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ABSTRACT With its rising incidence, non-alcoholic fatty liver disease (NAFLD) has become a global health problem. Hepatic lipid buildup, inflammation, and oxidative stress are the results of complex interactions between metabolic, genetic, and environmental variables in the development of nonalcoholic fatty liver disease. The potential significance of antioxidants generated from phytochemicals in alleviating non-alcoholic liver damage has garnered substantial interest among the many treatment methods. The goal of this thorough review is to summarize and assess the body of research on the application of antioxidants derived from phytochemicals in the treatment of non-alcoholic fatty liver disease. A comprehensive examination of peer-reviewed research from many databases demonstrates a wide variety of phytochemicals with antioxidant characteristics and their possible effects on oxidative stress, inflammation, and hepatic lipid metabolism. Prominent phytochemicals such as curcumin, resveratrol, quercetin, silymarin, and green tea catechins are among those whose antioxidative processes are included in the review. Preclinical and clinical research on these substances have revealed encouraging results, suggesting that they may be able to lessen inflammation and hepatic steatosis while also enhancing liver function. We investigate the molecular mechanisms underlying their protective benefits, including reduction of pro-inflammatory cytokines and modification of nuclear factor-erythroid 2-related factor 2 (Nrf2). The study also discusses the shortcomings and difficulties in the existing research, highlighting the necessity of more clinical trials, standardized dosing schedules, and research into the possible synergistic effects of mixing several phytochemicals. To present a fair picture of the therapeutic application of phytochemical antioxidants, safety issues and possible negative effects are also included. This review emphasizes the potential use of phytochemical-derived antioxidants in the treatment of non-alcoholic hepatic damage. Including these organic substances in all-encompassing lifestyle interventions might be a good way to both prevent and cure NAFLD. Keywords: Phytochemicals, Non-alcoholic fatty liver disease (NAFLD), Anti-oxidants, Non-alcoholic steatohepatitis (NASH), Toxicity.

We selected three superstorms (disturbance storm time [Dst] index less than −350 nT) of 2003–04 to study the thermospheric energy budget with a particular emphasis on the thermospheric cooling emission by nitric oxide via a wavelength of 5.3 μm. The nitric oxide radiative emission data are obtained from the Sounding of the Atmosphere by Broadband Emission Radiometry (SABER) instrument onboard the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite and the thermosphere ionosphere electrodynamic general circulation model (TIEGCM) simulation. Different energy sources for the magnetospheric energy injection and the thermospheric/ionospheric dissipation processes are calculated using empirical formulations, model simulations, and space-borne and ground-based measurements. The Joule heating rates calculated from different sources showed similar variations but significant differences in the magnitude. The nitric oxide cooling power is calculated by zonally and meridionally integrating the cooling flux in the altitude range of 100–250 km. The satellite observed that cooling flux responds faster to the energy input, as compared to the modeled results. The cooling power increases by an order of magnitude during storm time with maximum radiation observed during the recovery phase. Both the satellite-observed and modeled cooling powers show a strong positive correlation with the Joule heating power during the main phase of the storm. It is found that the maximum radiative power does not occur during the strongest storm, and it strongly depends on the duration of the main phase. The model simulation predicts a higher cooling power than that predicted by the observation. During a typical superstorm, on average, a cooling power of 1.87 × 105 GW exiting the thermosphere is estimated by the TIEGCM simulation. On average, it is about 40% higher than the satellite observation.

Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood–brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.

Despite more than 20 years of combination antiretroviral therapy (cART), complete eradication of HIV remains a daunting task. While cART has been very effective in limiting new cycles of infection and keeping viral load below detectable levels with partial restoration of immune functions, it cannot provide a cure. Evidently, the interruption of cART leads to a quick rebound of the viral load within a few weeks. These consistent observations have revealed HIV ability to persist as an undetectable latent reservoir in a variety of tissues that remain insensitive to antiretroviral therapies. The ‘Block-and-Lock’ approach to drive latent cells into deep latency has emerged as a viable strategy to achieve a functional cure. It entails the development of latency-promoting agents with anti-HIV functions. Recent reports have suggested sulforaphane (SFN), an inducer of NRF-2 (nuclear erythroid 2-related factor 2)-mediated antioxidative signaling, to possess anti-HIV properties by restricting HIV replication at the early stages. However, the effect of SFN on the expression of integrated provirus remains unexplored. We have hypothesized that SFN may promote latency and prevent reactivation. Our results indicate that SFN can render latently infected monocytes and CD4+ T cells resistant to reactivation. SFN treatments antagonized the effects of known latency reactivating agents, tumor necrosis pactor (TNF-α), and phorbol 12-myristate 13-acetate (PMA), and caused a significant reduction in HIV transcription, viral RNA copies, and p24 levels. Furthermore, this block of reactivation was found to be mediated by SFN-induced NRF-2 signaling that specifically decreased the activation of NFκB signaling and thus restricted the HIV-1 promoter (5′LTR) activity. Overall, our study provides compelling evidence to highlight the latency-promoting potential of SFN which could be used in the ‘Block-and-Lock’ approach to achieve an HIV cure.

Abstract Background and objectives Data on the association of vitamin D levels and clinical phenotype and disease activity in systemic lupus erythematosus (SLE) is controversial. Further, the optimal dose of oral vitamin D supplementation in SLE is not clear. Thus, the present study was designed to determine the association of plasma vitamin D levels with clinical phenotype, disease variables and serology in a large, cohort of SLE from South Asia and to evaluate the short-term effect of two different dosage regimens of oral vitamin D supplementation on disease flares and plasma vitamin D levels. Methods This is a two-phase study. Phase I was a cross-sectional analytical study of patients from north (26.85° N) and south India (11.94° N). Plasma 25-hydroxyvitamin-D(25(OH)D) was measured, and its association with demography, serology, disease activity, Galectin-9 and CXCL-10 was analysed. In phase II, patients with SLEDAI-2KG

IntroductionDue to advances in combined anti-retroviral treatment (cART), there is an increased burden of age-related cerebrovascular disease (CBVD), in people living with HIV (PWH). The underlying CNS injury can be assessed by measuring cerebral blood flow (CBF) and cerebrovascular reactivity (CVR).Methods35 treatment-naïve PWH and 53 HIV negative controls (HC) were enrolled in this study. Study participants underwent T1-weighted anatomical, pseudo-continuous arterial spin labeling, and resting-state functional MRI to obtain measures of CBF and CVR prior to starting cART treatment and at two-time points (12 weeks and 2 years) post-cART initiation. Controls were scanned at the baseline and 2-year visits. We also measured plasma levels of microparticles of endothelial and glial origin and well-known endothelial inflammation markers, ICAM-1 and VCAM-1, to assess HIV-associated endothelial inflammation and the interaction of these peripheral markers with brain neurovascular function.ResultsHIV infection was found to be associated with reduced CVR and increased levels of endothelial and glial microparticles (MPs) prior to initiation of cART. Further, CVR correlated negatively with peripheral MP levels in PWH.DiscussionOur results suggest that while cART treatment has a beneficial effect on the neurovascular function after initiation, these benefits are suboptimal over time.

IntroductionOvarian cancer recurs in most High Grade Serous Ovarian Cancer (HGSOC) patients, including initial responders, after standard of care. To improve patient survival, we need to identify and understand the factors contributing to early or late recurrence and therapeutically target these mechanisms. We hypothesized that in HGSOC, the response to chemotherapy is associated with a specific gene expression signature determined by the tumor microenvironment. In this study, we sought to determine the differences in gene expression and the tumor immune microenvironment between patients who show early recurrence (within 6 months) compared to those who show late recurrence following chemotherapy.MethodsPaired tumor samples were obtained before and after Carboplatin and Taxol chemotherapy from 24 patients with HGSOC. Bioinformatic transcriptomic analysis was performed on the tumor samples to determine the gene expression signature associated with differences in recurrence pattern. Gene Ontology and Pathway analysis was performed using AdvaitaBio’s iPathwayGuide software. Tumor immune cell fractions were imputed using CIBERSORTx. Results were compared between late recurrence and early recurrence patients, and between paired pre-chemotherapy and post-chemotherapy samples.ResultsThere was no statistically significant difference between early recurrence or late recurrence ovarian tumors pre-chemotherapy. However, chemotherapy induced significant immunological changes in tumors from late recurrence patients but had no impact on tumors from early recurrence patients. The key immunological change induced by chemotherapy in late recurrence patients was the reversal of pro-tumor immune signature.DiscussionWe report for the first time, the association between immunological modifications in response to chemotherapy and the time of recurrence. Our findings provide novel opportunities to ultimately improve ovarian cancer patient survival.

This investigation focuses on the wear resistance and surface morphology of multi-walled carbon nanotube (MWCNT)-filled bio-based epoxy composites. This study examines the impact of different MWCNT concentrations (0 Wt.%, 0.25 Wt.%, 0.50 Wt.%, and 0.75 Wt.%) on the wear properties of these composites. Techniques such as scanning electron microscopy (SEM) and atomic force microscopy (AFM) were utilized for comprehensive surface characterization. The results demonstrated a direct correlation between the MWCNT content and the wear resistance of the composites, which were corroborated by robust statistical analysis. Furthermore, SEM and AFM observations disclosed incremental enhancements in both wear resistance and surface quality as the MWCNT concentration increased. This research not only augments the understanding of wear mechanisms in bio-based epoxy composites but also aligns with the burgeoning focus on sustainable materials.

Background and Objectives: Saline adenine glucose mannitol (SAGM) with citrate phosphate dextrose (CPD) or CPD adenine (CPDA) are two common red cell preservatives used in our country. This study analyzed and compared serial biochemical changes on different days of storage in irradiated packed red blood cells stored in CPDA and SAGM solutions. The aim of this study was to see if these changes are influenced by or different, if any, in these two storage solutions. Patients and Methods: Ninety units of RBCs were randomly chosen, with 45 units each collected in CPDA and SAGM, respectively. Nine units each were irradiated by gamma irradiator using cobalt 60 (BI 2000) on days 1, 7, 14, and 21 of their storage, respectively. Nine units were not irradiated and used as controls. All the units were weekly assessed for their plasma levels of potassium, sodium, glucose, lactate dehydrogenase (LDH), and lactate by Clinical Chemistry Auto-analyzer, Beckman Coulter AU680. The values were documented and analyzed by SPSS. Results: Baseline values on day 1 for potassium, lactate, and LDH were similar between SAGM- and CPDA-stored blood bags. Glucose and sodium levels were slightly higher in SAGM bags compared to CPDA. Postirradiation, the changes (increase in K+, Lactate, LDH and decrease in Na+, glucose) were higher in CPDA bags than SAGM bags, and the difference in this trend was not significantly different from that seen in nonirradiated blood bags stored in these two preservative solutions. Conclusion: Storage lesions (biochemical parameters) after irradiation were severe, but paralleled that observed in nonirradiated bags. The storage solution, either SAGM or CPDA, made no difference to these changes.

Objective: The objective of this study is to identify factors associated with active tuberculosis (TB) in patients with systemic lupus erythematosus (SLE) and to study the impact of TB on SLE disease activity. Methodology: We screened case records of 643 individuals with SLE for the diagnosis of TB. SLE patients with TB (cases) (n = 29) were matched for age, sex, and disease duration in the ratio of 1:3 with controls (n = 94) (SLE without TB). Results: Pulmonary TB was seen in 41% (n = 12) and extrapulmonary TB in 59% (n = 17). Musculoskeletal TB (n = 6; 34.2%) was the most common extrapulmonary manifestation. TB was seen among those with lupus nephritis (55% vs. 38.4%) (P < 0.005) and those with autoimmune hemolytic anemia (48% vs. 38%). A higher median dose of daily glucocorticoids 11.5 (7.5–30) in 1 month preceding TB diagnosis was associated with a higher incidence of TB. Upon multivariable analysis, 1 month mean daily dose of glucocorticoids ≥ 7.5 mg (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.07–2) was independently associated with TB. On a follow-up duration of 16 months, SLE flare was more among those with TB as compared to the controls (OR-2.49 95%; CI-1.39–4.48; P = 0.002). Conclusion: Extrapulmonary TB is the most common form in individuals with SLE. A higher steroid dose seems to predispose to TB infection. TB infection may increase the risk of SLE disease flare.

The temporal response of thermospheric CO2 and NO cooling emissions is investigated during ICME and CIR-driven geomagnetic storms by using data from the SABER instrument onboard the TIMED, GRACE, and DMSP satellites. The superposed epoch analysis reveals that the cooling emissions experience a strong enhancement and quick recovery to pre-event value within 3–4 days during CME storms. Whereas, it shows slower recovery that lasts for more than 6–7 days during CIR-driven storms. We performed detailed study of NO cooling emission owing to the fact that the production of NO depends on the external energy input. The different response of thermospheric NO cooling during CME and CIR storms can be attributed to differences in precipitation of particle (electron and ion) fluxes. A strong correlation with a positive timelag is observed between NO cooling emission and Dst index, coupling functions and particle flux. Further, the correlation between NO cooling flux and particle flux displays a distinct and stronger correlation during CIR storms as compared to CME. This study also shows that the Newell coupling function (normalized cross-correlation, r = 0.90 for CME and r = 0.92 for CIR) and the Akasofu parameter (r = 0.92 for CME, r = 0.76 for CIR) are better correlated with NO cooling flux, respectively, during CIR- and ICME-driven storms.

Abstract The “quantum complexity” of a unitary operator measures the difficulty of its construction from a set of elementary quantum gates. While the notion of quantum complexity was first introduced as a quantum generalization of the classical computational complexity, it has since been argued to hold a fundamental significance in its own right, as a physical quantity analogous to the thermodynamic entropy. In this paper, we present a unified perspective on various notions of quantum complexity, viewed as functions on the space of unitary operators. One striking feature of these functions is that they can exhibit non-smooth and even fractal behaviour. We use ideas from Diophantine approximation theory and sub-Riemannian geometry to rigorously quantify this lack of smoothness. Implications for the physical meaning of quantum complexity are discussed.

The geomagnetic storm is the manifestation of the solar wind–magnetosphere interaction. It deposits huge amount of the solar energy into the magnetosphere–ionosphere–thermosphere (MIT) system. This energy creates global perturbations in the chemistry, dynamics, and energetics of the MIT system. The high latitude energy deposition results in the Joule and particle heating that subsequently increases the thermospheric temperature. The thermospheric temperature is effectively regulated by the process of thermospheric cooling emission by nitric oxide via 5.3 µm. A peculiar, intense geomagnetic storm (Dst = −105 nT) occurred during 21–22 January 2005, where the main phase developed during the northward orientation of the z-component of interplanetary magnetic field. We utilized the nitric oxide 5.3 µm infrared emission from the NCAR’s Thermosphere–Ionosphere–Electrodynamics General Circulation Model (TIEGCM) simulation and the Sounding of Atmosphere using Broadband Emission Radiometry (SABER) onboard the thermosphere–ionosphere–mesosphere energetic and dynamics satellite to investigate its response to this anomalous geomagnetic storm. We compared the model results with the observations on both the local and global scales. It is observed that the model results agree very well with the observations during quiet times. However, the model severely underestimates the cooling emission by one-fourth of the observations, although it predicts an enhancement in the thermospheric temperature and densities of atomic oxygen and nitric oxide during the geomagnetic storm.

Abstract It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.

Background: Till date, SARS CoV2 (COVID-19) is a pandemic viral infection in the world with the main and strong impact on respiratory airway, but this virus can affect any system of the human body. Aims: This research is aimed to dictating the effect of SARS CoV2 infections on hematological, biochemical, and arterial blood gas parameters by using their mean values. Settings and Design: This retrospective study was included a total no. of 97 SARS CoV2 positive patients from 27 March to 15 May 2020. All positive patients were consented and took all the significant details. Materials and Methods: We review the total 97 COVID-19 positive patients after obtaining all the hematological and other relevant clinical data from laboratory and medical records. The subjects were tabulated into three categories named; admitted (Gp A), discharged (Gp B), and expired (Gp C) patients and compared their hematological, biochemical parameters, and arterial blood gas analysis by using blood or serum and processed by proper methods. Statistical Analysis: The data was cleaned, edited, checked for completeness, and processed then entered in SPSS version 20 statistical software. Results: Blood samples were collected of all positive patients. Most of the patients had X-ray changes. Blood parameters showed that patients who were expired (Gp-C) suffered from anemia, lymphopenia, leucoytosis, neutrophilia, and thrombocytopenia with high ALT, pCO2 and low pO2 than admitted and expelled patients. Conclusions: Result from this study provides that WBC count, absolute lymphocyte count, neutrophil count, and pO2 were independently associated and an important forecaster of mortality from SARS CoV2. All healthcare provides to regularly monitor above parameters indicators of COVID-19 infected patients to improve their quality of life and to reduce the risk of mortality rate.

INTRODUCTION: Gamma Irradiation of blood products accentuates biochemical changes in the blood stored at 4°C. This study tried to compare the changes in potassium, sodium, glucose, lactate, and lactate dehydrogenase (LDH) levels in packed red blood cell (PRBC) units irradiated at various time points and then stored versus those stored for a particular period then irradiated.METHODOLOGY: One hundred and eighty units of RBCs were randomly assigned equally to be irradiated or not. Eighteen units each were irradiated by gamma irradiator using cobalt 60 (BI 2000) on day 1, 7, 14, 21, and 28 of their storage, respectively, in the irradiation group. All the units were assessed for their plasma levels of potassium, sodium, glucose, LDH, and lactate by clinical chemistry auto analyzer Beckman coulter AU680 weekly. The values were documented and analyzed by SPSS.RESULTS: Baseline values on day 1 for studied biochemical parameters were comparable between irradiated and nonirradiated groups. Mean values of potassium, lactate and LDH were higher in irradiated than nonirradiated PRBC bags. In contrast, Sodium and Glucose mean values were lower than baseline values. Maximum cumulative mean values were noted in day-21 irradiated bags when the parameters were measured on day-28 for potassium and lactate levels. This was followed by day 14 irradiated bags, followed by day 7 irradiated bags.CONCLUSION: The study indicates that irradiation of red cells later in their storage period had comparatively more detrimental changes in relation to potassium and lactate than irradiation in earlier days. Consideration of irradiation to be performed as close to the issue as possible to reduce a lesser number of days of storage postirradiation is to be explored.

JAK1 plays a significant role in the intracellular signaling by interacting with cytokine receptors in different types of cells and is linked to the pathogenesis of various cancers and in the pathology of the immune system. In this study, ligand-based pharmacophore modeling combined with virtual screening and molecular docking methods was incorporated to identify the potent and selective lead compounds for JAK1. Initially, the ligand-based pharmacophore models were generated using a set of 52 JAK1 inhibitors named C-2 methyl/hydroxyethyl imidazopyrrolopyridines derivatives. Twenty-seven pharmacophore models with five and six pharmacophore features were generated and validated using potency and selectivity validation methods. During potency validation, the Guner-Henry score was calculated to check the accuracy of the generated models, whereas in selectivity validation, the pharmacophore models that are capable of identifying selective JAK1 inhibitors were evaluated. Based on the validation results, the best pharmacophore models ADHRRR, DDHRRR, DDRRR, DPRRR, DHRRR, ADRRR, DDHRR, and ADPRR were selected and taken for virtual screening against the Maybridge, Asinex, Chemdiv, Enamine, Lifechemicals, and Zinc database to identify the new molecules with novel scaffold that can bind to JAK1. A total of 4,265 hits were identified from screening and checked for acceptable drug-like properties. A total of 2,856 hits were selected after ADME predictions and taken for Glide molecular docking to assess the accurate binding modes of the lead candidates. Ninety molecules were shortlisted based on binding energy and H-bond interactions with the important residues of JAK1. The docking results were authenticated by calculating binding free energy for protein–ligand complexes using the MM-GBSA calculation and induced fit docking methods. Subsequently, the cross-docking approach was carried out to recognize the selective JAK1 lead compounds. Finally, top five lead compounds that were potent and selective against JAK1 were selected and validated using molecular dynamics simulation. Besides, the density functional theory study was also carried out for the selected leads. Through various computational studies, we observed good potency and selectivity of these lead compounds when compared with the drug ruxolitinib. Compounds such as T5923555 and T5923531 were found to be the best and can be further validated using in vitro and in vivo methods.

Abstract Background Kratom is a habit-forming opioid-like substance with an acute toxidrome of various symptoms such as diaphoresis, dizziness, nausea, and vomiting. Chronic users require increasing dosages for the analgesic effects. Although kratom use dates back to the 1800s in Asia, kratom intoxication is still a novel (but increasing) toxidrome in the Western world. Here, we present a novel case of acute toxicity from overdose in a kratom-naïve patient, taking place through recommendation by a family member who chronically takes this substance. Case presentation We present the case of a 62-year-old woman arriving to the emergency department (ED) with a chief complaint of intractable vomiting after ingestion of kratom. After a day of yard work, she was in pain, secondary to her osteoporotic joints. She was recommended kratom from a family member, who stated he was using kratom to transition away from opioid dependence. She took two “scoops.” She proceeded to have multiple episodes of vomiting at home. She came to the ED, where she required multiple rounds of anti-emetic medication for resolution of her symptoms. Discussion We present a classic case of a novel acute toxicity: kratom. A unique aspect of this case is the circumstance by which this toxicity took place: a family member who chronically takes this substance (that requires increasing dosages to remain effective) recommended a dosage to this kratom-naïve patient, leading to overdose. This opioid family alternative substance is gaining popularity across the USA in the era of the opioid crisis. Further documentation of case reports and research is required to learn the associated risks of the use of this substance.

Background: We surveyed rheumatology consultants regarding their perceptions about rheumatology practice and training in India. Materials and Methods: A structured questionnaire was administered during two national rheumatology meetings to evaluate practice settings and demographic characteristics of patients seen. We also assessed perceptions regarding junior doctors, auxiliary health professionals (AHPs), ancillary facilities (daycare, intra-articular injections, musculoskeletal ultrasound [MSKUS]), and possible government-driven strategies for improving rheumatology care delivery. Results: The response rate was 56% (70/125); 68 complete responses were further analyzed. Most respondents were in the private sector (56/68), had been in practice for a mean of 11.5 (±8.4) years, attended to a mean of 150 (±91) patients every week, a majority of whom were educated upto intermediate level and belonged to the middle class. About 60% had junior doctors to assist them in care delivery; 82.5% (52/63) felt that junior doctors had limited competence in managing rheumatic diseases. More than 90% felt the need for AHPs in the clinic, although less than one-half had access to such personnel. Most utilized ancillary services like intra-articular injections (97%), daycare facilities for infusions (92%), and MSKUS (71%). More than 90% respondents felt that government-funded programs for the management of rheumatic diseases, coupled with a structured referral system, would be useful. Conclusion: Rheumatology practice in India may improve by better training junior doctors in skills related to rheumatology at the undergraduate and postgraduate internal medicine levels. The development of specialist AHPs may help enhance service delivery. Government programs for community management of rheumatic diseases and management guidelines suited to the needs of a developing economy majorly reliant on out-of-pocket expenditure for healthcare are significant areas for development.

Instructional Dairy Farm at Pantnagar University was studied for evaluating its energetic efficiency, an important measure to evaluate the functioning of a production system. The total organic inputs and outputs of the dairy farm were converted into their respective energy values. Of the total energy flows involved in the dairy farm, 72.6% was the input energy suggesting that most of the energy flow in the dairy farm takes place through feeds. Of the total energy output, dung accounted for 54.83% and milk 44.86%. Only 0.31% of the total output energy was contained in the new born calves. The energy balance of the dairy farm reflected that dung was the most important product, though milk was regarded as most valuable product as it is used for direct human consumption. Gross energetic efficiency of the farm worked out to be 37.7%. This reflects that 62.3% of the total energy was being used for nonproductive purposes (methane production or others).

Objectives: To assess the performance of clinical and biochemical parameters in identifying renal histopathology. To assess the performance of a combination of demographic, clinical, serological and histopathological parameters in determining renal response at one year. Methods: Data of biopsy-proven (ISN/RPS—2003 criteria) Lupus Nephritis (LN) were extracted from the institute database. Demographic, clinical and biochemical parameters at the time of biopsy were noted, and their associations with histopathological class, activity and chronicity scores were evaluated. Follow-up data at one year were collected. Complete, partial or no response (CR, PR, NR) for renal outcomes at one year and the predictors of NR were assessed. Results: Out of the 333 renal biopsies, 240 (71.8%) were Class III/IV. More patients with Class III/IV LN had hypertension (52.1%) and low eGFR (p < 0.001). Among Class III/IV, AS correlated weakly with UPCR (r = 0.31, p < 0.01), eGFR (r = −0.172; p < 0.01) and CS with eGFR (r = −0.212; p < 0.01). The presence of either hypertension, UPCR > 0.5 g/day, active urinary sediments or serum creatinine >1.3 g/dL had a sensitivity of >96% and specificity of p < 0.001), those with abnormal baseline creatinine (aOR: 1.9, 95% CI: 1.1–3.2, p < 0.001), higher renal SLEDAI (p < 0.05), higher AS, CS (p < 0.001) and interstitial inflammation (p < 0.005). In the binary logistic regression, the combination of male sex, baseline creatinine, UPCR and CS performed best in predicting NR (AUC: 0.762; 95% CI: 0.684–0.840, p < 0.001). Conclusions: Clinical and biochemical parameters alone have a poor specificity in identifying renal histopathology. A combination of demographic, clinical and histopathology parameters can better predict renal outcomes at one year.

Animals, environment and sustainability are related with each other. The intricate soil-plant-animal relationship is vital for the very ecological integrity of the biosphere. Animal diversity, both inter- and intra-species, has multiple socio-economic attributes. In an agroecosystem with uncultivated land, cultivated land, livestock and households as the integral components, livestock play crucial role in transferring nutrients from ecologically more sustainable ecosystem (forest/ rangeland/ grassland) to ecologically vulnerable one (cultivated land), and in the recycling of nutrients in the cultivated lands. Draught animal power (DAP) is a key source for realizing sustainability in traditional agricultural systems which is ensured by their role in enhancing ecological processes—cropping diversification, agro-biodiversity maintenance, and soil fertility management. Farm animals also play negative role leading to environmental degradation through overgrazing and carbon emissions. Grazing animals significantly affect an ecosystem in triple ways, viz. herbivory, physical effects, and deposition. Overgrazing alters community structure as well as ecosystem functioning, including primary productivity and it has triggering effects on an ecosystem. Farm animals are key agents as well as sufferers of the on-going climate change. Their role in land degradation, water pollution, biodiversity erosion and release of GHGs contributes to exacerbate global warming.

Mastery of ear anatomy and otologic surgical skills is challenging for trainees, and educational resources are limited. Advancements in 3-dimensional (3D) printing have enabled the construction of complex microscopic models. Otoendoscopy provides excellent visualization and has been shown to enhance anatomic learning. Our aim was to develop a 3D model of the middle ear and external auditory canal using computed tomography images of a pediatric temporal bone for use with otoendoscopes. Resulting models are life sized, anatomically accurate, and allow for identification of relevant middle ear structures. Forty-six trainees were recruited for a pilot study and randomized to study using the model or standard resources. There were no differences in pretest, posttest, or 1-week posttest performance between groups; however, trainees assigned to the model reported higher prospective interest, satisfaction, and subjective improvement. This model may be used with otoendoscopes for anatomic and surgical training and represents an advancement in otologic surgical simulation.

One of the ways to address the critical gap of trained human resources in health is to train frontline workers (FLW) on health prevention and health promotion. The FLW play an important role in community mobilization, outreach activities, and service delivery at the last mile. In rural India, the number of internet and smartphone users is rapidly increasing, presenting an opportunity to reach and virtually train FLW. The current evidence base shows progress towards creating and using mobile-based training, but significant work is needed to improve the quality of mobile-based training programs. This study showcases Project *Samvad*’s experience in creating and rolling out a virtual training course for FLW, highlighting the feasibility of virtual training at scale and the quality of engagement of the participants with the course content. The method for this descriptive study is divided into two broad categories: (i) course development, promotion, and rollout processes, and (ii) course evaluation. Both qualitative and quantitative approaches were used to collect and analyze data. We found that the overall average course completion rate was 82% (992 out of 1211 registrants). The average increase in the endline question accuracy was around 15 percentage points from the baseline. We conclude that mobile-based virtual training of FLW is feasible and program managers and policymakers should consider creating hyperlocal course content, ensure participation of partners at various stages of development and rollout of the course and use a peer-to-peer and community-led system to support the learners.

Early onset pre-eclampsia (pre-eclampsia at less than 34 gestational weeks) is a severe form of preeclampsia; in addition, some women may also develop nephrotic range proteinuria. De novo diagnosis of lupus nephritis (LN) in pregnancy is challenging as it may present with features similar to commonly occurring preeclampsia. We report three cases of early onset pre-eclampsia with nephrotic range proteinuria and subsequent diagnosis of LN at the Women and Children hospital attached to Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, between 2014 and 2017. These cases highlights the need for further evaluation of the association between nephrotic-range proteinuria and early onset pre-eclampsia. The index of suspicion for underlying LN of these type of cases should be high. Earlier detection of LN will prompt better management that can avert or delay short- and long-term morbidity. Keywords: Lupus Nephritis; Pre-Eclampsia; Nephrotic Syndrome; Proteinuria; Case Reports; India.

Autoimmune inflammatory rheumatic diseases, also termed as autoimmune collagen vascular diseases, as the name suggests are the group of illness arising from a combination of loss of tolerance to self-antigens and shifting of the immune system into self-destructive overdrive. These are commonly classified under six mutually exclusive diseases which include systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis, polymyositis, rheumatoid arthritis (RA), and primary Sjögren syndrome, the so-called definitive connective tissue diseases. Undifferentiated and mixed connective tissue disease and overlap syndrome have also been added to the classification. An initially undifferentiated connective tissue disease may later evolve into a differentiated connective tissue disease. Here, we define the various connective tissue diseases and elaborate more upon SLE and its overlap, including the overlap of RA (RHUPUS).

Background We hypothesize that the addition of local infiltration analgesia (LIA) to a multimodal pain protocol will reduce the total amount of opioids consumed for acute pain control post total knee arthrolplasty (TKA). Methods This study was a retrospective, matched pair study including patients who had primary TKA. All patients included in the analysis had preoperative oral celecoxib and acetaminophen, had single-dose spinal anesthetic with intrathecal morphine, and had intravenous patient-controlled analgesia with an opioid agent in addition to gabapentin and celecoxib in the first 48 h. Patients whose charts were excluded from the study had revision TKA, received opioid therapy prior to the surgery, were classified as American Society of Anesthesiology (ASA) IV, and had general anesthesia. Fifty patients who underwent TKA and had LIA were matched for age, body mass index (BMI), and gender with patients who did not receive LIA. The primary outcome measures were total doses of opioids consumed post TKA. Results Patients receiving LIA consumed on average significantly less intravenous (IV) morphine equivalents than patients not receiving LIA, with a mean difference (±SD) of 88.9 ± 15.6 mg IV morphine equivalents. Furthermore, pain control was better in the LIA group. The incidences of nausea and vomiting, pruritis, and excessive sedation were higher in the non-LIA group compared to the LIA group. There was no difference in the hospital length of stay between both groups. Conclusions The addition of LIA to our multimodal pain protocol for TKA was associated with a reduction in total opioid consumption.

Heritability of Spondyloarthritis (SpA) is highlighted by several familial studies and a high association with the presence of human leukocyte antigen (HLA)-B*27. Though it has been over four decades since the association of HLA-B*27 with SpA was first determined, the pathophysiological roles played by specific HLA-B*27 allotypes are not fully understood. Popular hypotheses include the presentation of arthritogenic peptides, triggering of endoplasmic reticulum (ER) stress by misfolded HLA-B*27, and the interaction between free heavy chains or heavy chain homodimers of HLA-B*27 and immune receptors to drive IL-17 responses. Several non-HLA susceptibility loci have also been identified for SpA, including endoplasmic reticulum aminopeptidases (ERAP) and those related to the IL-23/IL-17 axes. In this review, we summarize clinical aspects of SpA including known characteristics of gut inflammation, enthesitis and new bone formation and the existing models for understanding the association of HLA-B*27 with disease pathogenesis. We also examine newer insights into the biology of HLA class I (HLA-I) proteins and their implications for expanding our understanding of HLA-B*27 contributions to SpA pathogenesis.

Allelopathic effects of Jatropha curcas L. aqueous stem extracts on two varieties each of five food crops, viz. Triticum aestivum (wheat), Zea mays (corn), Oryza sativa (rice), Glycine max (soybean) and Brassica juncea (mustard) were observed in the Tarai area of Uttarakhand in 2017-18. Different concentrations (0%, 5%, 10%, 15% and 20% w/v indicated as T0, T1, T2, T3 and T4, respectively) of Jatrophastem aqueous extract were bio-assayed against germination and seedling growth (plumule and radicle length) of the experimental crops. Significant differences in the normal germination between crops as well as their varieties were observed. Seed germination was significantly reduced (P

Background Microvesicles are cell membrane–derived vesicles that have been shown to augment inflammation. Specifically, monocyte‐derived microvesicles (MDMVs), which can express the coagulation protein tissue factor, contribute to thrombus formation and cardiovascular disease. People living with HIV experience higher prevalence of cardiovascular disease and also exhibit increased levels of plasma microvesicles. The process of microvesicle release has striking similarity to budding of enveloped viruses. The surface protein tetherin inhibits viral budding by physically tethering budding virus particles to cells. Hence, we investigated the role of tetherin in regulating the release of MDMVs during HIV infection. Methods and Results The plasma of aviremic HIV‐infected individuals had increased levels of tissue factor + MDMVs, as measured by flow cytometry, and correlated to reduced tetherin expression on monocytes. Superresolution confocal and electron microscopy showed that tetherin localized at the site of budding MDMVs. Mechanistic studies revealed that the exposure of monocytes to HIV‐encoded Tat triggered tetherin loss and subsequent rise in MDMV production. Overexpression of tetherin in monocytes led to morphologic changes in the pseudopodia directly underneath the MDMVs. Further, tetherin knockout mice demonstrated a higher number of circulating MDMVs and less time to bleeding cessation. Conclusions Our studies define a novel regulatory mechanism of MDMV release through tetherin and explore its contribution to the procoagulatory state that is frequently observed in people with HIV. Such insights could lead to improved therapies for individuals infected with HIV and also for those with cardiovascular disease.

Cet article analyse le film How Not to Be Seen: A Fucking Didactic Educational .MOV File qui, au-delà de ses apparences absurdes et humoristiques, offre une réflexion sur deux concepts émergents en art vidéo, celui du seuil de visibilité et celui d’inforensique. Pour ce faire, l’auteur retrace l’origine des images assemblées et problématise leurs liens avec l’histoire de la photographie aérienne et avec celle de la cartographie. Il examine également le sens des références symboliques et métaphoriques qui indiquent les échanges entre les mondes réel et virtuel.

Introduction: Microparticles (MPs) are submicron sized heterogeneous membrane-bound vesicles released from cells undergoing cell activation or apoptosis. Elevated platelet-derived MPs (PMPs) are reported in rheumatic diseases. We profiled Annexin-V+ MPs and CD61+ MPs in plasma and synovial fluid of patients with rheumatoid arthritis (RA) and their clinical correlates. Methods: Twenty-three newly diagnosed disease-modifying anti-rheumatic drug naïve patients with RA, 17 with osteoarthritis (OA) and 22 healthy controls (HC) were enrolled. Five milliliters of synovial fluid from the knee joint of patients with RA and OA was collected; 5 ml of peripheral blood was collected from patients with RA, OA, and HC. Cell-free synovial fluid and platelet poor plasma samples were stained with Annexin-V-APC and Anti-CD61-BV510 antibodies followed by flow cytometry analysis (FACSAria III) (results expressed as the mean ± standard deviation of % population). Results: Significantly greater levels of synovial fluid MPs (Annexin-V+ MPs) were observed in RA versus OA (P < 0.0001), significantly higher synovial fluid PMPs (Annexin V+ CD61+ MPs) levels in RA compared to HC (P = 0.0472). MPs other than those of platelet origin (Annexin V+ CD61− MPs) were also increased in the synovial fluid of RA patients compared to OA (P < 0.0001). Kruskal–Wallis test revealed the significant difference in the levels of plasma MPs (Annexin-V+), PMPs (Annexin V+ CD61+ MPs), and MPs other than those of platelet origin (Annexin V+ CD61− MPs) between RA, OA, and HC groups (P < 0.0001) with a higher percentage in RA group. Conclusions: Higher levels of Annexin-V+ MPs in both plasma and synovial fluid of RA suggest a role for MPs in the pathogenesis of RA. Elevated plasma PMPs (Annexin V+ CD61+ MPs) in RA may suggest their role in systemic involvement. Furthermore, increased levels of MPs other than those of platelet origin (Annexin V+ CD61− MPs) indicate the necessity to study the MPs from other cell lineages.