Phenolic Compounds of Therapeutic Interest in Neuroprotection.

The number of elderly people is projected to double in the next 50 years worldwide, resulting in an increased prevalence of neurodegenerative diseases. Aging causes changes in brain tissue homeostasis, thus contributing to the development of neurodegenerative disorders. Current treatments are not entirely effective, so alternative treatments or adjuvant agents are being actively sought. Antioxidant properties of phenolic compounds are of particular interest for neurodegenerative diseases whose psychopathological mechanisms strongly rely on oxidative stress at the brain level. Moreover, phenolic compounds display other advantages such as the permeability of the blood-brain barrier (BBB) and the interesting molecular mechanisms that we reviewed in this work. We began by briefly outlining the physiopathology of neurodegenerative diseases to understand the mechanisms that result in irreversible brain damage, then we provided an overall classification of the phenolic compounds that would be addressed later. We reviewed in vitro and in vivo studies, as well as some clinical trials in which neuroprotective mechanisms were demonstrated in models of different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia, and traumatic brain injury (TBI).

Optimizing Interprofessional Simulation with Intentional Pre-Briefing and Debriefing.

The use of simulation and interprofessional education (IPE) has been shown to enhance healthcare student and provider confidence, strengthen teamwork, and improve patient outcomes. Although debriefing has been widely practiced and studied, the value of intentional pre-briefing has been recently recognized. At the University of the Incarnate Word (UIW), Doctor of Physical Therapy (DPT) and Bachelor of Science in Nursing (BSN) students engaged in a simulation with multiple acute care scenarios. The goal of this activity was to foster competence and confidence in coordinating care for patients with complex medical conditions while functioning as integral members of a team. Faculty members recognized an opportunity to practice interprofessional care coordination behaviors through this simulation. The activity was intentionally structured with three key components: (1) thorough advanced preparation, (2) a well-organized pre-briefing session encompassing pre-simulation orientation, and (3) a structured debrief that encouraged reflection on patient care prioritization. The simulation addressed the activity goals and provided students with opportunities for growth in the Interprofessional Education Collaborative (IPEC) core competencies.

Endothelial APC/PAR1 distinctly regulates cytokine-induced pro-inflammatory VCAM-1 expression.

Introduction: Dysfunction of the endothelium impairs its' protective role and promotes inflammation and progression of vascular diseases. Activated Protein C (APC) elicits endothelial cytoprotective responses including barrier stabilization, anti-inflammatory and anti-apoptotic responses through the activation of the G protein-coupled receptor (GPCR) protease-activated receptor-1 (PAR1) and is a promising therapeutic. Despite recent advancements in developing new Activated protein C variants with clinical potential, the mechanism by which APC/PAR1 promotes different cytoprotective responses remains unclear and is important to understand to advance Activated protein C and new targets as future therapeutics. Here we examined the mechanisms by which APC/PAR1 attenuates cytokine-induced pro-inflammatory vascular cell adhesion molecule (VCAM-1) expression, a key mediator of endothelial inflammatory responses. Methods: Quantitative multiplexed mass spectrometry analysis of Activated protein C treated endothelial cells, endothelial cell transcriptomics database (EndoDB) online repository queries, biochemical measurements of protein expression, quantitative real-time polymerase chain reaction (RT-qPCR) measurement of mRNA transcript abundance, pharmacological inhibitors and siRNA transfections of human cultured endothelial cells. Results: Here we report that Activated Protein C modulates phosphorylation of tumor necrosis factor (TNF)-α signaling pathway components and attenuates of TNF-α induced VCAM-1 expression independent of mRNA stability. Unexpectedly, we found a critical role for the G protein-coupled receptor co-receptor sphingosine-1 phosphate receptor-1 (S1PR1) and the G protein receptor kinase-2 (GRK2) in mediating APC/PAR1 anti-inflammatory responses in endothelial cells. Discussion: This study provides new knowledge of the mechanisms by which different APC/PAR1 cytoprotective responses are mediated through discrete ß-arrestin-2-driven signaling pathways modulated by specific G protein-coupled receptor co-receptors and GRKs.

Adaptación y evaluación de la eficacia de un programa psicoeducativo de navegación para disminuir síntomas de ansiedad y depresión en mu-jeres mexicanas con cáncer de mama / Design and evaluation of the efficacy of a psychoeducational navigation program to reduce symptoms of anxiety and depression in Mexican women with breast cancer

Objetivo:El cáncer de mama (CAM) es un problema de salud pública mundial. La ansiedad y depresión son las principales comorbilidades que aquejan a este sector, el programa psicoeducativo de navegación (PPN) se presenta como una estrategia psicosocial eficaz en hospitales públicos de México. Método: Se realizó la adaptación del PPN y la evaluación de eficacia en 47 mujeres con CAM de tres hospitales de la Zona Metropolitana de Guadalajara. El PPN integró acompañamiento emocional, educación para la salud y técnicas de relajación. Se evaluaron los síntomas y los niveles de ansiedad y depresión, pre-post intervención con la Escala Hospitalaria de Ansiedad y Depresión (HADS). Resultados: Se encontró una disminución en los síntomas de ansiedad pre-test (M= 6,79, DT= 4,01) y pos-test (M= 4,19, DT= 3,03), igual que en los síntomas de depresión antes (M= 6,02, DT= 4,07) y después (M= 4,23, DT= 3,05). Se obtuvieron diferencias estadísticamente significativas entre las evaluaciones pre y post intervención tanto en las dimensiones, como en la puntuación global (p<0,001). Conclusiones: El PPN mostró eficacia para disminuir los síntomas y los niveles de ansiedad y depresión en mujeres mexicanas con CAM. Sugerimos replicar el programa en otros contextos de atención oncológica en seguimiento a las normativas nacionales (AU)

Objective: Breast cancer (BC) is a public health problem. Anxiety and depression are the main comorbidities that afflict this sector, the navigation psychoeducational program (NPP) is presented as an effective psychosocial strategy in public hospitals in Mexico.Method: The NPP was adapted and its efficacy evaluated in 47 women with BC from three hospitals in the Guadalajara Metropolitan Area. The NPP integrated emotional accompaniment, health education and relaxation techniques. Symptoms and levels of anxiety and depression were evaluated pre-post intervention with the Hospital Anxiety and Depression Scale (HADS). Results: A decrease was found in anxiety symptoms pre-test (M= 6.79, SD= 4.01) and post-test (M= 4.19, SD= 3.03), the same as in depression symptoms before (M= 6.02, SD= 4.07) and after (M= 4.23, SD= 3.05). Statistically significant differences were obtained between the pre- and post-intervention evaluations both in the dimensions and in the global score (p<0.001).Conclusions: The NPP showed efficacy in reducing symptoms and levels of anxiety and depression in Mexican women with BC. We suggest replicating the program in other cancer care contexts in compliance with national regulations (AU)

Evaluation of sample pooling for the detection of SARS-CoV-2 in a resource-limited setting, Dominican Republic.

INTRODUCTION: COVID-19 is a worldwide public health threat. Diagnosis by RT-PCR has been employed as the standard method to confirm viral infection. Sample pooling testing can optimize the resources by reducing the workload and reagents shortage, and be useful in laboratories and countries with limited resources. This study aims to evaluate SARS-CoV-2 detection by sample pooling testing in comparison with individual sample testing. MATERIALS AND METHODS: We created 210 pools out of 245 samples, varying from 4 to 10 samples per pool, each containing a positive sample. We conducted detection of SARS-CoV-2-specific RdRp/E target sites. RESULTS: Pooling of three samples for SARS-CoV-2 detection might be an efficient strategy to perform without losing RT-PCR sensitivity. CONCLUSIONS: Considering the positivity rate in Dominican Republic and that larger sample pools have higher probabilities of obtaining false negative results, the optimal sample size to perform a pooling strategy shall be three samples.

Evaluation of sample pooling for the detection of SARS-CoV-2 in a resource-limited setting, Dominican Republic / Evaluación del análisis de muestras agrupadas para la detección de SARS-CoV-2 en entornos con recursos limitados, República Dominicana

Introduction: COVID-19 is a worldwide public health threat. Diagnosis by RT-PCR has been employed as the standard method to confirm viral infection. Sample pooling testing can optimize the resources by reducing the workload and reagents shortage, and be useful in laboratories and countries with limited resources. This study aims to evaluate SARS-CoV-2 detection by sample pooling testing in comparison with individual sample testing. Materials and methods: We created 210 pools out of 245 samples, varying from 4 to 10 samples per pool, each containing a positive sample. We conducted detection of SARS-CoV-2-specific RdRp/E target sites. Results: Pooling of three samples for SARS-CoV-2 detection might be an efficient strategy to perform without losing RT-PCR sensitivity. Conclusions: Considering the positivity rate in Dominican Republic and that larger sample pools have higher probabilities of obtaining false negative results, the optimal sample size to perform a pooling strategy shall be three samples.(AU)

Introducción: La COVID-19 es una amenaza de salud pública mundial. La RT-PCR es el método estándar para confirmar la infección. La estrategia de pruebas de muestras agrupadas puede reducir la carga de trabajo y la escasez de reactivos, y ser útil en países con escasos recursos. Evaluamos la detección del SARS-CoV-2 mediante esta estrategia en comparación con pruebas individuales. Materiales y métodos: Creamos 210 grupos de 245 muestras, de 4 a 10 muestras por grupo, cada uno con una muestra positiva. Realizamos extracción de ARN y qRT-PCR para detectar la presencia de la diana RdRp/E. Resultados: La combinación de hasta 3 muestras para la detección del SARS-CoV-2 podría ser una estrategia eficaz sin perder la sensibilidad. Conclusiones: Considerando la tasa de positividad en República Dominicana y que los grupos con más muestras tienen mayor probabilidad de obtener resultados falsos negativos, el tamaño óptimo para realizar esta estrategia es de 3 muestras.(AU)

Evaluation of sample pooling for the detection of SARS-CoV-2 in a resource-limited setting, Dominican Republic.

Introduction: COVID-19 is a worldwide public health threat. Diagnosis by RT-PCR has been employed as the standard method to confirm viral infection. Sample pooling testing can optimize the resources by reducing the workload and reagents shortage, and be useful in laboratories and countries with limited resources. This study aims to evaluate SARS-CoV-2 detection by sample pooling testing in comparison with individual sample testing. Materials and methods: We created 210 pools out of 245 samples, varying from 4 to 10 samples per pool, each containing a positive sample. We conducted detection of SARS-CoV-2-specific RdRp/E target sites. Results: Pooling of three samples for SARS-CoV-2 detection might be an efficient strategy to perform without losing RT-PCR sensitivity. Conclusions: Considering the positivity rate in Dominican Republic and that larger sample pools have higher probabilities of obtaining false negative results, the optimal sample size to perform a pooling strategy shall be three samples.

Introducción: La COVID-19 es una amenaza de salud pública mundial. La RT-PCR es el método estándar para confirmar la infección. La estrategia de pruebas de muestras agrupadas puede reducir la carga de trabajo y la escasez de reactivos, y ser útil en países con escasos recursos. Evaluamos la detección del SARS-CoV-2 mediante esta estrategia en comparación con pruebas individuales. Materiales y métodos: Creamos 210 grupos de 245 muestras, de 4 a 10 muestras por grupo, cada uno con una muestra positiva. Realizamos extracción de ARN y qRT-PCR para detectar la presencia de la diana RdRp/E. Resultados: La combinación de hasta 3 muestras para la detección del SARS-CoV-2 podría ser una estrategia eficaz sin perder la sensibilidad. Conclusiones: Considerando la tasa de positividad en República Dominicana y que los grupos con más muestras tienen mayor probabilidad de obtener resultados falsos negativos, el tamaño óptimo para realizar esta estrategia es de 3 muestras.

In Peripheral Blood Mononuclear Cells Helicobacter pylori Induces the Secretion of Soluble and Exosomal Cytokines Related to Carcinogenesis.

Helicobacter pylori promotes the secretion of cytokines that regulate inflammation and carcinogenesis. Immune cells secrete cytokines into the extracellular medium or packaged in exosomes. The objective of this study was to analyze the profile of soluble and exosomal cytokines that were secreted by human peripheral blood mononuclear cells (PBMCs) that were infected with H. pylori and to build a network of interaction between cytokines and cellular proteins. PBMCs were obtained by density gradient centrifugation and infected with H. pylori for 24 h. The infection was verified by immunofluorescence and Western blot for CagA. The exosomes were obtained from culture supernatant by ultracentrifugation and characterized by transmission electron microscopy, particle size analysis, and Western blot for CD9 and CD81. Cytokines were quantified using a multiplex immunoassay in the culture supernatant, intact exosomes, and lysed exosomes. H. pylori adheres to lymphocytes and translocates CagA. In PBMCs, H. pylori induces an increase in the soluble and exosomal IL-1ß, IL-6, TNF-α, IL-10, IL-17A, IL-21, and IL-22. The protein-protein interaction (PPI) network shows that soluble and exosomal cytokines interact with proteins that participate in signaling pathways such as NF-κB, MAPK, PI3K-Akt, Jak-STAT, FoxO, and mTOR, that are related to carcinogenesis; moreover, TNF-α had the highest number of interactions. Cytokine-loaded exosomes represent another means of intercellular communication that is activated by H. pylori to stimulate inflammation, carcinogenesis, or cancer progression. Cytokine-loaded exosomes are likely to be associated with extragastrointestinal diseases of inflammatory origin.

CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma.

Background: Exosomes are microvesicles that actively participate in signaling mechanisms and depending on their content can contribute to the development of different pathologies, such as diabetes and cardiovascular disease. Objective: The aim of this study was to evaluate the association of cystatin C, CD26, and CD14 proteins in serum exosomes from patients with Type 2 Diabetes (T2D), metabolic syndrome (MetS), and atherogenic index of plasma (AIP). Methods: Serum exosomes were isolated by ultracentrifugation from 147 individuals with and without diabetes. Both anthropometric and metabolic parameters were registered from everyone. The levels of exosomal proteins cystatin C, CD26, and CD14 were quantified by ELISA. The association between protein levels and T2D or atherogenic risk factors was analyzed by linear regression and generalized regression models. Results: We observed a significant correlation of increased glucose with elevated levels of Cystatin C, and an effect of T2D on the levels of CD26 (ß = 45.8 pg/µg; p = 0.001) and CD14 (ß = 168 pg/µg; p < 0.001) compared to subjects without T2D. CD14 was significantly related to T2D, metabolic syndrome, glucose, and the Atherogenic Index of Plasma (AIP). Additionally, we observed a significant effect of metabolic syndrome MetS on the increase of exosomal Cystatin C and CD14. Conclusions: T2D may contribute to the increase of CD14 protein contained in exosomes, as well as to the predisposition of atherogenic events development due to its relationship with the increase in serum triglyceride concentrations and the AIP score. Finally, the increased levels of CD14 and Cystatin C in exosomes are related to MetS. The analysis of exosome contents of diabetic patients remains an incipient field, so extensive characterization is crucial for their use as biomarkers or to analyze their possible contribution to diabetic complications.

Symptom attribution in patients with medically unexplained symptoms. A scale development and validation study.

INTRODUCTION: In the care of patients with medically unexplained physical symptoms (MUPS) it is important what they think about their symptoms. OBJECTIVE: To validate the psychometric properties of a symptom attribution scale in patients with MUPS and to verify its reliability. METHODS: A non-probabilistic sample of 400 male and female adult patients were interviewed in the outpatient services of a family medicine hospital, 200 with MUPS and 200 with a defined organic pathology. Each group was diagnosed with defined criteria, and a scale with content and construct validity was applied by means of principal component analysis with varimax rotation. RESULTS: The scale was made up of 12 items with two factors, one of symptom psychosocial attribution and other with organic attribution. The psychosocial-origin factor showed a variance of 49.7%. The goodness-of-fit test demonstrated that the correlation matrix was adequate, and Bartlett's sphericity test indicated statistical significance (p < 0.0001); Cronbach's alpha was 0.841. CONCLUSION: The scale showed acceptable construct validity and good reliability and stability. The implications of these results for future measurement research are discussed.

INTRODUCCIÓN: En la atención de pacientes con síntomas físicos médicamente no explicables (SFMNE) es importante lo que el paciente piensa de sus síntomas. OBJETIVO: Validar propiedades psicométricas de una escala de atribución del síntoma en pacientes con SFMNE y verificar su confiabilidad. MÉTODOS: Se entrevistó a una muestra no probabilística de 400 pacientes adultos, hombres y mujeres, en la consulta de un hospital con medicina familiar, 200 con SFMNE y 200 con patología orgánica concreta. Se diagnosticó a cada grupo con criterios definidos y se aplicó una escala con validez de contenido y de constructo por medio de análisis de componentes principales con rotación varimax. RESULTADOS: La escala quedó integrada por 12 reactivos con dos factores, uno de atribución psicosocial y otro de atribución orgánica del síntoma. El factor de origen psicosocial tuvo una varianza de 49.7 %. La prueba de bondad de ajuste mostró que la matriz de correlaciones fue adecuada y la prueba de esfericidad de Bartlett indicó significación estadística (p < 0.0001); el alfa de Cronbach fue de 0.841. CONCLUSIÓN: La escala mostró una validez de constructo aceptable y buena confiabilidad y estabilidad. Se discuten las implicaciones de estos resultados para la investigación de mediciones futuras.

Resurrection of an ancient inflammatory locus reveals switch to caspase-1 specificity on a caspase-4 scaffold.

Pyroptosis is a mechanism of inflammatory cell death mediated by the activation of the prolytic protein gasdermin D by caspase-1, caspase-4, and caspase-5 in human, and caspase-1 and caspase-11 in mouse. In addition, caspase-1 amplifies inflammation by proteolytic activation of cytokine interleukin-1ß (IL-1ß). Modern mammals of the order Carnivora lack the caspase-1 catalytic domain but express an unusual version of caspase-4 that can activate both gasdermin D and IL-1ß. Seeking to understand the evolutionary origin of this caspase, we utilized the large amount of data available in public databases to perform ancestral sequence reconstruction of an inflammatory caspase of a Carnivora ancestor. We expressed the catalytic domain of this putative ancestor in Escherichia coli, purified it, and compared its substrate specificity on synthetic and protein substrates to extant caspases. We demonstrated that it activates gasdermin D but has reduced ability to activate IL-1ß. Our reconstruction suggests that caspase-1 was lost in a Carnivora ancestor, perhaps upon a selective pressure for which the generation of biologically active IL-1ß by caspase-1 was detrimental. We speculate that later, a Carnivora encountered selective pressures that required the production of IL-1ß, and caspase-4 subsequently gained this activity. This hypothesis would explain why extant Carnivora possess an inflammatory caspase with caspase-1 catalytic function placed on a caspase-4 scaffold.

Effects of exposure to environmental pollutants on mitochondrial DNA copy number: a meta-analysis.

Exposure to environmental pollutants has been associated with alteration on relative levels of mitochondrial DNA copy number (mtDNAcn). However, the results obtained from epidemiological studies are inconsistent. This meta-analysis aimed to evaluate whether environmental pollutant exposure can modify the relative levels of mtDNAcn in humans. We performed a literature search using PubMed, Scopus, and Web of Science databases. We selected and reviewed original articles performed in humans that analyzed the relationship between environmental pollutant exposure and the relative levels of mtDNAcn; the selection of the included studies was based on inclusion and exclusion criteria. Only twenty-two studies fulfilled our inclusion criteria. A total of 6011 study participants were included in this systematic review and meta-analysis. We grouped the included studies into four main categories according to the type of environmental pollutant: (1) heavy metals, (2) polycyclic aromatic hydrocarbons (PAHs), (3) particulate matter (PM), and (4) cigarette smoking. Inconclusive results were observed in all categories; the pooled analysis shows a marginal increase of relative levels of mtDNAcn in response to environmental pollutant exposure. The trial sequential analysis and rate confidence in body evidence showed the need to perform new studies. Therefore, a large-scale cohort and mechanistic studies in this area are required to probe the possible use of relative levels of mtDNAcn as biomarkers linked to environmental pollution exposure.

Cat Coat Color, Personality Traits and the Cat-Owner Relationship Scale: A Study with Cat Owners in Mexico.

Studies regarding the cat-owner bond are quite rare, and several aspects merit more research, including personality trait differences in cats related to coat color and the cat-owner relationship. The objectives of the study were to describe, from the perspective of their owners, the personality traits of cats based on their coat colors and to evaluate the relationships among the Cat Owner Relationship Scale (CORS), its subscales and the traits of cats. Therefore, the CORS was translated into Spanish, and its psychometric properties were assessed. For the personality traits of cats, participants answered a 7-point Likert scale indicating the extent to which they agreed with the following characteristics in describing their cats: active, aloof, bold, calm, friendly, intolerant, shy, stubborn, tolerant and trainable. 211 cat owners living in Mexico participated. Owners perceived their cats as being bold and friendly. Gray cats had the highest score for being as shy, aloof and intolerant, while orange cats had the highest scores for being trainable, friendly and calm. Tabbies the highest for bold and active, tricolor cats for stubborn, and bicolor cats for tolerant. The 3 CORS subscales had adequate psychometric properties when evaluated separately. Cat-owner interaction was positively correlated with an active and friendly personality and negatively correlated with aloofness. Emotional closeness was positively correlated with an active, bold and friendly personality, and perceived cost was negatively correlated with boldness.

Planificación digital en tratamiento de fibroma osificante juvenil psamomatoide maxilar. Presentación de un caso / Digital planning in the treatment of juvenile maxillary psamomatoid ossifying fibroma. Presentation of a case

Los fibromas osificantes son neoplasias fibro-óseas benignas que afectan al esqueleto craneofacial y mandibular. El fibroma osificante psamomatoide juvenil es una variante rara del fibroma osificante, la que puede ser localmente agresiva y con una alta tasa de recidiva. Se presenta el caso de una paciente de 15 años con antecedentes mórbidos de hipotiroidismo e hiperparatiroidismo, quien consulta por aumento de volumen y desplazamiento de dientes en maxilar derecho. El resultado histopatológico fue compatible con fibroma osificante psamomatoide juvenil. Dado el contexto hospitalario durante la pandemia de COVID-19, el tratamiento consistió en hemimaxilectomía con autoinjerto libre de cresta ilíaca mediante planificación digital. (AU)

Ossifying fibromas are benign fibro-osseous neoplasms that affect the craniofacial and mandibular skeleton. Juvenile psamomatoid ossifying fibroma is a rare variant of ossifying fibroma, which can be locally aggressive, and with a high recurrence rate. We present the clinical case of a 15-year-old patient with a morbid history of hypothyroidism and hyperparathyroidism, who consulted for increased volume and displacement of teeth in the right maxilla. The histopathological result was consistent with juvenile psamomatoid ossifying fibroma. Owing to the hospital situation during the COVID-19 the treatment consisted of hemimaxillectomy with iliac crest autograft using digital planning. (AU)

Phosphoproteomic analysis of thrombin- and p38 MAPK-regulated signaling networks in endothelial cells.

Endothelial dysfunction is a hallmark of inflammation and is mediated by inflammatory factors that signal through G protein-coupled receptors including protease-activated receptor-1 (PAR1). PAR1, a receptor for thrombin, signals via the small GTPase RhoA and myosin light chain intermediates to facilitate endothelial barrier permeability. PAR1 also induces endothelial barrier disruption through a p38 mitogen-activated protein kinase-dependent pathway, which does not integrate into the RhoA/MLC pathway; however, the PAR1-p38 signaling pathways that promote endothelial dysfunction remain poorly defined. To identify effectors of this pathway, we performed a global phosphoproteome analysis of thrombin signaling regulated by p38 in human cultured endothelial cells using multiplexed quantitative mass spectrometry. We identified 5491 unique phosphopeptides and 2317 phosphoproteins, four distinct dynamic phosphoproteome profiles of thrombin-p38 signaling, and an enrichment of biological functions associated with endothelial dysfunction, including modulators of endothelial barrier disruption and a subset of kinases predicted to regulate p38-dependent thrombin signaling. Using available antibodies to detect identified phosphosites of key p38-regulated proteins, we discovered that inhibition of p38 activity and siRNA-targeted depletion of the p38α isoform increased basal phosphorylation of extracellular signal-regulated protein kinase 1/2, resulting in amplified thrombin-stimulated extracellular signal-regulated protein kinase 1/2 phosphorylation that was dependent on PAR1. We also discovered a role for p38 in the phosphorylation of α-catenin, a component of adherens junctions, suggesting that this phosphorylation may function as an important regulatory process. Taken together, these studies define a rich array of thrombin- and p38-regulated candidate proteins that may serve important roles in endothelial dysfunction.

COVID-19 threatens faculty diversity: postdoctoral scholars call for action.

Despite substantial investment and effort by federal agencies and institutions to improve the diversity of the professoriate, progress is excruciatingly slow. One program that aims to enhance faculty diversity is the Institutional Research and Academic Career Development Award (IRACDA) funded by the National Institutes of Health/National Institute of General Medical Sciences. IRACDA supports the training of a diverse cohort of postdoctoral scholars who will seek academic research and teaching careers. The San Diego IRACDA program has trained 109 postdoctoral scholars since its inception in 2003; 59% are women and 63% are underrepresented (UR) Black/African-American, Latinx/Mexican-American, and Indigenous scientists. Sixty-four percent obtained tenure-track faculty positions, including a substantial 32% at research-intensive institutions. However, the COVID-19 pandemic crisis threatens to upend IRACDA efforts to improve faculty diversity, and academia is at risk of losing a generation of diverse, talented scholars. Here, a group of San Diego IRACDA postdoctoral scholars reflects on these issues and discusses recommendations to enhance the retention of UR scientists to avoid a "lost generation" of promising UR faculty scholars.

Chronic Leptin Treatment Induces Epithelial-Mesenchymal Transition in MCF10A Mammary Epithelial Cells.

Leptin is a cytokine-like hormone that functions as a link between obesity and breast cancer (BC). Leptin treatment induces Epithelial to Mesenchymal Transition (EMT) in BC cell lines. In non-tumoral breast epithelial MCF10A cells, acute leptin treatment induces partial EMT. However, the effect of chronic leptin treatment on EMT in non-tumorigenic breast cells has not been fully explored. This study aimed to evaluate the effect of chronic leptin treatment on the induction of EMT in MCF10A cells. We found that chronic leptin treatment induces a switch from an epithelial to a mesenchymal morphology, partial loss of E-cadherin and gain of vimentin expression. Immunolocalization experiments showed a partial loss of E-cadherin at cell junctions and increased cytoplasmic localization of vimentin in leptin-treated cells. Moreover, chronic leptin treatment increased collective cell migration and invasion. Furthermore, when cultured in non-adherent conditions leptin treated cells exhibited reduced cell aggregation, increased survival, and decreased apoptosis, which correlates with increased FAK and AKT phosphorylation. Finally, bioinformatic analysis in two publicly available RNAseq datasets from normal breast tissue shows that high levels of leptin mRNA correlate positively with the expression of mesenchymal markers, and negatively with epithelial markers. Thus, our results demonstrate that chronic leptin treatment induces EMT in non-tumorigenic MCF10A cells and suggest that high leptin expression in normal breast tissue may induce EMT and contribute to increased risk of breast cancer.

Atribución de síntomas en pacientes con síntomas médicamente inexplicables. Un estudio de validación y desarrollo de la escala / Symptom attribution in patients with medically unexplained symptoms. A scale development and validation study

Resumen Introducción: En la atención de pacientes con síntomas físicos médicamente no explicables (SFMNE) es importante lo que el paciente piensa de sus síntomas. Objetivo: Validar propiedades psicométricas de una escala de atribución del síntoma en pacientes con SFMNE y verificar su confiabilidad. Métodos: Se entrevistó a una muestra no probabilística de 400 pacientes adultos, hombres y mujeres, en la consulta de un hospital con medicina familiar, 200 con SFMNE y 200 con patología orgánica concreta. Se diagnosticó a cada grupo con criterios definidos y se aplicó una escala con validez de contenido y de constructo por medio de análisis de componentes principales con rotación varimax. Resultados: La escala quedó integrada por 12 reactivos con dos factores, uno de atribución psicosocial y otro de atribución orgánica del síntoma. El factor de origen psicosocial tuvo una varianza de 49.7 %. La prueba de bondad de ajuste mostró que la matriz de correlaciones fue adecuada y la prueba de esfericidad de Bartlett indicó significación estadística (p < 0.0001); el alfa de Cronbach fue de 0.841. Conclusión.: La escala mostró una validez de constructo aceptable y buena confiabilidad y estabilidad. Se discuten las implicaciones de estos resultados para la investigación de mediciones futuras.

Abstract Introduction: In the care of patients with medically unexplained physical symptoms (MUPS) it is important what they think about their symptoms. Objective: To validate the psychometric properties of a symptom attribution scale in patients with MUPS and to verify its reliability. Methods: A non-probabilistic sample of 400 male and female adult patients were interviewed in the outpatient services of a family medicine hospital, 200 with MUPS and 200 with a defined organic pathology. Each group was diagnosed with defined criteria, and a scale with content and construct validity was applied by means of principal component analysis with varimax rotation. Results: The scale was made up of 12 items with two factors, one of symptom psychosocial attribution and others with organic attribution. The psychosocial-origin factor showed a variance of 49.7%. The goodness-of-fit test demostrated that the correlation matrix was adequate, and Bartlett's sphericity test indicated statistical significance (p < 0.0001); Cronbach's alpha was 0.841. Conclusion: The scale showed acceptable construct validity and good reliability and stability. The implications of these results for future measurement research are discussed.

The activation of hypothalamic AMP-activated protein kinase by oxidative stress is related to hyperphagia in diabetic rats.

OBJECTIVE: During diabetes, there are increased blood glucose levels and oxidative stress. The relationship between oxidative stress and the phosphorylation of AMP-activated protein kinase at the hypothalamic level has been little studied. The objective of this study was to analyze the relationship between oxidative stress and AMP-activated protein kinase activation in Wistar rats with hyperphagia and hyperglycemia. METHODS: Rats at 7, 14, and 28 days with diabetes were used. Control rats were included. Food intake was calculated to determine hyperphagia. The hypothalamus was extracted to evaluate oxidative stress markers by spectrophotometry; phosphorylation of AMP-activated protein kinase, growth hormone receptor 1a, and neuropeptide Y expression were determined by Western blot. RESULTS: There was a significant increase in the consumption of food in the experimental groups. The level of malondialdehyde decreased in the 7-day group (33%) and increased significantly in the 28-day group (90%), glutathione peroxidase activity increased in the 7-day group (70%) and decreased in the 28-day group (34%), and the phosphorylation of AMP-activated protein kinase increased significantly in the 28-day group (86%). Under ex-vivo conditions in animals with 28 days of hyperglycemia, glutathione peroxidase activity increased 195%, the malondialdehyde level decreased 87%, phosphorylation of AMP-activated protein kinase decreased 53%, and growth hormone receptor 1a expression decreased 66%, when treating hyperglycemic hypothalamic tissue with an antioxidant. NPY expression increased in hyperglycemia, and antioxidant treatment did not regulate its expression. CONCLUSIONS: The activation of AMP-activated protein kinase is related with an increase in oxidative stress markers in hyperglycemic and hyperphagic rats.