A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan.

The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity.

Recommendations on the use of the flash continuous glucose monitoring system in hospitalized patients with diabetes in Latin America.

BACKGROUND: Continuous glucose monitoring can improve glycemic control for hospitalized patients with diabetes, according to current evidence. However, there is a lack of consensus-established recommendations for the management of hospitalized patients with diabetes using flash continuous glucose monitoring system (fCGM) in Latin America. Therefore, this expert consensus exercise aimed to establish guidelines on the implementation of fCGM in the management of hospitalized patients with diabetes in Latin America. METHODS: The modified Delphi method was applied on a panel of nine specialists, establishing consensus at 80%. A twenty-two-question instrument was developed to establish recommendations on the use of fCGM in hospitalized patients living with diabetes. RESULTS: Based on consensus, experts recommend the use of fCGM in hospitalized patients with diabetes starting at admission or whenever hyperglycemia (> 180 mg/dl) is confirmed and continue monitoring throughout the entire hospital stay. The recommended frequency of fCGM scans varies depending on the patient's age and diabetes type: ten scans per day for pediatric patients with type 1 and 2 diabetes, adult patients with type 1 diabetes and pregnant patients, and seven scans for adult patients with type 2 diabetes. Different hospital services can benefit from fCGM, including the emergency room, internal medicine departments, intensive care units, surgery rooms, and surgery wards. CONCLUSIONS: The use of fCGM is recommended for patients with diabetes starting at the time of admission in hospitals in Latin America, whenever the necessary resources (devices, education, personnel) are available.

The Dicentrarchus labrax estrogen screen test: A relevant tool to screen estrogen-like endocrine disrupting chemicals in the aquatic environment.

In response to the need for the diversification of regulatory bioassays to screen estrogen-like endocrine disrupting chemical (EEDC) in the environment, we propose the use of a reporter gene assay involving all nuclear estrogen receptors from Dicentrarchus labrax (i.e., sbEsr1, sbEsr2a, or sbEsr2b). Named DLES test (D. labrax estrogen screen), it aims at complementing existing standardized in vitro tests by implementing more estrogen receptors notably those that do not originate from humans. Positive responses were obtained with all three estrogen receptors, and-consistently with observations from other species-variations in sensitivity to E2 were measured. Sensitivity and EC50 values could be classified as follows: sbEsr2b < sbEsr2a < sbEsr1. The pharmacological characterization with a human estrogen receptor antagonist (fulvestrant) successfully validated the specific involvement of each sbEsr and evidenced the capacity of the DLES test to highlight antagonist interactions. The DLES test was applied to WWTP contaminant extracts. A positive response was detected in the inflow sample in accordance with the YES test, but not in the outflow sample. Notwithstanding, the DLES test (sbEsr2b) exhibited greater sensitivity for the screening of those samples. This study demonstrates the need for more comprehensive testing including representatives of marine species for a better detection of EEDCs. The DLES test appears as a pertinent tool to predict adverse effects and to widen the scope of screening and hazard assessment of EEDCs in the environment.

Type 2 diabetes in latin America: recommendations on the flash glucose monitoring system.

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

Occupational Therapy in Psychiatric Short-Term Hospitalization Units: Scoping Review.

Given the context, the overarching aim is to identify scientific publications on occupational therapy in Psychiatric-Short-Term-Hospitalization-Units. Specific objectives include: (a) Analyzing the historical development of this research area; (b) Synthesizing existing evidence on the nature of documentary sources on occupational therapy in in Psychiatric-Short-Term-Hospitalization-Units; (c) Detailing the volume of scientific literature on occupational therapy in these units; (e) Evaluating available evidence on occupational therapy interventions to improve functionality, quality of life, and recovery in individuals admitted to in Psychiatric-Short-Term-Hospitalization-Units. A scoping review method was employed to conduct a historical mapping of research on in Psychiatric-Short-Term-Hospitalization-Units. The review proceeded in five stages following PRISMA guidelines. After applying selection criteria, the search identified 446 references. Findings are presented under three headings: (a) Historical trends in the scientific literature on occupational therapy and in Psychiatric-Short-Term-Hospitalization-Units; (b) Nature and volume of articles included in the occupational therapy synthesis in Psychiatric Short-Term Hospitalization Units; (c) Data extraction on methodological variables in the research of occupational therapy articles in in Psychiatric-Short-Term-Hospitalization-Units; and (d) Data extraction on research outcome variables of occupational therapy articles in Psychiatric Short-Term Hospitalization Units. The growth of occupational therapy in in Psychiatric-Short-Term-Hospitalization-Units is emphasized, with an increase in qualitative studies. Occupational therapy is underscored as an integral part of care, supporting the diversity and effectiveness of interventions. Common diagnoses include schizophrenia and depressive disorders. Group interventions and the spiritual dimension positively influence the quality of care and meaningful routines for recovery in in Psychiatric-Short-Term-Hospitalization-Units.

Stress factors and food purchase prioritization during the pandemic of coronavirus disease 2019.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) pandemic confinement has an impact on stress levels, which causes changes in food purchase and consumption behaviors. The objective of this study is to associate food purchase prioritization with stress level during the COVID-19 pandemic confinement. METHODS: Multicenter, observational and cross-sectional study, an online questionnaire that included data on sociodemographic variables, stress factors and food purchase prioritization was disseminated through digital platforms and social networks. RESULTS: A number of 6357 participants were included, of whom 83.6% were female, 56.3% were from the middle socioeconomic level, 71.2% had completed higher education and 78.3% had a job. At greater stress levels it was observed a higher prioritization of canned foods (Odds ratio (OR): 1.91, 95% CI: 1.56; 2.34), sweets (OR: 1.58, 95% CI: 1.06; 2.34) and flours (OR: 1.45, 95% CI: 1.25; 1.68). While lower stress levels are associated with nuts (OR: 0.75, 95% CI: 0.66; 0.85), vegetables (OR: 0.82, 95% CI: 0.72; 0.94), and fruits (OR: 0.90, 95% CI: 0.80; 1.01), after adjusting for confounders. CONCLUSIONS: There is an association between food purchase prioritization and stress level during the COVID-19 confinement. At greater stress levels, individuals purchase more food, both healthy and unhealthy. The later may have a negative impact on people's health, leading to or further aggravating malnutrition by excess and nutrition-related noncommunicable diseases.

Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure.

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.

HSDL2 links nutritional cues to bile acid and cholesterol homeostasis.

In response to energy and nutrient shortage, the liver triggers several catabolic processes to promote survival. Despite recent progress, the precise molecular mechanisms regulating the hepatic adaptation to fasting remain incompletely characterized. Here, we report the identification of hydroxysteroid dehydrogenase-like 2 (HSDL2) as a mitochondrial protein highly induced by fasting. We show that the activation of PGC1α-PPARα and the inhibition of the PI3K-mTORC1 axis stimulate HSDL2 expression in hepatocytes. We found that HSDL2 depletion decreases cholesterol conversion to bile acids (BAs) and impairs FXR activity. HSDL2 knockdown also reduces mitochondrial respiration, fatty acid oxidation, and TCA cycle activity. Bioinformatics analyses revealed that hepatic Hsdl2 expression positively associates with the postprandial excursion of various BA species in mice. We show that liver-specific HSDL2 depletion affects BA metabolism and decreases circulating cholesterol levels upon refeeding. Overall, our report identifies HSDL2 as a fasting-induced mitochondrial protein that links nutritional signals to BAs and cholesterol homeostasis.

Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

Combining anaerobic digestion slurry and different biochars to develop a biochar-based slow-release NPK fertilizer.

In this research, we developed a biochar-based fertilizer using biogas slurry and biochar derived from lignocellulosic agro-residues. Biogas slurry was obtained through the anaerobic digestion of the organic fraction of municipal solid waste (fresh vegetable biomass and/or prepared food), while biochars were derived from residues from quinoa, maize, rice, and sugarcane. The biochar-based fertilizers were prepared using an impregnation process, where the biogas slurry was mixed with each of the raw biochars. Subsequently, we characterized the N, P and K concentrations of the obtained biochar-based fertilizers. Additionally, we analyzed their surface properties using SEM/EDS and FTIR and conducted a slow-release test on these biochar-based fertilizers to assess their capability to gradually release nutrients. Lastly, a bioassay using cucumber plants was conducted to determine the N, P, and K bioavailability. Our findings revealed a significant correlation (r > 0.67) between the atomic O/C ratio, H/C ratio, cation exchange capacity, surface area, and the base cations concentration with N, P, and/or K adsorption on biochar. These properties, in turn, were linked to the capability of the biochar-based fertilizer to release nutrients in a controlled manner. The biochar-based fertilizer derived from corn residues showed <15 % release of N, P and K at 24 h. Utilization of these biochar-based fertilizers had a positive impact on the mineral nutrition of cucumber plants, resulting in an average increase of 61 % in N, 32 % in P, and 19 % in K concentrations. Our results underscore the potential of biochar-based fertilizers in controlled nutrient release and enhanced plant nutrition. Integration of biochar and biogas slurry offers a promising and sustainable approach for NPK recovery and fertilizer production in agriculture. This study presents an innovative and sustainable approach combining the use of biochar for NPK recovery from biogas slurry and its use as a biochar-based fertilizer in agriculture.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic / Inseguridad alimentaria y factores sociodemográficos en América Latina durante la pandemia de COVID-19 / Insegurança alimentar e fatores sociodemográficos na América Latina durante a pandemia de COVID-19

[ABSTRACT]. Objective. To understand the association of food insecurity with sociodemographic factors in a sample popu- lation in Latin America during the COVID-19 pandemic. Methods. This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results. Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, house- hold with children younger than 10 years of age, and socioeconomic level. Conclusions. These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeco- nomic level; household with more than four persons; and household with children younger than 10 years of age.

[RESUMEN]. Objetivo. Determinar la asociación de la inseguridad alimentaria con factores sociodemográficos en una muestra de población de América Latina durante la pandemia de COVID-19. Métodos. Se llevó a cabo un estudio transversal multicéntrico en diez países de América Latina mediante una encuesta en línea a través de diversas plataformas digitales, entre el 14 de octubre del 2020 y el 15 de febrero del 2021. Se realizó un análisis estadístico de los datos usando procedimientos de estadística descriptiva, la prueba ji al cuadrado y un análisis de regresión logística. Resultados. En un total de 6 357 encuestas, el 58,2% de las personas encuestadas gozaba de seguridad ali- mentaria, el 29,3% tenía una inseguridad alimentaria leve, el 9,2% una inseguridad alimentaria moderada y el 3,3% una inseguridad alimentaria grave. Por lo que respecta a la asociación entre la inseguridad alimentaria y las variables sociodemográficas, hay una asociación significativa para algunas de las variables estudiadas, como la zona de residencia, el nivel de estudios, la actividad laboral, el número de personas en el hogar, el hogar con menores de 10 años y el nivel socioeconómico. Conclusiones. Estos resultados indican que los factores sociodemográficos asociados a la inseguridad alimentaria durante la pandemia de COVID-19 en América Latina fueron la residencia en zonas rurales; la edu- cación primaria y secundaria completa o no; la actividad laboral (trabajo doméstico, personas desempleadas y trabajadores autónomos); el nivel socioeconómico bajo, medio bajo, y medio; el hogar con más de cuatro personas; y el hogar con menores de 10 años.

[RESUMO]. Objetivo. Compreender a relação entre insegurança alimentar e fatores sociodemográficos em uma amostra populacional da América Latina durante a pandemia de COVID-19. Métodos. Estudo transversal multicêntrico realizado em 10 países da América Latina por meio de uma pesquisa on-line conduzida em diferentes plataformas digitais de 14 de outubro de 2020 a 15 de fevereiro de 2021. A análise estatística dos dados foi realizada por meio da aplicação de estatísticas descritivas, teste qui-quadrado e análise de regressão logística. Resultados. De um total de 6 357 questionários, 58,2% dos entrevistados afirmaram ter segurança alimentar, 29,3% indicaram um nível de insegurança alimentar leve, 9,2% tinham insegurança alimentar moderada e 3,3%, insegurança alimentar grave. No que diz respeito à relação entre insegurança alimentar e variáveis sociodemográficas, há uma relação significativa com as variáveis estudadas, incluindo área de residência, nível de escolaridade, ocupação, número de pessoas no domicílio, domicílio com crianças com menos de 10 anos de idade e nível socioeconômico. Conclusões. Os achados apontam que os fatores sociodemográficos associados à insegurança alimentar durante a pandemia de COVID-19 na América Latina foram residência em zona rural; ensino fundamental e médio completo e incompleto; ocupação (do lar, desempregado(a) e autônomo(a)); nível socioeconômico baixo, médio-baixo e médio; domicílio com mais de quatro pessoas; e domicílio com crianças menores de 10 anos de idade.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.

Tyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2-deficient (Tyk2-/-) mice. Splenic B cell subpopulations were altered in Tyk2-/- compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged. Likewise, there was an imbalance in transitional B cells in juvenile Tyk2-/- mice. RNA sequencing analysis of adult MZ and FO cells isolated from Tyk2-/- and WT mice in homeostasis revealed altered expression of IFN-I and Toll-like receptor 7 (TLR7) signaling pathway genes. Flow cytometry assays corroborated a lower expression of TLR7 in MZ B cells from Tyk2-/- mice. Splenic B cell cultures showed reduced proliferation and differentiation responses after activation with TLR7 ligands in Tyk2-/- compared to WT mice, with a similar response to lipopolysaccharide (LPS) or anti-CD40 + IL-4. IgM, IgG, IL-10 and IL-6 secretion was also decreased in Tyk2-/- B cell cultures. This reduced response of the TLR7 pathway in Tyk2-/- mice was partially restored by IFNα addition. In conclusion, there is a crosstalk between TYK2 and TLR7 mediated by an IFN-I feedback loop, which contributes to the establishment of MZ B cells and to B cell proliferation and differentiation.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic.

Objective: To understand the association of food insecurity with sociodemographic factors in a sample population in Latin America during the COVID-19 pandemic. Methods: This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results: Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, household with children younger than 10 years of age, and socioeconomic level. Conclusions: These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeconomic level; household with more than four persons; and household with children younger than 10 years of age.

Artificial intelligence, applications and challenges in simulation-based education

The rapid advancement of Artificial Intelligence (AI) has taken the world by "surprise" due to the lack of regulation over this technological innovation which, while promising application opportunities in different fields of knowledge, including education, simultaneously generates concern, rejection and even fear. In the field of Health Sciences Education, clinical simulation has transformed educational practice; however, its formal insertion is still heterogeneous, and we are now facing a new technological revolution where AI has the potential to transform the way we conceive its application.

El rápido avance de la inteligencia artificial (IA) ha tomado al mundo por "sorpresa" debido a la falta de regulación sobre esta innovación tecnológica, que si bien promete oportunidades de aplicación en diferentes campos del conocimiento, incluido el educativo, también genera preocupación e incluso miedo y rechazo. En el campo de la Educación en Ciencias de la Salud la Simulación Clínica ha transformado la práctica educativa; sin embargo, aún es heterogénea su inserción formal, y ahora nos enfrentamos a una nueva revolución tecnológica, en la que las IA tienen el potencial de transformar la manera en que concebimos su aplicación.