Janus zirconium halide ZrXY (X, Y = Br, Cl and F) monolayers with high lattice thermal conductivity and strong visible-light absorption.

In this work, the structural, mechanical, and electronic properties of Janus zirconium halide monolayers have been systematically investigated using the first-principles calculations. After verifying the mechanical and dynamical stability of these monolayers, their electronic band structures have been predicted. These Janus monolayers have band gaps of 1.51-1.96 eV, which indicates their suitability for visible light absorption. The relaxation time and mobility of charge carriers are estimated using deformation potential theory, and the mobility of these monolayers has been predicted to be of the order ∼102 cm2 V-1 s-1. The lattice thermal conductivity has been calculated by solving the phonon Boltzmann transport equation using ShengBTE software. At 300 K, the in-plane lattice thermal conductivity has values of 76.94, 54.18, and 95.87 W m-1 K-1 for ZrBrCl, ZrBrF, and ZrClF monolayers, respectively. The higher group velocity and small anharmonic three-phonon scattering rate are the main reasons for the high lattice thermal conductivity of the ZrClF monolayer. The real and imaginary parts of the dielectric function are calculated to find the absorption coefficients and these monolayers have a high absorption coefficient of the order ∼106 cm-1 in the visible light range. Our results show that Janus zirconium halide monolayers are potential candidates for optoelectronic and photocatalytic applications.

Survival of COVID-19 Patients With Respiratory Failure is Related to Temporal Changes in Gas Exchange and Mechanical Ventilation.

Background: Respiratory failure due to coronavirus disease of 2019 (COVID-19) often presents with worsening gas exchange over a period of days. Once patients require mechanical ventilation (MV), the temporal change in gas exchange and its relation to clinical outcome is poorly described. We investigated whether gas exchange over the first 5 days of MV is associated with mortality and ventilator-free days at 28 days in COVID-19. Methods: In a cohort of 294 COVID-19 patients, we used data during the first 5 days of MV to calculate 4 daily respiratory scores: PaO2/FiO2 (P/F), oxygenation index (OI), ventilatory ratio (VR), and Murray lung injury score. The association between these scores at early (days 1-3) and late (days 4-5) time points with mortality was evaluated using logistic regression, adjusted for demographics. Correlation with ventilator-free days was assessed (Spearman rank-order coefficients). Results: Overall mortality was 47.6%. Nonsurvivors were older (P < .0001), more male (P = .029), with more preexisting cardiopulmonary disease compared to survivors. Mean PaO2 and PaCO2 were similar during this timeframe. However, by days 4 to 5 values for all airway pressures and FiO2 had diverged, trending lower in survivors and higher in nonsurvivors. The most substantial between-group difference was the temporal change in OI, improving 15% in survivors and worsening 11% in nonsurvivors (P < .05). The adjusted mortality OR was significant for age (1.819, P = .001), OI at days 4 to 5 (2.26, P = .002), and OI percent change (1.90, P = .02). The number of ventilator-free days correlated significantly with late VR (-0.166, P < .05), early and late OI (-0.216, P < .01; -0.278, P < .01, respectively) and early and late P/F (0.158, P < .05; 0.283, P < .01, respectively). Conclusion: Nonsurvivors of COVID-19 needed increasing intensity of MV to sustain gas exchange over the first 5 days, unlike survivors. Temporal change OI, reflecting both PaO2 and the intensity of MV, is a potential marker of outcome in respiratory failure due to COVID-19.

Clinical Outcomes of COVID-19 Patients Treated with Convalescent Plasma or Remdesivir Alone and in Combination at a Community Hospital in California's Central Valley.

PURPOSE: The purpose of this study was to compare how treatment with convalescent plasma (CP) monotherapy, remdesivir (RDV) monotherapy, and combination therapy (CP + RDV) in patients with COVID-19 affected clinical outcomes. METHODS: Patients with COVID-19 infection who were admitted to the hospital received CP, RDV, or combination of both. Mortality, discharge disposition, hospital length of stay (LOS), intensive care unit (ICU) LOS, and total ventilation days were compared between each treatment group and stratified by ABO blood group. An exploratory analysis identified risk factors for mortality. Adverse effects were also evaluated. RESULTS: RDV monotherapy showed an increased chance of survival compared to combination therapy or CP monotherapy (p = 0.052). There were 15, 3, and 6 deaths in the CP, RDV, and combination therapy groups, respectively. The combination therapy group had the longest median ICU LOS (8, IQR 4.5-15.5, p = 0.220) and hospital LOS (11, IQR 7-15.5, p = 0.175). Age (p = 0.036), initial SOFA score (p = 0.013), and intubation (p = 0.005) were statistically significant predictors of mortality. Patients with type O blood had decreased ventilation days, ICU LOS, and total LOS. Thirteen treatment-related adverse events occurred. CONCLUSION: No significant differences in clinical outcomes were observed between patients treated with RDV, CP, or combination therapy. Elderly patients, those with a high initial SOFA score, and those who require intubation are at increased risk of mortality associated with COVID-19. Blood type did not affect clinical outcomes.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Inhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia.

Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreased erythropoietin (Epo) production, iron deficiency, and inflammation, and it is currently treated with injections of synthetic Epo. However, the use of recombinant Epo has several adverse effects. We previously reported that high fibroblast growth factor 23 (FGF23) levels in mice are associated with decreased red blood cell production, whereas genetic inactivation of Fgf23 results in expansion of the erythroid lineage. The present study is the first to show that high FGF23 levels in a mouse model of renal failure contribute to renal anemia, and inhibiting FGF23 signaling stimulates erythropoiesis and abolishes anemia and iron deficiency. Moreover, we show that inhibition of FGF23 signaling significantly decreases erythroid cell apoptosis and influences the commitment of hematopoietic stem cells toward the erythroid linage. Furthermore, we show that blocking FGF23 signaling attenuates inflammation, resulting in increased serum iron and ferritin levels. Our data clearly demonstrate that elevated FGF23 is a causative factor in the development of renal anemia and iron deficiency, and importantly, blocking FGF23 signaling represents a novel approach to stimulate erythropoiesis and possibly improve survival for millions of chronic kidney disease patients worldwide.-Agoro, R., Montagna, A., Goetz, R., Aligbe, O., Singh, G., Coe, L. M., Mohammadi, M., Rivella, S., Sitara, D. Inhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia.

Impact of PAP therapy on hospitalization rates in Medicare beneficiaries with COPD and coexisting OSA.

OBJECTIVE: Growing evidence supports that patients with chronic obstructive pulmonary disease (COPD) and coexisting obstructive sleep apnea (OSA) have poor prognosis. This association is described as overlap syndrome. Positive airway pressure (PAP) therapy is now the preferred treatment for OSA. We hypothesized that use of PAP therapy in elderly patients with overlap syndrome would be associated with lower healthcare utilization. METHODS: In this retrospective cohort study, we analyzed data from 5% national sample of fee-for-service Medicare beneficiaries with a diagnosis of COPD who were newly started on PAP therapy in 2011. We examined the effect of PAP therapy on emergency room (ER) visits and hospitalizations for all-cause and COPD-related conditions in the 1 year pre- and 1 year post-initiation of PAP therapy. RESULTS: In year 2011, we identified 319 patients with overlap syndrome who were new users of PAP therapy. In this cohort of patients, hospitalization rates for COPD-related conditions were significantly lower in the 1 year post-initiation of PAP therapy compared to the 1-year pre-initiation period (19.4 vs 25.4%, P value = 0.03). However, ER visits (for any cause or COPD-related conditions) and hospitalization rates for any cause did not differ significantly in the pre- and post-initiation periods. PAP therapy was more beneficial in older adults, those with higher COPD complexity, and those with three or more comorbidities. CONCLUSION: Initiation of PAP therapy in elderly patients with overlap syndrome is associated with a reduction in hospitalization for COPD-related conditions, but not for all-cause hospitalizations and ER visits.

High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction.

The intestinal microbe-derived metabolite trimethylamine N-oxide (TMAO) is implicated in the pathogenesis of cardiovascular diseases (CVDs). The molecular mechanisms of how TMAO induces atherosclerosis and CVDs' progression are still unclear. In this regard, high-mobility group box protein 1 (HMGB1), an inflammatory mediator, has been reported to disrupt cell-cell junctions, resulting in vascular endothelial hyper permeability leading to endothelial dysfunction. The present study tested whether TMAO associated endothelial dysfunction results via HMGB1 activation. Biochemical and RT-PCR analysis showed that TMAO increased the HMGB1 expression in a dose-dependent manner in endothelial cells. However, prior treatment with glycyrrhizin, an HMGB1 binder, abolished the TMAO-induced HMGB1 production in endothelial cells. Furthermore, Western blot and immunofluorescent analysis showed significant decrease in the expression of cell-cell junction proteins ZO-2, Occludin, and VE-cadherin in TMAO treated endothelial cells compared with control cells. However, prior treatment with glycyrrhizin attenuated the TMAO-induced cell-cell junction proteins' disruption. TMAO increased toll-like receptor 4 (TLR4) expression in endothelial cells. Inhibition of TLR4 expression by TLR4 siRNA protected the endothelial cells from TMAO associated tight junction protein disruption via HMGB1. In conclusion, our results demonstrate that HMGB1 is one of the important mediators of TMAO-induced endothelial dysfunction.

MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy.

Mitogen-activated protein kinases (MAPKs) (ERK1/2, JNK, and p38) are upregulated in diabetic cardiomyopathy (DCM). Dual-specific phosphatase-1 (DUSP-1) has been reported to regulate the activity of MAPKs in cardiac hypertrophy; however, the role of DUSP-1 in regulating MAPKs activity in DCM is not known. MicroRNAs have been reported to regulate the expression of several genes in hypertrophied failing hearts. However, little is known about the microRNAs regulating DUSP-1 expression in diabetes-related cardiac hypertrophy. In the present study, we investigated the role of DUSP-1 and miR-200c in diabetes-induced cardiac hypertrophy. DCM was induced in Wistar rats by low-dose Streptozotocin high-fat diet for 12 weeks. Cardiac expression of ERK, p-38, JNK, DUSP-1, miR-200c, and hypertrophy markers (ANP and ß-MHC) was studied in DCM in control rats and in high-glucose (HG)-treated rat neonatal cardiomyocytes. miR-200c inhibition was performed to validate DUSP-1 as target. A significant increase in phosphorylated ERK, p38, and JNK was observed in DCM model and in HG-treated cardiomyocytes (p < 0.05). Expression of DUSP-1 was significantly decreased in diabetes group and in HG-treated cardiomyocytes (p < 0.05). Increased expression of miR-200c was observed in DCM model and in HG-treated cardiomyocytes (p < 0.05). Inhibition of miR-200c induces the expression of the DUSP-1 causing decreased expression of phosphorylated ERK, p38, and JNK and attenuated cardiomyocyte hypertrophy in HG-treated cardiomyocytes. miR-200c plays a role in diabetes-associated cardiac hypertrophy by modulating expression of DUSP-1.

miR-30c and miR-181a synergistically modulate p53-p21 pathway in diabetes induced cardiac hypertrophy.

p53-p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53-p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53-p21 pathway in DbCM.

Understanding the adsorption behavior of surface active molecules on ZnO nanostructures by experimental and first-principles calculations.

Zinc oxide (ZnO) nanostructures with different morphologies are prepared in the presence of surface active molecules such as sodium dodecyl sulphate (SDS), Tween 80 and Triton X-100 by a chemical method. The experimental and first principles methods are employed to understand the microscopic origin of the asymmetric growth mechanism of ZnO in the presence of various surface active molecules. Effect of increase in the amount of surface active molecules and temperature is studied on the growth morphology of ZnO. An innovative method is developed to synthesize ZnO nanowires (NWs) in the presence of SDS. Spherical nanoparticles (NPs) to spherical clusters are obtained in the presence of Triton X-100 and Tween 80. These results are then supported by first principles calculations. The adsorption of the -OH functional group on both polar and nonpolar surfaces of ZnO is modelled by using density functional theory (DFT). The calculated binding energy (BE) is almost equivalent on both the surfaces with no preference on any particular surface. The calculated value of BE shows that the -OH group is physio-adsorbed on both the surfaces. This results in the spherical morphology of nanoparticles prepared in the presence of Tween 80. Bader charge analysis shows that the charge transfer mainly takes place on top two layers of the ZnO(101[combining macron]0) surface. The absence of high values of electron localization function (ELF) reflects the lack of covalent bonding between the -OH group and the ZnO(101[combining macron]0) surface.

Nitric oxide synthases and diabetic cardiomyopathy.

Cardiovascular complications associated with diabetes significantly contribute to high mortality and morbidity worldwide. The pathophysiology of diabetic cardiomyopathy (DCM), although extensively researched upon, is partially understood. Impairment in various signaling pathways including nitric oxide (NO) signaling has been implicated in the pathogenesis of diabetes induced myocardial damage. Nitric oxide synthases (NOS), the enzymes responsible for NO generation, play an important role in various physiological processes. Altered expression and activity of NOS have been implicated in cardiovascular diseases, however, the role of NOS and their regulation in the pathogenesis of DCM remain poorly understood. In the present review, we focus on the role of myocardial NOS in the development of DCM. Since epigenetic modifications play an important role in regulation of gene expression, this review also describes the epigenetic regulation of NOS.

Optimization (central composite design) and validation of HPLC method for investigation of emtricitabine loaded poly(lactic-co-glycolic acid) nanoparticles: in vitro drug release and in vivo pharmacokinetic studies.

The objective of the current study is to develop nanoparticles (NPs) drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid) (PLGA) and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD). NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 µm) column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8), methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v) at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040-2.0 µg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4). In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs.

Thoracic Intervertebral Disc Herniation Associated With Chronic Anabolic Androgenic Steroid Use: A Case Report.

Anabolic androgenic steroids (AAS) are relatively cheap and accessible medications, commonly used by athletes and bodybuilders for performance enhancement and muscle growth stimulation. AAS usage has been associated with musculoskeletal injuries, such as tendon and ligament ruptures, and numerous other detrimental health effects. Despite these risks, individuals continue to self-administer these drugs in supraphysiologic doses. Here, we present a case of a male bodybuilder with chronic AAS use who developed a spinal thoracic intervertebral disc herniation requiring decompression and fusion. We use this case to highlight a severe potential risk associated with chronic AAS abuse and review the current literature on the biochemical, physical, and physiologic mechanisms linking chronic AAS use, weight-bearing exercise, and the risk of musculoskeletal injuries such as intervertebral disc herniations.

Mucosa-Associated Lymphoid Tissue Surgeries as a Possible Risk for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and affects a significant portion of the global population. The gut-associated lymphoid tissue (GALT) is known to play a crucial role in immune modulation and maintaining gut microbiota balance. Dysbiosis in the latter has a known link to IBD. Therefore, the increasing prevalence of adenoidectomy in children should be explored for its potential association with IBD. The objective of this paper was to assess the association between adenoid tissue removal and the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a pooled meta-analysis to evaluate the extended clinical outcomes in patients who underwent appendicectomy and tonsillectomy compared to those who did not. Our approach involved systematically searching the PubMed database for relevant observational studies written in English. We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines to collect data from various time periods, and to address the diversity in study results; we employed a random-effects analysis that considered heterogeneity. For outcomes, odds ratios (ORs) were pooled using a random-effects model. Results: Seven studies, out of a total of 114,537, met our inclusion criteria. Our meta-analysis revealed a significant association between appendicectomy and CD (OR: 1.57; 95% confidence interval (CI): 1.01 - 2.43; heterogeneity I2 = 93%). Similarly, we found a significant association between tonsillectomy and CD (OR: 1.93; 95% CI: 0.96 - 3.89; I2 = 62%). However, no significant association was observed between appendicectomy and UC (OR: 0.60; 95% CI: 0.24 - 1.47; I2 = 96%), while a modest association was found between tonsillectomy and UC (OR: 1.24; 95% CI: 1.18 - 1.30; I2 = 0%). Conclusions: In summary, we found that the trend of appendicectomy is linked to higher odds of CD, and tonsillectomy is more likely associated with increased odds for both CD and UC, with a risk of bias present.

Advances and Challenges in the Management of Brugada Syndrome: A Comprehensive Review.

Brugada syndrome (BrS) is an inherited arrhythmogenic disorder marked by distinctive ST-segment elevations on electrocardiograms (ECG) and an increased risk of sudden cardiac death. Characterized by mutations primarily in the SCN5A gene, BrS disrupts cardiac ion channel function, leading to abnormal electrical activity and arrhythmias. Although BrS primarily affects young, healthy males, it poses significant diagnostic challenges due to its often concealed or intermittent ECG manifestations and clinical presentation that can mimic other cardiac disorders. Current management strategies focus on symptom control and prevention of sudden death, with implantable cardioverter-defibrillators (ICD) serving as the primary intervention for high-risk patients. However, the complications associated with ICDs and the lack of effective pharmacological options necessitate a cautious and personalized approach. Recent advancements in catheter ablation have shown promise, particularly for managing ventricular fibrillation (VF) storms and reducing ICD shocks. Additionally, pharmacological treatments such as quinidine have been effective in specific cases, though their use is limited by availability and side effects. This review highlights significant gaps in the BrS literature, particularly in terms of long-term management and novel therapeutic approaches. The importance of genetic screening and tailored treatment strategies to better identify and manage at-risk individuals is emphasized. The review aims to enhance the understanding of BrS and improve patient outcomes, advocating for a multidisciplinary approach to this complex syndrome.

Management of Long QT Syndrome: A Systematic Review.

Long QT syndrome (LQTS) is a cardiac disorder characterized by prolonged repolarization of the heart's electrical cycle, which can be observed as an extended QT interval on an electrocardiogram (ECG). The safe and effective management of LQTS often necessitates a multifaceted approach encompassing pharmacological treatment, lifestyle modifications, and, in high-risk cases, the implantation of implantable cardioverter-defibrillators (ICDs). Beta-blockers, particularly nadolol and propranolol, are foundational in treating LQTS, especially for high-risk patients, though ICDs are recommended for those with a history of cardiac arrest or recurrent arrhythmic episodes. Intermediate and low-risk patients are usually managed with medical therapy and regular monitoring. Lifestyle modifications, such as avoiding strenuous physical activities and certain medications, play a critical role. Additionally, psychological support is essential due to the anxiety and depression associated with LQTS. Left cardiac sympathetic denervation (LCSD) offers an alternative for those intolerant to beta-blockers or ICDs. For diagnosis and management, advancements in artificial intelligence (AI) are proving beneficial, enhancing early detection and risk stratification. Despite these developments, significant gaps in understanding the pathophysiology and optimal management strategies for LQTS remain. Future research should focus on refining risk stratification, developing new therapeutic approaches, and generating robust data to guide treatment decisions, ultimately aiming for a personalized medicine approach.

Interaction of aromatic amines with iron oxides: implications for prebiotic chemistry.

The interaction of aromatic amines (aniline, p-chloroaniline, p-toludine and p-anisidine) with iron oxides (goethite, akaganeite and hematite) has been studied. Maximum uptake of amines was observed around pH 7. The adsorption data obtained at neutral pH were found to follow Langmuir adsorption. Anisidine was found to be a better adsorbate probably due to its higher basicity. In alkaline medium (pH > 8), amines reacted on goethite and akaganeite to give colored products. Analysis of the products by GC-MS showed benzoquinone and azobenzene as the reaction products of aniline while p-anisidine afforded a dimer. IR analysis of the amine-iron oxide hydroxide adduct suggests that the surface acidity of iron oxide hydroxides is responsible for the interaction. The present study suggests that iron oxide hydroxides might have played a role in the stabilization of organic molecules through their surface activity and in prebiotic condensation reactions.

Conjunctival papilloma: a case report and a brief review of literature.

Background: Conjunctival papilloma commonly develops in infants and children. It is believed that the etiologic agent, human papillomavirus (HPV), gets implanted from the infected maternal birth canal in the conjunctival sac of the new borne while parturition. It grows as solitary or multiple pedunculated benign masses adjacent to the caruncle. It is uncommon but if growing in adults it grows on the limbal conjunctiva and could be malignant. Case Description: An Afro-American adult male developed two distinct conjunctival growths on his left lower lid. One growth was pedunculated and the second one sessile. The initial diagnosis of 'benign conjunctival papillomas' was made. Patient was recommended to wait and watch. After about two years the neoplasia had doubled their sizes. Surgical excisional biopsy was performed for diagnostic and therapeutic reasons. The tumor beds were treated with intra-operative cryotherapy using liquid nitrogen and applying double-freeze-thaw technique. Histopathology proved the masses to be benign and caused by HPV. Recurrence and seeding of virus during surgical excision leading to multiple new masses are dreaded complications during management of conjunctival papilloma. Though a short follow-up, yet after three months there were no signs of recurrence. Conclusions: A brief review of literature is presented to highlight the fact that rarely such conjunctival papillomas may develop at unusual sites and in adults. We believe that the uncommon demographic and anatomic presentation of this case is worth sharing with ophthalmic community.

Contribution of membrane raft redox signalling to visfatin-induced inflammasome activation and podocyte injury.

Recently we have shown that adipokine visfatin-induced NLRP3 inflammasome activation contributes to podocyte injury. However, the molecular mechanisms of how visfatin-induces the Nlrp3 inflammasome activation and podocyte damage is still unknown. The present study tested whether membrane raft (MR) redox signalling pathway plays a central role in visfatin-induced NLRP3 inflammasomes formation and activation in podocytes. Upon visfatin stimulation an aggregation of NADPH oxidase subunits, gp91phox and p47phox was observed in the membrane raft (MR) clusters, forming a MR redox signalling platform in podocytes. The formation of this signalling platform was blocked by prior treatment with MR disruptor MCD or NADPH oxidase inhibitor DPI. In addition, visfatin stimulation significantly increased the colocalization of Nlrp3 with Asc or Nlrp3 with caspase-1, IL-ß production, cell permeability in podocytes compared to control cells. Pretreatment with MCD, DPI, WEHD significantly abolished the visfatin-induced colocalization of NLRP3 with Asc or NLRP3 with caspase-1, IL-1ß production and cell permeability in podocytes. Furthermore, Immunofluorescence analysis demonstrated that visfatin treatment significantly decreased the podocin and nephrin expression (podocyte damage) and prior treatments with DPI, WEHD, MCD attenuated this visfatin-induced podocin and nephrin reduction. In conclusion, our results suggest that visfatin stimulates membrane raft clustering in the membrane of podocytes to form redox signaling platforms by aggregation and activation of NADPH oxidase subunits enhancing O2·- production and leading to NLRP3 inflammasome activation in podocytes and ultimate podocyte injury.

An Evaluation of Malaria Surveillance System in Punjab, India, 2020.

Background: India accounted for 6% of global burden of malaria with 95% population residing in malaria endemic areas. However, Punjab is in the malaria elimination phase with annual parasite incidence (API) <1/1000 population. Objectives: We evaluated malaria surveillance system in Punjab using CDC's updated guidelines for evaluating public health surveillance systems to provide recommendations for strengthening the existing system and to overcome the challenges in the path of malaria free Punjab. Methods: We chose two districts of Punjab, Amritsar (lowest API) and Mansa (highest API), interviewed stakeholders, and performed a retrospective desk review. We evaluated the overall usefulness of the system and assessed seven attributes at state, district, health facility, and village level during July-August 2020. Results: In Punjab, there was progressive decline in the malaria cases from 2,955 cases in 2009 to 1,140 in 2019 and no malaria deaths since 2011. Regarding various attributes, overall score for flexibility was good (85.9%); average for simplicity (77%), acceptability (74%), data quality (74%), and timeliness (70%); and poor for representativeness (59%) and stability (57%). Conclusions: Malaria surveillance system was useful in analyzing the trends of morbidity and mortality and for generating data to drive policy decisions. To improve stability, representativeness, and acceptability, surveillance staff should not be engaged in supplemental work, and reports from private sector must be ensured. Supportive supervision and regular trainings should be carried out regarding reporting formats, guidelines, and timely epidemiological investigations to improve timeliness, data quality, and simplicity.