Aluminium, Nitrogen-Dual-Doped Reduced Graphene Oxide Co-Existing with Cobalt-Encapsulated Graphitic Carbon Nanotube as an Activity Modulated Electrocatalyst for Oxygen Electrocatalyst for Oxygen Electrochemistry Applications.

There is a rising need to create high-performing, affordable electrocatalysts in the new field of oxygen electrochemistry. Here, a cost-effective, activity-modulated electrocatalyst with the capacity to trigger both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) in an alkaline environment is presented. The catalyst (Al, Co/N-rGCNT) is made up of aluminium, nitrogen-dual-doped reduced graphene oxide sheets co-existing with cobalt-encapsulated carbon nanotube units. Based on X-ray Absorption Spectroscopy (XAS) studies, it is established that the superior reaction kinetics in Al, Co/N-rGCNT over their bulk counterparts can be attributed to their electronic regulation. The Al, Co/N-rGCNT performs as a versatile bifunctional electrocatalyst for zinc-air battery (ZAB), delivering an open circuit potential ≈1.35 V and peak power density of 106.3 mW cm-2, which are comparable to the system based on Pt/C. The Al, Co/N-rGCNT-based system showed a specific capacity of 737 mAh gZn -1 compared to 696 mAh gZn -1 delivered by the system based on Pt/C. The DFT calculations indicate that the adsorption of Co in the presence of Al doping in NGr improves the electronic properties favoring ORR. Thus, the Al, Co/N-rGCNT-based rechargeable ZAB (RZAB) emerges as a highly viable and affordable option for the development of RZAB for practical applications.

Patterns of brain metastases response to immunotherapy with pembrolizumab.

PURPOSE: Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome. METHODS: This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions). RESULTS: Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks. CONCLUSION: Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.

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.

Keras/TensorFlow in Drug Design for Immunity Disorders.

Homeostasis of the host immune system is regulated by white blood cells with a variety of cell surface receptors for cytokines. Chemotactic cytokines (chemokines) activate their receptors to evoke the chemotaxis of immune cells in homeostatic migrations or inflammatory conditions towards inflamed tissue or pathogens. Dysregulation of the immune system leading to disorders such as allergies, autoimmune diseases, or cancer requires efficient, fast-acting drugs to minimize the long-term effects of chronic inflammation. Here, we performed structure-based virtual screening (SBVS) assisted by the Keras/TensorFlow neural network (NN) to find novel compound scaffolds acting on three chemokine receptors: CCR2, CCR3, and one CXC receptor, CXCR3. Keras/TensorFlow NN was used here not as a typically used binary classifier but as an efficient multi-class classifier that can discard not only inactive compounds but also low- or medium-activity compounds. Several compounds proposed by SBVS and NN were tested in 100 ns all-atom molecular dynamics simulations to confirm their binding affinity. To improve the basic binding affinity of the compounds, new chemical modifications were proposed. The modified compounds were compared with known antagonists of these three chemokine receptors. Known CXCR3 compounds were among the top predicted compounds; thus, the benefits of using Keras/TensorFlow in drug discovery have been shown in addition to structure-based approaches. Furthermore, we showed that Keras/TensorFlow NN can accurately predict the receptor subtype selectivity of compounds, for which SBVS often fails. We cross-tested chemokine receptor datasets retrieved from ChEMBL and curated datasets for cannabinoid receptors. The NN model trained on the cannabinoid receptor datasets retrieved from ChEMBL was the most accurate in the receptor subtype selectivity prediction. Among NN models trained on the chemokine receptor datasets, the CXCR3 model showed the highest accuracy in differentiating the receptor subtype for a given compound dataset.

Achieving UNAIDS Viral Suppression Goal: Experience from a Tertiary Care Public Hospital, Western India.

INTRODUCTION: Targeted HIV 1 viral load testing has been recommended in 2010 only for suspected cases of antiretroviral therapy failure. India is committed to achieve UNAIDS '90-90-90' target by 2020. The third 90 target was to ensure all people receiving antiretroviral therapy (ART) are virologically suppressed. Implementation of routine viral load testing in national programme helps us in assessing early treatment failure and the need to switch to second line therapy; thus eventually reducing drug resistance and improving patient outcomes. AIMS: Study was aimed to determine the proportion of patients responding to antiretroviral therapy, correlates of viral suppression & the discordance between virological and immunological failure. DESIGN: Retrospective analysis. MATERIAL & METHODS: As per the NACO policy, all patients diagnosed as HIV positive are started on antiretroviral therapy and are monitored regularly. The patient's adherence details are noted down during regular follow up visit and patient is referred for routine HIV 1 VL and/or CD4 testing as per National guidelines. Analysis of data was carried out retrospectively for all patients referred for HIV 1 viral load and/or CD4 testing during the study period from July 2019 to June 2020. Confidentiality of the patient was maintained at all times as per routine protocol. RESULTS: A total of 7601 PLHIV on antiretroviral therapy, 3813 samples were tested for both HIV 1 VL and CD4 counts and these results were further analyzed. 3616 (94.8%) showed virological suppression and 197(5.2%) showed virological failure. Among virologically failed group, 46.2% (91/197) underwent retesting after adherence counseling and among these 48.4%(44/91) showed viral suppression. Virological failure was significantly high in younger PLHIV receiving second or third line ART for less than 5 years duration who were non adherent. Immunological discordance was seen in 28.3 % of PLHIV. CONCLUSION: In the present study, 95.99% patients showed virological suppression indicating that the third "90"target is being exceeded.

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.

DART: deep learning enabled topological interaction model for energy prediction of metal clusters and its application in identifying unique low energy isomers.

Recently, machine learning (ML) has proven to yield fast and accurate predictions of chemical properties to accelerate the discovery of novel molecules and materials. The majority of the work is on organic molecules, and much more work needs to be done for inorganic molecules, especially clusters. In the present work, we introduce a simple topological atomic descriptor called TAD, which encodes chemical environment information of each atom in the cluster. TAD is a simple and interpretable descriptor where each value represents the atom count in three shells. We also introduce the DART deep learning enabled topological interaction model, which uses TAD as a feature vector to predict energies of metal clusters, in our case gallium clusters with sizes ranging from 31 to 70 atoms. The DART model is designed based on the principle that the energy is a function of atomic interactions and allows us to model these complex atomic interactions to predict the energy. We further introduce a new dataset called GNC_31-70, which comprises structures and DFT optimized energies of gallium clusters with sizes ranging from 31 to 70 atoms. We show how DART can be used to accelerate the process of identification of low energy structures without geometry optimization. Albeit using a topological descriptor, DART achieves a mean absolute error (MAE) of 3.59 kcal mol-1 (0.15 eV) on the test set. We also show that our model can distinguish core and surface atoms in the Ga-70 cluster, which the model has never encountered earlier. Finally, we demonstrate the transferability of the DART model by predicting energies for about 6k unseen configurations picked up from molecular dynamics (MD) data for three cluster sizes (46, 57, and 60) within seconds. The DART model was able to reduce the load on DFT optimizations while identifying unique low energy structures from MD data.

Improving handover competency in preclinical medical and health professions students: establishing the reliability and construct validity of an assessment instrument.

BACKGROUND: As part of the worldwide call to enhance the safety of patient handovers of care, the Association of American Medical Colleges (AAMC) requires that all graduating students "give or receive a patient handover to transition care responsibly" as one of its Core Entrustable Professional Activities (EPAs) for Entering Residency. Students therefore require educational activities that build the necessary teamwork skills to perform structured handovers. To date, a reliable instrument designed to assess teamwork competencies, like structured communication, throughout their preclinical and clinical years does not exist. METHOD: Our team developed an assessment instrument that evaluates both the use of structured communication and two additional teamwork competencies necessary to perform safe patient handovers. This instrument was utilized to assess 192 handovers that were recorded from a sample of 229 preclinical medical students and 25 health professions students who participated in a virtual course on safe patient handovers. Five raters were trained on utilization of the assessment instrument, and consensus was established. Each handover was reviewed independently by two separate raters. RESULTS: The raters achieved 72.22 % agreement across items in the reviewed handovers. Krippendorff's alpha coefficient to assess inter-rater reliability was 0.6245, indicating substantial agreement among the raters. A confirmatory factor analysis (CFA) demonstrated the orthogonal characteristics of items in this instrument with rotated item loadings onto three distinct factors providing preliminary evidence of construct validity. CONCLUSIONS: We present an assessment instrument with substantial reliability and preliminary evidence of construct validity designed to evaluate both use of structured handover format as well as two team competencies necessary for safe patient handovers. Our assessment instrument can be used by educators to evaluate learners' handoff performance as early as their preclinical years and is broadly applicable in the clinical context in which it is utilized. In the journey to optimize safe patient care through improved teamwork during handovers, our instrument achieves a critical step in the process of developing a validated assessment instrument to evaluate learners as they seek to accomplish this goal.

Clinical Study of Use of Remdesivir and Tocilizumab in Severely Ill COVID-19 Patients.

Introduction: Remdesivir and Tocilizumab are two experimental drugs used in severely ill COVID-19 patients. Various clinical trials studying these drugs are giving conflicting results. Our aim is to study these two drugs and share the experience in our setting. Methods: Our Study is a retrospective analysis of Clinico-laboratory details and outcome of three groups of patients who were given either (i) Remdesivir or (ii) Tocilizumab or (iii)both Remdesivir and Tocilizumab . We compared the outcome of these patients with other patients who did not receive either of these drugs, when it was not available or not introduced as experimental drugs earlier in treatment guidelines. Results: Out of a total of 521 patients, in the above three groups who received either or both Remdesivir or Tocilizumab, 334 survived. Out of 214 patients who did not receive any of the two drugs only 74 survived. The outcome was better individually for all the three groups of patients receiving either or both of the drugs as compared to neither of the drugs.(p <0.01) Conclusion: Remdesivir and Tocilizumab were useful drugs in treatment of severely ill covid -19 patients as compared with the patients who did not receive any of the above drugs.

Double - Trouble- Relapsing Leishmaniasis in a Virologically Suppressed HIV Positive Patient.

We present a case of a middle aged male, with long standing retroviral disease on second line ART (Anti-Retroviral Therapy) with three episodes of visceral leishmaniasis diagnosed on bone marrow examination treated with a combination of liposomal amphotericin B and miltefosine.

Hepatotoxicity in HIV Patients, An Observational Study in Patients from Tertiary Care Centre of Western India.

OBJECTIVE: HIV AIDS has currently become a chronic manageable condition with HAART, but with its chronicity and lifelong therapy currently the adverse drug reactions to these drugs are the main concern for any treating physician. Hepatotoxicity is one of the prime concerns of any physician managing HIV patients. We observe a number of patients reporting hepatotoxicity in our cohort and this had great impact on the efficacy and intake of the HAART drugs, this led us to explore this area and to find out the prevalence and etiologies in our cohort. METHODS: Thus we conducted this observational study to determine the prevalence of hepatotoxicity, the various etiologies for hepatotoxicity and assess HAART as the etiology of hepatotoxicity .The study was conducted in the virology department after obtaining ethics committee approval and incompliance with ICH, GCP guidelines. The study was conducted over a span of 3 months and data was collected and analyzed. RESULTS: Data of 178 Subjects was considered for evaluation of which 10 were excluded due to incomplete information. 168 patients with hepatotoxicity were assessed in the study, the prevalence of hepatotoxicity in our cohort was around 2.25%. Of the 168 patients 111 were male and 57 were female.52 patients were on Antituberculosis therapy (ATT) and thus 30.95% was the incidence rate of hepatotoxicity due to ATT. 23.80% (40 out of 168) were alcoholic and hence it was the etiological agent. HAART as the etiology was observed in 5 patients,2.97%being the incidence .Hepatitis B as the causative agent for hepatotoxicity was observed in 3.57% patients. CONCLUSIONS: We thus concluded that ATT and alcoholism are major areas of concern in HIV patients and thus a strict monitoring is warranted while prescribing ATT at the same time deaddiction is equally important. HAART induced hepatotoxicity is observed only in a small section of patients and thus these drugs need not be attributed as culprits blindly and put to disrepute.

Indian Adolescent Living with HIV-AIDS: Current Clinical Scenario.

INTRODUCTION: Statistics suggest that, HIV has now largely become the disease of young patients. Hence, the adolescent HIV/AIDS needs to be handled and managed separately from adult HIV. Relatively fewer Indian data exist to characterize the associations in adolescents and young adults infected with HIV disease. The present study explores the current challenges in the management of HIV infected adolescents. OBJECTIVE: The study was aimed at evaluating, relationship between CD4 count and duration of antiretroviral therapy (ART), effects of ART on body mass index and the adverse effects of antiretroviral drugs in adolescent HIV positive patients. METHODS: This was a cross-sectional study involving 60 HIV positive adolescent patients attending tertiary care Institute KEM Hospital, Parel over duration of one year conducted at Mumbai. Patients on ART between age group 12 to 19 years. ART naïve patients were excluded from the study. RESULTS: 60 adolescent HIV positive patients attended our OPD including 37 males (61.67%) and 23 females (38.33%).The most common mode of transmission was vertical (80%). Education level was: school dropouts - 15%, primary education - 30%, Completed SSC - 31.7%, higher secondary - 23%. Among ADRs were 12 (63.15%) cases of anaemia due to Zidovudine, 4 (21.05%) hepatitis due to Nevirapine, 2 (10.52%) Tenofovir induced AKI and 1 (5.26%) Nevirapine rash. Wilcoxon matched pairs test showed a highly significant increase in the BMI (p <0.0001) post therapy. The mean CD4 of the patients at baseline and current presentation was 295.57 ± 109.81 and 630.93 ± 188.70 cells/mm3 respectively. The CD4 count was seen to be increasing with the increase in the duration of HAART treatment. CONCLUSIONS: High efficacy of HAART and availability of free ART under government programme has increased the duration of survival of the adolescent population with HIV. Treatment with HAART showed a favourable response with a statistical significant increase in CD4 count. Longer the duration of HAART, higher was the gain in CD4 count. Indian adolescent receiving long term ART, Lipodystrophy is not a troubling issue. Indian adolescent seems to be more tolerance of ART than the other parts of world.

Myasthenia Gravis with Amyotropic Lateral Sclerosis: A Rare Co-existence.

The co-occurrence of myasthenia gravis with motor neurone disease is not a very common association and may pose problem and confusion in the minds of the treating physician because of the gamut of neurological symptoms. This case intends to highlight these dilemmas.

Terahertz Spectroscopy and Solid-State Density Functional Theory Calculations of Cyanobenzaldehyde Isomers.

Spectral signatures in the terahertz (THz) frequency region are mainly due to bulk vibrations of the molecules. These resonances are highly sensitive to the relative position of atoms in a molecule as well as the crystal packing arrangement. To understand the variation of THz resonances, THz spectra (2-10 THz) of three structural isomers: 2-, 3-, and 4-cyanobenzaldehyde have been studied. THz spectra obtained from Fourier transform infrared (FTIR) spectrometry of these isomers show that the resonances are distinctly different especially below 5 THz. For understanding the intermolecular interactions due to hydrogen bonds, four molecule cluster simulations of each of the isomers have been carried out using the B3LYP density functional with the 6-31G(d,p) basis set in Gaussian09 software and the compliance constants are obtained. However, to understand the exact reason behind the observed resonances, simulation of each isomer considering the full crystal structure is essential. The crystal structure of each isomer has been determined using X-ray diffraction (XRD) analysis for carrying out crystal structure simulations. Density functional theory (DFT) simulations using CRYSTAL14 software, utilizing the hybrid density functional B3LYP, have been carried out to understand the vibrational modes. The bond lengths and bond angles from the optimized structures are compared with the XRD results in terms of root-mean-square-deviation (RMSD) values. Very low RMSD values confirm the overall accuracy of the results. The simulations are able to predict most of the spectral features exhibited by the isomers. The results show that low frequency modes (<3 THz) are mediated through hydrogen bonds and are dominated by intermolecular vibrations.

Scaling up the shape: a novel growth pattern of gallium clusters.

Putative global minima for Ga(N)⁺ clusters with size "N" ranging from 49 to 70 are found by employing the Kohn-Sham formulation of the density functional theory, and their evolution is described and discussed in detail. We have discovered a unique growth pattern in these clusters, all of which are hollow core-shell structures. They evolve with size from one spherical core-shell to the next spherical core-shell structure mediated by prolate geometries, with an increase in overall diameter of the core, as well as the shell, without putting on new layers of atoms. We also present a complete picture of bonding in gallium clusters by critically analyzing the molecular orbitals, the electron localization function, and Bader charges. Bonding in these clusters is a mixture of metallic and covalent type that leans towards covalency, accompanied by marginal charge transfer from the surface to the core. Most molecular orbitals of Ga clusters are non-jellium type. Covalency of bonding is supported by a wide localization window of electron localization function, and joining of its basins along the bonds.

Single-atom alloys of Cu(211) with earth-abundant metals for enhanced activity towards CO2 dissociation.

CO2, a byproduct from various industrial reactions, must not be released into the atmosphere and should be managed through capture, conversion, and utilization. The first step in converting CO2 into valuable products is to break the C-O bond. This work focuses on designing Single Atom Catalysts (SACs) by doping Cu(211) surface with 13 different s, p, and d block elements with an aim to minimize the activation barrier for C-O bond cleavage. Our work demonstrates that SACs of Mg/Al/Pt@Cu(211) favor CO2 chemisorption compared to Cu(211) where CO2 physisorbs. The barrier for CO2 dissociation is lowest for Mg@Cu(211) and it increases in the order Mg@Cu(211) < Al@Cu(211) < Pt@Cu(211) < Zn@Cu(211) < Ga@Cu(211) < Cu@Cu(211) < Pd@Cu(211). These findings suggest that doping Cu(211) with earth-abundant metal like Mg can potentially be a viable catalyst for CO2 conversion, providing a promising solution to reduce carbon footprint and mitigate climate change.

Clinical Profile and Adverse Effects of Dolutegravir Treatment in HIV-Positive Patients: A Prospective Observational Study.

Background The emergence of dolutegravir (DTG) within antiretroviral therapy (ART) has drastically improved the management of HIV/AIDS, marking a shift toward a chronic manageable condition. Nevertheless, concerns persist regarding the real-world tolerability and adverse effects (AEs) of DTG. Objective This study aims to explore the clinical characteristics, adverse reactions, and adherence to treatment with DTG among HIV-positive individuals. Methods Through a prospective approach, we examined HIV-positive patients undergoing DTG-based ART regimens. Key parameters, including socio-demographic data, treatment adherence, and clusters of differentiation 4 (CD4) count, were evaluated. Enrolled patients were followed up for six months for the development of comorbidities and AEs. Results Initial observations indicate successful viral suppression and enhanced CD4 counts with DTG-based regimens, t(318)=2.0664, p=0.0392. However, a subset of participants experienced AEs such as neuropsychiatric symptoms (headaches and mood fluctuations), unintended weight gain, and other comorbidities linked to prolonged ART usage. Conclusion While DTG-based therapies offer substantial advantages in HIV/AIDS management, such as rapid viral suppression and reduced toxicity, ongoing vigilance for adverse effects, particularly neuropsychiatric symptoms and metabolic disturbances, is imperative for optimizing patient care. Further research is necessary to fully elucidate the safety profile of DTG in real-world scenarios and mitigate potential adverse reactions.

Evaluation of the Efficacy of Tofacitinib, a JAK Inhibitor, in Alleviating Sepsis-Induced Multiple Organ Dysfunction Syndrome.

Sepsis, a life-threatening condition triggered by an uncontrolled response to infection, results in a systemic inflammatory response syndrome (SIRS) and the failure of multiple organs leading to multiple organ dysfunction (MODS). In the present study, we investigated the therapeutic potential of tofacitinib (TOFA), an FDA-approved inhibitor of JAK1 and JAK3 against sepsis, using a mouse model induced by cecal ligation puncture (CLP). Swiss albino mice were employed to replicate the CLP-induced sepsis model and were randomly divided into four groups: control, CLP, 150 mg/kg TOFA, and 300 mg/kg TOFA. Six hours after the last TOFA dose, we collected blood and tissue samples from the liver, lungs, kidneys, and spleen for histological analysis. Blood samples were used to assess granulocyte and lymphocyte percentages. Throughout the experiment, we monitored body weight and short-term survival. Our comparative histological analysis revealed that 150 mg/kg TOFA had a protective effect against multiple organ damage. Conversely, the study highlighted the harmful effects of 300 mg/kg TOFA, primarily due to liver and renal toxicity within this group. In summary, our findings demonstrate that tofacitinib at an optimal dose of 150 mg/kg showed promise as a potential therapeutic intervention for sepsis-induced multiple organ failure. However, caution is warranted when considering higher dosages.

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.

Extremozymes and compatible solute production potential of halophilic and halotolerant bacteria isolated from crop rhizospheric soils of Southwest Saurashtra Gujarat.

Halophiles are one of the classes of extremophilic microorganisms that can flourish in environments with very high salt concentrations. In this study, fifteen bacterial strains isolated from various crop rhizospheric soils of agricultural fields along the Southwest coastline of Saurashtra, Gujarat, and identified by 16S rRNA gene sequencing as Halomonas pacifica, H. stenophila, H. salifodinae, H. binhaiensis, Oceanobacillus oncorhynchi, and Bacillus paralicheniformis were investigated for their potentiality to produce extremozymes and compatible solute. The isolates showed the production of halophilic protease, cellulase, and chitinase enzymes ranging from 6.90 to 35.38, 0.004-0.042, and 0.097-0.550 U ml-1, respectively. The production of ectoine-compatible solute ranged from 0.01 to 3.17 mg l-1. Furthermore, the investigation of the ectoine-compatible solute production at the molecular level by PCR showed the presence of the ectoine synthase gene responsible for its biosynthesis in the isolates. Besides, it also showed the presence of glycine betaine biosynthetic gene betaine aldehyde dehydrogenase in the isolates. The compatible solute production by these isolates may be linked to their ability to produce extremozymes under saline conditions, which could protect them from salt-induced denaturation, potentially enhancing their stability and activity. This correlation warrants further investigation.