Direct activation of the proton channel by albumin leads to human sperm capacitation and sustained release of inflammatory mediators by neutrophils

Human voltage-gated proton channels (hHv1) extrude protons from cells to compensate for charge and osmotic imbalances due metabolism, normalizing intracellular pH and regulating protein function. Human albumin (Alb), present at various levels throughout the body, regulates oncotic pressure and transports ligands. Here, we report Alb is required to activate hHv1 in sperm and neutrophils. Dose-response studies reveal the concentration of Alb in semen is too low to activate hHv1 in sperm whereas the higher level in uterine fluid yields proton efflux, allowing capacitation, the acrosomal reaction, and oocyte fertilization. Likewise, Alb activation of hHv1 in neutrophils is required to sustain production and release of reactive oxygen species during the immune respiratory burst. One Alb binds to both voltage sensor domains (VSDs) in hHv1, enhancing open probability and increasing proton current. A computational model of the Alb-hHv1 complex, validated by experiments, identifies two sites in Alb domain II that interact with the VSDs, suggesting an electrostatic gating modification mechanism favoring the active “up” sensor conformation. This report shows how sperm are triggered to fertilize, resolving how hHv1 opens at negative membrane potentials in sperm, and describes a role for Alb in physiology that will operate in the many tissues expressing hHv1.Fil: Zhao, Ruiming. University of California at Irvine; Estados UnidosFil: Dai, Hui. University of California at Irvine; Estados UnidosFil: Arias, Rodolfo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: de Blas, Gerardo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Orta, Gerardo. Universidad Nacional Autónoma de México; MéxicoFil: Pavarotti, Martin Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Shen, Rong. University of Chicago; Estados UnidosFil: Perozo, Eduardo. University of Chicago; Estados UnidosFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Goldstein, Steve A. N.. University of California at Irvine; Estados Unido

Tratamientos pulpares en dentición temporal

Estos protocolos se basan en una revisión de la literatura, siguiendo la directrices de los Protocolos (Guidelines) de la Academia Americana de Odontopediatría, además de la supervisión por profesionales expertos en la materia. La intención es mejorar la práctica clínica de la Odontopediatría y animar la investigación en áreas donde las evidencias científicas no son claras, como es el caso de los procedimientos en los tratamientos pulpares y los fármacos utilizados

Cdc42 localized in the CatSper signaling complex regulates cAMP‐dependent pathways in mouse sperm

Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca2+ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1-null sperm. Cdc42 inhibition impaired CatSper activity and other Ca2+-dependent downstream events resulting in a severe compromise of the sperm fertilizing potential. We also demonstrate that Cdc42 is essential for CatSper function by modulating cAMP production by soluble adenylate cyclase (sAC), providing a new regulatory mechanism for the stimulation of CatSper by the cAMP-dependent pathway. These results reveal a broad mechanistic insight into the regulation of Ca2+ in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.Fil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Xu, Xinran. State University of Colorado - Fort Collins; Estados UnidosFil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. State University of Colorado - Fort Collins; Estados UnidosFil: Gervasi, María G.. University of Massachussets; Estados UnidosFil: Orta, Gerardo. Universidad Autonoma de México. Instituto de Biotecnología; MéxicoFil: De la Vega Beltrán, José L.. Universidad Autonoma de México. Instituto de Biotecnología; MéxicoFil: Stival, Cintia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Gilio, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Visconti, Pablo E.. University of Massachussets; Estados UnidosFil: Krapf, Diego. State University of Colorado - Fort Collins; Estados UnidosFil: Darszon, Alberto. Universidad Autonoma de México. Instituto de Biotecnología; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Output Feedback Finite-Time Stabilization of Systems Subject to Hölder Disturbances via Continuous Fractional Sliding Modes

The problem of designing a continuous control to guarantee finite-time tracking based on output feedback for a system subject to a Hölder disturbance has remained elusive. The main difficulty stems from the fact that such disturbance stands for a function that is continuous but not necessarily differentiable in any integer-order sense, yet it is fractional-order differentiable. This problem imposes a formidable challenge of practical interest in engineering because (i) it is common that only partial access to the state is available and, then, output feedback is needed; (ii) such disturbances are present in more realistic applications, suggesting a fractional-order controller; and (iii) continuous robust control is a must in several control applications. Consequently, these stringent requirements demand a sound mathematical framework for designing a solution to this control problem. To estimate the full state in finite-time, a high-order sliding mode-based differentiator is considered. Then, a continuous fractional differintegral sliding mode is proposed to reject Hölder disturbances, as well as for uncertainties and unmodeled dynamics. Finally, a homogeneous closed-loop system is enforced by means of a continuous nominal control, assuring finite-time convergence. Numerical simulations are presented to show the reliability of the proposed method

Motilidad gastrointestinal en ratas: ¿una práctica de laboratorio adecuada para estudiantes de medicina?

In this study, the feasibility of establishing, as a regular lab practice for second year medical students taking the Human Physiology course, the recently published “hands on” activity by Souza et al. ( 2002), to assess gastrointestinal motility in awake rats, was determinate. The gastric emptying and the intestinal motility were evaluated in three different times after administering a hypertonic bolus or under hypoglycemia conditions, by the method of phenol red dye fractional recovery in the stomach and in the proximal, middle and distal portions of the small intestine of male Wistar rats. Significant differences in the gastric emptying between the hypertonic group and the control group were found only 20 min after the injection of the bolus (53.8 ± 7.4 vs 25.5 ± 3.0. p<0.05). However the hypoglycemic group did not show differences versus the control group at any time. Under experimental conditions of our work, the hypertonic bolus does delay the gastric emptying but not intestinal motility, whereas the hypoglycemia does not modify either the gastric emptying or the intestinal motility. Although illustrative and adequate to establish as a discussion activity in the group, this lab practice is technically difficult to carry out in less of 5 h.Se determinó la viabilidad de establecer, como una práctica regular de laboratorio para estudiantes del segundo año de medicina que toman el curso de Fisiología Humana, la actividad “manual” publicada recientemente por Souza et al. (2002), para analizar la motilidad gastrointestinal en ratas despiertas. Se evaluaron el vaciamiento gástrico y la motilidad intestinal a tres diferentes tiempos después de administrar un bolo hipertónico o bajo condiciones de hipoglucemia, por el método de recuperación fraccional del colorante rojo de fenol en el estómago y en las porciones proximal, media y distal del intestino de ratas Wistar macho. Se encontraron diferencias significativas en el vaciamiento gástrico entre el grupo hipertónico y el control sólo a los 20 min después de la inyección del bolo (53.8 ± 7.4 vs 25.5 ± 3.0. p<0.05). Sin embargo, el grupo de hipoglucemia no mostró diferencias con el grupo control en ningún momento. En las condiciones experimentales de nuestro trabajo, el bolo hipertónico retarda el vaciamiento gástrico pero no la motilidad intestinal, mientras que la hipoglucemia no modifica ni el vaciamiento gástrico ni la motilidad intestinal. Aunque demostrativa y adecuada para establecer la discusión con los estudiantes esta práctica de laboratorio es técnicamente difícil de efectuar en menos de 5 horas