Combination of unsupervised discretization methods for credit risk.

Creating robust and explainable statistical learning models is essential in credit risk management. For this purpose, equally spaced or frequent discretization is the de facto choice when building predictive models. The methods above have limitations, given that when the discretization procedure is constrained, the underlying patterns are lost. This study introduces an innovative approach by combining traditional discretization techniques with clustering-based discretization, specifically k means and Gaussian mixture models. The study proposes two combinations: Discrete Competitive Combination (DCC) and Discrete Exhaustive Combination (DEC). Discrete Competitive Combination selects features based on the discretization method that performs better on each feature, whereas Discrete Exhaustive Combination includes every discretization method to complement the information not captured by each technique. The proposed combinations were tested on 11 different credit risk datasets by fitting a logistic regression model using the weight of evidence transformation over the training partition and contrasted over the validation partition. The experimental findings showed that both combinations similarly outperform individual methods for the logistic regression without compromising the computational efficiency. More importantly, the proposed method is a feasible and competitive alternative to conventional methods without reducing explainability.

The invasive twospot livebearer's biology, and its current and potential global distribution.

Poeciliids are widely recognized as successful invaders, possessing traits associated with invasion success. Native to Central America and south-eastern Mexico, the twospot livebearer (Pseudoxiphophorus bimaculatus) is a species recently recognized as invasive in both Central and northern Mexico. Despite its invasive status, limited research exists on its invasion process and the potential threats it poses to native species. In this study, we conducted a comprehensive review of the current knowledge on the twospot livebearer and mapped its current and potential distribution worldwide. The twospot livebearer shares similar traits with other successful invaders within the same family. Notably, it exhibits high fecundity throughout the year and demonstrates resilience to highly polluted and oxygen-deprived water conditions. This fish serves as a host for several parasites, including generalists, and has been extensively translocated for commercial purposes. Recently, it has also been used for biocontrol within its native range. Apart from existing outside its native range, the twospot livebearer, under current climate conditions and if transported there, could readily colonize biodiversity hotspots in tropical zones worldwide, including the Caribbean Islands, the Horn of Africa, North of Madagascar Island, south-eastern Brazil, and others located in southern and eastern Asia. Given that this fish is highly plastic and our Species Distribution Model, we consider that all areas with a habitat suitability >0.2 should prevent its arrival and establishment. Our findings underscore the urgent need to recognize this species as a threat to freshwater native topminnows and prevent its introduction and spread.

Comportamiento del tiempo de conducción retrógrada al momento de la inducción de las taquicardias supraventriculares y su rol en el diagnóstico diferencial / Behavior of Retrograde Conduction Time at Supraventricular Tachycardia Induction and its Role in Differential Diagnosis

RESUMEN Antecedentes : El diagnóstico diferencial entre la taquicardia reentrante ortodrómica (TRO) y la taquicardia por reentrada nodal atípica (TRNa) puede ser dificultoso. Nuestra hipótesis es que las TRNa tienen más variabilidad en el tiempo de con ducción retrógrada al comienzo de la taquicardia que las TRO. Nuestros objetivos fueron evaluar la variabilidad en el tiempo de conducción retrógrada al inicio de la taquicardia en TRNa y TRO, y proponer una nueva herramienta diagnóstica para diferenciar estas dos arritmias. Métodos : Se midió el intervalo ventrículo-auricular (VA) de los primeros latidos tras la inducción de la taquicardia, hasta su estabilización. La diferencia entre el intervalo VA máximo y el mínimo se definió como delta VA (ΔVA). También contamos el número de latidos necesarios para que se estabilice el intervalo VA. Se excluyeron las taquicardias auriculares. Resultados : Se incluyeron 101 pacientes. Se diagnosticó TRO en 64 pacientes y TRNa en 37. El ΔVA fue 0 (rango intercuartílico, RIC, 0-5) milisegundos (ms) en la TRO frente a 40 (21-55) ms en la TRNa (p < 0,001). El intervalo VA se estabilizó significativamente antes en la TRO (1,5 [1-3] latidos) que en la TRNa (5 [4-7] latidos; p < 0,001). Un ΔVA < 10 ms diagnosticó TRO con 100% de sensibilidad, especificidad y valores predictivos positivo y negativo. La estabilización del intervalo VA en menos de 3 latidos predijo TRO con buena precisión diagnóstica. Los resultados fueron similares considerando sólo vías accesorias septales. Las TRN típicas tuvieron una variación intermedia. Conclusión : Un ΔVA < 10 ms es un criterio simple, que distingue con precisión la TRO de la TRNa, independientemente de la localización de la vía accesoria.

ABSTRACT Background : Differential diagnosis between orthodromic reentrant tachycardia (ORT) and atypical nodal reentrant tachy cardia (ANRT) can be challenging. Our hypothesis was that ANRT presents more variability in retrograde conduction time at tachycardia onset than ORT. Objectives : The objectives of this study were to assess retrograde conduction time variability at the start of tachycardia in ANRT and ORT, and postulate a new diagnostic tool to differentiate these two types of arrhythmias. Methods : The ventriculoatrial (VA) interval of the first beats after tachycardia induction was measured until stabilization. The difference between the maximum and minimum VA interval was defined as delta VA (ΔVA), and the number of beats needed for VA interval stabilization was also assessed. Atrial tachycardias were excluded. Results : In a total of 101 patients included in the study, ORT was diagnosed in 64 patients and ANRT in 37. ΔVA interval was 0 (interquartile range [IQR] 0-5) milliseconds (ms) in ORT vs. 40 (21-55) ms in ANRT (p <0.001). The VA interval significantly stabilized earlier in ORT (1.5 [1-3] beats) than in ANRT (5 [4-7] beats) (p<0.001). A ΔVA <10 ms diagnosed ORT with 100% sensitivity, specificity, and positive and negative predictive values. Ventriculoatrial interval stabilization in less than 3 beats predicted ORT with good diagnostic accuracy. The results were similar considering only accessory septal pathways. Typical NRTs presented an intermediate variation. Conclusion : Presence of DVA <10 ms is a simple criterion that accurately differentiates ORT from ANRT, independently of the accessory pathway localization.

Analyzing Mitochondrial Morphology Through Simulation Supervised Learning.

The quantitative analysis of subcellular organelles such as mitochondria in cell fluorescence microscopy images is a demanding task because of the inherent challenges in the segmentation of these small and morphologically diverse structures. In this article, we demonstrate the use of a machine learning-aided segmentation and analysis pipeline for the quantification of mitochondrial morphology in fluorescence microscopy images of fixed cells. The deep learning-based segmentation tool is trained on simulated images and eliminates the requirement for ground truth annotations for supervised deep learning. We demonstrate the utility of this tool on fluorescence microscopy images of fixed cardiomyoblasts with a stable expression of fluorescent mitochondria markers and employ specific cell culture conditions to induce changes in the mitochondrial morphology.

Variability of the VA interval at tachycardia induction: a simple method to differentiate orthodromic reciprocating tachycardia from atypical atrioventricular nodal reentrant tachycardia.

BACKGROUND: The differential diagnosis between orthodromic atrioventricular reentry tachycardia (AVRT) and atypical AV nodal reentrant tachycardia (aAVNRT) is sometimes challenging. We hypothesize that aAVNRTs have more variability in the retrograde conduction time at tachycardia onset than AVRTs. METHODS: We aimed to assess the variability in retrograde conduction time at tachycardia onset in AVRT and aAVNRT and to propose a new diagnostic tool to differentiate these two arrhythmia mechanisms. We measured the VA interval of the first beats after tachycardia induction until it stabilized. The difference between the maximum and minimum VA intervals (∆VA) and the number of beats needed for the VA interval to stabilize was analyzed. Atrial tachycardias were excluded. RESULTS: A total of 107 patients with aAVNRT (n = 37) or AVRT (n = 64) were included. Six additional patients with decremental accessory pathway-mediated tachycardia (DAPT) were analyzed separately. All aAVNRTs had VA interval variability. The median ∆VA was 0 (0 - 5) ms in AVRTs vs 40 (21 - 55) ms in aAVNRTs (p < 0.001). The VA interval stabilized significantly earlier in AVRTs (median 1.5 [1 - 3] beats) than in aAVNRTs (5 [4 - 7] beats; p < 0.001). A ∆VA < 10 ms accurately differentiated AVRT from aAVNRT with 100% of sensitivity, specificity, and positive and negative predictive values. The stabilization of the VA interval at < 3 beats of the tachycardia onset identified AVRT with sensitivity, specificity, and positive and negative predictive values of 64.1%, 94.6%, 95.3%, and 60.3%, respectively. A ∆VA < 20 ms yielded good diagnostic accuracy for DAPT. CONCLUSIONS: A ∆VA < 10 ms is a simple and useful criterion that accurately distinguished AVRT from atypical AVNRT. Central panel: Scatter plot showing individual values of ∆VA in atypical AVNRT and AVRT. Left panel: induction of atypical AVNRT. The VA interval stabilizes at the 5th beat and the ∆VA is 62 ms (maximum VA interval: 172 ms - minimum VA interval: 110 ms). Right panel: induction of AVRT. The tachycardia has a fixed VA interval from the first beat. ∆VA is 0 ms.

Effect of a temperature gradient on the behaviour of an endangered Mexican topminnow and an invasive freshwater fish.

Climate change and biological invasions are two of the major threats to biodiversity. They could act synergistically to the detriment of natives as non-native species may be more plastic and resilient when facing changing environments. The twoline skiffia (Skiffia bilineata) is an endangered Mexican topminnow that cohabits with invasive guppies (Poecilia reticulata) in some areas in central Mexico. Guppies have been found to take advantage from associating with the twoline skiffia and are considered partially responsible for the decline of its populations. Refuge use and exploratory behaviours are trade-offs between being safe from the unknown and the opportunity to explore novel areas in search for better resources or to disperse. The aim of this study is to investigate how a change in temperature affects the refuge use and exploratory behaviours for both species. We found that temperature affects the refuge use of twoline skiffias, and the swimming activity of both species. Skiffias explored the rock more than guppies regardless of the temperature scenario. Also, smaller fish spent more time performing exploratory behaviours than bigger ones. Our study is the first to test the effect of temperature on the refuge use and exploratory behaviour of a goodeid species, and our results contribute to the idea that some natives could be more affected by climate change than some invaders.

CONVERSION OF DOSE DISTRIBUTION TO CELL SURVIVAL FRACTION THROUGH DNA DAMAGE: A MONTE CARLO STUDY.

Ionizing radiation plays an important role in cancer treatment. Radiation is able to damage the genetic material of cells, blocking their ability to divide and proliferate further. Since radiation affects both healthy and malignant tissues, for all radiation treatments, the design of an accurate treatment plan is fundamental. Usually, weight factors, such as the relative biological effectiveness, are applied to estimate the impact of the kind of radiation and the irradiated medium on the dose deposition. However, these factors can only provide a partial estimation of the real effect on tissues. In this work, a flexible system that is able to predict cell survival fractions according to the planned dose distribution is presented. Dose deposition and subsequent DNA damage were simulated with a multi-scale modeling approach by first applying the FLUKA Monte Carlo (MC) code to estimate the absorbed doses and fluence energy spectra and then using the MC Damage Simulation code to compute the DNA damage yields. Lastly, the results are converted into cell survival fraction using a theoretical model. The comparisons between the simulated survival fractions with experimental data are reported for a proton spread out Bragg peak at several doses. The presented approach helps to elucidate radiobiological responses along the Bragg curve and has the flexibility to be extended to a wide range of situations of clinical interest.

Nanosecond Pulsed Electric Field (nsPEF): Opening the Biotechnological Pandora's Box.

Nanosecond Pulsed Electric Field (nsPEF) is an electrostimulation technique first developed in 1995; nsPEF requires the delivery of a series of pulses of high electric fields in the order of nanoseconds into biological tissues or cells. They primary effects in cells is the formation of membrane nanopores and the activation of ionic channels, leading to an incremental increase in cytoplasmic Ca2+ concentration, which triggers a signaling cascade producing a variety of effects: from apoptosis up to cell differentiation and proliferation. Further, nsPEF may affect organelles, making nsPEF a unique tool to manipulate and study cells. This technique is exploited in a broad spectrum of applications, such as: sterilization in the food industry, seed germination, anti-parasitic effects, wound healing, increased immune response, activation of neurons and myocites, cell proliferation, cellular phenotype manipulation, modulation of gene expression, and as a novel cancer treatment. This review thoroughly explores both nsPEF's history and applications, with emphasis on the cellular effects from a biophysics perspective, highlighting the role of ionic channels as a mechanistic driver of the increase in cytoplasmic Ca2+ concentration.

Exploring the Conformational Changes Induced by Nanosecond Pulsed Electric Fields on the Voltage Sensing Domain of a Ca2+ Channel.

Nanosecond Pulsed Electric Field (nsPEF or Nano Pulsed Stimulation, NPS) is a technology that delivers a series of pulses of high-voltage electric fields during a short period of time, in the order of nanoseconds. The main consequence of nsPEF upon cells is the formation of nanopores, which is followed by the gating of ionic channels. Literature is conclusive in that the physiological mechanisms governing ion channel gating occur in the order of milliseconds. Hence, understanding how these channels can be activated by a nsPEF would be an important step in order to conciliate fundamental biophysical knowledge with improved nsPEF applications. To get insights on both the kinetics and thermodynamics of ion channel gating induced by nsPEF, in this work, we simulated the Voltage Sensing Domain (VSD) of a voltage-gated Ca2+ channel, inserted in phospholipidic membranes with different concentrations of cholesterol. We studied the conformational changes of the VSD under a nsPEF mimicked by the application of a continuous electric field lasting 50 ns with different intensities as an approach to reveal novel mechanisms leading to ion channel gating in such short timescales. Our results show that using a membrane with high cholesterol content, under an nsPEF of 50 ns and E→ = 0.2 V/nm, the VSD undergoes major conformational changes. As a whole, our work supports the notion that membrane composition may act as an allosteric regulator, specifically cholesterol content, which is fundamental for the response of the VSD to an external electric field. Moreover, changes on the VSD structure suggest that the gating of voltage-gated Ca2+ channels by a nsPEF may be due to major conformational changes elicited in response to the external electric field. Finally, the VSD/cholesterol-bilayer under an nsPEF of 50 ns and E→ = 0.2 V/nm elicits a pore formation across the VSD suggesting a new non-reported effect of nsPEF into cells, which can be called a "protein mediated electroporation".

Torsión interna de rodilla. Protocolo tomográfico patelofemoral en posición de marcha / Axial torsion of the knee. Patellofemoral CT protocol in gait position

La mala alineación patelofemoral se manifiesta con dolor y/o inestabilidad y genera deterioro articular precoz. La etiología es multifactorial y es un desafío valorar todos los factores que la producen para realizar un tratamiento adecuado para cada paciente. Las alteraciones torsionales, tanto femorales como tibiales, han demostrado su influencia en la articulación patelofemoral. La combinación entre la anteversión femoral, la torsión tibial y el ángulo de progresión de la marcha pueden generar torsión interna o externa de la rodilla. El objetivo de este estudio es presentar nuestro protocolo tomográfico funcional, con la medición de la torsión interna de rodilla en una posición de simulación de marcha; este índice torsional es una nueva herramienta útil para la toma de decisiones.Relevancia clínica: este es el primer protocolo tomográfico en estudiar la torsión de rodilla en relación con la línea de dirección de avance del cuerpo.Tipo de estudio: Metanálisis

Patellofemoral malalignment manifest with pain or instability, generating early arthritis. The etiology is multifactorial, and it is a challenge to assess all the factors involved, to perform an individualized treatment. Torsional disorders, both femoral and tibial, has shown their influence in patellofemoral joint. The correlation between femoral anteversion, tibial torsion and foot progression angle, can generate internal or external torsion of the knee. The objective of this study is to present our CT functional patellofemoral joint protocol, with the measurement of the knee internal torsion, in a simulating gait position of the knee in the space, and the description of a torsional index as a new tool for the decision making in treatment.Clinical relevance: this is the first CT protocol that assess the axial torsion of the knee in relationship to the direction of movement of the body. Type of study: Meta-analysis

High tibial derotation osteotomy for distal extensor mechanism alignment in patients with squinting patella due to increased external tibial torsion.

BACKGROUND: The patellofemoral joint is often affected by torsionaldisorders of the lower limb, causing pain, instability and knee degeneration. The aims of this study were to determine functional outcomes of patients who underwent a high tibial derotation osteotomy (HTDO) for symptomatic squinting patella due to increased external tibial torsion. Moreover, factors associated with inferior clinical outcomes were investigated. METHODS: Patients with symptomatic squinting patella, increased external tibial torsion (>30°) treated with this technique, and with 2 years of follow up were included. Fulkerson and Kujala patellofemoral joint scores were assessed. Age, body mass index, history of prior surgery, increased femoral anteversion, association of lateral retinaculum release and patellar cartilage lesions were analysed. RESULTS: Sixty HTDOs were included in this retrospective study with an average of 66 months of follow up. The mean Kujala score improved from 47.5 preoperatively to 93 postoperatively. The mean Fulkerson score improved from 40.6 to 91.6. Kujala subscores for pain improved from 8.6 to 30.4, for instability improved from 6.4 to 17.9, and their ability to climb stairs increased from 6.9 to 17.9 (all P < 0.0001). Multivariate logistic regression model identified that patient age (P < 0.005) and advanced chondral damage (P < 0.001) were the dominant factors predicting inferior clinical outcomes using Kujala's score. CONCLUSION: HTDO provided good results regarding the pain symptoms, instability and the ability to climb stairs. Advanced chondral damage and advanced age had negative effects on outcomes.

Risk Factors for Community-Acquired Acute Kidney Injury in Medical Patients: A Nested Case-Control Study.

INTRODUCTION: Research about the risk factors associated with community-acquired acute kidney injury (CA-AKI) in acute medical diseases is scarce. Data extrapolation from surgical to medical illnesses is questionable. OBJECTIVES: To evaluate potential risk factors and hospital outcomes associated with a CA-AKI in medical illnesses. METHODS: We performed an unmatched nested case-control study from a previous prospective cohort study. We included adult patients with acute illnesses treated with internal medicine. Cases were defined as patients with a CA-AKI diagnosis upon hospital admission, and controls included patients from the same cohort who did not develop AKI during the first 5 days of hospitalisation. A logistic regression model was used to assess the association between potential risk factors and -CA-AKI. RESULTS: A total of 868 patients were included in the study (223 cases and 645 controls). The median age was 65 years (interquartile range 50-78). In a logistic regression model, the risk factors associated with CA-AKI included chronic kidney disease (CKD; OR 6.27; 95% CI 2.95-13.3, p < 0.001), ≥65 years old (OR 1.72; 95% CI 1.16-2.57, p = 0.007), acute bacterial infection (OR 1.95; 95% CI 1.36-2.80, p < 0.001), hypovolaemia (OR 1.88; 95% CI 1.32-2.69, p < 0.001), pre-hospital nephrotoxic drugs (OR 1.77; 95% CI 1.23-2.55, p = 0.002), anaemia (OR 1.49; 95% CI 1.03-2.14, p = 0.031) and systolic blood pressure (SBP) <107 mm Hg (OR 2.25; 95% CI 1.38-3.67, p = 0.001). A significant interaction between CKD and age was found (p = 0.017) and included in the model (patients with CKD and ≥65 years old [OR 10.85; 95% CI 4.14-28.41, p < 0.001]). The area under the receiver operating characteristic curve of the final model was 0.743. CONCLUSIONS: CKD is strongly associated with CA-AKI upon hospital admission in medical illnesses patients. Older age enhances the risk of CA-AKI in patients with CKD. Other risk factors include pre-hospital nephrotoxic drugs, acute bacterial infection, anaemia, low SBP and hypovolaemia.

l-DOPA modulates the kinetics but not the thermodynamic equilibrium of TTA+ amphiphiles forming lyotropic nematic liquid crystals.

Lyotropic liquid crystals (LLCs) are mixtures of amphiphile molecules usually studied as mimetic of biological membrane. The equilibrium dynamics of tetradecyltrimethyl ammonium cation (TTA+) molecules forming nematic LLCs (LNLCs) is guided by a dive-in mechanism where TTA+ molecules spontaneously leave and re-enter the bicelle. Of note, this dynamic behavior could be exploited to produce drug nano-delivery systems based on LNLCs. Therefore, the understanding of the effect of pharmaceutically interesting molecules in the dynamics of the dive-in mechanism should be crucial for drug delivery applications. In this work, we studied the effects of l-DOPA in the equilibrium dynamics of TTA+ bicelles forming LNLCs, employing a transdisciplinary approach based on 2H-NMR together with molecular modeling and molecular dynamics simulations. Our data suggest that l-DOPA perturbs the kinetic of the dive-in mechanism but not the thermodynamics of this process. As whole, our results provide fundamental insights on the mechanisms by which l-DOPA govern the equilibrium of LNLCs bicelles.

Remisión espontánea a largo plazo de la forma congénita de la taquicardia ectópica de la unión / Long-term Spontaneous Remission of Congenital Junctional Ectopic Tachycardia

RESUMEN Introducción: La forma congénita de la taquicardia ectópica de la unión (junctional ectopic tachycardia, JET) es una taquicardia supraventricular poco común, con alta morbimortalidad. Su tratamiento requiere, frecuentemente, el uso de múltiples fármacos durante períodos prolongados. En algunos casos se necesita, además, realizar un procedimiento invasivo, como la crioablación. Algunos estudios han demostrados la existencia de casos de remisión espontánea de la arritmia a largo plazo (con la reversión a ritmo sinusal o a un ritmo nodal acelerado), sin requerimiento de fármacos y sin mediar intervención alguna. Objetivos: Evaluar la incidencia de remisión espontanea de la JET congénita en una población pediátrica en el seguimiento a largo plazo. Material y métodos: Se incluyeron 23 pacientes consecutivos con JET congénita evaluados en el Hospital J.P. Garrahan y en el Hospital Italiano de Buenos Aires, entre los años 1999 y 2017, con un seguimiento medio de 8,8 años (rango intercuartil, RIC: 5,5-14,1). Se evaluó a largo plazo la incidencia de remisión espontánea de la arritmia. Resultados: La mediana para la edad de presentación fue 2 meses (RIC: 0,625-3); 15 pacientes (62,5%) presentaron signos de insuficiencia cardíaca y 11 pacientes (45,8%), taquicardiomiopatía. A 2 pacientes se les realizó una crioablación en forma exitosa. La tasa de remisión espontánea fue del 52%. En aquellos pacientes con un seguimiento mayor a 10 años (15 sujetos), la remisión fue del 62,5%. La media para edad de remisión fue 9,6 años. Conclusiones: La JET congénita es una taquicardia potencialmente grave en los primeros meses de vida, pero con alta tasa de remisión espontánea a largo plazo.

ABSTRACT Background: The congenital form of junctional ectopic tachycardia (JET) is a rare supraventricular tachycardia with high morbidity and mortality. Its treatment frequently requires the prolonged use of multiple drugs and, in some cases, an inva-sive procedure, such as cryoablation, is necessary. Some studies have demonstrated the existence of spontaneous remission of arrhythmia in the long term (with reversal to sinus rhythm or to an accelerated nodal rhythm), without need of drugs or any other form of intervention. Objectives: The aim of this study was to evaluate the long-term incidence of spontaneous remission of congenital JET in a pediatric population. Methods: Twenty-three consecutive patients with congenital JET were evaluated at Hospital J.P. Garrahan and Hospital Italiano de Buenos Aires, between 1999 and 2017, with a mean follow-up of 8.8 years interquartile range (IQR): 5.5-14.1). The incidence of spontaneous arrhythmia remission was evaluated in the long term. Results: Median presentation age was 2 months (IQR: 0.625-3); 15 patients (62.5%) presented signs of heart failure and 11 patients (45.8%) tachycardiomyopathy. Two patients underwent successful cryoablation. The spontaneous remission rate was 52%. In patients with follow-up above 10 years (15 subjects), remission was 62.5%. Mean remission age was 9.6 years. Conclusions: Congenital JET is a potentially severe tachycardia in the first months of life, but with a high rate of long-term spontaneous remission.

Mining EEG with SVM for Understanding Cognitive Underpinnings of Math Problem Solving Strategies.

We have developed a new methodology for examining and extracting patterns from brain electric activity by using data mining and machine learning techniques. Data was collected from experiments focused on the study of cognitive processes that might evoke different specific strategies in the resolution of math problems. A binary classification problem was constructed using correlations and phase synchronization between different electroencephalographic channels as characteristics and, as labels or classes, the math performances of individuals participating in specially designed experiments. The proposed methodology is based on using well-established procedures of feature selection, which were used to determine a suitable brain functional network size related to math problem solving strategies and also to discover the most relevant links in this network without including noisy connections or excluding significant connections.

Molecular Modeling of Structures and Interaction of Human Corticotropin-Releasing Factor (CRF) Binding Protein and CRF Type-2 Receptor.

The corticotropin-releasing factor (CRF) system is a key mediator of the stress response and addictive behavior. The CRF system includes four peptides: The CRF system includes four peptides: CRF, urocortins I-III, CRF binding protein (CRF-BP) that binds CRF with high affinity, and two class B G-protein coupled receptors CRF1R and CRF2R. CRF-BP is a secreted protein without significant sequence homology to CRF receptors or to any other known class of protein. Recently, it has been described a potentiation role of CRF-BP over CRF signaling through CRF2R in addictive-related neuronal plasticity and behavior. In addition, it has been described that CRF-BP is capable to physically interact specifically with the α isoform of CRF2R and acts like an escort protein increasing the amount of the receptor in the plasma membrane. At present, there are no available structures for CRF-BP or for full-length CRFR. Knowing and studying the structure of these proteins could be beneficial in order to characterize the CRF-BP/CRF2αR interaction. In this work, we report the modeling of CRF-BP and of full-length CRF2αR and CRF2ßR based on the recently solved crystal structures of the transmembrane domains of the human glucagon receptor and human CRF1R, in addition with the resolved N-terminal extracellular domain of CRFRs. These models were further studied using molecular dynamics simulations and protein-protein docking. The results predicted a higher possibility of interaction of CRF-BP with CRF2αR than CRF2ßR and yielded the possible residues conforming the interacting interface. Thus, the present study provides a framework for further investigation of the CRF-BP/CRF2αR interaction.

Usefulness of remote Monitoring of Pediatric Patients with Cardiac implantable electronic devices / Utilidad de los dispositivos cardíaco-eléctricos con monitoreo a distancia en pacientes pediátricos

ABSTRACT: Background: The aim of this study is to evaluate the usefulness of cardiac implantable electronic devices with remote monitoring system in a pediatric population and the limitations of its implementation in Argentina. Methods: Twenty-seven patients receiving a cardiac implantable electronic device with remote monitoring system at Hospital Nacional Garrahan and Hospital Italiano de Buenos Aires were included in the study. The rate of events, complications and device-related therapies were evaluated. The anticipated actions taken in response to alert notifications were described. Mean follow-up was 46.6 ± 32.1 months. results: Median age was 12.2 years (IQR: 8.75-13.3). An implantable cardioverter defibrillator device was placed in 7 patients (25.9%) and 20 (74%) underwent pacemaker implant. Five patients (18.5%) presented seven red alerts: 3 due to ventricular arrhyth-mia in monitoring zone of ventricular fibrillation and 4 due to lead dysfunction. Twelve patients (44%) presented a yellow alert: 6 due to lead dysfunction, 4 due to deactivation of the monitoring system because of lack of signal reception, one due to ventricular tachycardia and another with sinus tachycardia in monitoring zone of ventricular tachycardia. Active actions were taken in 9 pa-tients (33.3%) to manage the alert notification: the atrial lead was replaced in one patient and the ventricular in lead in another; in 2 patients non-compliance with pharmacological treatment and exercise limitation were detected and in the rest of the patients, the device was reprogrammed according to the abnormalities observed in the recording or capture. Conclusions: Remote monitoring of cardiac implantable electronic devices is very useful in the pediatric population, allowing for the rapid detection and management of device failure or significant arrhythmias.

RESUMEN: Objetivo: Evaluar la utilidad de los dispositivos cardíacos eléctricos con sistema de monitoreo a distancia en una población pediátrica y las limitaciones de su implementación en la República Argentina. Material y métodos: Se incluyeron 27 pacientes a quienes se le implantó un dispositivo cardíaco-eléctrico implantable con sistema de monitoreo a distancia en el Hospital Nacional Garrahan y en el Hospital Italiano de Bs. As. Se evaluó la tasa de eventos, complicaciones y terapias por parte de los dispositivos. Se describieron las conductas anticipadas según la alerta recibida. Se realizó un seguimiento medio de 46,6 meses ± 32,1. resultados: La edad fue 12,2 años (RIC: 8,75-13,3), a 7 pacientes (28%) se les implantó un cardiodesfibrilador implantable y 20 pacientes (78%) un marcapaso endocavitario. Cinco pacientes (18,5%) presentaron 7 alertas rojas: 3 por arritmia ventricular en rango de fibrilación ventricular y 4 por alteraciones en alguno de los cables. Doce pacientes (44%) presentaron una alerta amarilla: 6, por alteraciones en los cables; 4, por desactivación del sistema por falta de recepción de señal; 1, por taquicardia ventricular; y 1, por taquicardia sinusal en rango de taquicardia ventricular. En 9 pacientes (33,3%) se tomó una conducta activa para resolver el aviso de alerta: en 2 pacientes se realizó recambio de cable auricular en uno y ventricular en otro, en 2 pacientes se detectó incumplimiento del tratamiento farmacológico y en la limitación del ejercicio, en el resto se reprogramó el dispositivo, según el tipo de alteración en el registro o la captura. Conclusiones: El sistema de monitoreo remoto de los dispositivos cardíaco-eléctricos implantables es muy útil en la población pediátrica, lo que permite una rápida detección y acción cuando se produce un fallo en el dispositivo o un evento arrítmico de relevancia clínica.