Portal vein Doppler tracks volume status in patients with severe tricuspid regurgitation: a proof-of-concept study.

AIMS: Renal and liver congestion are associated with adverse outcomes in patients with tricuspid regurgitation (TR). Currently, there are no valid sonographic indicators of fluid status in this population. Intra-renal venous Doppler (IRVD) is a novel method for quantifying renal congestion but its interpretation can be challenging in severe TR due to altered haemodynamics. This study explores the potential of portal vein Doppler (PVD) as an alternative marker for decongestion during volume removal in patients with severe TR. METHODS AND RESULTS: Forty-two patients with severe TR undergoing decongestive therapy were prospectively enrolled. Inferior vena cava diameter, PVD, and IRVD were sequentially assessed during volume removal. Improvement criteria were portal vein pulsatility fraction (PVPF) < 70% and renal venous stasis index (RVSI) < 0.5 for partial improvement, and PVPF < 30% and RVSI < 0.2 for complete improvement. After volume removal, PVPF significantly improved from 130 ± 39% to 47 ± 44% (P < 0.001), while IRVD improved from 0.72 ± 0.08 to 0.54 ± 0.22 (P < 0.001). A higher proportion of patients displayed improvement in PVD compared to IRVD (partial: 38% vs. 29%, complete: 41% vs. 7%) (P < 0.001). Intra-renal venous Doppler only improved in patients with concomitant improvement in severe TR. Portal vein Doppler was the only predictor of achieving ≥5 L of negative fluid balance [area under the ROC curve (AUC) 0.83 P = 0.001]. CONCLUSION: This proof-of-concept study suggests that PVD is the only sonographic marker that can track volume removal in severe TR, offering a potential indicator for decongestion in this population. Further intervention trials are warranted to determine if PVD-guided decongestion improves patient outcomes in severe TR.

Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis.

Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.

Oocyte dynamics for Atlantic bluefin tuna (Thunnus thynnus) in the southern Gulf of Mexico: A comparative assessment of Mediterranean spawners using two stereological methods.

Although most research focused on the northern Gulf of Mexico for western Atlantic bluefin tuna, the histological records of reproductive activity of this species in the southern Gulf of Mexico (Mexican waters) have been presented for the first time. This work is the first to study oocyte dynamics in Atlantic bluefin tuna caught in the southern Gulf of Mexico by assessing and comparing them with Mediterranean stock (BFT-E) through stereology using two different methods. Regardless of Atlantic bluefin tuna females returning to their respective spawning grounds at different months in the southern Gulf of Mexico and the Mediterranean, both stocks arrived reproductively inactive and remained in these zones during periods of similar length; they were reproductively active until March for the southern Gulf of Mexico and May for the Mediterranean females. The comparison of the size structure between the two stocks examined using kernel density estimators demonstrated a quite remarkable difference in mean fork lengths between stocks. The ovarian oocyte density, that is, the number of oocytes per gram of ovary, for each gonad stage predicted using the Weibel and Gomez and oocyte packing density (OPD) methods did not significantly differ between stocks and showed that advanced vitellogenic oocytes from spawning-capable females are an appropriate indicator to estimate potential fecundity, presenting values of c. 1273 and ~1355 eggs per gram for the southern Gulf of Mexico and Mediterranean females, respectively. Females caught in Mexican waters (southern Gulf of Mexico) were larger than those caught in the Mediterranean; however, it was demonstrated that the length and weight of females did not affect ovarian oocyte density production. In addition, densities estimated for each gonad stage using W&G and OPD methods did not differ between stocks and presented equal patterns in their oocyte dynamics. These findings contribute to a better understanding of the reproductive biology of Atlantic bluefin tuna, especially in the southern Gulf of Mexico, due to the lack of information regarding this zone, and may allow to support strategies for proper assessment, management, and conservation.

Transcriptome-Wide Analysis of Low-Concentration Exposure to Bisphenol A, S, and F in Prostate Cancer Cells.

Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease.

Δ9-Tetrahydrocannabinol Treatment Modifies Insulin Secretion in Pancreatic Islets from Prediabetic Mice Under Hypercaloric Diet.

Background: The endocannabinoid system over-activation is associated with type-2 diabetes mellitus onset, involving physiological, metabolic, and genetic alterations in pancreatic islets. The use of Δ9-Tetrahydrocannabinol (THC) as treatment is still controversial since its effects and mechanisms on insulin secretion are unclear. The aim of this study was to evaluate the effects of THC treatment in pancreatic islets from prediabetic mice. Methods: Prediabetes was induced in mice by hypercaloric diet, and then treated with THC for 3 weeks. Blood glucose and body weight were determined, after behavior tests. Histological changes were evaluated in whole pancreas; in isolated islets we analyzed the effect of THC exposure in glucose-stimulated insulin secretion (GSIS), gene expression, intracellular cyclic adenosine monophosphate (cAMP), and cytosolic calcium changes. Results: THC treatment in prediabetic mice enhanced anxiety and antidepressive behavior without changes in food ingestion, decreased oral-glucose tolerance test, plasma insulin and weight, with small alterations on pancreatic histology. In isolated islets from healthy mice THC increased GSIS, cAMP, and CB1 receptor (CB1r) expression, meanwhile calcium release was diminished. Small changes were observed in islets from prediabetic mice. Conclusions: THC treatment improves some clinical parameters in prediabetic mice, however, in isolated islets, modifies GSIS, intracellular calcium and gene expression, suggesting specific effects related to diabetes evolution.

Medicamentos bioterapéuticos: uso de toxinas botulínicas en la era de biosimilares / Biotherapeutic medicines: use of botulinum toxins in the era of biosimilars

Introducción: Las toxinas botulínicas son medicamentos bioterapéuticos con grandes aplicaciones en el campo de la neurología, como la cefalea y los movimientos anormales. Debido a la importancia médica y al incremento de las indicaciones terapéuticas de la toxina botulínica, este artículo pretende hacer claridad acerca de la terminología básica con respecto a la naturaleza de este medicamento, a las diferencias estructurales con medicamentos convencionales y aspectos importantes en relación con su potencia biológica e inmunogenicidad, para así comprender las potenciales diferencias entre las toxinas disponibles y conceptuar en torno a la no intercambiabilidad o sustitución de una toxina por otra. Materiales y métodos: Revisión no sistemática, según lo recomendado en la Escala para la Verificación de los Artículos Revisiones Narrativas (Sanra). Conclusiones: Los medicamentos biológicos no son intercambiables entre sí, aunque demuestren bioequivalencia. No se pueden evaluar como medicamentos genéricos intercambiables porque son biológicos; no existen estudios comparativos cabeza a cabeza; son diferentes, debido al proceso individual de manufactura.

Introduction: Botulinum toxins are biotherapeutic drugs with great applications in the field of neurology such as headache and abnormal movements. Due to the medical importance and the increase in therapeutic indications of botulinum toxin, this article aims to clarify the basic terminology regarding the nature of this drug, the structural differences with conventional drugs and important aspects in relation to its biological potency and immunogenicity in order to understand the potential differences between the available toxins and conceptualize regarding the non-interchangeability or substitution of one toxin for another. Materials and methods: Non-systematic review as recommended in the Scale for the Verification of Narrative Review Articles (SANRA). Conclusions: Biological drugs are not interchangeable with each other, even if they demonstrate bioequi-valence. They cannot be evaluated as interchangeable generic drugs because they are biologics. There are no head-to-head comparative studies. They are different due to the individual manufacturing process.

First account of microplastics in pelagic sporting dolphinfish from the eastern Mexican coast of Baja California Sur.

This study is a baseline data on the presence of MPs from the gastro-intestinal tracts (GITs) in Coryphaena hippurus Linnaeus, from eastern Baja California Sur, México. 878 MPs items (in %) of fibers (29%), fragments (68%) and films (1.3%) were detected from 51 GITs of Coryphaena hippurus. Transparent, white, blue and black were the prevalent colours. Morphological features observed through SEM analysis, the presence of heavily weathered MPs is due to the mechanical, microbiological and chemical weathering process. PP (29%), Nylon (29%), PS (17%), PE (11%), PET (6%) and HDPE (8%) presence indicates their source from regional anthropogenic stress. Trophic level transition is enforced by polymer derivative, permitting the sinking behavior of MPs and increased ingestion probability. Fishes were classified as slim despite their higher feeding capabilities and ingested MPs indicates a relationship with environmental contaminants. Current study emphasizes the health risk linked to biological aspects of MPs ingestion.

SFRP1 induces a stem cell phenotype in prostate cancer cells.

Prostate cancer (PCa) ranks second in incidence and sixth in deaths globally. The treatment of patients with castration-resistant prostate cancer (CRPC) continues to be a significant clinical problem. Emerging evidence suggests that prostate cancer progression toward castration resistance is associated with paracrine signals from the stroma. SFRP1 is one of the extracellular proteins that modulate the WNT pathway, and it has been identified as a mediator of stromal epithelium communication. The WNT pathway is involved in processes such as cell proliferation, differentiation, cell anchoring, apoptosis, and cell cycle regulation as well as the regulation of stem cell populations in the prostatic epithelium. In the present study, we explored the role of exogenous SFRP1 on the stem cell phenotype in prostate cancer. The results reveal that cancer stem cell markers are significantly increased by exogenous SFRP1 treatments, as well as the downstream target genes of the Wnt/-catenin pathway. The pluripotent transcription factors SOX2, NANOG, and OCT4 were also up-regulated. Furthermore, SFRP1 promoted prostate cancer stem cell (PCSC) properties in vitro, including tumorsphere formation, migration, bicalutamide resistance, and decreased apoptosis. Taken together, our results indicate that SFRP1 participates in the paracrine signaling of epithelial cells, influencing them and positively regulating the stem cell phenotype through deregulation of the WNT/ß-catenin pathway, which could contribute to disease progression and therapeutic failure. This research increases our molecular understanding of how CRPC progresses, which could help us find new ways to diagnose and treat the disease.

Metacognición, insight clínico y sintomatología en pacientes ambulatorios chilenos con Esquizofrenia

Introducción: Las personas con esquizofrenia presentan graves dificultades para formar ideas complejas sobre sí mismos y otros, definidas como déficits metacognitivos, junto a menor insight clínico o capacidad para tomar conciencia de poseer un trastorno de salud mental. El presente estudio evaluó dichas alteraciones y las correlaciones entre metacognición, insight clínico y sintomatología en pacientes ambulatorios con esquizofrenia. Metodología: Se diseñó un estudio cuantitativo, relacional, prospectivo, transversal y observacional. Treinta y un pacientes ambulatorios del Centro Diurno "Luz y Esperanza" de Talca (Chile) fueron evaluados utilizando la Metacognitive Assessment Scale-Abbreviated, Scale of Unawareness of Mental Disorder y la Escala de Síndromes Positivo y Negativo, en el período 2019-2020. Resultados: Se encontraron bajos puntajes metacognitivos y de insight clínico, destacando las correlaciones estadísticamente significativas de puntaje metacognitivo total, Autorreflexividad y Maestría con escasa Conciencia de poseer un trastorno y las subescalas de síntomas negativos y desorganización. Conclusiones: Nuestros resultados respaldan la inclusión de los déficits metacognitivos y de insight clínico en los modelos de esquizofrenia. Se discute sobre su potencial aporte en el diseño de intervenciones psicoterapéuticas que promuevan estas capacidades e influyan en los síntomas negativos y de desorganización. Es necesario replicar estudios sobre estas variables en nuestro país, que incluyan un mayor número de participantes.

Introduction: People with schizophrenia have serious disturbances in forming complex ideas about themselves and others, defined as metacognitive deficits, along with less clinical insight or awareness of mental disorder The present study assessed these disturbances and the correlations between metacognition, clinical insight and symptomatology in outpatients with schizophrenia. Methods: A quantitative, relational, prospective, cross-sectional and observational study was designed. Thirty-one outpatients of the "Luz y Esperanza" Day Center in Talca (Chile) were evaluated using the Metacognitive Assessment Scale-Abbreviated, Scale of Unawareness of Mental Disorder and the Positive and Negative Syndrome Scale, in the period 2019-2020. Results: Low metacognitive and clinical insight scores were found, highlighting statistically significant correlations of total metacognitive score, Self-Reflectivity and Mastery with low Awareness of mental disorder and the subscales of negative symptoms and disorganization. Conclusions: Our results support the inclusion of metacognitive deficits and clinical insight in schizophrenia models. Its potential contribution to the design of psychotherapeutic interventions that promote these abilities and influence negative and disorganized symptoms is discussed. It is necessary to replicate studies about these variables in our country, including a greater number of participants.

Cardiopulmonary Imaging Utilization and Findings among Hospitalized COVID-19 Patients in Latin America: (From "RIMAC: Registry IMAging Cardiopulmonary among Hospitalized COVID-19 Patients in LATAM").

Objectives: Describe the use and findings of cardiopulmonary imaging-chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS), and/or cardiac magnetic resonance imaging (cMRI)-in COVID-19 hospitalizations in Latin America (LATAM). Background: There is a lack of information on the images used and their findings during the SARS-CoV-2 pandemic in LATAM. Methods: Multicenter, prospective, observational study of COVID-19 inpatients, conducted from March to December 2020, from 12 high-complexity centers, in nine LATAM countries. Adults (>18 years) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. Results: We studied 1,435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: Mexico (Mx), 262; Central America and Caribbean (CAC), 428; and South America (SAm), 745. More frequent comorbidities were overweight/obesity, hypertension, and diabetes. During hospitalization, 58% were admitted to the ICU. The in-hospital mortality was 28%, and it was highest in Mx (37%).The most frequent images performed were cCT (61%), mostly in Mx and SAm, and cX-ray (46%), significant in CAC. The cEcho was carried out in 18%, similarly among regions, and LUS was carried out in 7%, with a higher frequently in Mx. Abnormal findings on the cX-ray were peripheral or basal infiltrates, and in cCT abnormal findings were the ground glass infiltrates, more commonly in Mx. In LUS, interstitial syndrome was the most abnormal finding, predominantly in Mx and CAC.Renal failure was the most prevalent complication (20%), predominant in Mx and SAm. Heart failure developed in 13%, predominant in Mx and CAC. Lung thromboembolism was higher in Mx while myocardial infarction was in CAC.Logistic regression showed associations of abnormal imaging findings and their severity, with comorbidities, complications, and evolution. Conclusions: The use and findings of cardiopulmonary imaging in LATAM varied between regions and had a great impact on diagnosis and prognosis.

Aptamers as Theragnostic Tools in Prostate Cancer.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

DNA aptamer selection for SARS-CoV-2 spike glycoprotein detection.

The rapid spread of SARS-CoV-2 infection throughout the world led to a global public health and economic crisis triggering an urgent need for the development of low-cost vaccines, therapies and high-throughput detection assays. In this work, we used a combination of Ideal-Filter Capillary Electrophoresis SELEX (IFCE-SELEX), Next Generation Sequencing (NGS) and binding assays to isolate and validate single-stranded DNA aptamers that can specifically recognize the SARS-CoV-2 Spike glycoprotein. Two selected non-competing DNA aptamers, C7 and C9 were successfully used as sensitive and specific biological recognition elements for the development of electrochemical and fluorescent aptasensors for the SARS-CoV-2 Spike glycoprotein with detection limits of 0.07 fM and 41.87 nM, respectively.

Recommendations for the diagnosis and management of persons with suspected vaccine-induced immune thrombotic thrombocytopenia (VITT) / Recomendaciones para diagnostico y manejo de personas con trombocitopenia trombotica inmune inducida por vacunas (VITT)

Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.

Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo

Recomendaciones de la Asociación Colombiana de Neurología para el uso de anticuerpos monoclonales antiCGRP en la profilaxis de migraña / Recommendations on the use of the antiCGRP monoclonal antibodies for migraine prophylaxis on behalf of the Colombian Association of Neurology

RESUMEN INTRODUCCIÓN: El desarrollo de anticuerpos monoclonales (mAbs) contra el péptido relacionado con el gen de la calcitonina (CGRP) ha determinado una nueva era terapéutica en la profilaxis de migraña, demostrando su efectividad en pacientes con migraña episódica (ME) y migraña crónica (MC), con respuesta desde pacientes naïve hasta refractarios a múltiples medicamentos. La disminución del 50% de los ataques de migraña al mes (DMM) durante los primeros 3 meses de uso es el desenlace aproximado en el 50% de los pacientes que reciben esta terapia. OBJETIVO: Este consenso de la Asociación Colombiana de Neurología (ACN) tiene el objetivo de guiar la selección y uso racional de los mAbs antiCGRP en pacientes con ME y MC. MATERIALES Y MÉTODOS: El comité de cefalea de la ACN mediante la aplicación de la metodología Delphi y discusiones en reuniones posteriores desarrolló un documento en formato de consenso soportado en literatura y recomendaciones de expertos. RESULTADOS: Se obtuvieron respuestas de 14 expertos en cefalea sobre moléculas utilizadas en profilaxis de migraña, analizando su aplicabilidad en situaciones clínicas frecuentes. DISCUSIÓN: Los mAbs antiCGRP han demostrado efectividad con adecuado soporte fisiopatológico, considerando que son moléculas de alto precio en una enfermedad de alta prevalencia, existe la necesidad de guíar la selección del paciente que mejor puede beneficiarse de su administración CONCLUSIONES: Los mAbs antiCGRP están recomendados en pacientes con ME y MC que presentan falla terapéutica a otras moléculas profilácticas.

ABSTRACT INTRODUCTION: The development of monoclonal antibodies (mAbs) against Calcitonin Gene Related Peptide (CGRP) has determined a new therapeutic era in migraine prophylaxis, demonstrating its effectiveness in patients with episodic migraine (EM) and chronic migraine (CM), obtaining a response in naive patients and in those who are refractory to multiple medications. A 50% decrease in migraine attacks per month during the first 3 months of use is the approximate outcome in 50% of patients receiving this therapy. OBJECTIVE: This consensus from the Colombian Association of Neurology (ACN) has the objective of serving as a guide for the rational use of antiCGRP mAbs in patients with EM and CM. METHODS AND MATERIALS: The headache committee through the application of the Delphi methodology and discussions in subsequent meetings, develops this consensus, supported in the published literature and expert recommendations. RESULTS: Fourteen answers from headache experts were received regarding the use of drugs for migraine prophylaxis, analyzing their applicability in frequent clinical situations. DISCUSSION: AntiCGRP mAbs have proved their effectiveness with adequate pathophysiological support, but with a high price in a highly prevalent disease, there is then a need to select the patient who best benefits from this therapy. CONCLUSIONS: AntiCGRP mAbs are recommended in patients with EM and CM that have previously failed to other prophylactic drugs.

Inhibition of Stearoyl-CoA Desaturase by Sterculic Oil Reduces Proliferation and Induces Apoptosis in Prostate Cancer Cell Lines.

Prostate cancer (PCa) is a common type of cancer affecting male population. PCa treatments have side effects and are temporarily effective, so new therapeutic options are being investigated. Due to the high demand of energy for cell proliferation, an increase in the expression and activity of lipogenic enzymes such as the stearoyl-CoA desaturase (SCD) have been observed in PCa. Sterculic acid, contained in the seed's oil of Malvales, is a natural inhibitor of SCD. The objective of our investigation was to evaluate the effects of sterculic oil (SO) from Sterculia apetala seeds on proliferation, cell cycle and apoptosis in prostate cancer cells. SO was administered to PC3 and LNCaP cells, and to prostate normal cells; cell viability, cell cycle, apoptosis, SCD gene and protein expression and enzymatic activity were analyzed. SO administration (4 mM sterculic acid) diminished cell viability in LNCaP and PC3 cells, arrested cell cycle in G2 and promoted apoptosis. SO diminished SCD enzymatic activity with no effects on gene nor protein expression. Our results suggest that SO might offer benefits as an adjuvant in hormonal and chemotherapy prostate cancer treatments. This is the first study to analyze the effect of SO on cancer cells.

Reclamos por atención en salud: experiencia en un centro privado / Analysis of healthcare claims received at an audit unit of a clinical hospital

Background: The resolution of claims at healthcare institutions is an important issue for administrators. Aim: To analyze the causes of healthcare-related claims in a private, clinical health center. Material and Methods: All claims processed at the audit unit of a clinical hospital between 2016 and 2019 were analyzed. Results: In the study period, 602 complaints were recorded, representing a rate of one claim for every 1,000 services provided. The two main causes of complaints were sub-standard interaction with the doctor such as communication or lack of empathy, corresponding to 21% of cases, and complaints related to care costs, quotes, and insurance coverage (21%). The highest number of complaints originated in emergency care, but the highest rate by number of healthcare services provided occurred in hospitalization in the Mental Health and the Adult Critical Care units. Roughly, 75% of the complaints were settled with a phone call to the patient, which allowed to explain what happened and to apologize accordingly. In 21% of the cases, one or more meetings were held with the patient, a family member, or his/her legal representative to settle an agreement. In 3.5% of cases a mediation process through an independent third party was required. Only 1% of the claims resulted in a legal action. Conclusions: The importance of cultivating an adequate physician-patient relationship for the prevention of complaints and eventual litigations associated with the provision of healthcare services, is emphasized. Quality control policies and processes within healthcare organizations should be strengthened.

Eficacia y seguridad del rituximab en el tratamiento de la esclerosis múltiple: una postura racional en el contexto colombiano / Efficacy and safety of rituximab in the treatment of multiple sclerosis: a rational position in the Colombian context

RESUMEN INTRODUCCIÓN: La esclerosis múltiple es una enfermedad neuroinflamatoria, crónica, degenerativa e incurable, asociada a pérdida neuronal, grados crecientes de discapacidad y deterioro cognoscitivo. Su manejo conlleva grandes costos para los sistemas de salud y la sociedad en general. OBJETIVO: Evaluar la eficacia y la seguridad del uso del rituximab en el manejo de la esclerosis múltiple. MATERIALES Y MÉTODOS: Revisión de la literatura y evaluación de la tecnología en salud tipo mini-HTA en red colaborativa con el Comité de Esclerosis Múltiple de la Asociación Colombiana de Neurología y el Instituto Global de Excelencia Clínica. RESULTADOS: Se identificaron 27 referencias de texto completo para el análisis de la seguridad y la eficacia del rituximab en el manejo de la esclerosis múltiple. Se utilizaron análisis de costos, indicadores epidemiológicos y estudios pivótales de rituximab. CONCLUSIÓN: La evidencia analizada confirma que la terapia con rituximab es efectiva y segura en el manejo de las formas de esclerosis múltiple remitente-recurrente (EMRR) y esclerosis múltiple primaria-progresiva (EMPP), con menor tasa de eventos adversos y tasas de interrupción o abandono del tratamiento más bajas que otras terapias modificadoras de la enfermedad (TME).

SUMMARY INTRODUCTION: Multiple sclerosis is a neuroinflammatory, chronic, degenerative, and incurable disease, associated with neuronal loss, increasing degrees of disability, and cognitive control. Its treatment causes great costs for health systems and society in general. OBJECTIVE: To evaluate the efficacy and safety of the use of rituximab in the management of multiple sclerosis. MATERIALS AND METHODS: Literature review and evaluation of mini-HTA type health technology in a collaborative network with the Multiple Sclerosis Committee of the Colombian Association of Neurology and the Global Institute of Clinical Excellence. RESULTS: 27 full-text references were identified for the safety and efficacy analysis of rituximab in the management of multiple sclerosis. Cost analysis, epidemiological indicators, and pivotal studies of rituximab were incorporated into the analysis. CONCLUSION: The evidence analyzed confirms that rituximab therapy is effective and safe in the management of the forms of Recurrent-Remittent Multiple Sclerosis (RRMS) and Primary-Progressive Multiple Sclerosis (PPMS), with a lower rate of adverse events and discontinuation or withdrawal rates of treatment lower than other disease-modifying therapies.

Transporters, TBC1D4, and ARID5B Variants to Explain Glycated Hemoglobin Variability in Patients with Type 2 Diabetes.

INTRODUCTION: Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. METHODS: HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. RESULTS: We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. CONCLUSIONS: Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.

Pseudoatetosis de los miembros superiores como manifestación del déficit de vitamina B12: a propósito de un caso / Pseudoathetosis of the upper limbs as a manifestation of vitamin B12 deficit: about a case

RESUMEN INTRODUCCIÓN: La ganglionopatía sensitiva es una rara complicación del déficit de vitamina B12, la cual da origen a un espectro de síntomas neurológicos que incluyen alteración de la sensibilidad vibratoria, propiocepción, ataxia y, con menor frecuencia, trastornos del movimiento. La pseudoatetosis es una presentación muy inusual. CASO CLÍNICO: Un paciente masculino de 73 años se presenta con parestesias y torpeza de las cuatro extremidades, dolor tipo urente en plantas de pies y manos, inestabilidad postural y limitación para la marcha. En la exploración neurológica se encuentra hipoestesia y ataxia sensitiva de las cuatro extremidades, con presencia de pseudoatetosis de los miembros superiores como consecuencia de ganglionopatía por déficit de vitamina B12 demostrada por la imagen típica de "V" invertida, debido a compromiso de las proyecciones centrales las neuronas sensitivas mielinizadas en RMN de columna cervicotoráccica. A los cuatro meses se reporta mejoría del déficit propioceptivo y corrección del trastorno de movimiento gracias a la reposición de la cianocobalamina intramuscular. Hasta el momento no se presenta patología neoplásica, autoinmune o infecciosa. CONCLUSIONES: La ganglionopatía sensitiva por déficit de vitamina B12 es una condición potencialmente reversible y subdiagnosticada que puede manifestarse ocasionalmente con trastornos del movimiento. Debe sospecharse en pacientes con déficits sensitivos por compromiso de fibra gruesa. Su pronóstico es favorable si la causa del déficit se documenta tempranamente y se hace reposición de dicha vitamina.

SUMMARY INTRODUCTION: Sensory ganglionopathy is a rare complication of vitamin B12 deficiency, causing an spectrum of neurologic symptoms such as abnormal vibratory sensitivity, proprioception, gait disturbance and rarely movement disorders like pseudoatetosis and dystonia. CLINICAL CASE: A73-year-old man was admitted with numbness and clumsiness of his extremities, burning pain on palms and soles, postural instability and impaired walking. Neurological examination demonstrated hypesthesia and sensory ataxia of four limbs with associated pseudo athetoid movements of the upper limbs as a consequence of ganglionopathy by vitamin B12 deficiency, showing typical MRI inverted "V" sign due to degeneration of central projections from large sensory neurons, which was successfully treated with IM cyanocobalamin 4 months later. CONCLUSIONS: Sensory ganglionopathy in B12 deficit is a potentially reversible and underdiagnosed condition, which occasionally can present with movement disorders. Must be suspected in patiens presenting with sensory deficits depending on richly myelinated axons. Usually with good prognosis after identifying the deficit's cause and giving propper treatment.

Paracoccidioidomicosis con compromiso de sistema nervioso central / Paracoccidioidomycosis with central nervous system involvement

RESUMEN La paracoccidioidomicosis (PMC) es una micosis endémica que afecta a diferentes regiones de América Central y América del Sur. Esta enfermedad es causada por el Paracoccidioides brasiliensis y por el Paracoccidioides lutzii. Su presentación clínica puede ser aguda, subaguda o crónica y afectar a diversos sistemas, incluido el sistema nervioso central. El compromiso pulmonar y el de mucosa suelen ser los más comunes. La neuroparacoccidioidomicosis (NPCM) se presenta hasta en un 25 % de los pacientes con PMC y puede ser clasificada como meníngea o pseudotumoral. Sus síntomas neurológicos pueden ir desde cefalea hasta déficit motor, dependiendo de la localización. El estudio del líquido cefalorraquídeo es inespecífico y el aislamiento microbiológico es muy raro. Las lesiones observadas en neuroimágenes pueden confundirse con otras infecciones micóticas o incluso tumores. El estudio histológico permite confirmar el diagnóstico. Para el tratamiento de la NPCM se puede utilizar trimetoprim-sulfametaxazol, anfotericina B y fluconazol. Algunos casos pueden requerir manejo quirúrgico.

SUMMARY Paracoccidioidomycosis (PMC) is an endemic mycosis that affects different regions of Central and South America. This disease is caused by Paracoccidioides brasiliensis and Paracoccidioides lutzii. Its clinical presentation can be acute, subacute or chronic, affecting different systems including the central nervous system. Lung and mucosal involvement are the most common. Neuroparacoccidioidomycosis (NPCM) occurs in 25 % of patients with PMC, it can be classified as meningeal or pseudotumoral form. Its neurological symptoms can present as headache or motor deficit, that depends on the location. The study of cerebrospinal fluid is nonspecific and microbiological isolation is very rare. Lesions seen on neuroimaging can be confused with other fungal infections or even tumors. Histological study confirms the diagnosis. Trimethoprim-sulfamethaxazole, amphotericin B, and fluconazole can be used for the treatment of NPCM. Some cases may require surgical management.