Decavanadate Salts of Cytosine and Metformin: A Combined Experimental-Theoretical Study of Potential Metallodrugs Against Diabetes and Cancer

Cytosine, a DNA and RNA building-block, and Metformin, the most widely prescribed drug for the treatment of Type 2 Diabetes mellitus were made to react separately with ammonium or sodium metavanadates in acidic aqueous solutions to obtain two polyoxovanadate salts with a 6:1 ratio of cation-anion. Thus, compounds [HCyt]6[V10O28]·4H2O, 1 and [HMetf]6[V10O28]·6H2O, 2 (where HCyt = Cytosinium cation, [C4H6N3O]+ and HMetf = Metforminium cation, [C4H12N5]+) were obtained and characterized by elemental analysis, single crystal X-ray diffraction, vibrational spectroscopy (IR and Raman), solution 51V-NMR, thermogravimetric analysis (TGA-DTGA), as well as, theoretical methods. Both compounds crystallized in P1¯ space group with Z' = 1/2, where the anionic charge of the centrosymmetric ion [V10O28]6− is balanced by six Cytosinium and six Metforminium counterions, respectively. Compound 1 is stabilized by π-π stacking interactions coming from the aromatic rings of HCyt cations, as denoted by close contacts of 3.63 Å. On the other hand, guanidinium moieties from the non-planar HMetf in Compound 2 interact with decavanadate μ2-O atoms via N−H···O hydrogen bonds. The vibrational spectroscopic data of both IR and Raman spectra show that the dominant bands in the 1000-450 cm−1 range are due to the symmetric and asymmetric ν(V−O) vibrational modes. In solution, 51V-NMR experiments of both compounds show that polyoxovanadate species are progressively transformed into the monomeric, dimeric and tetrameric oxovanadates. The thermal stability behavior suggests a similar molecular mechanism regarding the loss of water molecules and the decomposition of the organic counterions. Yet, no changes were observed in the TGA range of 540–580°C due to the stability of the [V10O28]6− fragment. Dispersion-corrected density functional theory (DFT-D) calculations were carried out to model the compounds in aqueous phase using a polarized continuum model calculation. Optimized structures were obtained and the main non-covalent interactions were characterized. Biological activities of these compounds are also under investigation. The combination of two therapeutic agents opens up a window toward the generation of potential metalopharmaceuticals with new and exciting pharmacological properties

Impacto y evaluación del riesgo en la deuda pensional contingente de Colombia

Este estudio esclarece los conceptos de deuda pública cierta, respecto a la deuda contingente e identifica su impacto en la sostenibilidad de las finanzas públicas del país. Los razonamientos que se hacen acerca de la sostenibilidad de la deuda es decir, si la deuda de un país puede ser otorgada sin una gran corrección futura en el balance de ingresos y gastos, se dirigen a determinar en qué momento es apropiado para un país refinanciar y sí una reestructuración de la deuda puede ser necesaria. En la parte siguiente se realiza un análisis sobre la incertidumbre alrededor de las proyecciones de la deuda y el servicio de la deuda, la cual se relaciona con los derechos contingentes, tales como los definidos con las garantías explícitas implícitas de la deuda de los pasivos pensionales contingentes. Bajo el enfoque de los derechos contingentes en un nivel agregado, se analizan los puntos de incertidumbre mencionados, estimando el riesgo de crédito del gobierno central en este caso (probabilidad de default), evaluando los costos potenciales de las transferencias y calculando el spread sobre la deuda pública. Posteriormente se examina la estructura y operación del sistema pensional colombiano en la actualidad, evaluando múltiples factores de riesgo que afectan el escenario del sistema colombiano de pensiones tanto en el presente como en el futuro. Finalmente, con base en una gama de alternativas técnicas de valoración del riesgo y su implementación para el escenario de la seguridad social se ilustra la problemática del riesgo que encierra la deuda pensional en Colombia proyectando variables clave como: el salario, las cotizaciones, el empleo y el PIB. Con base en dichas proyecciones, se analiza el costo fiscal y la viabilidad de la garantía de pensión mínima.This study clarifies, the concepts of certain national debt with respect to the contingent debt as well as it identifies his impact in the sustainability of the public finances of the country. The reasoning that become about the sustainability of the debt, that is to say, if the debt of a country can be granted without a great future correction in the balance of income and expenses, go to determine in what moment a country is appropriate to refinance and when a reconstruction of the debt can be necessary. In the following pan, an analysis is made on the uncertainty around the projections of the debt and the service of the debt, which is related to the contingent rights, such as the defined ones with the explicit or implicit guarantees of the debt or the contingent pensionales liabilities. Under the approach of the contingent rights in a added level, the mentioned points of uncertainty are analyzed. We consider the risk of credit of the central government in this case (probability of default), evaluating the potential costs of the transferences and calculating spread on the national debt. Later it is examined the structure and operation del Colombian pensional system at the present time, evaluating multiple factors of risk that affect the scene as much of the Colombian system of pensions today as in the future. Finally, with base in a range of technical alternatives of valuation of the risk and its implementation for the scene of the social security the problematic one of the risk acquires knowledge that looks up the pensional debt in variable Colombia projecting key like: the wage, the quotations, the employment and the GDF. With base in these projections, one analyzes the fiscal cost and the viability of the guarantee of minimum pension

Bean Golden Mosaic: Research Advances

El frijol (Phaseolus vulgaris L.) es una de las fuentes de proteina (15-35%) y calorías (ca. 340 caI./100 gr) más importantes en la América Latina. En esta región, centro de origen de esta especie, se producen más de cuatro millones de toneladas de frijol al año, lo cual equivale al 88% de la semilla de frijol producida en las regiones tropicales del mundo. Brasil, el mayor productor de frijol del mundo, posee un consumo per capita de cerca de 20 kg/año. En America Central, el frijol es igualmente importante, siendo consumido en la mayoría de los países centroamericanos hasta tres veces por día. Proporcionalmente, en la America Central se cultiva el doble del área que en Brasil, relativo a sus extensiones territoriales. El frijol es también producido en islas del Caribe, tales como Cuba (ca. 26.000 TM), Haití (56.000 TM) y República Dominicana (55.000 TM) según datos de 1990 (CIAT). México, el segundo productor de frijol en la America Latina, consume aproximadamente 1.2 millones de toneladas métricas de frijol al año. A pesar de que México cultiva cerca de 1.800.000 hectáreas de frijol, la demanda interna no es satisfecha en algunos años dado la baja productividad del cultivo. Esta baja productividad relativa del frijol, no solo en México sino también en el resto de la América Latina (700 kg/ha vs. 1.600 kg/ha en los Estados Unidos), es una consecuencia de los múltiples problemas bióticos y abióticos que inciden en el cultivo, en el trópico Americano. Es precisamente en las regiones productoras de frijol situadas en climas cálidos, de altitud baja a intermedia (0-1200 m.s.n.m), donde el mosaico dorado del frijol alcanza su mayor incidencia.The common bean (Phaseolus vulgaris L.) is an important source of protein and calories in Latin America. In this region, the center of origin of this legume species, over 4 million tons of dry beans are produced per year. Nevertheless, many Latin American countries, including two of the largest producers of beans in the world, Brazil and Mexico, have to import beans to meet internal demand. This shortage of beans is related to the low productivity of this crop in Latin America (700 kg /ha vs. 1,600 kg/ ha average in the USA). The low productivity in the main bean production regions of tropical America is associated to the incidence of several biotic and abiotic constraints. Among the biotic constraints, bean golden mosaic virus is undoubtedly the main bean production problem in the lowland tropics, particularly, during the dry seasons of the year.Programa Cooperativo Regional de Frijol para Centroamérica, México y el Caribe (PROFRIJOL)Cooperación Suiza para el Desarrollo (COSUDE)Centro Internacional de Agricultura Tropical (CIAT)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental Agrícola Fabio Baudrit Moreno (EEAFBM

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

EDUCACIÓN AMBIENTAL Y SOCIEDAD. SABERES LOCALES PARA EL DESARROLLO Y LA SUSTENTABILIDAD

Este texto contribuye al análisis científico de varias áreas del conocimiento como la filosofía social, la patología, la educación para el cuidado del medio ambiente y la sustentabilidad que inciden en diversas unidades de aprendizaje de la Licenciatura en Educación para la Salud y de la Maestría en Sociología de la SaludLas comunidades indígenas de la sierra norte de Oaxaca México, habitan un territorio extenso de biodiversidad. Sin que sea una área protegida y sustentable, la propia naturaleza de la región ofrece a sus visitantes la riqueza de la vegetación caracterizada por sus especies endémicas que componen un paisaje de suma belleza

General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants

Background Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension. Methods We used data from studies carried out from 1990 to 2023 on BMI, WHtR and hypertension in people aged 20–64 years in representative samples of the general population in eight world regions. We graphically compared the regional distributions of BMI and WHtR, and calculated Pearson’s correlation coefficients between BMI and WHtR within each region. We used mixed-effects linear regression to estimate the extent to which WHtR varies across regions at the same BMI. We graphically examined the prevalence of hypertension and the distribution of people who have hypertension both in relation to BMI and WHtR, and we assessed how closely BMI and WHtR discriminate between participants with and without hypertension using C-statistic and net reclassification improvement (NRI). Findings The correlation between BMI and WHtR ranged from 0·76 to 0·89 within different regions. After adjusting for age and BMI, mean WHtR was highest in south Asia for both sexes, followed by Latin America and the Caribbean and the region of central Asia, Middle East and north Africa. Mean WHtR was lowest in central and eastern Europe for both sexes, in the high-income western region for women, and in Oceania for men. Conversely, to achieve an equivalent WHtR, the BMI of the population of south Asia would need to be, on average, 2·79 kg/m² (95% CI 2·31–3·28) lower for women and 1·28 kg/m² (1·02–1·54) lower for men than in the high-income western region. In every region, hypertension prevalence increased with both BMI and WHtR. Models with either of these two adiposity metrics had virtually identical C-statistics and NRIs for every region and sex, with C-statistics ranging from 0·72 to 0·81 and NRIs ranging from 0·34 to 0·57 in different region and sex combinations. When both BMI and WHtR were used, performance improved only slightly compared with using either adiposity measure alone. Interpretation BMI can distinguish young and middle-aged adults with higher versus lower amounts of abdominal adiposity with moderate-to-high accuracy, and both BMI and WHtR distinguish people with or without hypertension. However, at the same BMI level, people in south Asia, Latin America and the Caribbean, and the region of central Asia, Middle East and north Africa, have higher WHtR than in the other regions

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effects of Co-Solvent Nature and Acid Concentration in the Size and Morphology of Wrinkled Mesoporous Silica Nanoparticles for Drug Delivery Applications

Hierarchically porous materials, such as wrinkled mesoporous silica (WMS), have gained interest in the last couple of decades, because of their wide range of applications in fields such as nanomedicine, energy, and catalysis. The mechanism of formation of these nanostructures is not fully understood, despite various groups reporting very comprehensive studies. Furthermore, achieving particle diameters of 100 nm or less has proven difficult. In this study, the effects on particle size, pore size, and particle morphology of several co-solvents were evaluated. Additionally, varying concentrations of acid during synthesis affected the particle sizes, yielding particles smaller than 100 nm. The morphology and physical properties of the nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic light scattering (DLS). Homogeneous and spherical WMS, with the desired radial wrinkle morphology and particle sizes smaller than 100 nm, were obtained. The effect of the nature of the co-solvents and the concentration of acid are explained within the frame of previously reported mechanisms of formation, to further elucidate this intricate process