Growth hormone biases amygdala network activation after fear learning

Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the ‘over-encoding’ of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the process by which neurons compete to encode memories, to favor neurons that have stronger inputs. Viral overexpression of GH in the amygdala increased the number of amygdala cells activated by fear memory formation. GH-overexpressing cells were especially biased to express the immediate early gene c-Fos after fear conditioning, revealing strong autocrine actions of GH in the amygdala. In addition, we observed dramatically enhanced dendritic spine density in GH-overexpressing neurons. These data elucidate a previously unrecognized autocrine role for GH in the regulation of amygdala neuron function and identify specific mechanisms by which chronic stress, by enhancing GH in the amygdala, may predispose an individual to excessive fear memory formation.National Institute of Mental Health (U.S.) (NIMH R01 MH084966)United States. Defense Advanced Research Projects Agency (DARPA grant W911NF-10-1-0059)United States. Army Research Offic

Effects of transcutaneous electric acupoint stimulation on drug use and responses to cue-induced craving: a pilot study

Background: Transcutaneous electric acupoint stimulation (TEAS) avoids the use of needles, and instead delivers a mild electric current at traditional acupoints. This technique has been used for treating heroin addiction, but has not been systematically tested for other drugs of abuse. This study aims to investigate the effects of TEAS on drug addiction. Methods: Volunteers who were either cocaine-dependent (n = 9) or cannabis-dependent (n = 11) but were not seeking treatment for their dependence participated in a within-subject, single-blind study. Treatment consisted of twice daily 30-minute sessions of TEAS or sham stimulation for 3.5 days. The active TEAS levels were individually adjusted to produce a distinct twitching response in the fingers, while the sham stimulation involved 2 minutes of stimulation at threshold levels followed by 28 minutes of stimulation below the detection levels. The participants recorded their drug use and drug cravings daily. At 1 hour after the last morning session of TEAS or sham stimulation, a cue-induced craving EEG evaluation was conducted. Event-related P300 potentials (ERPs) were recorded, sorted, and analyzed for specific image types (neutral objects, non-drug-related arousing images, or drug-related images). Results: TEAS treatment did not significantly reduce the drug use or drug cravings, or significantly alter the ERP peak voltage or latency to peak response. However, the TEAS treatment did significantly modulate several self-reported measures of mood and anxiety. Conclusion: The results of this pilot study with a limited sample size suggest that the acupoint stimulation techniques and protocol used in this trial alone do not significantly reduce cravings for or use of cocaine or cannabis. The findings that TEAS modulates mood and anxiety suggest that TEAS could be used as an adjunct in a multimodal therapy program to treat cocaine and cannabis dependence if confirmed in a full randomized controlled clinical trial

Role of the Intracellular pH in the Metabolic Switch between Oxidative Phosphorylation and AerobicGlycolysis - Relevance to Cancer

Cellular energy in the form of ATP can be produced through oxidative phosphorylation and through glycolysis. Since oxidative phosphorylation requires oxygen and generates ATP more efficiently than glycolysis, it has been assumed for many years that the presence or absence of oxygen determines that cells generate energy through oxidative phosphorylation or through glycolysis. Although cells must activate glycolysis in the absence of oxygen to produce ATP, it is now accepted that they can activate both glycolysis and oxidative phosphorylation in the presence of oxygen. In fact, normal proliferating cells and tumor cells are known to have a high glycolytic activity in the presence of adequate oxygen levels, a phenomenon known as aerobic glycolysis or the Warburg effect. Recent observations have demonstrated that the activation of aerobic glycolysis plays a major role in carcinogenesis and tumor growth. Understanding the mechanisms involved in the metabolic switch between oxidative phosphorylation and aerobic glycolysis may therefore be important for the development of potential preventive and therapeutic interventions. In this article, we discuss the role of the intracellular pH in the metabolic switch between oxidative phosphorylation and aerobic glycolysis. We propose that, in the presence of adequate oxygen levels, the intracellular pH may play a key role in determining the way cells obtain energy, an alkaline pH driving aerobic glycolysis and an acidic pH driving oxidative phosphorylation

Cultural beliefs and attitudes among Latinos with end stage renal disease

The purpose of this study was to provide a quantitative analysis of beliefs and attitudes among Latinos who are diagnosed with end stage renal disease. This study explored the common attitudes and beliefs of this population, which may be both beneficial and harmful in their medical care

Incidencia y formas clínicas de tuberculosis durante el quinquenio 2018-2022 en derechohabientes de la unidad de medicina familiar No. 3 de Cd. Valles, San Luis Potosí

Incidencia y formas clínicas de tuberculosis durante el quinquenio 2018- 2022 en derechohabientes de la unidad de medicina familiar No. 03 de Cd. Valles, San Luis Potosí. AUTORES: Miriam Gpe. Robles Burgos (tesista), residente de 3° año de la especialidad en Medicina Familiar, Dr. Freddy Morales Hernández, Neumólogo (asesor clínico), Dra. Mahogani Oyarvide Ramiro, epidemióloga (asesor metodológico), Dr. Rafael Correa Cano, Oncólogo Médico (asesor estadístico). INTRODUCCIÓN: La tuberculosis es una de las principales causas de muerte por un único agente infeccioso y se ha convertido en un problema de salud pública mundial debido al creciente número de casos. La descripción de su incidencia proporciona información sobre la enfermedad en la región, lo que permite a las autoridades de salud pública entender la magnitud del problema y diseñar estrategias de prevención, control y tratamiento. OBJETIVO GENERAL: Identificar la incidencia y formas clínicas de tuberculosis durante el quinquenio 2018-2022 en derechohabientes de la UMF No.3 en Cd. Valles, SLP. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, transversal y retrospectivo. Se trabajó con la totalidad de expedientes de casos nuevos en el periodo enero 2018 a diciembre del 2022. Se identificó sociodemográficamente a la población de estudio, se describieron las comorbilidades más frecuentes, se determinó la incidencia general y las formas clínicas registradas durante el periodo establecido de estudio. La incidencia se calculó tomando en cuenta los casos nuevos/la totalidad de la población expuesta en el periodo de tiempo del estudio. RESULTADOS: En este estudio se observa una incidencia de 4.8 casos por 10,000 habitantes en un periodo de 5 años, con una predominancia de casos en hombres y en edades medias. Se identificó una prevalencia significativa de sobrepeso, obesidad, diabetes e hipertensión arterial. EL 95.5% de casos fue Tb pulmonar, un 2.3% correspondió al tipo ganglionar y 2.3% al miliar. CONCLUSIONES: Se identificaron áreas clave para futuros estudios, como la evaluación de factores de riesgo específicos, la efectividad de intervenciones de prevención y la resistencia a los medicamentosInvestigadoresEstudiante

Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.National Institutes of Health (U.S.) (Award 1R25-MH092912-01)National Institute of Mental Health (U.S.) (Grant R01- MH102441-01)National Institutes of Health (U.S.) (Award DP2- DK-102256-01

Development of a moisture-in-solid-insulation sensor for power transformers

Moisture is an important variable that must be kept under control to guarantee a safe operation of power transformers. Because of the hydrophilic character of cellulose, water mainly remains in the solid insulation, while just a few parts per million are dissolved in oil. The distribution of moisture between paper and oil is not static, but varies depending on the insulation temperature, and thus, water migration processes take place continuously during transformers operation. In this work, a sensor is presented that allows the determination of the moisture content of the transformer solid insulation in the steady state and during the moisture migration processes. The main objective of the design is that the electrodes of the sensor should not obstruct the movement of water from the solid insulation to the oil, so the proposed prototype uses a metallic-mesh electrode to do the measurements. The measurement setup is based on the characterization of the insulation dielectric response by means of the frequency dielectric spectroscopy (FDS) method. The sensitivity of the proposed sensor has been tested on samples with a moisture content within 1% to 5%, demonstrating the good sensitivity and repeatability of the measurements.This work has been supported by the Spanish Government under Contract DPI2012-35819

On the Fluid Dynamics of the Make-Up Inlet Air and the Prediction of Anomalous Fire Dynamics in a Large-Scale Facility

The present paper is focused on the fluid dynamics of the make-up air at the vents in case of an atrium fire, its influence on the fire-induced conditions and the necessity of properly model it to obtain an accurate numerical prediction. For this aim, experimental data from two full-scale atrium fire tests conducted in a 20 m cubic facility, with venting conditions involving mechanical smoke exhaust and make-up air velocities larger than 1 m/s, and with different fire powers, are presented. Subsequent numerical simulations of these tests have been performed with the code Fire Dynamics Simulator v5.5.3. Two different approaches have been followed to simulate the make-up air inlet fluid dynamics, involving one domain which only considers the inside of the building and another which includes part of the outside. In the former simulations, anomalous phenomena around the fire appear, while the inclusion of the exterior domain provides with a completely different fluid dynamics inside the facility which agrees better with the experimental data. A detailed analysis of the fluid mechanics at the air inlet vents is conducted to explain these discrepancies. Finally, further simulations are performed varying the make-up area to assess the appearance of the aforementioned phenomenon.This research was supported by the Spanish MCyT and Junta de Andalucia under Projects # DPI2008-06624-C03-02 and # P07-TEP02693, respectively. CGM wants to acknowledge the research stay grants IAC-2010-3 and A-13-2010 from the Junta de Andalucia and the University of Jaén, respectivel

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

A hippocampal Cdk5 pathway regulates extinction of contextual fear

Treatment of emotional disorders involves the promotion of extinction processes, which are defined as the learned reduction of fear. The molecular mechanisms underlying extinction have only begun to be elucidated. By employing genetic and pharmacological approaches in mice, we show here that extinction requires downregulation of Rac-1 and cyclin-dependent kinase 5 (Cdk5), and upregulation of p21 activated kinase-1 (PAK-1) activity. This is physiologically achieved by a Rac-1–dependent relocation of the Cdk5 activator p35 from the membrane to the cytosol and dissociation of p35 from PAK-1. Moreover, our data suggest that Cdk5/p35 activity prevents extinction in part by inhibition of PAK-1 activity in a Rac-1–dependent manner. We propose that extinction of contextual fear is regulated by counteracting components of a molecular pathway involving Rac-1, Cdk5 and PAK-1. Our data suggest that this pathway could provide a suitable target for therapeutic treatment of emotional disorders.National Institutes of Health (U.S.) (Grant NS051874)Alexander von Humboldt-Stiftung (German Research Foundation Fellowship)European Neuroscience Institute Goettinge