Critical appraisal of the Colombian clinical practice guide for the prevention, diagnosis and treatment of suicidal ideation and/or behaviour (adoption).

INTRODUCTION: Suicide is a complex, global public health problem. The Colombian clinical practice guideline provides relevant input for its prevention, diagnosis and treatment. The objective was to evaluate the methodological quality, credibility and applicability of the Colombian clinical practice guideline for suicidal behaviour. METHODS: An academic group of 12 evaluators was established to assess the guide and its recommendations in a standardised way, using the AGREE-II and AGREE-REX instruments. The evaluations were given in the range of 0.0-1.0 with 0.7 as a cut-off point for appropriate quality. RESULTS: The global assessment of the AGREE-II was greater than 0.7 in the dimensions: "scope and objective" (0.86), "clarity of presentation" (0.89), "applicability" (0.73) and "editorial independence" (0.89). The lowest scores were for "participation of those involved" (0.67) and "rigour in preparation" (0.69). With the AGREE-REX, the results in all dimensions were below 0.70, which indicates lower quality and suitability for use. CONCLUSIONS: The adoption process of the Colombian guideline for suicidal behaviour was a rigorous methodological process, while the practice recommendations were valued as of low applicability due to low support in local evidence. It is necessary to strengthen the generation and synthesis of evidence at the national level to give greater support and applicability to the practice recommendations.

Inpatient glycemic management in noncritically ill patients: Updated guidelines.

Hyperglycemia is common in hospitalized patients and is traditionally managed with scheduled and correctional doses of insulin. The authors present an overview of the latest (2022) guidelines from the Endocrine Society on inpatient hyperglycemia management in noncritically ill patients, which includes a role for newer diabetes technologies and nontraditional insulin and noninsulin therapies.

Analysis of Diffusion Coefficients of Iron Monoboride and Diiron Boride Coating Formed on the Surface of AISI 420 Steel by Two Different Models: Experiments and Modelling.

In the present work, two mathematical diffusion models have been used to estimate the growth of the iron monoboride and diiron boride coating formed on AISI 420 steel. The boronizing of the steel was carried out with the solid diffusion packing method at a boronizing temperature of 1123 K-1273 K. Experimental results show the two-coating system consists of an outer monoboride and an inner diiron boride coating with a predominantly planar structure at the propagation front. The depth of the boride coating increases according to temperature and treatment time. A parabolic curve characterizes the propagation of the boride coatings. The two proposed mathematical models of mass transfer diffusion are founded on the solution corresponding to Fick's second fundamental law. The first is based on a linear boron concentration-penetration profile without time dependence, and the second model with time dependence (exact solution). For both models, the theoretical law of parabolic propagation and the average flux of boron atoms (Fick's first fundamental law) at the growth interfaces (monoboride/diiron boride and diiron boride/substrate) are considered to estimate the propagation of the boride coatings (monoboride and diiron boride). To validate the mathematical models, a programming code is written in the MATLAB program (adaptation 7.5) designed to simulate the growth of the boride coatings (monoboride and diiron boride). The following parameters are used as input data for this computer code: (the layer thicknesses of the FeB and Fe2B phases, the operating temperature, the boronizing time, initial formation time of the boride coating, the surface boron concentration limits, FeB/Fe2B and Fe2B/Fe growth interfaces, and the mass transfer diffusion coefficient of boron in the iron monoboride and diiron boride phases). The outputs of the computer code are the constants εFeB and εFe2B. The assessment of activation energies of AISI 420 steel for the two mathematical models of mass transfer is coincident (QFeB=221.9 kJ∙mol-1 and QFe2B=209.1 kJ∙mol-1). A numerical analysis was performed using a standard Taylor series for clarification of the proximity between the two models. SEM micrographs exhibited a strong propensity toward a flat-fronted composition at expansion interfaces of the iron monoboride and diiron boride coating, confirmed by XRD analysis. Tribological characterizations included the Vickers hardness test method, pin-on-disc, and Daimler-Benz Rockwell-C indentation adhesion tests. After thorough analysis, the energies were compared to the existing literature to validate our experiment. We found that our models and experimental results agreed. The diffusion models we utilized were crucial in gaining a deeper understanding of the boronizing behavior of AISI 420 steel, and they also allowed us to predict the thicknesses of the iron monoboride and diiron boride coating. These models provide helpful approaches for predicting the behavior of these steels.

Geological context and human exposures to element mixtures in mining and agricultural settings in Colombia.

Anthropogenic and natural sources contribute to chemical mixtures in air, water, and soil, posing potential risks to the environment and human health. To understand the interplay between element profiles in the human body, geographical location, and associated economic activities, we carried out an observational analytic cross-sectional study. The study recruited 199 participants from three municipalities, two of which had gold-mining as their primary economic activity, while the other was dedicated to agricultural and other local activities not related to mining. The concentrations of a total of 30 elements in human hair samples and 21 elements in environmental soil samples were measured using various spectrometry techniques. Unsupervised clustering analysis using Self-Organizing Maps was applied to human hair samples to analyze element concentrations. Distinct clusters of individuals were identified based on their hair element profiles, which were mapped to geographical location and economic activities. While higher levels of heavy metals (Ag, As, Hg, and Pb) were observed in individuals engaged in mining activities in certain clusters, individuals in agricultural areas show higher concentrations of elements found in pesticides (Ba and Sr). However, the elemental composition of hair is influenced not only by the anthropogenic activities but also by the inherent geological context where people live. Our findings highlight the significance of accounting for environmental factors when evaluating human health risks, as the intricate mixture of elements can yield valuable insights for targeted health interventions.

IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.

Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of IFNL4-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

Allopatric speciation is more prevalent than parapatric ecological divergence in a recent high-Andean diversification (Linochilus: Asteraceae).

Elucidating how species accumulate in diversity hotspots is an ongoing debate in evolutionary biology. The páramo, in the Northern Andes, has remarkably high indices of plant diversity, endemicity, and diversification rates. A hypothesis for explaining such indices is that allopatric speciation is high in the páramo given its island-like distribution. An alternative hypothesis is that the altitudinal gradient of the Andean topography provides a variety of niches that drive vertical parapatric ecological speciation. A formal test for evaluating the relative roles of allopatric and parapatric ecological speciation is lacking. The main aim of our study is to test which kind of speciation is more common in an endemic páramo genus. We developed a framework incorporating phylogenetics, species' distributions, and a morpho-ecological trait (leaf area) to compare sister species and infer whether allopatric or parapatric ecological divergence caused their speciation. We applied our framework to the species-rich genus Linochilus (63 spp.) and found that the majority of recent speciation events in it (12 events, 80%) have been driven by allopatric speciation, while a smaller fraction (one event, 6.7%) is attributed to parapatric ecological speciation; two pairs of sister species produced inconclusive results (13.3%). We conclude that páramo autochthonous (in-situ) diversification has been primarily driven by allopatric speciation.

Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. CONCLUSIONS: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. PATIENT SUMMARY: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.

[The Pan American Health Organization's Revolving Fund for access to vaccines: 43 years responding to the regional immunization programO Fundo Rotativo para Acesso a Vacinas da Organização Pan-Americana da Saúde: 43 anos respondendo ao Programa Regional de Imunizações]. / El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones.

The Pan American Health Organization's Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund's operation and analyzing its contributions to achievements in immunization, a review was conducted of historical documents and grey literature related to the Fund's history and current processes, as well as data from platforms fed by countries' annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administering them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund's contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interprogrammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procurement of high-cost vaccines are current and future challenges.

O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua contribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimentadas pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A abordagem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones

[RESUMEN]. El Fondo Rotatorio para el acceso a las vacunas (FR) de la Organización Panamericana de la Salud es un fondo común de capital y compra mancomunada de vacunas, jeringas y equipo de cadena de frío para los Estados Miembros de la Organización. Con el objetivo de evaluar los resultados obtenidos durante su funcio- namiento y analizar su contribución a los logros de inmunización, se llevó a cabo una revisión de documentos históricos y literatura gris relacionados con la historia del FR, y se revisaron los procesos actuales, los datos de plataformas alimentadas por los informes anuales de los países, los indicadores de crecimiento, la carga de enfermedades prevenibles por vacunación, la introducción de nuevas vacunas en la Región de las Amé- ricas, y lecciones aprendidas. Se encontró que, en sus 43 años de funcionamiento, el FR ha crecido y ha contribuido a la introducción de nuevas vacunas, y que la Región ha avanzado de manera acelerada en el ámbito de las inmunizaciones. Sin embargo, varios países y territorios de la Región todavía no han introducido ciertas vacunas debido a sus altos precios y al impacto económico del mantenimiento de su administración. La cláusula del precio más bajo posible y del precio uniforme para todos los Estados Miembros participantes ha sido fundamental para la contribución del FR a las metas de vacunación de los programas nacionales de inmunización, así como para la planeación oportuna de la demanda acompañada por la asesoría técnica. El abordaje interprogramático y la planeación de insumos auxiliares son necesarios para el éxito de los progra- mas. La preparación ante pandemias, la producción regional de vacunas y la protección de presupuestos nacionales para la compra de vacunas de alto costo y su sostenibilidad constituyen aún retos en el presente y el futuro.

[ABSTRACT]. The Pan American Health Organization’s Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund’s operation and analyzing its contributions to achievements in immunization, a review was conducted of historical docu- ments and grey literature related to the Fund’s history and current processes, as well as data from platforms fed by countries’ annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administe- ring them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund’s contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interpro- grammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procure- ment of high-cost vaccines are current and future challenges.

[RESUMO]. O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua con- tribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimenta- das pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A aborda- gem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

Genome assemblies and comparison of two Neotropical spiral gingers: Costus pulverulentus and C. lasius.

The spiral gingers (Costus L.) are a pantropical genus of herbaceous perennial monocots; the Neotropical clade of Costus radiated rapidly in the past few million years into over 60 species. The Neotropical spiral gingers have a rich history of evolutionary and ecological research that can motivate and inform modern genetic investigations. Here, we present the first 2 chromosome-level genome assemblies in the genus, for C. pulverulentus and C. lasius, and briefly compare their synteny. We assembled the C. pulverulentus genome from a combination of short-read data, Chicago and Dovetail Hi-C chromatin-proximity sequencing, and alignment with a linkage map. We annotated the genome by mapping a C. pulverulentus transcriptome and querying mapped transcripts against a protein database. We assembled the C. lasius genome with Pacific Biosciences HiFi long reads and alignment to the C. pulverulentus genome. These 2 assemblies are the first published genomes for non-cultivated tropical plants. These genomes solidify the spiral gingers as a model system and will facilitate research on the poorly understood genetic basis of tropical plant diversification.

Chemical Element Mixtures and Kidney Function in Mining and Non-Mining Settings in Northern Colombia.

The exposure to chemical mixtures is a problem of concern in developing countries and it is well known that the kidney is the major target organ for toxic elements. This cross-sectional study aimed to estimate the individual and composite mixture effect of a large number of chemical elements on kidney function in gold-mining and surrounding non-mining populations in northeast Colombia. We measured concentrations of 36 chemical elements in hair as indicators of chronic exposure from 199 adult participants. We estimated the effect of exposure to mixtures of chemical elements on estimated glomerular filtration rate (eGFR) using weighted quantile sum regression (WQS). The WQS index of the mixture was associated with reduced eGFR (Coefficient -2.42; 95%CI: -4.69, -0.16) being Be, Cd, Pb, As, and Mn, the principal contributors of the toxic mixture. Mining activities and Hg concentration were not associated with decreased kidney function. Our results suggest that complex mixtures of chemical elements, mainly heavy metals, act as nephrotoxic in these populations and therefore the analysis of chemical element mixtures is a better approach to identify environmental and occupational chemical risks for kidney damage.

El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones / The Pan American Health Organization's Revolving Fund for access to vaccines: 43 years responding to the regional immunization program / O Fundo Rotativo para Acesso a Vacinas da Organização Pan-Americana da Saúde: 43 anos respondendo ao Programa Regional de Imunizações

RESUMEN El Fondo Rotatorio para el acceso a las vacunas (FR) de la Organización Panamericana de la Salud es un fondo común de capital y compra mancomunada de vacunas, jeringas y equipo de cadena de frío para los Estados Miembros de la Organización. Con el objetivo de evaluar los resultados obtenidos durante su funcionamiento y analizar su contribución a los logros de inmunización, se llevó a cabo una revisión de documentos históricos y literatura gris relacionados con la historia del FR, y se revisaron los procesos actuales, los datos de plataformas alimentadas por los informes anuales de los países, los indicadores de crecimiento, la carga de enfermedades prevenibles por vacunación, la introducción de nuevas vacunas en la Región de las Américas, y lecciones aprendidas. Se encontró que, en sus 43 años de funcionamiento, el FR ha crecido y ha contribuido a la introducción de nuevas vacunas, y que la Región ha avanzado de manera acelerada en el ámbito de las inmunizaciones. Sin embargo, varios países y territorios de la Región todavía no han introducido ciertas vacunas debido a sus altos precios y al impacto económico del mantenimiento de su administración. La cláusula del precio más bajo posible y del precio uniforme para todos los Estados Miembros participantes ha sido fundamental para la contribución del FR a las metas de vacunación de los programas nacionales de inmunización, así como para la planeación oportuna de la demanda acompañada por la asesoría técnica. El abordaje interprogramático y la planeación de insumos auxiliares son necesarios para el éxito de los programas. La preparación ante pandemias, la producción regional de vacunas y la protección de presupuestos nacionales para la compra de vacunas de alto costo y su sostenibilidad constituyen aún retos en el presente y el futuro.

ABSTRACT The Pan American Health Organization's Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund's operation and analyzing its contributions to achievements in immunization, a review was conducted of historical documents and grey literature related to the Fund's history and current processes, as well as data from platforms fed by countries' annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administering them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund's contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interprogrammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procurement of high-cost vaccines are current and future challenges.

RESUMO O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua contribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimentadas pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A abordagem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

Comparison and Analysis of Diffusion Models: Growth Kinetics of Diiron Boride Layers on ASTM A283 Steel.

Hard-coated surfacing of a few micrometers is widely applied to increase the efficiency of tools, e.g., for cutting, forming, and casting applications. Therefore, the base thermodiffusion surface treatment is a practical solution to these issues by hardening surface layers with interstitial elements such as carbon, nitrogen, and boron. In particular, within this study, the growth kinetics of an iron boride layer on ASTM 283 steel were investigated with two diffusion models of the powder-pack boriding technique in the temperature range of 1123-1273 K with different treatment periods. The first model, called the steady-state diffusion model, used the modified version of the mass balance equations at the Fe2B/substrate growth interface, the parabolic growth law, and the solution of Fick's second law without time dependence. At the same time, the second diffusion model was based on Goodman's method, also called the integral heat balance method. Afterward, the diffusion coefficient of boron in the Fe2B phase was calculated by fitting the experimental data to the models. Nevertheless, the estimated value for the activation energy of ASTM A238 steel in both diffusion models was coincident (168.2 kJ∙mol-1). A mathematical analysis was implemented by means of a power series (Taylor series) to explain this similarity. The SEM examinations showed a solid tendency to saw-tooth morphology at the growth interface with the formation of the Fe2B layer, whose presence was verified by XRD analysis. The tribological characterizations, including the tests of Rockwell-C indentation, pin-on-disc, and Vickers hardness test method, were used to analyze the antiwear features of the Fe2B layers. Finally, this value of energy was compared to the literature for its experimental validation.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.

The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.

Perioperative management of diabetes in patients undergoing bariatric and metabolic surgery: a narrative review and the Cleveland Clinic practical recommendations.

Bariatric and metabolic surgery is an effective treatment for patients with severe obesity and obesity-related diseases. In patients with type 2 diabetes, it provides marked improvement in glycemic control and even remission of diabetes. In patients with type 1 diabetes, bariatric surgery may offer improvement in insulin sensitivity and other cardiometabolic risk factors, as well as amelioration of the mechanical complications of obesity. Because of these positive outcomes, there are increasing numbers of patients with diabetes who undergo bariatric surgical procedures each year. Prior to surgery, efforts should be made to optimize glycemic control. However, there is no need to delay or withhold bariatric surgery until a specific glycosylated hemoglobin target is reached. Instead, treatment should focus on avoidance of early postoperative hyperglycemia. In general, oral glucose-lowering medications and noninsulin injectables are not favored to control hyperglycemia in the inpatient setting. Hyperglycemia in the hospital is managed with insulin, aiming for perioperative blood glucose concentrations between 80 and 180 mg/dL. Following surgery, substantial changes of the antidiabetic medication regimens are common. Patients should have a clear understanding of the modifications made to their treatment and should be followed closely thereafter. In this review article, we describe practical recommendations for the perioperative management of diabetes in patients with type 2 or type 1 diabetes undergoing bariatric surgery. Specific recommendations are delineated based on the different treatments that are currently available for glycemic control, including oral glucose-lowering medications, noninsulin injectables, and a variety of insulin regimens.

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

BACKGROUND: By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants. OBJECTIVES: In this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes. METHODS: We analyzed data from two large case-control studies-the New England Bladder Cancer Study (n/n=989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study (n/n=706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis. RESULTS: Of the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte-specific protein 1 (LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in meta-analysis. In the highest exposure category, we observed OR=1.66 (95% CI: 1.17, 2.34, p-trend=0.005) for those with the rs907611-GG genotype and p-interaction=0.02. No other genetic variants tested showed consistent evidence of interaction. DISCUSSION: We found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895.

Intracellular Accumulation of IFN-λ4 Induces ER Stress and Results in Anti-Cirrhotic but Pro-HCV Effects.

IFNL3/IFNL4 polymorphisms are inversely associated with the risk of chronic hepatitis C virus (HCV) infection and cirrhosis, two major risk factors for developing hepatocellular carcinoma (HCC). To further explore these inverse associations and their molecular underpinnings, we analyzed IFNL3/IFNL4 polymorphisms represented by the IFNL4 genotype (presence of rs368234815-dG or rs12979860-T alleles) in HCV patients: 2969 from Japan and 2931 from Taiwan. IFNL4 genotype was associated with an increased risk of HCV-related HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058) in the general population of Japanese patients, but not in Taiwanese patients who achieved treatment-induced viral clearance. IFNL4 genotype was also associated with a decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwanese patients). We then engineered HepG2 cells to inducibly express IFN-λ4 in the presence or absence of interferon lambda receptor 1 (IFNLR1). Induction of IFN-λ4 resulted in its intracellular accumulation, mainly in lysosomes and late endosomes, and increased ER stress, leading to apoptosis and reduced proliferation. We identified the very-low-density lipoprotein receptor (VLDLR), which facilitates HCV entry into hepatocytes, as a transcript induced by IFN-λ4 but not IFN-λ3. Our results suggest that the molecular mechanisms underlying the anti-cirrhotic but pro-HCV associations observed for IFNL3/IFNL4 polymorphisms are, at least in part, contributed by intracellular accumulation of IFN-λ4 causing ER stress in hepatic cells.

Enhanced Performance of Zn/Br Flow Battery Using N-Methyl-N-Propylmorpholinium Bromide as Complexing Agent.

Redox flow batteries (RFB) are one of the most interesting technologies in the field of energy storage, since they allow the decoupling of power and capacity. Zinc-bromine flow batteries (ZBFB) are a type of hybrid RFB, as the capacity depends on the effective area of the negative electrode (anode), on which metallic zinc is deposited during the charging process. Gaseous bromine is generated at the positive electrode (cathode) during the charging process, so the use of bromine complexing agents (BCA) is very important. These BCAs are quaternary amines capable of complexation with bromine and generating an organic phase, immiscible with the aqueous electrolyte. One of the most commonly used BCAs in RFB technology is 4-methylethylmorpholinium bromide (MEM-Br). In this work, an alternative quaternary amine 4-methylpropylmorpholinium bromide (MPM-Br) was studied. MPM-Br was integrated into the electrolyte, and 200 charge-discharge cycles were performed on the resulting ZBFBs. The obtained results were compared with those when MEM-Br was used, and it was observed that the electrolyte with MPM-Br displays a higher resistance in voltage and higher energy efficiency, making it a promising alternative to MEM-Br.

Admixture may be extensive among hyperdominant Amazon rainforest tree species.

Admixture is a mechanism by which species of long-lived plants may acquire novel alleles. However, the potential role of admixture in the origin and maintenance of tropical plant diversity is unclear. We ask whether admixture occurs in an ecologically important clade of Eschweilera (Parvifolia clade, Lecythidaceae), which includes some of the most widespread and abundant tree species in Amazonian forests. Using target capture sequencing, we conducted a detailed phylogenomic investigation of 33 species in the Parvifolia clade and investigated specific hypotheses of admixture within a robust phylogenetic framework. We found strong evidence of admixture among three ecologically dominant species, E. coriacea, E. wachenheimii and E. parviflora, but a lack of evidence for admixture among other lineages. Accepted species were largely distinguishable from one another, as was geographic structure within species. We show that hybridization may play a role in the evolution of the most widespread and ecologically variable Amazonian tree species. While admixture occurs among some species of Eschweilera, it has not led to widespread erosion of most species' genetic or morphological identities. Therefore, current morphological based species circumscriptions appear to provide a useful characterization of the clade's lineage diversity.