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BackgroundSARS-CoV-2 has spread substantially within India over multiple waves of the ongoing COVID-19 pandemic. However, the risk factors and disease burden associated with COVID-19 in India remain poorly understood. We aimed to assess predictors of infection and mortality within an active surveillance study, and to probe the completeness of case and mortality surveillance.MethodsIn this prospective, active surveillance study, we used data collected under expanded programmatic surveillance testing for SARS-CoV-2 in the district of Madurai, Tamil Nadu, India (population of 3 266 000 individuals). Prospective testing via RT-PCR was done in individuals with fever or acute respiratory symptoms as well as returning travellers, frontline workers, contacts of laboratory-confirmed COVID-19 cases, residents of containment zones, patients undergoing medical procedures, and other risk groups. Standardised data collection on symptoms and chronic comorbid conditions was done as part of routine intake. Additionally, seroprevalence of anti-SARS-CoV-2 immunoglobulin G was assessed via a cross-sectional survey recruiting adults across 38 clusters within Madurai District from Oct 19, 2020, to Nov 5, 2020. We estimated adjusted odds ratios (aORs) for positive RT-PCR results comparing individuals by age, sex, comorbid conditions, and aspects of clinical presentation. We estimated case-fatality ratios (CFRs) over the 30-day period following RT-PCR testing stratified by the same variables, and adjusted hazard ratios (aHRs) for death associated with age, sex, and comorbidity. We estimated infection-fatality ratios (IFRs) on the basis of age-specific seroprevalence.ResultsBetween May 20, 2020, and Oct 31, 2020, 13·5 diagnostic tests were done per 100 inhabitants within Madurai, as compared to 7·9 tests per 100 inhabitants throughout India. From a total of 440 253 RT-PCR tests, 15 781 (3·6%) SARS-CoV-2 infections were identified, with 8720 (5·4%) of 160 273 being positive among individuals with symptoms, and 7061 (2·5%) of 279 980 being positive among individuals without symptoms, at the time of presentation. Estimated aORs for symptomatic RT-PCR-confirmed infection increased continuously by a factor of 4·3 from ages 0-4 years to 80 years or older. By contrast, risk of asymptomatic RT-PCR-confirmed infection did not differ across ages 0-44 years, and thereafter increased by a factor of 1·6 between ages 45-49 years and 80 years or older. Seroprevalence was 40·1% (95% CI 35·8-44·6) at age 15 years or older by the end of the study period, indicating that RT-PCR clinical testing and surveillance testing identified only 1·4% (1·3-1·6%) of all infections in this age group. Among RT-PCR-confirmed cases, older age, male sex, and history of cancer, diabetes, other endocrine disorders, hypertension, other chronic circulatory disorders, respiratory disorders, and chronic kidney disease were each associated with elevated risk of mortality. The CFR among RT-PCR-confirmed cases was 2·4% (2·2-2·6); after age standardisation. At age 15 years or older, the IFR based on reported deaths was 0·043% (0·039-0·049), with reported deaths being only 11·0% (8·2-14·5) of the expected count.InterpretationIn a large-scale SARS-CoV-2 surveillance programme in Madurai, India, we identified equal risk of asymptomatic infection among children, teenagers, and working-age adults, and increasing risk of infection and death associated with older age and comorbidities. Establishing whether surveillance practices or differences in infection severity account for gaps between observed and expected mortality is of crucial importance to establishing the burden of COVID-19 in India.FundingThe Bill & Melinda Gates Foundation, the National Science Foundation, and the National Institute of General Medical Sciences.TranslationFor the Hindi translation of the abstract see Supplementary Materials section.

Bronchopulmonary dysplasia (BPD) is a chronic condition affecting preterm infants, characterized by lung alveolar simplification/hypoalveolarization and vascular remodeling. The nuclear factor erythroid 2 like 2 (Nfe2l2, or Nrf2) plays a critical role in the cytoprotective response to neonatal hyperoxia, and its global deficiency exacerbates hypoalveolarization in mice. The abnormal recruitment and activation of myeloid cells are associated with the pathogenesis of BPD. Therefore, we employed a genetic approach to investigate the role of myeloid Nrf2 in regulating hyperoxia-induced hypoalveolarization. Pups, both wild-type (Nrf2f/f) and those with a myeloid Nrf2 deletion (abbreviated as Nrf2∆/∆mye), were exposed to hyperoxia for 72 h at postnatal day 1 (Pnd1), and then sacrificed at either Pnd4 or Pnd18 following a two-week recovery period. We analyzed the hypoalveolarization, inflammation, and gene expression related to cytoprotective and inflammatory responses in the lungs of these pups. The hypoalveolarization induced by hyperoxia was significantly greater in Nrf2∆/∆mye pups compared to their Nrf2f/f counterparts (35.88% vs. 21.01%, respectively) and was accompanied by increased levels of inflammatory cells and IL-1β activation in the lungs. Antioxidant gene expression in response to neonatal hyperoxia was lower in Nrf2∆/∆mye pups compared to their Nrf2f/f counterparts. Furthermore, Nrf2-deficient macrophages exposed to hyperoxia exhibited markedly decreased cytoprotective gene expression and increased IL-1β levels compared to Nrf2-sufficient cells. Our findings demonstrate the crucial role of myeloid Nrf2 in mitigating hyperoxia-induced lung hypoalveolarization and inflammatory responses in neonatal mice.

Abstract Globally, excess deaths during 2020–21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India—an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27–33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0–13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.

Background: Bilateral kidney stones are commonly treated in staged procedures. Objective: To evaluate outcomes after same-sitting bilateral retrograde intrarenal surgery (SSB-RIRS) for renal stones. Design, setting, and participants: Data from adults who underwent bilateral RIRS in 21 centers were retrospectively reviewed (from January 2015 to June 2022). The inclusion criteria were unilateral/bilateral symptomatic bilateral stone(s) of any size/location in both kidneys and bilateral stones on follow-up with symptom/stone progression. Stone-free rate (SFR) was defined as absence of any fragment >3 mm at 3 mo. Outcome measurements and statistical analysis: Continuous variables are presented as medians and 25–75th percentiles. A multivariable logistic regression analysis was performed to evaluate independent predictors of sepsis and bilateral SFR. Results and limitations: A total of 1250 patients were included. The median age was 48.0 (36–61) yr. Of the patients, 58.2% were prestented. The median stone diameter was 10 mm on both sides. Multiple stones were present in 45.3% and 47.9% of the left and right kidneys, respectively. Surgery was stopped in 6.8% of cases. The median surgical time was 75.0 (55–90) min. Complications were transient fever (10.7%), fever/infection needing prolonged stay (5.5%), sepsis (2%), and blood transfusion (1.3%). Bilateral and unilateral SFRs were 73.0% and 17.4%, respectively. Female (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.18–7.49, p = 0.02), no antibiotic prophylaxis (OR 5.99, 95% CI 2.28–15.73, p

Background: In this article, the authors discuss how they utilized the genetic mutation data in Sri Lankan Duchenne muscular dystrophy (DMD), Spinal muscular atrophy (SMA), Spinocerebellar ataxia (SCA) and Huntington’s disease (HD) patients and compare the available literature from South Asian countries to identifying potential candidates for available gene therapy for DMD, SMA, SCA and HD patients. Methods: Rare disease patients (n = 623) with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy were genetically confirmed using Multiplex Ligation Dependent Probe Amplification (MLPA), and single plex PCR. A survey was conducted in the “Wiley database on Gene Therapy Trials Worldwide” to identify DMD, SMA, SCA, and HD gene therapy clinical trials performed worldwide up to April 2021. In order to identify candidates for gene therapy in other neighboring countries we compared our findings with available literature from India and Pakistan which has utilized the same molecular diagnostic protocol to our study. Results: From the overall cohort of 623 rare disease patients with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy, n = 343 (55%) [Muscular Dystrophy- 65%; (DMD-139, Becker Muscular Dystrophy -BMD-11), SCA type 1–3–53% (SCA1–61,SCA2- 23, SCA3- 39), HD- 52% (45) and SMA- 34% (22)] patients were positive for molecular diagnostics by MLPA and single plex PCR. A total of 147 patients in Sri Lanka amenable to available gene therapy; [DMD-83, SMA-15 and HD-49] were identified. A comparison of Sri Lankan finding with available literature from India and Pakistan identified a total of 1257 patients [DMD-1076, SMA- 57, and HD-124] from these three South Asian Countries as amenable for existing gene therapy trials. DMD, SMA, and HD gene therapy clinical trials (113 studies) performed worldwide up to April 2021 were concentrated mostly (99%) in High Income Countries (HIC) and Upper Middle-Income Countries (UMIC). However, studies on the potential use of anti-sense oligonucleotides (ASO) for treatment of SCAs have yet to reach clinical trials. Conclusion: Most genetic therapies for neurodegenerative and neuromuscular disorders have been evaluated for efficacy primarily in Western populations. No multicenter gene therapy clinical trial sites for DMD, SMA and HD in the South Asian region, leading to lack of knowledge on the safety and efficacy of such personalized therapies in other populations, including South Asians. By fostering collaboration between researchers, clinicians, patient advocacy groups, government and industry in gene therapy initiatives for the inherited-diseases community in the developing world would link the Global North and Global South and breathe life into the motto “Together we can make a difference”.

Abstract Background We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity. Methods We studied biologic-treatment-naïve AS and healthy control (HC) patients’ sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein–protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis. Results Of the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q

Abstract Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.

Background: Congenital fibrinogen disorder is a rare autosomal recessive blood coagulation disorder, where majority of patients present with bleeding, whereas a few may paradoxically develop thrombosis. While many of the affected children have prolonged umbilical cord bleeding during the neonatal period, manifestations may go unnoticed till adolescence. We describe such a child with congenital afibrinogenemia Clinical Description: A 12-year-old boy presented with painless diffuse scalp swelling for 2 weeks without any antecedent history of trauma, hemarthrosis, muscle hematoma, or any skin bleed, except a history of prolonged bleeding post trauma since toddler age. Examination revealed diffuse, boggy, nonpulsatile swelling over the entire scalp, more prominent on the right side, without any focal neurological deficit. A noncontrast computed tomography head showed a scalp hematoma without any intracranial bleeding. Blood investigations revealed extremely elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) with normal platelet counts and normal platelet morphology on peripheral smear. A detailed coagulation work-up revealed an extremely high thrombin time and an almost undetectable Factor I (fibrinogen) level. Genetic analysis revealed a homozygous single-base pair deletion in exon 5 of the fibrinogen gene of alpha chain, thus confirming the diagnosis of congenital afibrinogenemia. Management: The child was managed with multiple fresh frozen plasma transfusions and serial PT/aPTT monitoring. Once PT and aPTT were normalized, transfusions were discontinued. The child is currently on regular follow-up maintaining a fibrinogen level of more than 0.5 g/L. Genetic counseling was done for the family. Conclusion: Congenital afibrinogenemia may be detected late in adolescence with atypical bleeding manifestations. Awareness of this entity may help the physician to suspect this disease. Early and appropriate investigations can be conducted to identify the condition, so that appropriate management can be initiated.

Introduction: The duties of nursing administration include tasks such as placing orders, conducting regular checks on ward supplies, and ensuring regular updation of the stock register. This study assesses the effect of a supportive supervision strategy on the process of indenting and stock management by senior nursing ward in-charges and the barriers faced by them during the discharge of this duty. Methods: A cross-sectional study with mixed-method approach was conducted. Senior nursing officers were administered structured questionnaires and in-depth interviews for the quantitative and qualitative approaches, respectively. Quantitative analysis was done using statistical software and qualitative content analysis was done manually for the audio recorded and transcribed in-depth interviews. Results: The availability, legibility, accuracy, completeness, chronology, continuity, timeliness, safety, etc., of records, saw improvements on successive follow-up visits. On analyzing the in-depth interviews, administrative and management issues such as constantly changing personnel, unsystematic handover process, and problems related to supply chain and disposal came up. Work-related issues, such as lack of training, workload pressure, as well as staff-related and personal issues, were also identified. Conclusion: Transfers of designated senior nursing ward in-charges should be avoided if possible. In case done, the process of proper charge transfer should be followed. Issues such as the lengthy process of indenting and lack of training of nursing staff should be addressed. Incentivizing such work should be encouraged along with increasing autonomy for handling wards by senior nursing officers. Communication with all the stakeholders should be improved.

Background: Tracheal extubation is a crucial step during general anesthesia involving the removal of artificial airway when the indication for its placement no longer exists. Airway and circulatory interferences could be due to diminished tolerance to the tracheal tube, catecholamine surge, surgical pain, and airway irritation on behalf of suctioning or change in posture of the tube. Complications are more common during extubation than that occurring during induction and intubation. Aim: The main aim of the study was to compare the effectiveness of a single dose of dexmedetomidine and lignocaine in alleviating hemodynamic and stress responses during extubation and recovery. Materials and Methodology: Sixty patients of the age group between 20 and 65 years belonging to ASA 1 and 2 undergoing elective surgical procedures with a minimum anticipated duration of 60 min requiring endotracheal intubation were included in the study. The patients were assigned randomly into two groups with 30 participants in each group and were called as Group D receiving dexmedetomidine 0.5 μg/kg and Group L receiving lignocaine 1.5 mg/kg. Observation and Results: Data were statistically analyzed with the SPSS version 20.0 software. Independent t-test analysis was used, and all the statistical test was examined with P ≤ 0.05 level of significance. Hemodynamic response was noted as more significant in Group D, whereas emergence and extubation time was noted sooner in Group L. Conclusion: We conclude that Dexmedetomidine 0.5 mcg/kg causes significant attenuation of hemodynamic stress response and deeper sedation when compared to lignocaine 1.5 mg/kg.

Abstract Background The study of molecular mechanisms characterizing disease progression may be relevant to get insights into systemic sclerosis (SSc) pathogenesis and to intercept patients at very early stage. We aimed at investigating the proteomic profile of preclinical systemic sclerosis (PreSSc) via a discovery/validation two-step approach. Methods SOMAcan aptamer-based analysis was performed on a serum sample of 13 PreSSc (discovery cohort) according to 2001 LeRoy and Medsger criteria (characterized solely by Raynaud phenomenon plus a positive nailfold capillaroscopy and SSc-specific antibodies without any other sign of definite disease) and 8 healthy controls (HCs) age, gender, and ethnicity matched. Prospective data were available up to 4±0.6 years to determine the progression to definite SSc according to the EULAR/ACR 2013 classification criteria. In proteins with relative fluorescence units (RFU) > |1.5|-fold vs HCs values, univariate analysis was conducted via bootstrap aggregating models to determine the predicting accuracy (progression vs non-progression) of categorized baseline protein values. Gene Ontologies (GO terms) and Reactome terms of significant proteins at the adjusted 0.05 threshold were explored. Significant proteins from the discovery cohort were finally validated via ELISAs in an independent validation cohort of 50 PreSSc with clinical prospective data up to 5 years. Time-to-event analysis for interval-censored data was used to evaluate disease progression. Results In the discovery cohort, 286 out of 1306 proteins analyzed via SomaScan, were differentially expressed versus HCs. Ten proteins were significantly associated with disease progression; analysis through GO and Reactome showed differentially enriched pathways involving angiogenesis, endothelial cell chemotaxis, and endothelial cell chemotaxis to fibroblast growth factor (FGF). In the validation cohort, endostatin (HR=10.23, CI95=2.2–47.59, p=0.003) was strongly associated with disease progression, as well as bFGF (HR=0.84, CI95=0.709-0.996, p=0.045) and PAF-AHβ (HR=0.372, CI95=0.171–0.809, p=0.013) Conclusions A distinct protein profile characterized PreSSc from HCs and proteins associated with hypoxia, vasculopathy, and fibrosis regulation are linked with the progression from preclinical to definite SSc. These proteins, in particular endostatin, can be regarded both as markers of severity and molecules with pathogenetic significance as well as therapeutic targets.

Although most cases of coronavirus disease 2019 (COVID-19) have occurred in low-resource countries, little is known about the epidemiology of the disease in such contexts. Data from the Indian states of Tamil Nadu and Andhra Pradesh provide a detailed view into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission pathways and mortality in a high-incidence setting. Reported cases and deaths have been concentrated in younger cohorts than would be expected from observations in higher-income countries, even after accounting for demographic differences across settings. Among 575,071 individuals exposed to 84,965 confirmed cases, infection probabilities ranged from 4.7 to 10.7% for low-risk and high-risk contact types, respectively. Same-age contacts were associated with the greatest infection risk. Case fatality ratios spanned 0.05% at ages of 5 to 17 years to 16.6% at ages of 85 years or more. Primary data from low-resource countries are urgently needed to guide control measures.

The goal of this study is to develop a rapid diagnostic test for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HCs). Observer scores and absolute signal intensities from the VFA were validated via ELISA. The rapid point-of-care VFA test that was engineered demonstrated a limit of detection of 0.5 IU/mL for ANA and αDNA autoantibodies in human plasma with an inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in SLE and HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and an 84% ROC AUC value in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease, and rapid turnaround, it can also be used to assess SLE prevalence estimates.

Terminal heat stress has become one of the major threats due to global climate change which is significantly affecting the production and productivity of wheat crop. Therefore, it is necessary to identify key traits and genotypes to breed heat-tolerant wheat. The present study was undertaken with the objective of comparing the effects of heat stress (HSE) and extended heat stress (EHSE) on phenological-physio-biochemical traits of contrasting heat-tolerant and heat-susceptible genotypes during the reproductive phase. Phenological traits exhibited significant reduction under EHSE compared to HSE. Heat-tolerant genotypes maintained balanced phenological-physio-biochemical traits, while heat-sensitive genotypes showed significant reductions under both stress regimes. Among phenological traits, DM (R2 = 0.52) and BY (R2 = 0.44) have shown a positive effect on seed yield, indicating that biomass and crop duration contributed to the yield advantage under stress. During the grain filling stage, both the normalized difference vegetation index (NDVI) and chlorophyll (Chl) exhibited consistently positive impacts on grain yield under both HSE and EHSE conditions. This could be attributed to the enhanced photosynthesis resulting from delayed senescence and improved assimilate remobilization under terminal heat stress. The biochemical activity of superoxide dismutase (SOD), peroxidase (POX), and ascorbate peroxidase (APX) was induced in tolerant genotypes under HSE. The correlation of canopy temperature with phenological-physio-biochemical traits remained static under HSE and EHSE, suggesting CT as the best selection parameter for heat tolerance. The traits showing a positive association with yield and that are less affected under stress could be used for selecting tolerant genotypes under stress environments. These tolerant genotypes can be used to develop mapping populations to decipher the genes conferring tolerance as well as to study the molecular basis of tolerance.

ObjectiveThere is an urgent need for novel biomarkers in lupus nephritis (LN). We report a non-invasive urinary biomarker, L-selectin, in two independent multi-ethnic cohorts.MethodsuL-selectin was tested cross-sectionally in a Chinese cohort (n=255) and a US cohort (n=219) of SLE patients and controls using ELISA. A longitudinal cohort includes 20 active Chinese LN patients.ResultsuL-selectin was significantly increased in active LN patients compared to active non-renal SLE, inactive LN, inactive non-renal SLE, chronic kidney disease patients, and healthy controls. uL-selectin positively correlated with global and renal disease activities and was significantly associated with histological activity index and chronicity index (CI). Low uL-selectin was an independent predictor for high CI. During follow-up, uL-selectin levels decreased significantly in the complete renal remission group.ConclusionuL-selectin is a novel biomarker of disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.

Introduction: Documented Duchenne Muscular Dystrophy (DMD) biomarkers are confined to Caucasians and are poor indicators of cognitive difficulties and neuropsychological alterations. Materials and methods: This study correlates serum protein signatures with cognitive performance in DMD patients of South Asian origin. Study included 25 DMD patients aged 6–16 years. Cognitive profiles were assessed by Wechsler Intelligence Scale for Children. Serum proteome profiling of 1317 proteins was performed in eight DMD patients and eight age-matched healthy volunteers. Results: Among the several novel observations we report, better cognitive performance in DMD was associated with increased serum levels of MMP9 and FN1 but decreased Siglec-3, C4b, and C3b. Worse cognitive performance was associated with increased serum levels of LDH-H1 and PDGF-BB but reduced GDF-11, MMP12, TPSB2, and G1B. Secondly, better cognitive performance in Processing Speed (PSI) and Perceptual Reasoning (PRI) domains was associated with intact Dp116, Dp140, and Dp71 dystrophin isoforms while better performance in Verbal Comprehension (VCI) and Working Memory (WMI) domains was associated with intact Dp116 and Dp140 isoforms. Finally, functional pathways shared with Alzheimer's Disease (AD) point towards an astrocyte-centric model for DMD. Conclusion: Astrocytic dysfunction leading to synaptic dysfunction reported previously in AD may be a common pathogenic mechanism underlying both AD and DMD, linking protein alterations to cognitive impairment. This new insight may pave the path towards novel therapeutic approaches targeting reactive astrocytes.

The main aim of this study was to evaluate the cytotoxic effects of chronic alcohol consumption on various regions of diabetic brain and preventive role of GTE. Clinical, experimental and histopathological observations indicate chronic, excessive alcohol consumption aggravates the free radical-mediated oxidative and nitrosative stress in several tissues including brain. Treatment with Epigallocatechin gallate (EGCG) significantly reduced the levels of oxidative/nitrosative stress paradigms, increased glutathione (GSH) levels and enhanced the activities of antioxidant enzymes. Histopathology evaluation revealed the possible influence of EGCG in reversing alcohol exacerbated diabetes-induced damage in cortex, cerebellum and hippocampus of brain. Furthermore, these studies have provided evidence to show how EGCG can exactly occupy the position in functional sites of nNOS (neuronal nitric oxide synthase) and induce a conformational change, inhibition of enzymatic activity and prevention of neurodegeneration/necrotic changes of tissue, in comparison with the rosiglitazone and glibenclamide. To summarise, this research has offered useful information on the action of EGCG that would provide potential protection against ethanol exacerbated diabetic brain damageand additional evidence for the use of EGCG as a lead compound for drug discovery.

Chitosan is known to possess excellent properties such as biodegradability, biocompatibility, antimicrobial activity and less toxicity due to which it has applications in various fields. Another important benefit of chitosan is that it can be processed into different forms like membranes, sponges, gels, scaffolds, microparticles, nanoparticles, nanofibers and 3D printed constructs. For these reasons, chitosan has found to be highly advantageous in biomedical field. The reactive amino and hydroxyl groups in its chemical structure make it an ideal candidate for a wide range of applications. However, the compromising mechanical strength of chitosan limits its applications, which can be improved using nanotechnology. Chitosan based nanocomposites have gained significant attention in the last two decades. In the present review, we discuss the advantages of chitosan based nanocomposites for biomedical applications majorly tissue engineering, wound dressing and drug delivery. This review emphasizes on recent findings concerning the use of innovative chitosan based nanocomposites in biomedical applications. It also covers brief overview of chitosan, its extraction, structure and modifications and its in vitro and in vivo efficacy. Then, a detailed summary of recent progress in biomedical applications are presented. Current chitosan based nanocomposite as product in market, future perspectives and challenges are also discussed.

Plastic pollution is an emerging environmental concern in recent years due to continuous mass production and its slow degradation. Microplastics measuring between 5 mm and 1 μm are being ingested by marine animals and eventually by human consumption in form of seafood. The aim of this research was to evaluate microplastics isolated from sea cucumber Acaudina molpadioides in Pulau Langkawi. A total of 20 animals were collected and their gastrointestinal tract were digested using NaOH. Microplastics were isolated, filtered and identified through microscopic examination based on the colour, shape and size. The chemical composition of microplastics were further analyzed by FTIR to identify the functional group of polymers. A total of 1652 microplastics were found in A. molpadioides. Fibres (99.4%) and black color (54.4%) were the majority of microplastics observed in terms of shapes and colors. The size range within 0.5–1 μm and 1–2 μm were the highest abundance observed. There were two identified polymer types of microplastics obtained through FTIR which were polyethylene (PE) and polymethyl methacrylate (PMMA). In conclusion, microplastics were isolated from the gastrointestinal tract of A. molpadioides indicating that the animals were contaminated. Further research can be done on the toxicity effects of these microplastics towards human upon consumption of these animals as seafood.

The present work deals with the development of cellulose-reinforced starch-based bioactive thermoplastic packaging films, from complete recycling of banana peel waste. The nanocellulose fibers, starch and bioactive compounds from banana peel were extracted and reconstituted to produce cellulose-reinforced starch-based bioactive thermoplastic packaging films. The banana peel starch was examined to have an abundance of amylopectin (88.55 ± 0.28% (w/w)) and high thermal stability (∼295 °C maximum degradation temperature), to serve as a matrix for the thermoplastic films. The ethanolic extract of the banana peel with major active compounds of β-sitosterol, and 1, 2 Benzenedicarboxylic acid mono (2-ethyl hexyl ester) was examined to be having high antioxidant (74.43 ± 0.26% DPPH inhibition) and antimicrobial properties, to serve as a potential bioactive ingredient for the development of bioactive thermoplastic films. The addition of banana peel-based nanocellulose fiber improved the mechanical (6-fold increase in tensile strength) and barrier properties (0.6-fold reduction in O2 permeability) of banana peel thermoplastic films (BPT). The developed bioactive BPT films were examined to have a UV blocking capacity of ∼98%. The produced Bioactive BPT films were found to be effective in the shelf life extension of bread by 10 days. The proposed methodology for the complete recycling of banana peel will take the state of research in agro-waste management one step closer to a green bio-circle economy.

Climate change has resulted in extreme temperature and drought around the globe, which poses serious threat to food security. Both heat and drought stress affects the production and productivity of wheat crop. The present study was undertaken to evaluate 34 landraces and elite cultivars of Triticum spp. for phenological and yield-related traits under optimum, heat, and combined heat–drought stress environments during 2020–2021 and 2021–2022. The pooled analysis of variance showed significant genotype × environment interaction, suggesting an influence of stress on trait expression. The trait performance of genotypes exhibited significant reduction under combined heat–drought stress as compared to optimum and heat stress environments. The maximum seed yield penalty was observed under combined heat–drought stress environment as compared to heat stress alone. Regression analysis indicated significant contribution of number of grains per spike towards stress tolerance. Based on Stress Tolerance Index (STI), genotypes Local-17, PDW 274, HI-8802, and HI-8713 were identified to be tolerant to both heat and combined heat and drought stress at Banda, whereas genotypes DBW 187, HI-8777, Raj 4120, and PDW 274 were tolerant at Jhansi location. The genotype PDW 274 showed stress tolerance under all treatments at both the locations. The genotypes PDW 233 and PDW 291 showed highest stress susceptibility index (SSI) across the environments. The number of grains per spike and test kernel weight were positively associated with seed yield across the environments and locations. The selected genotypes Local-17, HI 8802, and PDW 274 were identified to be the potential sources of heat and combined heat–drought tolerance, which may be utilized in hybridization to develop tolerant wheat genotypes and also for mapping of underlying genes/quantitative trait loci (QTLs).

The intensity of trait association and genetic variability of yield attributing variables in 217 rice genotypes was investigated during kharif 2018. The existence of genetic variability among the genotypes was demonstrated by analysis of variance, which recorded significant differences for all the seven studied parameters. The estimation of variability indicated that The full grain number per panicle (37.2 % and 34.1 %) & single plant yield (24.7 % and 20.55 %) had the highest intensity of phenotypic coefficients of variation (PCV) and genotypic coefficients of variation ( GCV), and High heritability along with high genetic advance as a per cent of mean (GAM) was found in Plant height (98.9 % and 20.8 %), panicle number per plant (95.4 % and 36 %), panicle length(96.8 % and 35.9 %), full grain number per panicle(99.5 % and 61.6 %), thousand seed weight (98.1 % and 40.25 %) and single plant yield (69.2 % and 35.2 %) , depicting additive gene action in inheritance of these parameters. A simple selection procedure can help to enhance these characteristics even further. Correlation and regression coefficient findings indicated that plant height (0.193**) and the full grain number per panicle (0.177**) had a significant impact on single plant yield. The full grain number per panicle (0.265**), followed by thousand seed weight (0.194**) and plant height (0.110**), had the maximum direct positive effect on single plant yield, as per path coefficient analysis. As a result, accessions with a higher full grain number per panicle, thousand seed weight and plant height would be suitable for yield enhancement programme.

Mungbean is known to be susceptible to waterlogging (WL) stress. Some of the wild species have the potential to tolerate this through various physiological and molecular mechanisms. Auxin Response Factor (ARF) and Auxin/Indole Acetic Acid (AUX/IAA), an early responsive gene family, has multiple functions in growth, development, and stress tolerance. Here, we report the first comprehensive analysis of the ARF and AUX/IAA gene family in mungbean. A total of 26 ARF and 19 AUX/IAA genes were identified from the mungbean genome. The ARF and AUX/IAA candidates were clearly grouped into two major clades. Further, the subgrouping within the major clades indicated the presence of significant diversity. The gene structure, motif analysis, and protein characterization provided the clue for further fundamental research. Out of the10 selected candidate genes, VrARF-5, VrARF-11, VrARF-25, and VrAUX/IAA-9 were found to significantly multiple-fold gene expression in the hypocotyl region of WL-tolerant wild relatives (PRR 2008-2) provides new insight into a role in the induction of lateral root formation under WL stress. The analysis provides an insight into the structural diversity of ARF and AUX/IAA genes in mungbean. These results increase our understanding of ARF and AUX/IAA genes and therefore offer robust information for functional investigations, which can be taken up in the future and will form a foundation for improving tolerance against waterlogging stress.

Proteomics has been a very informative tool in uncovering several biomarkers that may have clinical utility in managing patients with lupus nephritis (LN). Both non-targeted (mass spectrometry-based) and targeted (ligand-based) proteomics point to promising biomarkers in the urine of LN patients. Aptamer-based interrogation of 1129 proteins using the Somascan platform, followed by ELISA-validation in two independent cohorts has indicated that the urine proteins that best distinguish active LN from controls were ALCAM, PF-4, properdin, and VCAM-1 among African Americans, E-selectin, VCAM-1, BFL-1 and Hemopexin among Caucasians, and ALCAM, VCAM-1, TFPI and PF-4 among Asians (PMID: 32366845). Most of these urine proteins correlate significantly with disease activity indices and surpass conventional metrics in identifying active LN. Several elevated urinary molecules are also expressed within LN kidneys, based on single-cell RNA-seq analysis. Of these, ALCAM has been validated in a large multi-ethnic, multi-national cohort of LN subjects, and has also been shown to be a pathogenic driver and therapeutic target in LN (PMID: 34981775). Antibody array based screening of 1000 proteins using the Raybiotech Kiloplex platform has identified urine L-selectin, Angptl4, TGF[Formula: see text] 1, TPP1, TSP-1, FOLR2, PDGFR[Formula: see text], and PRX2, as markers of active renal lupus, outperforming conventional metrics, with L-selectin, Angptl4 and TGF[Formula: see text] 1 tracking well with concurrent or pending disease flares in LN (PMID: 32651195). Of these, urine L-selectin has been validated in large multi-ethnic/national cohorts of LN subjects (under review). Proteomic screens of LN urine using an electrochemiluminescence platform (Mesoscale/MSD) has identified IL-7, IL-12p40, IL-15, IP-10, and TARC as markers of active renal lupus that correlated significantly with disease activity (PMID: 30618193). Very recent global proteomic screens of LN urine using a proximity ligation assay platform from Olink has added several additional biomarker candidates that have been successfully ELISA-validated (under review). Given the plethora of urine biomarkers that have been identified using proteomics, it now becomes important to validate the clinical utility of these urine proteins, using multiple well-annotated patient cohorts, across ethnicities. Among the completed studies, we now know that some urine proteins are diagnostic of concurrent renal pathology LN Class or Activity Index or Chronicity index (e.g. CD163: PMID: 32351512; VCAM-1: PMID: 29076253; Angiostatin: PMID: 29076253; Hemopexin, Kim-1 and Lipoxcalin-2/NGAL; Renin and SAP; PMID: 20065116), while others exhibit prognostic value (e.g., ALCAM and VCAM-1; PMID: 31722419). Ongoing studies also show that most of the urine proteins interrogated in LN are not elevated in circulation (PMID: 36091001), but are expressed within LN kidneys, as ascertained by immunohistochemistry (Clinical Immunology, 2022) and Imaging Mass Cytometry (Tissue CyTOF). To facilitate monitoring of urinary biomarkers in outpatient clinics or to enable self-monitoring of disease status by the patient from the comfort of one’s home, we have recently engineered a smartphone-readable nanophosphor-based lateral flow assay for point of care monitoring of urine ALCAM (Frontiers in Immunology, 2022). The long-term goal is to decipher the clinical utility of different urine biomarkers in managing lupus and LN in the clinics, to empower LN patients with easy-to-use tools to monitor their own disease status, and to understand the mechanistic significance of the uncovered molecules in renal disease pathogenesis. Ongoing research on this front is summarized at: https://mohanlab.bme.uh.edu/.

In this study, a combination of “Cordia Dichotoma” natural fiber and “granite powder” as filler has been reinforced into epoxy resin making a hybrid composite. In this study, unused industrial waste obtained from the granite polishing industry, known as granite powder (GP) is being utilized for its usefulness as a reinforcement in polymer composite. Hybrid composite was prepared by reinforcing a constant Cordia Dichotoma fiber content of 20 wt. % and varying the granite powder weight (wt. %) percentages (0, 5, 10, 15 and 20) into epoxy matrix. Mechanical properties (tensile, flexural and impact) of hybrid composites were investigated. Following the results obtained, granite powder could be evidenced as a good filler material for the betterment of composite’s mechanical properties. Also, the ability of this filler material is proved in decreasing water absorption and chemical resistance. SEM morphology was performed to investigate the bonding and distribution of granite powder within the Cordia Dichotoma reinforced composite material. Besides, presence of chemical functional groups in the composite was traced by Infra-Red Spectroscopy. Also, Thermo-Gravimetric Analysis (TGA) was carried out and the composite was found to be thermally stable up to 455°C.

Summary: Objectives: The biological membranes are important for cell structure and function but, during diseased conditions such as diabetes and in chronic alcoholism, they may be impaired. Nitroxidative stress mediated by persistent hyperglycemia is a major complication in diabetics with alcohol abuse. The present study is intended to investigate the antioxidant, anti-diabetic, and hepatoprotective effects of aqueous green tea extract (GTE) against cumulative effects of alcohol and diabetic pathology, focusing liver mitochondrial membranes. Methods: Mitochondrial membrane fluidity and membrane Na+/K+ and Mg2+ATPases were measured. Displacement loop (D-loop) of mitochondrial DNA (mt-DNA) was screened by PCR-Sanger's sequencing method. In addition, nuclear and mitochondrial encoded genes were analyzed. Molecular docking studies were performed to screen potential targets using the docking module implemented in Pyrx2010. Results: In the present study, marked mitochondrial-DNA deletions were observed in diabetic-alcohol group which were ameliorated by GTE treatment. Also, GTE restored the alterations in the exacerbated levels of membrane fluidity and activities of Na+/K+ and Mg2+ ATPase to normalcy. ADME properties were evaluated for the ligand, Epigallocatechin 3 Gallate (EGCG) and reference drug, Rosiglitazone (RTG). It showed that, higher binding affinities and energy profiles of EGCG with the active site ofinducible nitric oxide synthase (iNOS) compared to RTG making non-bonded interactions with their active residues and surrounding allosteric residues. Discussion: The present investigation demonstrated that, EGCG would be a promising next generation anti-diabetic compound as well as anti-inflammatory drug, and may be effectively used in the treatment of hepatopathy induced by double jeopardy of diabetes and alcohol abuse.

Foxtail millet (Setaria italica (L.) P. Beauv.) is highly valued for nutritional traits, stress tolerance and sustainability in resource-poor dryland agriculture. However, the low productivity of this crop in semi-arid regions of Southern India, is further threatened by climate stress. Landraces are valuable genetic resources, regionally adapted in form of novel alleles that are responsible for cope up the adverse conditions used by local farmers. In recent years, there is an erosion of genetic diversity. We have hypothesized that plant genetic resources collected from the semi-arid climatic zone would serve as a source of novel alleles for the development of climate resilience foxtail millet lines with enhanced yield. Keeping in view, there is an urgent need for conservation of genetic resources. To explore the genetic diversity, to identify superior genotypes and novel alleles, we collected a heterogeneous mixture of foxtail millet landraces from farmer fields. In an extensive multi-year study, we developed twenty genetically fixed foxtail millet landraces by single seed descent method. These landraces characterized along with four released cultivars with agro-morphological, physiological, yield and yield-related traits assessed genetic diversity and population structure. The landraces showed significant diversity in all the studied traits. We identified landraces S3G5, Red, Black and S1C1 that showed outstanding grain yield with earlier flowering, and maturity as compared to released cultivars. Diversity analysis using 67 simple sequence repeat microsatellite and other markers detected 127 alleles including 11 rare alleles, averaging 1.89 alleles per locus, expected heterozygosity of 0.26 and an average polymorphism information content of 0.23, collectively indicating a moderate genetic diversity in the landrace populations. Euclidean Ward’s clustering, based on the molecular markers, principal coordinate analysis and structure analysis concordantly distinguished the genotypes into two to three sub-populations. A significant phenotypic and genotypic diversity observed in the landraces indicates a diverse gene pool that can be utilized for sustainable foxtail millet crop improvement.

Abstract Objectives To assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations. Methods Saliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated. Results Salivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p

Introduction: Our aim is to evaluate the clinical efficiency and safety of 60W Thulium fiber laser (TFL) during retrograde intrarenal surgery (RIRS). The performance of the TFL across different ranges of stone volumes and stone densities is assessed. Materials and Methods: Between October 2019 and August 2020, a prospective study was done on 135 patients with < 20 mm renal stones, who underwent RIRS using TFL. Stone parameters, total laser time, total energy delivered (kJ), and fiber burn-back were recorded. Laser efficacy (J/mm3) and ablation speed (mm3/s) were calculated. Results: Data of 126 of 135 patients included in the study were analyzed. The mean patient age was 45.04 ± 12.30 years. Mean stone size was 15.19 ± 4.52 mm, and mean stone volume was 1061.85 ± 806.81 mm3. Mean laser time was 19.78 ± 12.32 min. At higher stone volume (>1000 mm3), J/mm3 decreased significantly from 16.18 ± 5.90 to 10.92 ± 3.21 (P < 0.001) and the ablation speed increased significantly (0.77 ± 0.28–1.04 ± 0.28 mm3/s [P < 0.001]). Stone density did not have a significant influence on the laser efficacy [B = -0.31 (-2.45 to 1.82, p=0.771)] or on the ablation speed [B = -0.06 (-0.17 to 0.05, p=0.278)]. Overall SFR was 93.6%. The complication rate was 16.6% (21/126). Out of the 21, 12 patients had hematuria and 9 had fever, which were of Clavien grades 1–2. Conclusion: Superpulse TFL is efficient and safe. The work efficiency increases for larger volume stones. The work efficiency remains the same across different stone densities. No complication more than Clavien grade 2 was encountered.

A heterocyclic compound of S and N with cyclic structures, like Furans, thiophenes and related azole analogs, is important as a ligand because of it is readily available, stable and easily functionalized. Various types of heterocyclic molecules quinazolines and their derivatives contain important chromophores with desirable electrochemical properties to be applied in the sensor field. Metal complexes of these compounds have demonstrated significant electrochemical properties as ionophore or electroactive materials for the fabrication of ISEs with different polymeric membranes. R. Selva Kumar et al. 2019 reported the use of dibutyl(8-hydroxyquinolin-2-yl)methylphosphonate as ionophore in a PVC matrix for the fabrication of a potentiometric thorium(IV) ion-selective electrode These quinazoline-based membranes with other additives and plasticizers are very useful for the development of a potential difference across the membrane at membrane-solution interface in the required proportions . Analytes, such as Butralin, Hydroxylamine, and Nitrite, and heavy metal ions, like Fe3+ and Th4+, have also been determined using quinazoline-based membrane sensors. ISE-based electrochemical sensors are very useful in the analysis of food products, drinking water, beverages, fertilizers, soil industrial effluents, etc. They also are applied in potentiometric titration as indicator electrodes.

Phytoalexins are naturally occurring molecules with antimicrobial activity deriving from the secondary metabolism of plants; they are synthesized in response to physical agents or stresses and phytopathogenic agents (fungi, bacteria and viruses), as well as numerous chemical compounds and biological control agents. Among these, grapevine phytoalexins, which belong to the chemical group of stilbenes, exhibit biocidal activity against a large number and variety of plant pathogens. It is important to investigate whether induction of stilbene phytoalexin production can serve to protect this plant against its pathogens. Quite a few chemical compounds, derivatives of phytohormones bio-elicitors as well as biocontrol agents, have been used to induce the synthesis of stilbene phytoalexins with the aim of conferring protection to grapevine against its main diseases (gray mold, downy mildew, powdery mildew and esca). This article reviews the experiments that have been carried out in this direction during the last 30 years and shows that the observed protective effects towards pathogens are generally linked to induction and priming of the grapevine phytoalexin response, confirming the interest in using, in a more general way, stimulation of the production of phytoalexins in plants as a basis for crop protection.

Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, “standing on one leg R”, “standing on one leg L”, and “walk”, declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial.

Introduction: Among children, one of the most serious public health challenges of the 21st century is childhood obesity, namely central obesity. This increases the risk of cardiovascular disease and diabetes. Studies show that, children who are physically active are less likely to have central obesity making it a key element in the prevention and treatment of both chronic diseases. Objectives: To assess the baseline knowledge and post-interventional knowledge of the students and teachers on the physical activity; to assess the utility and acceptability of the intervention module. Methods: An interventional study in 2 schools by administering tests prior to and after giving a class on the importance of physical activity and focused group discussion with teachers to assess the utility and acceptability of intervention. Data analysed using SPSS software, tabulated and interpreted by applying statistical tests. Results: Among the 120 students who participated, a significant increase in knowledge regarding the need for physical activity after health education was observed. Conclusion: Health education approach in schools was found to be effective and feasible in improving the knowledge and behavioural practices regarding physical activity among adolescents to reduce childhood obesity and to improve overall health.

IntroductionThe gold standard for diagnosis of active lupus nephritis (ALN), a kidney biopsy, is invasive with attendant morbidity and cannot be serially repeated. Urinary ALCAM (uALCAM) has shown high diagnostic accuracy for renal pathology activity in ALN patients.MethodsLateral flow assays (LFA) for assaying uALCAM were engineered using persistent luminescent nanoparticles, read by a smartphone. The stability and reproducibility of the assembled LFA strips and freeze-dried conjugated nanoparticles were verified, as was analyte specificity.ResultsThe LFA tests for both un-normalized uALCAM (AUC=0.93) and urine normalizer (HVEM)-normalized uALCAM (AUC=0.91) exhibited excellent accuracies in distinguishing ALN from healthy controls. The accuracies for distinguishing ALN from all other lupus patients were 0.86 and 0.74, respectively.ConclusionPeriodic monitoring of uALCAM using this easy-to-use LFA test by the patient at home could potentially accelerate early detection of renal involvement or disease flares in lupus patients, and hence reduce morbidity and mortality.

Objective Urine proteomic approaches have shown promise in identifying biological pathways in lupus nephritis (LN) which are not captured on renal histopathology or by measurement of proteinuria alone. We investigated how the urine proteome changes with treatment response and with belimumab therapy.Methods Urine samples from 54 Belimumab International Systemic Lupus Erythematosus–Lupus Nephritis trial participants (all with biopsy-proven LN) were collected at weeks 0, 24 and 52. At each time point, 1000 urinary proteins were quantified using antibody microarrays (Raybiotech Kiloplex), and their abundance was compared in responders (n=31) versus non-responders (n=22) and with belimumab treatment (n=28) versus standard of care therapy (n=26). Response was defined as proteinuria