Effect of Sensory Feedback from the Proximal Upper Limb on Voluntary Isometric Finger Flexion and Extension in Hemiparetic Stroke Subjects

This study investigated the potential influence of proximal sensory feedback on voluntary distal motor activity in the paretic upper limb of hemiparetic stroke survivors and the potential effect of voluntary distal motor activity on proximal muscle activity. Ten stroke subjects and 10 neurologically intact control subjects performed maximum voluntary isometric flexion and extension, respectively, at the metacarpophalangeal (MCP) joints of the fingers in two static arm postures and under three conditions of electrical stimulation of the arm. The tasks were quantified in terms of maximum MCP torque [MCP flexion (MCPflex) or MCP extension (MCPext)] and activity of targeted (flexor digitorum superficialis or extensor digitorum communis) and nontargeted upper limb muscles. From a previous study on the MCP stretch reflex poststroke, we expected stroke subjects to exhibit a modulation of voluntary MCP torque production by arm posture and electrical stimulation and increased nontargeted muscle activity. Posture 1 (flexed elbow, neutral shoulder) led to greater MCPflex in stroke subjects than posture 2 (extended elbow, flexed shoulder). Electrical stimulation did not influence MCPflex or MCPext in either subject group. In stroke subjects, posture 1 led to greater nontargeted upper limb flexor activity during MCPflex and to greater elbow flexor and extensor activity during MCPext. Stroke subjects exhibited greater elbow flexor activity during MCPflex and greater elbow flexor and extensor activity during MCPext than control subjects. The results suggest that static arm posture can modulate voluntary distal motor activity and accompanying muscle activity in the paretic upper limb poststroke

Modulation of Stretch Reflexes of the Finger Flexors by Sensory Feedback from the Proximal Upper Limb Poststroke

Neural coupling of proximal and distal upper limb segments may have functional implications in the recovery of hemiparesis after stroke. The goal of the present study was to investigate whether the stretch reflex response magnitude of spastic finger flexor muscles poststroke is influenced by sensory input from the shoulder and the elbow and whether reflex coupling of muscles throughout the upper limb is altered in spastic stroke survivors. Through imposed extension of the metacarpophalangeal (MCP) joints, stretch of the relaxed finger flexors of the four fingers was imposed in 10 relaxed stroke subjects under different conditions of proximal sensory input, namely static arm posture (3 different shoulder/elbow postures) and electrical stimulation (surface stimulation of biceps brachii or triceps brachii, or none). Fast (300°/s) imposed stretch elicited stretch reflex flexion torque at the MCP joints and reflex electromyographic (EMG) activity in flexor digitorum superficialis. Both measures were greatest in an arm posture of 90° of elbow flexion and neutral shoulder position. Biceps stimulation resulted in greater MCP stretch reflex flexion torque. Fast imposed stretch also elicited reflex EMG activity in nonstretched heteronymous upper limb muscles, both proximal and distal. These results suggest that in the spastic hemiparetic upper limb poststroke, sensorimotor coupling of proximal and distal upper limb segments is involved in both the increased stretch reflex response of the finger flexors and an increased reflex coupling of heteronymous muscles. Both phenomena may be mediated through changes poststroke in the spinal reflex circuits and/or in the descending influence of supraspinal pathways

A Study of RO5217790 (HPV Targeted Immunotherapy) in Patients With High Grade Cervical Intraepithelial Neoplasia Associated With High Risk HPV Infection

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionThis is a randomized, double blind, placebo controlled, parallel group multicenter study in women with biopsy confirmed Grade 2 or Grade 3 cervical intraepithelial neoplasia (CIN). Two hundred patients will be enrolled and randomized in a 2: 1 ratio of RO5217790: placebo. They will be stratified on the basis of their HPV genotyping with stratum 1 consisting of those women with HPV 16 single infection and stratum 2 consisting of those with single or multiple infections with other high risk genotypes. Three injections of RO5217790 (5 x 107pfu) will be administered subcutaneously, each one week apart. Interim colposcopy, cytology and HPV assessments will be performed at Month 3. All patients will undergo conization at Month 6. The primary endpoint is histologic response at Month 6 in HPV 16 single infected patients, as assessed by central pathology review. The secondary endpoints include histologic response in all CIN2/3 patients enrolled regardless of genotype, viral clearance, safety, and immune response (cellular and humoral). After the Month 6 conization, the study will be unblinded and patients will undergo follow-up for an additional 2 years for efficacy and safety. This includes visits at Months 12, 18, 24 and 30 to assess histologic relapse/recurrence and viral re-infection as well as reporting of any serious adverse events. An interim analysis will be conducted when a minimum of 80 patients (at least 20 of whom have single infection with HPV 16 and 20 of whom have infection with HPV 16 plus HPV 16 related genotypes) have undergone conization. NCT0102234

Tuberculosis and Hepatic Steatosis Are Prevalent Liver Pathology Findings among HIV-Infected Patients in South Africa

Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.\ud \u

Analysis of Five Field Event Performances at the Drake Relays by Age and Gender, 1978-2008

Advisor: David S. SenchinaWe analyzed gender and age differences in Drake Relays performance distances for 2 jumping (long jump and triplejump) and 3 throwing (discus, javelin, shotput) field events for 31 years (1978-2008). The top 10 performances were taken each year for 4 groups: high school (HS) boys, HS girls, college/university (C/U) men, C/U women. Our data set included 4403 performances total, because not all ages/genders competed in all events or for the same number of years. Generally, females significantly improved their jumping or throwing distances whereas males showed no improvements or significantly declined in performance. HS girls showed statistically significant improvements in all 3 of their events (discus, shotput, long jump), and C/U women showed improvements in 4 of their 5 events (discus, javelin, shotput, triplejump) and demonstrated no change in long jump performance. In comparison, HS boys showed no changes in 2 of their 3 events (discus and shotput) and significantly shorter distance in long jump, and C/U men demonstrated significantly shorter throwing or jumping distances in 4 of their 5 events (javelin, shotput, long jump, triplejump) and no change in discus. Despite the improvements in female performance distances, males threw or jumped further than females in all events for all years except for discus, where C/U women were out-throwing HS boys by 2008. As the Drake Relays includes athletes from across the country, these differences likely reflect national trends and are possibly explained by forces such as increased pressure for youth sport specialization, declining popularity of track-and-field, and Title IX.Drake University, College of Arts and Sciences, Department of Biology, Biochemistry, Cell and Molecular Biology ; College of Pharmacy and Health Science

A systematic review of vitamin D status in populations worldwide

Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2nmol/l), with 37·3% of the studies reporting mean values below 50nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D statu

Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags

Intense interest centers on the role of the human gut microbiome in health and disease, but optimal methods for analysis are still under development. Here we present a study of methods for surveying bacterial communities in human feces using 454/Roche pyrosequencing of 16S rRNA gene tags. We analyzed fecal samples from 10 individuals and compared methods for storage, DNA purification and sequence acquisition. To assess reproducibility, we compared samples one cm apart on a single stool specimen for each individual. To analyze storage methods, we compared 1) immediate freezing at -80°C, 2) storage on ice for 24 or 3) 48 hours. For DNA purification methods, we tested three commercial kits and bead beating in hot phenol. Variations due to the different methodologies were compared to variation among individuals using two approaches--one based on presence-absence information for bacterial taxa (unweighted UniFrac) and the other taking into account their relative abundance (weighted UniFrac). In the unweighted analysis relatively little variation was associated with the different analytical procedures, and variation between individuals predominated. In the weighted analysis considerable variation was associated with the purification methods. Particularly notable was improved recovery of Firmicutes sequences using the hot phenol method. We also carried out surveys of the effects of different 454 sequencing methods (FLX versus Titanium) and amplification of different 16S rRNA variable gene segments. Based on our findings we present recommendations for protocols to collect, process and sequence bacterial 16S rDNA from fecal samples--some major points are 1) if feasible, bead-beating in hot phenol or use of the PSP kit improves recovery; 2) storage methods can be adjusted based on experimental convenience; 3) unweighted (presence-absence) comparisons are less affected by lysis method

Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant numbers 11/15682-4, 12/02270-2, 15/18121-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Regenera INCT Process Grant 465656/2014-5). JL is funded by the NIH/NIDDK R01DK106210. GDB is funded by the Wellcome Trust and the MRC Centre for Medical Mycology. Open access journalPeer reviewedPublisher PD

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder