Habitual physical activity and cardiometabolic risk factors in adults with cerebral palsy

2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/3.0/).This article has been made available through the Brunel Open Access Publishing Fund.Adults with cerebral palsy (CP) are known to participate in reduced levels of total physical activity. There is no information available however, regarding levels of moderate-to-vigorous physical activity (MVPA) in this population. Reduced participation in MVPA is associated with several cardiometabolic risk factors. The purpose of this study was firstly to compare levels of sedentary, light, MVPA and total activity in adults with CP to adults without CP. Secondly, the objective was to investigate the association between physical activity components, sedentary behavior and cardiometabolic risk factors in adults with CP. Adults with CP (n = 41) age 18–62 yr (mean ± SD = 36.5 ± 12.5 yr), classified in Gross Motor Function Classification System level I (n = 13), II (n = 18) and III (n = 10) participated in this study. Physical activity was measured by accelerometry in adults with CP and in age- and sex-matched adults without CP over 7 days. Anthropometric indicators of obesity, blood pressure and several biomarkers of cardiometabolic disease were also measured in adults with CP. Adults with CP spent less time in light, moderate, vigorous and total activity, and more time in sedentary activity than adults without CP (p < 0.01 for all). Moderate physical activity was associated with waist-height ratio when adjusted for age and sex (β = −0.314, p < 0.05). When further adjustment was made for total activity, moderate activity was associated with waist-height ratio (β = −0.538, p < 0.05), waist circumference (β = −0.518, p < 0.05), systolic blood pressure (β = −0.592, p < 0.05) and diastolic blood pressure (β = −0.636, p < 0.05). Sedentary activity was not associated with any risk factor. The findings provide evidence that relatively young adults with CP participate in reduced levels of MVPA and spend increased time in sedentary behavior, potentially increasing their risk of developing cardiometabolic disease

Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni

Schistosomes infect more than 200 million people. These parasitic flatworms rely on a syncytial outer coat called the tegument to survive within the vasculature of their host. Although the tegument is pivotal for their survival, little is known about maintenance of this tissue during the decades schistosomes survive in the bloodstream. Here, we demonstrate that the tegument relies on stem cells (neoblasts) to specify fusogenic progenitors that replace tegumental cells lost to turnover. Molecular characterization of neoblasts and tegumental progenitors led to the discovery of two flatworm-specific zinc finger proteins that are essential for tegumental cell specification. These proteins are homologous to a protein essential for neoblast-driven epidermal maintenance in free-living flatworms. Therefore, we speculate that related parasites (i.e., tapeworms and flukes) employ similar strategies to control tegumental maintenance. Since parasitic flatworms infect every vertebrate species, understanding neoblast-driven tegumental maintenance could identify broad-spectrum therapeutics to fight diseases caused by these parasites

Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland

Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression

Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice

Allograft transplantation requires chronic immunosuppression, but there is no effective strategy to evaluate the long-term maintenance of immunosuppression other than assessment of graft function. The ability to monitor naive alloreactive T cells would provide an alternative guide for drug therapy at early, preclinical stages of graft rejection and for evaluating tolerance-inducing protocols. To detect and quantify naive alloreactive T cells directly ex vivo, we used the unique ability of naive T cells to rapidly produce TNF-alpha but not IFN-gamma. Naive alloreactive T cells were identified by the production of TNF-alpha after a 5-hour in vitro stimulation with alloantigen and were distinguished from effector/memory alloreactive T cells by the inability to produce IFN-gamma. Moreover, naive alloreactive T cells were not detected in mice tolerized against specific alloantigens. The frequency of TNF-alpha-producing cells was predictive for rejection in an in vivo cytotoxicity assay and correlated with skin allograft rejection. Naive alloreactive T cells were also detected in humans, suggesting clinical relevance. We conclude that rapid production of TNF-alpha can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection

Comparative Proteomic Analyses of the Parietal Lobe from Rhesus Monkeys Fed a High-Fat/Sugar Diet With and Without Resveratrol Supplementation, Relative to a Healthy Diet: Insights Into the Roles of Unhealthy Diets and Resveratrol on Function

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. Our results contribute to a better understanding of the mechanisms by which resveratrol functions through the up- or down-regulation of proteins in different cellular sub-systems to affect the overall health of the brain

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

Epidemiology of subway-related fatalities in New York City, 1990-2003

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61349/1/gershon_epidemiology of subway fatalities_2008.pd

Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t

Genomic epidemiology and population structure of Neisseria gonorrhoeae from remote highly endemic Western Australian populations

Background: Neisseria gonorrhoeae causes gonorrhoea, the second most commonly notified sexually transmitted infection in Australia. One of the highest notification rates of gonorrhoea is found in the remote regions of Western Australia (WA). Unlike isolates from the major Australian population centres, the remote community isolates have low rates of antimicrobial resistance (AMR). Population structure and whole-genome comparison of 59 isolates from the Western Australian N. gonorrhoeae collection were used to investigate relatedness of isolates cultured in the metropolitan and remote areas. Core genome phylogeny, multilocus sequencing typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) in addition to hierarchical clustering of sequences were used to characterize the isolates. Results: Population structure analysis of the 59 isolates together with 72 isolates from an international collection, revealed six population groups suggesting that N. gonorrhoeae is a weakly clonal species. Two distinct population groups, Aus1 and Aus2, represented 63% of WA isolates and were mostly composed of the remote community isolates that carried no chromosomal AMR genotypes. In contrast, the Western Australian metropolitan isolates were frequently multi-drug resistant and belonged to population groups found in the international database, suggesting international transmission of the isolates. Conclusions: Our study suggests that the population structure of N. gonorrhoeae is distinct between the communities in remote and metropolitan WA. Given the high rate of AMR in metropolitan regions, ongoing surveillance is essential to ensure the enduring efficacy of the empiric gonorrhoea treatment in remote WA