Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection

RATIONALE: Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). Interpretation: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis

Dietary Conjugated Linoleic Acid and Hepatic Steatosis: Species-Specific Effects on Liver and Adipose Lipid Metabolism and Gene Expression

Objective. To summarize the recent studies on effect of conjugated linoleic acid (CLA) on hepatic steatosis and hepatic and adipose lipid metabolism highlighting the potential regulatory mechanisms. Methods. Sixty-four published experiments were summarized in which trans-10, cis-12 CLA was fed either alone or in combination with other CLA isomers to mice, rats, hamsters, and humans were compared. Summary and Conclusions. Dietary trans-10, cis-12 CLA induces a severe hepatic steatosis in mice with a more muted response in other species. Regardless of species, when hepatic steatosis was present, a concurrent decrease in body adiposity was observed, suggesting that hepatic lipid accumulation is a result of uptake of mobilized fatty acids (FA) from adipose tissue and the liver's inability to sufficiently increase FA oxidation and export of synthesized triglycerides. The potential role of liver FA composition, insulin secretion and sensitivity, adipokine, and inflammatory responses are discussed as potential mechanisms behind CLA-induced hepatic steatosis

SYNTHESIS AND IN-VITRO STUDY OF NOVEL (Z)-1-BENZHYDRYL-4-CINNAMYLPIPERAZINE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS

Objective: The objective of this study was to synthesize Z- 1-benzhydryl-4-cinnamylpiperazines by novel stereo selective synthetic method and evaluation of their anticancer properties.Methods: A series of novel (Z)-1-benzhydryl-4-cinnamylpiperazine derivatives (9a-j) were synthesized, starting from benzophenones in six steps. Wittig condensation of appropriate benzyltriphenyl phosphonium halides with various 1-benzhydryl- 4-(2-ethanal) piperazines (3a-j), and column purification over silica gel afforded pure Z- 1-benzhydryl-4-cinnamylpiperazines.Results: The structures of newly synthesized compounds 9a-j were established by 1H &amp; 13C NMR and mass spectral analysis. The anticancer potential (MTT assay) of synthesized compounds was tested against human cervical cancer (HeLa) and murine microglial (BV-2) cell lines. Results indicated that the most of the Z-derivatives exhibited moderate to good anticancer activity on both the cell lines over their E- antipodes.Conclusion: Compound 9i (cis- flunarizine) exhibited exceptionally superior activity against both HeLa and BV-2 cell lines with IC50 value of 13.23±3.51 µM and 23.1±4.12 µM respectively. Hence, this compound may be considered to be a potential lead molecule for further developmentÂ

Understanding Cerebellum Granular Layer Network Computations through Mathematical Reconstructions of Evoked Local Field Potentials

Background: The cerebellar granular layer input stage of cerebellum receives information from tactile and sensory re- gions of the body. The somatosensory activity in the cerebellar granular layer corresponds to sensory and tactile input has been observed by recording Local Field Potential (LFP) from the Crus-IIa regions of cerebellum in brain slices and in anesthetized animals. Purpose: In this paper, a detailed biophysical model of Wistar rat cerebellum granular layer net- work model and LFP modelling schemas were used to simulate circuit\u2019s evoked response. Methods: Point Source Ap- proximation and Line Source Approximation were used to reconstruct the network LFP. The LFP mechanism in in vitro was validated in network model and generated the in vivo LFP using the same mechanism. Results: The network simulations distinctly displayed the Trigeminal and Cortical (TC) wave components generated by 2 independent bursts implicating the generation of TC waves by 2 independent granule neuron populations. Induced plasticity was simulated to estimate granule neuron activation related population responses. As a prediction, cerebellar dysfunction (ataxia) was also studied using the model. Dysfunction at individual neurons in the network was affected by the population response. Conclusion: Our present study utilizes available knowledge on known mechanisms in a single cell and associates network function to population responses

Disease Control and Plant Growth Promotion of \u3cem\u3e Miscanthus \u3c/em\u3e × \u3cem\u3e giganteus \u3c/em\u3e with \u3cem\u3e Trichoderma \u3c/em\u3e Bio-Inoculants

The second-generation bioenergy crop Miscanthus (Miscanthus × giganteus) is being assessed in New Zealand for its potential to provide shelter on irrigated dairy farms. Miscanthus is a perennial sterile hybrid vegetatively propagated rhizomatous C4 grass and the young rhizomes and roots are prone to infection by soil-borne fungal pathogens (Glynn et al., 2015) which can cause deleterious effects on plant establishment and growth. In Europe, several species of Fusarium such as F. avenaceum, F. culmorum, F. moniliforme and F. oxysporum have been implicated as causal agents of root and rhizome rot (Thinggaard, 1997; Covarelli et al., 2012) leading to poor field establishment of in-vitro propagated Miscanthus plants. When tested for their ability to cause disease of Miscanthus, Rhizoctonia solani (Kuhn) was reported as the most aggressive species among nineteen fungal pathogens of cereal crops (Glynn et al. 2015). In New Zealand, R. solani reduces seedling emergence and plant establishment of several herbage species and the problem may be alleviated through biocontrol using Trichoderma fungi (Kandula et al., 2015). In a glass-house study, the effect of four T. atroviride isolates on growth of tissue culture propagated Miscanthus plants in a soil naturally infested with R. solani was investigated

Structural Evolution of Tungsten Surface Exposed to Sequential Low-Energy Helium Ion Irradiation and Transient Heat Loading

Structural damage due to high flux particle irradiation can result in significant changes to the thermal strength of the plasma facing component surface (PFC) during off-normal events in a tokamak. Low-energy He+ ion irradiation of tungsten (W), which is currently the leading candidate material for future PFCs, can result in the development of a fiber form nanostructure, known as “fuzz”. In the current study, mirror-finished W foils were exposed to 100 eV He+ ion irradiation at a fluence of 2.6 × 1024 ions m−2 and a temperature of 1200 K. Then, samples were exposed to two different types of pulsed heat loading meant to replicate type-I edge-localized mode (ELM) heating at varying energy densities and base temperatures. Millisecond (ms) laser exposure done at 1200 K revealed a reduction in fuzz density with increasing energy density due to the conglomeration and local melting of W fibers. At higher energy densities (∼ 1.5 MJ m−2), RT exposures resulted in surface cracking, while 1200 K exposures resulted in surface roughening, demonstrating the role of base temperature on the crack formation in W. Electron beam heating presented similar trends in surface morphology evolution; a higher penetration depth led to reduced melt motion and plasticity. In situ mass loss measurements obtained via a quartz crystal microbalance (QCM) found an exponential increase in particle emission for RT exposures, while the prevalence of melting from 1200 K exposures yielded no observable trend

Xanthine oxidase-derived reactive oxygen metabolites contribute to liver necrosis: protection by 4-hydroxypyrazolo[3,4-d]pyrimidine

AbstractXanthine oxidase (XO) generates reactive oxygen metabolites (ROM) as a by-product while catalyzing their reaction. The present study implicates these ROM in the pathogenesis of liver necrosis produced in rats by the intraperitoneal administration of thioacetamide (TAA; 400 mg/kg b.wt.). After 16 h of TAA administration, the activity of rat liver XO increased significantly compared to that of the control group. At the same time, the level of serum marker enzymes of liver necrosis (aminotransferases and alkaline phosphatase) and tissue malondialdehyde content also increased in TAA treated rats. Tissue malondialdehyde concentration is an indicator of lipid peroxidation and acts as a useful marker of oxidative damage. Pretreatment of rats with XO inhibitor (4-hydroxypyrazolo[3,4-d]pyrimidine; allopurinol (AP)) followed by TAA could lower the hepatotoxin-mediated rise in malondialdehyde level as well as the level of marker enzymes associated with liver necrosis. The survival rate also increased in rats given AP followed by the lethal dose of TAA. In either case, the effect of AP was dose-dependent. Results presented in the paper indicate that increased production of XO-derived ROM contributes to liver necrosis, which can be protected by AP

The EXERRT Trial: EXErcise to Regadenoson in Recovery Trial : a Phase 3b, Open-label, Parallel Group, Randomized, Multicenter Study to Assess Regadenoson Administration Following an Inadequate Exercise Stress Test as Compared to Regadenoson Without Exercise for Myocardial Perfusion Imaging Using a SPECT Protocol

BACKGROUND: This study assessed the non-inferiority and safety of regadenoson administration during recovery from inadequate exercise compared with administration without exercise. METHODS: Patients unable to achieve adequate exercise stress were randomized to regadenoson 0.4 mg either during recovery (Ex-Reg) or 1 hour after inadequate exercise (Regadenoson) (MPI1). All patients also underwent non-exercise regadenoson MPI 1-14 days later (MPI2). The number of segments with reversible perfusion defects (RPDs) detected using single photon emission computerized tomography imaging was categorized. The primary analysis evaluated the majority agreement rate between Ex-Reg and Regadenoson groups. RESULTS: 1,147 patients were randomized. The lower bound of the 95% confidence interval of the difference in agreement rates (-6%) was above the -7.5% non-inferiority margin, demonstrating non-inferiority of Ex-Reg to Regadenoson. Adverse events were numerically less with Ex-Reg (MPI1). In the Ex-Reg group, one patient developed an acute coronary syndrome and another had a myocardial infarction following regadenoson after exercise. Upon review, both had electrocardiographic changes consistent with ischemia prior to regadenoson. CONCLUSIONS: Administering regadenoson during recovery from inadequate exercise results in comparable categorization of segments with RPDs and with careful monitoring appears to be well tolerated in patients without signs/symptoms of ischemia during exercise and recovery