Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese

Background: Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods: To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results: Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion: SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection. © 2014 Fox et al

Four Generations: SUSY and SUSY Breaking

We revisit four generations within the context of supersymmetry. We compute the perturbativity limits for the fourth generation Yukawa couplings and show that if the masses of the fourth generation lie within reasonable limits of their present experimental lower bounds, it is possible to have perturbativity only up to scales around 1000 TeV. Such low scales are ideally suited to incorporate gauge mediated supersymmetry breaking, where the mediation scale can be as low as 10-20 TeV. The minimal messenger model, however, is highly constrained. While lack of electroweak symmetry breaking rules out a large part of the parameter space, a small region exists, where the fourth generation stau is tachyonic. General gauge mediation with its broader set of boundary conditions is better suited to accommodate the fourth generation.Comment: 27 pages, 5 figure

Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM

<p>Abstract</p> <p>Background</p> <p>Hemophilia A represents the most common and severe inherited hemorrhagic disorder. It is caused by mutations in the F8 gene, which leads to a deficiency or dysfunctional factor VIII protein, an essential cofactor in the factor X activation complex.</p> <p>Methods</p> <p>We used long-distance polymerase chain reaction and denaturing high performance liquid chromatography for mutation scanning of the F8 gene. We designed the competitive multiplex PCR to identify the carrier with exonal deletions. In order to facilitate throughput and minimize the cost of mutation scanning, we also evaluated a new mutation scanning technique, high resolution melting analysis (HRM), as an alternative screening method.</p> <p>Results</p> <p>We presented the results of detailed screening of 122 Taiwanese families with hemophilia A and reported twenty-nine novel mutations. There was one family identified with whole exons deletion, and the carriers were successfully recognized by multiplex PCR. By HRM, the different melting curve patterns were easily identified in 25 out of 28 cases (89%) and 15 out of 15 (100%) carriers. The sensitivity was 93 % (40/43). The overall mutation detection rate of hemophilia A was 100% in this study.</p> <p>Conclusion</p> <p>We proposed a diagnostic strategy for hemophilia A genetic diagnosis. We consider HRM as a powerful screening tool that would provide us with a more cost-effective protocol for hemophilia A mutation identification.</p

The prevalence and correlates of physical inactivity among adults in Ho Chi Minh City

<p>Abstract</p> <p>Background</p> <p>Socioeconomic changes have led to profound changes in individuals' lifestyles, including the adoption of unhealthy food consumption patterns, prevalent tobacco use, alcohol abuse and physical inactivity, especially in large cities like Ho Chi Minh City (HCMC). The Stepwise Approach to Surveillance of Non-communicable Disease Risk Factors survey was conducted to identify physical activity patterns and factors associated with 'insufficient' levels of physical activity for health in adults in HCMC.</p> <p>Methods</p> <p>A cross-sectional survey was conducted in 2005 among 1906 adults aged 25–64 years using a probability proportional to size cluster sampling method to estimate the prevalence of non-communicable disease risk factors including physical inactivity. Data on socioeconomic status, health behaviours, and time spent in physical activity during work, commuting and leisure time were collected. Physical activity was measured using the validated Global Physical Activity Questionnaire (GPAQ). Responders were classified as 'sufficiently active' or 'insufficiently active' using the GPAQ protocol. Correlates of insufficient physical activity were identified using multivariable logistic regression.</p> <p>Results</p> <p>A high proportion of adults were physically inactive, with only 56.2% (95% CI = 52.1–60.4) aged 25–64 years in HCMC achieving the minimum recommendation of 'doing 30 minutes moderate-intensity physical activity for at least 5 days per week'. The main contributors to total physical activity among adults were from working and active commuting. Leisure-time physical activity represented a very small proportion (9.4%) of individuals' total activity level. Some differences in the pattern of physical activity between men and women were noted, with insufficient activity levels decreasing with age among women, but not among men. Physical inactivity was positively associated with high income (OR = 1.77, 95% CI = 1.05–2.97) and high household wealth index (OR = 1.86, 95% CI = 1.29–2.66) amongst men.</p> <p>Conclusion</p> <p>Public health policies and programs to preserve active commuting in HCMC and to promote time spent in recreational physical activity in both genders and across all age groups, but especially among young adults, will be critical in any comprehensive national plan to tackle inactivity. Clear and consistent national recommendations about how much physical activity Vietnamese people need for preventing and managing non-communicable diseases should also be part of this population-wide promotional effort.</p

Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines

Pertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedule was associated with a marked reduction in pertussis cases in the vaccinated cohort. However, due to the frequency of local and systemic adverse events after immunization with wPV, work on a less reactive vaccine was undertaken based on isolated B. pertussis components that induced protective immune responses with fewer local and systemic reactions. These component vaccines were termed acellular vaccines and contained one or more pertussis antigens, including pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN), and fimbrial proteins 2 (FIM2) and 3 (FIM3). Preparations containing up to five components were developed, and several efficacy trials clearly demonstrated that the aPVs were able to confer comparable short-term protection than the most effective wPVs with fewer local and systemic reactions. There has been a resurgence of pertussis observed in recent years. This paper reports the results of a Consensus Conference organized by the World Association for Infectious Disease and Immunological Disorders (WAidid) on June 22, 2018, in Perugia, Italy, with the goal of evaluating the most important reasons for the pertussis resurgence and the role of different aPVs in this resurgence

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma

10.1038/bjc.2011.333British Journal of Cancer1057945-952BJCA

An empirical analysis of the determinants of mobile instant messaging appropriation in university learning

Published ArticleResearch on technology adoption often profiles device usability (such as perceived usefulness) and user dispositions (such as perceived ease of use) as the prime determinants of effective technology adoption. Since any process of technology adoption cannot be conceived out of its situated contexts, this paper argues that any pre-occupation with technology acceptance from the perspective of device usability and user dispositions potentially negates enabling contexts that make successful adoption a reality. Contributing to contemporary debates on technology adoption, this study presents flexible mobile learning contexts comprising cost (device cost and communication cost), device capabilities (portability, collaborative capabilities), and learner traits (learner control) as antecedents that enable the sustainable uptake of emerging technologies. To explore the acceptance and capacity of mobile instant messaging systems to improve student performance, the study draws on these antecedents, develops a factor model and empirically tests it on tertiary students at a South African University of Technology. The study involved 223 national diploma and bachelor’s degree students and employed partial least squares for statistical analysis. Overall, the proposed model displayed a good fit with the data and rendered satisfactory explanatory power for students’ acceptance of mobile learning. Findings suggest that device portability, communication cost, collaborative capabilities of device and learner control are the main drivers of flexible learning in mobile environments. Flexible learning context facilitated by learner control was found to have a positive influence on attitude towards mobile learning and exhibited the highest path coefficient of the overall model. The study implication is that educators need to create varied learning opportunities that leverage learner control of learning in mobile learning systems to enhance flexible mobile learning. The study also confirmed the statistical significance of the original Technology Acceptance Model constructs

Decoding Face Information in Time, Frequency and Space from Direct Intracranial Recordings of the Human Brain

Faces are processed by a neural system with distributed anatomical components, but the roles of these components remain unclear. A dominant theory of face perception postulates independent representations of invariant aspects of faces (e.g., identity) in ventral temporal cortex including the fusiform gyrus, and changeable aspects of faces (e.g., emotion) in lateral temporal cortex including the superior temporal sulcus. Here we recorded neuronal activity directly from the cortical surface in 9 neurosurgical subjects undergoing epilepsy monitoring while they viewed static and dynamic facial expressions. Applying novel decoding analyses to the power spectrogram of electrocorticograms (ECoG) from over 100 contacts in ventral and lateral temporal cortex, we found better representation of both invariant and changeable aspects of faces in ventral than lateral temporal cortex. Critical information for discriminating faces from geometric patterns was carried by power modulations between 50 to 150 Hz. For both static and dynamic face stimuli, we obtained a higher decoding performance in ventral than lateral temporal cortex. For discriminating fearful from happy expressions, critical information was carried by power modulation between 60–150 Hz and below 30 Hz, and again better decoded in ventral than lateral temporal cortex. Task-relevant attention improved decoding accuracy more than10% across a wide frequency range in ventral but not at all in lateral temporal cortex. Spatial searchlight decoding showed that decoding performance was highest around the middle fusiform gyrus. Finally, we found that the right hemisphere, in general, showed superior decoding to the left hemisphere. Taken together, our results challenge the dominant model for independent face representation of invariant and changeable aspects: information about both face attributes was better decoded from a single region in the middle fusiform gyrus

Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit through Trophic Support in Huntington's Disease Mouse Models

We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy