Microwave assisted preparation of 1,3-dithiolanes under solvent free conditions

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Association of Long-Term Exposure to Fine Particulate Matter and Cardio-Metabolic Diseases in Low- and Middle-Income Countries: A Systematic Review.

: Background: Numerous epidemiological studies indicated high levels of particulate matter less than2.5 μm diameter (PM2.5) as a major cardiovascular risk factor. Most of the studies have been conducted in high-income countries (HICs), where average levels of PM2.5 are far less compared to low- and middle- income countries (LMICs), and their socio-economic profile, disease burden, and PM speciation/composition are very different. We systematically reviewed the association of long-term exposure to PM2.5 and cardio-metabolic diseases (CMDs) in LMICs. METHODS: Multiple databases were searched for English articles with date limits until March 2018. We included studies investigating the association of long-term exposure to PM2.5 (defined as an annual average/average measure for 3 more days of PM2.5 exposure) and CMDs, such as hospital admissions, prevalence, and deaths due to CMDs, conducted in LMICs as defined by World Bank. We excluded studies which employed exposure proxy measures, studies among specific occupational groups, and specific episodes of air pollution. RESULTS: A total of 5567 unique articles were identified, of which only 17 articles were included for final review, and these studies were from Brazil, Bulgaria, China, India, and Mexico. Outcome assessed were hypertension, type 2 diabetes mellitus and insulin resistance, and cardiovascular disease (CVD)-related emergency room visits/admissions, death, and mortality. Largely a positive association between exposure to PM2.5 and CMDs was found, and CVD mortality with effect estimates ranging from 0.24% to 6.11% increased per 10 μg/m3 in PM2.5. CVD-related hospitalizations and emergency room visits increased by 0.3% to 19.6%. Risk factors like hypertension had an odds ratio of 1.14, and type 2 diabetes mellitus had an odds ratio ranging from 1.14-1.32. Diversity of exposure assessment and health outcomes limited the ability to perform a meta-analysis. CONCLUSION: Limited evidence on the association of long-term exposure to PM2.5 and CMDs in the LMICs context warrants cohort studies to establish the association

The gender perspective in climate change and global health

Background: Population health is a primary goal of sustainable development. United Nations international conferences like the Beijing Platform for Action have highlighted the key role of women in ensuring sustainable development. In the context of climate change, women are affected the most while they display knowledge and skills to orient themselves toward climate adaptation activities within their societies. Objective: To investigate how the gender perspective is addressed as an issue in research and policy-making concerning climate change and global health. Methods: A broad literature search was undertaken using the databases Pubmed and Web of Science to explore the terms ‘climate change,’ ‘health,’ ‘gender,’ and ‘policy.’ Climate change and health-related policy documents of the World Health Organization (WHO) and National Communications and National Adaptation Programs of Action reports submitted to the United Nations Framework Convention on Climate Change of selected countries were studied. Assessment guidelines to review these reports were developed from this study's viewpoint. Results: The database search results showed almost no articles when the four terms were searched together. The WHO documents lacked a gender perspective in their approach and future recommendations on climate policies. The reviewed UN reports were also neutral to gender perspective except one of the studied documents. Conclusion: Despite recognizing the differential effects of climate change on health of women and men as a consequence of complex social contexts and adaptive capacities, the study finds gender to be an underrepresented or non-existing variable both in research and studied policy documents in the field of climate change and health

Assessing the Effectiveness of Chemical Marker Extraction from Amazonian Plant Cupuassu (Theobroma grandiflorum) by PSI-HRMS/MS and LC-HRMS/MS.

Acknowledgments The authors acknowledge the institutional and financial support from the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) and the Brazilian Research Council (CNPq). Funding This research received no external funding.Peer reviewedPublisher PD

Leveraging Existing Cohorts to Study Health Effects of Air Pollution on Cardiometabolic Disorders:India Global Environmental and Occupational Health Hub

Air pollution is a growing public health concern in developing countries and poses a huge epidemiological burden. Despite the growing awareness of ill effects of air pollution, the evidence linking air pollution and health effects is sparse. This requires environmental exposure scientist and public health researchers to work more cohesively to generate evidence on health impacts of air pollution in developing countries for policy advocacy. In the Global Environmental and Occupational Health (GEOHealth) Program, we aim to build exposure assessment model to estimate ambient air pollution exposure at a very fine resolution which can be linked with health outcomes leveraging well-phenotyped cohorts which have information on geolocation of households of study participants. We aim to address how air pollution interacts with meteorological and weather parameters and other aspects of the urban environment, occupational classification, and socioeconomic status, to affect cardiometabolic risk factors and disease outcomes. This will help us generate evidence for cardiovascular health impacts of ambient air pollution in India needed for necessary policy advocacy. The other exploratory aims are to explore mediatory role of the epigenetic mechanisms (DNA methylation) and vitamin D exposure in determining the association between air pollution exposure and cardiovascular health outcomes. Other components of the GEOHealth program include building capacity and strengthening the skills of public health researchers in India through variety of training programs and international collaborations. This will help generate research capacity to address environmental and occupational health research questions in India. The expertise that we bring together in GEOHealth hub are public health, clinical epidemiology, environmental exposure science, statistical modeling, and policy advocacy

Incidencia de los hábitos de estudio y las estrategias de evaluación que implementan los docentes, en el rendimiento académico de los estudiantes de III y IV año de la carrera de Educación Comercial, en las asignaturas de Cálculo Mercantil I y Cálculo Mercantil II, en la Facultad de Educación e Idiomas de la Universidad Nacional Autónoma de Nicaragua (UNAN-Managua), durante el primer semestre del año 2016

La presente investigación tiene como propósito general analizar la Incidencia de los hábitos de estudio y las estrategias de evaluación que implementan los docentes, en el rendimiento académico de los alumnos de III y IV año de la carrera de Educación Comercial, en las asignaturas de Cálculo Mercantil I y Cálculo Mercantil II, en la Facultad de Educación e Idiomas de la Universidad Nacional Autónoma de Nicaragua (UNAN-Managua), durante el primer semestre del año 2016. La investigación está centrada en un enfoque sociológico cuantitativo, es de tipo ex post facto o no experimental, de corte transversal, descriptiva y correlacional. Tiene una cierta implicación cualitativa porque intenta comprender la realidad del fenómeno, desde la visión de alumnos y docentes que son las unidades de análisis involucradas. El alcance de este estudio considera dos grandes componentes relacionadas con el rendimiento académico, como son los hábitos de estudio y las formas de evaluación, en la revisión bibliográfica se encontró estudios que tratan una u otra componente, pero no las dos simultáneamente. La metodología utilizada consideró una muestra probabilística representativa de treinta y tres alumnos de III y IV año de la carrera de Educación Comercial, a los cuales se les aplicó un instrumento de medición acerca de sus hábitos de estudio, el que fue analizado con técnicas estadísticas descriptivas e inferenciales. También se realizaron dos grupos focales, el primero con una muestra intencional de doce alumnos y el segundo con ocho docentes que han impartido Cálculo Mercantil. Además de una entrevista dirigida al coordinador de la carrera. Entre los principales resultados obtenidos, se obtuvo que en general los alumnos no practican hábitos de estudio, y que estas prácticas tienen una mínima relación lineal con el rendimiento académico. Además que las formas tradicionales de evaluación inciden negativamente en los aprendizajes significativos de los alumno

Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma.

UNLABELLED: Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial-mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs. SIGNIFICANCE: The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors

Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA

The Time to Offer Treatments for COVID-19

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization

ZikaPLAN: Zika Preparedness Latin American Network

The ongoing Zika virus (ZIKV) outbreak in Latin America, the Caribbean, and the Pacific Islands has underlined the need for a coordinated research network across the whole region that can respond rapidly to address the current knowledge gaps in Zika and enhance research preparedness beyond Zika. The European Union under its Horizon 2020 Research and Innovation Programme awarded three research consortia to respond to this need. Here we present the ZikaPLAN (Zika Preparedness Latin American Network) consortium. ZikaPLAN combines the strengths of 25 partners in Latin America, North America, Africa, Asia, and various centers in Europe. We will conduct clinical studies to estimate the risk and further define the full spectrum and risk factors of congenital Zika virus syndrome (including neurodevelopmental milestones in the first 3 years of life), delineate neurological complications associated with ZIKV due to direct neuroinvasion and immune-mediated responses in older children and adults, and strengthen surveillance for birth defects and Guillain-Barré Syndrome. Laboratory-based research to unravel neurotropism and investigate the role of sexual transmission, determinants of severe disease, and viral fitness will underpin the clinical studies. Social messaging and engagement with affected communities, as well as development of wearable repellent technologies against Aedes mosquitoes will enhance the impact. Burden of disease studies, data-driven vector control, and vaccine modeling as well as risk assessments on geographic spread of ZIKV will form the foundation for evidence-informed policies. While addressing the research gaps around ZIKV, we will engage in capacity building in laboratory and clinical research, collaborate with existing and new networks to share knowledge, and work with international organizations to tackle regulatory and other bottlenecks and refine research priorities. In this way, we can leverage the ZIKV response toward building a long-term emerging infectious diseases response capacity in the region to address future challenges