypertension is confounded by a range of factors. The positive relation between leptin and adiponectin with hypertension severity may reflect an underlying adaptive response that is attenuated during pharmacological hypertension management.

The effects of neonatal isoflurane exposure in mice on brain cell viability, adult behavior, learning, and memory.

BACKGROUND: Volatile anesthetics, such as isoflurane, are widely used in infants and neonates. Neurodegeneration and neurocognitive impairment after exposure to isoflurane, midazolam, and nitrous oxide in neonatal rats have raised concerns regarding the safety of pediatric anesthesia. In neonatal mice, prolonged isoflurane exposure triggers hypoglycemia, which could be responsible for the neurocognitive impairment. We examined the effects of neonatal isoflurane exposure and blood glucose on brain cell viability, spontaneous locomotor activity, as well as spatial learning and memory in mice. METHODS: Seven-day-old mice were randomly assigned to 6 h of 1.5% isoflurane with or without injections of dextrose or normal saline, or to 6 h of room air without injections (no anesthesia). Arterial blood gases and glucose were measured. After 2 h, 18 h, or 11 wk postexposure, cellular viability was assessed in brain sections stained with Fluoro-Jade B, caspase 3, or NeuN. Nine weeks postexposure, spontaneous locomotor activity was assessed, and spatial learning and memory were evaluated in the Morris water maze using hidden and reduced platform trials. RESULTS: Apoptotic cellular degeneration increased in several brain regions early after isoflurane exposure, compared with no anesthesia. Despite neonatal cell loss, however, adult neuronal density was unaltered in two brain regions significantly affected by the neonatal degeneration. In adulthood, spontaneous locomotor activity and spatial learning and memory performance were similar in all groups, regardless of neonatal isoflurane exposure. Neonatal isoflurane exposure led to an 18% mortality, and transiently increased Paco(2), lactate, and base deficit, and decreased blood glucose levels. However, hypoglycemia did not seem responsible for the neurodegeneration, as dextrose supplementation failed to prevent neuronal loss. CONCLUSIONS: Prolonged isoflurane exposure in neonatal mice led to increased immediate brain cell degeneration, however, no significant reductions in adult neuronal density or deficits in spontaneous locomotion, spatial learning, or memory function were observed.