Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Survival Outcomes of Patients With Breast Cancer in a Mexican Population.

PURPOSE: The Instituto Mexicano del Seguro Social is a tripartite contribution providing care to more than 74 million beneficiaries, representing more than 50% of the country's general population. This study aims to describe the survival outcomes and clinicopathologic characteristics of patients with breast cancer at our Center. METHODS: A retrospective cohort of patients with breast cancer treated between January 2012 and December 2020 was conducted. Survival outcomes were assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: There were 5,264 patients included with a median follow-up of 54.9 months. Forty-three percent (n = 2,274) were diagnosed in stage I-IIA, 43.1% (n = 2,269) in stage IIB-III, and 7% (n = 383) in stage IV. At 5 years, disease-free survival was 74.9% (95% CI, 73.5 to 76.3) and overall survival (OS) 90.4% (95% CI, 89.4 to 91.3). For stage IV, it was 22.7% (95% CI, 17.3 to 28.5). High histologic grade (hazard ratio, 1.51 [95% CI, 1.34 to 1.7]; P < .001) and lymphovascular invasion (LVI; hazard ratio, 1.85 [95% CI, 1.62 to 2.1]; P < .001) were associated with a higher risk of recurrence. CONCLUSION: Histologic grade and LVI should be considered in the decision to treat with adjuvant chemotherapy in sites where genomic signatures are not available. Our OS data are comparable with other Mexican series; however, it is lower in stage IV. Much remains to be done at the national level, mainly regarding access to additional therapies for each breast cancer subtype. This work contributes to the evaluation of areas for improvement in outcomes in our population.

Factors related to bladder catheterization in older patients and its possible association with prognosis: results of the EDEN-30 study. / Factores relacionados con la práctica de sondaje vesical en urgencias en pacientes ancianos y su relación con el pronóstico: resultados del estudio EDEN-30.

OBJECTIVES: The aims of this study in the Emergency Department and Elder Needs (EDEN) series were to explore associations between clinical variables on arrival at the ED (baseline) and the insertion of a bladder catheter, and the relation between catheterization and deterioration to a more complex or serious clinical state. MATERIAL AND METHODS: Included were all patients aged 65 years or older attended during 1 week in 52 Spanish EDs. Patients were grouped according to whether a bladder catheter was or was not inserted in the ED. We used multivariable logistical regression to explore associations between catheterization and patient age, sex, 10 comorbidities, 7 baseline status variables, and 6 clinical variables. Progression was considered serious or complex if the patient died or required hospitalization, a prolonged hospital stay, or discharge to a care facility. We also explored the association between age and catheterization using adjusted restricted cubic spline (RCS) curves with a cutoff value of 65 years. RESULTS: Participating hospitals enrolled 24 573 patients; bladder catheters were inserted in 976 (4%). Of these, 44.3% were discharged from the ED. Fifteen of the 24 variables were independently associated with bladder catheterization. Factors with the strongest associations according to odds ratios (ORs) were impaired consciousness (OR, 2.50; 95% CI, 1.90-3.30), dehydration (OR, 2.24; 95% CI, 1.85-2.72), and male sex (OR, 2.12; 95% CI, 1.84- 2.44). Age 80 years or older was also associated with bladder catheterization (OR, 1.17; 95% CI, 1.01-1.358). The adjusted RCS curves showed a progressive linear increase in the probability of catheterization with age. The increase was constant in men and stabilized after the age of 85 years in women (P-interaction .001). Bladder catheterization was associated with hospitalization (OR, 2.31; 95% CI, 1.99-2.68), intensive care unit admission (OR, 4.64; 95% CI, 3.04-7.09), prolonged stay in the ED for discharged patients (OR, 2.28; 95% CI, 1.75-2.96), in-hospital death (OR, 1.99; 95% CI, 1.54-2.57), and 30-day death (OR, 1.66; 95% CI, 1.33-2.08). No associations were found between catheterization and prolonged hospital stay (OR, 1.11; 95% CI, 0.92-1.34) or need for a care facility on discharge (OR, 1.50; 95% CI, 0.98-2.29). CONCLUSION: Certain patient characteristics and baseline clinical conditions are associated with bladder catheterization in patients of advanced age. The main factors were decreased consciousness, dehydration, and male sex. Even after adjustment for related factors, catheterization is independently associated with progression to more complex or serious clinical states.

OBJETIVO: Estudiar las variables de estado basal y de situación clínica a la llegada a urgencias relacionadas con la práctica de sondaje vesical (SV) en pacientes mayores, y si el SV está asociado a una evolución más compleja o grave. METODO: Se incluyeron todos los pacientes de edad 65 años atendidos durante una semana en 52 servicios de urgencias (SU) españoles, que fueron clasificados en función de si se practicó o no SV en el SU. Se investigó la relación de SV con edad, sexo, 10 variables de comorbilidad, 7 de estado basal y 6 de situación clínica mediante un modelo de regresión logística multivariable. Se consideró la evolución como grave o compleja si existió necesidad de hospitalización, estancia prolongada, necesidad de residencia al alta o muerte. La relación entre edad y SV se exploró también mediante curvas spline cúbicas restringidas (SCR) ajustadas, tomando la edad de 65 años como referencia. RESULTADOS: Se incluyeron 24.573 pacientes, de los que 976 (4%) recibieron SV. De éstos, el 44,3% fueron dados de alta desde urgencias. De las 25 variables exploradas, 15 se relacionaron independientemente con el SV, y las más manifiestas fueron disminución de consciencia (OR = 2,50, IC 95% = 1,90-3,30), deshidratación (OR = 2,24, IC 95% = 1,85-2,72) y sexo masculino (OR = 2,12, IC 95% = 1,84-2,44). La edad 80 años también se asoció a SV (OR = 1,17, IC 95% = 1,01-1,358), y las curvas SCR ajustadas mostraron un incremento progresivo y lineal de la probabilidad de SV con la edad, constante en hombres y que se estabilizaba a partir de los 85 años en mujeres (p interacción 0,001). El SV se asoció a necesidad de hospitalización (OR = 2,31, IC 95% = 1,99-2,68), hospitalización en intensivos (OR = 4,64, IC 95% = 3,04-7,09), estancia prolongada en urgencias en los pacientes dados de alta (OR = 2,28, IC 95% = 1,75-2,96) y mortalidad intrahospitalaria (OR = 1,99, IC 95% = 1,54-2,57) y a 30 días (OR=1,66, IC 95% = 1,33-2,08), pero no con hospitalización prolongada (OR = 1,11, IC 95% = 0,92-1,34) ni con necesidad de residencia al alta (OR = 1,50, IC 95% = 0,98-2,29). CONCLUSIONES: Determinadas características del paciente mayor y de su estado clínico se asocian con realizar un SV en urgencias, entre las que destacan la disminución de consciencia, la deshidratación y el sexo masculino. Aun teniendo en cuenta los factores asociados a SV en urgencias, este procedimiento se asocia independientemente con evoluciones más complejas o graves.

Design and evaluation of a digital health intervention with proactive follow-up by nurses to improve healthcare and outcomes for patients with breast cancer in Mexico: protocol for a randomised clinical trial.

INTRODUCTION: Nearly 30 000 Mexican women develop breast cancer annually, frequently presenting unmet supportive care needs. In high-income countries, incorporating electronic patient-reported outcomes (ePROs) into cancer care has demonstrated potential for increasing patient-centred care and reducing unmet needs. No such ePRO interventions have been implemented in Mexico. This paper presents the study protocol for designing and evaluating an ePRO digital health application combined with proactive follow-up by nurses. METHODS AND ANALYSIS: We designed a two-component intervention for women receiving breast cancer treatment: a responsive web application for monitoring ePROs and clinical algorithms guiding proactive follow-up by nurses. We will conduct a pilot test of the intervention with 50 patients with breast cancer for 6 weeks to assess feasibility and adjust the application. We will conduct a parallel arm randomised controlled trial assigning 205 patients each to intervention and control in one of Mexico's largest public oncology hospitals. The intervention will be provided for 6 months, with additional 3 months of post-intervention observation. The control group will receive usual healthcare and a list of breast cancer information sources. Women diagnosed with stages I, II or III breast cancer who initiate chemotherapy and/or radiotherapy will be invited to participate. The primary study outcome will be supportive care needs; secondary outcomes include global quality of life and breast symptoms. Information on the outcomes will be obtained through web-based self-administered questionnaires collected at baseline, 1, 3, 6 and 9 months. ETHICS AND DISSEMINATION: The National Research and Ethics Committees of the Mexican Institute of Social Security approved the study (R-2021-785-059). Participants will sign an informed consent form prior to their inclusion. Findings will be disseminated through a policy brief to the local authorities, a webinar for patients, publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05925257.

An Interuniversity Competition for Medical Students to Learn Radiology in the Second Life Metaverse.

PURPOSE: The aim of this study was to evaluate an interuniversity competition online to learn radiology held in a 3-D virtual world, the Second Life metaverse, by analyzing the results of the game and students' perceptions. METHODS: Medical students voluntarily participated in teams of four, for 6 weeks, successively covering radiologic anatomy and radiologic semiology of the chest, abdomen, and musculoskeletal. Each week, participants had 4.5 days to study self-learning presentations and 2.5 days to complete an individual multiple-choice test and a team task, the results of which determined the game's ranking. Participants were asked to complete a cognitive-load test, a perception questionnaire, and a postexposure knowledge test. RESULTS: The competition was repeated for 2 years (editions), in 2020 and 2021. Seventy-five of 102 teams (73.5%) registered completed the game; 76% of them included third-year students. The average percentage of correct answers in the individual tests and team tasks was 74.2 ± 15.1 and 71.6 ± 14.7 respectively, without significant differences between both competitions. In general, the experience was valued positively (scores >8 on a 10-point scale). A lower perception score was found in 2021 among students from universities other than the organizing university, showing a positive correlation with the in-game score. CONCLUSIONS: An interuniversity competition in the Second Life metaverse for undergraduate learning radiology is feasible and reproducible. Participating medical students considered it interesting and useful and also identified this activity during the 2 years of the coronavirus disease 2019 pandemic as a playful learning and social interaction experience.

Equilibrio ocupacional en adultas mayores rurales y urbanas, región de los lagos, Chile / Occupational balance in rural and urban aged females, los lagos region, Chile

Objetivos: investigar desde la Ciencia de la Ocupación la influencia del contexto en el equilibrio ocupacional de mujeres mayores de la ciudad de Puerto Montt. Métodos: metodología cualitativa, transversal, la población corresponde a ocho personas adultas mayores que habitan en la Provincia de Llanquihue; cuatro pertenecen a una agrupación de personas adultas mayores de zona rural y cuatro residen en zona urbana, seleccionadas aleatoriamente. Resultados: dentro de los resultados generales, se observa que, los relatos están enmarcados principalmente en cuatro categorías: equilibrio ocupacional, ocupaciones, satisfacción personal y bienestar. Conclusiones: existen diferencias en el concepto de equilibrio ocupacional de adultas mayores residentes en ambas zonas, viéndose afectado por la salud, limitando la participación en ocupaciones. Las residentes en zona rural perciben mayor equilibrio ocupacional en comparación con las de zona urbana, destacando satisfacción con la vida, estrechamente relacionada con la maternidad.(AU)

Objective: To investigate, from the perspective of Occupational Science, the influence of context on the occupational balance of older women in the city of Puerto Montt. Methods: Qualitative, cross-sectional methodology. The sample consists of 8 older women residing in the Llanquihue province: 4 belong to an Association of Aged Females from a rural area, and 4 reside in an urban area, randomly selected. Results: Within the general results, the findings are mainly categorized into four themes: occupational balance, occupations, personal satisfaction, and well-being. Conclusions: Differences exist in the concept of occupational balance among older women residing in both areas, influenced by health conditions that limit participation in occupations. Residents in rural areas perceive greater occupational balance compared to those in urban areas, with a notable emphasis on life satisfaction, closely linked to motherhood.(AU)

Socioeconomic inequality in Latin America and the Caribbean: the post-pandemic future for the training of health professionals. / Desigualdades socioeconômicas na América Latina e Caribe: o futuro pós-pandemia para a formação profissional na saúde.

Inequality is a global, structural problem that is particularly marked in the world's poorest countries. The covid-19 pandemic exacerbated this historic problem in Latin America and the Caribbean and deepened uncertainties in relation to basic human needs. This study presents an overview of the subject on the basis of official reports from international agencies (PAHO, WHO, ECLAC) between 2019 and 2022 and discusses some paths for the training of health professionals in Brazil. It also investigates how health practices could be changed to ensure greater social protection for vulnerable populations, based on the proposals of Paulo Freire and Edgar Morin, which highlight current social and health problems.

A desigualdade é um problema global e estrutural que aflige com maior intensidade as populações dos países mais empobrecidos. A pandemia da covid-19 agravou esse problema histórico na América Latina e Caribe e aprofundou as incertezas relacionadas às necessidades humanas básicas. O estudo apresenta um painel sobre o tema produzido pelos relatórios oficiais de agências internacionais (Opas, OMS, Cepal) entre 2019 e 2022, e discute alguns caminhos para a formação profissional em saúde no Brasil, bem como as mudanças nas práticas em saúde que podem impulsionar a proteção social das populações vulneráveis, com base nas propostas de Paulo Freire e Edgar Morin, que colocam em evidência as problemáticas sociossanitárias atuais.

Constitutional MLH1 Methylation Is a Major Contributor to Mismatch Repair-Deficient, MLH1-Methylated Colorectal Cancer in Patients Aged 55 Years and Younger.

BACKGROUND: Most mismatch repair-deficient (MMRd) colorectal cancer (CRC) cases arise sporadically, associated with somatic MLH1 methylation, whereas approximately 20% have germline mismatch repair pathogenic variants causing Lynch syndrome (LS). Universal screening of incident CRC uses presence of MLH1 methylation in MMRd tumors to exclude sporadic cases from germline testing for LS. However, this overlooks rare cases with constitutional MLH1 methylation (epimutation), a poorly recognized mechanism for LS. We aimed to assess the frequency and age distribution of constitutional MLH1 methylation among incident CRC cases with MMRd, MLH1-methylated tumors. METHODS: In retrospective population-based studies, we selected all CRC cases with MMRd, MLH1-methylated tumors, regardless of age, prior cancer, family history, or BRAF V600E status, from the Columbus-area HNPCC study (Columbus) and Ohio Colorectal Cancer Prevention Initiative (OCCPI) cohorts. Blood DNA was tested for constitutional MLH1 methylation by pyrosequencing and real-time methylation-specific PCR, then confirmed with bisulfite-sequencing. RESULTS: Results were achieved for 95 of 98 Columbus cases and all 281 OCCPI cases. Constitutional MLH1 methylation was identified in 4 of 95 (4%) Columbus cases, ages 34, 38, 52, and 74 years, and 4 of 281 (1.4%) OCCPI cases, ages 20, 34, 50, and 55 years, with 3 showing low-level mosaic methylation. Mosaicism in blood and normal colon, plus tumor loss of heterozygosity of the unmethylated allele, demonstrated causality in 1 case with sample availability. Age stratification showed high rates of constitutional MLH1 methylation among younger patients. In the Columbus and OCCPI cohorts, respectively, these rates were 67% (2 of 3) and 25% (2 of 8) of patients aged <50 years but with half of the cases missed, and 75% (3 of 4) and 23.5% (4 of 17) of patients aged ≤55 years with most cases detected. CONCLUSIONS: Although rare overall, a significant proportion of younger patients with MLH1-methylated CRC had underlying constitutional MLH1 methylation. Routine testing for this high-risk mechanism is warranted in patients aged ≤55 years for a timely and accurate molecular diagnosis that will significantly alter their clinical management while minimizing additional testing.

POLE-Mutant Colon Cancer Treated with PD-1 Blockade Showing Clearance of Circulating Tumor DNA and Prolonged Disease-Free Interval.

Colon cancer with high microsatellite instability is characterized by a high tumor mutational burden and responds well to immunotherapy. Mutations in polymerase ɛ, a DNA polymerase involved in DNA replication and repair, are also associated with an ultra-mutated phenotype. We describe a case where a patient with POLE-mutated and hypermutated recurrent colon cancer was treated with pembrolizumab. Treatment with immunotherapy in this patient also led to the clearance of circulating tumor DNA (ctDNA). ctDNA is beginning to emerge as a marker for minimal residual disease in many solid malignancies, including colon cancer. Its clearance with treatment suggests that the selection of pembrolizumab on the basis of identifying a POLE mutation on next-generation sequencing may increase disease-free survival in this patient.

PTPN2 Is a Critical Regulator of Ileal Paneth Cell Viability and Function in Mice.

BACKGROUND & AIMS: Loss-of-function variants in the PTPN2 gene are associated with increased risk of inflammatory bowel disease. We recently showed that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice, restricting expansion of a small intestinal pathobiont associated with inflammatory bowel disease. Here, we aimed to identify how Ptpn2 loss affects ileal IEC subtypes and their function in vivo. METHODS: Constitutive Ptpn2 wild-type, heterozygous, and knockout (KO) mice, as well as mice with inducible deletion of Ptpn2 in IECs, were used in the study. Investigation was performed using imaging techniques, flow cytometry, enteroid culture, and analysis of gene and protein levels of IEC markers. RESULTS: Partial transcriptome analysis showed that expression of Paneth cell-associated antimicrobial peptides Lyz1, Pla2g2a, and Defa6 was down-regulated markedly in Ptpn2-KO mice compared with wild-type and heterozygous. In parallel, Paneth cell numbers were reduced, their endoplasmic reticulum architecture was disrupted, and the endoplasmic reticulum stress protein, C/EBP-homologous protein (CHOP), was increased in Ptpn2-KO mice. Despite reduced Paneth cell number, flow cytometry showed increased expression of the Paneth cell-stimulatory cytokines interleukin 22 and interferon γ+ in CD4+ T cells isolated from Ptpn2-KO ileum. Key findings in constitutive Ptpn2-KO mice were confirmed in epithelium-specific Ptpn2ΔIEC mice, which also showed impaired lysozyme protein levels in Paneth cells compared with Ptpn2fl/fl control mice. CONCLUSIONS: Constitutive Ptpn2 deficiency affects Paneth cell viability and compromises Paneth cell-specific antimicrobial peptide production. The observed effects may contribute to the increased susceptibility to intestinal infection and dysbiosis in these mice.

Improving Oral Presentation Skills for Radiology Residents through Clinical Session Meetings in the Virtual World Second Life.

BACKGROUND: The objective of this study was to conduct a clinical session meeting in the virtual world of Second Life to improve the oral presentation skills of radiology residents and to assess the perception of the attendees. METHODS: A clinical session meeting (10 two-hour sessions over four weeks), where participants presented their own clinical sessions, followed by a turn of interventions by the attendees, was designed and carried out. Attendees were asked to complete an evaluation questionnaire. Descriptive statistics were performed. RESULTS: Twenty-eight radiology residents attended the meeting, and 23 (81.2%) completed the evaluation questionnaire; 95.7-100% of them agreed that the virtual environment was attractive and suitable for holding the meeting and that the content was appropriate for their training as residents. They rated with ≥8.9 points (from 1 to 10) different aspects of the experience, highlighting the role of teachers (9.7 ± 0.6) and the usefulness of their training (9.4 ± 0.9). CONCLUSIONS: Second Life can be used effectively to train oral communication skills in public, in an environment perceived as attractive and suitable for learning, through an experience described by the attendees as interesting and useful, highlighting the advantages of social contact with their peers.

MLH1-methylated endometrial cancer under 60 years of age as the "sentinel" cancer in female carriers of high-risk constitutional MLH1 epimutation.

OBJECTIVE: Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to determine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1-methylated tumors. METHODS: We screened blood for constitutional MLH1 methylation using pyrosequencing and real-time methylation-specific PCR in patients with MMRd, MLH1-methylated EC ascertained from (i) cancer clinics (n = 4, <60 years), and (ii) two population-based cohorts; "Columbus-area" (n = 68, all ages) and "Ohio Colorectal Cancer Prevention Initiative (OCCPI)" (n = 24, <60 years). RESULTS: Constitutional MLH1 methylation was identified in three out of four patients diagnosed between 36 and 59 years from cancer clinics. Two had mono-/hemiallelic epimutation (∼50% alleles methylated). One with multiple primaries had low-level mosaicism in normal tissues and somatic "second-hits" affecting the unmethylated allele in all tumors, demonstrating causation. In the population-based cohorts, all 68 cases from the Columbus-area cohort were negative and low-level mosaic constitutional MLH1 methylation was identified in one patient aged 36 years out of 24 from the OCCPI cohort, representing one of six (∼17%) patients <50 years and one of 45 patients (∼2%) <60 years in the combined cohorts. EC was the first/dual-first cancer in three patients with underlying constitutional MLH1 methylation. CONCLUSIONS: A correct diagnosis at first presentation of cancer is important as it will significantly alter clinical management. Screening for constitutional MLH1 methylation is warranted in patients with early-onset EC or synchronous/metachronous tumors (any age) displaying MLH1 methylation.

Assessing pH-dependent activities of virulence factors secreted by Candida albicans.

Candida albicans is an opportunistic pathogen that can thrive under adverse conditions including suboptimal pH, nutrient scarcity, and low levels of oxygen. Its pathogenicity is associated with the production of virulence factors such as extracellular hydrolytic enzymes and toxins. This study was aimed at determining the effect of external pH, substrate nature, and strain origin on protease, lipase, and hemolysin production. To achieve this objective, agar plate assays were performed at pH 5.0, 6.5, and 7.5 with substrates suitable for the detection of each family of enzymes. Moreover, the study was conducted with 20 clinical C. albicans isolates from blood, oral cavity, skin, urine, and vagina. The hydrolytic zones formed around the colonies were further measured to calculate the Ez (enzymatic zone) indexes. We found that detection of proteases in skim milk agar plates was possible for most isolates only at pH 5 (80%) and pH 6.5 (75%), whereas BSA plates could confer protease detection exclusively at pH 5 (80%). Similarly, the percentage of isolates possessing lipolytic activities was higher at pH 5 (90%) than at pH 6.5 (70%) and pH 7.5 (35%). In contrast, hemolytic activities were detected in all isolates at pH 6.5 and 7.5 but not at pH 5. Further analysis revealed that some differences in the detected activities could potentially be attributed to the anatomical origin of these isolates. Collectively, these findings suggest that the pH of the site of infection might be critical for mimicking the microenvironment employed to experimentally discover the key virulence factors.

Desigualdades socioeconômicas na América Latina e Caribe: o futuro pós-pandemia para a formação profissional na saúde / Socioeconomic inequality in Latin America and the Caribbean: the post-pandemic future for the training of health professionals

Resumo A desigualdade é um problema global e estrutural que aflige com maior intensidade as populações dos países mais empobrecidos. A pandemia da covid-19 agravou esse problema histórico na América Latina e Caribe e aprofundou as incertezas relacionadas às necessidades humanas básicas. O estudo apresenta um painel sobre o tema produzido pelos relatórios oficiais de agências internacionais (Opas, OMS, Cepal) entre 2019 e 2022, e discute alguns caminhos para a formação profissional em saúde no Brasil, bem como as mudanças nas práticas em saúde que podem impulsionar a proteção social das populações vulneráveis, com base nas propostas de Paulo Freire e Edgar Morin, que colocam em evidência as problemáticas sociossanitárias atuais.

Abstract Inequality is a global, structural problem that is particularly marked in the world's poorest countries. The covid-19 pandemic exacerbated this historic problem in Latin America and the Caribbean and deepened uncertainties in relation to basic human needs. This study presents an overview of the subject on the basis of official reports from international agencies (PAHO, WHO, ECLAC) between 2019 and 2022 and discusses some paths for the training of health professionals in Brazil. It also investigates how health practices could be changed to ensure greater social protection for vulnerable populations, based on the proposals of Paulo Freire and Edgar Morin, which highlight current social and health problems.

Multimodal Imaging in Iris Vascular Tumors: A Case Series.

Iris vascular tumors are very unusual and tend to affect middle-aged and older adults. We report a case series of four adult patients with vascular alterations of the iris. Two patients were diagnosed with simple iris arteriovenous malformation (IAVM) and two with iris microhemangiomatosis (IM). Although the diagnosis is typically clinic, multimodal imaging techniques, especially anterior segment fluorescein angiography (AS-FA), anterior segment optical coherence tomography (AS-OCT), and optical coherence tomography angiography (OCT-A), improve the accuracy and delimitation of their attributes and extension. Differential diagnosis with angle or iris neovascularization, melanoma, and other iris vascular tumors is essential to avoid unnecessary tests and treatments.

Methylated Septin9 (mSEPT9): A promising blood-based biomarker for the detection and screening of early-onset colorectal cancer.

Early-onset colorectal cancer (EOCRC), defined as a diagnosis under age 50, is an emerging public health burden. As many of these individuals fall outside of screening guidelines, the development of a minimally invasive, accurate screening modality for this population is warranted. We evaluated the FDA-approved blood-based biomarker methylated Septin9 (mSEPT9) test as screening tool for EOCRC. EOCRC plasma, healthy plasma, and serum-free conditioned media from cancer cell lines was collected. Cell-free DNA (cfDNA) was isolated and bisulfite converted for use in the assay. mSEPT9 and ACTB measured using Epi proColon® V2.0. EOCRC plasma was collected at Massachusetts General Hospital (2005-2019) and controls were collected at the National Institutes of Health and by ZenBio Inc. (prior to 2019). Twenty-seven EOCRC cases, 48 healthy controls <50 years old, and 39 healthy controls ≥50 years old were included in this study. mSEPT9 was detected more frequently in EOCRC cases (88.9%) compared to healthy controls age <50 (4.2%) and ≥50 (15.4%), respectively (p<0.001). The sensitivity, specificity, positive predictive value, and negative predictive values of the mSEPT9 assay to detect EOCRC was 90.8% (95% CI: 84.7-96.9%), 88.9% (95% CI: 77.0-100.0%), 96.3% (95% CI: 92.3-100.0%), and 75.0% (95% CI 60.0-90.0%), respectively, compared to all healthy controls. mSEPT9 cfDNA level was an independent predictor of survival (p=0.02). mSEPT9 is a sensitive and specific biomarker for EOCRC detection. These results suggest that mSEPT9 may be useful in the detection of EOCRC, providing a minimally invasive method for screening in this growing population of CRC patients.

Proteína tau como biomarcador en Alzheimer preclínico / Tau protein as a biomarker in preclinical Alzheimer's disease

El desarrollo de biomarcadores de la proteína tau para el diagnóstico temprano de la enfermedad de Alzheimer (EA) emerge como un desafío fundamental, pudiendo mejorar la efectividad de un tratamiento preventivo o que enlentezca la progresión de la enfermedad. Esta revisión analiza las evidencias que justificarían el uso de la proteína tau como biomarcador en Alzheimer preclínico. Para esto se seleccionaron artículos científicos (2011-2021) que incluyeran a la proteína tau en plasma y plaquetas como biomarcador. La presencia de la proteína tau fosforilada en el líquido cefalorraquídeo presenta limitaciones por su carácter invasivo mientras que las técnicas de imagen son costosas. La medición de tau en plaquetas se correlaciona con la severidad de la demencia, y sería útil en el seguimiento de la EA. Sin embargo, la pertinencia de su uso en la detección temprana de EA se mantiene en discusión. La presencia de proteína tau fosforilada en plasma correspondería al biomarcador con mayor nivel de desarrollo, respecto de beta amiloide. La proteína tau plasmática detecta la EA con gran precisión en casos de demencia y ha sido validada por estudios neuropatológicos. p-tau217 plasmática medida por primera vez junto a técnicas de imagen, fue importante en la etapa preclínica de EA pudiendo predecir la formación de ovillos neurofibrilares. La correlación entre especies fosforiladas de tau en plasma y EA preclínica ha sido bien establecida, por lo que su uso como biomarcador podría ser de utilidad para la comprensión del proceso fisiopatológico de la neurodegeneración y la detección temprana de EA

The development of tau protein biomarkers for the early diagnosis of Alzheimer's disease (AD) emerges as a fundamental challenge, which may improve the effectiveness of preventive treatment or slow the progression of the disease. This review analyzes the evidence that would justify the use of tau protein as a biomarker in preclinical Alzheimer's disease. For this purpose, we selected scientific articles (2011-2021) that included tau protein in plasma and platelets as a biomarker. Phosphorylated tau protein in cerebrospinal fluid has limitations due to its invasiveness, while imaging techniques are expensive. The tau measurement in platelets correlates with the severity of dementia and would be helpful in the follow-up of AD. However, the relevance of its use in the early detection of AD remains under discussion. Plasma phosphorylated tau protein would correspond to the biomarker with the highest level of development for beta-amyloid. Plasma tau protein detects AD with high accuracy in cases of dementia, and neuropathological studies validate its use. Plasma p-tau217 measured for the first time with imaging techniques was important in preclinical AD and could predict the formation of neurofibrillary tangles. The correlation between plasma phosphorylated tau species and preclinical AD is well-established, so its use as a biomarker would help understand the pathophysiological process of neurodegeneration and early AD detection.

Circulating tumor DNA dynamics and response to immunotherapy in colorectal cancer.

Circulating tumor DNA (ctDNA) is increasingly being investigated as a tool to detect minimal residual disease in resected, stage I-III colorectal cancer. Recent ctDNA studies have indicated that detection of ctDNA following surgery for resectable colorectal cancer confers a significantly higher risk of recurrence than those with negative ctDNA postoperatively. In those with postoperative ctDNA positivity, clearance of minimal residual disease with adjuvant chemotherapy is a positive prognostic indicator. Lastly, ctDNA has demonstrated superior sensitivity to the conventional blood tumor marker carcinoembryonic antigen (CEA) and can offer median lead times of up to 11 months for radiographic detection of recurrence during the surveillance of resected, stage I-III colorectal cancer. In metastatic colorectal cancer (mCRC), there is growing evidence to suggest that plasma ctDNA can be used to monitor tumor response to conventional chemotherapy as well. The present case series demonstrated that plasma ctDNA is a predictor of tumor response to immunotherapy in patients with mCRC that are microsatellite stable or microsatellite instability high. Plasma ctDNA could serve as a dynamic marker of immunotherapy response even in colorectal tumors that were CEA non-producers. Overall, these findings add to ongoing efforts to establish the role of plasma ctDNA in monitoring response to immunotherapy in CRC.

Modos de vida durante la pandemia por COVID 19: experiencia en territorio de la zona sur de la ciudad de Córdoba / Ways of living during the COVID19 pandemic. Experience in the territory of the South area of the City of Córdoba

La pandemia por COVID19 impuso cambios en los modos de vida de las familias con las que trabajamos desde la Carrera de Especialización en Medicina Familiar, en el territorio "Las Tablitas", Villa El Libertador, Córdoba. Objetivos: Explorar los modos de vida de las familias de "Las Tablitas'' durante el período de pandemia 2020-2021. Metodología: estudio cualitativo, diseño fenomenológico y enfoque crítico. Se realizaron 10 entrevistas en profundidad con criterio de saturación teórica. Resultados: Se reconocen las modificaciones ocurridas durante el periodo aislamiento social preventivo obligatorio en la dinámica familiar. Los trabajos remunerados en condiciones irregulares fueron interrumpidos. El trabajo doméstico no remunerado aumentó para las mujeres, quienes sumaron las tareas educativas, presentando dificultades para el acompañamiento escolar. Las mujeres asumieron tareas de cuidado y gestión para la subsistencia sin problematizar ese rol. La atención de problemas no-COVID fue postergada, principalmente por miedo a los contagios. Si bien las redes comunitarias se activaron para resolver la situación alimentaria, con organización de copas de leche y ollas populares, se profundizó el aislamiento de las familias. Problemáticas planteadas: el agua, la falta de cloacas, el aumento de hechos delictivos y el deterioro ambiental. Conclusión: Reconocer los modos de vivir de las familias, explorar las representaciones de las mujeres, sus modos de organización familiar y prácticas de cuidado en tiempos de pandemia constituye una clave para poder diseñar estrategias en conjunto, oportunas y adecuadas (AU)

The COVID19 pandemic imposed changes in the lifestyles of the families with whom we work as of 2016 the Specialization Career in Family Medicine in the territory "Las Tablitas", Villa El Libertador, Córdoba. Explore the lifestyles of the families of "Las Tablitas" during the 2020-2021 pandemic period. Recognize health-disease processes, health care modes, and family and collective care practices. Qualitative study, phenomenological design, and critical approach. 10 in-depth interviews were conducted with key informants with theoretical saturation criteria. The modifications that occurred during the period of compulsory preventive social isolation in family dynamics are recognized. Most of the paid jobs under irregular conditions were interrupted. Unpaid domestic work increased for women, who added educational tasks, presenting difficulties for school accompaniment. The women with whom they assume care and management tasks for subsistence without problematizing that role. Health care for various chronic diseases or emerging situations was postponed, mainly due to fear of COVID infections. Although the community networks were activated to resolve the food situation, with the organization of milk cups and popular pots, the isolation within the families deepened. The problems raised with respect to the neighborhood are mainly the question of habitat, with water as its axis, the lack of sewers, the increase in criminal acts and environmental deterioration. The recognition of the ways of living of families, the exploration of the representations of women, their ways of family organization and care practices in times of pandemic constitute a key to be able to design timely strategies to comprehensively the Health - Disease - Attention - Care Process (AU)

Large Cancer Pedigree Involving Multiple Cancer Genes including Likely Digenic MSH2 and MSH6 Lynch Syndrome (LS) and an Instance of Recombinational Rescue from LS.

Lynch syndrome (LS), caused by heterozygous pathogenic variants affecting one of the mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2), confers moderate to high risks for colorectal, endometrial, and other cancers. We describe a four-generation, 13-branched pedigree in which multiple LS branches carry the MSH2 pathogenic variant c.2006G>T (p.Gly669Val), one branch has this and an additional novel MSH6 variant c.3936_4001+8dup (intronic), and other non-LS branches carry variants within other cancer-relevant genes (NBN, MC1R, PTPRJ). Both MSH2 c.2006G>T and MSH6 c.3936_4001+8dup caused aberrant RNA splicing in carriers, including out-of-frame exon-skipping, providing functional evidence of their pathogenicity. MSH2 and MSH6 are co-located on Chr2p21, but the two variants segregated independently (mapped in trans) within the digenic branch, with carriers of either or both variants. Thus, MSH2 c.2006G>T and MSH6 c.3936_4001+8dup independently confer LS with differing cancer risks among family members in the same branch. Carriers of both variants have near 100% risk of transmitting either one to offspring. Nevertheless, a female carrier of both variants did not transmit either to one son, due to a germline recombination within the intervening region. Genetic diagnosis, risk stratification, and counseling for cancer and inheritance were highly individualized in this family. The finding of multiple cancer-associated variants in this pedigree illustrates a need to consider offering multicancer gene panel testing, as opposed to targeted cascade testing, as additional cancer variants may be uncovered in relatives.