Sodium bicarbonate and high-intensity-cycling capacity: variability in responses

Purpose: The aim of this study was to determine whether gastrointestinal (GI) distress affects the ergogenicity of sodium bicarbonate and whether the degree of alkalaemia or other metabolic responses are different between individuals who improve exercise capacity and those who do not. Methods: Twenty-one males completed two cycling capacity tests at 110% of maximum power output. Participants were supplemented with 0.3 g∙kg-1BM of either placebo (maltodextrin) or sodium bicarbonate (SB). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, immediately post-exercise and 5 minutes post-exercise. Results: SB supplementation did not significantly increase total work done (TWD) (P = 0.16, 46.8 ± 9.1 vs. 45.6 ± 8.4 kJ, d = 0.14), although magnitude based inferences suggested a 63% likelihood of a positive effect. When data were analysed without four participants who experienced GI discomfort, TWD (P = 0.01) was significantly improved with SB. Immediately post-exercise blood lactate was higher in SB for the individuals who improved but not for those who didn’t. There were also differences in the pre to post-exercise change in blood pH, bicarbonate and base excess between individuals who improved and individuals who did not. Conclusions: SB improved high intensity cycling capacity, but only with the exclusion of participants experiencing GI discomfort. Differences in blood responses suggest that sodium bicarbonate may not be beneficial to all individuals. Magnitude based inferences suggested that the exercise effects are unlikely to be negative; therefore individuals should determine whether they respond well to sodium bicarbonate supplementation prior to competition

Characterization of the Poly-T Variant in the TOMM40 Gene in Diverse Populations

We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimer's disease and with cognitive performance in elderly. Three allele groups were defined for rs10524523, hereafter ‘523’, based on the number of ‘T’-residues: ‘Short’ (S, T≤19), ‘Long’ (L, 20≤T≤29) and ‘Very Long’ (VL, T≥30). Homopolymers, particularly long homopolymers like ‘523’, are difficult to genotype because ‘slippage’ occurs during PCR-amplification. We initially genotyped this locus by PCR-amplification followed by Sanger-sequencing. However, we recognized the need to develop a higher-throughput genotyping method that is also accurate and reliable. Here we describe a new ‘523’ genotyping assay that is simple and inexpensive to perform in a standard molecular genetics laboratory. The assay is based on the detection of differences in PCR-fragment length using capillary electrophoresis. We discuss technical problems, solutions, and the steps taken for validation. We employed the novel assay to investigate the ‘523’ allele frequencies in different ethnicities. Whites and Hispanics have similar frequencies of S/L/VL alleles (0.45/0.11/0.44 and 0.43/0.09/0.48, respectively). In African-Americans, the frequency of the L-allele (0.10) is similar to Whites and Hispanics; however, the S-allele is more prevalent (0.65) and the VL-allele is concomitantly less frequent (0.25). The allele frequencies determined using the new methodology are compared to previous reports for Ghanaian, Japanese, Korean and Han Chinese cohorts. Finally, we studied the linkage pattern between TOMM40-‘523’ and APOE alleles. In Whites and Hispanics, consistent with previous reports, the L is primarily linked to ε4, while the majority of the VL and S are linked to ε3. Interestingly, in African-Americans, Ghanaians and Japanese, there is an increased frequency of the ‘523’S-APOEε4 haplotype. These data may be used as references for ‘523’ allele and ‘523’-APOE haplotype frequencies in diverse populations for the design of research studies and clinical trials

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Prion protein interaction with soil humic substances: environmental implications

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders caused by prions. Animal TSE include scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids. Effective management of scrapie in many parts of the world, and of CWD in North American deer population is complicated by the persistence of prions in the environment. After shedding from diseased animals, prions persist in soil, withstanding biotic and abiotic degradation. As soil is a complex, multi-component system of both mineral and organic components, it is important to understand which soil compounds may interact with prions and thus contribute to disease transmission. Several studies have investigated the role of different soil minerals in prion adsorption and infectivity; we focused our attention on the interaction of soil organic components, the humic substances (HS), with recombinant prion protein (recPrP) material. We evaluated the kinetics of recPrP adsorption, providing a structural and biochemical characterization of chemical adducts using different experimental approaches. Here we show that HS act as potent anti-prion agents in prion infected neuronal cells and in the amyloid seeding assays: HS adsorb both recPrP and prions, thus sequestering them from the prion replication process. We interpreted our findings as highly relevant from an environmental point of view, as the adsorption of prions in HS may affect their availability and consequently hinder the environmental transmission of prion diseases in ruminants

A computational-based update on microRNAs and their targets in barley (Hordeum vulgare L.)

<p>Abstract</p> <p>Background</p> <p>Many plant species have been investigated in the last years for the identification and characterization of the corresponding miRNAs, nevertheless extensive studies are not yet available on barley (at the time of this writing). To extend and to update information on miRNAs and their targets in barley and to identify candidate polymorphisms at miRNA target sites, the features of previously known plant miRNAs have been used to systematically search for barley miRNA homologues and targets in the publicly available ESTs database. Matching sequences have then been related to Unigene clusters on which most of this study was based.</p> <p>Results</p> <p>One hundred-fifty-six microRNA mature sequences belonging to 50 miRNA families have been found to significantly match at least one EST sequence in barley. As expected on the basis of phylogenetic relations, miRNAs putatively orthologous to those of <it>Triticum </it>are significantly over-represented inside the set of identified barley microRNA mature sequences. Many previously known and several putatively new miRNA/target pairs have been identified. When the predicted microRNA targets were grouped into functional categories, biological processes previously known to be regulated by miRNAs, such as development and response to biotic and abiotic stress, have been highlighted and most of the target molecular functions were related to transcription regulation. Candidate microRNA coding genes have been reported and genetic variation (SNPs/indels) both in functional regions of putative miRNAs (mature sequence) and at miRNA target sites has been found.</p> <p>Conclusions</p> <p>This study has provided an update of the information on barley miRNAs and their targets representing a foundation for future studies. Many of previously known plant microRNAs have homologues in barley with expected important roles during development, nutrient deprivation, biotic and abiotic stress response and other important physiological processes. Putative polymorphisms at miRNA target sites have been identified and they can represent an interesting source for the identification of functional genetic variability.</p

Consumer input into research: the Australian Cancer Trials website

<p>Abstract</p> <p>Background</p> <p>The Australian Cancer Trials website (ACTO) was publicly launched in 2010 to help people search for cancer clinical trials recruiting in Australia, provide information about clinical trials and assist with doctor-patient communication about trials. We describe consumer involvement in the design and development of ACTO and report our preliminary patient evaluation of the website.</p> <p>Methods</p> <p>Consumers, led by Cancer Voices NSW, provided the impetus to develop the website. Consumer representative groups were consulted by the research team during the design and development of ACTO which combines a search engine, trial details, general information about trial participation and question prompt lists. Website use was analysed. A patient evaluation questionnaire was completed at one hospital, one week after exposure to the website.</p> <p>Results</p> <p>ACTO's main features and content reflect consumer input. In February 2011, it covered 1, 042 cancer trials. Since ACTO's public launch in November 2010, until the end of February 2011, the website has had 2, 549 new visits and generated 17, 833 page views. In a sub-study of 47 patient users, 89% found the website helpful for learning about clinical trials and all respondents thought patients should have access to ACTO.</p> <p>Conclusions</p> <p>The development of ACTO is an example of consumers working with doctors, researchers and policy makers to improve the information available to people whose lives are affected by cancer and to help them participate in their treatment decisions, including consideration of clinical trial enrolment. Consumer input has ensured that the website is informative, targets consumer priorities and is user-friendly. ACTO serves as a model for other health conditions.</p

Scoliosis treatment using a combination of manipulative and rehabilitative therapy: a retrospective case series

BACKGROUND: The combination of spinal manipulation and various physiotherapeutic procedures used to correct the curvatures associated with scoliosis have been largely unsuccessful. Typically, the goals of these procedures are often to relax, strengthen, or stretch musculotendinous and/or ligamentous structures. In this study, we investigate the possible benefits of combining spinal manipulation, positional traction, and neuromuscular reeducation in the treatment of idiopathic scoliosis. METHODS: A total of 22 patient files were selected to participate in the protocol. Of these, 19 met the study criterion required for analysis of treatment benefits. Anteroposterior radiographs were taken of each subject prior to treatment intervention and 4–6 weeks following the intervention. A Cobb angle was drawn and analyzed on each radiograph, so pre and post comparisons could be made. RESULTS: After 4–6 weeks of treatment, the treatment group averaged a 17° reduction in their Cobb angle measurements. None of the patients' Cobb angles increased. A total of 3 subjects were dismissed from the study for noncompliance relating to home care instructions, leaving 19 subjects to be evaluated post-intervention. CONCLUSIONS: The combined use of spinal manipulation and postural therapy appeared to significantly reduce the severity of the Cobb angle in all 19 subjects. These results warrant further testing of this protocol

Development of the lateral ventricular choroid plexus in a marsupial, Monodelphis domestica

<p>Abstract</p> <p>Background</p> <p>Choroid plexus epithelial cells are the site of blood/cerebrospinal fluid (CSF) barrier and regulate molecular transfer between the two compartments. Their mitotic activity in the adult is low. During development, the pattern of growth and timing of acquisition of functional properties of plexus epithelium are not known.</p> <p>Methods</p> <p>Numbers and size of choroid plexus epithelial cells and their nuclei were counted and measured in the lateral ventricular plexus from the first day of its appearance until adulthood. Newborn <it>Monodelphis </it>pups were injected with 5-bromo-2-deoxyuridine (BrdU) at postnatal day 3 (P3), P4 and P5. Additional animals were injected at P63, P64 and P65. BrdU-immunopositive nuclei were counted and their position mapped in the plexus structure at different ages after injections. Double-labelling immunocytochemistry with antibodies to plasma protein identified post-mitotic cells involved in protein transfer.</p> <p>Results</p> <p>Numbers of choroid plexus epithelial cells increased 10-fold between the time of birth and adulthood. In newborn pups each consecutive injection of BrdU labelled 20-40 of epithelial cells counted. After 3 injections, numbers of BrdU positive cells remained constant for at least 2 months. BrdU injections at an older age (P63, P64, P65) resulted in a smaller number of labelled plexus cells. Numbers of plexus cells immunopositive for both BrdU and plasma protein increased with age indicating that protein transferring properties are acquired post mitotically. Labelled nuclei were only detected on the dorsal arm of the plexus as it grows from the neuroependyma, moving along the structure in a 'conveyor belt' like fashion.</p> <p>Conclusions</p> <p>The present study established that lateral ventricular choroid plexus epithelial cells are born on the dorsal side of the structure only. Cells born in the first few days after choroid plexus differentiation from the neuroependyma remain present even two months later. Protein-transferring properties are acquired post-mitotically and relatively early in plexus development.</p

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65–69 year old community sample

<p>Abstract</p> <p>Background</p> <p>While the evidence of an association between the apolipoprotein E (<it>APOE</it>) <it>*E4 </it>allele and Alzheimer's disease is very strong, the effect of the <it>*E4 </it>allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the <it>*E4 </it>allele <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> failed to find any effect of the <it>*E4 </it>allele on cognitive performance at ages 20–24, 40–44 or 60–64 years.</p> <p>Methods</p> <p>In this four year follow-up study, we reexamine the effect of <it>*E4 </it>in the sample of 2,021 individuals, now aged 65–69 years.</p> <p>Results</p> <p>Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for <it>*E4 </it>homozygotes than heterozygotes or non-carriers. The effects of the <it>*E4 </it>genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change.</p> <p>Conclusion</p> <p>It is possible that <it>*E4 </it>carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65–69 years of age.</p