Membrane phospholipids activate the inflammatory response in macrophages by various mechanisms.

Exosomes, which are small membrane-encapsulated particles derived from all cell types, are emerging as important mechanisms for intercellular communication. In addition, exosomes are currently envisioned as potential carriers for the delivery of drugs to target tissues. The natural population of exosomes is very variable due to the limited amount of cargo components present in these small vesicles. Consequently, common components of exosomes may play a role in their function. We have proposed that membrane phospholipids could be a common denominator in the effect of exosomes on cellular functions. In this regard, we have previously shown that liposomes made of phosphatidylcholine (PC) or phosphatidylserine (PS) induced a robust alteration of macrophage (Mϕ) gene expression. We herewith report that these two phospholipids modulate gene expression in Mϕs by different mechanisms. PS alters cellular responses by the interaction with surface receptors, particularly CD36. In contrast, PC is captured by a receptor-independent process and likely triggers an activity within endocytic vesicles. Despite this difference in the capture mechanisms, both lipids mounted similar gene expression responses. This investigation suggests that multiple mechanisms mediated by membrane phospholipids could be participating in the alteration of cellular functions by exosomes.

Transgene-Free Cynomolgus Monkey iPSCs Generated under Chemically Defined Conditions.

Non-human primates (NHPs) are pivotal animal models for translating novel cell replacement therapies into clinical applications, including validating the safety and efficacy of induced pluripotent stem cell (iPSC)-derived products. Preclinical development and the testing of cell-based therapies ideally comprise xenogeneic (human stem cells into NHPs) and allogenic (NHP stem cells into NHPs) transplantation studies. For the allogeneic approach, it is necessary to generate NHP-iPSCs with generally equivalent quality to the human counterparts that will be used later on in patients. Here, we report the generation and characterization of transgene- and feeder-free cynomolgus monkey (Macaca fascicularis) iPSCs (Cyno-iPSCs). These novel cell lines have been generated according to a previously developed protocol for the generation of rhesus macaque, baboon, and human iPSC lines. Beyond their generation, we demonstrate the potential of the novel Cyno-iPSCs to differentiate into two clinically relevant cell types, i.e., cardiomyocytes and neurons. Overall, we provide a resource of novel iPSCs from the most frequently used NHP species in the regulatory testing of biologics and classical pharmaceutics to expand our panel of iPSC lines from NHP species with high relevance in preclinical testing and translational research.

Intestinal intussusception as a postoperative complication of gastric bypass.

The gold standard for bariatric surgery is the laparoscopic gastric bypass, which consists in forming a small gastric pouch and a Roux-en-Y anastomosis. We present the case of a 41-year-old female who underwent a laparoscopic gastric bypass 8 years prior to her admission to the emergency room, where she arrived complaining of severe and colicky epigastric abdominal pain. The abdominal computed tomography showed a jejuno-jejunal intussusception, for which the patient underwent urgent exploratory laparotomy with intussusception reduction. Intestinal intussusception is a possible postoperative complication of a Roux-en-Y gastric bypass.

El Método de referencia en la cirugía bariátrica es el bypass gástrico laparoscópico, que consiste en la creación de una bolsa gástrica pequeña, anastomosada al tracto digestivo mediante una Y de Roux. Presentamos el caso de una mujer de 41 años con el antecedente de un bypass gástrico laparoscópico realizado 8 años antes, quien ingresó al servicio de urgencias refiriendo dolor abdominal grave. La tomografía computarizada abdominal evidenció una intususcepción a nivel de la anastomosis yeyuno-yeyuno, por lo que se realizó una laparotomía exploradora con reducción de la intususcepción. Se debe considerar la intususcepción intestinal como complicación posoperatoria de bypass gástrico.

ZNF692 regulates nucleolar morphology by interacting with NPM1 and modifying its self-assembly properties.

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells.

In vitro bioassays to monitor complex chemical mixtures at a carbon-based indirect potable reuse plant.

Potable water reuse technologies are used to treat wastewater to drinking water quality to help sustain a community's water resources. California has long led the adoption of potable water reuse technologies in the United States and more states are exploring these technologies as water resources decline. Reuse technologies also need to achieve adequate reductions in microbial and chemical contaminant risks to meet public health goals and secure public acceptance. In vitro bioassays are a useful tool for screening if reuse treatment processes adequately reduce toxicity associated with a range of chemical classes that are contaminants of concern. In this study, we used an aryl hydrocarbon receptor (AhR) and an estrogen receptor luciferase bioassay to detect the presence of dioxin-like and estrogenic compounds across a 3800 m3/d carbon-based indirect potable reuse plant that uses carbon-based treatment (SWIFT-RC). Our results demonstrate significant removal of dioxin-like compounds across the SWIFT-RC treatment train. Estrogenicity declined across the treatment train for some months but was extremely variable and low with many samples falling below the method quantification level; consequently, we were not able to reliably determine estrogenicity trends for SWIFT-RC. Comparing the bioanalytical equivalent concentrations detected in the SWIFT-RC water with established monitoring trigger levels from the state of California suggests that SWIFT-RC produced water that met the bioassay guidelines. The log total organic carbon concentration and AhR assay equivalent concentrations are weakly correlated when data across all SWIFT-RC processes are included. Overall, this research demonstrates the performance of in vitro bioassays at a demonstration-scale carbon-based IPR system and highlights both the potential utility and challenges associated with these methods for assessing system performance.

Robotic-assisted sigmoidectomy with intracorporeal anastomosis and endoscopic management of deep infiltrating intestinal endometriosis.

Deep endometriosis, defined as external adenomyosis, is a late stage of endometriosis. Associated with very severe pain, in addition to probably being a cofactor of infertility, with a low prevalence, the diagnosis is integrated by high clinical suspicion and confirmed with imaging studies. Deep infiltration can reach sigmoid colon, which would have surgical indication as resolving treatment. We report the case of deep infiltrating endometriosis affecting sigmoid colon of a 42-year-old woman, who was diagnosed with colicky pain in the left lower quadrant and chronic constipation. Colonoscopy revealed a 90% stenosis in the proximal portion of sigmoid colon, as well as mural thickening proximal to the site of stenosis, reported by computed tomography with oral contrast, for which it was decided to perform robot-assisted sigmoidectomy, with a 6-month follow-up and with imaging control, patient continues asymptomatic and without the presence of lesions suggestive of recurrence, and there is no functional impairment.

Redox stress shortens lifespan through suppression of respiratory complex I in flies with mitonuclear incompatibilities.

Incompatibilities between mitochondrial and nuclear genes can perturb respiration, biosynthesis, signaling and gene expression. Here we investigate whether mild mitonuclear incompatibilities alter the physiological response to redox stress induced by N-acetyl cysteine (NAC). We studied three Drosophila melanogaster lines with mitochondrial genomes that were either coevolved (WT) or mildly mismatched (BAR, COX) to an isogenic nuclear background. Responses to NAC varied substantially with mitonuclear genotype, sex, tissue and dose. NAC caused infertility and high mortality in some groups, but not others. Using tissue-specific high-resolution fluorespirometry, we show that NAC did not alter H2O2 flux but suppressed complex I-linked respiration in female flies, while maintaining a reduced glutathione pool. The high mortality in BAR females was associated with severe (>50 %) suppression of complex I-linked respiration, rising H2O2 flux in the ovaries, and significant oxidation of the glutathione pool. Our results suggest that redox stress is attenuated by the suppression of complex-I linked respiration, to the point of death in some mitonuclear lines. We propose that suppression of complex I-linked respiration is a general mechanism to maintain redox homeostasis in tissues, which could offset oxidative stress in ageing, producing a metabolic phenotype linked with epigenetic changes and age-related decline.

Immuno(T)herapy for age-related diseases.

During the last decade, the stimulation of T-cell function by the blockage of immunosuppressive checkpoints has experienced an outstanding impact in the treatment of cancer. Development of the chimeric antigen receptor T-cell technology has also emerged as a powerful alternative for patients suffering from oncological processes, especially those affected by hematological neoplasms. Recent evidence suggest that the use of immunotherapy could be extended to non-oncological diseases and could be especially relevant for age-associated disorders, opening exciting therapeutic options for a wide range of diseases of the elderly. Here we comment on the emergence of T-cell-based immunotherapies as feasible approaches that could revolutionize the future of GeroScience.

Anestesia intravenosa total para cirugía videolaparoscópica electiva en pacientes geriátricos / Total intravenous anesthesia for elective videolaparoscopic surgery in geriatric patients

Introducción: El surgimiento de fármacos anestésicos de corta duración estimularon a los anestesiólogos a plantearse un nuevo enfoque para la cirugía videolaparoscópica en el adulto mayor. Analgesia intensa, menor consumo de opioides, rápida recuperación de la conciencia y ventilación espontánea; extubación precoz, disminución de complicaciones y reducción de la estancia hospitalaria. Objetivo: Evaluar en los pacientes geriátricos programados para colecistectomía videolaparoscópica electiva, el efecto de la anestesia intravenosa total con la asociación ketamina/propofol en comparación con fentanil/propofol. Métodos: Se realizó un estudio cuasiexperimental en 40 pacientes con 60 años y más, estado físico II-III según la clasificación de ASA, en el Hospital Universitario "Faustino Pérez Hernández" de Matanzas, programados para cirugía videolaparoscópica electiva. Resultados: La edad promedio osciló entre 63 y 78 años, con una superioridad del sexo femenino y la raza blanca, la clasificación ASA II fue la más representativa en ambos grupos. Imperaron los antecedentes cardiovasculares, hubo ligera disminución de valores espirados de CO2 respecto a los basales, sin diferencias significativas. Hubo variación de la TAM indistintamente en ambos grupos. En el grupo 1 la frecuencia cardiaca posterior a la inducción disminuyó (70 ± 5 lat/min) y se mantuvieron valores inferiores a los basales durante los primeros 20 min, el tiempo medio de recuperación fue significativamente menor en el grupo 2. Conclusiones: La asociación ketamina/propofol proporciona resultados positivos finales.

Introduction: The emergence of short-acting anesthetic drugs stimulated the anesthesiologist to consider a new approach for videolaparoscopic surgery in the elderly. Intense analgesia, decreased opioid consumption, rapid recovery of consciousness, and spontaneous ventilation; early extubation, reduction of complications and reduction of hospital stay. Objective: To evaluate in geriatric patients scheduled for elective videolaparoscopic cholecystectomy the effects of total intravenous anesthesia with the combination of ketamine / propofol, comparing it with fentanyl / propofol. Materials and methods: a descriptive, prospective, longitudinal study was carried out in 40 patients aged 60 years and over, ASA II-III at the "Faustino Pérez Hernández" University Hospital in Matanzas in 2018, scheduled for elective videolaparoscopic surgery. Results: The average age ranged between 63 and 78 years, with a superiority of the female sex and the white race. The ASA II classification was the most representative in both groups. Cardiovascular antecedents prevailed, there was a slight decrease in expired CO2 values compared to baseline, without significant differences. There was variation of the TAM indistately in both groups. In group 1, the heart rate after induction decreased (70 ± 5 beats/min) and values lower than baseline were maintained during the first 20 min. The mean recovery time was significantly shorter in group 2. Conclusions: The association ketamine / propofol provides final positive results.

Coumel tachycardia in children / Taquicardia de Coumel en niños

Abstract Background: Coumel tachycardia is an infrequent form of supraventricular tachycardia (SVT) that usually occurs in infants and children. It is a tachycardia mediated by an accessory pathway with retrograde slow conduction that explains the classic ECG pattern with long RP' interval and negative P waves in leads II, III, and aVF. In this study, we describe the clinical course and management of Coumel tachycardia in children. Case report: We conducted a retrospective review of five consecutive pediatric patients, mean age 11 ± 3 years (range 6 to 14). The first episode of SVT was at a mean age of 10.4 ± 4.8 years (range 2 to 14) with a mean evolution of 7.4 ± 9.4 months (range 1 to 24). Pharmacological therapy was unsuccessful despite the combination of antiarrhythmic drugs. The tachycardia was incessant with a density > 85% by 24-hour Holter monitoring; one patient developed tachycardia-induced cardiomyopathy. All children underwent successful radiofrequency catheter ablation, mean 5 ± 3 applications (range 1 to 8) with a single session and with no complications. After a mean follow-up of 24 ± 16 months, all patients were asymptomatic and recurrence-free without antiarrhythmic treatment. Conclusions: Coumel tachycardia is clinically persistent and usually refractory to antiarrhythmic treatment with substantial risk of tachycardia-mediated cardiomyopathy. Catheter ablation is effective and safe in children; thus, it should be indicated promptly and based on individual selection.

Resumen Introducción: La taquicardia de Coumel es una forma poco frecuente de taquicardia supraventricular que suele presentarse en lactantes. Es una taquicardia mediada por una vía accesoria de conducción lenta retrógrada que explica el patrón ECG clásico con intervalo RP' largo y ondas P negativas en las derivaciones II, III y aVF. En este trabajo se describe el curso clínico y el manejo de la taquicardia de Coumel en niños. Caso clínico: Se llevó a cabo una revisión retrospectiva de cinco pacientes pediátricos consecutivos, con una media de edad de 11 ± 3 años (intervalos 6 a 14). El primer episodio de taquicardia 10.4 ± 4.8 años con evolución de 7.4 ± 9.4 meses. El tratamiento farmacológico fue ineficaz a pesar de la combinación de antiarrítmicos. La taquicardia era incesante con una densidad > 85% por Holter-24h; un paciente desarrolló miocardiopatía inducida por taquicardia. Todos los niños fueron sometidos a ablación con catéter y radiofrecuencia con éxito, y un promedio de 5 ± 3 aplicaciones en una sola sesión y sin complicaciones. Después de un seguimiento de 24 ± 16 meses, todos los pacientes fueron asintomáticos y libres de recurrencia sin tratamiento antiarrítmico. Conclusiones: La taquicardia de Coumel es clínicamente persistente y generalmente refractaria al tratamiento antiarrítmico con un riesgo sustancial de miocardiopatía mediada por taquicardia. La ablación con catéter es eficaz y segura en niños, por lo que debe indicarse de forma temprana y en lactantes de una selección individual.

The ethics of nursing care for transgender people / A ética do cuidado de enfermagem às pessoas transgênero / La ética de la atención de enfermería a las personas transgénero

ABSTRACT Objectives: to discuss ethical aspects in nursing care for transgender people. Methods: reflective study based on the dilemmas that emerges in nursing care for transgender people. The report was structured around the four bioethical principles. Results: health care for trans people is complex, transversal to many devices and specialties and longitudinal in time, that is why it requires coordinated action. There is an ethical framework in which the nursing care must be observed in the care of this group. Final Considerations: the nurse as a health worker can assume several general lines in the care of transgender patients. So, complementary training should be provided not only to professionals, but also to students of nursing and other health sciences.

RESUMO Objetivos: discutir aspectos éticos na assistência de enfermagem às pessoas transgênero. Métodos: estudo reflexivo a partir dos dilemas que surgem no cuidado de enfermagem às pessoas transgênero. O relato foi estruturado em torno dos quatro princípios bioéticos. Resultados: a atenção à saúde de pessoas trans é complexa, transversal a muitos dispositivos e especialidades e longitudinal no tempo, por isso requer ação coordenada. Existe um referencial ético no qual se enquadram os cuidados de enfermagem que devem ser observados no atendimento a esse grupo. Considerações Finais: o enfermeiro como agente de saúde pode assumir diversas linhas gerais no atendimento a pacientes transgênero. Para tal, deve ser proporcionada formação complementar não só aos profissionais, mas também aos estudantes de enfermagem e outras ciências da saúde.

RESUMEN Objetivos: debatir sobre aspectos éticos en la atención de enfermería a personas transgénero. Métodos: estudio reflexivo fundamentado sobre los dilemas que se plantean en los cuidados de enfermería a personas transgénero. El relato se ha estructurado en torno a los cuatro principios bioéticos. Resultados: la atención sanitaria a las personas trans es compleja, transversal a muchos dispositivos y especialidades y longitudinal en el tiempo por lo que precisa de la actuación coordinada. Existe un marco ético en el que se encuadran los cuidados de enfermería que se precisan en la atención a este colectivo. Consideraciones Finales: la enfermera como agente de salud puede asumir diversas líneas generales en la atención a pacientes transgénero. Para ello, se debe brindar formación adicional no solo a los profesionales, también a los estudiantes de enfermería y de las demás ciencias de la salud.

Synovial Sarcoma of the Foot as an Atypical Cause of Persistent Metatarsalgia: A Report of 3 Cases.

CASE: Three cases of atypical metatarsalgia are presented, all diagnosed with foot synovial sarcomas (SSs) at different stages of evolution, after a year of medical consultations. One case was treated with marginal excision without requiring bone excision; the second patient required amputation of the first ray; and the third patient, with advanced disease, required amputation through Chopart's joint. CONCLUSION: Metatarsalgia is a recurrent reason for consultation in orthopaedics. Even so, patients with persistent symptoms should be studied further in depth. Computed tomography or magnetic resonance imaging can detect tumor pathology, such as SS, of insidious development.

Anestesia espinal con bupivacaína más morfina en cirugía de urgencia de fractura intertrocantérica de cadera / Spinal anesthesia with bupivacaine plus morphine in urgent intertrochanteric hip fracture surgery

Introducción: La fractura de cadera en el anciano es una entidad frecuente y tiene gran incidencia en el mundo y en Cuba por el envejecimiento. Objetivo: Evaluar la eficacia de la anestesia espinal con bupivacaína más morfina en la cirugía de fractura intertrocantérica de cadera. Métodos: Se realizó un estudio clínico, experimental, no aleatorizado, prospectivo y de corte longitudinal en el Hospital Universitario Faustino Pérez Hernández de Matanzas de octubre de 2017 a octubre de 2019. El universo estuvo conformado por todos los pacientes quirúrgicos con fractura de cadera del hospital. La muestra se realizó por muestreo intencional, por 120 pacientes elegidos a criterio de los investigadores. Grupo control (B): Anestesia subaracnoidea con bupivacaína 0,5 por ciento 10 mg. Grupo estudio (M): Anestesia subaracnoidea con bupivacaína 0,5 por ciento 7 mg más 0,2 mg de morfina. Cada grupo estuvo integrado por 60 pacientes. Las variables analizadas fueron las siguientes: grupos de edades, género, estado físico, nivel de punción, tiempo de inicio del bloqueo motor, hipotensión arterial, uso de vasopresores y complicaciones secundarias a la técnica anestésica. Resultados: Predominó grupo de 84 y 90 años, género femenino y ASA III. La punción lumbar se realizó entre L3-L4. El tiempo de inicio del bloqueo motor fue 1,3 veces menor en el grupo M. Prevaleció la hipotensión arterial en el grupo B; y uso de vasopresores en ambos grupos. Predominó el prurito, grupo M, y la bradicardia, grupo B como complicaciones. Conclusiones: La asociación bupivacaína/morfina en anestesia espinal en adulto mayor para fractura de cadera proporciona mejores resultados sin complicaciones mayores(AU),

Introduction: Hip fracture in the elderly patient is a frequent entity with a high incidence worldwide and in Cuba due to aging. Objective: To assess the efficacy of spinal anesthesia with bupivacaine plus morphine in intertrochanteric hip fracture surgery. Methods: A clinical, experimental, nonrandomized, prospective, prospective and longitudinal study was carried out in Faustino Pérez Hernández University Hospital of Matanzas, from October 2017 to October 2019. The universe consisted of all surgical patients with hip fracture attended in the hospital. The sample was made by purposive sampling, consisting of 120 patients chosen at the discretion of the researchers. The control group (B) was administered subarachnoid anesthesia with 10 mg of bupivacaine 0.5 percent. The study group (M) was administered subarachnoid anesthesia with 7 mg of bupivacaine 0.5 percent. plus 0.2 mg of morphine. Each group consisted of 60 patients. The following variables were analyzed: age groups, gender, physical condition, puncture level, motor block onset time, arterial hypotension, use of vasopressors, and complications secondary to the anesthetic technique. Results: The predominant age group was 84 and 90 years old, together with female gender and ASA III. Lumbar puncture was performed between L3 and L4. The motor block onset time was 1.3 times shorter in the M group. Arterial hypotension prevailed in the B group; apart from the use of vasopressors in both groups. As complications, there was a predominance of pruritus in the M group and bradycardia in the B group. Conclusions: The association bupivacaine/morphine in spinal anesthesia for hip fracture among elderly adults provides better outcomes without major complications(AU)

Idiopathic left fascicular ventricular tachycardia in children and adolescents / Taquicardia ventricular fascicular izquierda idiopática en niños y adolescentes

Abstract Background: Idiopathic ventricular tachycardia (VT) in children with structurally normal hearts is generally unrelated to the risk of sudden arrhythmic death. Still, it may be associated with deterioration in the quality of life. VT involving the fascicular conduction system is the most typical form of idiopathic left VT. In this retrospective study, we describe the experience of the clinical presentation, catheter ablation, and long-term follow-up of left fascicular VT in children. Methods: An electrophysiological study was performed on consecutive children at a single tertiary center. Clinical fascicular left VT was induced by programmed stimulation, and catheter ablation was guided searching for Purkinje potentials. Results: We included 18 patients (0.8 patients/year): 14 (77.8%) males and four females. The mean age of the first VT episode was 8.5 ± 5 years. Intravenous verapamil administration was effective for paroxysmal fascicular VT but not for prevention of recurrences. The mean age at the time of catheter ablation was 11.1 ± 3.8 years (8 months-16 years). The mean weight was 36.8 ± 16.4 kg (8.7-58 kg). A 100% success rate was observed with catheter ablation after repeated procedures without major complications. Mean follow-up was 2.0 ± 1.2 years (1.0-4.0 years, median 1.5), with permanent success in all patients and no antiarrhythmic drug administration. Conclusions: Fascicular VT has an adverse clinical course in children. In most cases, this condition is drug refractory. Catheter ablation is successful and safe treatment and should represent the first-line approach in symptomatic children.

Resumen Introducción: La taquicardia ventricular (TV) idiopática en niños con corazón estructuralmente normal generalmente no se relaciona con el riesgo de muerte súbita arrítmica, pero puede asociarse con deterioro de la calidad de vida. La TV que involucra el sistema de conducción fascicular es la forma más común de TV izquierda idiopática. En este estudio retrospectivo se describe la experiencia de presentación clínica, ablación con catéter y seguimiento a largo plazo de TV fascicular en niños. Métodos: Se llevó a cabo un estudio electrofisiológico en niños consecutivos en un centro terciario. La TV fascicular clínica se indujo mediante la estimulación programada y la ablación con catéter fue guiada buscando el registro de potenciales de Purkinje. Resultados: Se incluyeron 18 pacientes (0.8 pacientes/año): 14 (77.8%) de sexo masculino y cuatro de sexo femenino. La media de edad a la cual ocurrió el primer episodio fue de 8.5 ± 5 años. La administración intravenosa de verapamilo fue eficaz para la TV fascicular paroxística, pero no para prevención de recurrencias. La media de edad de la ablación con catéter fue de 11.1 ± 3.8 años (8 meses-16 años). La media del peso fue 36.8 ± 16.4 kg (8.7-58 kg). Se observó el 100% de éxito con la ablación con catéter después de procedimientos repetidos sin complicaciones mayores. La media de seguimiento fue de 2.0 ± 1.2 años (1.0-4.0, mediana de 1.5 años) con éxito permanente en todos los pacientes y sin administración de fármacos antiarrítmicos. Conclusiones: En niños, el curso clínico de la TV fascicular es adverso. Además, en la mayoría de los casos, esta condición es refractaria a fármacos. La ablación con catéter resulta exitosa y segura y debe representar el abordaje de primera línea en niños sintomáticos.

The "diagnose and leave in" strategy for diminutive rectosigmoid polyps in Lynch syndrome: a post hoc analysis from a randomized controlled trial.

BACKGROUND: The "diagnose-and-leave-in" policy has been established to reduce the risks and costs related to unnecessary polypectomies in the average-risk population. In individuals with Lynch syndrome, owing to accelerated carcinogenesis, the general recommendation is to remove all polyps, irrespective of size, location, and appearance. We evaluated the feasibility and safety of the diagnose-and-leave-in strategy in individuals with Lynch syndrome. METHODS : We performed a post hoc analysis based on per-polyp data from a randomized, clinical trial conducted by 24 dedicated colonoscopists at 14 academic centers, in which 256 patients with confirmed Lynch syndrome underwent surveillance colonoscopy from July 2016 to January 2018. In vivo optical diagnosis with confidence level for all detected lesions was obtained before polypectomy using virtual chromoendoscopy alone or with dye-based chromoendoscopy. Primary outcome was the negative predictive value (NPV) for neoplasia of high-confidence optical diagnosis among diminutive (≤ 5 mm) rectosigmoid lesions. Histology was the reference standard. RESULTS: Of 147 rectosigmoid lesions, 128 were diminutive. In 103 of the 128 lesions (81 %), the optical diagnostic confidence was high and showed an NPV of 96.0 % (95 % confidence interval [CI] 88.9 %-98.6 %) and accuracy of 89.3 % (95 %CI 81.9 %-93.9 %). By following the diagnose-and-leave-in policy, we would have avoided 59 % (75/128) of polypectomies at the expense of two diminutive low grade dysplastic adenomas and one diminutive sessile serrated lesion that would have been left in situ. CONCLUSION: In patients with Lynch syndrome, the diagnose-and-leave-in strategy for diminutive rectosigmoid polyps would be feasible and safe.

Disnatremias: un enfoque preciso, macizo y conciso / Dysnatremia: a precise, solid and concise approach / Disnatremia: uma abordagem precisa, sólida e concisa

Resumen: La disnatremia es la alteración electrolítica más frecuente en el paciente en estado crítico, con repercusión en la morbimortalidad. El sodio es el electrolito regulador más importante de la osmolaridad sanguínea; la relación inherente con la molécula del agua hace que esta dupla tenga una proporción interdependiente y recíproca. A través de esta revisión no sistemática de la literatura se pretende exponer la fisiología de sodio y la interacción con el agua, los mecanismos fisiopatológicos que conllevan a los extremos en la concentración sérica, así como los algoritmos diagnósticos y terapéuticos; para que de una manera precisa, maciza y concisa se puedan tomar decisiones médicas.

Abstract: Dysnatremia is the most frequent electrolyte alteration in critically ill patients, with repercussions on morbidity and mortality. Sodium is the most important regulating electrolyte of blood osmolarity; the inherent relationship with the water molecule makes this pair have an interdependent and reciprocal ratio. Through this unsystematic review of the literature, the aim is to expose the physiology of sodium and the interaction with water, the pathophysiological mechanisms that lead to extremes in serum concentration, as well as diagnostic and therapeutic algorithms; so that medical decisions can be made in a precise, solid and concise manner.

Resumo: A disnatremia é o distúrbio eletrolítico mais comum em pacientes críticos, com repercussões na morbidade e mortalidade. O sódio é o eletrólito regulador mais importante da osmolaridade do sangue; a relação inerente com a molécula de água faz com que este par tenha uma proporção interdependente e recíproca. Por meio desta revisão não sistemática da literatura, pretende-se expor a fisiologia do sódio e sua interação com a água, os mecanismos fisiopatológicos que levam a extremos na concentração sérica, bem como algoritmos diagnósticos e terapêuticos; para que de forma precisa, sólida e concisa as decisões médicas possam ser tomadas.

Mitonuclear Interactions Produce Diverging Responses to Mild Stress in Drosophila Larvae.

Mitochondrial function depends on direct interactions between respiratory proteins encoded by genes in two genomes, mitochondrial and nuclear, which evolve in very different ways. Serious incompatibilities between these genomes can have severe effects on development, fitness and viability. The effect of subtle mitonuclear mismatches has received less attention, especially when subject to mild physiological stress. Here, we investigate how two distinct physiological stresses, metabolic stress (high-protein diet) and redox stress [the glutathione precursor N-acetyl cysteine (NAC)], affect development time, egg-to-adult viability, and the mitochondrial physiology of Drosophila larvae with an isogenic nuclear background set against three mitochondrial DNA (mtDNA) haplotypes: one coevolved (WT) and two slightly mismatched (COX and BAR). Larvae fed the high-protein diet developed faster and had greater viability in all haplotypes. The opposite was true of NAC-fed flies, especially those with the COX haplotype. Unexpectedly, the slightly mismatched BAR larvae developed fastest and were the most viable on both treatments, as well as control diets. These changes in larval development were linked to a shift to complex I-driven mitochondrial respiration in all haplotypes on the high-protein diet. In contrast, NAC increased respiration in COX larvae but drove a shift toward oxidation of proline and succinate. The flux of reactive oxygen species was increased in COX larvae treated with NAC and was associated with an increase in mtDNA copy number. Our results support the notion that subtle mitonuclear mismatches can lead to diverging responses to mild physiological stress, undermining fitness in some cases, but surprisingly improving outcomes in other ostensibly mismatched fly lines.

Conocimientos, actitudes y prácticas sobre covid-19 en argentina. estudio tranversal / Knowledge, attitudes, and practices about COVID-19 in Argentina. A cross-sectional study

Resumen Nuestro objetivo fue evidenciar el nivel de conocimientos, actitudes y prácticas frente al COVID-19. Fueron encuestados 3774 individuos mayores de 16 años entre el 18/09/20 y el 16/10/20. El 80% residía en la ciudad de Buenos Aires o la Provincia de Buenos Aires. El 58% había completado estudio terciario. El 72% tenía actividad laboral independiente o en relación de dependencia pública o privada. Utilizaban el sistema de salud prepago el 51%, obra social laboral el 34%, y sistema público de salud cerca del 10%. De acuerdo a las variables socio-demográficas analizadas, la mayoría de la población fue representativa de la clase media. Del total de encuestados, el 7% tuvo diagnóstico de COVID-19. Observamos un alto nivel de conocimiento de la enfermedad, con 80 a 90% de respuestas correctas. En relación a las medidas adoptadas por las autoridades, los juicios emitidos variaron entre "correctas", "insuficientes", "perjudiciales", "innecesarias", etc. El 44% se sentía protegido por el sistema de salud. En cuanto a los referentes válidos para transmitir información, la respuesta preponderante fue el personal médico. En cuanto al momento deconsultar por síntomas, un porcentaje impor tante (28%) lo haría en forma tardía. Observamos un alto grado de cumplimiento de las medidas de protección, a excepción del ítem "Asistencia a reuniones" (50%). Los resultados de estos estudios contribuyen a establecer estrategias comunicacionales para la prevención y el control de la enfermedad y de ese modo enfrentar de forma más eficiente eventuales rebrotes de la enfermedad.

Abstract Our objective was to assess levels of knowledge, attitudes, and practices against COVID-19. A total of 3774 persons were surveyed between September 18 and October 16, 2020. Eighty% resided in Buenos Aires City or Buenos Aires Province: 58% had completed tertiary education; 72% worked either independently or as employees in the public or the private sector; 51% used a prepaid health care plan, 34% were covered by a trade union-based health system, and near 10% used the public health services. According to the socio-demographic variables analyzed, the population studied was representative of the middle class. A total of 7% had been diag nosed with COVID-19. There was a high level of knowledge about the disease, judging by the high proportion of correct answers (80-90%). Regarding the measures taken by the government, the answers varied widely ("correct", "inadequate", "harmful", "unnecessary", etc.). The medical staff was the preferred source of information; 44% of respondents felt protected by their health system; 28% would only seek healthcare when feeling very sick. There was a high degree of compliance with most protection measures, except for attendance to social events in poorly ventilated spaces (50%). The results of these studies contribute to establishing communication strategies for the prevention and control of COVID-19 and thus deal more efficiently with eventual outbreaks of the disease.

Diferencia de edad entre parejas sexuales como riesgo de infecciones de trasmisión sexual / Age difference in the choice of the sexual partner as a risk factor for sexually transmitted infections

Resumen Una diferencia de edad > 5 años en la elección de la pareja sexual puede constituir un factor de riesgo de infecciones de trasmisión sexual (ITS), incluida la infección por HIV. Se realizó una encuesta de salud sexual y reproductiva a personas que consultaron por ITS o serología para HIV en dos centros de salud del conurbano bonaerense, con el objetivo de brindar información para el diseño de medidas de prevención y conocer si en nuestra área existe asociación entre la máxima diferencia de edad (MDE) en la elección de la pareja sexual y la adquisición de HIV y/o ITS. Se incluyeron 120 consultantes. En 108 (90%) se investigó sero logía, resultando 15 (13.9%) positivos para HIV y 46 (42.6%) para sífilis. La MDE con la pareja fue ≤ 5 años en 65 (54.6%) y > 5 años en 54 (45.4%) de 119 que respondieron la encuesta. Los hombres que tenían sexo con hombres refirieron una MDE > 5 años con mayor frecuencia (p = 0.022, OR: 3.59). El riesgo de HIV aumentó 9% por cada año de diferencia de edad con la pareja sexual (OR: 1.093). El porcentaje de casos de uretritis fue significativamente menor en el grupo de edad ≥ 25 años. Ninguna de las personas con uretritis tenía infección HIV. En conclusión: en esta población los hombres que tenían sexo con hombres tendieron a elegir sus parejas sexuales con una MDE mayor, y una MDE mayor fue un factor de riesgo de infección HIV.

Abstract An age difference > 5 years in the choice of sexual partner may constitute a risk factor for sexually transmitted infections (STIs), including HIV infection. A sexual and reproductive health survey was carried out on people who consulted for STIs or HIV serology in two health centers in Buenos Aires suburbs, with the aim of providing information for the design of prevention measures and to know if in this area there is an association between the maximum age difference (MAD) in the choice of sexual partner and the acquisition of HIV and/or STIs. A total of 120 patients consulted, 90% (108) performed serology, resulting 15 of them (13.9%) infected with HIV and 46 (42.6%) with syphilis. The MAD with the partner was ≤ 5 years in 65 (54.6%) and > 5 years in 54 (45.4%) of 119 who answered the survey. Men who have sex with men reported a MAD > 5 years more frequently (p = 0.022 OR: 3.59). The risk for HIV increased 9% for each year of age difference with the sexual partner (OR: 1.093). The percentage of urethritis cases was significantly lower in the age group ≥ 25 years. None of the people with urethritis had HIV infection. In conclusion: Men who have sex with men tended to choose their sexual partners with a higher MAD, and a higher MAD was a risk factors for HIV infection.

Extracellular Tuning of Mitochondrial Respiration Leads to Aortic Aneurysm.

BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the FBN1 (fibrillin-1) gene encoding a large glycoprotein in the extracellular matrix called fibrillin-1. The major complication of this connective disorder is the risk to develop thoracic aortic aneurysm. To date, no effective pharmacologic therapies have been identified for the management of thoracic aortic disease and the only options capable of preventing aneurysm rupture are endovascular repair or open surgery. Here, we have studied the role of mitochondrial dysfunction in the progression of thoracic aortic aneurysm and mitochondrial boosting strategies as a potential treatment to managing aortic aneurysms. METHODS: Combining transcriptomics and metabolic analysis of aortas from an MFS mouse model (Fbn1c1039g/+) and MFS patients, we have identified mitochondrial dysfunction alongside with mtDNA depletion as a new hallmark of aortic aneurysm disease in MFS. To demonstrate the importance of mitochondrial decline in the development of aneurysms, we generated a conditional mouse model with mitochondrial dysfunction specifically in vascular smooth muscle cells (VSMC) by conditional depleting Tfam (mitochondrial transcription factor A; Myh11-CreERT2Tfamflox/flox mice). We used a mouse model of MFS to test for drugs that can revert aortic disease by enhancing Tfam levels and mitochondrial respiration. RESULTS: The main canonical pathways highlighted in the transcriptomic analysis in aortas from Fbn1c1039g/+ mice were those related to metabolic function, such as mitochondrial dysfunction. Mitochondrial complexes, whose transcription depends on Tfam and mitochondrial DNA content, were reduced in aortas from young Fbn1c1039g/+ mice. In vitro experiments in Fbn1-silenced VSMCs presented increased lactate production and decreased oxygen consumption. Similar results were found in MFS patients. VSMCs seeded in matrices produced by Fbn1-deficient VSMCs undergo mitochondrial dysfunction. Conditional Tfam-deficient VSMC mice lose their contractile capacity, showed aortic aneurysms, and died prematurely. Restoring mitochondrial metabolism with the NAD precursor nicotinamide riboside rapidly reverses aortic aneurysm in Fbn1c1039g/+ mice. CONCLUSIONS: Mitochondrial function of VSMCs is controlled by the extracellular matrix and drives the development of aortic aneurysm in Marfan syndrome. Targeting vascular metabolism is a new available therapeutic strategy for managing aortic aneurysms associated with genetic disorders.