Association Between Alcohol Use and HIV-Related Sexual Risk Behaviors Among Men Who Have Sex with Men (MSM): Findings from a Multi-Site Bio-Behavioral Survey in India

This paper examines the association between alcohol use and HIV-related sexual risk behaviors among men who have sex with men (MSM). A cross-sectional bio-behavioral survey was conducted among 3,880 MSM, recruited using time-location cluster sampling from cruising sites in three Indian states. Nearly three-fifths of the participants reported alcohol use. Among frequent users (40 % of the sample), defined as those who consumed alcohol daily or at least once a week, 66 % were aged 25 years and above, 53 % self-identified as kothi (feminine/receptive), and 63 % consistently used condoms with male paying partners. Multivariate logistic regression demonstrated that frequent users were more likely to be aged 25 years and above, less likely to self-identify as kothi, and less likely to consistently use condoms with male paying (AOR = 0.7; 95 % CI 0.5–0.9) and male regular (AOR = 0.7; 95 % CI 0.6–0.9) partners. HIV prevention interventions for MSM need to provide tailored information on alcohol use-related sexual risk, especially for MSM in sex work and MSM with male regular partners.     

Perioperative blood transfusion affects hepatitis C virus (HCV)-specific immune responses and outcome following liver transplantation in HCV-infected patients

Objectives:Perioperative factors can affect outcomes of liver transplantation (LT) in recipients with hepatitis C virus (HCV) infection. This study was conducted to investigate whether the immunomodulatory effects of packed red blood cells (PRBC) and platelets administered in the perioperative period might affect immune responses to HCV and thus outcomes in LT recipients.Methods:Data for a total of 257 HCV LT recipients were analysed. Data on clinical demographics including perioperative transfusion (during and within the first 24 h), serum cytokine concentration, HCV-specific interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing cells, and outcomes including graft and patient survival were analysed.Results:Patient survival was higher in HCV LT recipients who did not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n = 192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02); 5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an increased post-transplant viral load (P = 0.032) and increased incidence of advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10, IL-17, IL-1β and IL-6, and decreased IFN-γ, and a significantly increased rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02), PRBC transfusion (P < 0.01) and platelets administration were associated with worse survival.Conclusions:Transfusion had a negative impact on LT recipients with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased IFN-γ, suggests that transfusion may be associated with the modulation of HCV-specific responses, increased fibrosis and poor transplant outcomes.     

Curcumin- and natural extract-loaded nanofibres for potential treatment of lung and breast cancer: in vitro efficacy evaluation

Drug-eluting medical implants are more common, particularly for fighting against cancers. FDA and other drug regulatory bodies have approved many nanoformulated devices eluting active pharmaceutical ingredients and thus there is growing demand for further value- added devices. Nanofibre membranes are known for its versatility of drug incorporation and sustained drug release. We intend to fabricate natural ingredient or extract, and their combination loaded polycaprolactone (PCL) nanofibre for usage as drug-eluting stents or implants for anticancer activity against lung and breast cancers. The fabricated nanofibre membranes were characterised by scanning electron microscope for morphology, FT-IR for chemical nature and tensile testing for mechanical strengths. Release of curcumin was studied with time to find the applicability of the device as drug-eluting implant. The activity of the nanofibre membranes was tested against human breast cancer (MCF7) and lung cancer (A459) cell lines in vitro. In both the cell lines tested, 1% aloe vera and 5% curcumin-loaded PCL nanofibre exhibited 15% more cytotoxicity in comparison with the commercial drug 1% cis-Platin-loaded PCL nanofibre after 24?h incubation.     

Genetic modifiers of EGFR dependence in non-small cell lung cancer

Lung adenocarcinomas harboring activating mutations in the epidermal growth factor receptor (EGFR) represent a common molecular subset of non-small cell lung cancer (NSCLC) cases. EGFR mutations predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and thus represent a dependency in NSCLCs harboring these alterations, but the genetic basis of EGFR dependence is not fully understood. Here, we applied an unbiased, ORF-based screen to identify genetic modifiers of EGFR dependence in EGFR-mutant NSCLC cells. This approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1. A subset of these genes can complement loss of EGFR activity across multiple EGFR-dependent models. Unbiased gene-expression profiling of cells overexpressing EGFR bypass genes, together with targeted validation studies, reveals EGFR-independent activation of the MEK-ERK and phosphoinositide 3-kinase (PI3K)-AKT pathways. Combined inhibition of PI3K-mTOR and MEK restores EGFR dependence in cells expressing each of the 18 EGFR bypass genes. Together, these data uncover a broad spectrum of kinases capable of overcoming dependence on EGFR and underscore their convergence on the PI3K-AKT and MEK-ERK signaling axes in sustaining EGFR-independent survival.The term “oncogene addiction” has been used to describe the phenomenon whereby tumor cells exhibit singular reliance on an oncogene or oncogenic pathway for their survival, despite the accumulation of multiple genetic lesions (1). In non-small cell lung cancer (NSCLC), this principle is perhaps best exemplified with the finding that epidermal growth factor receptor (EGFR) mutations predict response to EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, and thus represent a dependency in the subset of tumors harboring these alterations (2–6). However, though EGFR-mutant NSCLCs typically respond dramatically to EGFR TKIs, clinical responses are not universal, even within this genetically defined cohort, with the rate of objective response estimated to be ∼71% (5, 6). Furthermore, the overwhelming majority of patients who initially respond to EGFR inhibitors ultimately develop resistance to therapy (7). A deeper understanding of the genetic underpinnings of EGFR addiction, and how EGFR-mutant cells can overcome reliance on EGFR, may improve clinical outcomes.Here, we have applied an unbiased screening approach to identify genetic modifiers of EGFR dependence in NSCLC. Mounting evidence supports the existence of several genetic modifiers of EGFR dependence in EGFR-mutant NSCLC, which can reduce the degree to which these tumors rely on EGFR and thereby contribute to EGFR TKI resistance (8). Examples include amplification of the MET receptor tyrosine kinase (RTK) (9), activation of the NF-κB pathway (8), amplification of the HER2 (ERBB2) RTK (10), amplification of the CRKL gene (11), and activation of the AXL kinase (12). Notably, MET bypass can be reciprocally achieved via EGFR activation in MET-dependent cells (13), and analogous examples of reciprocal kinase switching have been reported in other kinase-driven cancer models (14, 15). These and other findings suggest that compensatory kinase switching may be a more general way in which oncogene-dependent cancers overcome reliance on their primary driver kinase (14, 16), but the full-range of kinases capable of mediating EGFR bypass has not been systematically studied.Recent advances in large-scale functional genetic libraries have made it possible to query a wide range of genetic perturbations for their ability to modulate specific cellular phenotypes in mammalian systems (17, 18). Using the model of EGFR-mutant, erlotinib-sensitive NSCLC cells, we have performed a systematic ORF-based screen to identify kinase and kinase-related genes whose overexpression can complement loss of EGFR activity in an EGFR-dependent context. Our findings indicate broad potential for EGFR substitution in the setting of EGFR dependence, with compensatory mechanisms commonly conferring EGFR-independent activation of the PI3K-AKT and MEK-ERK signaling pathways. Importantly, this approach has recovered known mechanisms of erlotinib resistance as well as identified novel mediators of EGFR bypass in EGFR-mutant NSCLC. These data support the idea that the EGFR-dependent state can be redundantly driven by diverse genetic inputs that commonly converge on shared downstream signaling nodes.     

A major new alliance in Australian healthcare: the Australian consensus framework for ethical collaboration in the healthcare sector

The 'Australian Consensus Framework for Ethical Collaboration in the Healthcare Sector' (ACF) is an Australian initiative aimed at countering dysfunction and growing mistrust in the health sector through the development of a cross‐sectoral consensus framework. The development of this framework arose from Australia's involvement in the Asia Pacific Economic Cooperative (APEC) and has since become the largest of its kind internationally, with over 70 signatories representing professional bodies, industry organisations, hospital and health services associations, regulators and patient and advocacy groups. In this article, we describe and critique the framework and outline its implementation.     

Peer-Led and Professional-Led Group Interventions for People with Co-occurring Disorders: A Qualitative Study

This pilot study evaluated the experience of people with co-occurring disorders (mental illness and addiction) in relation to peer-led and professional-led group interventions. The study used a qualitative (phenomenological) approach to evaluate the experience of a convenience sample of 6 individuals with co-occurring disorders who participated in up to 8 sessions each of both peer-led and professional-led group interventions (with a similar rate of attendance in both groups). The semi-structured interview data were coded and thematically analyzed. We found 5 themes within and across the 2 interventions. In both groups, participants experienced a positive environment and personal growth, and learned, albeit different things. They were more comfortable in the peer-led group and acquired more knowledge and skills in the professional-led group. Offering both peer-led and professional-led group interventions to people with co-occurring disorders may be better than offering either alone     

Correlation of myocardial perfusion SPECT with invasive and computed tomography coronary angiogram

BackgroundThe consequences of atherosclerosis can be detected by multislice computed tomography (MSCT), invasive coronary angiogram (CAG) and the resultant myocardial ischaemia by myocardial perfusion single photon emission computed tomography (MPS). In this study an attempt is made to compare MSCT with MPS and also to compare the MSCT findings with that of invasive CAG in patients suspected to have coronary artery disease (CAD).Materials and methodsA total of 99 patients suspected to have CAD underwent both MSCT and MPS with ^99mTc sestamibi. The MSCT studies were classified as having no CAD, significant CAD (>50% diameter stenosis), and insignificant CAD (<50% diameter stenosis). Myocardial perfusion single photon emission computed tomography was reported as normal and reversible ischaemia. In a subgroup of 33 patient invasive CAG was done.ResultsIn 99 patients, 396 coronaries were evaluated with MSCT and MPS. Coronary artery calcium scoring (CACS) in these patient ranged from 0 to 2200. No CAD was noted in 128 (32%) coronaries but MPS was found abnormal in 9 (7%) coronaries. Insignificant CAD was noted in 169 (43%) coronaries amongst which reversible ischaemia was noted in 23 (14%). Significant CAD was noted in 99 (25%) coronaries of which only 54 (55%) were MPS positive for reversible ischaemia. The MSCT has a negative predictive value (NPV) of 97%. When MSCT was normal, MPS was almost normal, but the reverse was not true. That is when MPS was normal MSCT was not always normal but showed lesion of insignificant obstruction.In the subset of 33 patients, who underwent invasive angiogram, 132 coronaries were evaluated. Coronary angiogram showed 48 coronaries (36%) to have significant CAD (>50% diameter stenosis). Multislice computed tomography correlated well in 46 (84%) with P value of <0.001 (χ²-test) but for 9 (16%) showing overestimation due to increased CACS (>800). Myocardial perfusion single photon emission computed tomography was normal in 15 (27%) coronaries.ConclusionMyocardial perfusion single photon emission computed tomography provides functional information of the anatomical lesions and MSCT provides anatomical information. Both are two different diagnostic modalities. The MSCT has high NPV in patients with less likelihood for CAD. When compared with CAG, the correlation with MSCT was good and is useful where the calcium score is low.     

Ventricular fibrillation after exposure to air freshener-death just a breath away

A case of ventricular fibrillation due to butane toxicity after unintentional inhalation of air freshener is reported for its rarity and to create awareness among practitioners and the public. A 25-year-old woman collapsed in the supermarket after unintended exposure to air freshener sprayed into her nostrils. Her husband started cardiopulmonary resuscitation immediately, and she was brought to the hospital. She had coarse ventricular fibrillation. Defibrillation with 360 J was given, and the rhythm reverted to normal sinus rhythm after the third shock. Epinephrine was not administered, and she was treated with esmolol infusion for ventricular ectopy. The patient recovered completely without any sequelae and was discharged on the fifth hospital day. On thin layer chromatography, the chemical content of the spray was identified to be isobutane. Avoiding epinephrine and administering β-adrenergic blockers may protect the catecholamine-sensitized heart early during resuscitation in butane exposure cases.