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Herein, we report sol-gel modified sulfonated poly(ether ether ketone) (SPEEK) organo-silane based composite proton exchange membranes for their suitability in direct methanol fuel cells (DMFCs). Different concentrations (0.2–1.5 wt%) of aminopropyl trimethoxysilane (APTES) are incorporated in SPEEK matrix by in-situ sol-gel method. Physico and electrochemical performances of composite membranes are enhanced by induced H-bonding interactions between free –NH 2 and –SO 3 H groups. With increase in APTES concentration to 0.8 wt%, the ionic conductivity illustrates improvement by ⁓80% while IEC and Proton conductivity (Pc) enhances by ∼21% and ∼70%, respectively than SPEEK. To further explore the feasibility of the membranes in DMFC. Methanol crossover resistance is calculated to as low as 5.30 × 10−7 cm2 s−1 and offers highest selectivity of 4.43 S s cm−3 in contrast to 12.55 × 10−7 cm2 s−1 and 0.31 S s cm−3 for SPEEK, respectively. This study reveals that the Si-SPEEK membrane is a potential alternate for DMFC. • SPEEK matrix is loaded with APTES to enhance membrane properties. • Organosilicon-based acid-base stable membranes are prepared. • 0.8 wt% APTES showed overall improved physiochemical and electrochemical properties. • H-bonding interaction improved thermal and mechanical stability. • Alternate cation exchange membrane for DMFC is prepared. [ABSTRACT FROM AUTHOR]

Background: Understanding the diversity and multiplicity of identities experienced by youth in Aotearoa (Te reo Māori name of the country) New Zealand (NZ) is vital to promoting their wellbeing. Ethnic minority youth (EMY) in NZ (defined as those identifying with Asian, Middle Eastern, Latin American and African ethnic origins) have been historically under-studied and under-counted, despite reporting high levels of discrimination, a major determinant of mental health and wellbeing and potentially a proxy for other inequities. In this paper, we describe the protocol for a multi-year study that examines, using an intersectional approach, how multiple marginalised identities impact mental and emotional wellbeing of EMY. Methods: This is a multiphase, multi-method study designed to capture the diversity of lived realities of EMY who self-identify with one or more additional marginalised intersecting identity (the population referred here as EMYi). Phase 1 (Descriptive study) will involve secondary analyses of national surveys to examine the prevalence and relationships between discrimination and wellbeing of EMYi. Phase 2 (Study on public discourse) will analyse data from media narratives, complemented by interviews with stakeholders to explore discourses around EMYi. Phase 3 (Study on lived experience) will examine lived experiences of EMYi to discuss challenges and sources of resilience, and how these are influenced by public discourse. Phase 4 (Co-design phase) will use a creative approach that is youth-centered and participatory, and will involve EMYi, creative mentors and health service, policy and community stakeholders as research partners and advisors. It will employ participatory generative creative methods to explore strengths-based solutions to discriminatory experiences. Discussion: This study will explore the implications of public discourse, racism and multiple forms of marginalisation on the wellbeing of EMYi. It is expected to provide evidence on the impacts of marginalisation on their mental and emotional wellbeing and inform responsive health practice and policy. Using established research tools and innovative creative means, it will enable EMYi to propose their own strength-based solutions. Further, population-based empirical research on intersectionality and health is still nascent, and even more scarce in relation to youth. This study will present the possibility of expanding its applicability in public health research focused on under-served communities. [ABSTRACT FROM AUTHOR]

Notch pathway is an evolutionarily conserved signalling system that operates to influence an astonishing array of cell fate decisions in different developmental contexts. Notch signalling plays important roles in many developmental processes, making it difficult to name a tissue or a developing organ that does not depend on Notch function at one stage or another. Thus, dysregulation of Notch signalling is associated with many developmental defects and various pathological conditions, including cancer. Although many recent advances have been made to reveal different aspects of the Notch signalling mechanism and its intricate regulation, there are still many unanswered questions related to how the Notch signalling pathway functions in so many developmental events. The same pathway can be deployed in numerous cellular contexts to play varied and critical roles in an organism's development and this is only possible because of the complex regulatory mechanisms of the pathway. In this review, we provide an overview of the mechanism and regulation of the Notch signalling pathway along with its multifaceted functions in different aspects of development and disease. [ABSTRACT FROM AUTHOR]

In 2020, the New Zealand (NZ) Parliament voted to decriminalise abortion. Although NZ's abortion law formally opposes sex selective abortions, there is considerable complexity in the gender politics of 'choice' and 'agency' in multi-ethnic societies, and interpretations of reproductive rights for ethnic minority women and for the girl child, respectively. This paper explores these complexities through the perspectives of reproductive and maternity care practitioners who are situated at the interface of legal systems, health service provision, and delivery of culturally sensitive care. Thirteen practitioners were interviewed as part of this study. The analysis highlights strains in framings of 'reproductive choice' (underpinned by western liberal notions of rights) and 'gender equality' (abortion rights that acknowledge the complexity of cultural son-preference) for ethnic minority women. These tensions are played out in three aspects of the post-reform landscape: (a) everyday practice and accountability; (b) consumerism and choice; (c) custodianship and gender rights. The findings point to the limitations in operationalising choices for ethnic women in health systems wherein trust deficit prevails, and cultural dynamics render complex responses to abortion. They also highlight reconfigurations of client-expert relationships that may have implications for practitioners' abilities to advocate for ethnic women's rights against cultural influences. [ABSTRACT FROM AUTHOR]

Background: Research and clinical outcomes that matter to people with lived experience can significantly differ from those outcomes studied by researchers. To inform a future Cochrane review of suicide and self‐harm prevention interventions, we aimed to work with young people with relevant lived experience to agree on priority outcomes. Design: Four participatory codesign workshops were completed across two sites (New Zealand, United Kingdom) with 28 young people in total. We iteratively adapted the methods over the course of the study. Results: 'Improved coping' and 'safer/more accepting environment to disclose' were the final top‐rated outcomes. 'Reduction of self‐harm' was considered a low priority as it could be misleading, stigmatizing and was considered a secondary consequence of other improvements. In contrast to typical research outcomes, young people emphasized the diversity of experience, the dynamic nature of improvement and holistic and asset‐based framing. Methodologically, dialogue using design materials (personas) to thematically explore outcomes was effective in overcoming the initial challenge of disparate quantitative ratings. Discussion: The results will directly inform the development of a Cochrane review, enabling identification of whether and how outcomes of most importance to young people are measured in trials. Rather than producing discrete measurable outcomes that could be easily added to the systematic review, the young people challenged the academic conceptualization of outcomes, with implications for future evidence synthesis and intervention research, and for future codesign. Patient or Public Contribution: Young people with lived experience were codesigners of the outcomes, and their feedback informed iterative changes to the study methods. [ABSTRACT FROM AUTHOR]

Notch signaling is an evolutionarily conserved pathway that is widely used for multiple cellular events during development. Activation of the Notch pathway occurs when the ligand from a neighboring cell binds to the Notch receptor and induces cleavage of the intracellular domain of Notch, which further translocates into the nucleus to activate its downstream genes. The involvement of the Notch pathway in diverse biological events is possible due to the complexity in its regulation. In order to maintain tight spatiotemporal regulation, the Notch receptor, as well as its ligand, undergoes a series of physical and biochemical modifications that, in turn, helps in proper maintenance and fine‐tuning of the signaling outcome. Ubiquitination is the post‐translational addition of a ubiquitin molecule to a substrate protein, and the process is regulated by E3 ubiquitin ligases. The present review describes the involvement of different E3 ubiquitin ligases that play an important role in the regulation and maintenance of proper Notch signaling and how perturbation in ubiquitination results in abnormal Notch signaling leading to a number of human diseases. [ABSTRACT FROM AUTHOR]

Toll pathway is the center for the function of immune system in both Drosophila and mammals. Toll pathway in Drosophila gets activated upon binding of the ligand Spätzle to the receptor, Toll, triggering a series of proteolytic cascade culminating into the activation of the NF‐κB factors Dorsal and/or Dif (Dorsal‐related immunity factor). Inappropriate activation of the Toll pathway is often associated with systemic inflammation phenotype in the absence of infection, and thus, it is important to understand the regulation of Toll signaling. Deltex (Dx) is a context‐dependent regulator of Notch signaling and has been linked with cell‐mediated immunity in the mammalian system lately. However, the unambiguous role of Dx in humoral and cell‐mediated immunity is yet to be explored. Our study unravels the novel role of Dx in Toll pathway activation. Gain of function of dx in Drosophila larvae results in increased melanotic mass formation and increased lamellocyte production. Our results also reveal the nuclear accumulation of transcription factors Dorsal and Dif and expression of Toll‐associated antimicrobial peptides (AMP) in Dx over‐expression background. Further, we also tried to elucidate the role of Dx in JNK‐independent Toll activation. Here we present Dx as a novel candidate in the regulation of Toll pathway. [ABSTRACT FROM AUTHOR]

JNK signaling is a highly conserved signaling pathway that regulates a broad spectrum of cellular processes including cell proliferation, migration, and apoptosis. In Drosophila, JNK signaling is activated by binding of the tumor necrosis factor (TNF) Eiger to its receptor Wengen, and a conserved signaling cascade operates that culminates into activation of dual phosphatase Puckered thereby triggering apoptosis. The tumor necrosis factor receptor (TNFR) associated factor 6 (TRAF6) is an adaptor protein, which transduces the signal from TNFRs and Toll‐like receptor/interleukin‐1 receptor superfamily to induce a wide spectrum of cellular responses. TRAF6 also acts as the adaptor protein that mediates Eiger/JNK signaling in Drosophila. In a genetic interaction study, deltex (Dx) was identified as a novel interactor of TRAF6. Dx is well known to regulate Notch signaling in a context‐dependent manner. Our data suggest that combinatorial action of Dx and TRAF6 enhances the Dx‐induced wing nicking phenotype by inducing caspase‐mediated cell death. Co‐expression of Dx and TRAF6 also results in enhanced invasive behavior and perturbs the normal morphology of cells. The cooperative action of Dx and TRAF6 is attributed to JNK activation, which also leads to ectopic wingless (Wg) and decapentaplegic (Dpp) expression. Our results also reveal that the endocytic pathway component Rab7 may play a pivotal role in the regulation of Dx–TRAF6‐mediated activation of JNK signaling. Here, we present the fact that Dx and TRAF6 together activate JNK signaling in an Eiger‐independent mechanism. [ABSTRACT FROM AUTHOR]

Potable clean water is in high demand for human life. Numerous technologies like reverse osmosis, flash distillation and electrodialysis are employed and explored to overcome the scarcity of potable water. Last decade has witnessed great attraction of researchers towards membrane capacitive deionization (MCDI) as an alternative technology for water desalination. MCDI holds ability to compete with benchmark desalination techniques as it involves adsorption of ions by porous carbon material on application of low voltage (<1.4 V). Ions are desorbed back into the stream on reversing the potential hence, regenerating the electrodes. Addition of ion exchange membranes enhances the desalination efficiency by reducing the effect of co-ions, which is not possible in traditional capacitive deionization (CDI). Present study aims to synthesize and explore the best fit carbon-based material for MCDI. SPEEK and QPPO polymers were used for CEM and AEM preparation over the porous carbon materials respectively. SEM, XRD and Raman spectroscopy were used to investigate the structural information about carbon materials. Nyquist plots were obtained to analyze diffusive behavior and formation of electrolyte double layer (EDL) on electrode-electrolyte interface. Capacitive behavior of the electrodes was analyzed through cyclic voltammetry (CV) and Galvanostatic charge discharge (GCD). Water desalination performance of membrane coated carbon materials was observed through batch-mode MCDI set-up. Important CDI parameters like salt adsorption capacity (SAC) and specific capacitance were also calculated to evaluate performance of the prepared MCDI electrodes. Among all four synthesized materials, CMGO (carbon spheres modified graphene oxide) reports highest SAC value i.e. 22.5 mg g−1 which suggest CMGO as a promising material for large scale MCDI application. [Display omitted] [ABSTRACT FROM AUTHOR]

Potable clean water is in high demand for human life. Numerous technologies like reverse osmosis, flash distillation and electrodialysis are employed and explored to overcome the scarcity of potable water. Last decade has witnessed great attraction of researchers towards membrane capacitive deionization (MCDI) as an alternative technology for water desalination. MCDI holds ability to compete with benchmark desalination techniques as it involves adsorption of ions by porous carbon material on application of low voltage (<1.4 V). Ions are desorbed back into the stream on reversing the potential hence, regenerating the electrodes. Addition of ion exchange membranes enhances the desalination efficiency by reducing the effect of co-ions, which is not possible in traditional capacitive deionization (CDI). Present study aims to synthesize and explore the best fit carbon-based material for MCDI. SPEEK and QPPO polymers were used for CEM and AEM preparation over the porous carbon materials respectively. SEM, XRD and Raman spectroscopy were used to investigate the structural information about carbon materials. Nyquist plots were obtained to analyze diffusive behavior and formation of electrolyte double layer (EDL) on electrode-electrolyte interface. Capacitive behavior of the electrodes was analyzed through cyclic voltammetry (CV) and Galvanostatic charge discharge (GCD). Water desalination performance of membrane coated carbon materials was observed through batch-mode MCDI set-up. Important CDI parameters like salt adsorption capacity (SAC) and specific capacitance were also calculated to evaluate performance of the prepared MCDI electrodes. Among all four synthesized materials, CMGO (carbon spheres modified graphene oxide) reports highest SAC value i.e. 22.5 mg g−1 which suggest CMGO as a promising material for large scale MCDI application. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Effective postoperative analgesia following Caesarean Section is important because parturients are at a higher risk for thromboembolic events due to immobility, increased likelihood of developing postpartum depression (PPD) following inadequate pain control which also can interrupt breastfeeding. Ketamine at sub anesthetic doses has been considered to reduce postoperative pain and analgesic consumption following caesarean section. Aims: The aim of this study was to evaluate the efficacy of sub anesthetic doses of ketamine on post caesarean analgesia. Material and Methods: This randomized double blind, placebo controlled study was conducted on 108 parturients, divided into three groups (36 in each group);Group C- received 2 ml of 0.9% normal saline; Group Ka- received 0.15 mg/kg of ketamine (2 ml) and Group Kb- 0.3 mg/kg of ketamine (2 ml) after 5 min of delivery. Postoperatively VAS score, consumption of rescue analgesic in 24 h and adverse effects were recorded. Statistical analysis was done with Analysis of variance (ANOVA) for continuous variables and Chi-square test for categorical scale. P values less than 0.05 were considered significant. Results: Postoperative VAS scores were significantly higher in control group while the time to the first analgesic requirement was significantly prolonged in Ka group (5.44 ± 1.45 h) and Kb group (6.18 ± 1.61 h) as compared to the control group (4.97 ± 1.48 h). The total number of doses and total dose of rescue analgesic (tramadol) required in 24 hours was significantly less in the Ka group (194.44 ± 53.15 mg) and Kb group (152.78 ± 50.63 mg) as compared to group C (136.11 ± 48.71 mg. Conclusion: Administration of sub-anesthetic doses (0.15 mg/kg and 0.3 mg/kg) of intravenous ketamine enhanced postoperative analgesia and reduced the total rescue analgesic consumption in first 24 h following CS. Ketamine 0.3 mg/kg also increased the time to first postoperative rescue analgesic request. [ABSTRACT FROM AUTHOR]

Oxygen evolution reaction (OER) is a vital electrochemical reaction for sustainable energy generation technologies. Due to the sluggish kinetics, exploration for an efficient non-precious metal catalyst is essential. Bimetallic nanohybrids are potential electrocatalysts for the OER due to their pore structure, large surface area, and inevitably dispersed metal centers. This work reports the synthesis of three bimetallic Ni–Co (NCMX), Fe–Co (FCMX), and Fe–Ni (FNMX) nanohybrids onto MXene for effective OER activity. An improved OER activity is observed on a plastic chip electrode (PCE) loaded with electrocatalysts. Among the synthesized electrocatalysts, NCMX exhibits excellent OER performance with an overpotential of 220 mV and a small Tafel slope of 94 mV/dec in a basic electrolyte (1 M KOH). The 3D MXenes framework promotes strong interaction with efficient charge transfer between the nanohybrids and MXene. Results demonstrate a promising recommendation for designing high-performance MXene-supported bimetallic nanohybrid electrocatalysts. • Bimetallic Fe/Ni/Co Nanohybrids on MXene have been synthesized successfully. • Uniform distribution of nanostructures on MXene. • NCMX exhibits excellent OER performance with overpotential of 220 mV. • NCMX shows the no degradation after electrochemical performance. [ABSTRACT FROM AUTHOR]

Needle and syringe sharing is common among people who inject drugs and so is unprotected sex, which consequently puts their sex partners at risk of sexually transmitted infections (STIs) including HIV and other blood-borne infections, like hepatitis. We undertook a nested study with the regular female partners of men who inject drugs participating in a longitudinal HIV incidence study in Delhi, India. In-depth interviews were conducted with female partners of 32 men. The interviews aimed to gather focused and contextual knowledge of determinants of safe sex and reproductive health needs of these women. Information obtained through interviews was triangulated and linked to the baseline behavioural data of their partner (index men who injected drugs). The study findings illustrate that women in monogamous relationships have a low perception of STI- and HIV-related risk. Additionally, lack of awareness about hepatitis B and C is a cause of concern. Findings also suggest impact of male drug use on the fertility of the female partner. It is critical to empower regular female partners to build their self-risk assessment skills and self-efficacy to negotiate condom use. Future work must explore the role of drug abuse among men who inject drugs in predicting fertility and reproductive morbidity among their female partners. [ABSTRACT FROM PUBLISHER]

Multicellular organisms depend on a handful of core signaling pathways that regulate a variety of cell fate choices. Often these relatively simple signals integrate to form a large and complex signaling network to achieve a distinct developmental fate in a context-specific manner. Various pathway-dependent and independent events control the assembly of signaling complexes. Notch pathway is one such conserved signaling mechanism that integrates with other signaling pathways to exhibit a context-dependent pleiotropic output. To understand how Notch signaling provides a spectrum of distinct outputs, it is important to understand various regulatory switches involved in mediating signaling cross-talk of Notch with other pathways. Here, we review our current understanding as to how Notch signal integrates with JNK and NF-κB signaling pathways in Drosophila to regulate various developmental events such as sensory organ precursor formation, innate immunity, dorsal closure, establishment of planar cell polarity as well as during proliferation and tumor progression. We highlight the importance of conserved signaling molecules during these cross-talks and debate further possibilities of novel switches that may be involved in mediating these cross-talk events. • Notch pathway cross-talks with other signaling pathways during development in a context-dependent manner. • In Drosophila , integration of Notch with other pathways such as JNK and NF-κB regulates several developmental processes. • Several novel interactors of the Notch pathway are involved in signaling cross-talk. • Notch interactors can form multiprotein complexes to regulate specific developmental output. [ABSTRACT FROM AUTHOR]

This study delves into the solution-phase incorporation of Ti 3 C 2 T x nanosheets into sulfonated poly(phenylene oxide) (SPPO) to prevail the conventional challenge of distant ionic channels in membranes. A series of membranes incorporating MXene (Ti 3 C 2 T x nanosheets) at varying weight percentages (1 wt%, 2 wt%, and 5 wt%) underwent meticulous scrutiny of their physicochemical and electrochemical attributes. Among this series, MXe-02 emerged as particularly noteworthy, showing remarkable water sorption (WS= 43.8%), ion exchange capacity (IEC: 1.65 ± 0.05 meqg−1), and ionic conductivity (IC: 2.83×10−2 S cm−1), coupled with minimal dimensional change of 8.57% compared to its pristine counterpart, SPPO-B (WS=35.70%, IEC: 1.03±0.05 meqg−1, IC: 1.98×10–2 S cm−1). Advanced analytical techniques such as atomic force microscopy (AFM) and field emission-scanning electron microscopy (FE-SEM) provided insights into hydrophilic-hydrophobic phase separation, ionic domain clustering, and membrane surface attributes pivotal for enhancing electrochemical properties. Beyond optimal concentrations (>2 wt%), a significant composite-agglomeration effect hindered further advancements in physicochemical and electrochemical aspects, as verified by zeta potential measurements. The optimized MXe-02 membrane boasted a notable transport number of 0.89 with a substantial limiting current density (I lim = 45 mA cm−2), offering a wide window for swift electrodialytic desalination. Moreover, MXe-02 membranes demonstrated an energy consumption of 0.98 kWh kg−1 and 93.52% energy efficiency, affirming their efficacy for brackish water desalination. Antibacterial properties were evaluated against Escherichia coli and Staphylococcus aureus , revealing MXe-02 and MXe-05's distinct zones of inhibition against S. aureus , highlighting their excellent antibacterial efficacy against Gram-positive bacteria. This comprehensive study shows the intricate interplay of MXene-incorporated membranes, offering valuable insights for advancing electrochemical and antibacterial performance in water desalination. [Display omitted] • Ti 3 C 2 T x nanosheets are incorporated into SPPO to trade-offs of long-range ionic conductivity. • MXe-02 membrane shows excellent electrochemical and physicochemical atributes. • A wide window for fast desalination is possible with 93.52% energy efficiency. • CEMs demonstrates strong antibacterial activity against gram-positive bacteria. [ABSTRACT FROM AUTHOR]

The stability and the performance of the bipolar membrane (BPM) are the critical issues to be resolved. The layer thickness plays an important role in improving the performance of bipolar membrane. Here, an efficient transparent asymmetric bipolar membrane has been fabricated by a layer-by-layer solution casting technique comprising cation and anion exchange layers. The thickness of the anion exchange layer was reduced to improve the performance in term of product purity and recovery by minimizing the co-ion leakage. The interface of BPM acts as a catalytic junction for dissociating the water into H+ and OH− ions. A clear membrane interface was confirmed by the scanning electron microscopy (SEM). All three BPMs show the adequate physicochemical and electrochemical properties in term of ionic conductivity and water uptake. Effect of applied potential was studied on the membrane performance through BMED for the dissociation of NaCl. We also performed the bipolar membrane electrodialysis (BMED) for the hydrolysis of different organic and inorganic salts into corresponding acid and alkali. Among the bipolar membranes, BPM with 40 % less AEL thickness (BPM-60 membrane) shows the better performance. BPM-60 shows the highest water splitting rate and alkali recovery of 0.491 g h−1 and 95.5 %, respectively with lowest energy consumption of 1.11 kW h kg−1 and high current efficiency of 90.32 %. Conversion of NaCl in to NaOH and HCl gives the highest product recovery as compared to other salts, due to higher dissociation of NaCl. BPM-60 with higher water splitting rate, lower energy consumption and higher current efficiency for conversion of salt into corresponding acid and alkali made asymmetric bipolar membrane as industrially applicable with high performance. [Display omitted] • Layer-by-layer solution casting provides the strong adhesion among the layers of BPMs. • Reduction in AEM improved the water splitting efficiency and stability. • 95.5 % product recovery was obtained using BPM-60 membrane by BMED. • BPM-60 shows better current efficiency and energy consumption as compared to reported membranes. • No delamination after multiple use of the membranes. [ABSTRACT FROM AUTHOR]

Background: We utilized multiple recruitment approaches to recruit IDUs in a longitudinal cohort study to examine HIV incidence and behavior change pre- and post-introduction of comprehensive HIV prevention services. Methods: IDUs were recruited through peer referral, targeted outreach by outreach workers (ORWs) and as walk-in clients at drop-in centers. Participants received monetary compensation for participation (USD 0.80). Participants were given recruitment coupons to recruit peers (regardless of recruitment method). For peer referral, participants received a food coupon, as secondary compensation, for each peer he/she successfully recruited. We report the profile of IDUs by recruitment method, based on the baseline behavioral survey and HIV test results. Cost per IDU recruited by recruitment method was also calculated. Results: A total of 3,818 IDUs were recruited between May 2011 and October 2011. More than half of the study participants were recruited through targeted outreach (ORW: 53.6%; peer-referral: 26.3%; walk-ins: 20.1%). Of the participants who were given recruitment coupons, 92.7% recruited no peers. Those who successfully recruited at least one peer were significantly more likely to be in a stable living accommodation compared to those who did not recruit any peers (51.1% versus 42.7%; p < 0.05). Only 45.9% of the food coupons were claimed for successful recruitment of peers. Peer-referred IDUs were more likely to be living with family or relatives (50.7% versus ORW: 40.1% and walk-in: 39.8%; p < 0.001) rather than on the street or shared housings compared to the other two recruitment modes. Walk-ins were more likely than peer-referred and ORW-referred IDUs to be HIV-positive (walk-ins: 26.1%; peer-referred: 19.1%; ORW: 19.9%; p < 0.01) and have risky injection practices (walk-ins: 62.2%; ORW: 57.0%; peer-referred: 58.6%; p < 0.05). The cost per IDU recruited through ORW referral method was the most costly at USD 16.30, followed by peer-referral at USD 8.40 and walk-in at USD 7.50. Conclusion: When recruiting a large number of IDUs, using multiple recruitment modes is ideal with regard to diversification of IDU characteristics and risk profile. Although it was the most costly, ORW recruitment was more effective than the other two methods. Lack of monetary compensation for successful recruitment of peers may have hampered peer-referral. [ABSTRACT FROM AUTHOR]

TNF-JNK signaling is one of the highly conserved signaling pathways that regulate a broad spectrum of cellular processes including proliferation and apoptosis. Eiger, the sole homologue of TNF in Drosophila , initiates the TNF-JNK pathway to induce cell death. Previously, Deltex (Dx) has been identified as a Notch signaling component that regulates vesicular trafficking of Notch. In the present study, we have investigated the interaction between these two proteins in order to identify how Dx influences the activity of Eiger. Dx is found to act as a novel modulator of JNK-mediated cell death inducing activity of Eiger. Additionally, we observe that dx genetically interacts with eiger during wing development, and these two proteins, Dx and Eiger, colocalize in the cytoplasm. Our analysis reveals that Dx is involved in the cytoplasmic relocalization of Eiger from the cell membrane, thereby influencing Eiger-mediated JNK-activation process. Moreover, we demonstrate that Dx potentiates the activity of Eiger to downregulate Notch signaling pathway by retaining the Notch protein in the cytoplasm. Together, our findings reveal a novel role of Dx to modulate the signaling activity of Eiger and subsequent JNK-mediated cell death. [ABSTRACT FROM AUTHOR]

Background: WHO, UNODC, and UNAIDS recommend a comprehensive package for prevention, treatment, and care of HIV among people who inject drugs (PWID). We describe the uptake of services and the cost of implementing a comprehensive package for HIV prevention, treatment, and care services in Delhi, India. Methods: A cohort of 3774 PWID were enrolled for a prospective HIV incidence study and provided the comprehensive package: HIV and hepatitis testing and counseling, hepatitis B (HB) vaccination, syndromic management of sexually transmitted infections, clean needles-syringes, condoms, abscess care, and education. Supplementary services comprising tea and snacks, bathing facilities, and medical consultations were also provided. PWID were referred to government services for antiretroviral therapy (ART), TB care, opioid substitution therapy, and drug dependence treatment/rehabilitation. Results: The project spent USD 1,067,629.88 over 36 months of project implementation: 1.7% on capital costs, 3.9% on participant recruitment, 26.7% for project management, 49.9% on provision of services, and 17.8% on supplementary services. Provision of HIV prevention and care services cost the project USD 140.41/PWID/year. 95.3% PWID were tested for HIV. Of the HIV-positive clients, only 17.8% registered for ART services after repeated followup. Reasons for not seeking ART services included not feeling sick, need for multiple visits to the clinic, and long waiting times. 61.8% of the PWID underwent HB testing. Of the 2106 PWID eligible for HB vaccination, 81% initiated the vaccination schedule, but only 29% completed all three doses, despite intensive follow-up by outreach workers. PWID took an average of 8 clean needles-syringes/PWID/year over the project duration, with a mid-project high of 16 needles-syringes/PWID/year. PWID continued to also procure needles from other sources, such as chemists. One hundred five PWID were referred to OST services and 267 for rehabilitation services. Conclusions: A comprehensive HIV prevention, treatment, and care package is challenging to implement. Extensive efforts are needed to ensure the uptake of and retention in services for PWID; peer educators and outreach workers are required on a continuous basis. Services need to be tailored to client needs, considering clinic timing and distance from hotspots. Programs may consider provision of ART services at selected drop-in centers to increase uptake. [ABSTRACT FROM AUTHOR]

Background: India has large PWID (persons who inject drugs) population estimated at 177,000. PWIDs are at high risk for HIV, Hepatitis B (HBV) and Hepatitis C (HCV) infections. We report the prevalence of HIV, HBV and HCV infections and correlates of HIV-HCV co-infection among male PWIDs in Delhi. Methods: 3748 male PWIDs were recruited for a longitudinal HIV incidence study. Participants were tested for HBV and HCV infections at their first follow-up visit (FV1) using serum HBV-surface antigen, and HCV-antibody tests followed by HCV RNA PCR, respectively. All PWIDs who were HIV-negative at enrollment, were re-tested for HIV at FV1. Multinomial logistic regression was employed to identify predictors of HIV, HCV and HIV-HCV co-infection. Results: Overall prevalence of HIV, HBV and HCV among 2,292 participants tested at FV1 was 25.9 %, 9.7 % and 53.7 %, respectively. 6.4 % of the participants had HIV mono-infection, 34.1 % had HCV mono-infection, and 19.6 % had HIV-HCV co-infection. 26 % of HIV-positive participants without HCV were HBsAg positive. In the regression model, having practiced at least one risky injection in the past month (relative risk ratio (RRR): 1.38; 95 % CI: 1.01-1.89) and not knowing his own HIV status (RRR: 1.65, 95 % CI: 1.25-2.17) were independent predictors for HIV-HCV co-infection. Longer duration of drug injections was associated with a higher likelihood of HCV mono-infection (2-5 years RRR: 2.13; 6-10 years RRR: 2.74; ≥11 years RRR: 3.14) and HIV-HCV co-infection (2-5 years RRR: 5.14; 6-10 years RRR: 8.53; >11 years RRR: 8.03). Higher frequency of injection days/month was associated with a higher likelihood of HCV mono-infection (≤10 days/month RRR: 1.61; 11-20 days/month RRR: 3.15; 21-30 days/month RRR: 3.47) and HIV-HCV co-infections (≤10 days/month RRR: 2.26; 11-20 days/month RRR: 3.46; 21-30 days/month RRR: 4.83). Conclusions: We report a high prevalence of HIV, HCV and HIV-HCV co-infection among male PWIDs in Delhi. A tenth of the participants were HBsAg positive. Targeted Intervention programs should make HBV/HCV testing, prevention and care more accessible for PWIDs. [ABSTRACT FROM AUTHOR]

Abstract: Background: India has an estimated 177,000 injection drug users (IDU) with a national HIV prevalence of 7.14%. Reliable estimates of HIV incidence are not available for this population. Methods: We report HIV incidence in a cohort of male, HIV-negative IDUs recruited through peer-referral, targeted outreach and as walk-in clients in Delhi from May to October, 2011. Fourth-generation Antigen–Antibody tests were used to diagnose new infections and results were confirmed using Western blot tests. HIV incidence based on HIV seroconversion was calculated as number of events/person-years. Cox regression was used to identify significant (p <0.05) seroconversion predictors. Results: A total of 2790 male HIV-negative IDUs were recruited at baseline; 67.4% (n =1880) returned for their first follow-up visit and 96% (n =1806) underwent HIV testing. Participants were followed for a median of 9.7 months. A total of 112 new HIV infections occurred over a cumulative 1398.5 person-years of follow-up resulting in an incidence rate of 8.01 new infections/100 person-years (95% CI: 6.65–9.64); 74% of these participants reported risky injection practices in the past month. In multivariate analysis, moderate-high risk injection behaviors (Adjusted Hazard Ratio [AHR] 2.59; 95% CI 1.45–4.62) were associated with a higher risk of new infections. Conclusions: Male IDUs in Delhi continue to practice unsafe injection practices leading to high sero-incidence despite the availability of HIV prevention services offered through targeted intervention programs. [Copyright &y& Elsevier]

Background: In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIVinfected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/ mm3 or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients. Methods: We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records. Results: Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen. Conclusion: In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIVinfected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme. [ABSTRACT FROM AUTHOR]

Background: The different interactions between viral proteins and cellular host proteins are required for efficient replication of HIV-1. Various reports implicated host cellular proteins as a key factor that either interact directly with HIV-1 integrase (IN) or get involved in the integration process of virus resulting in the modulation of integration step. Polypyrimidine tract binding protein and associated splicing factor (PSF) has diverse functions inside the cell such as transcriptional regulation, DNA repair, acts as nucleic acids binding protein and regulate replication and infectivity of different viruses. Results: The protein binding study identified the association of host protein PSF with HIV-1 integrase. The siRNA knockdown (KD) of PSF resulted in increased viral replication in TZM-bl cells, suggesting PSF has negative influence on viral replication. The quantitative PCR of virus infected PSF knockdown TZM-bl cells showed more integrated DNA and viral cDNA as compared to control cells. We did not observe any significant difference between the amount of early reverse transcription products as well as infectivity of virus in the PSF KD and control TZM-bl cells. Molecular docking study supported the argument that PSF hinders the binding of viral DNA with IN. Conclusion: In an attempt to study the host interacting protein of IN, we have identified a new interacting host protein PSF which is a splicing factor and elucidated its role in integration and viral replication. Experimental as well as in silico analysis inferred that the host protein causes not only change in the integration events but also targets the incoming viral DNA or the integrase-viral DNA complex. The role of PSF was also investigated at early reverse transcript production as well as late stages. The PSF is causing changes in integration events, but it does not over all make any changes in the virus infectivity. MD trajectory analyses provided a strong clue of destabilization of Integrase-viral DNA complex occurred due to PSF interaction with the conserved bases of viral DNA ends that are extremely crucial contact points with integrase and indispensable for integration. Thus our study emphasizes the negative influence of PSF on HIV-1 replication. [ABSTRACT FROM AUTHOR]