The CRTC-1 transcriptional domain is required for COMPASS complex-mediated longevity in C. elegans.

Loss of function during aging is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy aging.

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective medications to reduce appetite and body weight. These actions are centrally mediated; however, the neuronal substrates involved are poorly understood. METHODS: We employed a combination of neuroanatomical, genetic, and behavioral approaches in the mouse to investigate the involvement of caudal brainstem cholecystokinin-expressing neurons in the effect of the GLP-1RA exendin-4. We further confirmed key neuroanatomical findings in the non-human primate brain. RESULTS: We found that cholecystokinin-expressing neurons in the caudal brainstem are required for the anorectic and body weight-lowering effects of GLP-1RAs and for the induction of GLP-1RA-induced conditioned taste avoidance. We further show that, while cholecystokinin-expressing neurons are not a direct target for glucose-dependent insulinotropic peptide (GIP), GIP receptor activation results in a reduced recruitment of these GLP-1RA-responsive neurons and a selective reduction of conditioned taste avoidance. CONCLUSIONS: In addition to disclosing a neuronal population required for the full appetite- and body weight-lowering effect of GLP-1RAs, our data also provide a novel framework for understanding and ameliorating GLP-1RA-induced nausea - a major factor for withdrawal from treatment.

Aneurismas de aorta abdominal infrarrenal y pararrenal: Resultados del reparo abierto

Objetivo: Determinar los resultados de los pacientes sometidos a cirugía de reparo abierto del aneurisma de aorta abdominal (AAA), infrarrenal (IR) y pararrenal (PR). Material y métodos: Estudio retrospectivo, tipo serie de casos. Se revisaron las historias de 75 pacientes con AAA, IR (55) y PR (20). Se determinó la mortalidad, complicaciones y reintervenciones. El seguimiento promedio fue de 5 años. Resultados : No hubo mortalidad operatoria en los 56 casos de reparo abierto electivo de AAA IR-PR. En los casos de AAA roto la mortalidad operatoria fue 31,6% (3/10 IR y 3/9 PR). Hubo disfunción renal KDIGO Estadio I en 14% de los IR y 33% de los PR, en ambos fue transitoria. Hubo 9% de reintervenciones que fueron tratados con resultado exitoso (4% tempranas y 5% tardías). Conclusiones : El reparo abierto electivo de los AAA IR y PR, puede realizarse con bajo riesgo de morbimortalidad operatoria y bajo riesgo de requerimiento de reintervención a corto y largo plazo. En los AAA rotos o de emergencia, el shock fue el factor asociado más importante para la mortalidad operatoria. Los resultados son equivalentes a publicaciones de centros especializados extranjeros.

SUMMARY Objective : To To determine the clinical outcomes of patients undergoing open surgical repairmen of abdominal aortic aneurisms (AAA), infrarenal abdominal aortic aneurisms (IAA) and pararenal abdominal aortic aneurisms (PAA). Methods : A case series involving the review of 75 patient records with AAA, 55 with IAA and 20 with PAA over a period of 5 years. Results: No intraoperatory mortality was detected in the 56 cases of elective surgeries for AAA, IAA and PAA. In cases of rupture AAA, the intraoperatory mortality was 31.6% (3/10 IAA and 3/9 PAA). Transient renal dysfunction KDIGO stage I in 14% of IAA and 33% of PAA. There was a need for re interventions in 9% all of them successful (4% early and 5% late). Conclusions: Elective open surgical repairmen of AAA, IAA and PAA can be performed at low intraoperatory risk for both morbidity and need for re intervention. In patients with rupture AAA, shock was associated with intraoperatory mortality. These results are similar to those reported from foreign specialized centers.

Efficacy of an Aquatic Exercise Program for 3 Cases of Rett Syndrome.

PURPOSE: To examine functional, physiological effects of participating in an aquatic exercise program by 3 girls, diagnosed with Rett syndrome (RS), to explore areas for possible new research. SUMMARY OF KEY POINTS: RS is a severe neurodevelopmental disorder, which causes multiple disabilities and serious impairments in neuromotor and cognitive abilities. Three girls (4, 6, and 7 years), diagnosed stage III RS, participated in 20 months of aquatic exercise, with individually tailored, full body exercises, progressively targeting functional, cardiorespiratory, muscle, and flexibility training. Assessments included resting and exercise heart rates, anthropometric measures, functional, clinical aspects, and psychosocial abilities. CONCLUSIONS: The participants improved functional ability, mood status, relations with family and schoolmates, joint mobility, muscle strength, and endurance during functional activities. Periodic evaluation of exercise heart rates averaged an increase in intensity of 33% above baseline, indicating cardiorespiratory stimulus. This pilot program provides clinical rationale for future studies and clinical interventions for RS children.

Rhabdomyosarcoma debut masquerading as acute lymphoblastic leukemia: A case report and review of the literature.

Bone marrow infiltration by alveolar rhabdomyosarcoma is uncommon, some cases can mimicry acute leukemia at presentation and mislead the diagnosis. The integration of diagnostics tests and techniques in uncommon malignancies is important to suspect and reach the diagnosis and avoid delay on treatment. We report a case of alveolar rhabdomyosarcoma bone marrow infiltration associated with hemophagocytosis and cell cannibalism, mimicking acute leukemia at presentation.

Urinary Metabolites Altered during the Third Trimester in Pregnancies Complicated by Gestational Diabetes Mellitus: Relationship with Potential Upcoming Metabolic Disorders.

Gestational diabetes mellitus (GDM) is a disorder in pregnancy with highest impact in the future life of both mother and newborn. Increasing incidence, economic impact, and potential for severe GDM-related pregnancy complications are some factors that have motivated the deep study of physiopathology, risk factors for developing GDM, and potential biomarkers for its diagnosis. In the present pilot study, we analyzed the urinary metabolome profile of GDM patients in the 3rd trimester of pregnancy, when GDM is already established and the patients are under dietary and pharmacological control. An untargeted metabolomics method based on liquid chromatography⁻mass spectrometry analysis was developed to identify differentially expressed metabolites in the GDM group. We identified 14 metabolites that are significantly upregulated in the urine of GDM patients, and, more importantly, we identified those related with the steroid hormone biosynthesis and tryptophan (TRP) metabolism pathways, which are associated with GDM pathophysiology. Thus, these metabolites could be screened as potential prognostic biomarkers of type two diabetes mellitus, coronary artery disease and chronic renal failure in future follow-up studies with GDM patients.

La superación y el desempeño profesional del tecnólogo en Rehabilitación desde la Educación Avanzada / A superação e a atuação profissional do tecnólogo em Reabilitação pela Educação Avançada / The overcoming and the professional performance of the technologist in Rehabilitation from Advanced Education

Introducción: la superación profesional debe ser un proceso que se caracterice por su papel transformador sobre el egresado de las universidades médicas y que a la vez permita que este se convierta en un agente de cambio en su radio de acción. Objetivo: exponer una breve síntesis de la superación y mejoramiento del desempeño del Tecnólogo en Rehabilitación en Salud. Método: se realizó un estudio de corte pedagógico en la Facultad de Ciencias Médicas de Guantánamo, durante el período 2017-2018, donde se emplearon como métodos de orden teórico el análisis documental y la sistematización, los cuales permitieron organizar y extraer información relevante, a partir de la amplia revisión bibliográfica realizada sobre el tema, que favoreció la argumentación de la superación para el mejoramiento del desempeño profesional del Tecnólogo en Rehabilitación en Salud desde la Educación Avanzada. Resultados: los elementos ofrecidos, conducen a comprender la interrelación que se establece entre superación y desempeño profesional, ambos procesos vinculados al progreso científico técnico a partir de garantizar la actualización de los profesionales altamente calificados y mejorar el trabajo que desempeñan. Conclusiones: entre los fundamentos teóricos asumidos, referidos a la superación y el desempeño profesional constituyeron referentes teóricos importantes las definciones de Añorga Morales(AU)

Introduction: professional improvement must be a process characterized by its transforming role over the graduate of medical universities and at the same time allowing it to become an agent of change in its radius of action. Objective: to present a brief summary of the overcoming and improvement of the performance of the Technologist in Health Rehabilitation. Method: a pedagogical study was carried out in the Faculty of Medical Sciences of Guantanamo, during the period 2017-2018, where documentary analysis and systematization were used as theoretical methods, which allowed to organize and extract relevant information, Based on the extensive bibliographical review carried out on the subject, which favored the argumentation of the overcoming for the improvement of the professional performance of the Technologist in Rehabilitation in Health from Advanced Education. Results: the offered elements, lead to understand the interrelation that is established between overcoming and professional performance, both processes linked to the scientific and technical progress from guaranteeing the updating of highly qualified professionals and improving the work they perform. Conclusions: among the assumed theoretical foundations, referred to the overcoming and the professional performance, the definitions of Añorga Morales constituted important theoretical referents(AU)

Introdução: o aprimoramento profissional deve ser um processo caracterizado por seu papel transformador sobre a formação das universidades médicas e, ao mesmo tempo, permitir que se torne agente de mudança em seu raio de ação. Objetivo: apresentar um breve resumo do aprimoramento e melhoria do desempenho do Tecnólogo em Reabilitação em Saúde. Método: um estudo de corte pedagógica foi realizada na Faculdade de Ciências Médicas de Guantánamo, durante o período 2017-2018, que foram usados como métodos de análise documento de ordem teórica e sistematização, que ajudaram a organizar e extrair informações relevantes, com base na extensa revisão bibliográfica realizada sobre o assunto, favoreceu a argumentação da melhoria para a melhoria da atuação profissional do Tecnólogo em Reabilitação em Saúde pela Educação Avançada. Resultados: os elementos oferecidos, levar à compreensão da interrelação estabelecida entre melhoria e desempenho profissional, ambos ligados ao progresso científico técnico de atualizar garantir profissionais altamente qualificados e melhorar os processos de trabalho jogados. Conclusões: entre os fundamentos teóricos assumidos, referidos à superação e à atuação profissional, as definições de Añorga Morales constituíram importantes referentes teóricos(AU)

[Persistent abdominal pain caused by superior mesenteric artery and celiac trunk dissection that does not respond to conservative treatment]. / Dolor abdominal persistente por disección de arteria mesentérica superior y tronco celiaco, que no responde a tratamiento conservador.

We report the case of a 32 year old male with recurrent colic abdominal pain due to superior mesenteric artery (SMA) and celiac trunk dissection, which resolved after placing 3 stents in SMA. The patient presented atypical clinical signs and symptoms, which made the diagnosis difficult. Clinical presentation, diagnostic methods and treatment options are discussed. We started with conservative management with pain medication, anticoagulation, antihypertensive drugs and image control, but on the seventh day, after restarting oral ingestion, he presented with abdominal angina, after which we proceeded to endovascular treatment with successful results and with an uneventfully 2 year follow up.

Lorcaserin improves glycemic control via a melanocortin neurocircuit.

OBJECTIVE: The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT2CR) agonist, improves glycemic control in association with weight loss in obese patients with T2D. Here we evaluate whether lorcaserin has an effect on glycemia without body weight loss and how this effect is achieved. METHODS: Murine models of common and genetic T2D were utilized to probe the direct effect of lorcaserin on glycemic control. RESULTS: Lorcaserin dose-dependently improves glycemic control in mouse models of T2D in the absence of reductions in food intake or body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin's glucoregulatory effects, brain pro-opiomelanocortin (POMC) peptides. To clarify further lorcaserin's therapeutic brain circuit, we examined the receptor target of POMC peptides. We demonstrate that lorcaserin requires functional melanocortin4 receptors on cholinergic preganglionic neurons (MC4RChAT) to exert its effects on glucose homeostasis. In contrast, MC4RChAT signaling did not impact lorcaserin's effects on feeding, indicating a divergence in the neurocircuitry underpinning lorcaserin's therapeutic glycemic and anorectic effects. Hyperinsulinemic-euglycemic clamp studies reveal that lorcaserin reduces hepatic glucose production, increases glucose disposal and improves insulin sensitivity. CONCLUSIONS: These data suggest that lorcaserin's action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease.

Aneurismas de carótida extracraneal: técnicas quirúrgicas y endovasculares. A propósito de 4 casos / Extracranial carotid aneurisms: surgical and endovascular techniques. Report of 4 cases

Se presentan 4 casos de aneurismas o pseudoaneurismas de la arteria carótida interna extracraneal. A diferencia de la estenosis carotídea, esta patología es poco frecuente; por lo que las recomendaciones en cuanto al diagnóstico y tratamiento no son uniformes y aun están en discusión, representando así un reto para los médicos de la especialidad. Cada uno de los casos descritos fue tratado de forma particular a las características de anatomía, forma de presentación y riesgos de cada paciente. Los casos fueron de sexo masculino y con un rango etario desde 24 años hasta 77 años de edad. Dos de ellos fueron tratados de forma quirúrgica convencional y dos de forma endovascular. Se presenta las opciones de tratamiento quirúrgico y endovascular en nuestro medio en una enfermedad en la que se tiene experiencia limitada en la mayoría de centros médicos a nivel mundial. (AU)

We present 4 cases of extracranial internal carotid aneurisms or pseudo aneurisms. Opposite to carotid stenosis, this entity is rare, and recommendations for its diagnosis and treatment are not standardized and subject to controversy. Each of the cases presented here were treated differently. All cases were males ranging in age from 24 to 77 years of age; 2 were treated using conventional surgical methods and the remaining two using an endovascular approach. We present here the surgical options for a rare entity with limited worldwide experience. (AU)

Dolor abdominal persistente por disección de arteria mesentérica superior y tronco celiaco, que no responde a tratamiento conservador / Persistent abdominal pain caused by superior mesenteric artery and celiac trunk dissection that does not respond to conservative treatment

Reportamos el caso de un paciente varón de 32 años con dolor abdominal recurrente tipo cólico a causa de disección de arteria mesentérica superior (AMS) y tronco celíaco, el cual se resolvió luego de la colocación de 3 stents en AMS. El paciente presentó una clínica atípica lo cual dificultó el diagnóstico. Discutimos la clínica, métodos diagnósticos y alternativas de tratamiento. Iniciamos con un manejo conservador con analgesia, anticoagulación plena, antihipertensivo y control de imágenes, pero al séptimo día luego de reiniciar la vía oral, presenta angina abdominal, por lo cual procedimos a tratamiento endovascular con resultado exitoso y buena evolución, sin eventos, a un seguimiento de 2 años

We report the case of a 32 year old male with recurrent colic abdominal pain due to superior mesenteric artery (SMA) and celiac trunk dissection, which resolved after placing 3 stents in SMA. The patient presented atypical clinical signs and symptoms, which made the diagnosis difficult. Clinical presentation, diagnostic methods and treatment options are discussed. We started with conservative management with pain medication, anticoagulation, antihypertensive drugs and image control, but on the seventh day, after restarting oral ingestion, he presented with abdominal angina, after which we proceeded to endovascular treatment with successful results and with an uneventfully 2 year follow up

Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice.

BACKGROUND: Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. METHODS: We combined neuroanatomic, pharmacologic, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-hydroxytryptamine (5-HT) 2C receptor (5-HT2CR) expressed by dopamine (DA) neurons in the regulation of binge-like eating behavior in mice. RESULTS: We showed that 5-HT stimulates DA neural activity through a 5-HT2CR-mediated mechanism, and activation of this midbrain 5-HT→DA neural circuit effectively inhibits binge-like eating behavior in mice. Notably, 5-HT medications, including fluoxetine, d-fenfluramine, and lorcaserin (a selective 5-HT2CR agonist), act on 5-HT2CRs expressed by DA neurons to inhibit binge-like eating in mice. CONCLUSIONS: We identified the 5-HT2CR population in DA neurons as one potential target for antibinge therapies, and provided preclinical evidence that 5-HT2CR agonists could be used to treat binge eating.

Building a Translengua in Latina Lesbian Organizing.

This article discusses the challenges and rewards, as well as the affective labor, involved in forging a Latina lesbian "translengua," in other words a common language in the context of Latina lesbian organizing. I explore how members of Latina Lesbians en Nuestro Ambiente (LLENA) and Amigas Latinas, Chicago-based Latina lesbian organizations, attempted to foster consensus for collective action in the face of language differences and preferences. Through analysis of archives and interviews with activists, I untangle how LLENA and Amigas Latinas negotiated deeply personal and sensitive issues around language use as they worked to build an inclusive movement. I also identify strategies used to enact a translengua that could bridge linguistic differences within the Latina lesbian community.

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation.

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HT2CR agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HT2CR expressing γ-aminobutyric acid (GABA) neurons, but not 5-HT2CR expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HT2CRCRE line to clarify the function of subset of 5-HT2C receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT2C receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT2C receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HT2CR neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity.

Algunas consideraciones teóricas sobre los antecedentes y evolución del proceso de superación del tecnólogo en Rehabilitación en salud / Some theoretical considerations about the background and evolution of the process of overcoming the technologist in Rehabilitation in health

Se realiza una investigación de corte descriptiva, con el objetivo de determinar los antecedentes y evolución del proceso de superación del tecnólogo en Rehabilitación en salud en la Universidad de Ciencias Médicas de Guantánamo. Se utilizaron métodos analíticos-sintéticos, inducción-deducción, histórico-lógico. Se concluyó que la concepción teórico general sobre la superación de los licenciados en Rehabilitación en Salud, ha transitado por diferentes momentos históricos que revelan características significativas para la Educación de Postgrado en la Salud Pública, igualmente constituye un requerimiento fundamental para el fortalecimiento y mantenimiento de la competencia profesional y en última instancia para elevar la calidad de asistencia médica integral al individuo, la familia y la comunidad. La actividad de postgrado es indispensable para mantenerse actualizado en cuanto a conocimientos novedosos, a los principales problemas de salud del área, cuyo objetivo es lograr un mejor bienestar para la salud del hombre, y para ello se requiere de una educación continuada para satisfacer las necesidades y aumentar el nivel del servicio asistencial de salud que se brinde(AU)

A descriptive research was carried out, with the objective of determining the antecedents and evolution of the process of overcoming the technologist in Rehabilitation in health at the University of Medical Sciences of Guantanamo.It was used analytic-synthetic methods, induction-deduction, historical-logical. It was concluded that the general theoretical conception about the graduation of graduates in Rehabilitation in Health, has traveled through different historical moments that reveal significant characteristics for Postgraduate Education in Public Health, is also a fundamental requirement for the strengthening and maintenance of the Professional competence and ultimately to raise the quality of comprehensive medical care to the individual, family and community. The postgraduate activity is essential to keep up to date with new knowledge, the main health problems in the area, whose objective is to achieve a better well-being for the health of the man, and for that it requires a continued education to satisfy the needs and to increase the level of the health care service that is provided(AU)

Sex difference in physical activity, energy expenditure and obesity driven by a subpopulation of hypothalamic POMC neurons.

OBJECTIVE: Obesity is one of the primary healthcare challenges of the 21st century. Signals relaying information regarding energy needs are integrated within the brain to influence body weight. Central among these integration nodes are the brain pro-opiomelanocortin (POMC) peptides, perturbations of which disrupt energy balance and promote severe obesity. However, POMC neurons are neurochemically diverse and the crucial source of POMC peptides that regulate energy homeostasis and body weight remains to be fully clarified. METHODS: Given that a 5-hydroxytryptamine 2c receptor (5-HT2CR) agonist is a current obesity medication and 5-HT2CR agonist's effects on appetite are primarily mediated via POMC neurons, we hypothesized that a critical source of POMC regulating food intake and body weight is specifically synthesized in cells containing 5-HT2CRs. To exclusively manipulate Pomc synthesis only within 5-HT2CR containing cells, we generated a novel 5-HT 2C R (CRE) mouse line and intercrossed it with Cre recombinase-dependent and hypothalamic specific reactivatable Pomc (NEO) mice to restrict Pomc synthesis to the subset of hypothalamic cells containing 5-HT2CRs. This provided a means to clarify the specific contribution of a defined subgroup of POMC peptides in energy balance and body weight. RESULTS: Here we transform genetically programed obese and hyperinsulinemic male mice lacking hypothalamic Pomc with increased appetite, reduced physical activity and compromised brown adipose tissue (BAT) into lean, healthy mice via targeted restoration of Pomc function only within 5-HT2CR expressing cells. Remarkably, the same metabolic transformation does not occur in females, who despite corrected feeding behavior and normalized insulin levels remain physically inactive, have lower energy expenditure, compromised BAT and develop obesity. CONCLUSIONS: These data provide support for the functional heterogeneity of hypothalamic POMC neurons, revealing that Pomc expression within 5-HT2CR expressing neurons is sufficient to regulate energy intake and insulin sensitivity in male and female mice. However, an unexpected sex difference in the function of this subset of POMC neurons was identified with regard to energy expenditure. We reveal that a large sex difference in physical activity, energy expenditure and the development of obesity is driven by this subpopulation, which constitutes approximately 40% of all POMC neurons in the hypothalamic arcuate nucleus. This may have broad implications for strategies utilized to combat obesity, which at present largely ignore the sex of the obese individual.