[Dietary diversity, anthropometric status and biochemical profile of centenarians of the Nicoya Peninsula, Costa Rica, and their offspring]. / Diversidad dietética, estado antropométrico y perfil bioquímico de centenarios de la Península de Nicoya, Costa Rica, y su descendencia.

BACKGROUND AND OBJECTIVE: Social relationships, physical activity and diet have been proposed as responsible for longevity; however, many of these conditions have changed in modern societies. The objective of this study was to identify if the anthropometric status, biochemical profile and diet of Nicoyan centenarians is different from that of their decency and if the quality and diversity of the diet of these Costa Ricans differs from that of adults from urban areas of the same country. MATERIALS AND METHODS: Anthropometric, biochemical and dietary assessments were carried out on 120 adults residing in the Nicoya Peninsula, including centenarians, their children and grandchildren. The data were analyzed using descriptive and inferential statistics. RESULTS: There is a significantly lower percentage of excess weight, central adiposity and blood lipids in Nicoyan centenarians compared to their children and grandchildren. The consumption of «Dairy¼ and «Other fruits¼ is higher in centenarians than in their descendants. Centenarians showed a higher dietary diversity index (DDI) compared to other age categories, and they also showed a higher DDI and a significantly more diverse diet than the urban population of Costa Rica. CONCLUSION: Nicoyan centenarians presented a better lipid and glycemic profile than their offspring, they have lower weight and a better quality and diversity of diet than their relatives and than adults from the urban area of Costa Rica.

An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

PURPOSE: Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. METHODS: This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. RESULTS: The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52 years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. CONCLUSIONS: This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

Institutional care in four Latin American countries: the importance of fostering public information and evaluation strategies / Atención en centros de cuidados a largo plazo en cuatro países de América Latina: importancia de fomentar la información pública y las estrategias de evaluación / Cuidados institucionais em quatro países da América Latina: a importância de promover informações públicas e estratégias de avaliação

[ABSTRACT]. More than 8 million older people in Latin America depend on long-term care (LTC), accounting for 12% of people aged ≥ 60 years and almost 27% of those aged ≥ 80. It is crucial to develop sustainable strategies for providing LTC in the area, including institutional care. This special report aims to characterize institutional LTC in four countries (Brazil, Chile, Costa Rica and Mexico), using available information systems, and to identify the strategies adopted to support institutional care in these countries. This narrative review used nationwide, open-access, public data sources to gather demographic estimates and information about institutional LTC coverage and the availability of open-access data for the proportion of people with LTC needs, the number of LTC facilities and the number of residents living in them. These countries have a larger share of older people than the average in Latin America but fewer LTC facilities than required by the demand. National surveys lack standardization in defining disability, LTC and dependency on care. Information about institutional care is mainly fragmented and does not regularly include LTC facilities, their residents and workers. Data are crucial to inform evidence-based decisions to favor prioritization and to support advances in promoting policies around institutional LTC in Latin America. Although information about institutional care in the region is fragmented and insufficient, this paper profiles the four selected countries. It highlights the need for a better structure for data- driven LTC information systems. The lack of information emphasizes the urgency of the need to focus on and encourage research into this topic.

[RESUMEN]. En América Latina, más de 8 millones de personas mayores dependen de los cuidados a largo plazo (CLP), lo que representa el 12% de las personas de 60 años o más y casi el 27% de las de 80 años o más Resulta crucial elaborar estrategias sostenibles para la prestación de CLP en la región, incluida la atención en centros de CLP. Este artículo especial tiene como finalidad determinar las características de la atención prestada en centros de CLP en cuatro países (Brasil, Chile, Costa Rica y México), utilizando los sistemas de información disponibles, así como determinar cuáles son las estrategias adoptadas en estos países para brindar apoyo a la atención en centros de CLP. En esta revisión descriptiva se utilizaron fuentes de datos públicas, de libre acceso y de ámbito nacional para recopilar estimaciones demográficas e información sobre la cobertura de la atención en centros de CLP, así como sobre la disponibilidad de datos de libre acceso acerca de la pro- porción de personas con necesidades de CLP, el número de centros de CLP y su correspondiente número de residentes. Estos países tienen una proporción de personas mayores superior a la media de América Latina, pero menos centros de CLP de los necesarios para cubrir la demanda. En las encuestas nacionales no hay una definición estandarizada de la discapacidad, los cuidados a largo plazo y la dependencia. La mayor parte de la información sobre la atención en centros de CLP está fragmentada y no incluye datos periódicos sobre los centros de CLP existentes, sus residentes o sus trabajadores. Estos datos son cruciales para funda- mentar decisiones basadas en la evidencia destinadas a propiciar la priorización y brindar apoyo a los avances en la promoción de políticas en materia de centros de CLP en América Latina. Aunque la información sobre la atención en centros de CLP en la región es fragmentaria e insuficiente, en este artículo se presenta el perfil de los cuatro países seleccionados. Se resalta la necesidad de mejorar la estructura de los sistemas de información sobre CLP basados en datos. Esta falta de información pone de relieve la necesidad urgente de centrarse en este tema y fomentar la investigación al respecto.

[RESUMO]. Na América Latina, mais de 8 milhões de pessoas idosas dependem de cuidados de longa duração (CLD), o que representa 12% das pessoas com mais de 60 anos e quase 27% das pessoas com mais de 80 anos. É fundamental criar estratégias sustentáveis para oferecer CLD na região, inclusive cuidados institucionais. O objetivo deste relatório especial é caracterizar CLD institucionais em quatro países (Brasil, Chile, Costa Rica e México), usando os sistemas de informação disponíveis, e identificar as estratégias adotadas para apoiar os cuidados institucionais nesses países. Esta revisão narrativa usou dados públicos de acesso aberto de âmbito nacional para coletar estimativas demográficas e informações sobre a cobertura de CLD institucio- nais e a disponibilidade de dados de acesso aberto sobre a porcentagem de pessoas com necessidades de CLD, o número de instituições de CLD e o número de residentes nessas instituições. Esses países têm uma parcela maior de pessoas idosas do que a média da América Latina, mas menos instituições de CLD do que a demanda exige. Falta padronização na definição de incapacidade, CLD e dependência de cuidados nas pesquisas nacionais. Em sua maior parte, as informações sobre cuidados institucionais são fragmen- tadas e não incluem instituições de CLD, seus residentes e trabalhadores de maneira regular. É essencial usar dados para guiar decisões baseadas em evidências a fim de favorecer a priorização e apoiar avanços que promovam políticas para CLD institucionais na América Latina. Embora as informações sobre cuidados institucionais na região sejam fragmentadas e insuficientes, este documento traça o perfil dos quatro países selecionados, destacando a necessidade de uma estrutura melhor para sistemas de informações de CLD orientados por dados. A falta de informações ressalta a urgência de aumentar o foco no tópico e encorajar pesquisas sobre o assunto.

Institutional care in four Latin American countries: the importance of fostering public information and evaluation strategies.

More than 8 million older people in Latin America depend on long-term care (LTC), accounting for 12% of people aged ≥ 60 years and almost 27% of those aged ≥ 80. It is crucial to develop sustainable strategies for providing LTC in the area, including institutional care. This special report aims to characterize institutional LTC in four countries (Brazil, Chile, Costa Rica and Mexico), using available information systems, and to identify the strategies adopted to support institutional care in these countries. This narrative review used nationwide, open-access, public data sources to gather demographic estimates and information about institutional LTC coverage and the availability of open-access data for the proportion of people with LTC needs, the number of LTC facilities and the number of residents living in them. These countries have a larger share of older people than the average in Latin America but fewer LTC facilities than required by the demand. National surveys lack standardization in defining disability, LTC and dependency on care. Information about institutional care is mainly fragmented and does not regularly include LTC facilities, their residents and workers. Data are crucial to inform evidence-based decisions to favor prioritization and to support advances in promoting policies around institutional LTC in Latin America. Although information about institutional care in the region is fragmented and insufficient, this paper profiles the four selected countries. It highlights the need for a better structure for data-driven LTC information systems. The lack of information emphasizes the urgency of the need to focus on and encourage research into this topic.

En América Latina, más de 8 millones de personas mayores dependen de los cuidados a largo plazo (CLP), lo que representa el 12% de las personas de 60 años o más y casi el 27% de las de 80 años o más Resulta crucial elaborar estrategias sostenibles para la prestación de CLP en la región, incluida la atención en centros de CLP. Este artículo especial tiene como finalidad determinar las características de la atención prestada en centros de CLP en cuatro países (Brasil, Chile, Costa Rica y México), utilizando los sistemas de información disponibles, así como determinar cuáles son las estrategias adoptadas en estos países para brindar apoyo a la atención en centros de CLP. En esta revisión descriptiva se utilizaron fuentes de datos públicas, de libre acceso y de ámbito nacional para recopilar estimaciones demográficas e información sobre la cobertura de la atención en centros de CLP, así como sobre la disponibilidad de datos de libre acceso acerca de la proporción de personas con necesidades de CLP, el número de centros de CLP y su correspondiente número de residentes. Estos países tienen una proporción de personas mayores superior a la media de América Latina, pero menos centros de CLP de los necesarios para cubrir la demanda. En las encuestas nacionales no hay una definición estandarizada de la discapacidad, los cuidados a largo plazo y la dependencia. La mayor parte de la información sobre la atención en centros de CLP está fragmentada y no incluye datos periódicos sobre los centros de CLP existentes, sus residentes o sus trabajadores. Estos datos son cruciales para fundamentar decisiones basadas en la evidencia destinadas a propiciar la priorización y brindar apoyo a los avances en la promoción de políticas en materia de centros de CLP en América Latina. Aunque la información sobre la atención en centros de CLP en la región es fragmentaria e insuficiente, en este artículo se presenta el perfil de los cuatro países seleccionados. Se resalta la necesidad de mejorar la estructura de los sistemas de información sobre CLP basados en datos. Esta falta de información pone de relieve la necesidad urgente de centrarse en este tema y fomentar la investigación al respecto.

Na América Latina, mais de 8 milhões de pessoas idosas dependem de cuidados de longa duração (CLD), o que representa 12% das pessoas com mais de 60 anos e quase 27% das pessoas com mais de 80 anos. É fundamental criar estratégias sustentáveis para oferecer CLD na região, inclusive cuidados institucionais. O objetivo deste relatório especial é caracterizar CLD institucionais em quatro países (Brasil, Chile, Costa Rica e México), usando os sistemas de informação disponíveis, e identificar as estratégias adotadas para apoiar os cuidados institucionais nesses países. Esta revisão narrativa usou dados públicos de acesso aberto de âmbito nacional para coletar estimativas demográficas e informações sobre a cobertura de CLD institucionais e a disponibilidade de dados de acesso aberto sobre a porcentagem de pessoas com necessidades de CLD, o número de instituições de CLD e o número de residentes nessas instituições. Esses países têm uma parcela maior de pessoas idosas do que a média da América Latina, mas menos instituições de CLD do que a demanda exige. Falta padronização na definição de incapacidade, CLD e dependência de cuidados nas pesquisas nacionais. Em sua maior parte, as informações sobre cuidados institucionais são fragmentadas e não incluem instituições de CLD, seus residentes e trabalhadores de maneira regular. É essencial usar dados para guiar decisões baseadas em evidências a fim de favorecer a priorização e apoiar avanços que promovam políticas para CLD institucionais na América Latina. Embora as informações sobre cuidados institucionais na região sejam fragmentadas e insuficientes, este documento traça o perfil dos quatro países selecionados, destacando a necessidade de uma estrutura melhor para sistemas de informações de CLD orientados por dados. A falta de informações ressalta a urgência de aumentar o foco no tópico e encorajar pesquisas sobre o assunto.

Institutional care in four Latin American countries: the importance of fostering public information and evaluation strategies / Atención en centros de cuidados a largo plazo en cuatro países de América Latina: importancia de fomentar la información pública y las estrategias de evaluación / Cuidados institucionais em quatro países da América Latina: a importância de promover informações públicas e estratégias de avaliação

ABSTRACT More than 8 million older people in Latin America depend on long-term care (LTC), accounting for 12% of people aged ≥ 60 years and almost 27% of those aged ≥ 80. It is crucial to develop sustainable strategies for providing LTC in the area, including institutional care. This special report aims to characterize institutional LTC in four countries (Brazil, Chile, Costa Rica and Mexico), using available information systems, and to identify the strategies adopted to support institutional care in these countries. This narrative review used nationwide, open-access, public data sources to gather demographic estimates and information about institutional LTC coverage and the availability of open-access data for the proportion of people with LTC needs, the number of LTC facilities and the number of residents living in them. These countries have a larger share of older people than the average in Latin America but fewer LTC facilities than required by the demand. National surveys lack standardization in defining disability, LTC and dependency on care. Information about institutional care is mainly fragmented and does not regularly include LTC facilities, their residents and workers. Data are crucial to inform evidence-based decisions to favor prioritization and to support advances in promoting policies around institutional LTC in Latin America. Although information about institutional care in the region is fragmented and insufficient, this paper profiles the four selected countries. It highlights the need for a better structure for data-driven LTC information systems. The lack of information emphasizes the urgency of the need to focus on and encourage research into this topic.

RESUMEN En América Latina, más de 8 millones de personas mayores dependen de los cuidados a largo plazo (CLP), lo que representa el 12% de las personas de 60 años o más y casi el 27% de las de 80 años o más Resulta crucial elaborar estrategias sostenibles para la prestación de CLP en la región, incluida la atención en centros de CLP. Este artículo especial tiene como finalidad determinar las características de la atención prestada en centros de CLP en cuatro países (Brasil, Chile, Costa Rica y México), utilizando los sistemas de información disponibles, así como determinar cuáles son las estrategias adoptadas en estos países para brindar apoyo a la atención en centros de CLP. En esta revisión descriptiva se utilizaron fuentes de datos públicas, de libre acceso y de ámbito nacional para recopilar estimaciones demográficas e información sobre la cobertura de la atención en centros de CLP, así como sobre la disponibilidad de datos de libre acceso acerca de la proporción de personas con necesidades de CLP, el número de centros de CLP y su correspondiente número de residentes. Estos países tienen una proporción de personas mayores superior a la media de América Latina, pero menos centros de CLP de los necesarios para cubrir la demanda. En las encuestas nacionales no hay una definición estandarizada de la discapacidad, los cuidados a largo plazo y la dependencia. La mayor parte de la información sobre la atención en centros de CLP está fragmentada y no incluye datos periódicos sobre los centros de CLP existentes, sus residentes o sus trabajadores. Estos datos son cruciales para fundamentar decisiones basadas en la evidencia destinadas a propiciar la priorización y brindar apoyo a los avances en la promoción de políticas en materia de centros de CLP en América Latina. Aunque la información sobre la atención en centros de CLP en la región es fragmentaria e insuficiente, en este artículo se presenta el perfil de los cuatro países seleccionados. Se resalta la necesidad de mejorar la estructura de los sistemas de información sobre CLP basados en datos. Esta falta de información pone de relieve la necesidad urgente de centrarse en este tema y fomentar la investigación al respecto.

RESUMO Na América Latina, mais de 8 milhões de pessoas idosas dependem de cuidados de longa duração (CLD), o que representa 12% das pessoas com mais de 60 anos e quase 27% das pessoas com mais de 80 anos. É fundamental criar estratégias sustentáveis para oferecer CLD na região, inclusive cuidados institucionais. O objetivo deste relatório especial é caracterizar CLD institucionais em quatro países (Brasil, Chile, Costa Rica e México), usando os sistemas de informação disponíveis, e identificar as estratégias adotadas para apoiar os cuidados institucionais nesses países. Esta revisão narrativa usou dados públicos de acesso aberto de âmbito nacional para coletar estimativas demográficas e informações sobre a cobertura de CLD institucionais e a disponibilidade de dados de acesso aberto sobre a porcentagem de pessoas com necessidades de CLD, o número de instituições de CLD e o número de residentes nessas instituições. Esses países têm uma parcela maior de pessoas idosas do que a média da América Latina, mas menos instituições de CLD do que a demanda exige. Falta padronização na definição de incapacidade, CLD e dependência de cuidados nas pesquisas nacionais. Em sua maior parte, as informações sobre cuidados institucionais são fragmentadas e não incluem instituições de CLD, seus residentes e trabalhadores de maneira regular. É essencial usar dados para guiar decisões baseadas em evidências a fim de favorecer a priorização e apoiar avanços que promovam políticas para CLD institucionais na América Latina. Embora as informações sobre cuidados institucionais na região sejam fragmentadas e insuficientes, este documento traça o perfil dos quatro países selecionados, destacando a necessidade de uma estrutura melhor para sistemas de informações de CLD orientados por dados. A falta de informações ressalta a urgência de aumentar o foco no tópico e encorajar pesquisas sobre o assunto.

In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis.

Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor-transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis.

Urinary KIM-1 Correlates with the Subclinical Sequelae of Tubular Damage Persisting after the Apparent Functional Recovery from Intrinsic Acute Kidney Injury.

Acute kidney injury (AKI) poses an increased risk factor for new AKI episodes, progression to chronic kidney disease, and death. A worsened evolution has been linked to an incomplete renal repair beyond the apparent functional recovery based on plasma creatinine (pCr) normalization. However, structural sequelae pass largely unnoticed due to the absence of specific diagnostic tools. The urinary kidney injury molecule 1 (KIM-1) participates in renal tissue damage and repair and is proposed as a biomarker of early and subclinical AKI. Thus, we study in this paper the evolution of KIM-1 urinary excretion alongside renal tissue sequelae after an intrinsic AKI episode induced by cisplatin in Wistar rats. Creatinine clearance, pCr, proteinuria and the fractional excretion of Na+ and glucose were used to monitor renal function. Renal tissue damage was blindly scored in kidney specimens stained with hematoxylin-eosin and periodic acid-Schiff. KIM-1 urinary excretion and renal mRNA expression were also assessed. Finally, we analyzed urinary KIM-1 in patients apparently recovered from AKI. Our results show that, after the normalization of the standard markers of glomerular filtration and tubular function, the extent of persistent histological findings of tissue repair correlates with the renal expression and urinary level of KIM-1 in rats. In addition, KIM-1 is also elevated in the urine of a significant fraction of patients apparently recovered from an AKI. Besides its potential utility in the early and subclinical diagnosis of renal damage, this study suggests a new application of urinary KIM-1 in the non-invasive follow-up of renal repair after AKI.

The bone marrow niche regulates redox and energy balance in MLL::AF9 leukemia stem cells.

Eradicating leukemia requires a deep understanding of the interaction between leukemic cells and their protective microenvironment. The CXCL12/CXCR4 axis has been postulated as a critical pathway dictating leukemia stem cell (LSC) chemoresistance in AML due to its role in controlling cellular egress from the marrow. Nevertheless, the cellular source of CXCL12 in the acute myeloid leukemia (AML) microenvironment and the mechanism by which CXCL12 exerts its protective role in vivo remain unresolved. Here, we show that CXCL12 produced by Prx1+ mesenchymal cells but not by mature osteolineage cells provide the necessary cues for the maintenance of LSCs in the marrow of an MLL::AF9-induced AML model. Prx1+ cells promote survival of LSCs by modulating energy metabolism and the REDOX balance in LSCs. Deletion of Cxcl12 leads to the accumulation of reactive oxygen species and DNA damage in LSCs, impairing their ability to perpetuate leukemia in transplantation experiments, a defect that can be attenuated by antioxidant therapy. Importantly, our data suggest that this phenomenon appears to be conserved in human patients. Hence, we have identified Prx1+ mesenchymal cells as an integral part of the complex niche-AML metabolic intertwining, pointing towards CXCL12/CXCR4 as a target to eradicate parenchymal LSCs in AML.

Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation.

Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the first time 14 intermediate cell states and 11 stages of differentiation in the endothelial and mesenchymal BM compartments, respectively. Our data provide the most comprehensive description to date of the murine HSC-regulatory microenvironment and suggest a higher level of specialization of the cellular circuits than previously anticipated. Furthermore, this deep characterization allows inferring conserved features in human, suggesting that the layers of microenvironmental regulation of hematopoiesis may also be shared between species. Our resource and methodology is a stepping-stone toward a comprehensive cell atlas of the BM microenvironment.

Neural Network-Based Calculator for Rat Glomerular Filtration Rate.

Glomerular filtration is a pivotal process of renal physiology, and its alterations are a central pathological event in acute kidney injury and chronic kidney disease. Creatinine clearance (ClCr), a standard method for glomerular filtration rate (GFR) measurement, requires a long and tedious procedure of timed (usually 24 h) urine collection. We have developed a neural network (NN)-based calculator of rat ClCr from plasma creatinine (pCr) and body weight. For this purpose, matched pCr, weight, and ClCr trios from our historical records on male Wistar rats were used. When evaluated on the training (1165 trios), validation (389), and test sets (660), the model committed an average prediction error of 0.196, 0.178, and 0.203 mL/min and had a correlation coefficient of 0.863, 0.902, and 0.856, respectively. More importantly, for all datasets, the NN seemed especially effective at comparing ClCr among groups within individual experiments, providing results that were often more congruent than those measured experimentally. ACLARA, a friendly interface for this calculator, has been made publicly available to ease and expedite experimental procedures and to enhance animal welfare in alignment with the 3Rs principles by avoiding unnecessary stressing metabolic caging for individual urine collection.

Nutrition competencies for undergraduate medical education: Results of an international interdisciplinary consensus.

BACKGROUND: The gap between the nutrition education provided to medical students and the nutrition competencies and attitudes needed for physicians to provide adequate nutrition care is a global concern. There is no universally accepted benchmark on nutrition competencies for doctors. The objective of this study was to establish, by expert consensus, the objectives of undergraduate nutrition medial education, the nutrition core competencies, and strategies for curriculum development in medical nutrition education. METHODS: We administered a Delphi survey to systematically gather the opinion of a panel of Latin American experts in nutrition. The survey questionnaire was constructed considering scientific literature by using a 5-point Likert scale. Consensus was defined as >70% agreement on the importance of an item (Likert scale 4 and 5). RESULTS: A four-round Delphi survey was conducted for this research. In the second, third, and fourth rounds, we validated a total of 130 competencies by consensus, which were distributed into four different thematic areas: (1) basic nutrition concepts, (2) public nutrition and nutrition prevention throughout the life cycle, (3) nutrition status and disease, and (4) nutrition care process. CONCLUSION: The curricula for general physician education in medical school must include health promotion, prevention, and treatment of diseases related to nutrition. This goal can be reached by integrating ≤130 competencies into four different fundamental areas.

Nutrition in medical education in Latin America: Results of a cross-sectional survey.

RATIONALE: The gap between the nutrition education provided to medical students and the nutrition competences and attitudes needed for doctors to provide effective nutrition care is a global concern. The goal of this study was to investigate the curricular content on nutrition education in Latin American medical schools and to evaluate the self-perceived knowledge, attitudes, and barriers to nutrition practice of final-year medical students. METHODS: Eighty-five public and private medical schools from 17 Latin American countries were invited to participate in the study. Two close-ended online questionnaires consisting of 25 and 43 questions were sent to medical school directors. Quantitative variables were expressed as frequencies, percentages, mean ± standard deviation, medians, and ranges. RESULTS: A total of 22 (26%) medical school directors responded, of which 11 schools (50%) offered stand-alone mandatory nutrition courses in preclinical and 8 (36%) in clinical years. The mean hours dedicated to nutrition education was 47 (range: 0-150). A total of 1530 of 1630 (94%) students from 12 countries responded. Students' average age was 25 ± 3 years, and 59% were female. Most students agreed that improving patients' health through nutrition (91%) is important and that nutrition counseling and assessment should be part of routine care provided by all physicians (89%), but they lack the level of education and training required to address nutrition-related issues. CONCLUSIONS: Positive attitude and interest in nutrition among final-year medical students is high, but nutrition education is not perceived as sufficient to adequately prepare doctors in the field of nutrition.

Shelter from the cytokine storm: Healthy living is a vital preventative strategy in the COVID-19 era.

Coronavirus disease 2019 (COVID-19) continues to have a devastating effect on a global scale. COVID-19 variants continue to arise and counteract vaccination efficacy. As such, preventative health measures, such as social distancing and stay at home mandates, will continue for the foreseeable future. Evidence on those at greatest risk for poor outcomes if infected with COVID-19 has rapidly come to light. It has become clear that those with unhealthy lifestyle characteristics, chronic disease risk factors and/or a confirmed diagnosis of one or more chronic conditions are at greatest risk for hospitalization, intensive care unit admission, mechanical ventilation, and death if infected with COVID-19. The cytokine storm is a phenomenon that has been posited as a pathophysiologic response to COVID-19 infection that leads to poor outcomes. The current graphical review illustrates the association between unhealthy lifestyle characteristics and increased vulnerability to the cytokine storm as well as the physiologic mechanisms healthy living behaviors elicit and decrease risk for the cytokine storm. Through this graphical review, we will demonstrate unhealthy lifestyle characteristics, chronic disease risk factors and diagnoses, and COVID-19 outcomes are intricately linked, creating a new global syndemic. It is also clear that a primary way to uncouple this syndemic is through increasing healthy living behaviors, as illustrated in this graphical review. Moving forward, healthy living medicine should be practiced with renewed vigor to improve human resiliency to health threats posed by both chronic disease and viral infections.

Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer.

PURPOSE: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or IHC-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. EXPERIMENTAL DESIGN: In FAIRLANE, 151 patients with early triple-negative breast cancer (TNBC) were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by MRI. We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. One hundred and twenty-five baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points. RESULTS: Tumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated AKT (pAKT) levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a downregulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment. CONCLUSIONS: We showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.

The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability.

The target of Rapamycin complex1 (TORC1) senses and integrates several environmental signals, including amino acid (AA) availability, to regulate cell growth. Folliculin (FLCN) is a tumor suppressor (TS) protein in renal cell carcinoma, which paradoxically activates TORC1 in response to AA supplementation. Few tractable systems for modeling FLCN as a TS are available. Here, we characterize the FLCN-containing complex in Schizosaccharomyces pombe (called BFC) and show that BFC augments TORC1 repression and activation in response to AA starvation and supplementation, respectively. BFC co-immunoprecipitates V-ATPase, a TORC1 modulator, and regulates its activity in an AA-dependent manner. BFC genetic and proteomic networks identify the conserved peptide transmembrane transporter Ptr2 and the phosphoribosylformylglycinamidine synthase Ade3 as new AA-dependent regulators of TORC1. Overall, these data ascribe an additional repressive function to Folliculin in TORC1 regulation and reveal S. pombe as an excellent system for modeling the AA-dependent, FLCN-mediated repression of TORC1 in eukaryotes.

Biomarkers of persistent renal vulnerability after acute kidney injury recovery.

Acute kidney injury (AKI) is a risk factor for new AKI episodes, chronic kidney disease, cardiovascular events and death, as renal repair may be deficient and maladaptive, and activate proinflammatory and profibrotic signals. AKI and AKI recovery definitions are based on changes in plasma creatinine, a parameter mostly associated to glomerular filtration, but largely uncoupled from renal tissue damage. The evolution of structural and functional repair has been incompletely described. We thus aimed at identifying subclinical sequelae persisting after recovery from cisplatin-induced AKI in rats. Compared to controls, after plasma creatinine recovery, post-AKI kidneys showed histological alterations and attendant susceptibility to new AKI episodes. Tubular function (assessed by the furosemide stress test, FST) also remained affected. Lingering parenchymal and functional subclinical alterations were paralleled by tapering, but abnormally high levels of urinary albumin, transferrin, insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and, especially, the [TIMP-2]*[IGFBP7] product. As subclinical surrogates of incomplete renal recovery, the FST and the urinary [TIMP-2]*[IGFBP7] product provide two potential diagnostic tools to monitor the sequelae and kidney vulnerability after the apparent recovery from AKI.

Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status.

Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue.

Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research.

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.

Better together: circulating tumor cell clustering in metastatic cancer.

Circulating tumor cells (CTCs) are vital components of liquid biopsies for diagnosis of residual cancer, monitoring of therapy response, and prognosis of recurrence. Scientific dogma focuses on metastasis mediated by single CTCs, but advancement of CTC detection technologies has elucidated multicellular CTC clusters, which are associated with unfavorable clinical outcomes and a 20- to 100-fold greater metastatic potential than single CTCs. While the mechanistic understanding of CTC cluster formation is still in its infancy, multiple cell adhesion molecules and tight junction proteins have been identified that underlie the outperforming attributes of homotypic and heterotypic CTC clusters, such as cell survival, cancer stemness, and immune evasion. Future directions include high-resolution characterization of CTCs at multiomic levels for diagnostic/prognostic evaluations and targeted therapies.

Optimization of Lyophilized Hyperacute Serum (HAS) as a Regenerative Therapeutic in Osteoarthritis.

Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined versions, to obtain a stable and standardized therapeutic in osteoarthritis (OA), which may be able to overcome the variability limitations of platelet-rich plasma (PRP). Primary human osteoarthritic chondrocytes were used for testing cellular viability and gene expression of OA-related genes. Moreover, a co-culture of human explants of cartilage, bone and synovium under inflammatory conditions was used for investigating the inflammatory control capacities of the different therapeutics. In this study, one formulation of lyophilized HAS achieved the high cell viability rates of liquid HAS and PRP. Gene expression analysis showed that HAS induced higher Col1a1 expression than PRP. Cytokine quantification from supernatant fluids revealed that HAS treatment of inflamed co-cultures significantly reduced levels of IL-5, IL-15, IL-2, TNFα, IL-7 and IL-12. To conclude, lyophilized HAS is a stable and standardized therapeutic with high potential in joint regeneration.