Community Health Workers Deliver Mental Health Intervention to Uninsured Latinx in Baltimore: Evaluation and Lessons Learned in a Pilot Program.

BACKGROUND: Implementation of evidence-based interventions to reduce depression among uninsured Latinx patients who are at high risk of depression are rare. OBJECTIVES: Our goal was to evaluate Strong Minds, a language and culturally tailored, evidence-based intervention adapted from cognitive behavioral therapy (CBT) for mild-moderate depression and anxiety, delivered by community health workers (CHWs) in Spanish to uninsured Latinx immigrants. METHODS: As part of the pilot, 35 participants, recruited from a free community primary care clinic, completed Strong Minds. Assessments and poststudy interviews were conducted. Paired t-tests were used to assess change of depressive symptoms at 3 and 6 months. LESSONS LEARNED: CHW delivery of depression care to this population was feasible and among those who completed the program, preliminary evidence of depression outcomes suggests potential benefit. CHWs had specific training and support needs related to mental health care delivery. CONCLUSIONS: Further implementation studies of depression care interventions using CHWs for underserved Latinx is needed.

Quantifying Imaging Agent Binding and Dissociation in 3-D Cancer Spheroid Tissue Culture Using Paired-Agent Principles.

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3-D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody mimetic) and IRDye-700DX carboxylate in 3-D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR-targeted ABY-029 agent. A statistically significant correlation was observed between apparent association rate constant (k3) and the receptor concentration experimentally and in simulations (r = 0.99, p < 0.05). A statistically significant difference was found between effective k3 (apparent rate constant of ABY-029 binding to EGFR) values for cell lines with varying levels of EGFR expression (p < 0.05), with no significant difference found between cell lines and controls for other fit parameters. Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3-D tumor spheroid models can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.

Causas precipitantes de crisis hiperglicémicas agudas en pacientes internados en el Centro Médico Nacional - Hospital Nacional / Precipiting causes of acute hyperglycemic crisis in patients in the Centro Médico Nacional - Hospital Nacional

Introducción: las crisis hiperglicémicas agudas son las emergencias endocrinológicas más frecuentes en la práctica clínica y junto a la hipoglucemia se las describe como las complicaciones metabólicas agudas graves del paciente diabético. Objetivo: identificar las causas precipitantes de crisis hiperglicémicas agudas en pacientes internados en el Centro Médico - Hospital Nacional. Metodología: estudio observacional, descriptivo, de corte transversal de pacientes internados en el Centro Médico Hospital Nacional, durante el periodo de mayo 2021 a octubre del 2023. Los datos fueron obtenidos con la revisión de las fichas clínicas. Resultados: de los 100 pacientes evaluados, la crisis hiperglicémica aguda más frecuente fue la Cetoacidosis diabética (CAD) 53 %, seguida del Estado hiperosmolar hiperglicémico (EHH) 25 % y el estado mixto 22 %. Los desencadenantes más frecuentes fueron el abandono del tratamiento, debut de la enfermedad e infecciones. La mortalidad global fue del 12 %. Conclusión: la causa más frecuente de descompensación fueron el abandono del tratamiento, la diabetes de novo y procesos infecciosos.

Introduction: hyperglycemic crises are the most frequent endocrinological emergencies in clinical practice and, along with hypoglycemia, are described as serious acute metabolic complications in diabetic patients. Objective: to identify the precipiting causes of acute hyperglycemic crisis in hospitalized patients in the Centro Médico Nacional - Hospital National. Methodology: this was an observational, descriptive, cross -sectional study of patients hospitalized at the Centro Médico Nacional - Hospital National, from May 2021 to October 2023. The data were obtained from a review of the clinical records. Results: Of the 100 patients evaluated, the most frequent acute hyperglycemic crisis was diabetic ketoacidosis (CAD) 53 %, followed by the hyperglycemic hyperosmolar state (EHH) 25 % and the mixed state 22 %. The most frequent triggers were the abandonment of treatment, disease debut and infections. Global mortality was 12 %. Conclusion: the most frequent causes of decompensations were abandoning treatment, novo diabetes and infectious processes.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

Paired-agent imaging as a rapid en face margin screening method in Mohs micrographic surgery.

Background: Mohs micrographic surgery is a procedure used for non-melanoma skin cancers that has 97-99% cure rates largely owing to 100% margin analysis enabled by en face sectioning with real-time, iterative histologic assessment. However, the technique is limited to small and aggressive tumors in high-risk areas because the histopathological preparation and assessment is very time intensive. To address this, paired-agent imaging (PAI) can be used to rapidly screen excised specimens and identify tumor positive margins for guided and more efficient microscopic evaluation. Methods: A mouse xenograft model of human squamous cell carcinoma (n = 8 mice, 13 tumors) underwent PAI. Targeted (ABY-029, anti-epidermal growth factor receptor (EGFR) affibody molecule) and untargeted (IRDye 680LT carboxylate) imaging agents were simultaneously injected 3-4 h prior to surgical tumor resection. Fluorescence imaging was performed on main, unprocessed excised specimens and en face margins (tissue sections tangential to the deep margin surface). Binding potential (BP) - a quantity proportional to receptor concentration - and targeted fluorescence signal were measured for each, and respective mean and maximum values were analyzed to compare diagnostic ability and contrast. The BP and targeted fluorescence of the main specimen and margin samples were also correlated with EGFR immunohistochemistry (IHC). Results: PAI consistently outperformed targeted fluorescence alone in terms of diagnostic ability and contrast-to-variance ratio (CVR). Mean and maximum measures of BP resulted in 100% accuracy, while mean and maximum targeted fluorescence signal offered 97% and 98% accuracy, respectively. Moreover, maximum BP had the greatest average CVR for both main specimen and margin samples (average 1.7 ± 0.4 times improvement over other measures). Fresh tissue margin imaging improved similarity with EGFR IHC volume estimates compared to main specimen imaging in line profile analysis; and margin BP specifically had the strongest concordance (average 3.6 ± 2.2 times improvement over other measures). Conclusions: PAI was able to reliably distinguish tumor from normal tissue in fresh en face margin samples using the single metric of maximum BP. This demonstrated the potential for PAI to act as a highly sensitive screening tool to eliminate the extra time wasted on real-time pathological assessment of low-risk margins.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: a retrospective assessment.

Importance: Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumor removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. Objective: To develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. Design: A retrospective cohort study was conducted using frozen cSCC section slides and adjacent tissues. Setting: This study was conducted in a tertiary care academic center. Participants: Patients undergoing Mohs micrographic surgery for cSCC between January and March 2020. Exposures: Frozen section slides were scanned and annotated, delineating benign tissue structures, inflammation, and tumor to develop an AI algorithm for real-time margin analysis. Patients were stratified by tumor differentiation status. Epithelial tissues including epidermis and hair follicles were annotated for moderate-well to well differentiated cSCC tumors. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC at 50-micron resolution. Main Outcomes and Measures: The performance of the AI algorithm in identifying cSCC at 50-micron resolution was reported using the area under the receiver operating characteristic curve. Accuracy was also reported by tumor differentiation status and by delineation of cSCC from epidermis. Model performance using histomorphological features alone was compared to architectural features (i.e., tissue context) for well-differentiated tumors. Results: The AI algorithm demonstrated proof of concept for identifying cSCC with high accuracy. Accuracy differed by differentiation status, driven by challenges in separating cSCC from epidermis using histomorphological features alone for well-differentiated tumors. Consideration of broader tissue context through architectural features improved the ability to delineate tumor from epidermis. Conclusions and Relevance: Incorporating AI into the surgical workflow may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumors/neoplasms. Further algorithmic improvement is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumors, and to map tumors to their original anatomical position/orientation. Future studies should assess the efficiency improvements and cost benefits and address other confounding pathologies such as inflammation and nuclei. Funding sources: JL is supported by NIH grants R24GM141194, P20GM104416 and P20GM130454. Support for this work was also provided by the Prouty Dartmouth Cancer Center development funds. Key Points: Question: How can the efficiency and accuracy of real-time intraoperative margin analysis for the removal of cutaneous squamous cell carcinoma (cSCC) be improved, and how can tumor differentiation be incorporated into this approach?Findings: A proof-of-concept deep learning algorithm was trained, validated, and tested on frozen section whole slide images (WSI) for a retrospective cohort of cSCC cases, demonstrating high accuracy in identifying cSCC and related pathologies. Histomorphology alone was found to be insufficient to delineate tumor from epidermis in histologic identification of well-differentiated cSCC. Incorporation of surrounding tissue architecture and shape improved the ability to delineate tumor from normal tissue.Meaning: Integrating artificial intelligence into surgical procedures has the potential to enhance the thoroughness and efficiency of intraoperative margin analysis for cSCC removal. However, accurately accounting for the epidermal tissue based on the tumor's differentiation status requires specialized algorithms that consider the surrounding tissue context. To meaningfully integrate AI algorithms into clinical practice, further algorithmic refinement is needed, as well as the mapping of tumors to their original surgical site, and evaluation of the cost and efficacy of these approaches to address existing bottlenecks.

Quantifying imaging agent binding and dissociation in 3D cancer spheroid tissue culture using paired-agent principles.

Binding kinetics play an important role in cancer diagnosis and therapeutics. However, current methods of quantifying binding kinetics fail to consider the three-dimensional environment that drugs and imaging agents experience in biological tissue. In response, a methodology to assay agent binding and dissociation in 3D tissue culture was developed using paired-agent molecular imaging principles. To test the methodology, the uptakes of ABY-029 (an IRDye 800CW-labeled epidermal growth factor receptor (EGFR)-targeted antibody-mimetic) and IRDye 700DX-carboxylate in 3D spheroids were measured in four different human cancer cell lines throughout staining and rinsing. A compartment model (optimized for the application) was then fit to the kinetic curves of both imaging agents to estimate binding and dissociation rate constants of the EGFR targeted ABY-029 agent. A linear correlation was observed between apparent association rate constant (k3) and the receptor concentration experimentally and in simulations (r=0.99, p<0.05). Additionally, a similar binding affinity profile compared to a gold standard method was determined by this model. This low-cost methodology to quantify imaging agent or drug binding affinity in clinically relevant 3D tumor spheroid models, can be used to guide timing of imaging in molecular guided surgery and could have implications in drug development.

The serotonin receptor 3E variant is a risk factor for female IBS-D.

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.

Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus.

OBJECTIVE: Racial and ethnic minority groups have excess morbidity related to renal disease in pediatric-onset systemic lupus erythematosus (SLE). This study was undertaken to evaluate temporal trends in renal outcomes and racial disparities among hospitalized children with SLE over a period of 14 years. METHODS: We identified patients 21 years old or younger with discharge diagnoses of SLE in the Pediatric Health Information System inpatient database (2006-2019). Adverse renal outcomes included end-stage renal disease (ESRD), dialysis, or transplant, analyzed as a composite and separately. We estimated the odds of adverse renal outcomes at any hospitalization or the first occurrence of an adverse renal outcome, adjusted for calendar period, patient characteristics, and clustering by hospital. We tested whether racial disparities differed by calendar period. RESULTS: There were 20,893 admissions for 7,434 SLE patients, of which 32%, 16%, 12%, and 8% were Black, Hispanic White, Hispanic Other, and Asian, respectively. Proportions of admissions with adverse renal outcomes decreased over time (P < 0.01). Black children remained at the highest risk of adverse renal outcomes at any admission (odds ratio [OR] 2.5 [95% confidence interval (95% CI) 1.8-3.5] versus non-Hispanic White patients). Black and Asian children remained at a higher risk of incident adverse renal outcomes, driven by ESRD among Black children (OR 1.6 [95% CI 1.2-2.1]) and dialysis among Asians (OR 1.7 [95% CI 1.1-2.7]). Relative disparities did not change significantly over time. CONCLUSION: Significant reductions in ESRD and dialysis occurred over time for children with SLE across all racial and ethnic groups. The lack of corresponding reductions in racial disparities highlights the need for targeted interventions to achieve greater treatment benefit among higher risk groups.

A Nudibranch Marine Extract Selectively Chemosensitizes Colorectal Cancer Cells by Inducing ROS-Mediated Endoplasmic Reticulum Stress.

The present study shows the putative antiproliferative mechanism of action of the previously analytically characterized nudibranch extract (Dolabella auricularia, NB) and its different effects in colon cancer cells vs. nontumor colon cells. NB extract increased the accumulation of reactive oxygen species (ROS) and increased endoplasmic reticulum (ER) stress via stimulation of the unfolded protein response. Stress scavengers, N-acetylcysteine (NAC) and 4-phenylbutyric acid (4-PBA), decreased the stress induced by NB. The results showed that NB extract increased ER stress through overproduction of ROS in superinvasive colon cancer cells, decreased their resistance threshold, and produced a nonreturn level of ER stress, causing DNA damage and cell cycle arrest, which prevented them from achieving hyperproliferative capacity and migrating to and invading other tissues. On the contrary, NB extract had a considerably lower effect on nontumor human colon cells, suggesting a selective effect related to stress balance homeostasis. In conclusion, our results confirm that the growth and malignancy of colon cancer cells can be decreased by marine compounds through the modification of one of the most potent resistance mechanisms present in tumor cells; this characteristic differentiates cancer cells from nontumor cells in terms of stress balance.

Lung Cancer Management with Silibinin: A Historical and Translational Perspective.

The flavonolignan silibinin, the major bioactive component of the silymarin extract of Silybum marianum (milk thistle) seeds, is gaining traction as a novel anti-cancer therapeutic. Here, we review the historical developments that have laid the groundwork for the evaluation of silibinin as a chemopreventive and therapeutic agent in human lung cancer, including translational insights into its mechanism of action to control the aggressive behavior of lung carcinoma subtypes prone to metastasis. First, we summarize the evidence from chemically induced primary lung tumors supporting a role for silibinin in lung cancer prevention. Second, we reassess the preclinical and clinical evidence on the effectiveness of silibinin against drug resistance and brain metastasis traits of lung carcinomas. Third, we revisit the transcription factor STAT3 as a central tumor-cell intrinsic and microenvironmental target of silibinin in primary lung tumors and brain metastasis. Finally, by unraveling the selective vulnerability of silibinin-treated tumor cells to drugs using CRISPR-based chemosensitivity screenings (e.g., the hexosamine biosynthesis pathway inhibitor azaserine), we illustrate how the therapeutic use of silibinin against targetable weaknesses might be capitalized in specific lung cancer subtypes (e.g., KRAS/STK11 co-mutant tumors). Forthcoming studies should take up the challenge of developing silibinin and/or next-generation silibinin derivatives as novel lung cancer-preventive and therapeutic biomolecules.

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Model-based system matrix for iterative reconstruction in sub-diffuse angular-domain fluorescence optical projection tomography.

This work concerns a fluorescence optical projection tomography system for low scattering tissue, like lymph nodes, with angular-domain rejection of highly scattered photons. In this regime, filtered backprojection (FBP) image reconstruction has been shown to provide reasonable quality images, yet here a comparison of image quality between images obtained by FBP and iterative image reconstruction with a Monte Carlo generated system matrix, demonstrate measurable improvements with the iterative method. Through simulated and experimental phantoms, iterative algorithms consistently outperformed FBP in terms of contrast and spatial resolution. Moreover, when projection number was reduced, in order to reduce total imaging time, iterative reconstruction suppressed artifacts that hampered the performance of FBP reconstruction (structural similarity of the reconstructed images with "truth" was improved from 0.15 ± 1.2 × 10-3 to 0.66 ± 0.02); and although the system matrix was generated for homogenous optical properties, when heterogeneity (62.98 cm-1 variance in µs ) was introduced to simulated phantoms, the results were still comparable (structural similarity homo: 0.67 ± 0.02 vs hetero: 0.66 ± 0.02).

Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol.

PURPOSE: Correctly identifying nodal status is recognized as a critical prognostic factor in many cancer types and is essential to guide adjuvant treatment. Currently, surgical removal of lymph nodes followed by pathological examination is commonly performed as a standard-of-care to detect node metastases. However, conventional pathology protocols are time-consuming, yet less than 1 % of lymph node volumes are examined, resulting in a 30-60 % rate of missed micrometastases (0.2-2 mm in size). PROCEDURES: This study presents a method to fluorescently stain excised lymph nodes using paired-agent molecular imaging principles, which entail co-administration of a molecular-targeted imaging agent with a suitable control (untargeted) agent, whereby any nonspecific retention of the targeted agent is accounted for by the signal from the control agent. Specifically, it was demonstrated that by dual-needle continuous infusion of either an antibody-based imaging agent pair (epidermal growth factor receptor (EGFR) targeted agent: IRDye-800CW labeled Cetuximab; control agent: IRDye-700DX-IgG) or an Affibody-based pair (EGFR targeted Affibody® agent: ABY-029; control agent IRDYe-700DX carboxylate) at 0.3 ml/min. RESULTS: The results demonstrated the possibility to achieve >99 % sensitivity and > 95 % specificity for detection of a single micrometastasis (~0.2 mm diameter) in a whole lymph node within 22 min of tissue processing time. CONCLUSION: The detection capabilities offer substantial improvements over existing intraoperative lymph node biopsy methods (e.g., frozen pathology has a micrometastasis sensitivity <20 %).

Characterization of an angular domain fluorescence optical projection tomography system for mesoscopic lymph node imaging.

Transmittance and fluorescence optical projection tomography can offer high-resolution and high-contrast visualization of whole biological specimens; however, applications are limited to samples exhibiting minimal light scattering. Our previous work demonstrated that angular-domain techniques permitted imaging of ∼1cm diameter noncleared lymph nodes because of their low scattering nature. Here, an angle-restricted transmittance/fluorescence system is presented and characterized in terms of geometric and fluorescence concentration reconstruction accuracy as well as spatial resolution, depth of focus, and fluorescence limits of detection. Using lymph node mimicking phantoms, results demonstrated promising detection and localization capabilities relevant for clinical lymph node applications.

Manifestaciones autoinmunes en pacientes con dengue. Casuística en el Departamento de Medicina Interna del Hospital Nacional, Paraguay / Autoimmune manifestations in patients with dengue. Casuistry in the Departamento de Medicina Interna of the Hospital Nacional, Paraguay

RESUMEN Introducción: en los últimos años se notifican cada vez más manifestaciones autoinmunes relacionadas con la infección por dengue. El dengue es una infección viral transmitida por la picadura de las hembras infectadas de mosquitos del género Aedes, es frecuente en los países tropicales y subtropicales de todo el mundo. Objetivo: reportar las características clínicas de las manifestaciones autoinmunes en pacientes infectados con el virus del dengue internados en el Hospital Nacional. Metodología: estudio observacional, descriptivo y retrospectivo, de casos de pacientes con infección por el virus del dengue internados durante la epidemia de dengue 2016, 2019 hasta julio 2020, en el Departamento de Medicina Interna del Hospital Nacional. El diagnóstico de la infección por el virus del dengue fue realizado, por el cuadro clínico, el antígeno NS1 y la serología IgM positivo. Resultados: presentamos siete casos. Tuvieron manifestaciones neurológicas tres pacientes (dos mujeres y un varón), una mujer desarrolló una neuritis óptica aislada, dos presentaron síndrome de Guillian- Barré, un caso en el curso de la infección por dengue y el otro con dengue asintomático. Cuatro pacientes presentaron manifestaciones hematológicas, 2 con anemia hemolítica autoinmune, una mujer presentó purpura trombocitopenia trombótica, con buena respuesta con sesiones de plasmaféresis, una mujer portadora de purpura trombocitopénica inmune, presentó recaída de la enfermedad en el día 7 de la infección por dengue. Conclusión: el síndrome de Guillain­Barré y la anemia hemolítica fueron las manifestaciones autoinmunes más frecuentes.

ABSTRACT Introduction: in recent years, more and more autoimmune manifestations related to dengue infection have been reported. Dengue is a viral infection transmitted by the bite of infected female mosquitoes of the genus Aedes, it is common in tropical and subtropical countries around the world. Objective: to report the clinical characteristics of autoimmune manifestations in patients infected with dengue virus admitted to the Hospital Nacional. Methodology: observational, descriptive and retrospective study of cases of patients with dengue virus infection hospitalized during the dengue epidemic 2016, 2019 until July 2020, in the Departamento de Medicina Interna of the Hospital Nacional. The diagnosis of dengue virus infection was made, based on the clinical picture, the NS1 antigen and the positive IgM serology. Results: we present seven cases. Three patients (two women and one man) had neurological manifestations, one woman developed isolated optic neuritis, two presented Guillian-Barré syndrome, one case in the course of dengue infection and the other with asymptomatic dengue. Four patients presented hematological manifestations, 2 with autoimmune hemolytic anemia, a woman presented with thrombotic thrombocytopenia purpura, with a good response with plasmapheresis sessions, a woman with immune thrombocytopenic purpura, presented relapse of the disease on day 7 of the dengue infection. Conclusion: Guillain ­ Barré syndrome and hemolytic anemia were the most frequent autoimmune manifestations.

Quercetin metabolites from Hibiscus sabdariffa contribute to alleviate glucolipotoxicity-induced metabolic stress in vitro.

Polyphenols from Hibiscus sabdariffa (HS) alleviate obesity-related metabolic complications but the metabolites responsible for such effects are unknown. We aimed to elucidate which of the potential plasma metabolites from a polyphenol-enriched HS (PEHS) extract contributed for the reversion of glucolipotoxicity-induced metabolic stress using 3T3-L1 adipocyte and INS 832/13 pancreatic ß-cell models under glucolipotoxic conditions. PEHS extract, quercetin (Q) and quercetin-3-O-glucuronide (Q3GA) showed stronger capacity to decrease glucolipotoxicity-induced ROS generation than ascorbic acid or chlorogenic acid. PEHS extract, Q and Q3GA decreased secretion of cytokines (leptin, TNF-α, IGF-1, IL-6, VEGF, IL-1α, IL-1ß and CCL2) and reduced CCL2 expression at transcriptional level. In addition, PEHS extract, Q and Q3GA reduced triglyceride accumulation, which occurred through fatty acid synthase (FASN) downregulation, AMPK activation and mitochondrial mass and biogenesis restoration via PPARα upregulation. Electron microscopy confirmed that PEHS extract and Q3GA decreased mitochondrial remodeling and mitophagy. Virtual screening leads us to postulate that Q and Q3GA might act as agonists of these protein targets at specific sites. These data suggest that Q and Q3GA may be the main responsible compounds for the capacity of PEHS extract to revert glucolipotoxicity-induced metabolic stress through AMPK-mediated decrease in fat storage and increase in fatty acid oxidation, though other compounds of the extract may contribute to this capacity.

Caracterización de la atención a distancia, preferencias y utilidad de redes sociales de los usuarios de Teletón Chile, en el período junio-agosto de 2020, con motivo de la contingencia de COVID-19, estudio descriptivo transversal / Characterization of remote care, preferences and usefulness of social networks of Teletón Chile patients, in the period June-August 2020, on COVID-19 contingency, descriptive cross-sectional study

INTRODUCCIÓN: Producto de la pandemia por COVID-19 y para establecer continuidad a los tratamientos de usuarios y familias, Teletón Chile implementó una encuesta para describir las características demográficas, de salud, sociales, ambientales, factores asociados, atención a distancia y problemas asociados por contingencia COVID-19. OBJETIVO: Describir el servicio de atención a distancia (AD) implementado por Teletón Chile, preferencias y utilidad de redes sociales (RR.SS.) de los usuarios. MATERIALES Y MÉTODOS: Estudio descriptivo transversal de tipo censal a usuarios activos de Teletón al 30 de abril de 2020 desarrollado a través de la aplicación de una encuesta para caracterizar el servicio de AD y RR.SS. RESULTADOS: Se presentan resultados obtenidos entre junio y agosto de 2020, que representan al 31,13% (n = 8.202) de la población total atendida; El 74,54% de los participantes de la encuesta señalan haber recibido AD, de los cuales un 82,02% logra el cumplimiento de las indicaciones siendo la principal razón de no cumplimiento no ser contactado para la modalidad AD desde el área médico-terapéutica (36,55%). Los principales beneficios de la AD son: aumento de la accesibilidad en la atención (44,13%) y disminución de las problemáticas del traslado (17,67%). La preocupación principal es la pérdida de la cantidad de atenciones presenciales (34,41%). CONCLUSIONES: La AD es considerada de utilidad para la continuidad de los programas de rehabilitación. Asimismo, toma relevancia el uso de redes sociales para contacto y seguimiento. Finalmente, para implementar este servicio se requiere considerar las necesidades personales de los usuarios para una rehabilitación remota.

INTRODUCTION: Due to the COVID-19 pandemic and to establish continuity in the treatment of users and families, Teletón Chile implemented a survey to describe the demographic, health, social and environmental characteristics, associated factors, distance care and associated problems due to COVID-19. Objective: To describe stance Attention (DA) service implemented by Teleton Chile, and the preferences and usefulness of users' social networks (RRSS). MATERIALS AND METHODS: A cross-sectional descriptive study of a census type which was developed through the application of a survey to characterize the DA and RRSS service, and includes active Teletón users as of April 30, 2020. RESULTS: Results obtained between June and August 2020 are presented, representing 31.13% (n = 8,202) of the total population served; 74.54% of the survey participants indicated having received of which 82.02% achieved compliance with the prescribed indications, the main reason for non-compliance was not being contacted by the medical-therapeutic area for the DA modality (36.55%). The main benefits of DA are: increased accessibility to care (44.13%) and reduction in transportation problems (17.67%). The main concern is the loss of the amount of face-to-face care (34.41%). CONCLUSIONS: DA is considered useful for the continuity of rehabilitation programs. The use of social networks for contact and follow-up is also relevant. Finally, to implement this service, it is necessary to consider the personal needs of the users for a remote rehabilitation.