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Uncertain information on input parameters of computer models is usually modeled by considering these parameters as random, and described by marginal distributions and a dependence structure of these variables. In numerous real-world applications, while information is mainly provided by marginal distributions, typically from samples, little is really known on the dependence structure itself. Faced with this problem of incomplete or missing information, risk studies that make use of these computer models are often conducted by considering independence of input variables, at the risk of including irrelevant situations. This approach is especially used when reliability functions are considered as black-box models. Such analyses remain weakened in absence of in-depth model exploration, at the possible price of a strong risk misestimation. Considering the frequent case where the reliability output is a quantile, this article provides a methodology to improve risk assessment, by exploring a set of pessimistic dependencies using a copula-based strategy. In dimension greater than two, a greedy algorithm is provided to build input regular vine copulas reaching a minimum quantile to which a reliability admissible limit value can be compared, by selecting pairwise components of sensitive influence on the result. The strategy is tested over toy models and a real industrial case-study. The results highlight that current approaches can provide non-conservative results.

Anxiety disorders have been on the rise among adolescents over the past decade. The COVID-19 pandemic appears to have contributed to this increase, putting further pressure on often already overburdened health systems. Universal prevention programs may offer a potential solution, but few have been evaluated in the context of a pandemic. The objective of this article is to measure the impact of a universal prevention program--the HORS-PISTE program--on several anxiety-related variables in the context of a pandemic. The HORS-PISTE program consists of 10 workshops spread over the two first years of high school, secondary 1 and 2 (grade 7 and 8 equivalent). Workshops are held in a classroom setting and focus on the development of psychosocial skills. The study was conducted in Quebec with 1,202 secondary 1 and 2 students (48.7% girls, 51.3% boys) with an average age of 12.58 years ("SD" = 0.75). They completed an assessment protocol before and after participating in the HORS-PISTE program in the autumn of 2020. Their answers were subjected to descriptive analysis and multivariate analysis of variance. Results indicate a significant decrease in symptoms for several of the measured variables between the two measurement times, such as those associated with panic disorder, generalized anxiety disorder, and test anxiety. The results also show a decrease in some variables related to the interference of anxiety symptoms and the cognitive and behavioral vulnerabilities targeted by the program. The discussion highlights possible explanations for the results, as well as how universal prevention programs may contribute to the prevention of anxiety during adolescence, especially in a pandemic context.

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis. Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids, such as docosahexaenoic acid, and exercise in Parkinson’s disease, we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway. First, mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation. Four weeks after lesion, animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks. During this period, the animals had access to a running wheel, which they could use or not. Docosahexaenoic acid treatment, voluntary exercise, or the combination of both had no effect on (i) distance traveled in the open field test, (ii) the percentage of contraversive rotations in the apomorphine-induction test or (iii) the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta. However, the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum. Compared to docosahexaenoic acid treatment or exercise alone, the combination of docosahexaenoic acid and exercise (i) improved forelimb balance in the stepping test, (ii) decreased the striatal DOPAC/dopamine ratio and (iii) led to increased dopamine transporter levels in the lesioned striatum. The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

Abstract The demographical history of France remains largely understudied despite its central role toward understanding modern population structure across Western Europe. Here, by exploring publicly available Europe-wide genotype datasets together with the genomes of 3234 present-day and six newly sequenced medieval individuals from Northern France, we found extensive fine-scale population structure across Brittany and the downstream Loire basin and increased population differentiation between the northern and southern sides of the river Loire, associated with higher proportions of steppe vs. Neolithic-related ancestry. We also found increased allele sharing between individuals from Western Brittany and those associated with the Bell Beaker complex. Our results emphasise the need for investigating local populations to better understand the distribution of rare (putatively deleterious) variants across space and the importance of common genetic legacy in understanding the sharing of disease-related alleles between Brittany and people from western Britain and Ireland.

There is now compelling evidence for the presence of pathological forms of Tau in tissues of both patients and animal models of Huntington's disease (HD). While the root cause of this illness is a mutation within the huntingtin gene, a number of studies now suggest that HD could also be considered a secondary tauopathy. However, the contributory role of Tau in the pathogenesis and pathophysiology of this condition, as well as its implications in cellular toxicity and consequent behavioral impairments are largely unknown. We therefore performed intracerebral stereotaxic injections of recombinant human Tau monomers and fibrils into the knock-in zQ175 mouse model of HD. Tau fibrils induced cognitive and anxiety-like phenotypes predominantly in zQ175 mice and increased the number and size of insoluble mutant huntingtin (mHTT) aggregates in the brains of treated animals. To better understand the putative mechanisms through which Tau could initiate and/or contribute to pathology, we incubated StHdh striatal cells, an in vitro model of HD, with the different Tau forms and evaluated the effects on cell functionality and heat shock proteins Hsp70 and Hsp90. Calcium imaging experiments showed functional impairments of HD StHdh cells following treatment with Tau fibrils, as well as significant changes to the levels of both heat shock proteins which were found trapped within mHTT aggregates. The accumulation of Hsp70 and 90 within aggregates was also present in mouse tissue which suggests that alteration of molecular chaperone-dependent protein quality control may influence aggregation, implicating proteostasis in the mHTT-Tau interplay.

Background: Buruli ulcer (BU) is an infectious skin disease caused by Mycobacterium ulcerans. It primarily affects disadvantaged rural populations and mainly impacts children who are chronically malnourished being especially vulnerable. In Côte d’Ivoire, the estimated prevalence of BU in children is 30 %. Malnutrition may further deteriorate the nutritional status of these individuals. This study aimed to compare the healing time of BU patients treated with the standard protocol (SP) of 8 weeks of rifampicin and clarithromycin combined with wound care versus those treated with the standard protocol plus nutritional support using Skin Renewal Medicine-1 (SPSRM-1) (UNHWA Medical Centre, Seoul, Republic of Korea). Additionally, the study measured the effects of SRM-1 on the patients’ nutritional status. Method: This was a prospective, randomized, single-blind paired interventional study conducted in BU-endemic health districts of Côte d’Ivoire. This 12-month study had two arms: the standard protocol versus the test treatment (SPSRM-1). SRM-1 is a cereal-based nutraceutical composed of 60 % cereal, 25 % vegetable, and 15 % plant concentrate. Patients included in the study had uncomplicated category I and II ulcerations without comorbidities. Nutritional status including haemoglobin, albumin levels, and body mass index (BMI) was evaluated from enrolment to the end of the study, alongside ulcer healing rates. Results: Sixty BU wound patients were enrolled: 30 in the control group and 30 in the test group, with a mean age of 22 years. Of the patients, 28.3 % were malnourished, and 42 % had hypoalbuminemia. At the primary endpoint, 6 patients (20.0 %) in the SPSRM1 and 5 patients (16.7 %) in the SP group achieved complete epithelialization, with a reduction rate of 0.7 % per day in the SPSRM1 group compared to 0.3 % per day in the SP group. Patients who received SRM-1 had a higher BMI than those who did not, with a mean difference of 1.72 kg/m2 favouring the test group. Haemoglobin and albumin levels also showed improvement at the secondary endpoint compared to the control group. Conclusion: This study demonstrated the potential benefit of adding nutritional support to improve BU treatment outcomes, by shortening the healing time of ulcerations. However, further studies with larger sample sizes are necessary to confirm these findings.

Over the last decade, the CO2 reduction reaction (CO2RR) has been increasingly exploited for the synthesis of high‐value raw materials in gaseous or liquid form, although no examples of CO2 fixation in nanoparticle systems have been demonstrated. Herein, CO2 fixation into solid nanomaterials by laser synthesis and processing of gold colloids in water, traditionally considered a green approach leading to ligand‐free nanoparticles without the formation of by‐products, is reported. If carbon monoxide‐rich gold nanoparticles are observable even after synthesis in deionized water, the presence of CO2 derivatives in alkaline water environment leads to C2 and C3 coupling with the production of carboxylic acids as a typical CO2RR fingerprint. While laser processing of preformed gold colloids is selective for C2 coupling, both C2 and C3 coupling to lactic acid are observed during pulsed laser ablation of a gold target. In the latter case, it is demonstrated that it is possible to synthesize photoluminescent organometallic nanocomposites in the blue spectral region with a quantum yield of about 20% under adequate experimental conditions. In this research, new pathways are offered to be explored in energetics, photonics, catalysis, and synthesis at the nanoscale.

A 7-y-old male Labrador Retriever dog was presented because of acute onset of dark-colored urine after a hunting session the day prior. Moderate hemoglobinemia was observed, associated with transient hemoglobinuria and hematuria with no concurrent evidence of underlying urinary tract disease. The patient's clinical signs resolved within 36 h post-exercise without specific treatment. The concurrent occurrence of exertional hemolysis and hematuria in a dog is uncommon; these conditions are commonly reported separately in human athletes.

Abstract Background The COVID-19 pandemic has required evidence to be made available more rapidly than usual, in order to meet the needs of decision makers in a timely manner. These exceptional circumstances have caused significant challenges for organizations and teams responsible for evidence synthesis. They had to adapt to provide rapid responses to support decision-making. This study aimed to document (1) the challenges and adaptations made to produce rapid responses during the pandemic, (2) their perceived usefulness, reported use and factors influencing their use and (3) the methodological adaptations made to produce rapid responses. Methods A qualitative study was conducted in 2021 with eight organizations in the health and social services system in Quebec (Canada), including three institutes with a provincial mandate. Data collection included focus groups (n = 9 groups in 8 organizations with 64 participants), interviews with decision makers (n = 12), and a document analysis of COVID-19 rapid responses (n = 128). A thematic analysis of qualitative data (objectives 1 and 2) and a descriptive analysis of documents (objective 3) were conducted. Results The results highlight the teams and organizations’ agility to deal with the many challenges encountered during the pandemic (e.g., increased their workloads, adoption of new technological tools or work processes, improved collaboration, development of scientific monitoring, adaptation of evidence synthesis methodologies and products). The challenge of balancing rigor and speed was reported by teams and organizations. When available at the right time, rapid responses have been reported as a useful tool for informing or justifying decisions in a context of uncertainty. Several factors that may influence their use were identified (e.g., clearly identify needs, interactions with producers, perceived rigor and credibility, precise and feasible recommendations). Certain trends in the methodological approaches used to speed up the evidence synthesis process were identified. Conclusions This study documented rapid responses producers’ experiences during the COVID-19 pandemic in Quebec, and decision makers who requested, consulted, or used these products. Potential areas of improvements are identified such as reinforce coordination, improve communication loops, clarify guidelines or methodological benchmarks, and enhance utility of rapid response products for decision makers.

Mathieu D Saint-Pierre1– 3 1University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada; 2Institut du Savoir Montfort, Ottawa, ON, Canada; 3Montfort Hospital, Division of Respirology, Ottawa, ON, CanadaCorrespondence: Mathieu D Saint-Pierre, Montfort Hospital, 713 Montreal Road, Ottawa, ON, K1K 0T2, Canada, Email mathieuspierre@montfort.on.caRationale: Current guidelines define a severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as an increase in symptoms requiring hospital admission or emergency department (ED) visit. Little is known about whether or not subjects requiring hospitalization and those needing only ED care have similar patient profiles and if their clinical outcomes appear comparable.Objective: The main goals of this study were to compare the demographic and clinical characteristics of patients treated for an AECOPD with an inpatient admission versus an ED visit and to review if hospital resource utilization was different between the 2 groups after discharge.Methods: Subjects treated in 2022 at Montfort Hospital for an AECOPD were reviewed. Patient demographic information was collected in addition to spirometry results and blood eosinophil counts on file. Supplemental oxygen use and medication lists were also recorded. Patients with an initial hospital admission were compared to those requiring only ED care with univariate and multivariate analyses. We also assessed if subjects were again treated for an AECOPD up to 6 months post initial discharge, and if so, the type of hospital visits (hospitalization or ED).Measurements and Main Results: A total of 135 individuals necessitated hospitalization and 79 received ED care for the treatment of an AECOPD. On univariate analysis, patients requiring an inpatient stay appeared older and were more likely to have spirometry results on file. A greater proportion of hospitalized individuals were on supplemental oxygen and prescribed at least one long-acting inhaled medication. These studied variables remained significant after multivariate logistic regression analysis. Subjects with an initial inpatient admission were also more likely to require hospitalization upon repeat presentation for a severe AECOPD.Conclusion: Given the important differences observed in both patient characteristics and hospital resource utilization, this study supports considering an AECOPD requiring inpatient admission versus an ED visit as distinct categories of events.Keywords: chronic obstructive pulmonary disease, guidelines, severe acute exacerbation, hospitalization, emergency department

In plant breeding, Multi-Environment Trials (METs) evaluate candidate genotypes across various conditions, which is financially costly due to extensive field testing. Sparse testing addresses this challenge by evaluating some genotypes in selected environments, allowing for a broader range of environments without significantly increasing costs. This approach integrates genomic information to adjust phenotypic data, leading to more accurate genetic effect estimations. Various sparse testing methods have been explored to optimize resource use. This study employed Incomplete Block Design (IBD) to allocate lines to environments, ensuring not all lines were tested in every environment. We compared IBD to Random line allocation, maintaining a consistent number of environments per line across both methods. The primary objective was to estimate grain yield performance of lines using Genomic Estimated Breeding Values (GEBVs) computed through six Genomic Best Linear Unbiased Predictor (GBLUP) methods. In the first five methods, missing values were predicted before cross-environment adjustment; in the sixth, adjustment was performed directly. Using the Bayesian GBLUP model, we analyzed genotype performance under both IBD and random allocation. Results indicate that computing GEBVs for a target population of environments (TPE) using available phenotype and marker data is effective for selection. The IBD method showed superior performance with less variability compared to random allocation. These findings suggest that using IBD designs can enhance selection accuracy and efficiency, and that pre-adjustment prediction of missing lines may not necessarily improve selection outcomes.

Just over thirty years is the span of a generation. It is also the time that has passed since the discovery of the gene responsible for cystic fibrosis. Today, it is safe to say that this discovery has revolutionized our understanding, research perspectives, and management of this disease, which was, thirty years ago, a pediatric condition with a grim prognosis. The aim of this review is to present the advances that science and medicine have brought to our understanding of the pathophysiology of the disease and its management, which in many ways, epitomizes modern molecular genetic research. Since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, modeling the CFTR protein, deciphering its function as an ion channel, and identifying its molecular partners have led to numerous therapeutic advances. The most significant advancement in this field has been the discovery of protein modulators that can target its membrane localization and chloride channel activity. However, further progress is needed to ensure that all patients can benefit from a therapy tailored to their mutations, with the primary challenge being the development of treatments for mutations leading to a complete absence of the protein. The present review delves into the history of the multifaceted world of CF, covering main historical facts, current landscape, clinical management, emerging therapies, patient perspectives, and the importance of ongoing research, bridging science and medicine in the fight against the disease.

IntroductionBecause Genomic selection (GS) is a predictive methodology, it needs to guarantee high-prediction accuracies for practical implementations. However, since many factors affect the prediction performance of this methodology, its practical implementation still needs to be improved in many breeding programs. For this reason, many strategies have been explored to improve the prediction performance of this methodology.MethodsWhen environmental covariates are incorporated as inputs in the genomic prediction models, this information only sometimes helps increase prediction performance. For this reason, this investigation explores the use of feature engineering on the environmental covariates to enhance the prediction performance of genomic prediction models.Results and discussionWe found that across data sets, feature engineering helps reduce prediction error regarding only the inclusion of the environmental covariates without feature engineering by 761.625% across predictors. These results are very promising regarding the potential of feature engineering to enhance prediction accuracy. However, since a significant gain in prediction accuracy was observed in only some data sets, further research is required to guarantee a robust feature engineering strategy to incorporate the environmental covariates.

Abstract A copper‐dependent self‐cleaving DNA (DNAzyme or deoyxyribozyme) previously isolated by in vitro selection has been analyzed by a combination of Molecular Dynamics (MD) simulations and advanced Electron Paramagnetic Resonance (Electron Spin Resonance) EPR/ESR spectroscopy, providing insights on the structural and mechanistic features of the cleavage reaction. The modeled 46‐nucleotide deoxyribozyme in MD simulations forms duplex and triplex sub‐structures that flank a highly conserved catalytic core. The DNA self‐cleaving construct can also form a bimolecular complex that has a distinct substrate and enzyme domains. The highly dynamic structure combined with an oxidative site‐specific cleavage of the substrate are two key‐aspects to elucidate. By combining EPR/ESR spectroscopy with selectively isotopically labeled nucleotides it has been possible to overcome the major drawback related to the “metal‐soup” scenario, also known as “super‐stoichiometric” ratios of cofactors versus substrate, conventionally required for the DNA cleavage reaction within those nucleic acids‐based enzymes. The focus on the endogenous paramagnetic center (Cu2+) here described paves the way for analysis on mixtures where several different cofactors are involved. Furthermore, the insertion of cleavage reaction within more complex architectures is now a realistic perspective towards the applicability of EPR/ESR spectroscopic studies.

Objectives: This study aims to assess the impact of care consumption patterns and individual characteristics on the cost of treating differentiated thyroid carcinoma (DTC), in France, with a specific emphasis on socioeconomic position.Methods: The methodology involved a net cost approach utilising cases from the EVATHYR cohort and controls from the French National Health Insurance database. Care consumption patterns were created using Optimal Matching and clustering techniques. The individual characteristics influence on patterns was assessed using multinomial logistic regression. The individual characteristics and patterns influence on care costs was assessed using generalised estimating equations.Results: The findings revealed an average cost of €13,753 per patient during the initial 3 years. Regression models suggested the main predictors of high DTC specific care consumption tended to include having a high risk of cancer recurrence (OR = 4.97), being a woman (OR = 2.00), and experiencing socio-economic deprivation (OR = 1.26), though not reaching statistical significance. Finally, high DTC-specific care consumers also incurred higher general care costs (RR = 1.35).Conclusion: The study underscores the increased costs of managing DTC, shaped by consumption habits and socioeconomic position, emphasising the need for more nuanced DTC management strategies.

En este trabajo se presentan los primeros resultados sobre el origen continental materno de las principales localidades de la provincia de Tierra del Fuego (TDF): Río Grande (RG) y Ushuaia (USH), mediante la tipificación de haplogrupos mitocondriales (Hg) de 333 participantes. La estimación de los Hg se realizó mediante PCR-APLP y secuenciación de la región HV1, evidenciando una significativa frecuencia de Hg maternos de origen americano a nivel provincial (64,9%). A nivel local, se observó una mayor proporción de linajes autóctonos en RG (75,1%) respecto de USH (57,5%). A partir de la información genealógica de los participantes, se evidenció que el origen geográfico más frecuente tanto de los participantes como de los ancestros, es la región Centro de Argentina. Las diferencias observadas entre dos localidades que distan a sólo 200 km, en una provincia de baja densidad demográfica, ponen en evidencia una vez más la importancia de conocer la información genealógica de los participantes, así como la historia fundacional y las actividades económicas de cada localidad que han motivado la llegada de migrantes, para una adecuada contextualización y comprensión de la actual composición genética de la provincia de TDF.

A field experiment was carried out to quantify the effect of a native bacterial inoculant on the growth, yield, and quality of the wheat crop, under different nitrogen (N) fertilizer rates in two agricultural seasons. Wheat was sown under field conditions at the Experimental Technology Transfer Center (CETT-910), as a representative wheat crop area from the Yaqui Valley, Sonora México. The experiment was conducted using different doses of nitrogen (0, 130, and 250 kg N ha−1) and a bacterial consortium (BC) (Bacillus subtilis TSO9, B. cabrialesii subsp. tritici TSO2T, B. subtilis TSO22, B. paralicheniformis TRQ65, and Priestia megaterium TRQ8). Results showed that the agricultural season affected chlorophyll content, spike size, grains per spike, protein content, and whole meal yellowness. The highest chlorophyll and Normalized Difference Vegetation Index (NDVI) values, as well as lower canopy temperature values, were observed in treatments under the application of 130 and 250 kg N ha−1 (the conventional Nitrogen dose). Wheat quality parameters such as yellow berry, protein content, Sodium dodecyl sulfate (SDS)-Sedimentation, and whole meal yellowness were affected by the N dose. Moreover, the application of the native bacterial consortium, under 130 kg N ha−1, resulted in a higher spike length and grain number per spike, which led to a higher yield (+1.0 ton ha−1 vs. un-inoculated treatment), without compromising the quality of grains. In conclusion, the use of this bacterial consortium has the potential to significantly enhance wheat growth, yield, and quality while reducing the nitrogen fertilizer application, thereby offering a promising agro-biotechnological alternative for improving wheat production.

Reconstitution of D radiodurans nucleotide excision repair provides insights into the kinetics of repair on different DNA substrates and determines the order and precise sites of incisions on the 5’ and 3’ sides of the lesion.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Genebanks hold comprehensive collections of wild species, wild relatives, and landraces that are useful for genetic improvement. Here, the authors report the genotype of nearly 80,000 wheat accessions using DArTseq technology to show the less explored genetic diversity.

No Brasil, cabe ao governo federal divulgar, a cada quatro anos, versões atualizadas de três documentos orientadores da defesa: a Política Nacional de Defesa, a Estratégia Nacional de Defesa e o Livro Branco de Defesa Nacional. Entre diversas normativas, as autoridades orientam as forças armadas brasileiras sobre seu emprego nesses documentos. Nesse sentido, o propósito do presente trabalho descritivo é contribuir com os estudos existentes sobre a política de defesa brasileira a partir do levantamento e da leitura dos documentos oficiais, publicados pelo governo brasileiro de 1996 a 2020, com foco nas concepções de segurança e defesa. Para além da pesquisa documental, a revisão da literatura corrente sobre o tema nos auxilia a compreender os impactos das normas e de suas atualizações no emprego das forças armadas. Nosso argumento central é que, apesar dos percalços nas atualizações, os sucessivos governos mantiveram certa inércia no esforço de modernizar a política de defesa do país. No entanto, ainda que atualizados, os documentos conservaram antigos conceitos que possibilitam o emprego intensivo das forças armadas em missões internas. O trabalho desenvolvido nos levou a concluir que, desde a primeira Política de Defesa Nacional, sucessivas concessões aos militares foram registradas nos documentos de modo a possibilitar intervenções em assuntos internos, entre eles missões militares relacionadas à segurança pública. Em suma, destacamos, neste artigo, a manutenção do obsoleto conceito da segurança nacional, a referência a documentos militares, como o Glossário das Forças Armadas e a Garantia da Lei e da Ordem, e uma descuidada ampliação do escopo da segurança para ameaças de qualquer natureza.

Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10 336 individuals from European and Asian origin, we discovered that variants >100 kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.

Introducción. La prevalencia de la infección por el virus de inmunodeficiencia humana (VIH) en Latinoamérica no ha sido estudiada de forma adecuada, pero se calcula que en Chile la mitad de los pacientes que están infectados no han sido diagnosticados y no están bajo control ni tratamiento. Presentación de los casos. Se presentan dos casos clínicos de pacientes masculinos de 22 y 33 años, sin antecedentes mórbidos, con múltiples consultas en diversos servicios clínicos. El diagnóstico se hizo en etapa sida (síndrome de inmunodeficiencia adquirida), con las complicaciones que se asocian cuando se diagnostica de manera tardía. Conclusiones. El VIH es una patología subdiagnosticada, en su mayoría por falta de sospecha y por los prejuicios de la población respecto a la realización del test de VIH. El cuerpo médico debe tomar la responsabilidad de pesquisar los casos de manera temprana para disminuir el impacto de la enfermedad, en especial en lugares con población vulnerable.

In December 2019, a case of atypical pneumonia was reported in Wuhan, China. It was named COVID-19 and caused by SARS-CoV-2. In a few months, scientific groups around the world developed vaccines to reduce the disease’s severity. The objective was to evaluate the humoral and cellular immune response post immunization with three different vaccination schedules administered in Chile until January 2022. Sixty volunteers were recruited with a three-dose schedule, who had no history of infection nor close contact with a positive patient. IgG against the spike antigenic domain was detected, and the neutralization capacity against two groups of variants, Original/Alpha and Beta/Gamma, was also measured. Finally, the cellular response with interferon release was measured through IGRA. Results showed that there were significant differences in the neutralizing antibodies for the original and alpha variant when comparing three Comirnaty doses with Coronavac and Vaxzevria. A high number of reactive subjects against the different SARS-CoV-2 variants, alpha, gamma, and delta, were observed, with no significant differences between any of the three schemes, confirming the existence of a cellular immune response against SARS-CoV-2. In conclusion, the three vaccine schemes generated a cellular immune response in these volunteers.

The Involvement in Subject Learning Scale (ISLS) was developed and validated as an educational outcome measure to be used in assessing higher education quality. The origins and development of the scale, its factor analysis, potential applications, limitations, and pilot use in France and Quebec (Canada) are described. The instrument is appended. (MSE)

Background The Rio Doce estuary, in Brazil, was impacted by the deposition of iron mine tailings, caused by the collapse of a dam in 2015. Based on published baseline datasets, the estuary has been experiencing chronic trace metal contamination effects since 2017, with potential bioaccumulation in fishes and human health risks. As metal and metalloid concentrations in aquatic ecosystems pose severe threats to the aquatic biota, we hypothesized that the trace metals in estuarine sediments nearly two years after the disaster would lead to bioaccumulation in demersal fishes and result in the biosynthesis of metal-responsive proteins. Methods We measured As, Cd, Cr, Cu, Fe, Mn, Pb, Se and Zn concentrations in sediment samples in August 2017 and compared to published baseline levels. Also, trace metals (As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Se and Zn) and protein (metallothionein and reduced glutathione) concentrations were quantified in the liver and muscle tissues of five fish species (Cathorops spixii, Genidens genidens, Eugerres brasilianus, Diapterus rhombeus and Mugil sp.) from the estuary, commonly used as food sources by local populations. Results Our results revealed high trace metal concentrations in estuarine sediments, when compared to published baseline values for the same estuary. The demersal fish species C. spixii and G. genidens had the highest concentrations of As, Cr, Mn, Hg, and Se in both, hepatic and muscle, tissues. Trace metal bioaccumulation in fish was correlated with the biosynthesis of metallothionein and reduced glutathione in both, liver and muscle, tissues, suggesting active physiological responses to contamination sources. The trace metal concentrations determined in fish tissues were also present in the estuarine sediments at the time of this study. Some elements had concentrations above the maximum permissible limits for human consumption in fish muscles (e.g., As, Cr, Mn, Se and Zn), suggesting potential human health risks that require further studies. Our study supports the high biogeochemical mobility of toxic elements between sediments and the bottom-dwelling biota in estuarine ecosystems.