Impact of HIV-associated conditions on mortality in people commencing anti-retroviral therapy in resource limited settings

<b>Objectives:</b> To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS).<br /><br /><b>Design, Setting: </b>Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.<br /><b><br />Subjects, Participants:</b> 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55&ndash;2.27).<br /><br /><b>Outcome Measures: </b>Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation.<br /><br /><b>Results: </b>There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21&ndash;5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with<br />increased mortality (HR: 2.21; 95% CI: 1.97&ndash;2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74&ndash;4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), nontuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80&ndash;3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80&ndash;3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary<br />tuberculosis, Kaposi&rsquo;s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates.<br /><b><br />Conclusions: </b>A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for<br />diagnostics, therapeutic interventions and research.

Ribosome inactivating proteins (RIPs) from momordica charantia for anti viral therapy

This review describes the nature and applications of ribosome inactivating proteins (RIPs) from Momordica charantia (bitter melon). RIPs from the plant kingdom have received much attention in biomedical research because they target conserved host protein synthesis machinery and show specificity towards human and animal cell targets. Recent studies aimed at unravelling the enzymatic activities of the M charantia RIPs provide a structural basis for their activities. It has been reported that RIPs are member of the single chain ribosome inactivating protein (SCRIP) family which act irreversibly on ribosome by removing adenine residue from eukaryotic ribosomal RNA. Various activities of RIPs include anti-tumor, broad anti-viral, ribonuclease and deoxyribonuclease. MAP30 (Momordica Anti-HIV Protein), alpha- and beta-momorcharins inhibit HIV replication in acutely and chronically infected cells and thus are considered potential therapeutic agent in HIV infection and AIDS. Further, MAP30 improved the efficacy of anti-HIV therapy when used in combination with other anti-viral drugs. MAP30 holds therapeutic promise over other RIPs because not only it is active against infection and replication of both HSV and HIV but is non toxic to normal cells. Here we review the nature, action, structure function relationship and applications of RIPs from Momordica charantia and evaluate their potential for anti-cancer and anti-viral therapy.<br />

Direct asymmetric aldol reactions in water catalysed by a highly active C2-Symmetrical bisprolinamide organocatalyst

A novel C2-symmetrical bisprolinamide organocatalyst was synthesised and used to facilitate asymmetric direct aldol reactions in a water emulsion. Reactions were performed at room temperature with very low catalyst loadings (12.5 mol%) without the required use of additives, co-catalysts or extended reaction times (24 h). This catalyst system was then used with a variety of aldehyde substrates showing good reaction generality for benzaldehydes with cyclohexanone (dr range 77/23 to &gt;99/1, anti/syn; ee range 33% to &gt;99%) and moderate scope with cyclopentanone (dr range 45/55 to 76/24, anti/syn; ee range 14% to 68%). Ultra-low catalysts loadings (0.1 and 0.05 mol%) were also investigated demonstrating catalyst turnover numbers in the order of 1000.

Sexual desire in women presenting for anti-androgen therapy

Women presenting with hirsuties/polycystic ovary syndrome have increased production of androgens. Clinical lore suggests that these women may have increased sexual desire. Treatment of hirsuties commonly involves antiandrogen therapy, a form of therapy with a potential for reducing sexual desire. The present study investigated sexual desire in 29 hirsute women aged 19 to 43 years presenting for therapy. We conducted a questionnaire appraisal of the women's sexual desire, body and self-esteem, and affect at baseline, 3 months, and 12 months and compared the data with a control group of 30 nonhirsute women of similar mean age. Those in the treatment group also had their Ferriman and Gallwey scores and body mass indices calculated at baseline and end of study for those in the treatment group. We determined hormone levels for those in the treatment group with baseline blood tests. Our hypotheses were that the hirsute women would experience different levels of sexual desire than the control group prior to therapy and that therapy would have a demonstrable effect on the self-reported sexual desire of these women. The study demonstrated that women with hirsuties had mean levels of sexual desire and body esteem that were significantly lower than the control group women. During the year-long course of therapy, the sexual desire levels of the hirsute women decreased progressively, while their self-esteem increased. The women's Ferriman and Gallwey scores fell, indicating diminishing hirsutism. These findings provide empirical data upon which clinicians can base advice to patients seeking therapy.

Anti-angiogenic therapy for high grade glioma

This is the protocol for a review and there is no abstract. The objectives are as follows:<br /><br />To evaluate the efficacy and toxicity of anti-angiogenic therapy, either alone or in combination with chemotherapy and/or radiotherapy in patients with HGG. Comparisons will be as follows:<br /><br />1. Newly diagnosed HGG treated with radiotherapy and chemotherapy in combination with angiogenesis inhibitor versus without angiogenesis inhibitors.<br />2. First relapse therapy with angiogenesis inhibitor versus without angiogenesis inhibitors.<br />3. Second or third line angiogenesis inhibitors versus therapy without angiogenesis inhibitors.

Anti-angiogenic therapy for lung cancer

This is the protocol for a review and there is no abstract. The objectives are as follows:<br /><br />To determine the benefits and harms of angiogenesis inhibitors in the treatment of lung cancer when given alone, following or in combination with chemotherapy or chemo-radiotherapy (in the case of locally advanced non-metastatic NSCLC or limited stage SCLC).

Electrosprayed PLGA smart containers for active anti-corrosion coating on magnesium alloy Amlite

A novel self-healing system, consisting of poly(lactic-co-glycolic) acid (PLGA) porous particles loaded with a corrosion inhibitor, i.e. benzotriazole (BTA), has been successfully achieved via direct electro-spray deposition and subsequent epoxy spraying upon magnesium (Mg) alloy AMlite. The two-step process greatly simplified the multi-step fabrication of smart coatings reported previously. The PLGA particles demonstrate rapid response to both water and pH increase incurred by corrosion of Mg, ensuring instant and ongoing release of BTA to self-heal the protective functionality and retard further corrosion. Furthermore, nanopores in the PLGA&ndash;BTA microparticles, formed by the fast evaporation of dichloromethane during the electrospray process, also contribute to the fast release of BTA. Using Mg alloy AMlite as a model substrate which requires corrosion protection, potentiodynamic polarisation characterisation and scratch testing were adopted to reveal the anti-corrosion capability of the active coating.

N-doped pierced graphene microparticles as a highly active electrocatalyst for li-air batteries

In this work we report a novel scalable strategy to prepare a lithium-air battery electrode from 3D Ndoped pierced graphene microparticles (N-PGM) with highly active performance. This approach has combined the merits of spray drying technology and the hard template method. The pierced structured graphene microparticles were characterized physically and electrochemically. An x-ray<br />photoelectron spectrometer and Raman spectra have revealed that the novel structure possesses a higher N-doping level than conventional graphene without the pierced structure. A much higher BET surface area was also achieved for the N-PGMthan the conventional N-doped graphene microparticles (N-GM). Cyclic voltammetry indicated that the lithium-air battery with the N-PGM electrode has a better utilization for the graphene mass and a higher void volume for Li2O2 formation than that of theN-GMelectrode. N-PGMalso exhibits improved decomposition kinetics for Li oxide<br />species yielded in the cathodic reaction. Charge and discharge measurements showed that theN-PGM lithium-air battery achieved an improved specific capacity and an enhanced cycle performance than when anN-GMelectrode is used.

Subnanometer molybdenum sulfide on carbon nanotubes as a highly active and stable electrocatalyst for hydrogen evolution reaction

Electrochemically splitting water for hydrogen evolution reaction (HER) has been viewed as a promising approach to produce renewable and clean hydrogen energy. However, searching for cheap and efficient HER electrocatalysts to replace the currently used Pt-based catalysts remains an urgent task. Herein, we develop a one-step carbon nanotube (CNT) assisted synthesis strategy with CNTs' strong adsorbability to mediate the growth of subnanometer-sized MoS(x) on CNTs. The subnanometer MoS(x)-CNT hybrids achieve a low overpotential of 106 mV at 10 mA cm(-2), a small Tafel slope of 37 mV per decade, and an unprecedentedly high turnover frequency value of 18.84 s(-1) at &eta; = 200 mV among all reported non-Pt catalysts in acidic conditions. The superior performance of the hybrid catalysts benefits from the presence of a higher number of active sites and the abundant exposure of unsaturated S atoms rooted in the subnanometer structure, demonstrating a new class of subnanometer-scale catalysts.

Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton

Eradication of HIV-1 with highly active antiretroviral therapy (HAART) is not possible due to the persistence of long-lived, latently infected resting memory CD4+ T cells. We now show that HIV-1 latency can be established in resting CD4+ T cells infected with HIV-1 after exposure to ligands for CCR7 (CCL19), CXCR3 (CXCL9 and CXCL10), and CCR6 (CCL20) but not in unactivated CD4+ T cells. The mechanism did not involve cell activation or significant changes in gene expression, but was associated with rapid dephosphorylation of cofilin and changes in filamentous actin. Incubation with chemokine before infection led to efficient HIV-1 nuclear localization and integration and this was inhibited by the actin stabilizer jasplakinolide. We propose a unique pathway for establishment of latency by direct HIV-1 infection of resting CD4+ T cells during normal chemokine-directed recirculation of CD4+ T cells between blood and tissue. <br />

Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants

The mitochondrial DNA A3243G mutation causes neuromuscular disease. To investigate the muscle-specific pathophysiology of mitochondrial disease, rhabdomyosarcoma transmitochondrial hybrid cells (cybrids) were generated that retain the capacity to differentiate to myotubes. In some cases, striated muscle-like fibres were formed after innervation with rat embryonic spinal cord. Myotubes carrying A3243G mtDNA produced more reactive oxygen species than controls, and had altered glutathione homeostasis. Moreover, A3243G mutant myotubes showed evidence of abnormal mitochondrial distribution, which was associated with down-regulation of three genes involved in mitochondrial morphology, Mfn1, Mfn2 and DRP1. Electron microscopy revealed mitochondria with ultrastructural abnormalities and paracrystalline inclusions. All these features were ameliorated by anti-oxidant treatment, with the exception of the paracrystalline inclusions. These data suggest that rhabdomyosarcoma cybrids are a valid cellular model for studying muscle-specific features of mitochondrial disease and that excess reactive oxygen species production is a significant contributor to mitochondrial dysfunction, which is amenable to anti-oxidant therapy. <br />

Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV infection

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.<br />