Differential role of bovine serum albumin and HCO3- in the regulation of GSK3 alpha during mouse sperm capacitation.

To become fertile, mammalian sperm are required to undergo capacitation in the female tract or in vitro in defined media containing ions (e.g. HCO3 -, Ca2+, Na+, and Cl-), energy sources (e.g. glucose, pyruvate) and serum albumin (e.g. bovine serum albumin (BSA)). These different molecules initiate sequential and concomitant signaling pathways, leading to capacitation. Physiologically, capacitation induces changes in the sperm motility pattern (e.g. hyperactivation) and prepares sperm for the acrosomal reaction (AR), two events required for fertilization. Molecularly, HCO3 - activates the atypical adenylyl cyclase Adcy10 (aka sAC), increasing cAMP and downstream cAMP-dependent pathways. BSA, on the other hand, induces sperm cholesterol release as well as other signaling pathways. How these signaling events, occurring in different sperm compartments and with different kinetics, coordinate among themselves is not well established. Regarding the AR, recent work has proposed a role for glycogen synthase kinases (GSK3α and GSK3ß). GSK3α and GSK3ß are inactivated by phosphorylation of residues Ser21 and Ser9, respectively, in their N-terminal domain. Here, we present evidence that GSK3α (but not GSK3ß) is present in the anterior head and that it is regulated during capacitation. Interestingly, BSA and HCO3 - regulate GSK3α in opposite directions. While BSA induces a fast GSK3α Ser21 phosphorylation, HCO3 - and cAMP-dependent pathways dephosphorylate this residue. We also show that the HCO3--induced Ser21 dephosphorylation is mediated by hyperpolarization of the sperm plasma membrane potential (Em) and by intracellular pH alkalinization. Previous reports indicate that GSK3 kinases mediate the progesterone-induced AR. Here, we show that GSK3 inhibition also blocks the Ca2+ ionophore ionomycin-induced AR, suggesting a role for GSK3 kinases downstream of the increase in intracellular Ca2+ needed for this exocytotic event. Altogether, our data indicate a temporal and biphasic GSK3α regulation with opposite actions of BSA and HCO3 -. Our results also suggest that this regulation is needed to orchestrate the AR during sperm capacitation.

Reorganization of the Flagellum Scaffolding Induces a Sperm Standstill During Fertilization.

Mammalian sperm delve into the female reproductive tract to fertilize the female gamete. The available information about how sperm regulate their motility during the final journey to the fertilization site is extremely limited. In this work, we investigated the structural and functional changes in the sperm flagellum after acrosomal exocytosis and during the interaction with the eggs. The evidence demonstrates that the double helix actin network surrounding the mitochondrial sheath of the midpiece undergoes structural changes prior to the motility cessation. This structural modification is accompanied by a decrease in diameter of the midpiece and is driven by intracellular calcium changes that occur concomitant with a reorganization of the actin helicoidal cortex. Although midpiece contraction may occur in a subset of cells that undergo acrosomal exocytosis, live-cell imaging during in vitro fertilization showed that the midpiece contraction is required for motility cessation after fusion is initiated. These findings provide the first evidence of the F-actin network's role in regulating sperm motility, adapting its function to meet specific cellular requirements during fertilization, and highlighting the broader significance of understanding sperm motility. Significant statement: In this work, we demonstrate that the helical structure of polymerized actin in the flagellum undergoes a rearrangement at the time of sperm-egg fusion. This process is driven by intracellular calcium and promotes a decrease in the sperm midpiece diameter as well as the arrest in motility, which is observed after the fusion process is initiated.

MEMORIA DEL ORGANISMO ANDINO DE SALUD CONVENIO HIPÓLITO UNANUE 1971­2021: ORAS-CONHU 2022 / 5 0 a ñ o s t r a b a ja n d o p o r la s a lu d, e l b ie n e s t a r y la in t e g r a c ió n a n d in a / ANNUAL REPORT OF THE ANDEAN HEALTH AGENCY HIPÓLITO UNANUE AGREEMENT 1971 ­ 2021 ORAS-CONHU; 2022

La presente publicación da cuenta de los principales hitos y logros obtenidos a través de las diferentes gestiones institucionales en los últimos cincuenta años. Estos sintetizan las apuestas y retos en la búsqueda de salud para todos, con sistemas nacionales de salud más accesibles y con el fortalecimiento de la ciudadanía en este terreno, coadyuvando a superar las brechas para alcanzar mayores niveles de equidad y bienestar para cada una de las personas. Ello permitirá enfrentar la actual pandemia con mayor eficacia, en estos tiempos, marcados por la emergencia, la experiencia y el compromiso de servicio, el ORAS-CONHU seguirá contribuyendo en responder los nuevos retos de los países andinos

Role of calcium oscillations in sperm physiology.

Intracellular Ca2+ is a key regulator of cell signaling and sperm are not the exception. Cells often use cytoplasmic Ca2+ concentration ([Ca2+]i) oscillations as a means to decodify external and internal information. [Ca2+]i oscillations faster than those usually found in other cells and correlated with flagellar beat were the first to be described in sperm in 1993 by Susan Suarez, in the boar. More than 20 years passed before similar [Ca2+]i oscillations were documented in human sperm, simultaneously examining their flagellar beat in three dimensions by Corkidi et al. 2017. On the other hand, 10 years after the discovery of the fast boar [Ca2+]i oscillations, slower ones triggered by compounds from the egg external envelope were found to regulate cell motility and chemotaxis in sperm from marine organisms. Today it is known that sperm display fast and slow spontaneous and agonist triggered [Ca2+]i oscillations. In mammalian sperm these Ca2+ transients may act like a multifaceted tool that regulates fundamental functions such as motility and acrosome reaction. This review covers the main sperm species and experimental conditions where [Ca2+]i oscillations have been described and discusses what is known about the transporters involved, their regulation and the physiological purpose of these oscillations. There is a lot to be learned regarding the origin, regulation and physiological relevance of these Ca2+ oscillations.

"Dating is pure suffering": violence within affective-sexual relationships between adolescents in a school in the Costa Verde, Rio de Janeiro, Brazil. / "Namorar é só sofrência": violências na relação afetivo-sexual de adolescentes de uma escola na região Costa Verde, Rio de Janeiro, Brasil.

This work is the result of a master's thesis that aimed to understand students' perceptions of violence within affective-sexual relationships between adolescents in a public school in the Costa Verde, Rio de Janeiro. The study corpus was derived from participant observation in the school and in-depth interviews with three girls and three boys aged between 18 and 24 years. The core areas of analysis were affective-sexual trajectories, experiences involving violence within relationships, and agency in the face of conflict. The findings reveal that violence is part of the everyday lives of adolescents and reinforce the victim/aggressor dichotomy. The adolescents' interpretations of violence were divided into two categories: "suffering" and "serious acts of violence". These understandings influence the recognition of violence and agency. The reproduction of gender norms contributes to sustaining gender hierarchy and inequalities, which affect girls and boys differently. Silence on this issue contributes to the invisibility of violence within relationships and the consequent failure to seek support from relevant organizations and services. Further research is needed to gain a deeper understanding of violence within affective-sexual relationships between adolescents.

O presente trabalho é resultado de uma pesquisa de mestrado que objetivou compreender como as violências nas relações afetivo-sexuais na adolescência são significadas por estudantes de uma escola estadual da região Costa Verde do Rio de Janeiro. O corpus da pesquisa deriva da observação participante no espaço escolar e de entrevistas em profundidade com 3 moças e 3 rapazes entre 18 e 24 anos. Os eixos de análise foram: as trajetórias afetivo-sexuais, as experiências que envolvem algum tipo de ação violenta no relacionamento e as agências diante dos conflitos. Os resultados revelam que as violências fazem parte do cotidiano e reforçam a dicotomia vítima e agressor. As interpretações da violência são divididas em dois sistemas, a "sofrência" e "ações violentas graves", essas compreensões interferem no reconhecimento da violência e em suas agências. A reprodução de padrões sociais de gênero contribui para a manutenção de hierarquias e desigualdades que atingem a moças e rapazes de diferentes formas. O silenciamento a respeito do tema contribui para a invisibilidade da violência no relacionamento e consequentemente a não procura de cuidado junto aos serviços de saúde. É posto como desafio a expansão de estudos que possibilitem compreender melhor a violência nas relações afetivo-sexuais de adolescentes.

"Namorar é só sofrência": violências na relação afetivo-sexual de adolescentes de uma escola na região Costa Verde, Rio de Janeiro, Brasil / "Dating is pure suffering": violence within affective-sexual relationships between adolescents in a school in the Costa Verde, Rio de Janeiro, Brazil

Resumo O presente trabalho é resultado de uma pesquisa de mestrado que objetivou compreender como as violências nas relações afetivo-sexuais na adolescência são significadas por estudantes de uma escola estadual da região Costa Verde do Rio de Janeiro. O corpus da pesquisa deriva da observação participante no espaço escolar e de entrevistas em profundidade com 3 moças e 3 rapazes entre 18 e 24 anos. Os eixos de análise foram: as trajetórias afetivo-sexuais, as experiências que envolvem algum tipo de ação violenta no relacionamento e as agências diante dos conflitos. Os resultados revelam que as violências fazem parte do cotidiano e reforçam a dicotomia vítima e agressor. As interpretações da violência são divididas em dois sistemas, a "sofrência" e "ações violentas graves", essas compreensões interferem no reconhecimento da violência e em suas agências. A reprodução de padrões sociais de gênero contribui para a manutenção de hierarquias e desigualdades que atingem a moças e rapazes de diferentes formas. O silenciamento a respeito do tema contribui para a invisibilidade da violência no relacionamento e consequentemente a não procura de cuidado junto aos serviços de saúde. É posto como desafio a expansão de estudos que possibilitem compreender melhor a violência nas relações afetivo-sexuais de adolescentes.

Abstract This work is the result of a master's thesis that aimed to understand students' perceptions of violence within affective-sexual relationships between adolescents in a public school in the Costa Verde, Rio de Janeiro. The study corpus was derived from participant observation in the school and in-depth interviews with three girls and three boys aged between 18 and 24 years. The core areas of analysis were affective-sexual trajectories, experiences involving violence within relationships, and agency in the face of conflict. The findings reveal that violence is part of the everyday lives of adolescents and reinforce the victim/aggressor dichotomy. The adolescents' interpretations of violence were divided into two categories: "suffering" and "serious acts of violence". These understandings influence the recognition of violence and agency. The reproduction of gender norms contributes to sustaining gender hierarchy and inequalities, which affect girls and boys differently. Silence on this issue contributes to the invisibility of violence within relationships and the consequent failure to seek support from relevant organizations and services. Further research is needed to gain a deeper understanding of violence within affective-sexual relationships between adolescents.

Membrane hyperpolarization abolishes calcium oscillations that prevent induced acrosomal exocytosis in human sperm.

Sperm capacitation is essential to gain fertilizing capacity. During this process, a series of biochemical and physiological modifications occur that allow sperm to undergo acrosomal exocytosis (AE). At the molecular level, hyperpolarization of the sperm membrane potential (Em) takes place during capacitation. This study shows that human sperm incubated under conditions that do not support capacitation (NC) can become ready for an agonist stimulated AE by pharmacologically inducing Em hyperpolarization with Valinomycin or Amiloride. To investigate how Em hyperpolarization promotes human sperm's ability to undergo AE, live single-cell imaging experiments were performed to simultaneously monitor changes in [Ca2+ ]i and the occurrence of AE. Em hyperpolarization turned [Ca2+ ]i dynamics in NC sperm from spontaneously oscillating into a sustained slow [Ca2+ ]i increase. The addition of progesterone (P4) or K+ to Valinomycin-treated sperm promoted that a significant number of cells displayed a transitory rise in [Ca2+ ]i which then underwent AE. Altogether, our results demonstrate that Em hyperpolarization is necessary and sufficient to prepare human sperm for the AE. Furthermore, this Em change decreased Ca2+ oscillations that block the occurrence of AE, providing strong experimental evidence of the molecular mechanism that drives the acquisition of acrosomal responsiveness.

Impact of the COVID-19 Lockdown on Air Quality and Resulting Public Health Benefits in the Mexico City Metropolitan Area.

Meteorology and long-term trends in air pollutant concentrations may obscure the results from short-term policies implemented to improve air quality. This study presents changes in CO, NO2, O3, SO2, PM10, and PM2.5 based on their anomalies during the COVID-19 partial (Phase 2) and total (Phase 3) lockdowns in Mexico City (MCMA). To minimise the impact of the air pollutant long-term trends, pollutant anomalies were calculated using as baseline truncated Fourier series, fitted with data from 2016 to 2019, and then compared with those from the lockdown. Additionally, days with stagnant conditions and heavy rain were excluded to reduce the impact of extreme weather changes. Satellite observations for NO2 and CO were used to contrast the ground-based derived results. During the lockdown Phase 2, only NO2 exhibited significant decreases (p < 0.05) of between 10 and 23% due to reductions in motor vehicle emissions. By contrast, O3 increased (p < 0.05) between 16 and 40% at the same sites where NO2 decreased. During Phase 3, significant decreases (p < 0.05) were observed for NO2 (43%), PM10 (20%), and PM2.5 (32%) in response to the total lockdown. Although O3 concentrations were lower in Phase 3 than during Phase 2, those did not decrease (p < 0.05) from the baseline at any site despite the total lockdown. SO2 decreased only during Phase 3 in a near-road environment. Satellite observations confirmed that NO2 decreased and CO stabilised during the total lockdown. Air pollutant changes during the lockdown could be overestimated between 2 and 10-fold without accounting for the influences of meteorology and long-term trends in pollutant concentrations. Air quality improved significantly during the lockdown driven by reduced NO2 and PM2.5 emissions despite increases in O3, resulting in health benefits for the MCMA population. A health assessment conducted suggested that around 588 deaths related to air pollution exposure were averted during the lockdown. Our results show that to reduce O3 within the MCMA, policies must focus on reducing VOCs emissions from non-mobile sources. The measures implemented during the COVID-19 lockdowns provide valuable information to reduce air pollution through a range of abatement strategies for emissions other than from motor vehicles.

RNAi Modulation of Chlorogenic Acid and Lignin Deposition in Nicotiana tabacum and Insufficient Compensatory Metabolic Cross-Talk.

Chlorogenic acid (CGA) and guaiacyl/syringyl (G/S) lignin formation involves hydroxycinnamoyl ester intermediacy, the latter formed via hydroxycinnamoyl CoA:shikimate hydroxycinnamoyl transferase (HCT) and hydroxycinnamoyl CoA:quinate hydroxycinnamoyl transferase (HQT) activities. HQT and HCT RNAi silencing of a commercial tobacco (Nicotiana tabacum) K326 line was examined herein. NtHQT gene silencing gave relatively normal plant phenotypes, with CGA levels reduced (down to 1% of wild type) with no effects on lignin. RNAi NtHCT silencing had markedly adverse phenotypes (e.g., stunted, multiple stems, delayed flowering, with senescence delayed by several months). Lignin contents were partially lowered, with a small increase in cleavable p-hydroxyphenyl (H) monomers; those plants had no detectable CGA level differences relative to wild type. In vitro NtHCT kinetic parameters revealed preferential p-coumaroyl CoA and shikimate esterification, as compared to other structurally related potential acyl group donors and acceptors. In the presence of coenzyme A, NtHCT catalyzed the reverse reaction. Site-directed mutagenesis of NtHCT (His153Ala) abolished enzymatic activity. NtHQT, by comparison, catalyzed preferential conversion of p-coumaroyl CoA and quinic acid to form p-coumaroyl quinate, the presumed CGA precursor. In sum, metabolic pathways to CGA and lignins appear to be fully independent, and previous conflicting reports of substrate versatilities and metabolic cross-talk are resolved.

Starvation induces an increase in intracellular calcium and potentiates the progesterone-induced mouse sperm acrosome reaction.

We have recently reported two different methodologies that improve sperm functionality. The first method involved transient exposure to the Ca2+ ionophore A23187 , and the second required sperm incubation in the absence of energy nutrients (starvation). Both methods were associated with an initial loss of motility followed by a rescue step involving ionophore removal or addition of energy metabolites, respectively. In this work, we show that starvation is accompanied by an increase in intracellular Ca2+ ([Ca2+ ]i ). Additionally, the starved cells acquire a significantly enhanced capacity to undergo a progesterone-induced acrosome reaction. Electrophysiological measurements show that CatSper channel remains active in starvation conditions. However, the increase in [Ca2+ ]i was also observed in sperm from CatSper null mice. Upon starvation, addition of energy nutrients reversed the effects on [Ca2+ ]i and decreased the effect of progesterone on the acrosome reaction to control levels. These data indicate that both methods have common molecular features.

Seeing is believing: Current methods to observe sperm acrosomal exocytosis in real time.

Acrosomal exocytosis (AR) is a critical process that sperm need to undergo to fertilize an egg. The evaluation of the presence or absence of the acrosome is usually performed by using lectins or dyes in fixed cells. With this approach, it is neither possible to monitor the dynamic process of exocytosis and related molecular events while discriminating between live and dead cells, nor to evaluate the acrosomal status while sperm reside in the female reproductive tract. However, over the last two decades, several new methodologies have been used to assess the occurrence of AR in living cells allowing different groups to obtain information that was not possible in the past. These techniques have revolutionized the whole study of this process. This review summarizes current methods available to analyze AR in living cells as well as the important information that emerged from studies using these approaches.

Lifestyle Practices, Satisfaction with Life and the Level of Perceived Stress of Polish and Foreign Medical Students Studying in Poland.

The adaptation of foreign students to a new country can be complicated due to different cultural values, language barriers and the way university courses are structured. The aim of the study was to analyze the lifestyle practices, satisfaction with life and the level of perceived stress of Polish and foreign students studying various medical disciplines in Poland with regard to chosen sociodemographic characteristics. The study included 231 foreign and 213 Polish students (n = 444) taking different medical disciplines at the medical university in eastern Poland. Three research tools were used: Fantastic Lifestyle Questionnaire (FLQ), Satisfaction with Life Scale (SWLS), Perceived Stress Scale (PSS-10). Additionally, students' sociodemographic data was collected. Two-factor analysis of variance (ANOVA) was performed and correlations between variables were also examined. Our research indicated that Polish students obtained higher results in FLQ than foreign students. It also demonstrated a significantly higher level of stress among Polish students in comparison to foreign students. The self-assessment of their health condition, lifestyle, and rank associated to being healthy correlated with FLQ, SWLS and PSS-10. The present research can aid the development of support programs for foreign students so that the cultural adaptation processes would more positively influence their lifestyle and an education environment.

Super-resolution imaging of live sperm reveals dynamic changes of the actin cytoskeleton during acrosomal exocytosis.

Filamentous actin (F-actin) is a key factor in exocytosis in many cell types. In mammalian sperm, acrosomal exocytosis (denoted the acrosome reaction or AR), a special type of controlled secretion, is regulated by multiple signaling pathways and the actin cytoskeleton. However, the dynamic changes of the actin cytoskeleton in live sperm are largely not understood. Here, we used the powerful properties of SiR-actin to examine actin dynamics in live mouse sperm at the onset of the AR. By using a combination of super-resolution microscopy techniques to image sperm loaded with SiR-actin or sperm from transgenic mice containing Lifeact-EGFP, six regions containing F-actin within the sperm head were revealed. The proportion of sperm possessing these structures changed upon capacitation. By performing live-cell imaging experiments, we report that dynamic changes of F-actin during the AR occur in specific regions of the sperm head. While certain F-actin regions undergo depolymerization prior to the initiation of the AR, others remain unaltered or are lost after exocytosis occurs. Our work emphasizes the utility of live-cell nanoscopy, which will undoubtedly impact the search for mechanisms that underlie basic sperm functions.This article has an associated First Person interview with the first author of the paper.

Las neurociencias como herramienta de comunicación y desarrollo de los procesos de globalización / The neurosciences as a communication and development tool of the globalization processes

Este artículo pretende elucidar las funciones que han cumplido las neurociencias como herramienta de comunicación en los procesos de diseminación de la aldea global. La globalización ha facilitado la masificación del uso de las nuevas Tecnologías de la Información y la Comunicación (TIC), del comercio y de la interconexión humana por medio de redes sociales. En éste proceso, el papel de las neurociencias ha sido decisivo, puesto que han permitido a las multinacionales y gobiernos de países desarrollados, contar con evidencias clínicas, experimentales y multicéntricas sobre la forma en que el cerebro selecciona un objeto por sobre los demás, siendo determinante en todos los movimientos financieros y bursátiles de la economía mundial. Los resultados indican que las neurociencias han llegado a todos los niveles de la sociedad a escala global; permitiendo que sus avances y desarrollos modifiquen la forma en que las multinacionales y los estados ofrecen sus productos y servicios a la humanidad de forma atractiva, eficaz y sugestiva.

This paper aims to elucidate the functions that neurosciences have fulfilled as a communication tool in the dissemination processes of the global village. Globalization has facilitated the massification of the use of new Information and Communication Technologies (ICT), commerce and human interconnection through social networks. In this process, the role of neuroscience has been decisive, since it has allowed multinational and developed country governments to have clinical, experimental and multicentric evidence on how the brain selects one object over others, being determinant in all financial and stock market movements of the world economy. The results indicate that neurosciences have reached all levels of society on a global scale; allowing their advances and developments to modify the way in which multinationals and states offer their products and services to humanity in an attractive, effective and suggestive way.

Role of Ion Channels in the Sperm Acrosome Reaction.

The acrosome reaction (AR) is a unique exocytotic process where the acrosome, a single membrane-delimited specialized organelle, overlying the nucleus in the sperm head of many species, fuses with the overlying plasma membrane. This reaction, triggered by physiological inducers from the female gamete, its vicinity, or other stimuli, discharges the acrosomal content modifying the plasma membrane, incorporating the inner acrosomal membrane, and exposing it to the extracellular medium. The AR is essential for sperm-egg coat penetration, fusion with the eggs' plasma membrane, and fertilization. As in most exocytotic processes Ca(2+) is crucial for the AR, as well as intracellular pH and membrane potential changes. Thus, among the required processes needed for this reaction, ion permeability changes involving channels are pivotal. In spite of the key role ion channels play in the AR, their identity and regulation is not fully understood. Though molecular and pharmacological evidence indicates that various ionic channels participate during the AR, such as store-operated Ca(2+) channels and voltage-dependent Ca(2+) channels, whole cell patch clamp recordings have failed to detect some of them until now. Since sperm display a very high resistance and a minute cytoplasmic volume, very few channels are needed to achieve large membrane potential and concentration changes. Functional detection of few channels in the morphologically complex and tiny sperm poses technical problems, especially when their conductance is very small, as in the case of SOCs. Single channel recordings and novel fluorescence microscopy strategies will help to define the participation of ionic channels in the intertwined signaling network that orchestrates the AR.

The tyrosine kinase FER is responsible for the capacitation-associated increase in tyrosine phosphorylation in murine sperm.

Sperm capacitation is required for fertilization. At the molecular level, this process is associated with fast activation of protein kinase A. Downstream of this event, capacitating conditions lead to an increase in tyrosine phosphorylation. The identity of the tyrosine kinase(s) mediating this process has not been conclusively demonstrated. Recent experiments using stallion and human sperm have suggested a role for PYK2 based on the use of small molecule inhibitors directed against this kinase. However, crucially, loss-of-function experiments have not been reported. Here, we used both pharmacological inhibitors and genetically modified mice models to investigate the identity of the tyrosine kinase(s) mediating the increase in tyrosine phosphorylation in mouse sperm. Similar to stallion and human, PF431396 blocks the capacitation-associated increase in tyrosine phosphorylation. Yet, sperm from Pyk2(-/-) mice displayed a normal increase in tyrosine phosphorylation, implying that PYK2 is not responsible for this phosphorylation process. Here, we show that PF431396 can also inhibit FER, a tyrosine kinase known to be present in sperm. Sperm from mice targeted with a kinase-inactivating mutation in Fer failed to undergo capacitation-associated increases in tyrosine phosphorylation. Although these mice are fertile, their sperm displayed a reduced ability to fertilize metaphase II-arrested eggs in vitro.

Grado de control metabólico en niños y adolescentes con diabetes mellitus tipo 1 / Metabolic control in children and adolescents with type 1 diabetes

Introducción: La diabetes mellitus tipo 1 (DM1) es una importante enfermedad en la población infanto-juvenil, que asociada a otros factores de riesgo cardiovascular, origina morbimortalidad a más temprana edad. Objetivo: Conocer el grado de control metabólico y determinar la prevalencia de factores de riesgo cardiovascular en pacientes con DM1. Pacientes y método: Estudio retrospectivo realizado entre abril y junio de 2011, en el cual se estudiaron menores de 19 años con DM1, controlados en el Hospital San Juan de Dios, en Santiago de Chile. Resultados: Se evaluaron 94 pacientes (edad promedio al diagnóstico: 7,3 años y edad actual: 11,9 años; tiempo de evolución: 4,5 años). El 79,8% presentó niveles de hemoglobina glucosilada (HbA1c) superiores a lo recomendado, con un promedio de 8,9%. El grupo entre 13 y 19 años fue el de peor control metabólico (86% con niveles de HbA1c anormal). El 26,6% presentó sobrepeso u obesidad. En el 20,3% se constató dislipidemia (colesterol LDL > 100 mg/dl) y en el 4,2% hipertensión arterial. Conclusiones: Solo el 20% de los pacientes presentan un control metabólico adecuado medido por HbA1c, aunque un perfil de riesgo cardiovascular aceptable. Es necesario incrementar los esfuerzos terapéuticos, especialmente en los adolescentes, enfatizando la importancia de un adecuado control nutricional como principal método de tratamiento de esta entidad.

Introduction: Type 1 diabetes mellitus (T1D) is an important disease in children and adolescent being a major risk factor for early morbidity and mortality. Objective: To know the degree of metabolic control and prevalence of cardiovascular risk factors in T1D patients. Patients and method: Retrospective study including patients under 19 years of age with T1D controlled at a Chilean hospital in 2011. Results: 94 patients were evaluated (average age at diagnosis: 7,3 years; current age: 11,9 years; evolution time: 4,5 years). Seventy-nine percent (79,8%) of patients presented glycated hemoglobin (HbA1c) over the recommended level with an average of 8,9%. The group between 13 and 19 years of age exhibited the worst metabolic control (86% with HbA1c abnormal levels). Overweight or obesity occurred in 26,6% of patients, 20,3% had LDL >100 mg/dl and 4,2% had hypertension. Conclusions: Only about twenty percent of patients had adequate metabolic control as measured by HbA1c, although cardiovascular risk profile was acceptable. Therapeutic and educational efforts must be reinforced mainly in adolescents, emphasizing the importance of adequate nutritional management as a primary method to treat this entity.

A Specific Transitory Increase in Intracellular Calcium Induced by Progesterone Promotes Acrosomal Exocytosis in Mouse Sperm.

During capacitation, sperm acquire the ability to undergo the acrosome reaction (AR), an essential step in fertilization. Progesterone produced by cumulus cells has been associated with various physiological processes in sperm, including stimulation of AR. An increase in intracellular Ca(2+) ([Ca(2+)]i) is necessary for AR to occur. In this study, we investigated the spatiotemporal correlation between the changes in [Ca(2+)]i and AR in single mouse spermatozoa in response to progesterone. We found that progesterone stimulates an [Ca(2+)]i increase in five different patterns: gradual increase, oscillatory, late transitory, immediate transitory, and sustained. We also observed that the [Ca(2+)]i increase promoted by progesterone starts at either the flagellum or the head. We validated the use of FM4-64 as an indicator for the occurrence of the AR by simultaneously detecting its fluorescence increase and the loss of EGFP in transgenic EGFPAcr sperm. For the first time, we have simultaneously visualized the rise in [Ca(2+)]i and the process of exocytosis in response to progesterone and found that only a specific transitory increase in [Ca(2+)]i originating in the sperm head promotes the initiation of AR.