Changes in Corticotropin-Releasing Factor Receptor Type 1, Co-Expression with Tyrosine Hydroxylase and Oxytocin Neurons, and Anxiety-Like Behaviors across the Postpartum Period in Mice.

INTRODUCTION: Corticotropin-releasing factor and its primary receptor (CRFR1) are critical regulators of behavioral and neuroendocrine stress responses. CRFR1 has also been associated with stress-related behavioral changes in postpartum mice. Our previous studies indicate dynamic changes in CRFR1 levels and coupling of CRFR1 with tyrosine hydroxylase (TH) and oxytocin (OT) neurons in postpartum mice. In this study, we aimed to determine the time course of these changes during the postpartum period. METHODS: Using a CRFR1-GFP reporter mouse line, we compared postpartum mice at five time points with nulliparous mice. We performed immunohistochemistry to assess changes in CRFR1 levels and changes in co-expression of TH/CRFR1-GFP and OT/CRFR1-GFP across the postpartum period. Mice were also assessed for behavioral stress responses in the open field test. RESULTS: Relative to nulliparous mice, CRFR1 levels were elevated in the anteroventral periventricular nucleus (AVPV/PeN) but were decreased in the medial preoptic area from postpartum day 1 (P1) through P28. In the paraventricular hypothalamus (PVN), there is a transient decline in CRFR1 mid-postpartum with a nadir at P7. Co-localization of CRFR1 with TH-expressing neurons was also altered with a transient decrease found in the AVPV/PeN at P7 and P14. Co-expression of CRFR1 and OT neurons of the PVN and supraoptic nucleus was dramatically altered with virtually no co-expression found in nulliparous mice, but levels increased shortly after parturition and peaked near P21. A transient decrease in open field center time was found at P7, indicating elevated anxiety-like behavior. CONCLUSION: This study revealed various changes in CRFR1 across the postpartum period, which may contribute to stress-related behavior changes in postpartum mice.

Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP-2ε in vomeronasal sensory neurons.

Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remain a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here, we demonstrated that the identity of postmitotic/maturing vomeronasal sensory neurons (VSNs), and vomeronasal-dependent behaviors can be reprogrammed through the rescue of Tfap2e/AP-2ε expression in the Tfap2eNull mice, and partially reprogrammed by inducing ectopic Tfap2e expression in mature apical VSNs. We suggest that the TF Tfap2e can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes.

Optimización de la protección en radiología y cardiología intervencionista pediatrica en América Latina y el Caribe (OPRIPALC) / Optimization of protection in pediatric interventional cardiology and radiology in Latin America and the Caribbean (OPRIPALC)

El objetivo del presente artículo ha sido describir el programa "Optimización de la Protección en Radiología Intervencionista Pediátrica en América Latina y el Caribe" (OPRIPALC) que nace el año 2018 como respuesta conjunta de la Organización Panamericana de la Salud y la Organización Mundial de la Salud, en cooperación con el Organismo Internacional de Energía Atómica, para colaborar con sus Estados miembros en asegurar que las exposiciones a la radiación de los pacientes pediátricos sean las mínimas necesarias durante los procedimientos intervencionistas. Actualmente, hay 18 centros de los siguientes 10 países que participan: Argentina, Brasil, Chile, Colombia, Costa Rica, Cuba, Ecuador, México, Perú y Uruguay. Para el desarrollo del programa se plantean una serie de objetivos, productos, actividades y resultados esperados. La puesta en marcha de la WEB de OPRIPALC ha significado un instrumento muy válido para seguir la información actualizada del programa. Un programa actualizado de formación en radioprotección para los profesionales implicados en el programa, se está realizando por medio de "webinars". Se deberá seguir actuando en la aplicación del programa de control de calidad básico para los equipos de rayos X participantes y validar los valores de los Niveles de Referencia para Diagnóstico (NRDs). Se propone formar un equipo de trabajo entre los Físicos Médicos y Tecnólogos Médicos participantes de OPRIPALC para implicarse en las pruebas de control básicas que todos los centros debieran realizar. Se han presentado algunos resultados iniciales de OPRIPALC en eventos científicos internacionales. Se está avanzando en proponer unos primeros valores sobre NRDs en procedimientos de intervencionismo cardiológico pediátrico por bandas de edad y peso. OPRIPALC es una de las pocas iniciativas de carácter regional para obtener valores de NRDs en procedimientos intervencionistas pediátricos. Se espera que tanto los valores de referencia como la metodología empleada en OPRIPALC, puedan ser utilizados en otras regiones del mundo.

The objective of this article has been to describe the program "Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean" (OPRIPALC) that was born in 2018 as a joint response of the Pan American Health Organization and the World Organization of the Health, in cooperation with the International Atomic Energy Agency, to collaborate with its member states in ensuring that radiation exposures of pediatric patients are the minimum necessary during interventional procedures. Currently, there are 18 centers from the following 10 countries participating: Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Mexico, Peru and Uruguay. For the development of the program, a series of objectives, products, activities and expected results are proposed. The launch of the OPRIPALC WEBSITE has been a very valid instrument for following up-to-date information on the program. An updated training program in radiation protection for the professionals involved in the program is being carried out through webinars. It should continue acting in the application of the basic quality control program for the participating X-ray equipment and validate the values of the Diagnostic Reference Levels (DRLs). It is proposed to form a work team among the OPRIPALC participating medical physicists to get involved in the basic control tests that all centers should carry out. Some initial results of OPRIPALC have been presented at international scientific events. Progress is being made in proposing first values on DRLs in pediatric cardiac intervention procedures by age and weight bands. OPRIPALC is one of the few regional initiatives to obtain DRLs values in pediatric interventional procedures. It is expected that both the reference values and the methodology used in OPRIPALC can be used in other regions of the world.

Alterations in corticotropin-releasing factor receptor type 1 in the preoptic area and hypothalamus in mice during the postpartum period.

Corticotropin-releasing factor (CRF) signaling through CRF receptor 1 (CRFR1) regulates autonomic, endocrine, and behavioral responses to stress, as well as behavioral changes during the maternal period. Previous work in our lab reported higher levels of CRFR1 in female, compared to male, mice within the rostral anteroventral periventricular nucleus (AVPV/PeN), a brain region involved in maternal behaviors. In this study, we used CRFR1-GFP reporter mice to investigate whether the reproductive status (postpartum vs. nulliparous) of acutely stressed females affects levels of CRFR1 in the AVPV/PeN and other regions involved in maternal functions. Compared to nulliparous, postpartum day 14 females showed increased AVPV/PeN CRFR1-GFP immunoreactivity and an elevated number of restraint stress-activated AVPV/PeN CRFR1 cells as assessed by immunohistochemical co-localization of CRFR1-GFP and phosphorylated CREB (pCREB). The medial preoptic area (MPOA) and paraventricular hypothalamus (PVN) of postpartum mice showed modest decreases in CRFR1-GFP immunoreactivity, while increased CRFR1-GFP/pCREB co-expressing cells were found in the PVN following restraint stress relative to nulliparous mice. Tyrosine hydroxylase (TH) and CRFR1-GFP co-localization was also assessed in the AVPV/PeN and other regions and revealed a decrease in co-localized neurons in the AVPV/PeN and ventral tegmental area of postpartum mice. Corticosterone analysis of restrained mice revealed blunted peak, but elevated recovery, levels in postpartum compared to nulliparous mice. Finally, we investigated projection patterns of AVPV/PeN CRFR1 neurons using female CRFR1-Cre mice and revealed dense efferent projections to several preoptic, hypothalamic, and hindbrain regions known to control stress-associated and maternal functions. Together, these findings contribute to our understanding of the neurobiology that might underlie changes in stress-related functions during the postpartum period.

Characteristics and Clinical Course of Adult in Patients with SARS-CoV-2 Pneumonia at High Altitude.

Background: SARS-CoV-2 has spread worldwide with different dynamics in each region. We aimed to describe the clinical characteristics and to explore risk factors of death, critical care admission, and use of invasive mechanical ventilation in hospitalized patients with SARS-CoV-2 pneumonia in a high-altitude population living in Bogotá, Colombia. Methods: We conducted a concurrent cohort study of adult patients with laboratory-confirmed SARS-CoV-2 pneumonia. Demographic, clinical, and treatment data were extracted from electronic records. Univariate and multivariable methods were performed to investigate the relationship between each variable and outcomes at 28 days of follow-up. Results: 377 adults (56.8% male) were included in the study, of whom 85 (22.6%) died. Nonsurvivors were older on average than survivors (mean age, 56.7 years [SD 15.8] vs. 70.1 years [SD 13.9]; p ≤ 0.001) and more likely male (28 [32.9%] vs. 57 [67.1%]; p=0.029). Most patients had at least one underlying disease (333 [88.3%]), including arterial hypertension (149 [39.5%]), overweight (145 [38.5%]), obesity (114 [30.2%]), and diabetes mellitus (82 [21.8%]). Frequency of critical care admission (158 [41.9%]) and invasive mechanical ventilation (123 [32.6%]) was high. Age over 65 years (OR 9.26, 95% CI 3.29-26.01; p ≤ 0.001), ICU admission (OR 12.37, 95% CI 6.08-25.18; p ≤ 0.001), and arterial pH higher than 7.47 (OR 0.25, 95% CI 0.08-0.74; p=0.01) were independently associated with in-hospital mortality. Conclusions: In this study of in-hospital patients with SARS-CoV-2 pneumonia living at high altitude, frequency of death was similar to what has been reported. ICU admission and use of invasive mechanical ventilation were high. Risk factors as older age, ICU admission, and arterial pH were associated with mortality.

Prediction of confirmed cases of and deaths caused by COVID-19 in Chile through time series techniques: A comparative study.

BACKGROUND: Chile has become one of the countries most affected by COVID-19, a pandemic that has generated a large number of cases worldwide. If not detected and treated in time, COVID-19 can cause multi-organ failure and even death. Therefore, it is necessary to understand the behavior of the spread of COVID-19 as well as the projection of infections and deaths. This information is very relevant so that public health organizations can distribute financial resources efficiently and take appropriate containment measures. In this research, we compare different time series methodologies to predict the number of confirmed cases of and deaths from COVID-19 in Chile. METHODS: The methodology used in this research consisted of modeling cases of both confirmed diagnoses and deaths from COVID-19 in Chile using Autoregressive Integrated Moving Average (ARIMA henceforth) models, Exponential Smoothing techniques, and Poisson models for time-dependent count data. Additionally, we evaluated the accuracy of the predictions using a training set and a test set. RESULTS: The dataset used in this research indicated that the most appropriate model is the ARIMA time series model for predicting the number of confirmed COVID-19 cases, whereas for predicting the number of deaths from COVID-19 in Chile, the most suitable approach is the damped trend method. CONCLUSION: The ARIMA models are an alternative to modeling the behavior of the spread of COVID-19; however, depending on the characteristics of the dataset, other methodologies can better predict the behavior of these records, for example, the Holt-Winter method implemented with time-dependent count data.

Differences in BMI between Mexican and Colombian patients receiving antipsychotics: results from the International Study of Latinos on Antipsychotics (ISLA).

Objective: The objective of this study is to examine the association of country of residence with body mass index (BMI) between Mexican and Colombian patients exposed to antipsychotics. We hypothesize that there will be a significant association between country of residence and BMI and that Mexican patients will have higher BMI than their Colombian counterparts.Design: The International Study of Latinos on Antipsychotics (ISLA) is a multisite, international, cross sectional study of adult Latino patients exposed to antipsychotics in two Latin American Countries (i.e. Mexico and Colombia). Data were collected from a total of 205 patients (149 from Mexico and 56 from Colombia). The sites in Mexico included outpatient clinics in Mexicali, Monterrey and Tijuana. In Colombia, data were collected from outpatient clinics in Bogotá. For this study we included patients attending outpatient psychiatric community clinics that received at least one antipsychotic (new and old generation) for the last 3 months. A linear regression model was used to determine the association of country of residence with BMI for participants exposed to an antipsychotic.Results: After controlling for demographics, behaviors, biological and comorbid psychiatric variables, there was a significant difference between Colombia vs. Mexico in the BMI of patients exposed to antipsychotics (ß = 4.9; p < 0.05).Conclusion: Our hypotheses were supported. These results suggest that differences in BMI in patients exposed to antipsychotics in Mexico and Colombia may reflect differences in prevalence of overweight/obesity at the population level in the respective countries, and highlights the involvement of other risk factors, which may include genetics.

Infecciones en Pie Diabético. Serie de Casos / Diabetic Foot Infections. Case Series

Introducción El objetivo de este trabajo es describir las características clínicas, gérmenes aislados en muestras tomadas en quirófano, tipo de procedimientos quirúrgicos y desenlaces en el tratamiento realizado a pacientes con pie diabético atendidos en nuestra institución. Materiales y Metodos Estudio descriptivo retrospectivo observacional tipo serie de casos, describiendo resultados obtenidos de los cultivos tomados en cirugía, características clínicas según la clasificación de Wagner, número y tipo de procedimientos entre Enero de 2012 y Diciembre de 2016 por complicaciones derivadas de pie diabético. Resultados Se obtuvieron 58 pacientes, con edad media de 65 años, 69% eran varones. El estadio clínico en la evaluación prequirúrgica fue de 39.7% Wagner III, 37.9% IV; en la evaluación intraquirúrgica fue 32.8% III, 50% IV. Los gérmenes aislados, en 1er lugar 15.5% Escherichia Coli, de estas 11.9% era BLEE positiva y 3.6% multisensible; otro 15.5% Pseudomona Aeruginosa, variantes multirresistentes 10.7% productoras de carbapenemasas 1.2%, y resistentes a meropenem 1.2% y multisensibles 2.4%. 77.5% de los pacientes requirió cambio de antibiótico. Un tercio de los pacientes requirieron amputaciones mayores de los cuales 46.6% presentaban infecciones por gérmenes de multirresistentes. Discusión Encontramos que los gérmenes predominantes son bacilos gram negativos en su mayoría multirresistente. Sugerimos la toma de muestras de manera intraquirúrgica previo al inicio de antibioticoterapia. Dado la flora bacteriana aislada en esta serie, al iniciar antibioticoterapia empírica se sugiere el uso de carbapenémicos.

Background The main purpose of the study is to describe the clinical characteristics, micro-organisms isolated in specimens taken in the operating room, types of surgical procedures, and outcomes in treatments performed on patients with diabetic foot. Methods A case series study is presented, describing results obtained from cultures taken in surgery, clinical characteristics according to Wagner's classification, and number and type of procedures performed between January 2012 and December 2016 due to complications derived from diabetic foot.. Results The study included 58 patients, with a mean age of 65 years, and 69% were men. The clinical stage in the pre-surgical evaluation was 39.7% and 37.9% Wagner III and IV, respectively, and during the operation it was 32.8% III, 50% IV. The isolated micro-organisms were 15.5% Escherichia Coli, of these 11.9% were ESBL positive and 3.6% multisensitive. Another 15.5% were Pseudomonas Aeruginosa, multiresistant variants 10.7%, producing carbapenemases 1.2%, resistant to meropenem 1.2%, and multiple sensitivity 2.4%. The large majority (77.5%) of the patients required a change of antibiotic. One third of the patients required major amputations, of which 46.6% had infections caused by multidrug-resistant germs. Discussion The predominant micro-organisms found were multi-resistant gram negative bacilli. It is suggested taking specimens intraoperative prior to the start of antibiotic therapy. Given the bacterial flora isolated in this series, when starting empirical antibiotic therapy, the use of carbapenems is suggested.

A computational design approach for virtual screening of peptide interactions across K(+) channel families.

Ion channels represent a large family of membrane proteins with many being well established targets in pharmacotherapy. The 'druggability' of heteromeric channels comprised of different subunits remains obscure, due largely to a lack of channel-specific probes necessary to delineate their therapeutic potential in vivo. Our initial studies reported here, investigated the family of inwardly rectifying potassium (Kir) channels given the availability of high resolution crystal structures for the eukaryotic constitutively active Kir2.2 channel. We describe a 'limited' homology modeling approach that can yield chimeric Kir channels having an outer vestibule structure representing nearly any known vertebrate or invertebrate channel. These computationally-derived channel structures were tested ""in silico for 'docking' to NMR structures of tertiapin (TPN), a 21 amino acid peptide found in bee venom. TPN is a highly selective and potent blocker for the epithelial rat Kir1.1 channel, but does not block human or zebrafish Kir1.1 channel isoforms. Our Kir1.1 channel-TPN docking experiments recapitulated published in vitro ""findings for TPN-sensitive and TPN-insensitive channels. Additionally, in silico site-directed mutagenesis identified 'hot spots' within the channel outer vestibule that mediate energetically favorable docking scores and correlate with sites previously identified with in vitro thermodynamic mutant-cycle analysis. These 'proof-of-principle' results establish a framework for virtual screening of re-engineered peptide toxins for interactions with computationally derived Kir channels that currently lack channel-specific blockers. When coupled with electrophysiological validation, this virtual screening approach may accelerate the drug discovery process, and can be readily applied to other ion channels families where high resolution structures are available.

Crisis gelásticas originadas en lóbulo temporal / Gelastic seizures originating in the temporal lobe

Las crisis gelásticas son una forma rara de epilepsia no convulsiva, más frecuente en población adulta joven y casi exclusiva de hamartomas hipotalámicos; sin embargo, hay otras localizaciones no hipotalámicas poco descritas en las cuales se presentan estas crisis, como el lóbulo temporal. El caso que presentamos muestra una manifestación atípica: un paciente de edad avanzada consultó por cambios en el comportamiento y risas inmotivadas; durante la hospitalización, se estableció la presencia de crisis gelásticas, las cuales fueron atribuidas a zona de gliosis temporal izquierda por antecedente de hematoma epidural en esta localización. Se concluye que este tipo de crisis epiléptica en población de la tercera edad es el resultado de etiologías distintas al hamartoma hipotalámico.

Gelastic seizures are a rare form of non-convulsive seizures, more common in young adults and almost exclusively of endocrine disorders and hypothalamic hamartomas, there another other places for this seizures as the temporal lobe. The case shows an atypical manifestation, an elderly patient who consults for changes in behavior and unmotivated laughter; during hospitalization, showed the presence of gelastic seizures, which were attributed to the left temporal area of gliosis by previous epidural hematoma at this location, we present clinical history, neuroimaging and EEG. In the conclusion on elderly, this type of seizure occurs by different etiologies and no only by hypothalamic hamartoma.