Influence of visceral adiposity on cardiovascular risk in patients with systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic inflammation, endothelial dysfunction, generalized fibrosis and high cardiovascular mortality. The evaluation of cardiovascular risk through the visceral adiposity index (VAI) has been helpful due to its direct relationship to the body and visceral fat percentage. We evaluated the influence of body composition and anthropometrics on cardiovascular risk as measured by VAI in healthy controls (HC) and SSc. An analytical cross-sectional study of 66 participants (33 SSc and 33 HC), mean age 52.7 ± 10, 95% women, was conducted from August 2020 to January 2021. Inclusion criteria in cases were consecutive patients with SSc (ACR/EULAR 2013), 63.6% were diffuse cutaneous (dcSS) subtype, and 36.4 were limited cutaneous (lcSS) subtype. HC was matched by age and gender. Serum lipid profiles and InBody anthropometrics were analyzed and compared. We performed descriptive statistics, bivariate analysis with Student's t, or Mann-Whitney U, correlation and chi-square according to the variable type and distribution. Total cholesterol was significantly higher in SSc than HC (345 vs 194, p = < 0.001). The BMI was higher in HC (26.2 vs 28.9, p < 0.001). Kilograms of muscle (19.8 vs 28.9, p < 0.001) and total fat (23.4 vs 28.9, p < 0.001) were lower in SSc patients compared to HC. VAI was similar when BMI < 25, but significantly higher when BMI > 25 in SSc than in HC (3 vs 1.9, p = 0.030). The increase in BMI at overweight or obese in SSc is associated with a significant increase in cardiovascular risk.

[Prevalence of persistent hypogammaglobulinemia in patients with autoimmune rheumatic disease who received treatment with Rituximab in a national medical center in Mexico]. / Prevalencia de hipogammaglobulinemia persistente en pacientes con enfermedad autoinmune que reciben rituximab en un centro de referencia nacional en México.

OBJECTIVE: To describe the prevalence of persistent hypogammaglobulinemia in patients receiving Rituximab as a treatment for autoimmune rheumatological diseases. METHODS: A transversal, retrospective and unicentric study, carried out in patients with autoimmune rheumatic diseases who were admitted to the Rheumatology service of the Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Mexico City, to receive treatment with rituximab between January 2013 and January 2018. Descriptive and inferential statistics of serum levels of immunoglobulins, clinical-demographic characteristics, diagnosis, and treatment received were performed. RESULTS: from 262 patients with autoimmune rheumatological disease who received treatment with Rituximab; We identified 8 patients with persistent hypogammaglobulinemia (6 women and 2 men), this is a prevalence of 3.1%. No associated factors with the development of hypogammaglobulinemia were identified. CONCLUSIONS: Until now, no associated prognostic or predictive factors have been identified with persistent hypogammaglobulinemia. Additional prospective studies are required to understand more precisely the implications of persistent hypogammaglobulinemia in patients with autoimmune diseases.

OBJECTIVO: Determinar la prevalencia de hipogammaglobulinemia persistente en pacientes con enfermedades reumatológicas autoinmunes que reciben rituximab. MÉTODOS: Estudio trasversal, retrospectivo y unicéntrico, emprendido en pacientes con enfermedades reumatológicas autoinmunes, que acudieron a la Consulta externa del servicio de Reumatología del Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Ciudad de México, entre enero de 2013 y enero de 2018, para recibir tratamiento con rituximab. El análisis de los datos se efectuó con estadística descriptiva e inferencial, para la evaluación de las concentraciones séricas de inmunoglobulinas, características clínico demográficas, diagnóstico y tratamiento. RESULTADOS: Estudio trasversal, retrospectivo y unicéntrico, emprendido en pacientes con enfermedades reumatológicas autoinmunes, que acudieron a la Consulta externa del servicio de Reumatología del Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Ciudad de México, entre enero de 2013 y enero de 2018, para recibir tratamiento con rituximab. El análisis de los datos se efectuó con estadística descriptiva e inferencial, para la evaluación de las concentraciones séricas de inmunoglobulinas, características clínico demográficas, diagnóstico y tratamiento. CONCLUSIONES: Hasta el momento no se han identificado factores asociados, pronósticos o predictivos, con hipogammaglobulinemia persistente. Se requieren estudios prospectivos adicionales para conocer con mayor precisión las implicaciones de la hipogammaglobulinemia persistente en pacientes con enfermedades autoinmunes.

Real-time inference in communication across cultures: Evidence from a nonindustrialized society.

In everyday communication, speakers and listeners make sophisticated inferences about their conversation partner's intended meaning. They combine their knowledge of the visuospatial context with reasoning about the other person's knowledge state and rely on shared assumptions about how language is used to express communicative intentions. However, these assumptions may differ between languages of nonindustrialized-where conversations often primarily take place within a, so-called, society of intimates-and industrialized cultures-societies of strangers. Here, we study inference in communication in the Tsimane', an indigenous people of the Bolivian Amazon, who have little contact with industrialization or formal education. Using a referential communication task, we probe how Tsimane' speakers refer to objects in the world around them when there are potential ambiguities (e.g., referring to a cup when there are multiple cups in view) across different visual contexts. Using an eye-tracking task, we probe the real-time inferences that Tsimane' listeners make about the speaker's intentions. We find that Tsimane' speakers use visual (color, size) contrasts to disambiguate referents (e.g., "Hand me the small cup"), much like English speakers, and they predictively direct their gaze to objects in a contrast set when they hear a modifier (e.g., "small"). Despite myriad cultural and linguistic dissimilarities between the two populations, the qualitative patterns of behavior and eye-gaze of Tsimane' and English speakers were strikingly similar, suggesting that the communicative expectations underlying many everyday inferences may be shared across cultures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mechanisms of Action of the Peptide Toxins Targeting Human and Rodent Acid-Sensing Ion Channels and Relevance to Their In Vivo Analgesic Effects.

Acid-sensing ion channels (ASICs) are voltage-independent H+-gated cation channels largely expressed in the nervous system of rodents and humans. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly pH-dependent gating properties. This review provides an update on the pharmacological profiles of animal peptide toxins targeting ASICs, including PcTx1 from tarantula and related spider toxins, APETx2 and APETx-like peptides from sea anemone, and mambalgin from snake, as well as the dimeric protein snake toxin MitTx that have all been instrumental to understanding the structure and the pH-dependent gating of rodent and human cloned ASICs and to study the physiological and pathological roles of native ASICs in vitro and in vivo. ASICs are expressed all along the pain pathways and the pharmacological data clearly support a role for these channels in pain. ASIC-targeting peptide toxins interfere with ASIC gating by complex and pH-dependent mechanisms sometimes leading to opposite effects. However, these dual pH-dependent effects of ASIC-inhibiting toxins (PcTx1, mambalgin and APETx2) are fully compatible with, and even support, their analgesic effects in vivo, both in the central and the peripheral nervous system, as well as potential effects in humans.

Heart transplantation at the Peruvian National Heart Institute: One-decade single-center experience.

BACKGROUND: Heart transplantations are ideal for most patients with end-stage heart failure refractory to medical treatment. The transplantation program at the Peruvian National Heart Institute started with a 10-year continuity in 2010. OBJECTIVE: To compare our 10-year heart transplantation experience results with international standards and reflect on our Transplant Program. METHODS: We studied 83 patients who underwent orthotopic heart transplantation at a single center between January 2010 and December 2019. The recipients' profiles and survival rates were analyzed according to sex and age group, ensuring the information's confidentiality. RESULTS: The recipients' mean age was 41.2 ± 17 years, 88% were adults, and 68.7% were male. The main indications for transplantation were idiopathic dilated cardiomyopathy. 85.5% of recipients were clinically categorized as INTERMACS profiles 1-3 before transplantation. There was a significant difference between sexes regarding the preoperative left ventricular ejection fraction and between age groups regarding the waiting time. The average ischemia time was 3.1 h, operating time was 6.1 h, cardiopulmonary bypass time was 3 h, and aortic cross-clamp time was 1.7 h. The principal early postoperative complications were hematological disorders and acute kidney failure. The principal late ones were kidney failure and severe anemia. The postoperative mortality was 15.9%, and the principal causes were infection and then acute rejection. The survival at 1, 5, and 10 years was 87.5%, 79.8%, and 79.8%, respectively. The survival results were not influenced by sex or age group. CONCLUSION: Our patients' postoperative complications, mortality, and survival rates coincided with those reported by the ISHLT registry.

Can the SARS-CoV-2 infection trigger systemic lupus erythematosus? A case-based review.

Systemic lupus erythematosus (SLE) is an autoimmune and multisystemic chronic inflammatory disease that can affect various organs, including skin, joints, kidneys, lungs and the nervous system. Infectious agents have long been implicated in the pathogenesis of SLE. The new viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown that, in genetically predisposed patients could trigger the presentation or exacerbation of the autoimmune disease. We herein report a case of a 45-year-old man who presented respiratory symptoms, bilateral pleural effusion, ascites, splenomegaly, severe thrombocytopenia and renal failure with proteinuria and hematuria. SARS-CoV-2 PCR confirmed the COVID-19 diagnosis. We diagnosed the patient with SLE based on the clinical manifestations and positive immunological markers (2019 European League Against Rheumatism/American College of Rheumatology, score of 18). Glucocorticoid pulses were administered to the patient, which improved renal function. However, thrombocytopenia was also refractory to IV immunoglobulin and rituximab, so the patient underwent splenectomy. Through a systematic search of the medical literature, we retrieved two cases with newly onset SLE and five cases with previous SLE diagnosis that showed activity of the disease due to SARS-CoV-2 infection. We herein present a systemic review of these cases and discuss the clinical manifestations that could help to the diagnosis of this clinical condition.

Mambalgin-1 pain-relieving peptide locks the hinge between α4 and α5 helices to inhibit rat acid-sensing ion channel 1a.

Acid-sensing ion channels (ASICs) are proton-gated cationic channels involved in pain and other processes, underscoring the potential therapeutic value of specific inhibitors such as the three-finger toxin mambalgin-1 (Mamb-1) from snake venom. A low-resolution structure of the human-ASIC1a/Mamb-1 complex obtained by cryo-electron microscopy has been recently reported, implementing the structure of the chicken-ASIC1/Mamb-1 complex previously published. Here we combine structure-activity relationship of both the rat ASIC1a channel and the Mamb-1 toxin with a molecular dynamics simulation to obtain a detailed picture at the level of side-chain interactions of the binding of Mamb-1 on rat ASIC1a channels and of its inhibition mechanism. Fingers I and II of Mamb-1 but not the core of the toxin are required for interaction with the thumb domain of ASIC1a, and Lys-8 of finger I potentially interacts with Tyr-358 in the thumb domain. Mamb-1 does not interfere directly with the pH sensor as previously suggested, but locks by several contacts a key hinge between α4 and α5 helices in the thumb domain of ASIC1a to prevent channel opening. Our results provide an improved model of inhibition of mammalian ASIC1a channels by Mamb-1 and clues for further development of optimized ASIC blockers.

Percutaneous endovascular management of ascending aortic pseudoaneurysm after heart transplantation in a pediatric patient.

Ascending aortic pseudoaneurysm is a rare complication after HT. Surgery is the most conventional management, but in some patients, it is risky. We report the case of a ten-year-old child who underwent HT and developed an ascending aortic pseudoaneurysm in the aortic anastomosis. He was successfully treated with two covered stents through endovascular management. Endovascular therapy is an alternative management in high-risk patients. To our knowledge, this is the first report about endovascular therapy of an AAP after HT in a pediatric patient.

Brigatinib in ALK-positive non-small cell lung cancer: real-world data in the Latin American population (Bri-world extend CLICaP).

Background: Brigatinib has demonstrated its efficacy as first-line therapy and in further lines for ALK-positive non-small cell lung cancer (NSCLC) patients; however, real-world data in Latin America are scarce. Methods: From January 2018 to March 2020, 46 patients with advanced ALK-positive NSCLC received brigatinib as second or further line of therapy in Mexico and Colombia. The primary end point was progression-free survival (PFS); secondary end point was time to treatment discontinuation (TTD). Results: At a median follow-up of 9.3 months, the median PFS was 15.2 months (95% CI: 11.6-18.8), and TTD was 18.46 months (95% CI: 9.54-27.38). The estimated overall survival at 12 months was 80%. Safety profile was consistent with previously published data. Conclusion: Brigatinib is an effective treatment for previously treated ALK-positive NSCLC patients in a real-world setting.

Locoregional control and toxicity after pleurectomy/decortication and intensity-modulated pleural radiation therapy in patients with malignant pleural mesothelioma.

BACKGROUND: Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM. METHODS: We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields. RESULTS: A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months. CONCLUSIONS: Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.

Disponibilidad de cirujanos cardiovasculares pediátricos en el Perú en el año 2019 / Availability of pediatric cardiovascular surgeons in Peru in 2019

RESUMEN Objetivo: describir la disponibilidad de los cirujanos cardiovasculares pediátricos e identificar los factores que influyen en la situación de la certificación de esta subespecialidad en el Perú. Materiales y métodos: estudio transversal y descriptivo. Se realizó un muestreo por bola de nieve discriminatorio exponencial partiendo de los cirujanos cardiovasculares pediátricos que trabajan en el Instituto Nacional Cardiovascular hacia abril, 2019. Se solicitó su participación y posteriormente se aplicaron encuestas virtuales. Los datos recolectados de las preguntas cerradas se procesaron con estadísticos descriptivos y los de las preguntas abiertas, en base a su sistematización, orden y relación, obteniéndose así las conclusiones. Resultados: se encuestó a 20 cirujanos. De ellos, 5 refirieron haber estudiado la subespecialidad, teniendo como principales motivaciones una rotación durante el pregrado o la especialidad, y la vocación quirúrgica. Los tres subespecialistas certificados refirieron haberlo realizado debido al deseo de formalizar su práctica quirúrgica en el Perú y los otros dos refirieron no haberlo realizado por falta de tiempo. Asimismo, 11 cirujanos manifestaron el deseo de certificarse. Por otro lado, 17 encuestados refirieron que el Perú necesita más subespecialistas. Conclusión: existe una carencia de oferta de cirujanos cardiovasculares pediátricos en el Perú, lo cual muestra la necesidad de un aumento de las plazas para la subespecialidad; además, aumentar, mejorar y articular los centros resolutivos.

ABSTRACT Objective: to describe availability of pediatric cardiovascular surgeons and to identify factors influencing accreditation for this specialty in Peru. Materials and methods: this is a cross-sectional and descriptive study. A discriminating exponential snowball sampling procedure was performed in pediatric cardiovascular surgeons working in the Peruvian National Cardiovascular Institute. This was carried out in April 2019. Their participation was requested and virtual surveys were carried out. Data collected from closed questions were processed using descriptive statistics. Data from open questions were processed on the basis of their systematization, order, and relationship, so conclusions could be drawn. Results: twenty surgeons were surveyed. Of them, 5 reported having had training for their subspecialty, and they declared their main motivation was having undergone a training period during pregraduate or specialty studies, as well as their interest in surgery. Three accredited subspecialists declared they wanted to formalize their practice in Peru, and the other two declared not having formalized their training because of lack of time. Also, eleven surgeons expressed their desire for achieving accreditation. On the other hand, seventeen surveyed professionals declared that Peru requires more subspecialists. Conclusion: there is lack of pediatric cardiovascular surgeons in Peru; so increasing posts for such subspecialists is necessary, and also there is an urgent need for increasing, improving, and articulating specialized centers.

Molecular weight distribution of the recalcitrant organic matter contained in kraft mill effluents and the identification of microbial consortia responsible for an anaerobic biodegradable fraction.

The objective of this research was to evaluate the distribution of the molecular weights of the recalcitrant organic matter contained in kraft mill effluents and identify microbial consortia responsible for an anaerobic biodegradable fraction. As a result, the average removal efficiencies of chemical organic demand (COD) and biological oxygen demand (BOD5) during the entire period of operation were 28% and 53%, respectively. The non-biodegradable organic matter was detected at molecular weights less than 1000 Da. However, most of the organic matter was in the molecular weight fraction higher than 10000 Da with 32 ± 11.6% COD as well as color (42.3 ± 8.7%), total phenolic compounds (35.9 ± 7.9%) and adsorbable organic compounds (AOX) (13.0 ± 2.7%). Methanogenic acetoclastic archaea of the genera Methanomethylovorans and Methanosarcina were found in the surface and middle zones of the reactor. Moreover, Methanosaeta and Methanolinea were identified in the low zone of the reactor. In all zones of the reactor, Desulfomicrobium and Desulfovibrio were found to be the most dominant genera of sulfate-reducing bacteria (SRB).

Evaluation of medical ethics competencies in rheumatology: local experience during national accreditation process.

INTRODUCTION: Rheumatologists are the primary healthcare professionals responsible for patients with rheumatic diseases and should acquire medical ethical competencies, such as the informed consent process (ICP). The objective clinical structured examination is a valuable tool for assessing clinical competencies. We report the performance of 90 rheumatologist trainees participating in a station designed to evaluate the ICP during the 2018 and 2019 national accreditations. METHODS: The station was validated and represented a medical encounter in which the rheumatologist informed a patient with systemic lupus erythematosus with clinically active nephritis about renal biopsy. A trained patient-actor and an evaluator were instructed to assess ICP skills (with a focus on kidney biopsy benefits, how the biopsy is done and potential complications) in obtaining formal informed consent, delivering bad news and overall communication with patients. The evaluator used a tailored checklist and form. RESULTS: Candidate performance varied with ICP content and was superior for potential benefit information (achieved by 98.9% of the candidates) but significantly reduced for potential complications (37.8%) and biopsy description (42.2%). Only 17.8% of the candidates mentioned the legal perspective of ICP. Death (as a potential complication) was omitted by the majority of the candidates (93.3%); after the patient-actor challenged candidates, only 57.1% of them gave a clear and positive answer. Evaluators frequently rated candidate communications skills as superior (≥80%), but ≥1 negative aspect was identified in 69% of the candidates. CONCLUSIONS: Ethical competencies are mandatory for professional rheumatologists. It seems necessary to include an ethics competency framework in the curriculum throughout the rheumatology residency.

Probiotics' effectiveness on symptoms, histological features and feeding tolerance in ulcerative colitis / Efectividad de probióticos sobre síntomas, histología y tolerancia alimentaria en colitis ulcerativa

Background: Probiotics have been used in the adjuvant treatment of Ulcerative Colitis (UC). Objective: To evaluate the role of a combination of probiotics on the clinical, histological changes and feeding tolerance in patients with UC. Methods: An open UC patients with mild to moderate activity and clinical trial was conducted. Patients were randomized to receive or a combination of 6 strains of probiotics for 3 months while continuing their drug treatment established. UC activity was assessed by Truelove and Witts scale and histological findings by Gupta index. Descriptive statistics, Chi square test and Student t test for comparison of the two groups was performed. Results: In each group 17 patients were included. An improvement was found in the disease activity (52.9% vs. 23.5%, p = 0.07) and in histologic index (82.3% vs. 41.1%, p = 0.03) in patients treated with probiotics compared to the control group. Improved food tolerance was also observed in patients treated with probiotics. Conclusion: The study shows a beneficial short-term effect on symptoms, histological findings and feeding tolerance with the administration of a combination of 6 strains of probiotics in patients with UC.

Introducción: los probióticos han sido utilizados en el tratamiento adyuvante de la colitis ulcerativa (CU). Objetivo: evaluar el papel de una combinación de probióticos sobre las manifestaciones clínicas, cambios histológicos y tolerancia alimentaria en pacientes con CU. Métodos: se realizó un ensayo clínico abierto de pacientes con CU y actividad leve a moderada. Los pacientes se aleatorizaron para recibir, o no, una combinación de 6 cepas de probióticos durante 3 meses, mientras continuaban con el tratamiento farmacológico establecido. Se evaluó la actividad de la CU mediante la escala de Truelove and Witts, y los hallazgos histológicos mediante el índice de Gupta. Se realizó estadística descriptiva, prueba de Chi cuadrada y t de Student para la comparación de ambos grupos. Resultados: se incluyeron 17 pacientes por grupo. Se encontró una mejoría en la actividad de la enfermedad (52.9% frente a 23.5%, p = 0.07) y en el índice histológico (82.3% frente a 41.1%, p = 0.03) en los pacientes tratados con probióticos en comparación con el grupo control. También se observó una mejor tolerancia alimentaria en los pacientes tratados con probióticos. Conclusión: el estudio muestra un efecto benéfico a corto plazo sobre los síntomas, hallazgos histológicos y tolerancia alimentaria con la administración de una combinación de 6 cepas de probióticos en pacientes con CU.

Asociación entre violencia, estrés y rendimiento académico en alumnos de medicina del primer y sexto años de una universidad pública, 2017 / Association between violence, stress and academy performance in 1º and 6º year of medical students of a public university, 2017

Introducción. Existen reportes nacionales e internacionales de presencia de estrés en estudiantes de medicina, mayor que en otras carreras profesionales; asimismo, la presencia de estrés se encuentra relacionada a bajo rendimiento académico. Objetivo. Determinar si existe asociación entre violencia, estrés y el rendimiento académico de los alumnos de primer y sexto año de medicina de la Universidad Nacional Mayor de San Marcos. Métodos. Se encuestó a 109 (47%) alumnos del 6to año, y 122 (53%) alumnos del 1er año. La percepción de violencia y estrés se determinaron con instrumentos validados; el rendimiento académico se determinó mediante el promedio ponderado anual. Se utilizó la prueba U de Mann Whitney para establecer diferencias entre las medias de las variables cuantitativas. Para establecer la correlación entre las variables de estudio se utilizó el coeficiente de correlación de Spearman. Valores p<0,05 se consideraron como significativos. Resultados. La percepción de violencia fue mayor en estudiantes de 6to año. Se estableció correlación positiva entre el estrés y violencia en estudiantes de 6to año. Conclusión. En ambos grupos estudiados se determinó percepción de violencia, mayor en estudiantes de 6to año. La correlación entre violencia y estrés fue significativa sólo en los estudiantes de 6to año. No hubo asociación significativa del estrés y violencia con el rendimiento académico.

Introduction. There are national and international reports of the presence of stress in medical students, higher than in other professional careers; likewise, the presence of stress is related to low academic performance. Objective. To determine if there is an association between violence, stress and the academic performance of the first and sixth year medical students of the National University of San Marcos. Methods. It was surveyed 109 (47%) students of the 6th year, and 122 (53%) students of the 1st year. The perception of violence and stress were determined with validated instruments; academic performance was determined by the annual weighted average. The Mann Whitney U test was used to establish differences between the means of the quantitative variables. To establish the correlation between the study variables, the Spearman correlation coefficient was used. Values p <0,05 were considered significant. Results. The perception of violence was higher in 6th grade students. Positive correlation was established between stress and violence in 6th grade students. Conclusion. In both groups studied, perception of violence was determined, higher in 6th grade students. The correlation between violence and stress was significant only in 6th grade students. There was no significant association of stress and violence with academic performance.

The VEGFA -1154G/A polymorphism is associated with reduced risk of rheumatoid arthritis but not with systemic lupus erythematosus in Mexican women.

BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention. Thus, the present study aimed to determine whether the VEGFA -2578C/A, -1154G/A and -634G/C polymorphisms confer risk or were associated with reduced risk of RA or SLE in a Mexican population. METHODS: The present study included 903 women from Mexico: 405 were patients with RA, 282 had SLE and 216 were healthy individuals. The genotypes were obtained with TaqMan probes. RESULTS: The data obtained in the present study suggest that the VEGFA -2578C/A and -634G/C polymorphisms are not risk factors for RA or SLE; however, VEGFA -1154G/A was associated with reduced risk in women with RA (odds ratio = 0.6, pc  = 0.0051) but not with SLE (odds ratio = 0.7, pc  = 0.13). CONCLUSIONS: The present study is the first to document an association between VEGFA -1154G/A and reduced risk in women with RA but not with SLE.

Pharmacological modulation of Acid-Sensing Ion Channels 1a and 3 by amiloride and 2-guanidine-4-methylquinazoline (GMQ).

Acid-Sensing Ion Channels (ASICs) are cation channels activated by extracellular acidification that emerge as potential pharmacological targets in pain and other neurological disorders. Here, we compare the pharmacological modulation of ASIC1a and ASIC3 channels by amiloride and 2-guanidine-4-methylquinazoline (GMQ), two compounds commonly used for their in vitro and in vivo investigation. We analyzed the effect of amiloride on the pH-dependent activation and inactivation, the relative influence of the extracellular domain and the transmembrane/cytosolic domains on the effect of amiloride and GMQ using chimeras between ASIC1a and ASIC3, and how these compounds potentiate the physiologically relevant ASIC3 sustained window current. We showed that amiloride and GMQ shift the pH-dependent activation and inactivation in the same directions, which depend on the channel, and that their effects rely on the nature of the extracellular domain but can be indirectly modulated in their amplitude by the transmembrane/cytosolic domains. The extracellular domain explains the pharmacological potentiating effect of amiloride and GMQ on the window current in ASIC3, and why these compounds failed to generate a window current in ASIC1a. Amiloride and GMQ have similar and purely additive effects suggesting that they act through a common unique binding site different from acidic pockets. Finally, a simple cycle analysis using GMQ that targets the nonproton ligand-sensor, and two peptide inhibitors of ASIC1a targeting the acidic pockets (PcTx1 and mambalgin-1), shows overlap between the mechanisms by which GMQ and PcTx1 modify inactivation and suggests shared mechanisms of regulation of the pH-dependent inactivation of ASIC1a between these two regions.

Low cost venom extractor based on Arduino(®) board for electrical venom extraction from arthropods and other small animals.

Extracting venom from small species is usually challenging. We describe here an affordable and versatile electrical venom extractor based on the Arduino(®) Mega 2560 Board, which is designed to extract venom from arthropods and other small animals. The device includes fine tuning of stimulation time and voltage. It was used to collect venom without apparent deleterious effects, and characterized for the first time the venom of Zoropsis spinimana, a common spider in French Mediterranean regions.

Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition.

Mambalgins are peptides isolated from mamba venom that specifically inhibit a set of acid-sensing ion channels (ASICs) to relieve pain. We show here the first full stepwise solid phase peptide synthesis of mambalgin-1 and confirm the biological activity of the synthetic toxin both in vitro and in vivo. We also report the determination of its three-dimensional crystal structure showing differences with previously described NMR structures. Finally, the functional domain by which the toxin inhibits ASIC1a channels was identified in its loop II and more precisely in the face containing Phe-27, Leu-32, and Leu-34 residues. Moreover, proximity between Leu-32 in mambalgin-1 and Phe-350 in rASIC1a was proposed from double mutant cycle analysis. These data provide information on the structure and on the pharmacophore for ASIC channel inhibition by mambalgins that could have therapeutic value against pain and probably other neurological disorders.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions.