Ciliary localization of GPR75 promotes fat accumulation in mice.

Obesity is a growing public health concern that affects the longevity and lifestyle of all human populations including children and older individuals. Diverse factors drive obesity, making it challenging to understand and treat. While recent studies highlight the importance of GPCR signaling for metabolism and fat accumulation, we lack a molecular description of how obesogenic signals accumulate and propagate in cells, tissues, and organs. In this issue of the JCI, Jiang et al. utilized germline mutagenesis to generate a missense variant of GRP75, encoded by the Thinner allele, which resulted in mice with a lean phenotype. GPR75 accumulated in the cilia of hypothalamic neurons. However, mice with the Thinner allele showed defective ciliary localization with resistance to fat accumulation. Additionally, GPR75 regulation of fat accumulation appeared independent of leptin and ADCY3 signaling. These findings shed light on the role of GPR75 in fat accumulation and highlight the need to identify relevant ligands.

Cu2O-Cu@Titanium Surface with Synergistic Performance for Nitrate-to-Ammonia Electrochemical Reduction.

Transition metals, such as titanium (Ti) and copper (Cu) along with their respective metal oxides (TiO2, Cu2O, and CuO), have been widely studied as electrocatalysts for nitrate electrochemical reduction with important outcomes in the fields of denitrification and ammonia generation. Based on this, this work conducted an evaluation of a composite electrode that integrates materials with different intrinsic activities (i.e., Cu and Cu2O for higher activity for nitrate conversion; Ti for higher faradaic efficiency to ammonia) looking for potential synergistic effects in the direction of ammonia generation. The specific performance of single-metal and composite electrodes has shown a strong dependence on pH and nitrate concentration conditions. Faradaic efficiency to ammonia of 92% and productivities of 0.28 mmolNH3 ·cm-2·h-1 at 0.5 V vs reversible hydrogen electrode (RHE) values are achieved, demonstrating the implicit potential of this approach in comparison to direct N2RR with values in the order of µmolNH3 ·h-1·cm-2. Finally, the electrochemical rate constants (k) for Ti, Cu, and Cu2O-Cu/Ti disk electrodes were determined by the Koutecky-Levich analysis with a rotating disk electrode (RDE) in 3.02 × 10-6, 3.88 × 10-4, and 4.77 × 10-4 cm·s-1 demonstrating an apparent synergistic effect for selective NiRR to ammonia with a Cu2O-Cu/Ti electrode.

Higroma quístico fetal / Fetal cystic hygroma

El higroma quístico congénito o linfangioma es un tumor del sistema linfático, es de origen embrionario y se origina por la obstrucción del drenaje de los sacos linfáticos. Su localización en orden de frecuencia es en las regiones cervical, axilar, intraperitoneal e inguinal, y muy raro como alteración única en el mediastino anterior. Paciente de 32 años de edad, con embarazo 16 sem ± 6 días y reporte de ecografía: Embarazo de 15 sem ± 20 días, normohidramnia, higroma quístico, Ausencia de hueso nasal además de una comunicación interventricular. Paciente en sala de legrado bajo sedación profunda, se obtiene producto de sexo masculino con alteraciones faciales y aumento de volumen en región cervical. Podemos concluir que, el control prenatal es importante realizar para obtener un diagnóstico precoz con examen ecográfico seriado, estudio genético, ecocardiografía fetal y para dar tratamiento quirúrgico es necesario conformar un equipo multidisciplinario.(AU)

The congenital cystic hygroma or lymphangioma is a tumor of the lymphatic system, is of embryonic origin and is caused by the obstruction of the drainage of the lymphatic sacs. Its location in order of frequency is in the cervical, axillary, intraperitoneal and inguinal regions, and very rare as a single alteration in the anterior mediastinum. A 32-year-old patient with a pregnancy of 16 weeks ± 6 days and an ultrasound report: Pregnancy of 15 weeks ± 20 days, normohydramnia, cystic hygroma, Absence of nasal bone in addition to interventricular communication. Patient in curettage room under deep sedation, male product with facial alterations and volume increase in cervical region is obtained. We can conclude that prenatal control is important to obtain an early diagnosis with serial ultrasound examination, genetic study, fetal echocardiography and to give surgical treatment it is necessary to form a multidisciplinary team.(AU)

Feto papiráceo en embarazo gemelar a término obtenido por cesárea / Fetus papyraceus in twin pregnancy obtained by cesarean

El feto papiráceo es un feto aplanado y momificado, sin cambios externos, se presenta en embarazo gemelar o múltiple, es de causa desconocida. Las causas de muerte ipueden ser fetales, ovulares y materna. Complicaciones: en la madre es coagulación intravascular diseminada y en el feto sobreviviente puede presentar Aplasia Cutánea Csongénita, disgenesia renal y atresia intestinal. Paciente de 42 años, con embarazo de 38 semanas, cesárea iterativa, diabetes gestacional no controlada, se realiza un manejo conservador con ecografías seriadas y control de laboratorio. Para la culminación del embarazo: cesárea bajo anestesia raquídea, recién nacido de sexo masculino, alumbramiento de placenta más feto papiráceo. En conclusión, manejo individual con control ecográfico seriado del feto sobreviviente, realizar ecografía Doppler, medir el volumen del líquido amniótico, perfil biofísico y control de los factores de riesgo modificables materno, para tomar una conducta optima y adecuada para la culminación del embarazo

The papyraceus fetus is a flat and mummified fetus, without external changes, it occurs in twin or multiple pregnancy, of unknown cause. Intrauterine death both fetal, ovular and maternal. Complications: in the mother it is disseminated intravascular coagulation and in the surviving fetus may present Congenital Cutaneous Aplasia, renal dysgenesis and intestinal atresia. A 42-year-old patient, with a 38-week pregnancy, iterative cesarean section, uncontrolled gestational diabetes, conservative management with serial ultrasound and laboratory control. For the culmination of pregnancy: caesarean section under spinal anesthesia, male newborn, delivery of placenta plus papiraceous fetus. In conclusion, individual management with serial ultrasound control of the surviving fetus, perform Doppler ultrasound, measure the volume of amniotic fluid, biophysical profile and control of maternal modifiable risk factors, to take an optimal and adequate behavior for the culmination of pregnancy

Situación actual de los sarcomas de partes blandas: registro de un instituto oncológico de Latinoamérica / Current situation of soft tissue sarcomas: Registry of a Latin American cancer institute

Objetivo: Los sarcomas de partes blandas (SFTS) conforman un grupo de neoplasias poco frecuentes y heterogéneas (menos del 1% en adultos y 15% en pediátricos), de los cuales no se cuenta con registros actualizados en población latinoamericana. El estudio tiene como objetivo describir la situación actual de los pacientes tratados en un instituto oncológico de Latinoamérica. Métodos: Se obtuvo un registro de 250 pacientes con diagnóstico de SFTS, tratados en el Instituto de Enfermedades Neoplásicas del Perú (INEN), durante el periodo 2009-2013, con una media de seguimiento de 62 meses, registrándose datos: epidemiológicos, clínicos, tratamiento y seguimiento; realizándose el análisis de sobrevida global mediante el modelo proporcional de Cox. Resultados: Los SFTS mostraron una mayor frecuencia en género masculino (60,8%), con un pico incidencia a partir de los 50 años (69,6%), la localización tumoral predominante fue en extremidades inferiores (64,4%), siendo los subtipos histológicos más frecuentes: sarcoma pleomórfico indiferenciado (34%) y liposarcomas (25,6%); el estadio clínico iii es el de mayor registro (30,8%). Se obtuvo una tasa de sobrevida global a 5 años del 63,9%, encontrándose en el análisis estadístico asociación significativa entre la sobrevida global y las variables: edad (> 50 años), tamaño tumoral (> 5cm), profundidad (subfascial), grado histológico (G3), recurrencia local y a distancia, mostrando en este grupo rangos menores de sobrevida. Conclusiones: Se ha logrado precisar la epidemiología, el tratamiento y el pronóstico, así como las variables que repercuten en la sobrevida de los pacientes latinoamericanos con SFTS estudiados

Introduction: Soft tissue sarcomas (SFT) are a group of rare and heterogeneous neoplasms (representing less than 1% of cancer in adults and 15% in pediatric patients), for which there is no updated records in the Latin American population. This study aims to describe the current situation of patients treated at a cancer institute in Latin America. Methods: We obtained records from 250 patients with a diagnosis of SFT, treated at the National Institute of Neoplastic Diseases of Peru (INEN) during the period 2009-2013, with a mean follow-up of 62 months. The following data were recorded: epidemiological, clinical, treatment and follow-up. The analysis of global survival was done with the Cox proportional hazards model. Results: SFT showed a greater frequency in males (60.8%), with a peak incidence after 50 years of age (69.6%). Tumor location was predominantly in the lower extremities (64.4%), and the most frequent histologic subtypes were: undifferentiated pleomorphic sarcoma (34%) and liposarcomas (25.6%); clinical stage iii was the most frequent (30.8%). The 5-year overall survival rate was 63.9%, while the statistical analysis found a significant association between global survival and the variables: age (>50 years), tumor size (>5cm), depth (subfascial), histologic grade (G3), local and distant recurrence, showing shorter survival times in these groups. Conclusions: This study has clarified the epidemiology, treatment and prognosis, as well as the variables that have an impact on the survival of the Latin American patients with SFT studied

Current situation of soft tissue sarcomas: Registry of a Latin American cancer institute. / Situación actual de los sarcomas de partes blandas: registro de un instituto oncológico de Latinoamérica.

INTRODUCTION: Soft tissue sarcomas (SFT) are a group of rare and heterogeneous neoplasms (representing less than 1% of cancer in adults and 15% in pediatric patients), for which there is no updated records in the Latin American population. This study aims to describe the current situation of patients treated at a cancer institute in Latin America. METHODS: We obtained records from 250 patients with a diagnosis of SFT, treated at the National Institute of Neoplastic Diseases of Peru (INEN) during the period 2009-2013, with a mean follow-up of 62 months. The following data were recorded: epidemiological, clinical, treatment and follow-up. The analysis of global survival was done with the Cox proportional hazards model. RESULTS: SFT showed a greater frequency in males (60.8%), with a peak incidence after 50 years of age (69.6%). Tumor location was predominantly in the lower extremities (64.4%), and the most frequent histologic subtypes were: undifferentiated pleomorphic sarcoma (34%) and liposarcomas (25.6%); clinical stage iii was the most frequent (30.8%). The 5-year overall survival rate was 63.9%, while the statistical analysis found a significant association between global survival and the variables: age (>50 years), tumor size (>5cm), depth (subfascial), histologic grade (G3), local and distant recurrence, showing shorter survival times in these groups. CONCLUSIONS: This study has clarified the epidemiology, treatment and prognosis, as well as the variables that have an impact on the survival of the Latin American patients with SFT studied.

Oncoplastic surgery for the conservative treatment of breast cancer in Perú's National Cancer Institute.

BACKGROUND: Oncoplastic surgery for breast cancer (OPS) has been a surgical trend for the past 25 years. In 2012, OPS has been introduced as the standard treatment for a selected group of patients at the National Cancer Institute of Peru (INEN). The aim of this study is to describe our findings. METHODS: This is a retrospective and descriptive study that identified demographics, tumour-pathologic features and includes patients solely treated since diagnosis until late follow-up at INEN. These OPS patients were identified from the conservative treatment patients group by review of medical charts and creation of a database for periods December 2005 through December 2015. RESULTS: A total of 146 patients were ruled in by the inclusion criteria. All patients were Peruvian females, 56.2% being 51 or older. 93.8% had core biopsy diagnosis of breast cancer and 52.1% located at the upper outer quadrant. 79.5% patients had upfront OPS and the round block (43.2%) and reduction/mastopexy (23.3%) were the most used techniques. pT2 was the most frequent size (54.7%). We achieved negative margins in 134 patients (93.2%) in a single procedure. Of 29 patients, who had neoadjuvant treatment, 11 achieved pCR. Only 5.5% had pN2 or higher. 95.2% received complimentary external beam radiotherapy. CONCLUSIONS: OPS has proven to be a reliable surgical option, both for aesthetic and oncologic outcomes. Important points for achieving these results are breast surgeons having properly trained under the OPS philosophy and knowing the patients' characteristics for correct technique selection.

Resultados oncológicos de la cirugía oncoplástica: seguimiento a largo plazo de pacientes tratados en un instituto oncológico de Latinoamérica. Un análisis de cohortes / Oncological results of oncoplastic surgery: Long-term follow-up of patients treated in an oncology institute in Latin America. A cohort analysis

Objetivo. La cirugía oncoplástica forma parte del grupo de cirugías de conservación mamaria, la cual permite la resección oncológica y la remodelación mamaria en el mismo acto quirúrgico. Actualmente es ampliamente usada en Latinoamérica, sin embargo, no cuentan con grandes reportes de resultados oncológicos. El propósito del estudio es evaluar la seguridad de la cirugía oncoplástica en el tratamiento del cáncer de mama invasivo. Método. Se comparan de forma retrospectiva 124 pacientes que recibieron cirugía oncoplástica por cáncer de mama invasivo no metastásico (grupo de estudio) con 302 pacientes que recibieron cirugía de conservación mamaria convencional (no oncoplástica; grupo control) durante el periodo 2007-2015. Resultados. El tiempo medio de seguimiento fue de 61 meses, la sobrevida global fue mayor en el grupo de cirugía oncoplástica frente al grupo control a 10 años (97,7 vs. 89.8%, p=0,04), así como la sobrevida libre de enfermedad (93 vs. 86,7% a 10 años, p=0,05). Discusión. Se han comparado pacientes que tuvieron cirugía primaria oncoplástica por cáncer de mama invasivo no metastásico (124) con un grupo control (302), realizándose un seguimiento por un periodo prolongado de tiempo, proporcionando el presente estudio evidencia para plantear que la cirugía oncoplástica es una opción de tratamiento seguro y confiable en pacientes con cáncer de mama en Latinoamérica (AU)

Objective. Oncoplastic surgery is a type of breast conservation surgery, which allows oncologic resection and breast remodelling in the same surgical procedure. It is now widely used in Latin America, but large studies of its results are lacking. The aim of this study was to evaluate the safety of oncoplastic surgery in the treatment of invasive breast cancer. Method. A total of 124 patients who underwent oncoplastic surgery between 2007 and 2015 for non-metastatic invasive breast cancer (study group) were retrospectively compared with 302 patients who underwent conventional (non-oncoplastic surgery) breast conservation surgery (control group) in the same period. Results. The mean length of follow-up was 61 months. Overall survival and disease-free survival was higher in the oncoplastic surgery group than in the control group at 10 years (97.7 vs. 89.8%, P=.04; 93 vs. 86.7% at 10 years, P=.05). Discussion. We compared patients who had oncoplastic primary surgery for non-metastatic invasive breast cancer (n=124) with a control (n=302) group who were followed-up for a long period, providing evidence to suggest that oncoplastic surgery is a safe and reliable treatment option in patients with breast cancer in Latin America (AU)

Modulation of Ciliary Phosphoinositide Content Regulates Trafficking and Sonic Hedgehog Signaling Output.

Ciliary transport is required for ciliogenesis, signal transduction, and trafficking of receptors to the primary cilium. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) have been associated with ciliary dysfunction; however, its role in regulating ciliary phosphoinositides is unknown. Here we report that in neural stem cells, phosphatidylinositol 4-phosphate (PI4P) is found in high levels in cilia whereas phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is not detectable. Upon INPP5E inactivation, PI(4,5)P2 accumulates at the ciliary tip whereas PI4P is depleted. This is accompanied by recruitment of the PI(4,5)P2-interacting protein TULP3 to the ciliary membrane, along with Gpr161. This results in an increased production of cAMP and a repression of the Shh transcription gene Gli1. Our results reveal the link between ciliary regulation of phosphoinositides by INPP5E and Shh regulation via ciliary trafficking of TULP3/Gpr161 and also provide mechanistic insight into ciliary alterations found in Joubert and MORM syndromes resulting from INPP5E mutations.

Homeostatic plasticity of striatal neurons intrinsic excitability following dopamine depletion.

The striatum is the major input structure of basal ganglia and is involved in adaptive control of behaviour through the selection of relevant informations. Dopaminergic neurons that innervate striatum die in Parkinson disease, leading to inefficient adaptive behaviour. Neuronal activity of striatal medium spiny neurons (MSN) is modulated by dopamine receptors. Although dopamine signalling had received substantial attention, consequences of dopamine depletion on MSN intrinsic excitability remain unclear. Here we show, by performing perforated patch clamp recordings on brain slices, that dopamine depletion leads to an increase in MSN intrinsic excitability through the decrease of an inactivating A-type potassium current, I(A). Despite the large decrease in their excitatory synaptic inputs determined by the decreased dendritic spines density and the increase in minimal current to evoke the first EPSP, this increase in intrinsic excitability resulted in an enhanced responsiveness to their remaining synapses, allowing them to fire similarly or more efficiently following input stimulation than in control condition. Therefore, this increase in intrinsic excitability through the regulation of I(A) represents a form of homeostatic plasticity allowing neurons to compensate for perturbations in synaptic transmission and to promote stability in firing. The present observations show that this homeostatic ability to maintain firing rates within functional range also occurs in pathological conditions, allowing stabilizing neural computation within affected neuronal networks.