Incidence of fever and bleeding after percutaneous nephrolithotomy: a prospective cohort study.

OBJECTIVE: Despite relative agreement on the need for immediate peri-operative antibiotic prophylaxis in percutaneous nephrolithotomy (PCNL), there is no consensus regarding antibiotic use the days leading up to PCNL. This study aimed to report the incidence of complications during and after PCNL based on a cohort study design. MATERIAL AND METHODS: We included 101 patients in a prospective schedule for PCNL. Patients were divided into 2 groups. In the exposed patients (positive urine culture) the antibiotic was indicated according to the antibiogram report, 7 days before surgery, and 7 days after surgery, and in the non-exposed patient's intravenous antibiotic empirically was administered 8 h and 1 h before surgery. RESULTS: The incidence of complications for both groups was 19%. The exposed group presented complications in 27%, and 16% for the non-exposed. The relative risk of complications, in general, was 1.68 (95% CI, 0.77-3.6), the attributable risk was 11.09, and the percentage of attributable risk was 40.68%. CONCLUSIONS: The presence of positive urine culture is the main risk factor for the development of post-PCNL fever. Each treatment center needs to standardize its protocols to reduce the morbidity associated with surgery and to identify the main risk factors.

OBJETIVO: El objetivo de este estudio es reportar la incidencia de complicaciones durante y después de la nefrolitotomía percutánea (NLP) con base en un diseño de cohorte prospectivo. MATERIAL Y MÉTODOS: Se incluyeron 101 pacientes de forma prospectiva programados para NLP. Los pacientes fueron divididos en 2 grupos. En el grupo de expuestos (cultivo de orina positivo) el antibiótico se indicó según el reporte del antibiograma, 7 días antes y 7 días después de la cirugía. En los pacientes no expuestos (cultivo de orina negativo) se administró empíricamente antibiótico intravenoso 8 h y 1 h antes de la cirugía. RESULTADOS: La incidencia de complicaciones para ambos grupos fue del 19%. El grupo de expuestos presentó ­complicaciones en 27% mientras que para los no expuestos fue de 16%. El riesgo relativo de complicaciones en general fue de 1.68 (IC 95%, 0.77-3.6), el riesgo atribuible fue de 11.09 y el porcentaje de riesgo atribuible fue de 40.68%. CONCLUSIONES: la presencia de urocultivo positivo es el principal factor de riesgo para el desarrollo de fiebre post-NLP. Es importante que cada centro de tratamiento estandarice sus protocolos para reducir la morbilidad asociada con la cirugía e identificar los principales factores de riesgo.

Psychological Science in the Wake of COVID-19: Social, Methodological, and Metascientific Considerations.

The COVID-19 pandemic has extensively changed the state of psychological science from what research questions psychologists can ask to which methodologies psychologists can use to investigate them. In this article, we offer a perspective on how to optimize new research in the pandemic's wake. Because this pandemic is inherently a social phenomenon-an event that hinges on human-to-human contact-we focus on socially relevant subfields of psychology. We highlight specific psychological phenomena that have likely shifted as a result of the pandemic and discuss theoretical, methodological, and practical considerations of conducting research on these phenomena. After this discussion, we evaluate metascientific issues that have been amplified by the pandemic. We aim to demonstrate how theoretically grounded views on the COVID-19 pandemic can help make psychological science stronger-not weaker-in its wake.

Language influences mass opinion toward gender and LGBT equality.

To improve gender equality and tolerance toward lesbian, gay, bisexual, and transgender (LGBT) communities, several nations have promoted the use of gender-neutral pronouns and words. Do these linguistic devices actually reduce biases that favor men over women, gays, lesbians, and transgender individuals? The current article explores this question with 3 large-scale experiments in Sweden, which formally incorporated a gender-neutral pronoun into its language alongside established gendered pronouns equivalent to he and she The evidence shows that compared with masculine pronouns, use of gender-neutral pronouns decreases the mental salience of males. This shift is associated with individuals expressing less bias in favor of traditional gender roles and categories, as reflected in more favorable attitudes toward women and LGBT individuals in public life. Additional analyses reveal similar patterns for feminine pronouns. The influence of both pronouns is more automatic than controlled.

Prevalencia y perfil de la persona frágil en la isla de La Palma / Prevalence and profile of the frail population in La Palma, Canary Islands

Introducción: El envejecimiento poblacional requiere que los sistemas sanitarios y sociales centren su atención en la identificación de la fragilidad en los ancianos. En Canarias, no existen estudios que determinen la prevalencia de fragilidad en su población. El objetivo del presente estudio es determinar la prevalencia y perfil de fragilidad en la isla de La Palma (Islas Canarias, España). Material y método: Estudio transversal para estimar la prevalencia y el perfil de la fragilidad. La muestra estuvo formada por residentes mayores de 70 años, valorados mediante los criterios de Fried, considerando otros factores relacionados. La prevalencia se ofrece en intervalo de confianza al 95% y se compara con la de otras poblaciones españolas. Para determinar el perfil se realizaron comparaciones simples de las variables, usadas posteriormente en modelos de regresión logística. Todas las pruebas fueron bilaterales a un nivel p ≤ 0,05. Resultados: La prevalencia de fragilidad en personas mayores de 70 años se estimó en un 20% (17-23%). Esta prevalencia muestra diferencias con las de otras poblaciones españolas. Los factores que mostraron asociación con la fragilidad fueron el ser mujer, estar viudo, vivir solo, baja actividad física, deterioro cognitivo, depresión, polimedicación y antecedentes clínicos adversos. El análisis multivariable identifica como asociadas a la fragilidad variables relacionadas con el estado civil, la convivencia, la polifarmacia, los estados depresivos y la falta de ejercicio físico. Conclusiones: Los ancianos de La Palma presentan mayor fragilidad en comparación con la descrita en otras regiones de España; su perfil es el de una persona viuda, con depresión, polimedicada, que vive sola y no realiza ejercicio

Introduction: Population ageing requires that health and social systems focus their attention on identifying frailty in the elderly. In the Canary Islands, there are no studies to determine the prevalence of frailty among its population. The objective of this study is to determine the prevalence and profile of frailty in the island of La Palma, Canary Islands, Spain. Material and method: A cross-sectional study was conducted to estimate the prevalence and the profile of frailty. The sample were residents over 70 years old, valued by the Fried criteria, and taking into account other related factors. The prevalence is offered with a confidence interval of 95% and is compared with that of other Spanish populations. To determine the profile, a simple comparison of variables was made, followed by using them in logistic regression models. All the tests were bilateral at a P≤0.05 level. Results: The prevalence of frailty in people over 70 years was estimated at 20% (17-23%). This prevalence shows differences with those of other Spanish populations. The factors that showed a relationship with frailty were, being female, widowed, living alone, low physical activity, cognitive impairment, depression, polymedication, and adverse clinical history. Multivariate analysis identifies factors associated with the frailty variables related to marital status, co-existence, polypharmacy, depressive states, and lack of physical exercise. Conclusions: The elderly population of La Palma have greater frailty compared to that described in other regions of Spain, with their profile being that of a widowed person, with depression, polymedicated, living alone, and not exercising

[Prevalence and profile of the frail population in La Palma, Canary Islands]. / Prevalencia y perfil de la persona frágil en la isla de La Palma.

INTRODUCTION: Population ageing requires that health and social systems focus their attention on identifying frailty in the elderly. In the Canary Islands, there are no studies to determine the prevalence of frailty among its population. The objective of this study is to determine the prevalence and profile of frailty in the island of La Palma, Canary Islands, Spain. MATERIAL AND METHOD: A cross-sectional study was conducted to estimate the prevalence and the profile of frailty. The sample were residents over 70 years old, valued by the Fried criteria, and taking into account other related factors. The prevalence is offered with a confidence interval of 95% and is compared with that of other Spanish populations. To determine the profile, a simple comparison of variables was made, followed by using them in logistic regression models. All the tests were bilateral at a P≤0.05 level. RESULTS: The prevalence of frailty in people over 70 years was estimated at 20% (17-23%). This prevalence shows differences with those of other Spanish populations. The factors that showed a relationship with frailty were, being female, widowed, living alone, low physical activity, cognitive impairment, depression, polymedication, and adverse clinical history. Multivariate analysis identifies factors associated with the frailty variables related to marital status, co-existence, polypharmacy, depressive states, and lack of physical exercise. CONCLUSIONS: The elderly population of La Palma have greater frailty compared to that described in other regions of Spain, with their profile being that of a widowed person, with depression, polymedicated, living alone, and not exercising.

Modulation of RXR function through ligand design.

As the promiscuous partner of heterodimeric associations, retinoid X receptors (RXRs) play a key role within the Nuclear Receptor (NR) superfamily. Some of the heterodimers (PPAR/RXR, LXR/RXR, FXR/RXR) are "permissive" as they become transcriptionally active in the sole presence of either an RXR-selective ligand ("rexinoid") or a NR partner ligand. In contrast, "non-permissive" heterodimers (including RAR/RXR, VDR/RXR and TR/RXR) are unresponsive to rexinoids alone but these agonists superactivate transcription by synergizing with partner agonists. Despite their promiscuity in heterodimer formation and activation of multiple pathways, RXR is a target for drug discovery. Indeed, a rexinoid is used in the clinic for the treatment of cutaneous T-cell lymphoma. In addition to cancer RXR modulators hold therapeutical potential for the treatment of metabolic diseases. The modulation potential of the rexinoid (as agonist or antagonist ligand) is dictated by the precise conformation of the ligand-receptor complexes and the nature and extent of their interaction with co-regulators, which determine the specific physiological responses through transcription modulation of cognate gene networks. Notwithstanding the advances in this field, it is not yet possible to predict the correlation between ligand structure and physiological response. We will focus on this review on the modulation of PPARγ/RXR and LXR/RXR heterodimer activities by rexinoids. The genetic and pharmacological data from animal models of insulin resistance, diabetes and obesity demonstrate that RXR agonists and antagonists have promise as anti-obesity agents. However, the treatment with rexinoids raises triglycerides levels, suppresses the thyroid hormone axis, and induces hepatomegaly, which has complicated the development of these compounds as therapeutic agents for the treatment of type 2 diabetes and insulin resistance. The discovery of PPARγ/RXR and LXR/RXR heterodimer-selective rexinoids, which act differently than PPARγ or LXR agonists, might overcome some of these limitations.

Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice.

BACKGROUND: Omega-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), have antidepressant and promnemonic functions. The mechanisms of such activities are still elusive and may involve retinoid X receptors (RXRs), transcription factors known to bind DHA in vitro. METHODS: Promnemonic and antidespair activities of acute DHA treatment were tested in BALBcByJ mice using spontaneous alternation and forced swim test, respectively. The involvement of retinoid receptors in such DHA activities was investigated using RXR and/or retinoic acid receptor (RAR) agonists to mimic DHA activities or a synthetic pan-RXR antagonist to block them. Involvement of RXR isotypes was analyzed using the same tasks and delayed nonmatch to place for working memory in RXRγ knockout mice. RESULTS: Docosahexaenoic acid decreased despair behavior and improved working memory in BALBcByJ mice. Such effects were suppressed by co-treatment with BR1211, a pan-RXR antagonist, whereas a pan-RXR agonist, UVI2108, mimicked DHA activities. Retinoic acid (RA), a natural ligand of RXRs, also reduced despair behavior and improved working memory and such activities did not require activation of RARs, as RA effects were abolished by co-treatment with BR1211 and they were not reproduced by TTNPB, a pan-RAR agonist. The RXRγ knockout mice displayed increased despair and deficits in working memory, which were insensitive to DHA and pan-RXR agonist treatments, whereas DHA or UVI2108 reversed these deficits in RXRγ heterozygous mice. CONCLUSIONS: Our data suggest that RXRs are a converging point in mediating DHA and RA modulations of despair behavior and working memory and that RXRγ is the predominant RXR isotype in these regulations.

Nuclear receptor ligand-binding domains: reduction of helix H12 dynamics to favour crystallization.

Crystallization trials of the human retinoid X receptor alpha ligand-binding domain (RXRalpha LBD) in complex with various ligands have been carried out. Using fluorescence anisotropy, it has been found that when compared with agonists these small-molecule effectors enhance the dynamics of the RXRalpha LBD C-terminal helix H12. In some cases, the mobility of this helix could be dramatically reduced by the addition of a 13-residue co-activator fragment (CoA). In keeping with these observations, crystals have been obtained of the corresponding ternary RXRalpha LBD-ligand-CoA complexes. In contrast, attempts to crystallize complexes with a highly mobile H12 remained unsuccessful. These experimental observations substantiate the previously recognized role of co-regulator fragments in facilitating the crystallization of nuclear receptor LBDs.

Deuterium exchange and mass spectrometry reveal the interaction differences of two synthetic modulators of RXRalpha LBD.

Protein amide hydrogen/deuterium (H/D) exchange was used to compare the interactions of two antagonists, UVI 2112 and UVI 3003, with that of the agonist, 9-cis-retinoic acid, upon binding to the human retinoid X receptor alpha ligand-binding domain (hRXRalpha LBD) homodimer. Analysis of the H/D content by mass spectrometry showed that in comparison to 9-cis-retinoic acid, the antagonists provide much greater protection toward deuterium exchange-in throughout the protein, suggesting that the protein-antagonist complex adopts a more restricted conformation or ensemble of conformations in which solvent accesses to amide protons are reduced. A comparison between the two antagonists shows that UVI 3003 is more protective in the C-terminal region due to the extra hydrophobic interactions derived from the atoms in the benzene ring of the carboxylic acid chain. It was less protective within regions comprising peptides 271-278 and 326-330 due to differences in conformational orientation, and/or shorter carboxylic acid chain length. Decreased deuterium exchange-in in the segment 234-239 where the residues do not involve interactions with the ligand was observed with the two antagonists, but not with 9-cis-RA. The amide protons of helix 12 of the agonist- or antagonist-occupied protein in solution have the same deuterium exchange rates as the unliganded protein, supporting a suggestion made previously that helix 12 can cover the occupied binding cavity only with the cofactor present to adjust its location.

Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function.

Retinoid X receptors (RXRalpha, -beta, and -gamma) occupy a central position in the nuclear receptor superfamily, because they form heterodimers with many other family members and hence are involved in the control of a variety of (patho)physiologic processes. Selective RXR ligands, referred to as rexinoids, are already used or are being developed for cancer therapy and have promise for the treatment of metabolic diseases. However, important side effects remain associated with existing rexinoids. Here we describe the rational design and functional characterization of a spectrum of RXR modulators ranging from partial to pure antagonists and demonstrate their utility as tools to probe the implication of RXRs in cell biological phenomena. One of these ligands renders RXR activity particularly sensitive to coactivator levels and has the potential to act as a cell-specific RXR modulator. A combination of crystallographic and fluorescence anisotropy studies reveals the molecular details accounting for the agonist-to-antagonist transition and provides direct experimental evidence for a correlation between the pharmacological activity of a ligand and its impact on the structural dynamics of the activation helix H12. Using RXR and its cognate ligands as a model system, our correlative analysis of 3D structures and dynamic data provides an original view on ligand actions and enables the establishment of mechanistic concepts, which will aid in the development of selective nuclear receptor modulators.

Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies.

Retinoid receptors (RARs and RXRs) are ligand-activated transcription factors that regulate the transcription of target genes by recruiting coregulator complexes at cognate promoters. To understand the effects of heterodimerization and ligand binding on coactivator recruitment, we solved the crystal structure of the complex between the RARbeta/RXRalpha ligand-binding domain heterodimer, its 9-cis retinoic acid ligand, and an LXXLL-containing peptide (termed NR box 2) derived from the nuclear receptor interaction domain (NID) of the TRAP220 coactivator. In parallel, we measured the binding affinities of the isolated NR box 2 peptide or the full-length NID of the coactivator SRC-1 for retinoid receptors in the presence of various types of ligands. Our correlative analysis of three-dimensional structures and fluorescence data reveals that heterodimerization does not significantly alter the structure of individual subunits or their intrinsic capacity to interact with NR box 2. Similarly, we show that the ability of a protomer to recruit NR box 2 does not vary as a function of the ligand binding status of the partner receptor. In contrast, the strength of the overall association between the heterodimer and the full-length SRC-1 NID is dictated by the combinatorial action of RAR and RXR ligands, the simultaneous presence of the two receptor agonists being required for highest binding affinity. We identified an LXXLL peptide-driven mechanism by which the concerted reorientation of three phenylalanine side chains generates an "aromatic clamp" that locks the RXR activation helix H12 in the transcriptionally active conformation. Finally, we show how variations of helix H11-ligand interactions can alter the communication pathway linking helices H11, H12, and the connecting loop L11-12 to the coactivator-binding site. Together, our results reveal molecular and structural features that impact on the ligand-dependent interaction of the RAR/RXR heterodimer with nuclear receptor coactivators.

Rational design of RAR-selective ligands revealed by RARbeta crystal stucture.

The crystal structure of the ligand-binding domain of RARbeta, a suspect tumour suppressor, reveals important features that distinguish it from the two other RAR isotypes. The most striking difference is an extra cavity allowing RARbeta to bind more bulky agonists. Accordingly, we identified a ligand that shows RARbeta selectivity with a 100-fold higher affinity to RARbeta than to alpha or gamma isotypes. The structural differences between the three RAR ligand-binding pockets revealed a rationale explaining how a single retinoid can be at the same time an RARalpha, gamma antagonist and an RARbeta agonist. In addition, we demonstrate how to generate an RARbeta antagonist by gradually modifying the bulkiness of a single substitution. Together, our results provide structural guidelines for the synthesis of RARbeta-selective agonists and antagonists, allowing for the first time to address pharmacologically the tumour suppressor role of RARbeta in vitro and in animal models.

Fractura de pene: urgencia urológica / Fracture of penis: urológica urgency

La fractura de pene (ruptura de los cuerpos cavernosos) es una emergencia urológica poco frecuente. El trabajo considera la hipótesis de que el abordaje quirúrgico inmediato disminuye la incidencia tanto de incurvaciones patológicas del pene, así como de disfunción eréctil secundaria. Se analizan retrospectivamente seis casos de ruptura de cuerpos cavernosos que se diagnosticaron y trataron en el Hospital Clínica Alcívar y el Hospital Luis Vernaza de Guayaquil. En todos los casos se procedió a una intervención quirúrgica inmediatamente a la presentación en la sala de emergencia, con drenaje del hematoma y rafia de la albugínea del cuerpo cavernosos afectado. Se presentaron seis pacientes entre 24 y 52 años (x=31 años) con diagnóstico clínico de fractura peneana...

Liposarcoma del cordón espermático / Liposarcoma of espermático cord

El liposarcoma del cordón espermático es raro. Se presenta el caso de un paciente masculino de 73 años, que acude por la presencia de una masa escrotal izquierda. Se sometió a ecografía inguinoescrotal, y posteriormente a orquiectomía radical izquierda, con resultado histopatológico de liposarcoma paratesticular bien diferenciado. Los estudios radiológicos fueron negativos para metástasis. El diagnóstico de este tipo de tumores generalmente es posoperatorio. Por ello. se debe poner mucho énfasis en que el liposarcoma debe ser considerado en el diagnóstico diferencial de las masas escrotales. Es importante su seguimiento para detectar recurrencias.

Incidencia de la torsión testicular en adultos pospuberales / Testicular torsion incidence in pospuberal adults

Se presentan 17 casos de torsión testicular en adultos jóvenes (pospuberales). En 53 por ciento existia algún antecedente de dolor previo en la glándula afectada. En seis pacientes (35.3 por ciento) se realizó orquiectomía simple, en todos hubo mal diagnóstico previo, con un retraso importante en su tratamiento quirúrgico. La pronta resolución de la isquemia evita que se produzca atrofia de la gónada, considerando que hay seguridad si el periodo es igual o menor a seis horas. Cuando la cirugía se realiza pasadas las 12 horas generalmente se pierde la glándula, ya sea por una hemicastracción o por atrofia posterior de la misma. Se recomienda que, ante la sospecha de torsión testicular se realice la exploración escrotal de manera inmediata, con fijación de la gónada contralateral ya que la anomalia congénita que ocasiona la torsión es siempre bilateral.