Wireless Handheld Computers in the Preclinical Undergraduate Curriculum

This report presents the results of a pilot project using wireless PDAs as teaching tools in an undergraduate medical curriculum. This technology was used to foster a transition from a passive to an interactive learning environment in the classroom and provided a solution for the implementation of computer-based exams for a large class. Wayne State Medical School recently provided model e570 Toshiba PocketPCs® (personal digital assistants or PDAs), network interface cards, and application software developed by CampusMobility® to 20 sophomore medical students. The pilot group of preclinical students used the PDAs to access web-based course content, for communication, scheduling, to participate in interactive teaching sessions, and to complete course evaluations. Another part of this pilot has been to utilize the PDAs for computer-based exams in a wireless environment. Server authentication that restricted access during the exams and a proctoring console to monitor and record the PDA screens will be described in this report. Results of a student satisfaction survey will be present

What Are Normal Cortisol Values for Young Children?

Normative ranges for cortisol levels in children remain controversial, because of diurnal variations, effects of age, sex, stressful experiences before sampling (blood, saliva), intercurrent illnesses/immunizations, sample preparation and analytical methods. Measuring hair cortisol concentrations (HCC) is unaffected by diurnal variations or many of these factors, and presents a summative measure of chronic stress. Depending on hair growth rates, approximately 1 cm of hair represents cortisol release over the past month. HCC does not fluctuate frequently and therefore represents cumulative stress over time. It is vitally important to establish normative cortisol levels in children, so that both maladaptive and toxic stress levels can be measured. Pilot data from children in the CANDLE Study (Conditions Affecting Neurocognitive Development & Learning in Early childhood) were analyzed to identify the 25th, 50th and 75th percentiles for HCC in 1-4 year-old children. Significantly higher HCC were noted in black vs. white children at 1, 2, 3, and 4-years (P\u3c0.001, for all ages). When measuring HCC we must also study the biochemical composition of an individual’s hair, primarily its lipid content. This lipid content is significantly different depending on one’s racial background and may account for some of the observed racial differences in HCC (Robbins, 2012). Establishing age-, sex-, and race-specific normative levels for HCC are essential for investigating the cumulative effects of chronic stress or “allostatic load” across the lifespan. If the normative ranges for HCC can be established, both the causes and effects of maladaptive and toxic stress can be subsequently identified, prevented and/or treated

ALOE-EMODIN GLYCOSIDES AMELIORATE GLUCOSE UTILIZATION VIA INSULIN DOWNSTREAM REGULATORS: AN IN VIVO INVESTIGATION

ABSTRACTObjective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. Thisstudy intended to investigate the insulin mimetic effect of AEG by in vivo method.Methods: Male Wistar albino rats were randomly allocated into two groups and fed for a period of 3-week. The high-fat diet group animals wereinjected with a low dose (35 mg/kg) of streptozotocin to induce Type-2 diabetes. The diabetic rats were then treated with low dose: 10 mg/kg andhigh dose: 30 mg/kg for a period of 21-day. A dose-dependent decrease in fasting blood glucose, cholesterol, and triglycerides levels on treatmentwith AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase,and fructose1,6-bisphosphatase with a concomitant increasein glycogencontent.Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatmentwith AEG (30 mg/kg) augmented the phosphorylation of insulin downstream regulators such as insulin receptor beta, insulin receptor substrate 1,PI3K, glucose transporter 4, glycogen synthase kinase 3 beta, and peroxisome proliferator activator receptor gamma in the skeletal muscle tissue ofthe Type-2 diabetic rats compared to vehicle-treated diabetic rats.Conclusion: The present results suggested that AEG could serve as an interesting candidate in the drug development for the management of diabetes.Keywords: Aloe-emodin glycoside, Type-2 diabetes, High-fat diet/streptozotocin, Carbohydrate Metabolism, Glycogen, Antioxidant enzyme

Differential postural effects of plantar-flexor muscles fatigue under normal, altered and improved vestibular and neck somatosensory conditions

The aim of the present study was to assess the effects of plantar-flexor muscles fatigue on postural control during quiet standing under normal, altered and improved vestibular and neck somatosensory conditions. To address this objective, young male university students were asked to stand upright as still as possible with their eyes closed in two conditions of No Fatigue and Fatigue of the plantar-flexor muscles. In Experiment 1 (n=15), the postural task was executed in two Neutral head and Head tilted backward postures, recognized to degrade vestibular and neck somatosensory information. In Experiment 2 (n=15), the postural task was executed in two conditions of No tactile and Tactile stimulation of the neck provided by the application of strips of adhesive bandage to the skin over and around the neck. Centre of foot pressure displacements were recorded using a force platform. Results showed that (1) the Fatigue condition yielded increased CoP displacements relative to the No Fatigue condition (Experiment 1 and Experiment 2), (2) this destabilizing effect was more accentuated in the Head tilted backward posture than Neutral head posture (Experiment 1) and (3) this destabilizing effect was less accentuated in the condition of Tactile stimulation than that of No tactile stimulation of the neck (Experiment 2). In the context of the multisensory control of balance, these results suggest an increased reliance on vestibular and neck somatosensory information for controlling posture during quiet standing in condition of altered ankle neuromuscular function

Cecal obstruction due to primary intestinal tuberculosis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Primary intestinal tuberculosis is a rare variant of tuberculosis. The preferred treatment is usually pharmaceutical, but surgery may be required for complicated cases.</p> <p>Case presentation</p> <p>We report two cases of primary intestinal tuberculosis where the initial diagnosis was wrong, with colonic cancer suggested in the first case and a Crohn's disease complication in the second. Both of our patients were Caucasians of Greek nationality. In the first case (a 60-year-old man), a right hemicolectomy was performed. In the second case (a 26-year-old man), excision was impossible due to the local conditions and peritoneal implantations. Histopathology revealed an inflammatory mass of tuberculous origin in the first case. In the second, cell culture and polymerase chain reaction tests revealed <it>Mycobacterium tuberculosis</it>. Both patients were given anti-tuberculosis therapy and their post-operative follow-up was uneventful.</p> <p>Conclusions</p> <p>Gastrointestinal tuberculosis still appears sporadically and should be considered in the differential diagnosis along with other conditions of the bowel. The use of immunosuppressants and new pharmaceutical agents can change the prevalence of tuberculosis.</p

Patterns of population differentiation of candidate genes for cardiovascular disease

<p>Abstract</p> <p>Background</p> <p>The basis for ethnic differences in cardiovascular disease (CVD) susceptibility is not fully understood. We investigated patterns of population differentiation (<it>F</it>_<it>ST</it>) of a set of genes in etiologic pathways of CVD among 3 ethnic groups: Yoruba in Nigeria (YRI), Utah residents with European ancestry (CEU), and Han Chinese (CHB) + Japanese (JPT). We identified 37 pathways implicated in CVD based on the PANTHER classification and 416 genes in these pathways were further studied; these genes belonged to 6 biological processes (apoptosis, blood circulation and gas exchange, blood clotting, homeostasis, immune response, and lipoprotein metabolism). Genotype data were obtained from the HapMap database.</p> <p>Results</p> <p>We calculated <it>F</it>_{<it>ST </it>}for 15,559 common SNPs (minor allele frequency ≥ 0.10 in at least one population) in genes that co-segregated among the populations, as well as an average-weighted <it>F</it>_{<it>ST </it>}for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions) or non-functional (intronic and synonymous sites). Mean <it>F</it>_{<it>ST </it>}values for common putatively functional variants were significantly higher than <it>F</it>_{<it>ST </it>}values for nonfunctional variants. A significant variation in <it>F</it>_{<it>ST </it>}was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high <it>F</it>_<it>ST</it>. Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of <it>F</it>_{<it>ST </it>}values was noted among pairwise population comparisons for different biological processes.</p> <p>Conclusion</p> <p>These results suggest a possible basis for varying susceptibility to CVD among ethnic groups.</p

Correction of Population Stratification in Large Multi-Ethnic Association Studies

The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification.We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification.Our results highlight the importance of carefully addressing population stratification and of carefully “cleaning” the sample prior to analyses to obtain stronger signals of association and to avoid spurious results

Folate Decorated Dual Drug Loaded Nanoparticle: Role of Curcumin in Enhancing Therapeutic Potential of Nutlin-3a by Reversing Multidrug Resistance

Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

<p>Abstract</p> <p>Background</p> <p>We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants.</p> <p>Methods</p> <p>From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at <it>P </it>< 5 × 10^-8. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, <it>F</it>_ST, was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas.</p> <p>Results</p> <p>Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global <it>F</it>_ST(0.1042) for 158 SNPs among the populations was not significantly higher than the mean global <it>F</it>_STof 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global <it>F</it>_ST(<it>P </it>< 0.05) was noted in eight SNPs, based on an empirical distribution of global <it>F</it>_STof 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score.</p> <p>Conclusion</p> <p>Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.</p