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BACKGROUND: In 2020, Ecuador had one of the highest death rates because of COVID-19. The role of clinical and biomolecular markers in COVID disease prognosis, is still not well supported by available data. In order for these markers to have practical application in clinical decision-making regarding patient treatment and prognosis, it is necessary to know an optimal cut-off point, taking into consideration ethnic differences and geographic conditions. AIM: To determine the value of clinical and biomolecular markers, to predict mortality of patients with severe COVID-19 living at high altitude. METHODS: In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of ROC, sensitivity, specificity and likelihood ratios were calculated to determine levels of clinical and biomolecular markers that best differentiate survivors versus non-survivors in severe COVID subjects that live at a high altitude setting. RESULTS: Selected cut-off values for ferritin (≥ 1225 ng/dl, p = 0.026), IL-6 (≥ 11 pg/ml, p = 0.005) and NLR (≥ 22, p = 0.008) at 24 h, as well as PaFiO2 (≤ 164 mmHg, p = 0.015), NLR (≥ 16, p = p = 0.013) and SOFA (≥ 6, p = 0.031) at 72 h, appear to have good discriminating power to differentiate survivors versus non-survivors. Additionally, odds ratios for ferritin (OR = 3.38); IL-6 (OR = 17.07); PaFiO2 (OR = 4.61); NLR 24 h (OR = 4.95); NLR 72 h (OR = 4.46), and SOFA (OR = 3.77) indicate increased risk of mortality when cut-off points were taken into consideration. CONCLUSIONS: We proposed a straightforward and understandable method to identify dichotomized levels of clinical and biomolecular markers that can discriminate between survivors and non-survivors patients with severe COVID-19 living at high altitudes.

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We are a group of 11 women in Albuquerque, New Mexico. Nine of us are immigrants from Mexico. One of us is from an immigrant household. One of us is neither. We have been working collaboratively on a research study called Tertulias (Spanish for "a social gathering"), which is an innovative women's peer support group approach we created to reduce social isolation, depression, and stress among women immigrants from Mexico, and to increase their resilience and sense of empowerment. In the process of implementing the Tertulias study, we are revealing the profound power of peer support, friendship, and small, quotidian kindnesses. But we are also exposing the immensity and scope of trauma, fear, loneliness, depression, and self-blame that exist in the Mexican immigrant community because of domestic violence. Our experience with domestic violence and with the consciousness-raising and support we found in Tertulias has made us want to be involved in a positive manner to do something about this issue in our community. We want our experience to mean something-to be used to make a difference. We are opening our hearts and sharing our stories and ideas. We wanted to be included as co-authors of this article because we want our stories to be received and heard by other women. We want to plant seeds to help other women find their inner strength to be able to escape from their chains. We have to return for others. It is a commitment-to understand how we were able to do it and share that with others. Through our experience participating in Tertulias, we learned that we could overcome what felt overwhelming and impenetrable. We could leave the violence and rediscover and recreate ourselves and our lives.

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INTRODUCTION: Central venous catheter (CVC)- related bacteremias are common in pediatric patients following surgery for complex congenital heart disease admitted to a pediatric cardiac intensive care unit (PCICU) and have a high morbidity and mortality. OBJECTIVE: To analyze the effectiveness of an interdisciplinary program for the prevention of CVC-related bacteremias in the PCICU. MATERIAL AND METHODS: Quasi-experimental, before and after implementation study without a control group. Study period: 01-01-2008 to 12- 31-2018. Population: PCICU staff who care for patients following surgery for complex heart disease at a hospital. Pre-intervention period: 01- 01-2008 to 12-31-2008; intervention period: 01-01- 2009 to 01-01-2018. Intervention: implementation of an ongoing improvement program. The rate of CVC-related bacteremias/1000 days and CVC use/100 days, RACHS score, standardized infection ratio (SIR), relative risk (RR), and 95% confidence interval (CI) were analyzed and a p value < 0.05 was considered statistically significant. The reference rate was estimated as the average for the 2008-2009 period and the annual and reference rates were compared. RESULTS: The bacteremia reference rate for 2008- 2009 was 10.6/1000 days of CVC to analyze the SIR. A RACHS score over 3 was similar across all studied periods. The annual comparison showed a statistically significant reduction (p < 0.05) in the SIR. The comparison between the baseline bacteremia rate/1000 days of CVC (11.9) and the final rate (3.8) showed a significant reduction (RR: 0.16; 95 % CI: 0.07-0.35; p < 0.001). CONCLUSIONS: The program was effective; the rate of CVC-related bacteremias in the PCICU showed a progressive, significant reduction.

Introducción. Las bacteriemias relacionadas con catéteres venosos centrales (CVC) son frecuentes en pacientes pediátricos posquirúrgicos de cardiopatías congénitas complejas internados en la unidad de cuidados intensivos pediátricos cardiovascular (UCIP-CV) y tienen alta morbimortalidad. OBJETIVO: Analizar la efectividad de un programa interdisciplinario para prevención de bacteriemias relacionadas con CVC en la UCIP-CV. Material y métodos. Estudio de implementación, cuasiexperimental, antes-después, sin grupo control. Período de estudio del 1 de enero de 2008 al 31 de diciembre de 2018. Población: equipo de salud de la UCIP-CV que atiende pacientes posquirúrgicos de cardiopatías complejas de un hospital. Período preintervención del 1 de enero de 2008 al 31 de diciembre de 2008; período de intervención del 1 de enero de 2009 al 1 de enero de 2018. Intervención: implementación de un programa de mejora continua. Se analizaron tasas de bacteriemias CVC/1000 días y de uso de CVC/100 días, puntaje de RACHS, razón estandarizada de infecciones (REI), riesgo relativo (RR), intervalo de confianza del 95 % (IC95%), estimando una p < 0,05 como estadísticamente significativa. La tasa de referencia se estimó como el promedio del período 2008/2009 y se comparó la tasa anual con la tasa de referencia. RESULTADOS: La tasa de referencia de bacteriemia 2008/2009 fue 10,6/1000 días CVC para analizar la REI. El puntaje de RACHS mayor a 3 fue similar en todos los períodos analizados. Se observó una reducción de la REI estadísticamente significativa (p < 0,05) en la comparación anual. Al comparar la tasa de bacteriemia/1000 días de CVC inicial de 11,9 vs. final de 3,8, se observó una reducción significativa (RR: 0,16; IC95%: 0,07-0,35; p < 0,001). CONCLUSIONES: El programa fue efectivo; se observó reducción progresiva y significativa de la tasa de bacteriemias relacionadas con CVC en la UCIP-CV.

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Introducción. Las bacteriemias relacionadas con catéteres venosos centrales (CVC) son frecuentes en pacientes pediátricos posquirúrgicos de cardiopatías congénitas complejas internados en la unidad de cuidados intensivos pediátricos cardiovascular (UCIP-CV) y tienen alta morbimortalidad. Objetivo. Analizar la efectividad de un programa interdisciplinario para prevención de bacteriemias relacionadas con CVC en la UCIP-CV. Material y métodos. Estudio de implementación, cuasiexperimental, antes-después, sin grupo control. Período de estudio del 1 de enero de 2008 al 31 de diciembre de 2018. Población: equipo de salud de la UCIP-CV que atiende pacientes posquirúrgicos de cardiopatías complejas de un hospital. Período preintervención del 1 de enero de 2008 al 31 de diciembre de 2008; período de intervención del 1 de enero de 2009 al 1 de enero de 2018. Intervención: implementación de un programa de mejora continua. Se analizaron tasas de bacteriemias CVC/1000 días y de uso de CVC/100 días, puntaje de RACHS, razón estandarizada de infecciones (REI), riesgo relativo (RR), intervalo de confianza del 95 % (IC95%), estimando una p < 0,05 como estadísticamente significativa. La tasa de referencia se estimó como el promedio del período 2008/2009 y se comparó la tasa anual con la tasa de referencia. Resultados. La tasa de referencia de bacteriemia 2008/2009 fue 10,6/1000 días CVC para analizar la REI. El puntaje de RACHS mayor a 3 fue similar en todos los períodos analizados. Se observó una reducción de la REI estadísticamente significativa (p < 0,05) en la comparación anual. Al comparar la tasa de bacteriemia/1000 días de CVC inicial de 11,9 vs. final de 3,8, se observó una reducción significativa (RR: 0,16; IC95%: 0,07-0,35; p < 0,001). Conclusiones. El programa fue efectivo; se observó reducción progresiva y significativa de la tasa de bacteriemias relacionadas con CVC en la UCIP-CV.

Introduction. Central venous catheter (CVC)related bacteremias are common in pediatric patients following surgery for complex congenital heart disease admitted to a pediatric cardiac intensive care unit (PCICU) and have a high morbidity and mortality. Objective.To analyze the effectiveness of an interdisciplinary program for the prevention of CVC-related bacteremias in the PCICU. Material and methods. Quasi-experimental,before and after implementation study without a control group. Study period: 01-01-2008 to 1231-2018. Population: PCICU staff who care for patients following surgery for complex heart disease at a hospital. Pre-intervention period: 0101-2008 to 12-31-2008; intervention period: 01-012009 to 01-01-2018. Intervention: implementation of an ongoing improvement program. The rate of CVC-related bacteremias/1000 days and CVC use/100 days, RACHS score, standardized infection ratio (SIR), relative risk (RR), and 95% confidence interval (CI) were analyzed and a p value < 0.05 was considered statistically significant. The reference rate was estimated as the average for the 2008-2009 period and the annual and reference rates were compared. Results. The bacteremia reference rate for 20082009 was 10.6/1000 days of CVC to analyze the SIR. A RACHS score over 3 was similar across all studied periods. The annual comparison showed a statistically significant reduction (p < 0.05) in the SIR. The comparison between the baseline bacteremia rate/1000 days of CVC (11.9) and the final rate (3.8) showed a significant reduction (RR: 0.16; 95 % CI: 0.07­0.35; p < 0.001). Conclusions. The program was effective; the rate of CVC-related bacteremias in the PCICU showed a progressive, significant reduction.

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Autoinflammatory diseases (AIDs) are a relatively new family disorders defined approximately 20 years ago. AIDs are caused by defect(s) or dysregulation of the innate immune system, characterized by recurrent or continuous inflammation and lack of a primary pathogenic role for the adaptive immune system. One AID, NLRP3-associated autoinflammatory disease (NLRP3-AID), involves a clinical presentation since the neonatal period or childhood, with multiple inflammatory recurrent symptoms that appear throughout the patient´s life. We present the first case of NLRP3-AID in Ecuador. The patient presented recurrent fever since 6 months of age associated with urticarial rash, arthralgias, and abdominal pain; recently, he had a seizure at 7 years of age. Brain MRI revealed demyelinating lesions, and genetic testing uncovered a de novo mutation in the NLRP3 gene. The patient had a good clinical response to treatment with canakinumab.

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Resumen Introducción: la patología gástrica es excepcionalmente benigna, se registra a nivel mundial un porcentaje de aparición de las mismas del 0,005 %-4 %. Además de lo anterior, suele plantearse como primer diagnóstico diferencial un carcinoma gástrico, por lo que la mayoría de los pacientes termina en un procedimiento quirúrgico mayor. El objetivo de este estudio fue describir una serie de casos registrados en una institución de alta complejidad, así como la revisión de la literatura al respecto del tema. Pacientes y métodos: se realizó la revisión de las bases de datos del servicio de cirugía general de la Clínica Universitaria Colombia y se encontraron 4 tumores gástricos de presentación inusual, de los cuales se hizo revisión de la historia clínica y las imágenes disponibles (diagnósticas y de las piezas de cirugía). Resultados: en la revisión de la base de datos, se encontraron 4 casos, 2 de sexo femenino y 2 de sexo masculino, con una media de edad de 51 años (26-75 años). El 100 % de los pacientes tenía una lesión en la región antral y solo uno de ellos tenía una segunda lesión a nivel prepilórico. La totalidad de los pacientes fue llevada a gastrectomía subtotal con reconstrucción en Y de Roux por abordaje laparoscópico y la media de estancia hospitalaria fue de 3,5 días (2-6 días). Conclusión: para determinar la mejor opción de tratamiento en general en pacientes con lesiones gástricas siempre hay que considerar tanto las características endoscópicas y endosonográficas como las histológicas.

Abstract Introduction: Gastric pathology is exceptionally benign with a percentage of appearance between 0.005% - 4% worldwide. Moreover, gastric carcinoma is often suggested as the first differential diagnosis and for that reason, the outcome for a vast majority of admitted patients is a major surgical procedure. This study aims to describe a series of cases recorded in a high complexity medical institution and to carry out a literature review related to that subject. Patients and Methods: Databases from the general surgery service of the Clínica Universitaria Colombia were reviewed, and four unusual gastric tumors were found. A review of the related medical records and available images (diagnostic images and surgical elements) was performed. Results: After the database review, four cases were found: two female cases and two male cases, with a mean age of 51 years (26-75 years). All the patients had lesions in the antrum area and only one of them has an additional lesion in the prepyloric region. All patients were treated with a laparoscopic subtotal gastrectomy with Roux-en-Y reconstruction and the mean length of hospital stay was 3.5 days (2-6 days). Conclusion: It is required to consider the endoscopic, endosonographic, and histological examinations and their features to determine the best treatment for patients with gastric lesions.

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There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between in vivo toxicity tests and in vitro surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A2), (d) in vitro coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity in vitro, (g) use of hens' eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more 'humane' protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new in vitro alternatives and more 'humane' experimental designs will emerge in this field.

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ABSTRACT Introduction: Colonic lipomas are low-risk lesions that require endoscopic or surgical management depending on their size and symptoms. However, diagnosing a lipomatous lesion in the colon is a difficult task, as the clinical or imaging findings point to a low prevalence of these lesions and a higher frequency in the female sex. The laparoscopic approach is the current method of choice as it represents fewer traumas and, therefore, a faster clinical recovery. Case presentation: 43-year-old female patient, Caucasian, from the city of Bogotá, housewife, without any medical history. She presented with acute abdominal pain associated with tarry stools. Diagnostic imaging tests were performed, finding colo-colonic intussusception, originated in a lipomatous lesion located in the transverse colon. This patient underwent an enlarged laparoscopic right hemicolectomy. Discussion: This case describes how colonic intussusception constitutes a preoperative complication that requires surgical management since its diagnosis considering the associated mortality rates. Conclusion: The analysis of this case is part of the scientific evidence indispensable to improve the diagnostic and therapeutic approach to colonic intussusception, as local and international literature have not addressed this condition sufficiently.

RESUMEN Introducción. Los lipomas en el colon son lesiones con pocos riesgos de malignización que, según su tamaño y sintomatologia, pueden requerir manejo endoscópico o quirúrgico. Sin embargo, es difícil establecer el diagnóstico de una lesión lipomatosa en el colon: los hallazgos clínicos o imagenológicos solo describen que la prevalencia de estas lesiones es baja y que es una patología común en el género femenino. Debido a que el abordaje laparoscópico causa menores traumas y por tanto la recuperación clínica es más rápida, en la actualidad suele elegirse esta opción. Presentación de caso. Paciente femenino de 43 años, raza blanca, procedente de Bogotá D.C., ama de casa y sin antecedentes médicos. La sintomatología que presentó fue dolor abdominal de instauración aguda asociado a deposiciones melénicas, por lo que fue llevada a toma de imágenes diagnósticas donde se documentó intususcepción colocolónica originada en una lesión lipomatosa y localizada en el colon transverso. Se le practicó hemicolectomía derecha ampliada por vía laparoscópica. Discusión. A partir de este caso se describe cómo la intususcepción colónica constituye una complicación preoperatoria que demanda la realización de un manejo quirúrgico desde el mismo diagnóstico dado el margen de los porcentajes de mortalidad. Conclusión. El análisis del presente caso constituye parte de la evidencia científica indispensable para mejorar el abordaje diagnóstico y terapéutico de la intususcepción colónica que la literatura nacional e internacional no ha tratado suficientemente.

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Resumen La granulomatosis con poliangeítis (GPA) es una vasculitis de pequeno y mediano calibre caracterizada por la formación de granulomas e inflamación necrosante con predilección de las vías respiratorias y los glomérulos. Se reporta el caso de una adolescente de 14 an os que comienza con hipoacusia y lesiones cutáneas; sinusitis, epiescleritis, PR3-ANCA positivo y biopsia de piel con infiltrado neutrofílico y necrosis. La GPA puede presentar manifestaciones otológicas y dermatológicas como signo inicial, es importante tomarlo en consideración en el diagnóstico diferencial.

Abstract Granulomatosis with polyangiitis is a small- and medium-sized vasculitis. It is characterised by formation of granulomas and necrotising inflammation with a predilection for the respiratory tract and glomeruli. The case is presented of a 14-year-old female debuting with hypoacusis, skin lesions, sinusitis; episcleritis, anti-PR3 ANCA positivity and histological findings from the skin lesions with neutrophilic infiltration, necrosis and fibrin. Granulomatosis with polyangiitis can present otological and skin manifestations as initial signs, and it is important to take the differential diagnosis into consideration.

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Routine laboratory animal tests necessary to assess the toxicity of snake venoms and the preclinical neutralizing ability of antivenoms and other inhibitory substances induce significant pain and distress. This has prompted initiatives to introduce the routine use of analgesia. In this study, the analgesic effect of morphine and tramadol was assessed in tests assessing the lethal, hemorrhagic, myotoxic and edema-forming activities of the venom of the viperid snake Bothrops asper. The Mouse Grimace Scale (MGS) and mouse-exploration activity were used to assess pain and its inhibition by the analgesics. Results demonstrate that tests assessing lethality and myotoxicity induce higher levels of pain than assays quantifying hemorrhagic and edema-forming activities. Our observations also indicate that pretreatment of mice with both analgesics, at the doses used, were similarly effective in reducing the MGS magnitude and increase mouse-exploration activity after the administration of B. asper venom. Moreover, the analgesic effect of both drugs was more evident in the myotoxic and lethality assays. Combined with previous observations showing that these analgesics do not alter the extent of toxic effects induced by B. asper venom, our results strongly indicate that the use of analgesia (using either morphine or tramadol) should be considered in the routine assessment of venom toxicity and antivenom efficacy.

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INTRODUCTION: Metalloproteinases play key roles in health and disease, by generating novel proteoforms with variable structure and function. Areas covered: This review focuses on the role of endogenous [a Disintegrin and Metalloproteinase (ADAMs), ADAMs with thrombospondin motifs (ADAMTS), and matrix metalloproteinases (MMPs)] and exogenous metalloproteinases in various disease conditions, and describes the application of mass spectrometry-based proteomics to detect qualitative and quantitative changes in protein profiles in tissues and body fluids in disease. Emphasis is placed on the proteomic analysis of exudates collected from affected tissues, including methods that enrich newly generated protein fragments derived from proteolysis in cells, stroma, or extracellular matrix. The use of proteomic analysis of exudates in the study of the local tissue damage induced by metalloproteinases derived from viperid snake venoms is discussed, particularly in relation to extracellular matrix degradation and to the overall pathology of these envenomings. Expert commentary: The information provided by these proteomics approaches is paving the way for the identification of biomarkers based on particular proteolytic signatures associated with different pathologies. Together with other methodological approaches, a comprehensive view of the mechanisms and dynamics of diseases can be achieved. Such basis of knowledge allows for the design of novel diagnostic and therapeutic approaches within the frame of 'precision' or 'personalized' medicine.

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The precise mechanisms by which Snake Venom Metalloproteinases (SVMPs) disrupt the microvasculature and cause haemorrhage have not been completely elucidated, and novel in vivo models are needed. In the present study, we compared the effects induced by BaP1, a PI SVMP isolated from Bothrops asper venom, and CsH1, a PIII SVMP from Crotalus simus venom, on cremaster muscle microvasculature by topical application of the toxins on isolated tissue (i.e., ex vivo model), and by intra-scrotal administration of the toxins (i.e., in vivo model). The whole tissue was fixed and immunostained to visualize the three components of blood vessels by confocal microscopy. In the ex vivo model, BaP1 was able to degrade type IV collagen and laminin from the BM of microvessels. Moreover, both SVMPs degraded type IV collagen from the BM in capillaries to a higher extent than in PCV and arterioles. CsH1 had a stronger effect on type IV collagen than BaP1. In the in vivo model, the effect of BaP1 on type IV collagen was widespread to the BM of arterioles and PCV. On the other hand, BaP1 was able to disrupt the endothelial barrier in PCV and to increase vascular permeability. Moreover, this toxin increased the size of gaps between pericytes in PCV and created new gaps between smooth muscle cells in arterioles in ex vivo conditions. These effects were not observed in the case of CsH1. In conclusion, our findings demonstrate that both SVMPs degrade type IV collagen from the BM in capillaries in vivo. Moreover, while the action of CsH1 is more directed to the BM of microvessels, the effects of BaP1 are widespread to other microvascular components. This study provides new insights in the mechanism of haemorrhage and other pathological effects induced by these toxins.

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Takayasu arteritis (TA) is the third most common childhood vasculitis and its clinical manifestations depend on the arteries involved. We report a case of a 9-year-old boy with multiple aneurysms in carotid and iliac arteries, subclavian and coronary arteries, and abdominal aorta. At the age of 7 years, he presented with recurrent fever and hepatosplenomegaly. An angio-computed tomography scan showed aneurysms in the left subclavian artery, abdominal aorta, and both proximal iliac arteries. He was diagnosed with TA and was treated with corticosteroids, aspirin, and enalapril. One year later, he was admitted to Dr Roberto Gilbert Children's Hospital because of intracranial hemorrhage. Angiography revealed enlargement of aneurysms enlargement and new aneurysms. He also developed portal hypertension. Treatment with intravenous corticosteroids, azathioprine, and monthly intravenous cyclophosphamide was begun. After 6 months of no improvement, infliximab was begun. The aim of this article was to report the concurrence of coronary involvement and portal vein hypertension in pediatric TA because there were scarce reports on this matter.

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Viperid snakebite envenomation is characterized by inflammatory events including increase in vascular permeability. A copious exudate is generated in tissue injected with venom, whose proteomics analysis has provided insights into the mechanisms of venom-induced tissue damage. Hereby it is reported that wound exudate itself has the ability to induce increase in vascular permeability in the skin of mice. Proteomics analysis of exudate revealed the presence of cytokines and chemokines, together with abundant damage associated molecular pattern molecules (DAMPs) resulting from both proteolysis of extracellular matrix and cellular lysis. Moreover, significant differences in the amounts of cytokines/chemokines and DAMPs were detected between exudates collected 1 h and 24 h after envenomation, thus highlighting a complex temporal dynamic in the composition of exudate. Pretreatment of mice with Eritoran, an antagonist of Toll-like receptor 4 (TLR4), significantly reduced the exudate-induced increase in vascular permeability, thus suggesting that DAMPs might be acting through this receptor. It is hypothesized that an "Envenomation-induced DAMPs cycle of tissue damage" may be operating in viperid snakebite envenomation through which venom-induced tissue damage generates a variety of DAMPs which may further expand tissue alterations.

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Snake venom metalloproteinases (SVMPs) affect the extracellular matrix (ECM) in multiple and complex ways. Previously, the combination of various methodological platforms, including electron microscopy, histochemistry, immunohistochemistry, and Western blot, has allowed a partial understanding of such complex pathology. In recent years, the proteomics analysis of exudates collected in the vicinity of tissues affected by SVMPs has provided novel and exciting information on SVMP-induced ECM alterations. The presence of fragments of an array of ECM proteins, including those of the basement membrane, has revealed a complex pathological scenario caused by the direct action of SVMPs. In addition, the time-course analysis of these changes has underscored that degradation of some fibrillar collagens is likely to depend on the action of endogenous proteinases, such as matrix metalloproteinases (MMPs), synthesized as a consequence of the inflammatory process. The action of SVMPs on the ECM also results in the release of ECM-derived biologically-active peptides that exert diverse actions in the tissue, some of which might be associated with reparative events or with further tissue damage. The study of the effects of SVMP on the ECM is an open field of research which may bring a renewed understanding of snake venom-induced pathology.

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The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM) and other extracellular matrix (ECM) proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs) or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

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The historical development of discoveries and conceptual frames for understanding the hemorrhagic activity induced by viperid snake venoms and by hemorrhagic metalloproteinases (SVMPs) present in these venoms is reviewed. Histological and ultrastructural tools allowed the identification of the capillary network as the main site of action of SVMPs. After years of debate, biochemical developments demonstrated that all hemorrhagic toxins in viperid venoms are zinc-dependent metalloproteinases. Hemorrhagic SVMPs act by initially hydrolyzing key substrates at the basement membrane (BM) of capillaries. This degradation results in the weakening of the mechanical stability of the capillary wall, which becomes distended owing of the action of the hemodynamic biophysical forces operating in the circulation. As a consequence, the capillary wall is disrupted and extravasation occurs. SVMPs do not induce rapid toxicity to endothelial cells, and the pathological effects described in these cells in vivo result from the mechanical action of these hemodynamic forces. Experimental evidence suggests that degradation of type IV collagen, and perhaps also perlecan, is the key event in the onset of microvessel damage. It is necessary to study this phenomenon from a holistic, systemic perspective in which the action of other venom components is also taken into consideration.

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OBJECTIVE: To describe condom use among Mexican women living with HIV and analyze factors that facilitate or impede its utilization. MATERIALS AND METHODS: Qualitative analysis of 55 interviews with women of reproductive age living with HIV. RESULTS: Inconsistent condom use and non-use at last sexual intercourse was common, and not clearly related to the male partners' HIV-status. Factors that influenced condom use included perceptions of health benefits, symbolic meaning assigned to the condom within the relationship, and the transformation or persistence of inequitable gender norms. CONCLUSIONS: Gender norms and male partners' attitudes strongly influence condom use among women living with HIV. To increase consistent condom use the health system must implement counseling and service delivery with a gender perspective and innovative actions to involve male partners.

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Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.

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Objetivo. Describir prácticas de uso del condón en mujeres mexicanas con VIH y analizar factores que lo facilitan u obstaculizan. Material y métodos. Análisis cualitativo de 55 entrevistas con mujeres que viven con VIH en edad reproductiva. Resultados. El uso inconsistente y el no uso del condón en la última relación sexual fueron comunes y no mostraron una relación clara con el estatus serológico de la pareja. Factores favorables al uso del condón fueron las percepciones de su beneficio para la salud, significados simbólicos del condón en relaciones de pareja y transformación o persistencia de normas de género. Conclusiones. Las normas de género y las actitudes de la pareja masculina intervienen en el uso del condón entre mujeres con VIH. Para incrementar su uso consistente, el sistema de salud debe ofrecer consejería y servicios con perspectiva de género e implementar acciones innovadoras que involucren a las parejas masculinas.

Objective. To describe condom use among Mexican women living with HIV and analyze factors that facilitate or impede its utilization. Materials and methods. Qualitative analysis of 55 interviews with women of reproductive age living with HIV. Results. Inconsistent condom use and non-use at last sexual intercourse was common, and not clearly related to the male partners' HIV-status. Factors that influenced condom use included perceptions of health benefits, symbolic meaning assigned to the condom within the relationship, and the transformation or persistence of inequitable gender norms. Conclusions. Gender norms and male partners' attitudes strongly influence condom use among women living with HIV. To increase consistent condom use the health system must implement counseling and service delivery with a gender perspective and innovative actions to involve male partners.

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