Vertical musculocutaneous trapezius flap for the closure of postpneumonectomy empyema.

OBJECTIVE: The aim of the study was to present our experience with the vertical musculocutaneous trapezius (VMCT) flap and highlight its utility in the thoracic wall reconstruction in patients with bronchopleural fistula (BPF). MATERIALS AND METHODS: We present a five case series of patients with long-standing cavities and BPF. The VMCT flap was used, and a direct pathway into the defect was made through a separate posterior thoracotomy shortening the distance between the flap and the defect. RESULTS: In 80% of the cases, the flap succeeded in solving the fistula and filling the defect, quality of life improved, and the need for oxygen decreased. CONCLUSIONS: Management of open window thoracostomy is challenging. Debridement, thoracoplasty, and flap coverage are the mainstream of their treatment, but these patients have scarce available muscle. The VMCT flap represents the major non-affected musculocutaneous unit in the thoracic area after lung surgery. Its dermal component offers a rigid matrix to form a seal over the bronchial stump. Its muscular component adds a good amount of vascularized tissue. No functional impairment has been described after its use.

OBJETIVO: Exponer nuestra experiencia con el colgajo vertical de trapecio y destacar su utilidad en la reconstrucción de la pared torácica en pacientes con fístulas broncopleurales. MATERIAL Y MÉTODOS: Presentamos una serie de cinco pacientes con cavidades y fístulas broncopleurales de larga evolución. Utilizamos el colgajo musculocutáneo vertical de Trapecio, con un redireccionamiento del mismo a través de una ventana costal que permite acortar la distancia entre el colgajo y el defecto. RESULTADOS: La fístula y el defecto fueron solucionados en el 80% de los casos. La calidad de vida mejoró y las necesidades de oxígeno disminuyeron. CONCLUSIONES: El manejo de las toracotomías es un reto. El desbridamiento, toracoplastia y cobertura con colgajo son los pilares de su tratamiento, pero estos pacientes tienen escasa disponibilidad muscular. El colgajo musculocutáneo vertical de Trapecio representa la mayor unidad intacta musculocutánea en el tórax tras cirugía pulmonar. Su componente dérmico ofrece una matriz rígida para sellar el muñón bronquial, su componente muscular añade una gran cantidad de tejido vascularizado. No se han descrito déficits funcionales tras su uso.

Clinical use of tranexamic acid: evidences and controversies

Abstract Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.

Chronic inhibition of the mitochondrial ATP synthase in skeletal muscle triggers sarcoplasmic reticulum distress and tubular aggregates.

Tubular aggregates (TA) are honeycomb-like arrays of sarcoplasmic-reticulum (SR) tubules affecting aged glycolytic fibers of male individuals and inducing severe sarcomere disorganization and muscular pain. TA develop in skeletal muscle from Tubular Aggregate Myopathy (TAM) patients as well as in other disorders including endocrine syndromes, diabetes, and ageing, being their primary cause unknown. Nowadays, there is no cure for TA. Intriguingly, both hypoxia and calcium dyshomeostasis prompt TA formation, pointing to a possible role for mitochondria in their setting. However, a functional link between mitochondrial dysfunctions and TA remains unknown. Herein, we investigate the alteration in muscle-proteome of TAM patients, the molecular mechanism of TA onset and a potential therapy in a preclinical mouse model of the disease. We show that in vivo chronic inhibition of the mitochondrial ATP synthase in muscle causes TA. Upon long-term restrained oxidative phosphorylation (OXPHOS), oxidative soleus experiments a metabolic and structural switch towards glycolytic fibers, increases mitochondrial fission, and activates mitophagy to recycle damaged mitochondria. TA result from the overresponse of the fission controller DRP1, that upregulates the Store-Operate-Calcium-Entry and increases the mitochondria-SR interaction in a futile attempt to buffer calcium overloads upon prolonged OXPHOS inhibition. Accordingly, hypoxic muscles cultured ex vivo show an increase in mitochondria/SR contact sites and autophagic/mitophagic zones, where TA clusters grow around defective mitochondria. Moreover, hypoxia triggered a stronger TA formation upon ATP synthase inhibition, and this effect was reduced by the DRP1 inhibitor mDIVI. Remarkably, the muscle proteome of TAM patients displays similar alterations in mitochondrial dynamics and in ATP synthase contents. In vivo edaravone treatment in mice with restrained OXPHOS restored a healthy phenotype by prompting mitogenesis and mitochondrial fusion. Altogether, our data provide a functional link between the ATP synthase/DRP1 axis and the setting of TA, and repurpose edaravone as a possible treatment for TA-associated disorders.

Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells.

Hepatocellular carcinoma (HCC) is one of the most frequent and essentially incurable cancers in its advanced stages. The tyrosine kinase inhibitor Sorafenib (Sfb) remains the globally accepted treatment for advanced HCC. However, the extent of its therapeutic benefit is limited. Sfb exerts antitumor activity through its cytotoxic, anti-proliferative and pro-apoptotic roles in HCC cells. To better understand the molecular mechanisms underlying these effects, we used RNA sequencing to generate comprehensive transcriptome profiles of HepG2 and SNU423, hepatoblastoma- (HB) and HCC-derived cell lines, respectively, following a Sfb treatment at a pharmacological dose. This resulted in similar alterations of gene expression in both cell lines. Genes functionally related to membrane trafficking, stress-responsible and unfolded protein responses, circadian clock and activation of apoptosis were predominantly upregulated, while genes involved in cell growth and cycle, DNA replication and repair, ribosome biogenesis, translation initiation and proteostasis were downregulated. Our results suggest that Sfb causes primary effects on cellular stress that lead to upregulation of selective responses to compensate for its negative effect and restore homeostasis. No significant differences were found specifically affecting each cell line, indicating the robustness of the Sfb mechanism of action despite the heterogeneity of liver cancer. We discuss our results on terms of providing rationalization for possible strategies to improve Sfb clinical outcomes.

Clinical use of tranexamic acid: evidences and controversies.

Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.

Smoking prevention with narrative messages. An experimental study on the joint effect of audience-character similarity and narrative voice. / Prevención del tabaquismo con mensajes narrativos. Estudio experimental sobre el efecto conjunto de la similitud con el protagonista y la voz narrativa.

This study focuses on smoking prevention using narrative messages. In particular, the role of two narrative attributes that can indirectly influence the intention to quit smoking, self-efficacy expectations and the perceived effectiveness of the preventive response were analysed. An experimental study was carried out (N = 680, 50% women and age range 18-55 years) with a 2 (narrative voice: first- vs. third-person message) x 2 (audience-protagonist similarity: low vs. high) between-subjects factorial design. Results showed that the optimal reception condition (first-person narrative with a highly similar protagonist to the audience) induced the highest levels of identification with the protagonist (a former smoker who described the process of quitting smoking and subsequent the improvements he has experienced). Mediational analyses showed that the optimal reception condition exerted significant indirect effects on the dependent variables, due to the increase in identification and reactance reduction. In addition, the optimal reception condition also exerted a significant indirect effect on the perceived effectiveness of the preventive response that was explained by stronger identification and weaker counterarguing. The present study opens an innovative line of research on the construction of narrative messages for smoking prevention. The relevance of the characteristics of these messages is highlighted in order to activate mediating processes that facilitate persuasion.

El presente trabajo se centra en la prevención del tabaquismo utilizando mensajes narrativos. En particular, se analiza el papel de dos características de los mensajes narrativos que pueden influir, de manera indirecta, en la intención de dejar de fumar, las expectativas de auto-eficacia y la percepción de la eficacia de la respuesta preventiva. Para ello, se llevó a cabo una investigación experimental (N = 680, 50% mujeres y rango de edad 18-55 años) con un diseño factorial 2 (voz narrativa: mensaje en primera vs. tercera persona) x 2 (similitud con el protagonista: baja vs. alta). Los resultados mostraron que la condición óptima de recepción (narración en primera persona protagonizada por un personaje similar a la audiencia) indujo niveles más elevados de identificación con el protagonista (un exfumador describía el proceso de abandono del tabaco y las mejoras que ha experimentado desde entonces). Los análisis mediacionales mostraron que la condición óptima de recepción ejercía efectos indirectos significativos sobre las variables dependientes que se debían al aumento de la identificación y la reducción de la reactancia. Además, la condición óptima de recepción también ejerció un efecto indirecto significativo sobre la eficacia percibida de la respuesta preventiva que se explicaba por el incremento de la identificación y la reducción de la contra-argumentación. El presente trabajo abre una línea de estudio sobre la construcción de mensajes narrativos para la prevención del tabaquismo. Se pone de manifiesto la relevancia de las características que dichos mensajes deben tener para que se activen procesos mediadores que faciliten la persuasión.

Narrative Voice Matters! Improving Smoking Prevention with Testimonial Messages through Identification and Cognitive Processes.

Narrative messages are increasingly being used in the field of tobacco prevention. Our study is based on narrative persuasion and aims to analyze the psychological mechanisms that explain why the narrative voice is relevant to promote persuasive impact. An online experiment with a 2 (narrative voice) × 2 (message) factorial design was carried out. Participants (525 adult smokers) were randomly assigned to two experimental conditions (first-person versus third-person narrative message). To increase the external validity of the study, two different messages were used within each condition. After reading the narrative message the mediating and dependent variables were evaluated. Participants who read the narrative in the first person experienced greater identification. Moreover, mediational analysis showed that both counterarguing and cognitive elaboration played a significant role in the relationship between narrative voice, identification, and persuasive impact. This study confirm that narrative voice is not only an anecdotal formal choice but that it indirectly affects variables related to tobacco prevention, due to the fact that first-person messages activate a mechanism of affective connection with the message (increasing the identification with the protagonist) that decreases resistance to prevention (the counterarguing process) while simultaneously stimulating reflection or cognitive elaboration.

Estrés en estudiantes de enfermería que realizan prácticas clínicas en una institución universitaria de Cartagena-Colombia, 2019 / Stress in nursing students who carry out clinical practices in a university institution of Cartagena-Colombia, 2019

Objetivo: determinar los niveles de estrés que experimentan los estudiantes de enfermería que realizan sus prácticas clínicas en una institución universitaria de la ciudad de Cartagena (Colombia). Materiales y métodos: se realizó un estudio descriptivo, transversal, con una muestra de 98 estudiantes de enfermería matriculados en semestres de IV a IX. Se aplicó cuestionario KEZKAK sobre percepción de estrés en estudiantes de enfermería en prácticas clínicas. Los análisis emplearon estadística descriptiva. Resultados: los estudiantes tuvieron edades comprendidas entre 20 ­ 24 años (61,2%), fueron mujeres (93,9%). Presentaron nivel alto de estrés (51%), durante las prácticas clínicas por considerar falta de competencias (68,4%), impotencia e incertidumbre, y el enfermo busca una relación íntima y/o amorosa con 48% respectivamente. Conclusiones: los estudiantes evidencian que la falta de competencias al brindar cuidado a los pacientes en situaciones críticas, se convierte en un determinante generador de estrés..Au

Objective: to determine the levels of stress experienced by nursing students who carry out their clinical practices in a university institution in the city of Cartagena (Colombia).Materials and methods: a descriptive, cross-sectional study was carried out.With a sample of 98 Nursing students enrolled in semesters from IV to IX. A KEZKAK questionnaire on the perception of stress in nursing students in clinical practices was applied. The analyzes were performed using descriptive statistics. Results: the students were aged 20-24 years (61.2%), were women (93.9%).They presented a high level of stress (51%), during clinical practices because they considered lack of skills (68.4%) impotence and uncertainty, and the patient seeks an intimate and / or loving relationship with 48%, respectively. Conclusions: students show that the lack of skills in providing care to patients in critical situations becomes a determinant of stress..Au

Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells.

BACKGROUND/AIMS: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells. METHODS: The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern. RESULTS: The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress, Ser15P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhanced Thr172P-Cdk4/Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells. CONCLUSION: The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cells.

Mitochondrial movement in Aralar/Slc25a12/AGC1 deficient cortical neurons.

The elevated energy demands in the brain are fulfilled mainly by glucose catabolism. In highly polarized neurons, about 10-50% of mitochondria are transported along microtubules using mitochondrial-born ATP to locations with high energy requirements. In this report, we have investigated the impact of Aralar deficiency on mitochondrial transport in cultured cortical neurons. Aralar/slc25a12/AGC1 is the neuronal isoform of the aspartate-glutamate mitochondrial carrier, a component of the malate-aspartate shuttle (MAS) which plays an important role in redox balance, which is essential to maintain glycolytic pyruvate supply to neuronal mitochondria. Using live imaging microscopy we observed that the lack of Aralar does not affect the number of moving mitochondria nor the Ca2+-induced stop, the only difference being a 10% increase in mitochondrial velocity in Aralar deficient neurons. Therefore, we evaluated the possible fuels used in each case by studying the relative contribution of oxidative phosphorylation and glycolysis to mitochondrial movement using specific inhibitors. We found that the ATP synthase inhibitor oligomycin caused a smaller inhibition of mitochondrial movement in Aralar-KO than control neurons, whereas the glycolysis inhibitor iodoacetate had similar effects in neurons from both genotypes. In line with these findings, the decrease in cytosolic ATP/ADP ratio caused by oligomycin was more pronounced in control than in Aralar-KO neurons, but no differences were observed with iodoacetate. Oligomycin effect was reverted by aralar re-expression in knock out cultures. As mitochondrial movement is not reduced in Aralar-KO neurons, these results suggest that these neurons may use an additional pathway for mitochondria movement and ATP/ADP ratio maintenance.

Hiperadrenocorticismo atípico canino asociado a hipotireoidismo / Canine atypical hyperadrenocorticism associated with hypothyroidism

RESUMEN El hiperadrenocorticismo (HAC) es una de las endocrinopatías más frecuentes en caninos, producida por la síntesis excesiva de cortisol. El HAC atípico u oculto es un síndrome caracterizado por la presentación de alteraciones clínicas, bioquímicas e imagenológicas compatibles con hipercortisolismo, pero con resultados normales en las pruebas endocrinológicas utilizadas convencionalmente para diagnóstico de HAC. Sin embargo, estos pacientes presentan elevada concentración sérica de precursores u otras hormonas corticoadrenales. El presente estudio describe el caso de una canina hembra, Bichón Frisé de 8 años de edad, epiléptica y tratada con fenobarbital, presentando signos clínicos asociados a HAC, en la que el test de supresión con dexametasona a dosis bajas y de estimulación con ACTH arrojaron valores normales. La medición de esteroides adrenales, post estimulación con ACTH, mostró elevación anormal de estrógenos y progesterona, persistiendo esta última después de que la paciente fuera esterilizada. El tratamiento con trilostano permitió la disminución de los niveles de progesterona y la resolución parcial de los signos clínicos. Sin em bargo, la recuperación clínica en su totalidad sólo se obtuvo después del diagnóstico y tratamiento del hipotiroidismo concomitante. El desafio que representa el diagnóstico del HAC atípico resalta la importância de realizar y disponer de paneles que incluyan medición de hormonas esteroideas adrenales diferentes al cortisol, además de considerar la ocurrencia de otras enfermedades endocrinas metabólicas concomitantes.

ABSTRACT Hyperadrenocorticism (HAC) is one of the most common endocrinopathies in dogs, caused by excessive synthesis of cortisol. Atypical or occult HAC is a syndrome characterized by the presentation of clinical, biochemical, and imaging alterations compatible with hypercortisolism, but normal results in endocrine tests that are conventionally used for HAC diagnosis. However, these patients present high serum concentrations of precursors or other corticoadrenal hormones. The present study describes the case of an 8 years old female canine, Bichón Frisé, epileptic and treated with phenobarbital, presenting clinical signs associated with HAC, in which the low-dose dexamethasone suppression test and stimulation with ACTH resulted within normal values. The measurement of adrenal steroids, after ACTH stimulation, showed abnormal elevation of estrogen and progesterone, the latter persisting after the patient was spayed. Treatment with trilostane allowed the reduction of progesterone levels and the partial resolution of clinical signs. However, full clinical recovery was only achieved after the diagnosis and treatment of concomitant hypothyroidism. The challenge that represent the diagnosis of atypical HAC highlights the importance of performing and having availability of panels that include measurement of adrenal steroid hormones other than cortisol, as well as considering the occurrence of other concomitant endocrine metabolic diseases.

Uso de antibióticos profilácticos en pacientes sometidos a cirugías electivas limpias. Estudio prospectivo comparativo / Use of prophylactic antibiotics in patients undergoing clean elective surgeries. Comparative prospective study

El uso indiscriminado de antibióticos y el mal manejo de los mismos por parte del personal médico es un problema frecuente a nivel mundial, esto ha incrementado la resistencia bacteriana, los costos del tratamiento y ha creado la necesidad de contar con nuevos antibióticos, frecuentemente más costosos y de mayor toxicidad.Objetivo : evaluar el uso de antibióticos profilácticos en pacientes sometidos a cirugías electivas limpias, en centros privados del estado Aragua, en el periodo comprendido entre febrero y agosto del año 2019.Métodos : estudio prospectivo, observacional, comparativo, longitudinal. La muestra fue no probabilística intencional, se dividió en 2 grupos: grupo A, a quienes se les administró antibioticoterapia profiláctica, y un grupo B, a quienes no se les administró antibiótico.Resultados : Se incluyeron 49 pacientes sometidos a cirugías electivas limpias de tipo colecistectomías (14/28.57%), herniorrafía umbilical (6/12.24%) y hernioplastia inguinal (29/59.18%). La edad promedio fue de 37,7±12,17 años. Predomino el sexo masculino. Al quinto día del postoperatorio no se observaron signos de complicación infecciosa en los grupos A y B. Al décimo día de postoperatorio se observaron signos de complicación infecciosa en un paciente (4.3%) perteneciente al grupo A. No se observó complicación infecciosa en el grupo sin administración de antibiótico, grupo B.Conclusión : La indicación y mantenimiento por 7-10 días de antibiótico profiláctico en cirugía limpia no presenta diferencia en la presentación de complicaciones infecciosas comparado con la no administración de antibióticos para este tipo de cirugía, con el riesgo potencial de producción de efectos adversos y desarrollo de resistencia bacteriana(AU)

The indiscriminate use of antibiotics and their mishandling by medical personnel is a frequent problem worldwide, which has increased bacterial resistance, treatment costs and the need for new antibiotics, often more expensive and of greater toxicity.Objective : to evaluate the use of prophylactic antibiotics in patients undergoing clean elective surgeries, in private centers in the Aragua state, in the period between February and August of 2019.Methods : we conducted a prospective, longitudinal, observational, analytical epidemiological clinical study. The participants consisted of non-probabilistic sample of the intentional type of 49 patients of the total study population, undergoing elective surgery, cholecystectomy (14 / 28.57%), umbilical herniorrhaphy (6 / 12.24%) and inguinal hernioplasty (29 /59.18%). The sample was classified into 2 groups, a group A, who received prophylactic antibiotic therapy and a group B, who did not receive it.Results : the mean age was 37.7 ± 12.17 years, predominantly male. On the fifth day of the postoperative period, no signs of infectious complication were observed neither in group A nor in group B. On the tenth day after the postoperative period, signs of infectious complication were observed in one patient (4.3%) belonging to the antibiotic administration group. No infectious complication was observed in the group without antibiotic administration.Conclusion : it was confirmed that the administration of antibiotics does not reduce the incidence of infection, when comparing an experimental group with a control group(AU)

Significados em puérperas da internaçao na Unidade de terapia intensiva / Significados en puérperas sobre la hospitalización en Unidad de Cuidados Intensivos / Meanings in postpartum on hospitalization in the Intensive Care Unit

Objetivo: Descrever o significado desde o olhar cultural que atribuem puérperas com morbidade materna extrema a sua internação na Unidade de Terapia Intensiva (UTI). Materiais eMétodos: Estudo qualitativo com abordagem etnográfica, utilizou-se como referente teórico a Madeleine Leininger. As entrevistas a profundidade e a aná-lise qualitativa realizou-se considerando o método de James Spradley. Obtiveram--se 21 entrevistas a profundidade em 9 mulheres puérperas com morbidade materna extrema e estiveram internadas numa UTI de uma clínica da cidade de Sincelejo, Sucre, Colômbia entre março e dezembro de 2017. Resultados: Os significados que atribuíram as puérperas com morbidade materna extrema respeito à sua internação na UTI incluíram oito domínios: conhecimento dos sinais de alarma, temor da mor-te, muito difícil para o meu parceiro, adiamento da amamentação, retorno à clinica, minha família cuida de mim, a enfermeira me cuida e aprender dessa experiência.Conclusões: Os significados de puérperas com morbidade materna extrema estão carregados de experiências, crenças culturais e sentimentos, onde o cuidado compas-sivo e congruente de enfermagem ajuda na sua sobrevivência e a internação na UTI constitui-se num ensinamento para a vida.

Objetivo: Describir el significado desde lo cultural que atribuyen puérperas con Morbilidad Materna Extrema a su hospitalización en la Unidad de Cuidados Intensi-vos. Materiales y Métodos: Estudio cualitativo con abordaje etnográfico, utilizando como referente teórico a Madeleine Leininger. Las entrevistas a profundidad y el análisis cualitativo se realizaron teniendo en cuenta el método de James Spradley. Se efectuaron 21 entrevistas a profundidad a 9 puérperas con Morbilidad Materna Extrema que estuvieron hospitalizadas en la Unidad de Cuidados Intensivos de una clínica de la ciu-dad de Sincelejo-Sucre - Colombia entre marzo y diciembre de 2017. Resultados: Los significados que atribuyen puérperas con Morbilidad Materna Extrema sobre su hospitalización en la Unidad de Cuidados Intensivos incluyeron 8 dominios: conocimiento de los signos de alarma, temor a morir, muy difícil para mi compañero, aplazar la lactancia materna, de regreso a la clínica, mi familia me cuida, la enfermera me cuida y aprender de esta experiencia. Conclusiones: Los significados de puérperas con Morbilidad Materna Extrema están colmados de experiencias, creencias culturales y sentimientos, donde el cuidado compasivo y congruente de enfermería les ayuda a sobrevivir y la hospitalización en la UCI se constituye en una enseñanza para la vida.

Objective: To describe the cultural significance attributed by postpartum women with Extreme Maternal Morbidity to their hospitalization in the Intensive Care Unit. Materials and Methods: Qualitative study with ethnographic approach, using Madeleine Leininger as theoretical reference. In-depth interviews and qualitative analysis were carried out using James Spradley's method. Twen-ty-one in-depth interviews were conducted with nine postpartum women with Extreme Maternal Morbidity who were hospitalized in the Intensive Care Unit of a clinic in the city of Sincelejo-Sucre - Colombia between March and December 2017. Results: The meanings attributed by postpartum women with Extreme Maternal Morbidity to their hospitalization in the Intensive Care Unit included 8 domains: knowledge of alarm signs, fear of death, very difficult for my partner, postponement of breastfeeding, return to the clinic, my family cares for me, the nurse cares for me and learning from this experience. Conclusions: The meanings of postpartum with Extreme Maternal Morbidity are full of experiences, cultural beliefs and feelings, where compassionate and congruent nursing care helps them to survive and hospitalization in the ICU becomes a teaching for life

Babesia bovis: Actualidad del desarrollo de una vacuna / Babesia bovis: An Update on vaccine development / Babesia bovis: Atualidade do desenvolvimento de uma vacina

Introducción. Babesia bovis es el principal agente causal de la babesiosis bovina, una importante enfermedad veterinaria transmitida por garrapatas a nivel mundial. Las estrategias convencionales para controlar esta parasitosis han presentado múltiples limitaciones por lo que el desarrollo de una vacuna basada en antígenos representa una estrategia apropiada para la prevención y el tratamiento. Objetivo. Describir los aspectos relevantes del ciclo de vida del parásito B. bovis, la epidemiología, diagnóstico y la aplicación de diferentes estrategias usadas para controlar esta parasitosis. Además, se discuten potenciales puntos de intervención para desarrollar una vacuna contra este parásito. Metodología. Se realizó una búsqueda en las bases de datos usando los términos: "Babesia bovis AND lyfe cycle", "B. bovis vaccine and Vaccine candidates", entre otras. Los estudios con mayor pertinencia publicados hasta la actualidad se revisaron completamente. Resultados. Los detalles de la biología de parásito B. bovis y el proceso molecular usado para ocasionar la enfermedad en el hospedador son poco conocidos, lo que explica que el desarrollado de estrategias para el control de esta parasitosis no hayan sido del todo eficientes. Por lo tanto, se requiere diseñar nuevas medidas, por ejemplo, desarrollar vacunas de nueva generación basadas en un enfoque funcional que permitan mejorar las condiciones de sanidad animal. Conclusiones. Comprender el complejo ciclo de vida de B. bovis permitirá estudiar las interacciones huésped-parásito-garrapata e identificar moléculas implicadas en la adhesión/invasión celular para evaluar su utilidad como componente de una vacuna que controle esta parasitosis.

Introduction. Babesia bovis is the main causal agent of babesiosis bovine, one important veterinary diseases transmitted by ticks worldwide. Conventional strategies to control this parasitosis have shown several limitations and therefore the development of a vaccine will be an appropriate strategy for prevention and treatment. Objective. To describe relevant aspects of B. bovis parasite's life cycle, the epidemiology, diagnosis, the application of different strategies used to control this parasitosis. In addition, potential points of intervention to develop a vaccine against this parasite has been discussed. Methodology. A search was made using keywords as "Babesia bovis AND lyfe cycle", "B. bovis vaccine and Vaccine candidates" and others. The most relevant studies published to date were completely revised. Results. The details of the B.bovis parasite biology and the molecular process used to cause disease in the host had not been describe in deep; explaining that the development of strategies for the control of this parasitosis have not been entirely efficient. Therefore, it is necessary to design new procedures, for example, to develop new generation vaccines based on a functional approach which improve the animal health conditions. Conclusions. Understand the B. bovise's life cycle complex will allow the host-parasite-tick interactions study and the identification of molecules involved in cell adhesion / invasion to evaluate its usefulness as a vaccine component that controls this parasitosis.

Introdução. Babesia bovis é o principal agente causador da babesiose bovina, uma importante doença veterinária transmitida por carrapatos a nível mundial. As estratégias convencionais para o controle das parasitoses têm presentado múltiplas limitações pelo que o desenvolvimento de uma vacina baseada em antígenos representa uma estratégia apropriada para a prevenção e o tratamento. Objetivo. Descrever os aspectos relevantes do ciclo de vida do parasita B. bovis, a epidemiologia, diagnostico e aplicação de diferentes estratégias usadas para o controle desta parasitose. Além disso, são discutidos possíveis pontos de intervenção para o desenvolvimento de uma vacina contra o parasita. Metodologia. Uma pesquisa foi realizada nas bases de dados usando os termos: "Babesia bovis AND lyfe cycle", "B. bovis vaccine and Vaccine candidates", entre outras. Os estudos mais relevantes publicados até o momento foram completamente revisados. Resultados. Os detalhes da biologia do parasita B. bovis e o processo molecular usado para causar doenças no hospedeiro é pouco conhecido, o que explica que o desenvolvimento de estratégias para o controle desta parasitose não foram completamente eficientes. Portanto, é necessário projetar novas medidas, por exemplo, desenvolver vacinas de nova geração com base em uma abordagem funcional que permita melhorar as condições de saúde animal. Conclusões. Compreender o complexo ciclo de vida de B. bovis permitirá estudar as interações hospede­parasita­carrapatos e identificar moléculas envolvidas na adesão/invasão celular para avaliar sua utilidade como componente de uma vacina que controla essa parasitose.

Molecular characterization of autophagic and apoptotic signaling induced by sorafenib in liver cancer cells.

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5'AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3-12 hr) ER stress characterized by an increase of Ser51 P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185 P-JNK1/2/JNK1/2, Thr172 P-AMPKα, Ser413 P-Foxo3a, Thr308 P-AKt/AKt and Thr32 P-Foxo3a/Foxo3a ratios, and reduction of Ser2481 P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL , Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308 P-AKt/AKt and Ser473 P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL , which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation.

Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients.

PURPOSE: MDH2 (malate dehydrogenase 2) has recently been proposed as a novel potential pheochromocytoma/paraganglioma (PPGL) susceptibility gene, but its role in the disease has not been addressed. This study aimed to determine the prevalence of MDH2 pathogenic variants among PPGL patients and determine the associated phenotype. METHODS: Eight hundred thirty patients with PPGLs, negative for the main PPGL driver genes, were included in the study. Interpretation of variants of unknown significance (VUS) was performed using an algorithm based on 20 computational predictions, by implementing cell-based enzymatic and immunofluorescence assays, and/or by using a molecular dynamics simulation approach. RESULTS: Five variants with potential involvement in pathogenicity were identified: three missense (p.Arg104Gly, p.Val160Met and p.Ala256Thr), one in-frame deletion (p.Lys314del), and a splice-site variant (c.429+1G>T). All were germline and those with available biochemical data, corresponded to noradrenergic PPGL. CONCLUSION: This study suggests that MDH2 pathogenic variants may play a role in PPGL susceptibility and that they might be responsible for less than 1% of PPGLs in patients without pathogenic variants in other major PPGL driver genes, a prevalence similar to the one recently described for other PPGL genes. However, more epidemiological data are needed to recommend MDH2 testing in patients negative for other major PPGL genes.

Significados de puérperas con Morbilidad Materna Extrema sobre su hospitalización y la del hijo(a) prematuro / Meanings of puerperal women with Extreme Maternal Morbidity on their hospitalization and that of the premature child

Objetivo: Describir el significado que atribuyen puérperas con Morbilidad Materna Extrema a su hospitalización en la Unidad de Cuidados Intensivos y la del hijo(a) prematuro en la Unidad Neonatal. Metodología: Estudio de tipo cualitativo con abordaje etnográfico, utilizando como referente teórico a Madeleine Leininger a través de la Teoría de la Universalidad y Diversidad de los Cuidados Culturales; las entrevistas a profundidad y el análisis cualitativo se realizó teniendo en cuenta el método de James Spradley. Se efectuaron 21 entrevistas a profundidad a 9 puérperas con Morbilidad Materna Extrema (MME) que estuvieron hospitalizadas al igual que sus hijos(as) prematuros en la UCIA y UCIN respectivamente de una clínica de la ciudad de Sincelejo-Sucre, entre Marzo y Diciembre de 2017. Resultados: Surgen 2 temas, los significados de puérperas con MME sobre su hospitalización incluye 8 dominios: conocimiento de los signos de alarma, temor a morir, muy difícil para mi compañero, aplazar la lactancia materna, de regreso a la clínica, mi familia me cuida, la enfermera me cuida y aprender de esta experiencia; y los significados sobre la hospitalización del hijo(a) prematuro conformado por 5 dominios: el mejor momento de mi vida, el canguro, cuidar al recién nacido prematuro, conocimientos educación sobre los cuidados del prematuro y milagro de Dios. Conclusión: Para las puérperas con MME su hospitalización en la Unidad de Cuidados Intensivos significo tener "temor a morir" y tener a su hijo(a) prematuro hospitalizado en la Unidad Neonatal significo "un milagro" porque es "hijo(a) de Dios".

Objective: Describe the significance conferred postpartum women with Maternal Near Miss about her hospitalization in the Intensive Care Unit and her premature child in the Neonatal Unit. Methodology: Qualitative study with ethnographic approach, using as a theoretical reference Madeleine Leininger through the Theory of Universality and Diversity of Cultural Care; the in-depth interviews and the qualitative analysis were carried out taking into account James Spradley's method. There were 21 in-depth interviews with 9 puerperal women with Maternal Near Miss who were hospitalized as well as their premature children in the ICU and NICU respectively of a clinic in the city of Sincelejo-Sucre, between March and December 2017. Results: 2 themes arise, the meanings of postpartum women with Near Miss Maternal Morbidity about their hospitalization includes 8 domains: knowledge of the warning signs, fear of dying, very difficult for my partner, postpone breastfeeding, back to the clinic, my family take care, the nurse takes care of me and learn from this experience; and the meanings about the hospitalization of the premature child conformed by 5 domains: the best moment of my life, the kangaroo, to care for the premature newborn, knowledge and education about the care of the premature and miracle of God. Conclusion: For the postpartum women with Maternal Near Miss, their hospitalization in the Intensive Care Unit meant having "fear of dying" and having their premature child hospitalized in the Neonatal Unit meant "a miracle" because it is "son of God"

De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise.

A series of simplex cases have been reported under various diagnoses sharing early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers, a distinctive facial gestalt, and prenatal and postnatal growth retardation. For historical reasons, we suggest naming the entity Fontaine syndrome. Exome sequencing of four unrelated affected individuals showed that all carried the de novo missense variant c.649C>T (p.Arg217Cys) or c.650G>A (p.Arg217His) in SLC25A24, a solute carrier 25 family member coding for calcium-binding mitochondrial carrier protein (SCaMC-1, also known as SLC25A24). SLC25A24 allows an electro-neutral and reversible exchange of ATP-Mg and phosphate between the cytosol and mitochondria, which is required for maintaining optimal adenine nucleotide levels in the mitochondrial matrix. Molecular dynamic simulation studies predict that p.Arg217Cys and p.Arg217His narrow the substrate cavity of the protein and disrupt transporter dynamics. SLC25A24-mutant fibroblasts and cells expressing p.Arg217Cys or p.Arg217His variants showed altered mitochondrial morphology, a decreased proliferation rate, increased mitochondrial membrane potential, and decreased ATP-linked mitochondrial oxygen consumption. The results suggest that the SLC25A24 mutations lead to impaired mitochondrial ATP synthesis and cause hyperpolarization and increased proton leak in association with an impaired energy metabolism. Our findings identify SLC25A24 mutations affecting codon 217 as the underlying genetic cause of human progeroid Fontaine syndrome.