Synthesis, characterization and biological evaluation of sulfonamide based transition metal complexes

In the present study a noval 4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic acid (OSPAB) was prepared by reaction of maleic anhydride with sulphanilamide. The prepared ligand was characterized by elemental analysis and spectral studies. The transition metal complexes viz. Cu2+, Ni2+ , Co2+ , Mn2+ and  Zn2+  of OSPAB were prepared and characterized by metal-ligand (M:L) ratio, IR, reflectance spectroscopies and magnetic properties. All the prepared metal complexes and ligand were studies as antimicrobial agent. Among all the metal complexes, Zn2+ and Cu2+ metal complexes have shown significant activity. Â

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report from the Pediatric Nephrology Research Consortium

Introduction Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose. Methods We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients \u3c 21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (\u3e 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival. Results Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07). Conclusion A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation

Clinical and epidemiological characterization of severe Plasmodium vivax malaria in Gujarat, India.

The mounting evidence supporting the capacity of Plasmodium vivax to cause severe disease has prompted the need for a better characterization of the resulting clinical complications. India is making progress with reducing malaria, but epidemics of severe vivax malaria in Gujarat, one of the main contributors to the vivax malaria burden in the country, have been reported recently and may be the result of a decrease in transmission and immune development. Over a period of one year, we enrolled severe malaria patients admitted at the Civil Hospital in Ahmedabad, the largest city in Gujarat, to investigate the morbidity of severe vivax malaria compared to severe falciparum malaria. Patients were submitted to standard thorough clinical and laboratory investigations and only PCR-confirmed infections were selected for the present study. Severevivax malaria (30 patients) was more frequent than severe falciparum malaria (8 patients) in our setting, and it predominantly affected adults (median age 32 years, interquartile range 22.5 years). This suggests a potential age shift in anti-malarial immunity, likely to result from the recent decrease in transmission across India. The clinical presentation of severe vivax patients was in line with previous reports, with jaundice as the most common complication. Our findings further support the need for epidemiological studies combining clinical characterization of severe vivax malaria and serological evaluation of exposure markers to monitor the impact of elimination programmes

Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits

Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac actin mutation. In both 3D engineered heart tissues and 2D monolayers, arrhythmogenesis was evident in all E99K-ACTC1 hiPSC-CMs. Aberrant phenotypes were most common in hiPSC-CMs produced from the heterozygote father. Unexpectedly, pathological phenotypes were less evident in E99K-expressing hiPSC-CMs from the two sons. Mechanistic insight from Ca2+ handling expression studies prompted pharmacological rescue experiments, wherein dual dantroline/ranolazine treatment was most effective. Our data are consistent with E99K mutant protein being a central cause of HCM but the three-way interaction between the primary genetic lesion, background (epi)genetics, and donor patient age may influence the pathogenic phenotype. This illustrates the value of isogenic hiPSC-CMs in genotype-phenotype correlations

A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 ?M in cardiomyocytes cultured on the co-polymer compared to 0.5 ?M on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials

Doing implementation research on health governance: a frontline researcher’s reflexive account of field-level challenges and their management

BACKGROUND: Implementation Research (IR) in and around health systems comes with unique challenges for researchers including implementation, multi-layer governance, and ethical issues. Partnerships between researchers, implementers, policy makers and community members are central to IR and come with additional challenges. In this paper, we elaborate on the challenges faced by frontline field researchers, drawing from experience with an IR study on Village Health Sanitation and Nutrition Committees (VHSNCs). METHODS: The IR on VHSNC took place in one state/province in India over an 18-month research period. The IR study had twin components; intervention and in-depth research. The intervention sought to strengthen the VHSNC functioning, and concurrently the research arm sought to understand the contextual factors, pathways and mechanism affecting VHSNC functions. Frontline researchers were employed for data collection and a research assistant was living in the study sites. The frontline research assistant experienced a range of challenges, while collecting data from the study sites, which were documented as field memos and analysed using inductive content analysis approach. RESULTS: Due to the relational nature of IR, the challenges coalesced around two sets of relationships (a) between the community and frontline researchers and (b) between implementers and frontline researchers. In the community, the frontline researcher was viewed as the supervisor of the intervention and was perceived by the community to have power to bring about beneficial changes with public services and facilities. Implementers expected help from the frontline researcher in problem-solving in VHSNCs, and feedback on community mobilization to improve their approaches. A concerted effort was undertaken by the whole research team to clarify and dispel concerns among the community and implementers through careful and constant communication. The strategies employed were both managerial, relational and reflexive in nature. CONCLUSION: Frontline researchers through their experiences shape the research process and its outcome and they play a central role in the research. It demonstrates that frontline researcher resilience is very crucial when conducting health policy and systems research.Scopu

Negotiating power relations, gender equality, and collective agency: are village health committees transformative social spaces in northern India?

BACKGROUND: Participatory health initiatives ideally support progressive social change and stronger collective agency for marginalized groups. However, this empowering potential is often limited by inequalities within communities and between communities and outside actors (i.e. government officials, policymakers). We examined how the participatory initiative of Village Health, Sanitation, and Nutrition Committees (VHSNCs) can enable and hinder the renegotiation of power in rural north India. METHODS: Over 18 months, we conducted 74 interviews and 18 focus groups with VHSNC members (including female community health workers and local government officials), non-VHSNC community members, NGO staff, and higherlevel functionaries. We observed 54 VHSNC-related events (such as trainings and meetings). Initial thematic network analysis supported further examination of power relations, gendered “social spaces,” and the “discourses of responsibility” that affected collective agency. RESULTS: VHSNCs supported some re-negotiation of intra-community inequalities, for example by enabling some women to speak in front of men and perform assertive public roles. However, the extent to which these new gender dynamics transformed relations beyond the VHSNC was limited. Furthermore, inequalities between the community and outside stakeholders were re-entrenched through a “discourse of responsibility”: The comparatively powerful outside stakeholders emphasized community responsibility for improving health without acknowledging or correcting barriers to effective VHSNC action. In response, some community members blamed peers for not taking up this responsibility, reinforcing a negative collective identity where participation was futile because no one would work for the greater good. Others resisted this discourse, arguing that the VHSNC alone was not responsible for taking action: Government must also intervene. This counter-narrative also positioned VHSNC participation as futile. CONCLUSIONS: Interventions to strengthen participation in health systems can engender social transformation. However they must consider how changing power relations can be sustained outside participatory spaces, and how discourse frames the rationale for community participation.ISIScopu

High throughput screening for discovery of materials that control stem cell fate

Insights into the complex stem cell niche have identified the cell–material interface to be a potent regulator of stem cell fate via material properties such as chemistry, topography and stiffness. In light of this, materials scientists have the opportunity to develop bioactive materials for stem cell culture that elicit specific cellular responses. To accelerate materials discovery, high throughput screening platforms have been designed which can rapidly evaluate combinatorial material libraries in two and three-dimensional environments. In this review, we present screening platforms for the discovery of material properties that influence stem cell behavior

Long COVID After Bamlanivimab Treatment

BackgroundProspective evaluations of long COVID in outpatients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to determine the frequency and predictors of long COVID after treatment with the monoclonal antibody bamlanivimab in ACTIV-2/A5401.MethodsData were analyzed from participants who received bamlanivimab 700 mg in ACTIV-2 from October 2020 to February 2021. Long COVID was defined as the presence of self-assessed COVID symptoms at week 24. Self-assessed return to pre-COVID health was also examined. Associations were assessed by regression models.ResultsAmong 506 participants, median age was 51 years. Half were female, 5% Black/African American, and 36% Hispanic/Latino. At 24 weeks, 18% reported long COVID and 15% had not returned to pre-COVID health. Smoking (adjusted risk ratio [aRR], 2.41 [95% confidence interval {CI}, 1.34- 4.32]), female sex (aRR, 1.91 [95% CI, 1.28-2.85]), non-Hispanic ethnicity (aRR, 1.92 [95% CI, 1.19-3.13]), and presence of symptoms 22-28 days posttreatment (aRR, 2.70 [95% CI, 1.63-4.46]) were associated with long COVID, but nasal severe acute respiratory syndrome coronavirus 2 RNA was not.ConclusionsLong COVID occurred despite early, effective monoclonal antibody therapy and was associated with smoking, female sex, and non-Hispanic ethnicity, but not viral burden. The strong association between symptoms 22-28 days after treatment and long COVID suggests that processes of long COVID start early and may need early intervention.Clinical trials registrationNCT04518410