Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat.

Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca(2+) cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced

OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection.

Pathogenic mycobacteria inhibit inflammasome activation to establish infection. Although it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux, and inflammasome activation has not been investigated. Here, we use Mycobacterium marinum infection of zebrafish embryos and Mycobacterium tuberculosis infection of THP-1 cells to demonstrate that pathogenic mycobacteria up-regulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance. We show that genetic depletion or inhibition of OXSR1 decreases bacterial burden and intracellular potassium levels. The protective effects of OXSR1 depletion are at least partially mediated by NLRP3 inflammasome activation, caspase-mediated release of IL-1β, and downstream activation of protective TNF-α. The elucidation of this druggable pathway to potentiate inflammasome activation provides a new avenue for the development of host-directed therapies against intracellular infections

The pharmaceutical death-ride of dihydroartemisinin

In the 2010 second edition of WHO's guidelines for the treatment of malaria, the relatively new fixed dose combination dihydroartemisinin-piperaquine is included as one of the recommended artemisinin combination therapies. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements. At a time when many efforts aim to ban counterfeit and substandard drugs from the malaria market, the obvious question rises how WHO and public-private partnerships, such as Medicine for Malaria venture (MMV), can support the production and marketing of anti-malarial drugs that do not even meet the International Pharmacopoeia requirements

Development of a life expectancy table for individuals with type 1 diabetes

Aims/hypothesis:Tables reporting life expectancies by common risk factors are available for individuals with type 2 diabetes; however, there is currently no published equivalent for individuals with type 1 diabetes. We aimed to develop a life expectancy table using a recently published simulation model for individuals with type 1 diabetes.Methods: The simulation model was developed using data from a real-world population of patients with type 1 diabetes selected from the Swedish National Diabetes Register. The following six important risk factors were included in the life table: sex; age; current smoking status; BMI; eGFR; and HbA1c. For each of 1024 cells in the life expectancy table, a synthetic cohort containing 1000 individuals was created, with other risk factors assigned values representative of the real-world population. The simulations were executed for all synthetic cohorts and life expectancy for each cell was calculated as mean survival time of the individuals in the respective cohort.Results: There was a substantial variation in life expectancy across patients with different risk factor levels. Life expectancy of 20-year-old men varied from 29.3 years to 50.6 years, constituting a gap of 21.3 years between those with worst and best risk factor levels. In 20-year-old women, this gap was 18.9 years (life expectancy range 35.0-53.9 years). The variation in life expectancy was a function of the combination of risk factor values, with HbA1c and eGFR consistently showing a negative and positive correlation, respectively, with life expectancy at any level combination of other risk factors. Individuals with the lowest level (20 kg/m2) and highest level of BMI (35 kg/m2) had a lower life expectancy compared with those with a BMI of 25 kg/m2. Non-smokers and women had a higher life expectancy than smokers and men, respectively, with the difference in life expectancy ranging from 0.4 years to 2.7 years between non-smokers and smokers, and from 1.9 years to 5.9 years between women and men, depending on levels of other risk factors.Conclusions/interpretation: The life expectancy table generated in this study shows a substantial variation in life expectancy across individuals with different modifiable risk factors. The table allows for rapid communications of risk in an easily understood format between healthcare professionals, health economists, researchers, policy makers and patients. Particularly, it supports clinicians in their discussion with patients about the benefits of improving risk factors

Development and use of prediction models for classification of cardiovascular risk of remote indigenous Australians

Background: Cardiovascular disease (CVD) is the leading cause of death for Indigenous Australians. There is widespread belief that current tools have deficiencies for assessing CVD risk in this high-risk population. We sought to develop a 5-year CVD risk score using a wide range of known risk factors to further improve CVD risk prediction in this population.Methods: We used clinical and demographic information on Indigenous people aged between 30 and 74 years without a history of CVD events who participated in the Well Person's Health Check (WPHC), a community-based survey. Baseline assessments were conducted between 1998 and 2000, and data were linked to administrative hospitalisation and death records for identification of CVD events. We used Cox proportional hazard models to estimate the 5-year CVD risk, and the Harrell's c-statistic and the modified Hosmer-Lemeshow (mH-L) χ2 statistic to assess the model discrimination and calibration, respectively.Results: The study sample consisted of 1,583 individuals (48.1% male; mean age 45.0 year). The risk score consisted of sex, age, systolic blood pressure, diabetes mellitus, waist circumference, triglycerides, and albumin creatinine ratio. The bias-corrected c-statistic was 0.72 and the bias-corrected mH-L χ2 statistic was 12.01 (p-value, 0.212), indicating good discrimination and calibration, respectively. Using our risk score, the CVD risk of the Indigenous Australians could be stratified to a greater degree compared to a recalibrated Framingham risk score.Conclusions: A seven-factor risk score could satisfactorily stratify 5-year risk of CVD in an Indigenous Australian cohort. These findings inform future research targeting CVD risk in Indigenous Australians

Location of chlorogenic acid biosynthesis pathway and polyphenol oxidase genes in a new interspecific anchored linkage map of eggplant

© Gramazio et al.; licensee BioMed Central. 2014. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Quality of life among people living with hypertension in a rural Vietnam community

Background - To respond to growing prevalence of hypertension in Vietnam, it is critical to have an in-depth understanding about quality of life (QOL) among people living with hypertension and related factors. This study aimed to measure QOL among hypertensive people in a rural community in Vietnam, and its association with socio-demographic characteristics and factors related to treatment. Methods - This study was conducted in a rural community located 60 km from Ho Chi Minh City. Face-to-face interviews were conducted among 275 hypertensive people aged 50 years and above using WHOQOL-BREF questionnaire. Descriptive statistics were used to examine mean scores of quality of life. Cronbach’s alpha coefficient and Pearson’s correlation coefficient were applied to estimate the internal consistency, and the level of agreement between different domains of WHOQOL-BREF, respectively. Independent T-test and ANOVA test followed by multiple linear regression analyses were used to measure the association between QOL domains and independent variables. Results - Both overall WHOQOL-BREF and each domain had a good internal consistency, ranging from 0.65 to 0.88. The QOL among hypertensive patients was found moderate in all domains, except for psychological domain that was fairly low (mean = 49.4). Backward multiple linear regressions revealed that being men, married, attainment of higher education, having physical activities at moderate level, and adherence to treatment were positively associated with QOL. However, older age and presence of co-morbidity were negatively associated with QOL. Conclusion - WHOQOL-BREF is a reliable instrument to measure QOL among hypertensive patients. The results revealed low QOL in psychological domain and inequality in QOL across socio-demographic characteristics. Given the results, encouraging physical activities and strengthening treatment adherence should be considered to improve QOL of hypertensive people, especially for psychological aspect. Actions to improve QOL among hypertensive patients targeted towards women, lower educated and unmarried patients are needed in the setting

Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic

Proteomic identification of immunodiagnostic antigens for <i>Trypanosoma vivax </i>infections in cattle and generation of a proof-of-concept lateral flow test diagnostic device

Trypanosoma vivax is one of the causative agents of Animal African Trypanosomosis in cattle, which is endemic in sub-Saharan Africa and transmitted primarily by the bite of the tsetse fly vector. The parasite can also be mechanically transmitted, and this has allowed its spread to South America. Diagnostics are limited for this parasite and in farm settings diagnosis is mainly symptom-based. We set out to identify, using a proteomic approach, candidate diagnostic antigens to develop into an easy to use pen-side lateral flow test device. Two related members the invariant surface glycoprotein family, TvY486_0045500 and TvY486_0019690, were selected. Segments of these antigens, lacking N-terminal signal peptides and C-terminal transmembrane domains, were expressed in E. coli. Both were developed into ELISA tests and one of them, TvY486_0045500, was developed into a lateral flow test prototype. The tests were all evaluated blind with 113 randomised serum samples, taken from 37 calves before and after infection with T. vivax or T. congolense. The TvY486_0045500 and TvY486_0019690 ELISA tests gave identical sensitivity and specificity values for T. vivax infection of 94.5% (95% CI, 86.5% to 98.5%) and 88.0% (95% CI, 75.7% to 95.5%), respectively, and the TvY486_0045500 lateral flow test prototype a sensitivity and specificity of 92.0% (95% CI, 83.4% to 97.0%) and 89.8% (95% CI, 77.8% to 96.6%), respectively. These data suggest that recombinant TvY486_0045500 shows promise for the development of a pen-side lateral flow test for the diagnosis of T. vivax animal African trypanosomosis