Head Position in Stroke Trial (HeadPoST)- sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial

Background Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. Methods/Design We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. Discussion HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. Trial registration ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014

The effects of tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats - animal model for menopause

<p>Abstract</p> <p>Background</p> <p>Honey is a highly nutritional natural product that has been widely used in folk medicine for a number of therapeutic purposes. We evaluated whether Malaysian Tualang honey (AgroMas, Malaysia) was effective in reducing menopausal syndrome in ovariectomised female rats; an animal model for menopause.</p> <p>Methods</p> <p>The rats were divided into two control groups and three test groups. The control groups were sham-operated (SH) and ovariectomised (OVX) rats. The SH and OVX control rats were fed on 0.5 ml of distill water. The rats in the test groups were fed with low dose 0.2 g/kg (THL), medium dose, 1.0 g/kg (THM) and high dose 2.0 g/kg (THH) of Tualang honey in 0.5 ml of distill water. The administration was given by oral gavage once daily for 2 weeks. The reproductive organs (uterus and vagina), tibia bone and aorta were taken for histopathological examination while serum for hormonal assays.</p> <p>Results</p> <p>Administration of Tualang honey for 2 weeks to ovariectomised rats significantly increased the weight of the uterus and the thickness of vaginal epithelium, restored the morphology of the tibia bones and reduced the body weight compared to rats in the ovariectomised group. The levels of estradiol and progesterone, in honey treated groups were markedly lower than that in the OVX group. At low doses (0.2 g/kg; THL group) of Tualang honey there was an increased in serum free testosterone levels compared to OVX group (P < 0.01). Progesterone concentrations was significantly decreased in the OVX group as compared to SHAM group (P < 0.05).</p> <p>Conclusions</p> <p>Tualang honey was shown to have beneficial effects on menopausal (ovariectomised) rats by preventing uterine atrophy, increased bone density and suppression of increased body weight. Honey could be an alternative to HRT.</p

Genome-Wide Analysis of Copy Number Variation in Type 1 Diabetes

Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D

Pre-Clinical Evaluation of a Replication-Competent Recombinant Adenovirus Serotype 4 Vaccine Expressing Influenza H5 Hemagglutinin

Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis.The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus.Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine

Process account of curiosity and interest: a reward-learning perspective

Previous studies suggested roles for curiosity and interest in knowledge acquisition and exploration, but there has been a long-standing debate about how to define these concepts and whether they are related or different. In this paper, we address the definition issue by arguing that there is inherent difficulty in defining curiosity and interest, because both curiosity and interest are naïve concepts, which are not supposed to have a priori scientific definitions. We present a reward-learning framework of autonomous knowledge acquisition and use this framework to illustrate the importance of process account as an alternative to advance our understanding of curiosity and interest without being troubled by their definitions. The framework centers on the role of rewarding experience associated with knowledge acquisition and learning and posits that the acquisition of new knowledge strengthens the value of further information. Critically, we argue that curiosity and interest are the concepts that they subjectively construe through this knowledge-acquisition process. Finally, we discuss the implications of the reward-learning framework for education and empirical research in educational psychology

Assessing chemical mechanisms underlying the effects of sunflower pollen on a gut pathogen in bumble bees

Many pollinator species are declining due to a variety of interacting stressors including pathogens, sparking interest in understanding factors that could mitigate these outcomes. Diet can affect host-pathogen interactions by changing nutritional reserves or providing bioactive secondary chemicals. Recent work found that sunflower pollen (Helianthus annuus) dramatically reduced cell counts of the gut pathogen Crithidia bombi in bumble bee workers (Bombus impatiens), but the mechanism underlying this effect is unknown. Here we analyzed methanolic extracts of sunflower pollen by LC-MS and identified triscoumaroyl spermidines as the major secondary metabolite components, along with a flavonoid quercetin-3-O-hexoside and a quercetin-3-O-(6-O-malonyl)-hexoside. We then tested the effect of triscoumaroyl spermidine and rutin (as a proxy for quercetin glycosides) on Crithidia infection in B. impatiens, compared to buckwheat pollen (Fagopyrum esculentum) as a negative control and sunflower pollen as a positive control. In addition, we tested the effect of nine fatty acids from sunflower pollen individually and in combination using similar methods. Although sunflower pollen consistently reduced Crithidia relative to control pollen, none of the compounds we tested had significant effects. In addition, diet treatments did not affect mortality, or sucrose or pollen consumption. Thus, the mechanisms underlying the medicinal effect of sunflower are still unknown; future work could use bioactivity-guided fractionation to more efficiently target compounds of interest, and explore non-chemical mechanisms. Ultimately, identifying the mechanism underlying the effect of sunflower pollen on pathogens will open up new avenues for managing bee health

Characteristics of users and implications for the use of complementary and alternative medicine in Ghanaian cancer patients undergoing radiotherapy and chemotherapy: a cross- sectional study

<p>Abstract</p> <p>Background</p> <p>There is widespread use of Complementary and Alternative Medicine (CAM) in Ghana, driven by cultural consideration and paradigm to disease causation. Whether there is concurrent use of conventional medicine and CAM in cancer patients is unknown. This study investigates the prevalence, pattern and predictors of CAM use in cancer patients. Overlapping toxicity, sources of information, and whether users inform their doctor about CAM use is examined.</p> <p>Method</p> <p>Cross-sectional study using a questionnaire administered to cancer patients, who were receiving radiotherapy and or chemotherapy or had recently completed treatment at a single institution was used.</p> <p>Results</p> <p>Ninety eight patients participated in the study with a mean age of 55.5 (18–89), made up of 51% females. Married individuals formed 56% of the respondents, whilst 49% had either secondary or tertiary education. Head and neck cancer patients were 15.3%, breast (21.4%), abdomen/pelvic cancers constituted (52%).Seventy seven (78.6%) patients received radiotherapy only, 16.3% received radiation and chemotherapy and 5.3% had chemotherapy only.</p> <p>Ninety five patients were diagnosed of cancer within the past 24 months,73.5% were CAM users as follows; massage(66.3%), herbal(59.2%), mega vitamins(55.1%), Chinese medicine(53.1%),and prayer(42.9%). Sixty eight percent were treated with curative intent. Overlapping toxicity was reported. Majority (83.3%) of users had not informed their doctor about CAM use.</p> <p>On univariate analysis, female (p=0.004) and palliative patients, p=0.032 were more likely to be CAM users. Multivariate analysis identified female (p<0.01), as significant for use, whilst head and neck site was significant for non use (p<0.028). Young, married and highly educated individuals are more likely to use CAM.</p> <p>Friends and Media are the main sources of information on CAM. There was increase in CAM use after the diagnosis of cancer mainly for Chinese Medicine and vitamins.</p> <p>Conclusion</p> <p>There is high CAM usage among Cancer patients, comparable to use in the general population, there is concurrent use of CAM and conventional medicine with reported overlapping toxicity but without informing Oncologist about use. Women and palliative patients are more likely to use CAM. Doctor patient communication on herbal-radiotherapy and drug treatment interaction needs to be strengthened. Standardization and regulation of CAM use is paramount.</p

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

<div><p>Introduction</p><p>Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS.</p><p>Methods</p><p>Serum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.</p><p>Results</p><p>We did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results.</p><p>Conclusion</p><p>We found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.</p></div