GOLPH3 Participates in Mitochondrial Fission and Is Necessary to Sustain Bioenergetic Function in MDA-MB-231 Breast Cancer Cells.

In this study, we investigated the inter-organelle communication between the Golgi apparatus (GA) and mitochondria. Previous observations suggest that GA-derived vesicles containing phosphatidylinositol 4-phosphate (PI(4)P) play a role in mitochondrial fission, colocalizing with DRP1, a key protein in this process. However, the functions of these vesicles and potentially associated proteins remain unknown. GOLPH3, a PI(4)P-interacting GA protein, is elevated in various types of solid tumors, including breast cancer, yet its precise role is unclear. Interestingly, GOLPH3 levels influence mitochondrial mass by affecting cardiolipin synthesis, an exclusive mitochondrial lipid. However, the mechanism by which GOLPH3 influences mitochondria is not fully understood. Our live-cell imaging analysis showed GFP-GOLPH3 associating with PI(4)P vesicles colocalizing with YFP-DRP1 at mitochondrial fission sites. We tested the functional significance of these observations with GOLPH3 knockout in MDA-MB-231 cells of breast cancer, resulting in a fragmented mitochondrial network and reduced bioenergetic function, including decreased mitochondrial ATP production, mitochondrial membrane potential, and oxygen consumption. Our findings suggest a potential negative regulatory role for GOLPH3 in mitochondrial fission, impacting mitochondrial function and providing insights into GA-mitochondria communication.

Biological role of fructose in the male reproductive system: Potential implications for prostate cancer.

BACKGROUND: Over the last 20 years, fructose has gradually emerged as a potential metabolic substrate capable of promoting the growth and progression of various cancers, including prostate cancer (PCa). The biological and molecular mechanisms that underlie the effects of fructose on cancer are beginning to be elucidated. METHODS: This review summarizes the biological function of fructose as a potential carbon source for PCa cells and its role in the functionality of the male reproductive tract under normal conditions. RESULTS: The most recent biological advances related to fructose transport and metabolism as well as their implications in PCa growth and progression suggest that fructose represent a potential carbon source for PCa cells. Consequently, fructose derivatives may represent efficient radiotracers for obtaining PCa images via positron emission tomography and fructose transporters/fructose-metabolizing enzymes could be utilized as potential diagnostic and/or predictive biomarkers for PCa. CONCLUSION: The existing data suggest that restriction of fructose from the diet could be a useful therapeutic strategy for patients with PCa.

Increasing radiation doses in Anastrepha obliqua (Diptera: Tephritidae) larvae improve parasitoid mass-rearing attributes.

Doses of 40, 80, 120, and 160 Gy were applied to 5-, 6-, 7-, and 8-day-old Anastrepha obliqua larvae, which were exposed to the Neotropical-native braconids Doryctobracon crawfordi and Utetes anastrephae and the Asian braconid Diachasmimorpha longicaudata. These tests were performed to know the effect of the increase in host radiation on the emergence of the aforementioned parasitoids and the related consequences of oviposition on the host. The study was based on the fact that higher radiation doses may cause a decrease in the host immune activity. There was a direct relationship between the increase in radiation dose and the parasitoid emergence. Both, the weight and the mortality of the host larvae were not affected by radiation. Although the larval weight of the larvae was lower and the mortality was higher in the younger larvae. Both, the number of scars and immature stages per host puparium originated from the younger larvae were lower than those from older larvae. Only U. anastrephae superparasitized more at lower radiation. Superparasitism by D. longicaudata was more frequent at 160 Gy. Qualitative measurements of melanin in the larvae parasitized showed that the levels were lower with increasing radiation. As radiation doses increased, the antagonistic response of the A. obliqua larva was reduced. Host larvae aged 5- and 6-day-old irradiated at 120-160 Gy significantly improve parasitoid emergence. This evidence is relevant for the mass production of the three tested parasitoid species.

Rehabilitación física en pacientes con obesidad post COVID19: Una revisión narrativa

El COVID19 ha afectado a millones de personas a nivel mundial. Entre los pacientes contagiados que se agravan y requieren de cuidados intensivos avanzados; además de largas estadías de hospitalización, se encuentran quienes tienen obesidad. Debido a la gran prevalencia de personas con obesidad, tanto en países desarrollados como en en vías de desarrollo, y a las distintas secuelas que experimentan debido al efecto directo del virus como al tratamiento que reciben, es necesario comprender la fisiopatología asociada a la severidad del contagio. Otro aspecto importante a considerar es ¿cómo las secuelas del tratamiento en las unidades de pacientes críticos pueden afectar el estado de salud de estas personas? El propósito de esta revisión fue indagar en la literatura sobre la rehabilitación fisica en pacientes con obesidad que han padecido COVID19 con el objetivo de tener una mirada integral que apunte a potenciar los resultados de la rehabilitación durante todo el curso de la enfermedad. Se revisaron antecedentes en bases de datos como Pubmed, la literatura y ante la escasa evidencia sobre el proceso de rehabilitación en las personas con obesidad se realizó una revisión narrativa del paciente con obesidad que enferma de COVID19 y que luego de una hospitalización prolongada debe ser reintegrado a sus actividades habituales. Se enfatiza en la fisiopatología asociada a la inmovilización prolongada de un paciente con comorbilidades previas y se proponen estrategias de rehabilitación basadas en el entrenamiento físico adaptado a su nueva condición de salud.

ABSTRACT COVID19 is a pandemic that has affected all of humanity and is still far from being eradicated, despite efforts to vaccinate the population. Among infected patients whose symptoms worsen and require advanced intensive care; in addition to long hospital stays, there are people with obesity. Due to the high prevalence of people with obesity, both in developed and developing countries, and the different sequelae they experience due to the direct effect of the virus and the treatment they receive, it is necessary to understand the pathophysiology associated with the severity of the contagion, as well as treatment sequelae among intensive care patients with the goal of having a comprehensive view that aims to enhance the results of rehabilitation throughout the course of the disease. Post-discharge sequelae depend on the severity of the disease, previous comorbidities, and length of hospitalization. This review presents a global panorama of obese patients who become ill with COVID19 and who, after a prolonged hospitalization, return to normal daily routines. Emphasis is placed on the pathophysiology associated with prolonged immobilization of a patient with previous comorbidities and on rehabilitation strategies based on physical training adapted to the new health condition.

TNF-α-activated eNOS signaling increases leukocyte adhesion through the S-nitrosylation pathway.

Nitric oxide (NO) is a key factor in inflammation. Endothelial nitric oxide synthase (eNOS), whose activity increases after stimulation with proinflammatory cytokines, produces NO in endothelium. NO activates two pathways: 1) soluble guanylate cyclase-protein kinase G and 2) S-nitrosylation (NO-induced modification of free-thiol cysteines in proteins). S-nitrosylation affects phosphorylation, localization, and protein interactions. NO is classically described as a negative regulator of leukocyte adhesion to endothelial cells. However, agonists activating NO production induce a fast leukocyte adhesion, which suggests that NO might positively regulate leukocyte adhesion. We tested the hypothesis that eNOS-induced NO promotes leukocyte adhesion through the S-nitrosylation pathway. We stimulated leukocyte adhesion to endothelium in vitro and in vivo using tumor necrosis factor-α (TNF-α) as proinflammatory agonist. ICAM-1 changes were evaluated by immunofluorescence, subcellular fractionation, immunoprecipitation, and fluorescence recovery after photobleaching (FRAP). Protein kinase Cζ (PKCζ) activity and S-nitrosylation were evaluated by Western blot analysis and biotin switch method, respectively. TNF-α, at short times of stimulation, activated the eNOS S-nitrosylation pathway and caused leukocyte adhesion to endothelial cells in vivo and in vitro. TNF-α-induced NO led to changes in ICAM-1 at the cell surface, which are characteristic of clustering. TNF-α-induced NO also produced S-nitrosylation and phosphorylation of PKCζ, association of PKCζ with ICAM-1, and ICAM-1 phosphorylation. The inhibition of PKCζ blocked leukocyte adhesion induced by TNF-α. Mass spectrometry analysis of purified PKCζ identified cysteine 503 as the only S-nitrosylated residue in the kinase domain of the protein. Our results reveal a new eNOS S-nitrosylation-dependent mechanism that induces leukocyte adhesion and suggests that S-nitrosylation of PKCζ may be an important regulatory step in early leukocyte adhesion in inflammation.NEW & NOTEWORTHY Contrary to the well-established inhibitory role of NO in leukocyte adhesion, we demonstrate a positive role of nitric oxide in this process. We demonstrate that NO induced by eNOS after TNF-α treatment induces early leukocyte adhesion activating the S-nitrosylation pathway. Our data suggest that PKCζ S-nitrosylation may be a key step in this process.

Phosphatidic acid-PKA signaling regulates p38 and ERK1/2 functions in ligand-independent EGFR endocytosis.

Ligand-independent epidermal growth factor receptor (EGFR) endocytosis is inducible by a variety of stress conditions converging upon p38 kinase. A less known pathway involves phosphatidic acid (PA) signaling toward the activation of type 4 phosphodiesterases (PDE4) that decrease cAMP levels and protein kinase A (PKA) activity. This PA/PDE4/PKA pathway is triggered with propranolol used to inhibit PA hydrolysis and induces clathrin-dependent and clathrin-independent endocytosis, followed by reversible accumulation of EGFR in recycling endosomes. Here we give further evidence of this signaling pathway using biosensors of PA, cAMP, and PKA in live cells and then show that it activates p38 and ERK1/2 downstream the PKA inhibition. Clathrin-silencing and IN/SUR experiments involved the activity of p38 in the clathrin-dependent route, while ERK1/2 mediates clathrin-independent EGFR endocytosis. The PA/PDE4/PKA pathway selectively increases the EGFR endocytic rate without affecting LDLR and TfR constitute endocytosis. This selectiveness is probably because of EGFR phosphorylation, as detected in Th1046/1047 and Ser669 residues. The EGFR accumulates at perinuclear recycling endosomes colocalizing with TfR, fluorescent transferrin, and Rab11, while a small proportion distributes to Alix-endosomes. A non-selective recycling arrest includes LDLR and TfR in a reversible manner. The PA/PDE4/PKA pathway involving both p38 and ERK1/2 expands the possibilities of EGFR transmodulation and interference in cancer.

D-Propranolol Impairs EGFR Trafficking and Destabilizes Mutant p53 Counteracting AKT Signaling and Tumor Malignancy.

Cancer therapy may be improved by the simultaneous interference of two or more oncogenic pathways contributing to tumor progression and aggressiveness, such as EGFR and p53. Tumor cells expressing gain-of-function (GOF) mutants of p53 (mutp53) are usually resistant to EGFR inhibitors and display invasive migration and AKT-mediated survival associated with enhanced EGFR recycling. D-Propranolol (D-Prop), the non-beta blocker enantiomer of propranolol, was previously shown to induce EGFR internalization through a PKA inhibitory pathway that blocks the recycling of the receptor. Here, we first show that D-Prop decreases the levels of EGFR at the surface of GOF mutp53 cells, relocating the receptor towards recycling endosomes, both in the absence of ligand and during stimulation with high concentrations of EGF or TGF-α. D-Prop also inactivates AKT signaling and reduces the invasive migration and viability of these mutp53 cells. Unexpectedly, mutp53 protein, which is stabilized by interaction with the chaperone HSP90 and mediates cell oncogenic addiction, becomes destabilized after D-Prop treatment. HSP90 phosphorylation by PKA and its interaction with mutp53 are decreased by D-Prop, releasing mutp53 towards proteasomal degradation. Furthermore, a single daily dose of D-Prop reproduces most of these effects in xenografts of aggressive gallbladder cancerous G-415 cells expressing GOF R282W mutp53, resulting in reduced tumor growth and extended mice survival. D-Prop then emerges as an old drug endowed with a novel therapeutic potential against EGFR- and mutp53-driven tumor traits that are common to a large variety of cancers.

Impacto del SARS-CoV2 en un Centro de desvinculación de la ventilación mecánica y rehabilitación / Impact of SARS-CoV2 on a Center for Mechanical Ventilation Weaning and Rehabilitation

Introducción: Desde diciembre de 2019, el virus SARS-CoV2 se ha propagado por todo el mundo a gran velocidad. Múltiples estudios describen su comportamiento en unidades de terapia intensiva, pero hay poca información sobre su impacto en centro de rehabilitación y cuidados críticos crónicos (CRCCC). Objetivo: Demostrar si la implementación de un protocolo de acción de contingencia podría disminuir la diseminación del virus entre los pacientes internados en un CRCCC. Materiales y Métodos: Estudio observacional, retrospectivo, transversal. Se incluyeron pacientes mayores de 18 años bajo aislamiento respiratorio, ya sea por caso sospechoso de SARS-CoV2, contacto estrecho con caso confirmado o ingreso a la institución, durante mayo de 2020. Los valores se expresaron como mediana y rango intercuantilo o frecuencia y porcentaje, según la variable. Las diferencias entre SARS-CoV2 positivos y negativos se evaluaron con test de la mediana y test exacto de Fisher. Resultados: Durante el periodo de estudio, se colocaron en aislamiento respiratorio 30 pacientes (53% por caso sospechoso, 13% por contacto estrecho y 34% por ingreso). De ellos, 5 fueron positivos para SARS-CoV2, con una mediana de 61 años (18-71), mayoría de sexo masculino (4/5), 80% traqueostomizados y 33% con asistencia ventilatoria mecánica invasiva. Un paciente murió por complicaciones relacionadas al SARS-CoV2. No se hallaron diferencias significativas en cantidad de casos positivos según la causa de aislamiento (p = 0.37) ni en las características clínico-demográficas entre positivos y negativos. Conclusión: La implementación de un protocolo de contingencia para pacientes potencialmente infectados con SARS-CoV2 en una CRCCC podría disminuir su diseminación dentro de la institución.

Impact of SARS-CoV2 on a Center for Mechanical Ventilation Weaning and Rehabilitation / Impacto del SARS-CoV2 en un Centro de desvinculación de la ventilación mecánica y rehabilitación

Introduction: Since December 2019, the SARS-CoV2 virus has propagated throughout the world at great speed. Multiple studies describe its behavior in Intensive Care Units, but there is little information about its impact on a Critical Care Recovery Center (CCRC). Objective: To show if the use of a contingency protocol could reduce virus dissemination among patients hospitalized in a CCRC. Materials and Methods: Observational, retrospective, cross-sectional study. The study included patients older than 18 years on respiratory isolation for being a suspected case of SARS-CoV2, or close contact of a confirmed case or for their admission to theinstitution, during May 2020.The values were expressed as median and interquartile range or frequency and percentage, according to the variable. The differences between positive and negative SARS-CoV2 cases were evaluated with the median test and the Fisher' s Exact Test. Results: During the study period, 30 patients were placed in respiratory isolation (53% suspected cases, 13% close contact and 34% admission to the institution). 5 of them tested positive for SARS-CoV2, with a median of 61 years (18-71), mostly males (4/5), 80% tracheostomized and 33% with invasive mechanical ventilatory assistance. One patient died from complications associated withSARS-CoV2. No significant differences were found in the number of positive cases according to the isolation cause (p = 0.37) or the clinicaldemographic characteristics between positive and negative cases. Conclusion: The use of a contingency protocol for patients potentially infected with SARS-CoV2 in a CCRC could reduce the virus dissemination inside the institution.

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation.

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.

Análisis de una cohorte de pacientes decanulados en un centro de cuidados críticos crónicos de Argentina / Analysis of a Cohort of Decannulated Patients in a Critical Care Center for Chronically Ill Patients in Argentina

Objetivos: Describir las características de una cohorte de pacientes decanulados que ingresan a un Centro de Neurorehabilitación y Cuidados Critico Crónicos y su condición al egreso. Como objetivo secundario analizar la existencia de posibles factores de riesgo asociados con su derivación a un centro de mayor complejidad. Materiales y Métodos: Estudio descriptivo, transversal, retrospectivo, en la Clínica de Neurorehabilitación Santa Catalina, Ciudad Autónoma de Buenos Aires, Argentina. Resultados: Se decanularon 87 pacientes. 29 ingresaron con AVMi y pudieron ser desvinculados en su totalidad. La mediana de días de TQT fue de 35 días (RIQ 22-68). De los pacientes decanulados, el 21% continuaba internado en la institución al cierre del estudio. El 53% egresó vivo a su domicilio, mientras que el 23% debió ser derivado a un centro de mayor complejidad. Dos pacientes decanulados fallecieron durante su internación. Se hallaron como variables independientemente asociadas a egresar hacia un centro de mayor complejidad la presencia de antecedentes neurológicos previos a la internación en UTI (OR = 4.22, IC 95% (1.03-10.5), p=0.02) y la internación en UTI por causa respiratoria (OR = 4.44, IC 95% (1.22-16.1), p = 0.02). Conclusión: La mayoría de los pacientes decanulados lograron egresar vivos a su domicilio. Presentar antecedentes neurológicos y patología respiratoria como motivo de ingreso a UTI podrían ser factores de riesgo para ser derivados a un centro de mayor complejidad.

Analysis of a Cohort of Decannulated Patients in a Critical Care Center for Chronically Ill Patients in Argentina

Objectives: To describe the characteristics of a cohort of decannulated patients admitted to a Neuro-rehabilitation and Critical Care Center and their condition upon discharge. The secondary objective was to analyze the existence of possible risk factors associated with referral of patients to a high complexity center. Materials and Method: Descriptive, cross-sectional, retrospective study in the Clínica de Neurorehabilitación Santa Catalina, Autonomous City of Buenos Aires, Argentina. Results: 87 patients were decannulated. 29 patients were admitted with IMVA and could be completely weaned. The median of TQT days was 35 days (IQR 22-68). 21% of decannulated patients were still hospitalized at the institution upon the end of the study. 53% were discharged home alive, whereas 23% had to be referred to a high complexity center. Two decannulated patients died while they were hospitalized. Some variables independently associated with referral to a high complexity center were found, the presence of a neurological history before ICU admission (OR [odds ratio] = 4.22, 95% CI [confidence interval] (1.03-10.5), p = 0.02) and ICU admission for respiratory causes (OR = 4.44, 95% CI (1.22-16.1), p = 0.02). Conclusion: Most decannulated patients were discharged home alive. Neurological history and respiratory disease as reasons for ICU admission could be risk factors to be referred to a high complexity center.

Radiation on Medfly Larvae of tsl Vienna-8 Genetic Sexing Strain Displays Reduced Parasitoid Encapsulation in Mass-Reared Diachasmimorpha longicaudata (Hymenoptera: Braconidae).

Improvements in the mass rearing of Diachasmimorpha longicaudata (Ashmead) on larvae of the Vienna-8 temperature-sensitive lethal genetic sexing strain of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) (= GSS Vienna-8) at the San Juan biofactory, Argentina, are currently under way. Lowering cost production is a key factor regarding parasitoid rearing. Thus, the variation in mass-reared parasitoid encapsulation levels and the incidence of superparasitism were determined; also, the gamma radiation dose-effect relation on host larvae and the influence of Mediterranean fruit fly strain were considered. Naked Mediterranean fruit fly larvae of both GSS Vienna-8 and a wild bisexual strain (= WBS) aged 6-d-old were irradiated at 0, 20, 40, 60, 80, 100, and 120 Gy, and exposed to parasitoid females. Melanization level was tested for encapsulated parasitoid larval first-instars (= L1). Non-irradiated and irradiated WBS larvae at 20-40 Gy displayed a significantly higher incidence of encapsulation when compared with GSS Vienna-8 larvae. The low melanized level in encapsulated parasitoid L1 was the most common melanization process at 72 h puparium dissection. A high melanized level was only found in non-irradiated WBS larvae. Irradiated GSS Vienna-8 larvae can neutralize the host immunological reactions over irradiated WBS larvae much more quickly. Superparasitism intensity in both Mediterranean fruit fly strains was not affected by radiation doses. High levels of superparasitism seemingly helped to overcome the host's immune reaction by the surviving parasitoid larva. Parasitoid emergence increased from 60 Gy onwards in both Mediterranean fruit fly strains. Radiation in GSS Vienna-8 larvae may favor host's antagonistic reactions decrease in relation with D. longicaudata development.

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors.

BACKGROUND: Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. RESULTS: We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. CONCLUSIONS: Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.

Evisceración intestinal transvaginal espontánea idiopática. Reporte de caso / Idiopathic spontaneous transvaginal intestinal evisceration. Case report

Resumen ANTECEDENTES: La evisceración por vía vaginal es una urgencia quirúrgica poco frecuente, con menos de 100 reportes en la bibliografía. Se asocia con múltiples factores, el más importante es la cirugía ginecológica por vía vaginal. La presentación clínica es variable y el tratamiento consiste en cirugía de urgencia para disminuir la morbilidad y mortalidad asociada con las complicaciones. CASO CLÍNICO: Paciente de 63 años, sin antecedentes quirúrgicos o procedimientos por vía vaginal, referida del segundo nivel al Hospital Regional de Alta Especialidad de Oaxaca, con diagnóstico de evisceración por vía vaginal, posterior a una maniobra de Valsalva cuando evacuaba, con posterior sensación de cuerpo extraño en el canal vaginal. Fue valorada en el servicio de Urgencias de un hospital de tercer nivel en donde se la encontró hemodinámicamente estable, con signos vitales en parámetros normales, taquicárdica, con 103 latidos por minuto. De inmediato fue intervenida y en el transoperatorio se evidenció la ruptura de la cúpula vaginal, con evisceración y necrosis de 100 cm de íleon terminal. Se le practicaron: resección, anastomosis y cierre primario del defecto vaginal. Se le tomó biopsia del cuello uterino; la colposcopia se reportó con malignidad negativa. El posoperatorio evolucionó sin contratiempos. CONCLUSIÓN: Hasta ahora, se encuentran menos de 100 reportes de esta complicación, que requiere de sospecha y tratamiento oportuno para disminuir la morbilidad y mortalidad asociada. Lo relevante de este caso es la ausencia de antecedentes quirúrgicos que pudieran ser la causa.

Abstract BACKGROUND: Vaginal evisceration is a rare entity, with less than 100 reports in the -literature, which is associated with multiple factors, the most important being the history of a gynecological surgical approach by vaginal approach. The clinical presentation is variable, and the treatment is based on emergency surgery to reduce the associated morbidity and mortality. CLINICAL CASE: The case of a 63-year-old female with no surgical history or vaginal procedures with a diagnosis of vaginal evisceration after performing a Valsalva maneuver when evacuating with a foreign body sensation in the vaginal canal, presenting a vaginal dome rupture, with evisceration and necrosis of the case is presented. 100 cm of terminal ileum who undergoes surgical time with resection, anastomosis as well as primary closure of vaginal defect, presents pathology report, cervical biopsy, as well as negative colposcopy of malignancy. CONCLUSION: So far, there are fewer than 100 reports of this complication, which requires suspicion and timely treatment to reduce the associated morbidity and mortality. What is relevant in this case is the absence of a surgical history that could be the cause.

Supervivencia y características de rebrotes en tocones de dos años de cultivos dendroenergéticos / Survival rates and characteristics of spreads in two years stumps of crops with dendroenergy potential

Resumen Varias especies de los géneros Eucalyptus y Acacia son adecuadas para la producción de biomasa útil en la generación de energía. El objetivo del presente estudio fue evaluar la supervivencia y características del rebrote en tocones de cuatro especies dendroenergéticas en tres diferentes densidades poblacionales. Se utilizó un diseño de bloques completos al azar con tres repeticiones, en tres sitios (Parcelas Collipulli, La Aguada y Pilpilco Abajo) con características edafoclimáticas contrastantes. Se estudió Eucalyptus globulus, Eucalyptus denticulata, Eucalyptus nitens y Acacia dealbata en tres densidades de plantación (5 000 árboles/ ha; 10 000 árboles/ha y 15 000 árboles/ha). Se evaluó el porcentaje de supervivencia y las características del rebrote por tocón. Las variables especie, densidad de plantación y sitio de siembra afectaron los parámetros analizados. La densidad de plantación afectó el diámetro y altura de los rebrotes dominantes de tipo proventicio en las cuatro especies estudiadas. La mayor tasa de supervivencia de tocones (97 %), la presentó Eucalyptus nitens en Pipilco Abajo, con 79 % de supervivencia de rebrotes a una densidad de 5 000 árboles/ha. Sin embargo, en densidades de 15 000 árboles/ha, la supervivencia de rebrote fue de 29 %. Acacia dealbata es una especie reconocida por su capacidad de colonización, sin embargo, en La Aguada, con densidades de siembra de 5 000 árboles/ha y 10 000 árboles/ha, mostró baja tasa de supervivencia de tocones (19 % y 18 %, respectivamente) y de rebrotes (57 % y 63 %, respectivamente). La especie Eucalyptus globulus mostró altas tasas de supervivencia de tocones y rebrotes en todos los sitios evaluados, por lo que puede ser considerada como una buena opción para optimizar el sistema de monte bajo.

Abstract Several species of the genera Eucalyptus and Acacia are suitable for biomass production useful in energy generation. The objective of this research was to evaluate the survival and chaof four dendroenergetic species in three population densities. A randomized block design with three replications was used in three sites (Collipulli, La Aguada and Pilpilco Abajo plots) with contrasting edaphoclimatic characteristics. Eucalyptus globulus, Eucalyptus denticulata, Eucalyptus nitens and Acacia dealbata were studied in three plantation densities (5 000 trees/ha, 10 000 trees/ha and 15 000 trees/ha). The survival percentage and characteristics of stump regrowth characteristics of each stump were evaluated. The variables specie, plantation density and planting site affected the analyzed parameters. Plantation density affected the diameter and height of prevalent sprouts of proventic proventitious shoots in all species. Hihest stump survival rate (97 %) was presented by Eucalyptus nitens in Pipilco Abajo, with 79 % shoots survival of sprouts at a density of 5 000 trees/ha. However, at densities of 15 000 trees/ ha, regrowth survival was 29%. The Acacia dealbata is a species characterized by its colonization capacity. However, at La Aguada, which had population densities of 5 000 trees/ha and 10 000 trees/ha, it showed a low stump (19% and 18 % respectively) and shoots (57 % and 63 % respectively) survival rate. The species Eucalyptus globulus showed high stump and shoot survival rates in all sites evaluated, therefore it can be considered a good option to optimize the scrub system.

Basal Serum Cortisol and Testosterone/Cortisol Ratio Are Related to Rate of Na+ Lost During Exercise in Elite Soccer Players.

During exercise, the human body maintains optimal body temperature through thermoregulatory sweating, which implies the loss of water, sodium (Na+), and other electrolytes. Sweat rate and sweat Na+ concentration show high interindividual variability, even in individuals exercising under similar conditions. Testosterone and cortisol may regulate sweat Na+ loss by modifying the expression/activity of the cystic fibrosis transmembrane conductance regulator. This has not been tested. As a first approximation, the authors aimed to determine whether basal serum concentrations of testosterone or cortisol, or the testosterone/cortisol ratio relate to sweat Na+ loss during exercise. A total of 22 male elite soccer players participated in the study. Testosterone and cortisol were measured in blood samples before exercise (basal). Sweat samples were collected during a training session, and sweat Na+ concentration was determined. The basal serum concentrations of testosterone and cortisol and their ratio were (mean [SD]) 13.6 (3.3) pg/ml, 228.9 (41.4) ng/ml, and 0.06 (0.02), respectively. During exercise, the rate of Na+ loss was related to cortisol (r = .43; p < .05) and to the testosterone/cortisol ratio (r = -.46; p < .01), independently of the sweating rate. The results suggest that cortisol and the testosterone/cortisol ratio may influence Na+ loss during exercise. It is unknown whether this regulation depends on the cystic fibrosis transmembrane conductance regulator.

KDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover.

Inter-organelle signalling has essential roles in cell physiology encompassing cell metabolism, aging and temporal adaptation to external and internal perturbations. How such signalling coordinates different organelle functions within adaptive responses remains unknown. Membrane traffic is a fundamental process in which membrane fluxes need to be sensed for the adjustment of cellular requirements and homeostasis. Studying endoplasmic reticulum-to-Golgi trafficking, we found that Golgi-based, KDEL receptor-dependent signalling promotes lysosome repositioning to the perinuclear area, involving a complex process intertwined to autophagy, lipid-droplet turnover and Golgi-mediated secretion that engages the microtubule motor protein dynein-LRB1 and the autophagy cargo receptor p62/SQSTM1. This process, here named 'traffic-induced degradation response for secretion' (TIDeRS) discloses a cellular mechanism by which nutrient and membrane sensing machineries cooperate to sustain Golgi-dependent protein secretion.

Functional Evidence of the Involvement of the Dynein Light Chain DYNLRB2 in Murine Leukemia Virus Infection.

How murine leukemia virus (MLV) travels from the cell membrane to the nucleus and the mechanism for nuclear entry of MLV DNA in dividing cells still remain unclear. It seems likely that the MLV preintegration complex (PIC) interacts with cellular proteins to perform these tasks. We recently published that the microtubule motor cytoplasmic dynein complex and its regulator proteins interact with the MLV PIC at early times of infection, suggesting a functional interaction between the incoming viral particles, the dynein complex, and dynein regulators. To better understand the role of the dynein complex in MLV infection, we performed short hairpin RNA (shRNA) screening of the dynein light chains on MLV infection. We found that silencing of a specific light chain of the cytoplasmic dynein complex, DYNLRB2, reduced the efficiency of infection by MLV reporter viruses without affecting HIV-1 infection. Furthermore, the overexpression of DYNLRB2 increased infection by MLV. We conclude that the DYNLRB2 light chain of the cytoplasmic dynein complex is an important and specific piece of the host machinery needed for MLV infection.IMPORTANCE Retroviruses must reach the chromatin of their host to integrate their viral DNA, but first they must get into the nucleus. The cytoplasm is a crowded environment in which simple diffusion is slow, and thus viruses utilize retrograde transport along the microtubule network, mediated by the dynein complex. Different viruses use different components of this multisubunit complex. We have found that murine leukemia virus (MLV) associates functionally and specifically with the dynein light chain DYNLRB2, which is required for infection. Our study provides more insight into the molecular requirements for retrograde transport of the MLV preintegration complex and demonstrates, for the first time, a role for DYNLRB2 in viral infection.

Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection.

UNLABELLED: During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE: Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm-a crowded environment where diffusion is slow-is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multisubunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for infection. Our study provides the first insight into the requirements for retrograde transport of the MLV preintegration complex.