Mycobacterium avium bacteremia and dual infection with mycobacterium avium and Mycobacterium wolinskyi in the gut of an AIDS patient--first case report

An AIDS patient was admitted to a tertiary care hospital in central India with fever, weight loss, breathlessness, night sweats, diarrhoea, BMI 14 kg/m2, Hemoglobin 8 gm% and CD4 counts 120 cells/cumm. His blood culture by BACTEC 460 TB system revealed Mycobacterium avium bacteremia and stool culture grew Mycobacterium avium and mycobacterium wolinskyi.     

Future dryness in the southwest US and the hydrology of the early 21st century drought

Recently the Southwest has experienced a spate of dryness, which presents a challenge to the sustainability of current water use by human and natural systems in the region. In the Colorado River Basin, the early 21st century drought has been the most extreme in over a century of Colorado River flows, and might occur in any given century with probability of only 60%. However, hydrological model runs from downscaled Intergovernmental Panel on Climate Change Fourth Assessment climate change simulations suggest that the region is likely to become drier and experience more severe droughts than this. In the latter half of the 21st century the models produced considerably greater drought activity, particularly in the Colorado River Basin, as judged from soil moisture anomalies and other hydrological measures. As in the historical record, most of the simulated extreme droughts build up and persist over many years. Durations of depleted soil moisture over the historical record ranged from 4 to 10 years, but in the 21st century simulations, some of the dry events persisted for 12 years or more. Summers during the observed early 21st century drought were remarkably warm, a feature also evident in many simulated droughts of the 21st century. These severe future droughts are aggravated by enhanced, globally warmed temperatures that reduce spring snowpack and late spring and summer soil moisture. As the climate continues to warm and soil moisture deficits accumulate beyond historical levels, the model simulations suggest that sustaining water supplies in parts of the Southwest will be a challenge.     

Role of HSP27 and reduced glutathione in modulating malathion-induced apoptosis of human peripheral blood mononuclear cells: Ameliorating effect of N-acetylcysteine and curcumin

Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.     

Surface energy changes and their relationship with the dispersibility of salmeterol xinafoate powders for inhalation after storage at high RH

This study investigated the relationship between surface energy of micronized lactose, coarse lactose and salmeterol xinafoate and dispersibility from a mixture after storage at 75% RH. Surface energies, dispersibility, morphology, and the presence of amorphous domains were determined by inverse gas chromatography, twin stage impinger, scanning electron microscope and dynamic vapour sorption, respectively. The fine particle fraction of mixture decreased significantly in 4 weeks (P < 0.05), reaching a static level in 3 months. Amorphous content was not detected in the micronized lactose, coarse lactose and salmeterol xinafoate. After conditioning stored samples at 75% RH for 2 h, dispersive surface energy of both micronized and coarse lactose significantly decreased (P < 0.05), while the polar surface energy of all significantly increased (P < 0.05) resulting in significant increase in total surface energy after storage. After conditioning stored samples at 0% RH for 2 h, no significant difference was observed in any surface energy parameter. This study concluded that the total surface energy increased during storage at high RH due to the adhered surface moisture. The mechanism of decreased dispersibility was related to increased capillary/solid bridging interactions and to possible increased interaction of contiguous particles due to increased polar surface energy.     

Risk for Infection with Highly Pathogenic Avian Influenza Virus (H5N1) in Backyard Chickens, Bangladesh

To evaluate risk factors for infection with highly pathogenic avian influenza A virus (H5N1) in backyard chickens in Bangladesh, we conducted a matched case–control study. We enrolled 25 case farms (cases March–November 2007) and 75 control farms (June–November 2007). We used a questionnaire to collect farm data, which were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors independently associated were offering slaughter remnants of purchased chickens to backyard chickens (odds ratio [OR] 13.29, 95% confidence interval [CI] 1.34–131.98, p = 0.027), having a nearby water body (OR 5.27, 95% CI 1.24–22.34, p = 0.024), and having contact with pigeons (OR 4.47, 95% CI 1.14–17.50, p = 0.032). Separating chickens and ducks at night was protective (OR 0.06, 95% CI 0.01–0.45, p = 0.006). Reducing these risks and taking protective measures might reduce the risk for influenza (H5N1) infection in backyard chickens.     

Inequalities in maternity care and newborn outcomes: one-year surveillance of births in vulnerable slum communities in Mumbai

Background  

Aggregate urban health statistics mask inequalities. We described maternity care in vulnerable slum communities in Mumbai, and examined differences in care and outcomes between more and less deprived groups.     

A Forward Chemical Screen Using Zebrafish Embryos with Novel 2‐Substituted 2H‐Chromene Derivatives

We synthesized 2‐substituted 2H‐chromene derivatives from salicylaldehyde using potassium vinylic borates in the presence of secondary amines. Our goal was to generate novel compounds that might modulate transforming growth factor‐β signaling, based on limited rational design. Potassium vinyl trifluoroborates react with salicylaldehydes at 80 °C in the presence of a secondary amine and produce 2‐substituted 2H‐chromene derivatives with a 70–90% yield. A small library of these compounds, predicted to potentially interact with transforming growth factor‐β receptors, was screened for bioactivity in living zebrafish embryos. We found that the related compounds differentially affect development, and demonstrate one compound that produces severe body axis alterations in early embryogenesis and at lower doses affects specifically cardiovascular development. This compound modulates specifically a Smad‐independent transforming growth factor‐β‐regulated mitogen‐activated protein kinase pathway, namely p‐SAPK/JNK. These compounds, as suggested by our biological assays, may prove useful to manipulate developmental programs and develop therapeutic tools.     

Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection

The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in this setting. We compared the effector function of total circulating and intrahepatic CD8 T cells in CHB patients and healthy donors. We demonstrated that CD8 T cells from CHB patients, regardless of their antigen specificity, were impaired in their ability to produce interleukin-2 and proliferate upon TCR-dependent stimulation. In contrast, these CD8 T cells had preserved production of the proinflammatory cytokines interferon-γ and tumor necrosis factor-α. This aberrant functional profile was partially attributable to down-regulation of the proximal T cell receptor signaling molecule CD3ζ, and could be corrected in vitro by transfection of CD3ζ or replenishment of the amino acid arginine required for its expression. We provide evidence for depletion of arginine in the inflamed hepatic microenvironment as a potential mechanism for these defects in global CD8 T cell signaling and function. These data imply that polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment.     

Genesis of hepatic fibrosis and its biochemical markers

Liver fibrosis is characterized by an abnormal hepatic accumulation of extracellular matrix (ECM) that results from both increased deposition and reduced degradation of collagen fibres. Fibrotic liver injury results in activation of the hepatic stellate cell (HSC). Surrogate markers are gradually being substituted for biomarkers that reflect the complex balance between synthesis and degradation of the extracellular matrix. Once the hepatic stellate cell is activated, the preceding matrix changes and recurrent injurious stimuli will perpetuate the activated state. The ECM directs cellular differentiation, migration, proliferation and fibrogenic activation or deactivation. The metabolism of the extracellular matrix is closely regulated by matrix metalloproteinases (MMP) and their specific tissue inhibitors (TIMP). Although liver biopsy combined with connective tissue stains has been a mainstay of diagnosis, there is a need for less invasive methods. These diagnostic markers should be considered in combination with liver function tests, ultrasonography and clinical manifestations.