Alcohol Use, HIV Stigma and Quality of Life Among Alcohol Consuming Men Living with HIV in India: A Mediation Analysis.

This study examined the hypothesis that HIV-related stigma mediates the effect of alcohol use on health-related quality of life (HRQoL) among alcohol consuming Indian men living with HIV (PLWH). The study used baseline data from a randomized controlled clinical trial entitled 'Alcohol and ART adherence: Assessment, Intervention, and Modeling in India. Participants completed surveys assessing demographic characteristics, alcohol use, HIV-related stigma, HRQoL. Mediation analysis was conducted to establish the mediation effect of HIV-related stigma on the relationship between alcohol use and HRQoL. The final mediation model showed that the effect of alcohol use on HRQoL were partially mediated by overall HIV-related stigma. Specially, 27.1% of the effects of alcohol use on HRQoL was mediated through overall HIV stigma. In the HIV stigma subdomain analyses, negative self-image mediated 14% and concerns with public attitudes (anticipated stigma) mediated 17.3% of the effect of alcohol use on HRQoL respectively. The findings suggest that efforts to reduce the negative impact of alcohol use on HRQoL and improve HRQoL among PLWH should include interventions addressing both alcohol use and specific forms of HIV-related stigma.

RESUMEN: Este estudio examinó la hipótesis de que el estigma relacionado con el VIH mediaría el efecto del consumo de alcohol en la calidad de vida relacionada con la salud entre hombres indios que consumen alcohol y viven con VIH. El estudio utilizó datos de línea base de un ensayo clínico aleatorizado controlado titulado "Consumo de alcohol y adherencia al TAR: evaluación, intervención y modelización en India". Los participantes completaron encuestas que evaluaron características demográficas, consumo de alcohol, estigma relacionado con el VIH y calidad de vida relacionada con la salud (CVRS). Se realizó un análisis de mediación para establecer el efecto de la mediación del estigma relacionado con el VIH en la relación entre el consumo de alcohol y la CVRS. El modelo final de mediación mostró que el efecto del consumo de alcohol en la CVRS fue parcialmente mediado por el estigma general relacionado con el VIH. Específicamente, el 27,1% de los efectos del consumo de alcohol en la CVRS se medió a través del estigma general relacionado con el VIH. En los análisis de subdominios del estigma del VIH, la imagen negativa de sí mismo medió el 14% y las preocupaciones sobre las actitudes públicas (estigma anticipado) mediaron el 17,3% del efecto del consumo de alcohol en la CVRS, respectivamente. Los resultados sugieren que los esfuerzos para reducir el impacto negativo del consumo de alcohol en la CVRS y mejorar la CVRS entre las personas que viven con VIH deberían incluir intervenciones que aborden tanto el consumo de alcohol como formas específicas de estigma relacionado con el VIH.

Multilevel and Multifactorial Interventions to Reduce Alcohol Consumption and Improve ART Adherence and Related Factors Among HIV Positive Men in Mumbai, India.

Alcohol use has a deleterious effect on the health status of persons living with HIV, negatively affecting antiretroviral adherence and increasing the risk of transmission. Alcohol use is not an isolated behavior but intimately linked to stigma and poor psychological status among other factors. This paper utilizes a crossover design to test the efficacy of three multilevel interventions, individual counselling (IC), group intervention (GI) and collective advocacy (CA) for change, among HIV positive males who consume alcohol, treated at five ART Centers in urban Maharashtra, India. While GI shows a significant effect on the largest number of outcome variables, IC through its psychosocial emphasis demonstrated a significant impact over time on stigma and depression, and CA with its emphasis on societal change showed positive impact on stigma and advocacy for self and others. Each of the interventions had variable effects on CD4 count and viral load.Clinical Registration Number: NCT03746457; Clinical Trial.Gov.

RESUMEN: El consumo de alcohol tiene un efecto nocivo en el estado de salud de las personas que viven con VIH, afectando negativamente la adherencia a los antirretrovirales y aumentando el riesgo de transmisión del virus. El consumo de alcohol no es un comportamiento aislado, sino que está íntimamente relacionado con el estigma y el mal estado psicológico, entre otros factores. Este documento utiliza un diseño cruzado para evaluar la eficacia de tres intervenciones: asesoramiento individual, intervención grupal y defensa colectiva para el cambio, entre hombres con VIH que consumen alcohol que reciben tratamiento en cinco centros de terapia antiretroviral en la zona urbana de Maharashtra, India. Si bien la intervención grupal muestra un efecto significativo en el mayor número de variables de interés, el asesoramiento individual a través de su énfasis psicosocial demostró un impacto significativo en el estigma y la depression a largo plazo, y la defensa colectiva con su énfasis en el cambio social mostró un impacto positivo en el estigma y la defensa de sí mismo y otros.

Acute Transverse Myelitis and Nicolau Syndrome after Benzathine Penicillin Injection.

Rare complications have been documented due to inadvertent intravascular administration of penicillin such as Nicolau syndrome (lipoatrophy), transverse myelitis, injury to sciatic nerve as well as Hoigne syndrome (transient central nervous system dysfunction).1 We present a case report where a young male developed Nicolau syndrome and transverse myelitis after receiving benzathine penicillin injection.

Longitudinal trajectories of depressive symptoms among alcohol consuming men with HIV in India.

BACKGROUND: Depression and alcohol use are common among people living with HIV (PLWH) and associated with adverse outcomes. However, there is a paucity of studies exploring trajectories of depressive symptom presence over time among alcohol consuming men PLWH. METHODS: Men PLWH were repeatedly assessed for depressive symptoms from baseline through 27 months using the 10-item Center for Epidemiologic Studies-Depression scale. Group-based trajectory modeling was used to identify trajectories of depressive symptoms over time among control (n = 188) and intervention participants (n = 564). Multinomial logistic regression was used to explore the relationship between trajectory subgroups and baseline independent variables. RESULTS: Among intervention participants, the three subgroups were characterized as 'low' (85.8 % of the participants), 'fluctuating' (8.7 %), and 'persistently increasing' symptoms (5.5 %). Similarly, three trajectory subgroups among control participants were labeled as: "low" (54.4 %); "fluctuating" (33.5 %) and "persistently increasing'" (12.1 %). Among intervention participants, longer duration since HIV diagnosis (aOR: 1.05, 95 % CI: 1.01-1.12) and HIV-related stigma (aOR: 1.09, 95 % CI: 1.02-1.18) were associated with persistently increasing depressive symptoms trajectory. Further, alcohol drinking problems (aOR: 1.10, 95 % CI: 1.04-1.17) was associated with fluctuating depressive symptoms trajectory. Among control participants, only lower overall self-rated health status was associated with persistently increasing depressive symptoms trajectory (aOR: 0.96, 95 % CI: 0.93-0.99). LIMITATIONS: Selection bias; Information bias; Lack of causal interference; Generalizability. CONCLUSION: Identifying subgroups of men PLWH with different depressive symptoms trajectories may inform effective and tailored intervention approaches to address mental health treatment and prevention among alcohol consuming men PLWH in India and elsewhere.

The Mediating Effect of Changes in Depression Symptoms on the Relationship between Health-Related Quality of Life and Alcohol Consumption: Findings from a Longitudinal Study among Men Living with HIV in India.

Heavy alcohol use is negatively affecting antiretroviral therapy adherence, mental health and health-related quality of life among people living with HIV (PLWH). This paper aims to test the mediation model examining whether changes in depression symptoms mediate in the relationship between health-related quality of life and alcohol use among male PLWH who consume alcohol in India. The study is guided by the stress-coping model, which posits that individuals facing stress may turn to maladaptive coping mechanisms such as alcohol use to alleviate their distress, which includes depression and a low health-related quality of life due to various physical, psychological, and social factors associated with the HIV infection. This study used the data from a randomized controlled clinical trial entitled 'Alcohol and ART adherence: Assessment, Intervention, and Modeling in India'. Participants completed surveys assessing demographic characteristics, health-related quality of life, depressive symptoms, and alcohol use. Multiple simple mediation models were investigated to examine whether changes in depression symptoms mediated the association between the changes in health-related quality of life and alcohol use after a 9-month follow-up. A total of 940 male PLWH were recruited and interviewed, with 564 participants in the intervention group and 376 participants in the control group. After a 9-month intervention, the mediation results showed that, among intervention participants, a decrease in depressiove symptoms mediated the relationship between improved health-related quality of life and lower alcohol use. However, among control participants, changes in depressive symptoms did not mediate the relationship between changes in health-related quality of life and alcohol use. The study findings have practical and theoretical implications. From a practical perspective, the results suggest that interventions aimed at simultaneously improving HRQoL and depressive symptoms among male PLWH with alcohol use may help reduce alcohol consumption. Therefore, interventions that address depressive symptoms in addition to improving HRQoL may have an even greater impact on reducing alcohol use among this population. Theoretically, the study supports the use of the stress-coping theory in understanding the association between HRQoL, mental health, and alcohol use among male PLWH, contributing to existing literature on a gap in our understanding of the interactions among these factors among PLWH.

Viral load outcomes in a cohort of alcohol-consuming people living with HIV receiving antiretroviral therapy in Mumbai, India.

We examined the association between alcohol consumption, adherence and viral load (VL) in a cohort of 940 alcohol-consuming, human immunodeficiency virus (HIV)-positive men receiving antiretroviral therapy in Mumbai. Some of the participants (16.7%) had missed >1 doses in the last four days and 17.6% reported >1 treatment interruptions in the last 12 months; 60.8% of the participants consumed alcohol >2 times/month, 62.8% consumed >3 drinks/typical day and 11.5% reported binge drinking >1 times/month; 76.4% of the participants had VL<200 copies/mL. Higher alcohol consumption was associated with nonadherence (odds ratio [OR]: 1.21; 95% confidence interval [CI]: 1.11-1.31) and treatment interruptions (OR: 1.20; 95% CI: 1.11-1.31). We found no association between alcohol use and VL. There was, however, a significant interaction effect of alcohol use and nonadherence on virological failure (Adjusted Odds Ratio [AOR]: 1.23; 95% CI: 1.03-1.47) implying that alcohol negatively impacts VL outcomes but mediated through adherence. Alcohol use was associated with poor adherence, which in turn was a strong predictor of virological failure.

Isolation, structure, and functional elucidation of a modified pentapeptide, cysteine protease inhibitor (CPI-2081) from Streptomyces species 2081 that exhibit inhibitory effect on cancer cell migration.

Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with respect to their biological activity and chemical nature. In this article, we have described the characterization of small molecule cysteine protease inhibitor, CPI-2081 (compound 1), a mixture of two novel pentapeptides, compound 1a (736.71 Da), and compound 1b (842.78 Da), isolated from Streptomyces species NCIM2081, following solvent extraction and repeated HPLC based on C18 chemistry, and completely characterized using a variety of both 1D and 2D NMR spectroscopy. Further, it was found that nanomolar concentration of compound 1 is able to inhibit papain hydrolytic activity. Also, compound 1 significantly inhibits tumor cell migration at sub cytotoxic concentration, indicating its remarkable potential to be developed as antimetastatic drug, which will make chemotherapy more localized and specific, thereby minimizing the hazardous side effects on normal tissues.

Rhodotorula aurantiaca penicillin V acylase: active site characterization and fluorometric studies.

Penicillin V acylase (PVA), a member of newly evolved Ntn-hydrolase superfamily, is a pharmaceutically important enzyme to produce 6-aminopenicillanic acid. Active site characterization of recently purified monomeric PVA from Rhodotorula aurantiaca (Ra-PVA), the yeast source, showed the involvement of serine and tryptophan in the enzyme activity. Modification of the protein with serine and tryptophan specific reagents such as PMSF and NBS showed partial loss of PVA activity and substrate protection. Ra-PVA was found to be a multi-tryptophan protein exhibiting one tryptophan, in native and, four in its denatured condition. Various solute quenchers and substrate were used to probe the microenvironment of the putative reactive tryptophan through fluorescence quenching. The results obtained indicate that the tryptophan residues of Ra-PVA were largely buried in hydrophobic core of the protein matrix. Quenching of the fluorescence by acrylamide was collisional. Acrylamide was the most effective quencher amongst all the used quenchers, which quenched 71.6% of the total intrinsic fluorescence of the protein, at a very less final concentration of 0.1M. Surface tryptophan residues were found to have predominantly more electropositively charged amino acids around them, however differentially accessible for ionic quenchers. Denaturation led to shift in lambda(max) from 336, in native state, to 357 nm and more exposed to the solvent, consequently increase in fluorescence quenching with all quenchers. This is an attempt towards the conformational studies of Ra-PVA.