O-GlcNAc transferase acts as a critical nutritional node for the control of liver homeostasis.

Background & Aims: O-GlcNAcylation is a reversible post-translational modification controlled by the activity of two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In the liver, O-GlcNAcylation has emerged as an important regulatory mechanism underlying normal liver physiology and metabolic disease. Methods: To address whether OGT acts as a critical hepatic nutritional node, mice with a constitutive hepatocyte-specific deletion of OGT (OGTLKO) were generated and challenged with different carbohydrate- and lipid-containing diets. Results: Analyses of 4-week-old OGTLKO mice revealed significant oxidative and endoplasmic reticulum stress, and DNA damage, together with inflammation and fibrosis, in the liver. Susceptibility to oxidative and endoplasmic reticulum stress-induced apoptosis was also elevated in OGTLKO hepatocytes. Although OGT expression was partially recovered in the liver of 8-week-old OGTLKO mice, hepatic injury and fibrosis were not rescued but rather worsened with time. Interestingly, weaning of OGTLKO mice on a ketogenic diet (low carbohydrate, high fat) fully prevented the hepatic alterations induced by OGT deletion, indicating that reduced carbohydrate intake protects an OGT-deficient liver. Conclusions: These findings pinpoint OGT as a key mediator of hepatocyte homeostasis and survival upon carbohydrate intake and validate OGTLKO mice as a valuable model for assessing therapeutical approaches of advanced liver fibrosis. Impact and Implications: Our study shows that hepatocyte-specific deletion of O-GlcNAc transferase (OGT) leads to severe liver injury, reinforcing the importance of O-GlcNAcylation and OGT for hepatocyte homeostasis and survival. Our study also validates the Ogt liver-deficient mouse as a valuable model for the study of advanced liver fibrosis. Importantly, as the severe hepatic fibrosis of Ogt liver-deficient mice could be fully prevented upon feeding on a ketogenic diet (i.e. very-low-carbohydrate, high-fat diet) this work underlines the potential interest of nutritional intervention as antifibrogenic strategies.

Membrane transporters in cell physiology, cancer metabolism and drug response.

By controlling the passage of small molecules across lipid bilayers, membrane transporters influence not only the uptake and efflux of nutrients, but also the metabolic state of the cell. With more than 450 members, the Solute Carriers (SLCs) are the largest transporter super-family, clustering into families with different substrate specificities and regulatory properties. Cells of different types are, therefore, able to tailor their transporter expression signatures depending on their metabolic requirements, and the physiological importance of these proteins is illustrated by their mis-regulation in a number of disease states. In cancer, transporter expression is heterogeneous, and the SLC family has been shown to facilitate the accumulation of biomass, influence redox homeostasis, and also mediate metabolic crosstalk with other cell types within the tumour microenvironment. This Review explores the roles of membrane transporters in physiological and malignant settings, and how these roles can affect drug response, through either indirect modulation of sensitivity or the direct transport of small-molecule therapeutic compounds into cells.

Evaluation of factors associated with recruitment rates in early phase clinical trials based on the European Clinical Trials Register data.

Effective participant recruitment is a critical challenge in clinical trials. Inadequate enrollment of participants can precipitate delays, escalated costs, and compromise scientific integrity. Despite its relevance, particularly during the early phases, it persists as an obstacle in the field of clinical research. The primary aim of this study was to analyze the recruitment rates of early-phase clinical trials and evaluate their potential associations with key trial characteristics. Using a descriptive and statistical analysis, a research study was conducted based on the early-phase trials registered at the European Clinical Trials Register (EU-CTR), spanning the timeframe from January 2017 to December 2021. Among the 194 trials examined, we found median recruitment rates of 68%. A more detailed exploration revealed a greater level of success in terms of recruitment achievement in pediatric trials when compared to trials involving adults, non-oncologic trials, or those also developed in non-European countries. It is important to underscore that only 69 trials out of the total managed to conclude recruitment, with the most prevalent reason for premature cessation being the presence of efficacy and safety issues or sponsor's strategy. This number can be greatly improved. Despite certain disparities observed in the information within EU-CTR, we have successfully determined the recruitment rates of the studies and established associations with some of the clinical trial characteristics analyzed. Owing to the inherent constraints of this study, further research is warranted to gain a comprehensive understanding of the intricate interplay between trial characteristics and their impact on recruitment rates in early-phase studies.

Academia and industry agreement on a feasibility tool for first-time-in-human clinical trial units.

First-time-in-human (FTIH) trials are designed to generate information on the safety, tolerability, as well as the pharmacokinetic and pharmacodynamics profile of new drugs. To ensure the safety of participants, these trials need to be conducted at specifically equipped phase I clinical trial units (CTUs). In accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP) and the European Union (EU) regulatory guidelines, one of the aims of the European Regime Accelerator for Tuberculosis (ERA4TB) project is to collaboratively create a feasibility tool, through a partnership between public and private entities, for the validation of CTUs selected to conduct FTIH trials. A feasibility form, encompassing nine sections, was created to gather information on the unit in relation to key attributes of FTIH trials. Collaboratively, industry and academic partners defined the minimal criteria to ensure the adherence of CTUs to the principles of ICH GCP and regulations outlined by the European Medicines Agency (EMA) for the execution of FTIH trials. Subsequently, all CTUs available for the project were assessed for FTIH trial eligibility. The introduction of the certification procedure through the feasibility tool within ERA4TB resulted in the accreditation of the five academic CTUs, which are now prepared to carry out FTIH trials as part of the Consortium. The developed feasibility tool aims to establish open and widely used minimum requirements for the validation of academic CTUs as FTIH units, marking it as the inaugural tool for CTU validation resulting from the collaboration between industry and academia within the ERA4TB project. The established partnership has enabled an innovative and novel way of working.

Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens.

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

Short-term Neuropsychiatric and Body Weight Changes in Patients Switching From EVG/Cobi/FTC/TAF to BIC/FTC/TAF (PreEC/RIS69).

BACKGROUND: We report NP, clinical and laboratory changes in patients switching from EVG/Cobi/FTC/TAF to BIC/FTC/TAF in clinical practice. METHODS: A group of subjects switching from EVG/Cobi/FTC/TAF to BIC/F/TAF was prospectively followed. A validated sleep quality questionnaire (Pittsburgh Sleep Quality Index), as well as the Hospital Anxiety and Depression Scale (HADS), were administered after 4 weeks from the treatment switch. Adverse events, side effects and discontinuation were recorded at weeks 4 and 24. Pretreatment switch and week 24 body weight and laboratory data were compared. RESULTS: A total of 96 virologically suppressed patients (86% male) were included. All patients received EVG/Cobi/FTC/TAF at least 1 year before the treatment switch. Median (IQR) nadir CD4 was 367 (263). The most common comorbidities were dyslipidemia, HTA and diabetes, 26%, 14% and 7%, respectively. Depression was reported by 8%. Five patients discontinued BIC/FTC/TAF before week 4 due to intolerance (2 insomnia, 1 headache and 2 GI symptoms). No changes in sleep quality, anxiety and depression outcomes were observed at week 4 (p = 0.1, p = 0.1 and p = 0.3, respectively). After 6 months, the median body weight change was statistically significant (0.6 kg, p = 0.003). All patients maintained HIV suppression. CONCLUSION: Except in a few cases, sleep quality, anxiety and depression symptoms remain stable in HIV virologically suppressed patients on EVG/Cobi/FTC/TAF who switch to BIC/F/TAF. NPAEs are mild and tend to occur in those with previous neuropsychiatric symptoms. Weight gain tends to be small but statistically significant. Long-term follow-up in "real-life" cohorts would be needed to confirm these findings.

Sembrando Salud: escuelas de campo para el mejoramiento de la seguridad alimentaria en Soracá, Boyacá, Colombia, en 2017 / Sembrando Salud: Farmer Schools for the Improvement of the Food Security in Soracá, Boyacá Colombia, in 2017

Resumen: Antecedentes: las escuelas de campo para agricultores constituyen una metodología en la que los participantes comparten conocimientos previos para brindar soluciones a problemas agrarios. Objetivo: fortalecer la disponibilidad, acceso y consumo de alimentos saludables, mediante la estrategia Sembrando Salud en dos veredas rurales y el centro poblado del municipio de Soracá, Boyacá, Colombia, en el año 2017. Materiales y métodos: se realizó un estudio mixto que incluyó observación participante para evidenciar el fenómeno del acceso a alimentos y encuestas para medir el cambio en acceso, disponibilidad y consumo de alimentos saludables. Con las escuelas de campo se desarrollaron cinco módulos de formación con una intensidad de siete horas cada uno. Resultados: Sembrando Salud contó con la participación de 100 personas, 40 % menores de 18 años y 60 % adultos; 74 % mujeres y 26 % hombres. El acceso, disponibilidad y consumo de frutas y verduras es limitado, por los elevados costos de los alimentos y por el desconocimiento de su preparación. El cambio en la inclusión y consumo de frutas y verduras se evidenció en el 59,4 %, que realizó cambios en la producción, 51,9 % en la preparación y 43 % en adquirir verduras por otra vía. Conclusión: Sembrando Salud demostró que los procesos de participación y educación rural permiten el mejoramiento en el acceso, la disponibilidad y el consumo de alimentos saludables en poblaciones rurales.

Abstract: Background: Farmer field schools are a methodology in which participants share prior knowledge to supply solutions to agrarian problems. Objective: To strengthen the availability, access, and consumption of healthy food through Sembrando Salud strategy in two rural villages and the town center of the municipality of Soracá, Boyacá, Colom bia, in 2017. Materials and Methods: A mixed study was conducted including participant observation to show the phenomenon of food access and surveys to measure the change in access, availability, and consumption of healthy foods. With the farmer schools were developed five training modules with seven hours of intensity each. Results: Sembrando Salud involved 100 participants, 40 % under 18 years of age and 60 % adults; 74 % female and 26 % male. Access, availability, and consumption of fruits and vegetables are limited, due to the high cost of food and lack of knowledge on how to prepare them. The change in the inclusion and consumption of fruit and vegetables was showed by 59.4 % making changes in production, 51.9 % in preparation, and 43% in acquiring vegetables by other means. Conclusion: Sembrando Salud demonstrated that rural participation and education processes allow the improvement of access, availability, and consumption of healthy food in rural populations.

Total and Unbound Doravirine Concentrations and Viral Suppression in CSF.

We determined total and unbound concentrations of doravirine (DOR) in cerebrospinal fluid and blood plasma. Total and unbound DOR concentrations in cerebrospinal fluid exceeded the half-maximal effective concentration against wild-type virus (5.1 ng/mL) in all patients, suggesting that DOR may contribute to inhibit viral replication in this compartment.

Chems4EU: chemsex use and its impacts across four European countries in HIV-positive men who have sex with men attending HIV services.

INTRODUCTION: Chemsex in a European context is the use of any of the following drugs to facilitate sex: crystal methamphetamine, mephedrone and gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) and, to a lesser extent, cocaine and ketamine. This study describes the prevalence of self-reported recreational drug use and chemsex in HIV-positive men who have sex with men (MSM) accessing HIV services in four countries. It also examines the problematic impacts and harms of chemsex and access to chemsex-related services. METHODS: This is a cross-sectional multi-centre questionnaire study of HIV-positive MSM accessing nine HIV services in the UK, Spain, Greece and Italy. RESULTS: In all, 1589 HIV-positive MSM attending HIV services in four countries completed the questionnaire. The median age of participants was 38 years (interquartile range: 32-46 years) and 1525 (96.0%) were taking antiretroviral therapy (ART). In the previous 12 months, 709 (44.6%) had used recreational drugs, 382 (24.0%) reported chemsex and 104 (6.5%) reported injection of chemsex-associated drugs ('slamsex'). Of the 382 engaging in chemsex, 155 (40.6%) reported unwanted side effects as a result of chemsex and 81 (21.2%) as a result of withdrawal from chemsex. The reported negative impacts from chemsex were on work (25.1%, 96), friends/family (24.3%, 93) and relationships (28.3%, 108). Fifty-seven (14.9%) accessed chemsex-related services in the past year, 38 of whom (67%) felt the service met their needs. DISCUSSION: A quarter of participants self-reported chemsex in the past 12 months. There were high rates of harms from chemsex across all countries, including negative impacts on work, friends/family and relationships. Although a minority of those engaging in chemsex accessed support, most found this useful.

Prácticas de alimentación del lactante y del niño pequeño en tres instituciones de salud en el Caribe colombiano, bajo la estrategia "Instituciones amigas de la mujer y la infancia integral" / Feeding practices of the infant and child, in three health institutions in the Colombian Caribbean / Práticas de alimentação do lactante y del niño pequeño en tres instituciones de salud en el Caribe colombiano, bajo la estrategia "Instituciones amigas de la mujer y la infancia integral "

Resumen Objetivo: Describir las prácticas de alimentación de niños lactantes y de niños pequeños atendidos en instituciones de tres municipios del Caribe colombiano, incluidos en el proceso de implementación de la estrategia "Instituciones amigas de la mujer y la infancia integral" de la Unicef. Metodología: Estudio cualitativo enmarcado en la etnografía, llevado a cabo mediante entrevistas semiestructuradas, cartografía social y grupos focales, dirigido a madres beneficiarias de instituciones de salud priorizadas. Resultados: Las madres reconocieron los beneficios nutricionales de la lactancia materna, y en dos de los territorios, los beneficios emocionales. Además, presentan apropiación en lo relacionado con la alimentación perceptiva. No obstante, no cumplen con el periodo de exclusividad de la lactancia, refieren algunas creencias populares acerca de la misma y se observa un inicio temprano de la alimentación complementaria. También reconocieron la importancia de las redes de apoyo familiar y social, como, por ejemplo, del Instituto Colombiano de Bienestar Familiar. Conclusión: Esta investigación permitió reconocer factores que favorecen y limitan las adecuadas prácticas de alimentación del lactante y del niño pequeño, en madres gestantes y lactantes y su red de apoyo, las cuales viven en condiciones de vulnerabilidad social y económica, y son atendidas en tres instituciones de salud del Caribe colombiano que se encuentran en proceso de implementación de la estrategia enunciada. Lo anterior brinda elementos para la formulación de procesos educativos en salud para la población materno infantil, tanto en la población objetivo como en instituciones que se encuentren en proceso de implementación de dicha estrategia, y de requerimientos políticos acerca de la salud materno infantil.

Abstract Objective: Describe the infant and young child feeding practices of children cared for in institutions of the Colombian Caribbean, includes in implementing the baby friendly hospital strategy. Methodology: Qualitative study framed in ethnography through semi-structured interviews, aimed at beneficiary mothers of prioritized health institutions. Results: The mothers recognized the nutrtitionals benefits of breastfeeding, in two territories also the emotional benefits. They also show appropriation in relation to perceptual feeding. However, they do not comply with the exclusive period of breastfeeding, they refer to some beliefs around it, an early start of complementary feeding is observed. In turn, the mothers recognized the importance of family and social support networks, such as the Instituto Colombiano de Bienestar Familiar. Conclusion: This research made it possible to recognize factors that favor and limit the adequate feeding practices of infants and young children, in pregnant and lactating mothers and their support network, who live in conditions of social and economic vulnerability and are cared for in three health institutions of the Colombian Caribbean that are in the process of implementing the baby-friendly hospitals initiative. The foregoing provides elements for the formulation of educational processes in health in the maternal and child population, both in the target population and in institutions that are in the process of implementing the baby-friendly hospitals initiative and policies to maternal and child health.

Resumo Objetivo: Descrever as práticas alimentares de lactentes e crianças atendidas em instituições de três municípios do Caribe colombiano, incluídas no processo de implementação da estratégia do Unicef "Instituições Amigas da Mulher e Infância Integral". Metodologia: Estudo qualitativo enquadrado na etnografia, realizado por meio de entrevistas semiestruturadas, cartografia social e grupos focais, dirigido a mães beneficiárias de instituições de saúde priorizadas. Resultados: As mães reconheceram os benefícios nutricionais da amamentação e, em dois dos territórios, os benefícios emocionais. Além disso, apresentam apropriação em relação à alimentação perceptiva. Porém, não cumprem o período exclusivo de aleitamento materno, referem-se a algumas crenças populares a respeito, e observa-se o início precoce da alimentação complementar. Também reconheceram a importância das redes de apoio familiar e social, como o Instituto Colombiano de Bem-Estar Familiar. Conclusão: Esta pesquisa permitiu reconhecer fatores que favorecem e limitam as práticas alimentares adequadas de lactentes e crianças pequenas, em gestantes e lactantes e sua rede de apoio, que vivem em condições de vulnerabilidade social e econômica, sendo atendidas em três. Instituições de saúde do Caribe colombiano que estão em processo de implementação da estratégia declarada. O exposto fornece elementos para a formulação de processos educativos em saúde para a população materno-infantil, tanto na população-alvo como nas instituições que estão em processo de implementação dessa estratégia, e de requisitos políticos relativos à saúde materno-infantil.

Reduction of chronic malnutrition for infants in Bogotá, Colombia.

BACKGROUND: According to the 2015 National Survey of the Nutritional Situation in Colombia the prevalence of stunting in children under 5 years of age was 10.8%. In terms of region, Bogotá, presented the highest prevalence rate (13%), a figure that exceeded national records. With the collaboration of local and national government, and nongovernmental it was decided to develop a pilot study involving a public health intervention with residents of Bogotá under 1 year of age with nutritional classification by anthropometry compatible with stunting risk or stunting. METHODS: Pre-experimental, before and after study that sought to determine the magnitude of the change in nutritional status through a 10 months public health nutrition intervention in children under one-year-old residing in 3 prioritized territories of Bogotá. RESULTS: The intervention comprised 1126 children living in the following territories in Bogotá: Kennedy, San Cristóbal, and Engativá. A total of 43.3% children presented delay in height for age, and 56.7% presented risk of short stature. In the final measurement, data were obtained from 686 children, identifying that 17% of the children progressed from stunting to a stunting risk and that 4.5% recovered their growth trajectory, achieving an adequate length for their age. CONCLUSION: That children classified as at risk or stunting at the beginning of the intervention showed an increased probability of approaching or being in the appropriate growth trajectory according to the length-for-age indicator after the intervention.

El estado de la investigación en educación en cirugía general en Colombia (2000-2020): un análisis bibliométrico / The state of research in general surgery education in Colombia(2000-2020): A bibliometric analysis

Introducción. Se desconoce el estado de la investigación en educación médica en cirugía general (IEMC) en Colombia en el siglo XXI. El objetivo de esta revisión bibliométrica de la literatura es realizar un análisis de las publicaciones relacionadas con la IEMC en Colombia a partir del año 2000. Métodos. Se incluyeron artículos originales, escritos en español o inglés, publicados por grupos de investigación que cuentan al menos con un investigador colombiano como autor principal o coautor. Se definieron variables demográficas e indicadores bibliométricos para cada estudio y autor. Resultados. Un total de 63 estudios fueron incluidos. Estas publicaciones se enfocaron predominantemente en investigación sobre bienestar, enseñanza clínica y simulación a nivel de postgrado. El 36 % de los artículos sobre IEMC fueron publicados en revistas sin indexación (ISI/SCOPUS); 13 artículos (20,6 %) fueron publicados en re-vistas en el cuartil 1 (Q1). El promedio de citas por artículo fue 9,3.Discusión. La producción intelectual en educación en cirugía en Colombia tiene bajo impacto a nivel internacional. Los hallazgos encontrados pueden ser utilizados para organizar y priorizar la investigación en educación quirúrgica en el país

Introduction. The state of research in medical education in general surgery (IEMC) in Colombia in the XXI century is unknown. The objective of this bibliometric review of the literature is to conduct an analysis of the publications related to the IEMC in Colombia from the year 2000.Methods. Original articles, written in Spanish or English, published by research groups that have at least one Co-lombian researcher as main author or co-author, were included. Demographic variables and bibliometric indicators were defined for each study and author.Results. A total of 63 studies were included. Publications predominantly focused on wellness research, clinical teaching, and simulation at the graduate level; 36% of the articles on IEMC were published in non-indexed journals (ISI / SCOPUS), 13 articles (20.6%) were published in journals in quartile 1 (Q1). The average number of citations per article was 9.3.Discussion. Intellectual production in Colombian surgery education shows low impact at international level. These findings can be used to prioritize research in surgical education in the country

Nitrogen influenced biomolecular changes on Physalis L. species studied using 2DCOS spectral analysis coupled with chemometric and Receiver operation characteristics analysis.

The determination of the molecular composition of plant leaves is essential to assist in nutritional management, whether for cultivated or non-cultivated species. In this sense, the study aimed to apply FTIR technique in combination with chemometrics and ROC analysis for the evaluation of changes in compositional of plant leaves of Physalis angulata and Physalis peruviana due to nitrogen fertilization treatments. Both species were grown under different doses of nitrogen (0, 200, 400, and 600 Kg ha-1) and leaf samples were evaluated using ATR-FTIR. Our results demonstrate that the spectra of both species were influenced by the nitrogen doses. The computed band area from the lipid/amide, lipid/carbohydrates, degree of esterification and calcium oxalate shows nitrogen fertilization due to 400 Kg ha-1 of N treatment is more effective for a better quality of yield. 2D correlation spectral analysis (2DCOS) reveals cellulose and pectin begins changes followed by amide of proteins due to nitrogen treatment in P. peruviana samples. The P. angulata plants shows hemicellulose changes predominating followed by proteins and polysaccharides. The obtained principle component analysis plot and loading values show the Physalis species samples distinctly separated from control with protein and carbohydrates are predominant in influencing separation among them. Receiver operation characteristic analysis shows a higher value of area under the curve reflecting better reliability of the experiments carried out. Hierarchical cluster analysis shows closed separation for a similar group on dissimilarity scale. Thus the use of 2DCOS coupled with chemometrics helps to identify changes in the composition of leaves of physalis species due to nitrogen doses, constituting a fast and precise measuring for the suitable management of this fertilization.

Prevención de enfermedades no transmisibles desde la gobernanza y seguridad alimentaria, Soracá-Colombia / Prevention of non-communicable diseases from governance and food security in Soraca, Colombia

RESUMEN Objetivo Evaluar si el municipio, en Colombia, es el escenario apropiado para el desarrollo de políticas en seguridad alimentaria y nutricional enfocadas en la prevención de enfermedades no transmisibles. Métodos A través del estudio de prevención en diabetes y obesidad de Soracá (Boyacá, Colombia) se efectuó un análisis de los dispositivos legales relacionados con enfermedades no transmisibles y seguridad alimentaria y nutricional (1990-2017). Se vincularon entrevistas realizadas a actores municipales y departamentales desde la gobernanza. Resultados El municipio cuenta con dirección y liderazgo, diseño y estructura institucional, intersectorialidad y capacidad del Gobierno municipal para la generación de políticas en salud, como la Política Municipal de Seguridad Alimentaria y Nutricional, que aborda enfermedades no transmisibles desde la situación alimentaria, nutricional y rural por medio de un enfoque ecosistémico e intersectorial. Conclusión El municipio es el escenario adecuado para la planificación de estrategias intersectoriales con claro liderazgo municipal en un marco de gobernanza.

ABSTRACT Objective To assess whether the municipality, in Colombia, is the appropriate setting for the development of food and nutrition security policies focused on the prevention of non-communicable diseases. Methods Through the study of diabetes and obesity prevention in Soracá (Boyacá, Colombia), an analysis of the legal provisions related to non-communicable diseases and food and nutrition security (1990-2017) was carried out. Interviews were conducted with municipal and departmental actors, based on governance. Results The municipality has direction and leadership, institutional design, and structure, intersectorality and capacity of the municipal government to generate health policies, such as the Municipal Policy on Food and Nutrition Security, addressing non-communicable diseases from the food, nutrition and rural situation through an eco-systemic and intersectoral approach. Conclusion The municipality is the appropriate setting for the planning of cross-sectoral strategies with clear municipal leadership in the governance framework.

[Prevention of non-communicable diseases from governance and food security in Soraca, Colombia]. / Prevención de enfermedades no transmisibles desde la gobernanza y seguridad alimentaria, Soracá-Colombia.

OBJECTIVE: To assess whether the municipality, in Colombia, is the appropriate setting for the development of food and nutrition security policies focused on the prevention of non-communicable diseases. METHODS: Through the study of diabetes and obesity prevention in Soracá (Boyacá, Colombia), an analysis of the legal provisions related to non-communicable diseases and food and nutrition security (1990-2017) was carried out. Interviews were conducted with municipal and departmental actors, based on governance. RESULTS: The municipality has direction and leadership, institutional design, and structure, intersectorality and capacity of the municipal government to generate health policies, such as the Municipal Policy on Food and Nutrition Security, addressing non-communicable diseases from the food, nutrition and rural situation through an eco-systemic and intersectoral approach. CONCLUSION: The municipality is the appropriate setting for the planning of cross-sectoral strategies with clear municipal leadership in the governance framework.

OBJETIVO: Evaluar si el municipio, en Colombia, es el escenario apropiado para el desarrollo de políticas en seguridad alimentaria y nutricional enfocadas en la prevención de enfermedades no transmisibles. MÉTODOS: A través del estudio de prevención en diabetes y obesidad de Soracá (Boyacá, Colombia) se efectuó un análisis de los dispositivos legales relacionados con enfermedades no transmisibles y seguridad alimentaria y nutricional (1990-2017). Se vincularon entrevistas realizadas a actores municipales y departamentales desde la gobernanza. RESULTADOS: El municipio cuenta con dirección y liderazgo, diseño y estructura institucional, intersectorialidad y capacidad del Gobierno municipal para la generación de políticas en salud, como la Política Municipal de Seguridad Alimentaria y Nutricional, que aborda enfermedades no transmisibles desde la situación alimentaria, nutricional y rural por medio de un enfoque ecosistémico e intersectorial. CONCLUSIÓN: El municipio es el escenario adecuado para la planificación de estrategias intersectoriales con claro liderazgo municipal en un marco de gobernanza.

Total and Unbound Bictegravir Concentrations and Viral Suppression in Cerebrospinal Fluid of Human Immunodeficiency Virus-Infected Patients (Spanish HIV/AIDS Research Network, PreEC/RIS 56).

We determined total and unbound concentrations of bictegravir (BIC) in cerebrospinal fluid (CSF) in 15 asymptomatic, virologically suppressed patients. The median plasma and CSF total BIC concentrations were 1837.1 ng/mL (interquartile range [IQR], 1237.2-2586.7) and 6.9 (IQR, 4.8-10.9), respectively. Median unbound BIC concentration was 2.48 ng/mL (IQR, 1.6-3.7). Total and unbound BIC CSF concentrations were above the half-maximal effective concentration value in all patients, and all subjects had human immunodeficiency virus viral suppression in plasma and CSF. Bictegravir may contribute to inhibit viral replication in this compartment.

Earliness per se×temperature interaction: consequences on leaf, spikelet, and floret development in wheat.

Wheat adaptation can be fine-tuned by earliness per se (Eps) genes. Although the effects of Eps genes are often assumed to act independently of the environment, previous studies have shown that they exhibit temperature sensitivity. The number of leaves and phyllochron are considered determinants of flowering time and the numerical components of yield include spikelets per spike and fertile floret number within spikelets. We studied the dynamics of leaf, spikelet, and floret development in near isogenic lines with either late or early alleles of Eps-D1 under seven temperature regimes. Leaf appearance dynamics were modulated by temperature, and Eps alleles had a greater effect on the period from flag leaf to heading than phyllochron. In addition, the effects of the Eps alleles on spikelets per spike were minor, and more related to spikelet plastochron than the duration of the early reproductive phase. However, fertile floret number was affected by the interaction between Eps alleles and temperature. So, at 9 °C, Eps-early alleles had more fertile florets than Eps-late alleles, at intermediate temperatures there was no significant difference, and at 18 °C (the highest temperature) the effect was reversed, with lines carrying the late allele producing more fertile florets. These effects were mediated through changes in floret survival; there were no clear effects on the maximum number of floret primordia.