Changes in left atrial deformation in hypertrophic cardiomyopathy: Evaluation by vector velocity imaging.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic process affecting both ventricular and atrial myocardium. We assessed the global and regional left atrial (LA) function and its relation to left ventricular (LV) mechanics and clinical status in patients with HCM using Vector Velocity Imaging (VVI). METHODS: VVI of the LA and LV was acquired from apical four- and two-chamber views of 108 HCM patients (age 40 ± 19years, 56.5% men) and 33 healthy subjects, all had normal LV systolic function. The LA subendocardium was traced to obtain atrial volumes, ejection fraction, velocities, and strain (ϵ)/strain rate (SR) measurements. RESULTS: Left atrial reservoir (ϵsys,SRsys) and conduit (early diastolic SRe) function were significantly reduced in HCM compared to controls (P  - 1.8s(- 1) was 81% sensitive and 30% specific, SRa> - 1.5s(- 1) was 73% sensitive and 40% specific. By multivariate analysis global LVϵsys and LV septal thickness are independent predictors for LAϵsys, while end systolic diameter is the only independent predictor for SRsys, P < .001. CONCLUSION: Left atrial reservoir and conduit function as measured by VVI were significantly impaired while contractile function was preserved among HCM patients. Left atrial deformation was greatly influenced by LV mechanics and correlated to severity of phenotype

Foreign national prisoners in the UK: explanations and implications

This article examines the rapid expansion of the foreign national prison population in the UK against a backdrop of public and political anxiety about immigration and crime. It explores official data considering some of the possible explanations for the growth in the number of foreign national prisoners and the implications this has for penal management. Whilst increases in both the number of foreign nationals entering the UK and the number of foreign nationals in UK prisons has strengthened the association between immigration and crime in the public imagination, there is little empirical evidence to suggest that foreign nationals are more dangerous than British nationals. Instead, the growth of the foreign national prison population appears to stem from a number of sources that may operate alone or in tandem

Use of a Semi-field System to Evaluate the Efficacy of Topical Repellents under user Conditions Provides a Disease Exposure free Technique Comparable with Field Data.

Before topical repellents can be employed as interventions against arthropod bites, their efficacy must be established. Currently, laboratory or field tests, using human volunteers, are the main methods used for assessing the efficacy of topical repellents. However, laboratory tests are not representative of real life conditions under which repellents are used and field-testing potentially exposes human volunteers to disease. There is, therefore, a need to develop methods to test efficacy of repellents under real life conditions while minimizing volunteer exposure to disease. A lotion-based, 15% N, N-Diethyl-3-methylbenzamide (DEET) repellent and 15% DEET in ethanol were compared to a placebo lotion in a 200 sq m (10 m x 20 m) semi-field system (SFS) against laboratory-reared Anopheles arabiensis mosquitoes and in full field settings against wild malaria vectors and nuisance-biting mosquitoes. The average percentage protection against biting mosquitoes over four hours in the SFS and field setting was determined. A Poisson regression model was then used to determine relative risk of being bitten when wearing either of these repellents compared to the placebo. Average percentage protection of the lotion-based 15% DEET repellent after four hours of mosquito collection was 82.13% (95% CI 75.94-88.82) in the semi-field experiments and 85.10% (95% CI 78.97-91.70) in the field experiments. Average percentage protection of 15% DEET in ethanol after four hours was 71.29% (CI 61.77-82.28) in the semi-field system and 88.24% (84.45-92.20) in the field. Semi-field evaluation results were comparable to full-field evaluations, indicating that such systems could be satisfactorily used in measuring efficacy of topically applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with field testing

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember&#8482;, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

Nutrient Retention and Haematological Indices of Broiler Starters Fed Lablab Seed Meal as the Source of Protein

Studies were carried out to determine the effect of feeding diets containing lablab seed meal (LSM) to replace groundnut cake (GNC) or full fat soya (FFS) as the major source of protein on nutrient retention and haematological parameters of broilers at the starter phase. Apparent crude protein, crude fibre and ether extract retentions (%) were highest (P0.05) between those fed LSM and FFS diets, but significantly lower (

Effects of pollution on marine crustaceans in Qatari waters : a baseline survey and a case study on genotoxicity indicators in an endemic shrimp

In this thesis the baseline and seasonal variations of the trace metals (TM) (Arsenic (As), Cadmium (Cd), Cobalt (Co), Chromium (Cr), Copper (Cu), Iron (Fe), Manganese (Mn), Nickel (Ni), Lead (Pb), Vanadium (V) and Zinc (Zn). Methylmercury (CH3Hg), organotins (OT) and polychlorinated biphenyls (PCBs) concentrations were investigated within the tissue of three selected marine organisms together with sediment and water. The first round of sampling was carried out in September, November and December 2014. Samples were then collected in May and June 2015, and finally in July 2016. The species used for the research are all indigenous to Qatari waters and included Portunus pelagicus, the blue swimming crab, a commercially important edible species, Balanus Amphitrite, the striped barnacle, an invasive species that arrived in Qatar on the hulls of merchant ships, and now part of the local fauna. This species is often used as bio-indicator of coastal pollutants. The final selected species is the endemic caridean shrimp, Palaemon khori which inhabits the Avicenna marina mangrove forest at Al-Khor, Qatar. The order of the heavy metal concentrations for the three species was Zn > Cu > As > Fe > Mn > Pb > Cr > Cd > Co > Ni > V for P. pelagicus, Zn > Fe > Cu > As > Cd > Mn > Ni > Cr > V > Pb > Co for B. Amphitrite and Zn ˃ Cu > Fe ˃ Mn > Ni ˃ Pb > As > Cr > Cd > Co > V for P. khori. Methylmercury was measured in all of the three species averaging 1.25μg/kg throughout. The three organotin monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) were detected in all three species. TBT levels were observed at 0.58ngSng-1, 0.78ngSng-1 and 1.91ngSng-1 for P. segnis, B. Amphitrite and P. khori respectively. The results also revealed that concentrations of the contaminants within water samples were negligible, the majority being below detection limits. However, PCB congeners 2,2,3,5-Tetrachlorobiphenyl and 2,2,4,5,5-Pentachlorobiphenyl were detected in the tissue of P. pelagicus averaging 1.70 μg/kg for the former and 4.56 μg/kg for the latter. Results from the tissue of P. khori ranged from 1.5μg/kg - 2μg/kg and 4.28μg/kg – 5.21μg/kg respectively. Seasonal variation studies showed fluctuating degrees of variability among pollutants depending on the target species and the pollutant. The results showed an increase in some pollutant concentrations from the winter months through to the summer, while subsequently other pollutants revealed a decrease in concentrations. The direct effect of varying levels and combinations of pollutants (the maximum concentrations of trace metals, OT and MeHg found in the environment according to the literature, and a tenfold increase in those concentrations in an individual setting and in a combined setting) under laboratory controlled conditions on the endemic P. khori was assessed using classical (mortality) and genotoxicological (aneuploidy) endpoints, after 4 and 8 weeks of exposure. Our results showed that with regards to mortality on average the highest mortality was observed in shrimps exposed to TM at x10 of the maximum environmentally observed levels or TM in combination with other pollutants. The pollutant inducing the highest aneuploidy levels were trace metals and CH3Hg in combination with OT (both at x10 concentration). The data presented in this study represents the first ever estimated baseline for seasonal variations of contaminants, in both the marine environment and associated animal tissues from the coastal waters of Qatar. The data obtained from the genotoxic investigations are a fundamental part in establishing the first ever record for the karyotype of P. khori, while also providing a genotoxicological overview of the effect of these pollutants on the species at a genetic level

Comparison of Yarrowia lipolytica and Pichia pastoris cellular response to different agents of oxidative stress

Yeast cells exposed to adverse conditions employ a number of defense mechanisms in order to respond effectively to the stress effects of reactive oxygen species. In this work, the cellular response of Yarrowia lipolytica and Pichia pastoris to the exposure to the ROSinducing agents’ paraquat, hydrogen peroxide, and increased air pressure was analyzed. Yeast cells at exponential phase were exposed for 3 h to 1 mM paraquat, to 50 mM H2O2, or to increased air pressure of 3 or 5 bar. For both strains, the cellular viability loss and lipid peroxidation was lower for the cells exposed to increased air pressure than for those exposed to chemical oxidants. The glutathione induction occurred only in Y. lipolytica strain and reached the highest level as a response to PQ exposure. In general, antioxidant enzymes were more expressed in Y. lipolytica than in P. pastoris. The enzyme superoxide dismutase was induced in both strains under all the oxidant conditions but was dependent on the cellular growth phase, being undetectable in non-growing cells, whereas glutathione reductase was more induced in those conditions. Hydrogen peroxide was the most efficient inducer of catalase. Both yeast cultures underwent no cellular growth inhibition with increased air pressure, indicating that these yeast species were able to adapt to the oxidative stressful environment.The authors acknowledge the financial support provided by "Fundacao para a Ciencia e Tecnologia" (Grant SFRH/BD/47371/2008)

A blood RNA signature for tuberculosis disease risk: a prospective cohort study.

BACKGROUND: Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. METHODS: In this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease. FINDINGS: Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2-68·9) and a specificity of 80·6% (79·2-82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6-64·3) and a specificity of 82·8% (76·7-86) in the 12 months preceding tuberculosis. INTERPRETATION: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. FUNDING: Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

Background Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO