First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers.

ApTOLL is an aptamer that antagonizes Toll-like receptor 4 and improves functional outcomes in models of ischemic stroke and myocardial infarction. The aim of this study was to characterize the safety and pharmacokinetics of ApTOLL in healthy volunteers. A first-in-human dose-ascending, randomized, placebo-controlled phase I clinical trial to assess safety and pharmacokinetics of ApTOLL (30-min infusion intravenously) was performed in 46 healthy adult male volunteers. The study was divided into two parts: part A included seven single ascending dose levels, and part B had one multiple dose cohort. Safety and pharmacokinetic parameters were evaluated. No serious adverse events or biochemistry alterations were detected at any dose nor at any administration pattern studied. Maximum concentration was detected at the end of the infusion and mean half-life was 9.3 h. Interestingly, exposure increased in the first four levels receiving doses from 0.7 mg to 14 mg (AUC of 2,441.26 h∗ng/mL to 23,371.11 h∗ng/mL) but remained stable thereafter (mean of 23,184.61 h∗ng/mL after 70 mg). Consequently, the multiple dose study did not show any accumulation of ApTOLL. These results show an excellent safety and adequate pharmacokinetic profile that, together with the efficacy demonstrated in nonclinical studies, provide the basis to start clinical trials in patients.This study was sponsored by aptaTargets S.L. (Madrid, Spain) and was conducted at the Clinical Trials Unit (La Princesa Hospital, Madrid, Spain). The study was supported by a grant from the Spanish Ministry of Science, Innovation and Universities (RTC-2017-6651- 1). Authors acknowledge David Segarra and M. Eugenia Zarabozo (aptaTargets S.L.) for their contribution in the management and funding of the trial, and Alba Singla (Anagram; Barcelona, Spain) for her contribution in the monitoring of the trial.S

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

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 <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (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 underweight 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 obesit

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Kirkir Warmi: identidad y rol de la mujer aymara en el desarrollo musical del norte chileno

Aymara women are inserted in the basic conception of duality as one of the basic principles of the Andean culture. Duality is a structure based upon a group of rules and values which are still valid in the Andean society. According to these rules, each member of the society is clearly aware of his/her identity, of his/her singularity, of his/her possibilities and of his/her roles that he she is expected to play within the Aymara society. In this dual and collective interaction, Aymara women fulfill functions oriented to this dual conception, denominated panipacha. This interaction is congruous with the sense of solidarity, reciprocity and the equality of conditions of men and women, following a scale of individual and collective values of the Andean culture. Each person is regulated by these rules provided by the same society. Therefore the theory of reciprocity and of mutual complement is part of the Aymara system of distribution and balance.La concepción básica de dualidad es uno de los principios de la cultura andina en la que está inserta la mujer aymara. Dualidad es una estructura basada sobre un conjunto de pautas y valores que persisten en la actualidad dentro de la sociedad andina. Según esa pauta, cada componente de la sociedad posee una clara conciencia de su identidad, de su singularidad, de sus posibilidades y los roles de su competencia en la sociedad. En esta interacción dual y colectiva, la mujer aymara cumple funciones que se orientan hacia el sentido dual, denominado panipacha. Esta interacción implica el sentido de solidaridad, reciprocidad e igualdad de condiciones entre el hombre y la mujer, de acuerdo a una escala de valores individuales o colectivos de la cultura andina. Cada persona está regulada por estas pautas dadas por la misma sociedad, por lo que la teoría de reciprocidad y complementariedad forma parte del sistema de distribución y equilibrio aymara

Kirkir Warmi: identidad y rol de la mujer aymara en el desarrollo musical del norte chileno Kirkir Warmi: Identity and Role of Aymara Women in the Musical Development of Northern Chile

La concepción básica de dualidad es uno de los principios de la cultura andina en la que está inserta la mujer aymara. Dualidad es una estructura basada sobre un conjunto de pautas y valores que persisten en la actualidad dentro de la sociedad andina. Según esa pauta, cada componente de la sociedad posee una clara conciencia de su identidad, de su singularidad, de sus posibilidades y los roles de su competencia en la sociedad. En esta interacción dual y colectiva, la mujer aymara cumple funciones que se orientan hacia el sentido dual, denominado panipacha. Esta interacción implica el sentido de solidaridad, reciprocidad e igualdad de condiciones entre el hombre y la mujer, de acuerdo a una escala de valores individuales o colectivos de la cultura andina. Cada persona está regulada por estas pautas dadas por la misma sociedad, por lo que la teoría de reciprocidad y complementariedad forma parte del sistema de distribución y equilibrio aymara.Aymara women are inserted in the baste conception of duality as one of the basic principles of the Andean culture. Duality is a structure based upon a group of rules and values, which are still valid in the Andean society. According to these rules, each member of the society is clearly aware of his/her identity, of his/her singularity, of his/her possibilities and of his/her roles that he she is expected to play within the Aymara society. In this dual and collective interaction, Aymara women fulfill functions oriented to this dual conception, denominated panipacha. This interaction is congruous with the sense of solidarity, reciprocity and the equality of conditions of msn and women, following a scale of individual and collective values of the Andean culture. Each person is regulated by these rules provided by the same society. Therefore, the theory of reciprocity and of mutual complement is part of the Aymara system of distribution and balance

Kirkir Warmi: identidad y rol de la mujer aymara en el desarrollo musical del norte chileno

La concepción básica de dualidad es uno de los principios de la cultura andina en la que está inserta la mujer aymara. Dualidad es una estructura basada sobre un conjunto de pautas y valores que persisten en la actualidad dentro de la sociedad andina. Según esa pauta, cada componente de la sociedad posee una clara conciencia de su identidad, de su singularidad, de sus posibilidades y los roles de su competencia en la sociedad. En esta interacción dual y colectiva, la mujer aymara cumple funciones que se orientan hacia el sentido dual, denominado panipacha. Esta interacción implica el sentido de solidaridad, reciprocidad e igualdad de condiciones entre el hombre y la mujer, de acuerdo a una escala de valores individuales o colectivos de la cultura andina. Cada persona está regulada por estas pautas dadas por la misma sociedad, por lo que la teoría de reciprocidad y complementariedad forma parte del sistema de distribución y equilibrio aymara

Determinación toxicológica de Cocaína, Marihuana y sus metabolitos en escolares de Educación Secundaria en Lima-Perú

Percentage of Drug abuse in Peruvian population is being determined only with inquiries and no toxiccological analysis is done. For the present study, 55 National High Schools from Lima, Perú, were selected considering those with high student population. The students age fluctuated between 15 and 19 years old, and 13 301 samples were analysed. The analysis results indicated that 15.9% of students had consumed cocaine; 9.9% marijuana; 0.7% benzodiazepine; 0.3% barbiturates and no one had consumed amphetamines. At the same time of sample collection, an inquiry, was performed results but the did not agree with the ones obtained from toxicological analysis. So, we concluded, that inquiries do not demonstrate the real percentage of drug abuse, since they are not answered with responsability by fue students, may be because of fear or shame to their drug-dependence situation.En el Perú, el porcentaje del consumo de drogas en la población viene siendo determinado mediante encuestas sin la realización de los análisis toxicológicos. Para el estudio se seleccionaron 55 colegios nacionales de educación secundaria del Departamento de Lima. Perú, considerando aquellos con gran cantidad de alumnos, con edades comprendidas entre los 15 y 19 años de edad, analizándose un total de 13 301 muestras. De los resultados de los análisis se concluye que el 15.9% de los alumnos consumían cocaína, el 9,9% marihuana, el 0,7% benzodiacepinas, el 0,3% barbitúricos y ninguno de ellos anfetaminas. Se realizó en forma paralela a la toma de muestra una encuesta, cuyo resultados no se aproximan a los obtenidos en los análisis toxicológicos, por lo que podemos afirmar que las encuestas no reflejan el porcentaje real del consumo de drogas