Boldine prevents the inflammatory response of cardiac fibroblasts induced by SGK1-NFκB signaling pathway activation.

Cardiac fibroblasts (CF) are mesenchymal-type cells responsible for maintaining the homeostasis of the heart's extracellular matrix (ECM). Their dysfunction leads to excessive secretion of ECM proteins, tissue stiffening, impaired nutrient and oxygen exchange, and electrical abnormalities in the heart. Additionally, CF act as sentinel cells in the cardiac tissue microenvironment, responding to various stimuli that may affect heart function. Deleterious stimuli induce an inflammatory response in CF, increasing the secretion of cytokines such as IL-1ß and TNF-α and the expression of cell adhesion molecules like ICAM1 and VCAM1, initially promoting damage resolution by recruiting immune cells. However, constant harmful stimuli lead to a chronic inflammatory process and heart dysfunction. Therefore, it is necessary to study the mechanisms that govern CF inflammation. NFκB is a key regulator of the cardiac inflammatory process, making the search for mechanisms of NFκB regulation and CF inflammatory response crucial for developing new treatment options for cardiovascular diseases. SGK1, a serine-threonine protein kinase, is one of the regulators of NFκB and is involved in the fibrotic effects of angiotensin II and aldosterone, as well as in CF differentiation. However, its role in the CF inflammatory response is unknown. On the other hand, many bioactive natural products have demonstrated anti-inflammatory effects, but their role in CF inflammation is unknown. One such molecule is boldine, an alkaloid obtained from Boldo (Peumus boldus), a Chilean endemic tree with proven cytoprotective effects. However, its involvement in the regulation of SGK1 and CF inflammation is unknown. In this study, we evaluated the role of SGK1 and boldine in the inflammatory response in CF isolated from neonatal Sprague-Dawley rats. The involvement of SGK1 was analyzed using GSK650394, a specific SGK1 inhibitor. Our results demonstrate that SGK1 is crucial for LPS- and IFN-γ-induced inflammatory responses in CF (cytokine expression, cell adhesion molecule expression, and leukocyte adhesion). Furthermore, a conditioned medium (intracellular content of CF subject to freeze/thaw cycles) was used to simulate a sterile inflammation condition. The conditioned medium induced a potent inflammatory response in CF, which was completely prevented by the SGK1 inhibitor. Finally, our results indicate that boldine inhibits both SGK1 activation and the CF inflammatory response induced by LPS, IFN-γ, and CF-conditioned medium. Taken together, our results position SGK1 as an important regulator of the CF inflammatory response and boldine as a promising anti-inflammatory drug in the context of cardiovascular diseases.

«Management of nurses specialized in the aero-evacuation of highly infectious critical patients, during the COVID-19 pandemic. Systematic review¼.

INTRODUCTION: Aeromedical evacuation missions to transport highly infectious critical COVID-19 patients involve multiple factors, therefore planning is essential in their preparation. The management of specialist nurses is cross-cutting, as they participate in the planning, organisation and implementation of aero-evacuation protocols, delivery of care and operational safety procedures throughout the operation, with an integrated aeromedical crew working as a team alongside the air crew. OBJECTIVE: To study the management of nurses specialised in the aero-evacuation of highly infectious critical patients during the COVID-19 pandemic. DESIGN: Through a systematic search of the biomedical literature, this study was conducted according to the standards of the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA. The literature search included articles published from 2019 to August 2020 and meta-search engines, yielding a total of 142 articles, and a triangulation of information was performed. A total of 11 articles were eventually included in the review, and the validity of each article was determined according to the guidelines of the Joanna Briggs Institute level of evidence. RESULTS AND DISCUSSION: The systematic review identified 11 studies that use different methodological considerations for conducting an aeromedical evacuation and covering key aspects for a successful operation. CONCLUSION: The management of specialist nurses has a direct impact on the aeromedical evacuation of the critical patient. It covers planning, organisation, and operational safety, applied in the instruction, training, execution and strict monitoring of the work of the aeromedical crew as a solid team. This contributes to the success of the aero-evacuation mission and the infectious patient's high likelihood of survival during the COVID-19 pandemic.

Gestión de enfermeras/os especializados en la aeroevacuación de pacientes críticos altamente infecciosos, durante la pandemia por COVID-19. Revisión Sistemática / Management of nurses specialized in the aero-evacuation of highly infectious critical patients, during the COVID-19 pandemic. Systematic review

Introducción: Las misiones de Evacuación Aeromédica de Paciente Crítico Altamente Infeccioso de paciente COVID-19, consideran múltiples factores, es por eso que la planificación, es la estructura fundamental de la preparación de la misión. La gestión de enfermeras/os especializados es transversal, ya que participa en gran parte en la planificación, organización y la aplicación de protocolos de aeroevacuación, ejecución de procedimientos asistenciales y de seguridad operacional durante toda la operación, con una Tripulación Aerosanitaria integrada trabajando en equipo junto a la tripulación aérea. Objetivo: Analizar la gestión de enfermeras/os especializados en la aeroevacuación de pacientes críticos altamente infecciosos, durante la pandemia por COVID-19. Diseño: Mediante una búsqueda sistemática de la literatura biomédica, este estudio se realiza según normas del manual Cochrane para las revisiones sistemáticas de las intervenciones y PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses). La búsqueda bibliográfica incluye artículos publicados desde el 2019 hasta agosto del 2020 y se utiliza metabuscadores, de lo cual se obtiene un total de 142 artículos, se realiza una triangulación de la información. Finalmente 11 artículos se incluyen en la revisión, y la validez de cada uno de ellos fue determinada de acuerdo con las directrices publicadas por el nivel de evidencia de Joanna Briggs. Resultados y discusión: La revisión sistemática evidencia 11 estudios que utilizan diferentes consideraciones metodológicas para la realización de una evacuación aeromédica considerando aspectos claves para una operación exitosa. Conclusión: La gestión de enfermeras/os especializados tiene un impacto directo en el proceso de Evacuación Aeromédica de Paciente Crítico Altamente Infeccioso, en diversos aspectos, como lo es la planificación, organización y seguridad operacional, aplicada en la instrucción...(AU)

Introduction: Aeromedical evacuation missions to transport highly infectious critical COVID-19 patients involve multiple factors, therefore planning is essential in their preparation. The management of specialist nurses is cross-cutting, as they participate in the planning, organisation and implementation of aero-evacuation protocols, delivery of care and operational safety procedures throughout the operation, with an integrated aeromedical crew working as a team alongside the air crew. Objective: To study the management of nurses specialised in the aero-evacuation of highly infectious critical patients during the COVID-19 pandemic. Design: Through a systematic search of the biomedical literature, this study was conducted according to the standards of the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA. The literature search included articles published from 2019 to August 2020 and meta-search engines, yielding a total of 142 articles, and a triangulation of information was performed. A total of 11 articles were eventually included in the review, and the validity of each article was determined according to the guidelines of the Joanna Briggs Institute level of evidence. Results and discussion: The systematic review identified 11 studies that use different methodological considerations for conducting an aeromedical evacuation and covering key aspects for a successful operation. Conclusion: The management of specialist nurses has a direct impact on the aeromedical evacuation of the critical patient. It covers planning, organisation, and operational safety, applied in the instruction, training, execution and strict monitoring of the work of the aeromedical crew as a solid team. This contributes to the success of the aero-evacuation mission and the infectious patient's high likelihood of survival during the COVID-19 pandemic.(AU)

[«Management of nurses specialized in the aero-evacuation of highly infectious critical patients, during the COVID-19 pandemic. Systematic review¼]. / «Gestión de enfermeras/os especializados en la aeroevacuación de pacientes críticos altamente infecciosos, durante la pandemia por COVID-19. Revisión Sistemática¼.

Introduction: Aeromedical evacuation missions to transport highly infectious critical COVID-19 patients involve multiple factors, therefore planning is essential in their preparation. The management of specialist nurses is cross-cutting, as they participate in the planning, organisation and implementation of aero-evacuation protocols, delivery of care and operational safety procedures throughout the operation, with an integrated aeromedical crew working as a team alongside the air crew. Objective: To study the management of nurses specialised in the aero-evacuation of highly infectious critical patients during the COVID-19 pandemic. Design: Through a systematic search of the biomedical literature, this study was conducted according to the standards of the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA. The literature search included articles published from 2019 to August 2020 and meta-search engines, yielding a total of 142 articles, and a triangulation of information was performed. A total of 11 articles were eventually included in the review, and the validity of each article was determined according to the guidelines of the Joanna Briggs Institute level of evidence. Results and discussion: The systematic review identified 11 studies that use different methodological considerations for conducting an aeromedical evacuation and covering key aspects for a successful operation. Conclusion: The management of specialist nurses has a direct impact on the aeromedical evacuation of the critical patient. It covers planning, organisation, and operational safety, applied in the instruction, training, execution and strict monitoring of the work of the aeromedical crew as a solid team. This contributes to the success of the aero-evacuation mission and the infectious patient's high likelihood of survival during the COVID-19 pandemic.

In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-ß1-induced collagen gel contraction.

Cardiac fibroblasts (CF) play a key role in the homeostasis of the extracellular matrix in cardiac tissue and are newly recognized as inflammatory supporter cells. Besides, CF-to-Cardiac myofibroblast differentiation is commanded by TGF-b, through SMAD signaling pathways, and these last cells are strongly implicated in cardiac fibrosis. In the heart IFN-ß is produced by CF; however, the role of IFN-ß, STAT proteins, and STAT-homo or heterodimers in the regulation of CF function with or without a fibrotic environment is unknown. CF were isolated from hearts of adult rats, and by western blot analysis we studied STAT1, STAT2, and STAT3 phosphorylation and through specific siRNA against these proteins we analyzed their role in CF functions such as differentiation (α-SMA expression); and pro-collagen type-I synthesis and secretion expression levels; collagen gels contraction and CF migration. In cultured adult rats CF, IFN-ß increases phosphorylation of STAT1, STAT2, and STAT3. Both STAT1 and STAT2 were involved in decreasing α-SMA and CF migration induced by TGF-ß1. Also, IFN-ß through STAT1 regulated pro-collagen type-I protein expression levels, and collagen gels contraction induced by TGF-ß1. STAT3 was not involved in any effects of IFN-ß studied. In conclusion, IFN-ß through STAT1 and STAT2 shows antifibrotic effects on CF TGF-ß1-treated, whereas STAT3 did not participate in such effect.

TGF-ß1 decreases CHOP expression and prevents cardiac fibroblast apoptosis induced by endoplasmic reticulum stress.

Transforming growth factor-beta 1 (TGF-ß1) is a cytokine with marked pro-fibrotic action on cardiac fibroblasts (CF). TGF-ß1 induces CF-to-cardiac myofibroblast (CMF) differentiation, defined by an increase in α-smooth muscle cells (α-SMA), collagen secretion and it has a cytoprotective effect against stimuli that induce apoptosis. In the Endoplasmic Reticulum (ER) lumen, misfolded protein accumulation triggers ER stress and induces apoptosis, and this process plays a critical role in cell death mediated by Ischemia/Reperfusion (I/R) injury and by ER stress inducers, such as Tunicamycin (Tn). Here, we studied the regulation of CHOP, a proapoptotic ER-stress-related transcription factor in CF under simulated I/R (sI/R) or exposed to Tn. Even though TGF-ß1 has been shown to participate in ER stress, its regulatory effect on CF apoptosis and ER stress-induced by sI/R or TN has not been evaluated yet. CF from neonatal rats were exposed to sI/R, and cell death was evaluated by cell count and apoptosis by flow cytometry. ER stress was assessed by western blot against CHOP. Our results evidenced that sI/R (8/24) h or Tn triggers CF apoptosis and an increase in CHOP protein levels. TGF-ß1 pre-treatment partially prevented apoptosis induced by sI/R or Tn. Furthermore, TGF-ß1 pre-treatment completely prevented CHOP increase by sI/R or Tn. Additionally, we found a decrease in α-SMA expression induced by sI/R and in collagen secretion induced by Tn, which were not prevented by TGF-ß1 treatment. In conclusion, TGF-ß1 partially protects CF apoptosis induced by sI/R or Tn, through a mechanism that would involve ER stress.

Experiencia clínica del manejo anestésico en craneotomía vigil / Clinical experience of anesthetic management of Awake Craniotomy

OBJECTIVES: Describe the demographic characteristics of patients undergoing awake craniotomy, which are the anesthetic techniques and most commonly used drugs, as well as to identify the type and frequency of anesthetic and surgical complications. MATERIAL AND METHODS: Perioperative awake craniotomy records were reviewed in the operating room. All cases of patients with gliomas in which the need for cortical mapping was determined between november 2015 and august 2018 were included. Of a total of 27 operated patients, data were collected for 18 surgeries. RESULTS: Two thirds of the patients were men and one third were women. The average age was 42 years. 39% of the patients presented overweight, being obese by 28%. The most used anesthetic technique was asleep-awake-asleep in 56% of the cases, the rest was under conscious sedation. In all cases, remifentanil and propofol were used, in addition to the scalp block. Intraoperative complications are described in two patients and new-onset neurological deficit in seven patients. There was no conversion to general anesthesia in any case. CONCLUSIONS: Awake craniotomy remains the gold standard for the surgical management of brain tumors in eloquent areas. It is a challenge that requires clear communication with the patient and between the team. We share the experience of our center, with favorable results for patients.

OBJETIVOS: Describir las características demográficas de los pacientes sometidos a craneotomía vigil, cuáles son las técnicas anestésicas y fármacos más utilizados, además de identificar el tipo y frecuencia de complicaciones anestésicas y quirúrgicas. MATERIAL Y MÉTODOS: Se revisaron los registros perioperatorios de craneotomía vigil en pabellón. Fueron incluidos todos los casos de pacientes con gliomas en que se determinó la necesidad de mapeo cortical entre noviembre de 2015 y agosto de 2018. De un total de 27 pacientes operados se recolectaron datos para 18 cirugías. RESULTADOS: Dos tercios de los pacientes fueron hombres y un tercio mujeres. El promedio de edad fue de 42 años. Un 39% de los pacientes presentaron exceso de peso, siendo obesos en un 28%. La técnica anestésica más usada fue dormido-despierto-dormido en 56% de los casos, el resto fue bajo sedación consciente. En todos los casos se usó remifentanilo y propofol, además, del bloqueo pericráneo. Se describen complicaciones intraoperatorias en dos pacientes y déficit neurológico de nueva aparición en siete pacientes. No hubo conversión a anestesia general en ningún caso. CONCLUSIONES: La craneotomía vigil permanece como el estándar de oro del manejo quirúrgico de los tumores cerebrales en áreas elocuentes. Es un desafío que requiere de comunicación clara con el paciente y entre el equipo. Compartimos la experiencia de nuestro centro, con resultados favorables a los pacientes.

Percepción de la vivencia del acceso oportuno al diagnóstico del VIH, en personas viviendo con VIH/SIDA: Acceso oportuno al test de VIH / Perceptions about the elisa test of people diagnosed at the aids stage

Background: The delay in the diagnosis of AIDS results in higher treatment costs. Aim: To reveal the experiences of people who were diagnosed in the AIDS stage about the access to the ELISA test. Material and Methods: In depth interviews were carried out to 15 participants from public hospitals who were in the AIDS stage at the moment of the diagnosis. The main questions asked were about the motivations to take the test, the barriers found and the help received from the health care personnel. All interviews were recorded and analyzed according to Kripperdorff. Results: The three categories that emerged were the motivations to take the test, the facilitators found and the difficulties to access to the test. The main motivation was a condition of vulnerability due to the suspicion or certainty of being infected. The main facilitator was the sensation of being accepted and not discriminated. The main difficulties were the fear of having a positive test and of being discriminated and the lack of information. Conclusions: Knowing these experiences will help to improve the early detection of HIV infections.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

BACKGROUND: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. METHODS: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. RESULTS: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.

[Perceptions about the elisa test of people diagnosed at the aids stage]. / Percepción de la vivencia del acceso oportuno al diagnóstico del VIH, en personas viviendo con VIH/SIDA: Acceso oportuno al test de VIH.

BACKGROUND: The delay in the diagnosis of AIDS results in higher treatment costs. AIM: To reveal the experiences of people who were diagnosed in the AIDS stage about the access to the ELISA test. MATERIAL AND METHODS: In depth interviews were carried out to 15 participants from public hospitals who were in the AIDS stage at the moment of the diagnosis. The main questions asked were about the motivations to take the test, the barriers found and the help received from the health care personnel. All interviews were recorded and analyzed according to Kripperdorff. RESULTS: The three categories that emerged were the motivations to take the test, the facilitators found and the difficulties to access to the test. The main motivation was a condition of vulnerability due to the suspicion or certainty of being infected. The main facilitator was the sensation of being accepted and not discriminated. The main difficulties were the fear of having a positive test and of being discriminated and the lack of information. CONCLUSIONS: Knowing these experiences will help to improve the early detection of HIV infections.

Buoyancy effects on the scaling characteristics of atmospheric boundary-layer wind fields in the mesoscale range.

We have analyzed long-term wind speed time series from five field sites up to a height of 300 m from the ground. Structure function-based scaling analysis has revealed that the scaling exponents in the mesoscale regime systematically depend on height. This anomalous behavior is likely caused by the buoyancy effects. In the framework of the extended self-similarity, the relative scaling exponents portray quasiuniversal behavior.

Barreras percibidas por los usuarios para acceder al test de Elisa para VIH / Uncovering the perceived barriers of users to access to test for HIV Elisa test

Objetivo: Develar las barreras percibidas por los usuarios con serología desconocida para acceder al test de Elisa, para el diagnóstico de VIH a nivel de Atención Primaria de Salud. Material y método: Estudio cualitativo descriptivo exploratorio en el que se realizaron 30 entrevistas en profundidad a usuarios con serología desconocida para Virus de la Inmunodeficiencia Humana (VIH) de dos centros de salud, quienes solicitaron el examen por iniciativa propia. Las entrevistas fueron grabadas y transcritas textualmente, con previo consentimiento de los participantes. El análisis de contenido se realizó según Kripperdorff y se cumplieron los criterios de rigor según Guba y Lincoln. Resultados: Del análisis emergieron 3 dimensiones que corresponden a las barreras: Temor por la connotación negativa del examen del VIH, escasa información entregada por el personal de los centros y burocracia en el proceso de toma del examen del VIH. Conclusión: Las barreras percibidas por los usuarios aparecen desde sus propios temores y de aspectos administrativos de los centros de salud, dificultando el acceso voluntario a la toma del examen del VIH.

Objective: Reveal the perceived barriers by users with unknown serology to access the Elisa test for HIV diagnosis. Method: A qualitative and descriptive study was undertaken through 30 in depth interviews to patients with unknown HIV status of two primary health care centers, which ones had request the test by themselves. The interviews were audiotaped and transcribed verbatim after gaining the consent of the participants. The content analysis was performed according to Kripperdorff and was ensured the rigor criterion according Guba and Lincoln. Results: Three dimensions were identified through content analysis that correspond to the barriers: Fear for negative connotation of HIV test, Limited information provided by the center staff and Bureaucracy in the process of taking the HIV test. Conclusion: The barriers perceived for the patients appears by their own fears and by administrative aspects of the health centers, making difficult the voluntary access to undertake the HIV screening test.

Cardiac fibroblasts as sentinel cells in cardiac tissue: Receptors, signaling pathways and cellular functions.

Cardiac fibroblasts (CF) not only modulate extracellular matrix (ECM) proteins homeostasis, but also respond to chemical and mechanical signals. CF express a variety of receptors through which they modulate the proliferation/cell death, autophagy, adhesion, migration, turnover of ECM, expression of cytokines, chemokines, growth factors and differentiation into cardiac myofibroblasts (CMF). Differentiation of CF to CMF involves changes in the expression levels of various receptors, as well as, changes in cell phenotype and their associated functions. CF and CMF express the ß2-adrenergic receptor, and its stimulation activates PKA and EPAC proteins, which differentially modulate the CF and CMF functions mentioned above. CF and CMF also express different levels of Angiotensin II receptors, in particular, AT1R activation increases collagen synthesis and cell proliferation, but its overexpression activates apoptosis. CF and CMF express different levels of B1 and B2 kinin receptors, whose stimulation by their respective agonists activates common signaling transduction pathways that decrease the synthesis and secretion of collagen through nitric oxide and prostacyclin I2 secretion. Besides these classical functions, CF can also participate in the inflammatory response of cardiac repair, through the expression of receptors commonly associated to immune cells such as Toll like receptor 4, NLRP3 and interferon receptor. The activation by their respective agonists modulates the cellular functions already described and the release of cytokines and chemokines. Thus, CF and CMF act as sentinel cells responding to a plethora of stimulus, modifying their own behavior, and that of neighboring cells.

H2 O2 activates matrix metalloproteinases through the nuclear factor kappa B pathway and Ca(2+) signals in human periodontal fibroblasts.

BACKGROUND: The mechanisms involved in reactive oxygen species and matrix metalloproteinase (MMP)-mediated periodontal tissue breakdown are unknown. OBJECTIVE: To determine the effect of H2 O2 in MMP-2 and MMP-9 activity, and the involvement of nuclear factor kappa B (NFκB) and Ca(2+) -mediated signals in human periodontal ligament fibroblasts. MATERIAL AND METHODS: Primary cultures were characterized for their phenotype and exposed for 24 h to sublethal doses (2.5-10 µm) of H2 O2 or control media. NFκB involvement was evaluated through immunofluorescence of p65 subunit, using the NFκB blocking peptide SN50 and catalase. Ca(2+) signals were analyzed by loading the cells with Fluo4-AM and recording the fluorescence changes in a confocal microscope before and after the addition of H2 O2 . 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl was used to chelate intracellular Ca(2+) . The activity and levels of MMP-2 and MMP-9 were analyzed by gelatin zymogram and densitometric scanning, and enzyme-linked immunosorbent assay, respectively. Statistical analysis was performed with stata V11.1 software using the ANOVA test. RESULTS: H2 O2 at concentrations of 2.5-5 µm induced Ca(2+) signaling and NFκB subunit p65 nuclear translocation, whereas catalase, SN50 and BAPTA-AM prevented p65 nuclear translocation. H2 O2 at 2.5-5 µm significantly increased MMP-9 and MMP-2 activity, while SN50 resulted in lower MMP-2 and MMP-9 activity rates compared with controls. CONCLUSION: Sublethal H2 O2 induces Ca(2+) -dependent NFκB signaling with an increase in MMP gelatinolytic activity in human periodontal ligament.

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).

AIMS: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment. METHODS AND RESULTS: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries. CONCLUSION: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.

4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast.

Cardiac fibroblast (CF) survival is important for the maintenance of the extracellular matrix homeostasis in the heart; providing a functional support to cardiomyocytes necessary for the correct myocardial function. Endoplasmic reticulum (ER) stress causes cellular dysfunction and cell death by apoptosis; and thapsigargin is a well-known ER stress inducer. On the other hand, the chemical chaperone, 4-phenylbutyric acid (4-PBA) had showed to prevent ER stress; however, in cardiac fibroblast both the ER stress induced by thapsigargin and prevention by 4-PBA, have not been studied in detail. Neonate rat CF were treated with thapsigargin in presence or absence of 4-PBA, and cell viability was evaluated by trypan blue exclusion and apoptosis by flow cytometry; whereas CHOP, BIP, PDI, ATF4 and procollagen protein levels were assessed by western blot. In CF, thapsigargin triggered the unfolded protein response detected by early increases in ATF4, CHOP, PDI and BIP protein levels as well as, the accumulation of intracellular procollagen. Thapsigargin also stimulated CF death in a time and concentration-dependent manner. ER stress, CF death and apoptosis induced by thapsigargin were prevented by 4-PBA. Conclusion our data suggest that 4-PBA prevent ER stress, intracellular procollagen accumulation, CF death and apoptosis induced by thapsigargin.

[Identification of educational needs among patients with HIV and their health care providers]. / Necesidades educativas de un grupo de personas viviendo con VIH: diagnóstico basado en la perspectiva de los usuarios y de los profesionales que los atienden.

BACKGROUND: The success of educational interventions depends on the integration of educational programs into clinical practice. AIM: To determine the educational needs and perceived barriers of people living with HIV (PHIV) and their health care providers (HCP). MATERIAL AND METHODS: Qualitative study conducted in 60 PHIV and 10 HCP. For data collection, a semi-structured in-depth interview was applied, addressing the educational needs (content, methodology, person, time, physical location) and identified barriers to implement an educational program for PHIV Content analysis technique was used for data analysis. RESULTS: PHIV and their HCP identified the same educational needs as the following: general-related content, psychological, sexual and secondary prevention aspects of the disease. Individual sessions with written material and web pages were identified as important resources to support education. Both PHIV and professionals expressed their willingness to participate in educational programs, but the most commonly identified barrier was lack of time. CONCLUSIONS: This study identifies the key elements to include in an educational program for Chilean PHIV from the user and professional perspective.

Necesidades educativas de un grupo de personas viviendo con VIH: diagnóstico basado en la perspectiva de los usuarios y de los profesionales que los atienden / Identification of educational needs among patients with HIV and their health care providers

Background: The success of educational interventions depends on the integration of educational programs into clinical practice. Aim: To determine the educational needs and perceived barriers of people living with HIV (PHIV) and their health care providers (HCP). Material and Methods: Qualitative study conducted in 60 PHIV and 10 HCP. For data collection, a semi-structured in-depth interview was applied, addressing the educational needs (content, methodology, person, time, physical location) and identified barriers to implement an educational program for PHIV Content analysis technique was used for data analysis. Results: PHIV and their HCP identified the same educational needs as the following: general-related content, psychological, sexual and secondary prevention aspects of the disease. Individual sessions with written material and web pages were identified as important resources to support education. Both PHIV and professionals expressed their willingness to participate in educational programs, but the most commonly identified barrier was lack of time. Conclusions: This study identifies the key elements to include in an educational program for Chilean PHIV from the user and professional perspective.

Descripción de la función sexual en mujeres con alteraciones de piso pélvico en un hospital público de Santiago / Sexual function of a group of women with any pelvic floor disorder in a public hospital of Santiago, Chile

Antecedentes: Se estima que entre 25-50 por ciento de las mujeres sufrirá de alguna alteración del piso pélvico durante su vida. La función sexual es un concepto complejo y multidimensional. Se ha planteado que a mayor sintomatología de alteraciones de piso pélvico, las mujeres presentan mayores inconvenientes en su respuesta sexual. Objetivo: Describir la función sexual de un grupo de mujeres que presentan algún tipo de trastorno de piso pélvico. Método: Estudio descriptivo a 195 mujeres con diagnóstico de alteraciones de piso pélvico utilizando un cuestionario que incluía evaluación de aspectos sociodemográficos y de la función sexual con instrumento PISQ-12. Para el análisis se utilizaron medidas de tendencia central y dispersión. Resultados: 73,7 por ciento de las mujeres refieren tener algún grado de insatisfacción con su vida sexual actual afectando principalmente el área del deseo sexual. Dentro de las limitaciones en la relación sexual reportadas se encuentran: orgasmos menos frecuentes (70,5 por ciento), dispareunia (89,5 por ciento), problemas de erección (40 por ciento) y eyaculación precoz (47,4 por ciento) en sus parejas. Conclusión: Las mujeres reportan niveles de insatisfacción con su vida sexual, disminución de su deseo sexual, dolor durante la relación sexual y disminución de la intensidad del orgasmo. Es importante incorporar en la atención de este grupo de mujeres una evaluación sistemática de la función sexual, centrándose no solo en la respuesta sexual femenina, sino que también identificando aquellas limitaciones de la mujer y de la pareja que pueden estar influyendo en su satisfacción sexual.

Background: It is estimated that between 25- 50 percent of women will suffer from a pelvic floor disorder during their lifetime. Sexual function is a complex and multidimensional concept. It has been suggested that to greater symptoms of pelvic floor disorders, women have major problems in sexual response. Objective: To describe the sexual function of a group of women with any pelvic floor disorder in a public hospital of Santiago, Chile. Method: A descriptive study of 195 women diagnosed with pelvic floor disorders using a questionnaire that included assessment of sociodemographic and sexual function instrument PISQ-12. For the analysis used measures of central tendency and dispersion. Results: 73.7 percent of referred women have some degree of dissatisfaction with their current sex life mainly affecting the area of sexual desire. Within the limitations in sexual intercourse reported are: less intense orgasms (70.5 percent), dyspareunia (89.5 percent), erectile dysfunction (40 percent) and premature ejaculation (47.4 percent) in their partners. Conclusion: Women report levels of dissatisfaction with their sex life, decreased sexual desire, pain during intercourse and decreased intensity of orgasm. It is important to incorporate in the care of these women a systematic assessment of sexual function focusing not only on the female sexual response, but also identifying those limitations of women and couples that may be influencing women's sexual satisfaction.

Simvastatin alters fibroblastic cell responses involved in tissue repair.

BACKGROUND AND OBJECTIVE: Statins have been used to control hypercholesterolemia. However, these drugs also exert pleiotropic effects that include the modulation of inflammation and cell signaling. The present study has analyzed the effects of simvastatin on several cell responses involved in tissue repair, including cell adhesion, cell migration and invasion, actin cytoskeleton remodeling and cell viability. MATERIAL AND METHODS: Primary cultures of gingival fibroblasts were stimulated with simvastatin. Cell adhesion was evaluated using a colorimetric assay. Cell spreading was evaluated microscopically. Cell migration and invasion were assessed using a scratch wound-healing assay and a bicameral cell culture system, respectively. Changes in actin cytoskeleton and focal adhesion assembly were evaluated through immunofluorescence for actin, vinculin and active ß1 integrin. Rac activation was evaluated by means of a pull-down assay. Cell viability was assessed using a colorimetric assay that determines mitochondrial functionality. Data analysis was performed using the Mann-Whitney U-test. RESULTS: Simvastatin diminished cell adhesion and spreading over a fibronectin matrix. It also altered the closure of scratch wounds induced on cell monolayers and cell invasion through a Transwell system. Simvastatin-treated cells displayed an altered lamellipodia with poorly developed focal adhesion contacts and reduced levels of ß1 integrin activation. During cell spreading, simvastatin diminished Rac activation. CONCLUSION: The present study shows that simvastatin may alter cell migration by disrupting the cell signaling networks that regulate the actin cytoskeleton dynamics. This mechanism may affect the response of gingival mesenchymal cells during wound healing.