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Spontaneous coronary artery dissection (SCAD) is a rare and underdiagnosed entity that can lead to acute coronary syndrome. This condition has a gender predilection, predominantly affecting women, especially those with known risk factors such as pregnancy and the postpartum period. Hormonal changes and hemodynamic stress during these stages significantly contribute to the occurrence of SCAD. Recognizing and understanding this entity, as well as its imaging findings, have a favorable impact on patient prognosis. Accurate diagnosis through imaging techniques such as coronary angiography and computed tomography is crucial for the appropriate management of SCAD, allowing for early and specific interventions that can significantly improve clinical outcomes and reduce associated mortality. Continuous education and awareness about this condition are essential to improve detection rates and effective treatment.
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The performance of dynamic body-feed filtration (DBF) in the removal of bulky solids produced during the manufacturing of snake antivenoms using the caprylic acid method was evaluated. For this purpose, diatomites with different filterability properties were compared in a bench-scale study to assess their effectiveness in removing the precipitated material formed after the addition of caprylic acid to equine hyperimmune plasma. C1000 diatomite at a concentration of 90 g/L of precipitated plasma showed the best performance. Then, the process was scaled up to three batches of 50 L of hyperimmune horse plasma. At this pilot scale, 108 ± 4% of the immunoglobulins present following plasma precipitation were recovered after DBF. The antivenoms generated using this procedure met quality specifications. When compared to open filtration systems commonly used at an industrial scale by many antivenom manufacturers, DBF has a similar yield and produces filtrates with comparable physicochemical characteristics. However, DBF ensures the microbiological quality of the primary clarification in a way that open systems cannot. This is because: 1) DBF is performed in a single-use closed device of depth filters which prevents microbial contamination, and 2) DBF removes bulky material in few minutes instead of the more than 24 h needed by open filtration systems, thus reducing the risk of contamination. It was concluded that DBF is a cost-effective, easily validated, and GMP-compliant alternative for primary clarification following caprylic acid precipitation of plasma in snake antivenom production.
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The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.
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Autoinmunidad , Linfocitos B , Humanos , Linfocitos B/inmunología , Animales , Hormonas/metabolismo , Hormonas/inmunología , Enfermedades Autoinmunes/inmunología , Diferenciación Celular/inmunología , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
As injectable therapeutics, snake antivenoms must meet specifications for endotoxin content. The Limulus amebocyte lysate (LAL) test was used to evaluate the endotoxin content in several commercially available antivenoms released for clinical use. It was found that some products have endotoxin concentrations higher than the accepted limit for these contaminants. These results emphasize the need to include endotoxin determination as part of the routine evaluation of antivenoms by manufacturers and regulatory agencies.
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The circadian clock is an endogenous time-tracking system that anticipates daily environmental changes. Misalignment of the clock can cause obesity, which is accompanied by reduced levels of the clock-controlled, rhythmic metabolite NAD+. Increasing NAD+ is becoming a therapy for metabolic dysfunction; however, the impact of daily NAD+ fluctuations remains unknown. Here, we demonstrate that time-of-day determines the efficacy of NAD+ treatment for diet-induced metabolic disease in mice. Increasing NAD+ prior to the active phase in obese male mice ameliorated metabolic markers including body weight, glucose and insulin tolerance, hepatic inflammation and nutrient sensing pathways. However, raising NAD+ immediately before the rest phase selectively compromised these responses. Remarkably, timed NAD+ adjusted circadian oscillations of the liver clock until completely inverting its oscillatory phase when increased just before the rest period, resulting in misaligned molecular and behavioral rhythms in male and female mice. Our findings unveil the time-of-day dependence of NAD+-based therapies and support a chronobiology-based approach.
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Relojes Circadianos , Enfermedades Metabólicas , Ratones , Masculino , Femenino , Animales , Ritmo Circadiano/fisiología , NAD/metabolismo , Dieta , Enfermedades Metabólicas/metabolismo , Hígado/metabolismoRESUMEN
Systemic lupus erythematosus (SLE) mainly affects females at reproductive age, which has been associated with hormones, such as prolactin (PRL). Different studies suggest that PRL exacerbates the clinical manifestations of SLE both in patients and in mouse models (e.g., the MRL/lpr strain), increasing the production of autoantibodies, which can be deposited as immune complexes and trigger inflammation and damage to different tissues. The objective of this work was to explore the potential mechanisms by which PRL increases the concentration of self-reactive antibodies in the MRL/lpr SLE model. To this end, we determined the role of PRL on the activation and proliferation of germinal center B cells (B-GCs) and their differentiation into antibody-secreting cells (ASCs). We show that the absolute number and percentage of B-GCs were significantly increased by PRL in vivo or upon in vitro treatment with anti-IgM and anti-CD40 antibodies and PRL. The augmented B-GC numbers correlated with enhanced proliferation, but we did not observe enhanced expression of CD80 and CD86 activation markers or the BCL6 transcription factor, arguing against a more effective differentiation. Nevertheless, we observed enhanced phosphorylation of STAT1, secretion of IL-6, expression of IRF4, numbers of ASCs, and levels of IgG3 antibodies directed against dsDNA. Altogether, these results support the hypothesis that a PRL-mediated expansion of B-GCs yields more self-reactive ASCs, potentially explaining the pathogenic immune complexes that steadily lead to tissue damage during SLE.
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Autoanticuerpos , Lupus Eritematoso Sistémico , Animales , Femenino , Ratones , Complejo Antígeno-Anticuerpo , Proliferación Celular , Centro Germinal , Inmunoglobulina G , Ratones Endogámicos MRL lpr , Células Plasmáticas , Prolactina/metabolismo , Linfocitos BRESUMEN
The higher frequency of autoimmune diseases in the female population compared to males suggests that certain hormones, such as prolactin (PRL), play a role in determining the prevalence of autoimmunity in women, particularly during childbearing age. PRL can act not only as a hormone but also as a cytokine, being able to modulate immune responses. Hyperprolactinemia has been implicated in the pathogenesis of various autoimmune diseases where it may affect disease activity. One of the conditions where PRL has such a role is systemic lupus erythematosus (SLE). PRL regulates the proliferation and survival of both lymphoid and myeloid cells. It also affects the selection of T-cell repertoires by influencing the thymic microenvironment. In autoimmune conditions, PRL interferes with the activity of regulatory T cells. It also influences B cell tolerance by lowering the activation threshold of anergic B cells. The production of CD40L and cytokines, such as interleukin IL-6, are also promoted by PRL. This, in turn, leads to the production of autoantibodies, one of the hallmarks of SLE. PRL increases the cytotoxic activity of T lymphocytes and the secretion of proinflammatory cytokines. The production of proinflammatory cytokines, particularly those belonging to the type 1 interferon (IFN) family, is part of the SLE characteristic genetic signature. PRL also participates in the maturation and differentiation of dendritic cells, promoting the presentation of autoantigens and high IFNα secretion. It also affects neutrophil function and the production of neutrophil traps. Macrophages and dendritic cells can also be affected by PRL, linking this molecule to the abnormal behavior of both innate and adaptive immune responses.This review aimed to highlight the importance of PRL and its actions on the cells of innate and adaptive immune responses. Additionally, by elucidating the role of PRL in SLE etiopathogenesis, this work will contribute to a better understanding of the factors involved in SLE development and regulation.
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Enfermedades Autoinmunes , Hiperprolactinemia , Lupus Eritematoso Sistémico , Masculino , Femenino , Humanos , Prolactina/metabolismo , CitocinasRESUMEN
RATIONALE: The gap between the nutrition education provided to medical students and the nutrition competences and attitudes needed for doctors to provide effective nutrition care is a global concern. The goal of this study was to investigate the curricular content on nutrition education in Latin American medical schools and to evaluate the self-perceived knowledge, attitudes, and barriers to nutrition practice of final-year medical students. METHODS: Eighty-five public and private medical schools from 17 Latin American countries were invited to participate in the study. Two close-ended online questionnaires consisting of 25 and 43 questions were sent to medical school directors. Quantitative variables were expressed as frequencies, percentages, mean ± standard deviation, medians, and ranges. RESULTS: A total of 22 (26%) medical school directors responded, of which 11 schools (50%) offered stand-alone mandatory nutrition courses in preclinical and 8 (36%) in clinical years. The mean hours dedicated to nutrition education was 47 (range: 0-150). A total of 1530 of 1630 (94%) students from 12 countries responded. Students' average age was 25 ± 3 years, and 59% were female. Most students agreed that improving patients' health through nutrition (91%) is important and that nutrition counseling and assessment should be part of routine care provided by all physicians (89%), but they lack the level of education and training required to address nutrition-related issues. CONCLUSIONS: Positive attitude and interest in nutrition among final-year medical students is high, but nutrition education is not perceived as sufficient to adequately prepare doctors in the field of nutrition.
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Curriculum , Educación Médica , Adulto , Estudios Transversales , Femenino , Humanos , América Latina , Facultades de Medicina , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Introduction: During the COVID-19 pandemic, women disproportionately assume more unpaid activities, affecting their employment. Objective: Describe the influence of COVID-19 on the employment of caregivers of children and adolescents from a gender perspective. Methods: Cross-sectional study in three high-complexity hospitals in Bogotá, Colombia from April 2020 to June 2021. A subsample of the FARA cohort was taken, including those patients with a positive test for SARS-COV2. We took as our analysis category children older than 8 years and younger than 18 years who had a positive SARS-COV2 test, as well as, caregivers of all children with a positive SARS-COV2 test. This subsample was drawn from the FARA cohort. A survey was applied to them. We carried out a descriptive and stratified analysis by age group, educational, and socioeconomic level. Results: We included 60 surveys of caregivers and 10 surveys of children. The main caregiver in 94.8% of the cases was a female. At the beginning of the pandemic, 63.3% of the caregivers were employed, and 78.9% of those lost their employment. The vast majority of these caregiver were women (96.6%, n = 29). A predominance of loss of work activity was documented in caregivers of children in early childhood 66.6% (n = 20), with lower education 66.6% (n = 20), and from lower strata 56.6% (n = 17). Conclusion: Caregivers of children with COVID-19 with low educational levels and lower socioeconomic conditions, as well as those with children under 5 years showed greater likelihood of employment loss between the interviewed subsample.
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BACKGROUND: The gap between the nutrition education provided to medical students and the nutrition competencies and attitudes needed for physicians to provide adequate nutrition care is a global concern. There is no universally accepted benchmark on nutrition competencies for doctors. The objective of this study was to establish, by expert consensus, the objectives of undergraduate nutrition medial education, the nutrition core competencies, and strategies for curriculum development in medical nutrition education. METHODS: We administered a Delphi survey to systematically gather the opinion of a panel of Latin American experts in nutrition. The survey questionnaire was constructed considering scientific literature by using a 5-point Likert scale. Consensus was defined as >70% agreement on the importance of an item (Likert scale 4 and 5). RESULTS: A four-round Delphi survey was conducted for this research. In the second, third, and fourth rounds, we validated a total of 130 competencies by consensus, which were distributed into four different thematic areas: (1) basic nutrition concepts, (2) public nutrition and nutrition prevention throughout the life cycle, (3) nutrition status and disease, and (4) nutrition care process. CONCLUSION: The curricula for general physician education in medical school must include health promotion, prevention, and treatment of diseases related to nutrition. This goal can be reached by integrating ≤130 competencies into four different fundamental areas.
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Educación de Pregrado en Medicina , Competencia Clínica , Consenso , Curriculum , Técnica Delphi , Humanos , Estado NutricionalRESUMEN
Los cálculos biliares se encuentran dentro de los motivos de consulta más frecuentes a nivel mundial, la entidad quirúrgica emergente es la colecistitis en el 90-95 % de los casos, la colecistectomía laparoscópica es la opción ideal de tratamiento, la persistencia de sintomatología postoperatoria, inclusive en el transcurrir de los años es frecuente, en este contexto, es preciso mencionar al síndrome post-colecistectomía que es poco reportado en la localidad. Se presenta el caso de paciente masculino de 71 años de edad con antecedente de colecistectomía abierta hace 13 años, que consulta por meteorismo abdominal, dispepsia, leve dolor en hipocondrio derecho. En los exámenes complementarios de imagen, por ecografía de abdomen, se evidencia colelitiasis en muñón vesicular remanente, diagnóstico certificado por resonancia magnética, indicada previamente por facultativo para control de sus comorbilidades, en el cual se da el hallazgo incidental de litiasis vesicular. Se realiza manejo quirúrgico, colecistectomía laparoscópica, sin ninguna complicación. El paciente mostró adecuada evolución postquirúrgica, siendo dado de alta con analgesia y antibioticoterapia.
Gallstones are among the most frequent reasons for consultation worldwide, the emerging surgical entity is cholecystitis in 90-95% of cases, laparoscopic cholecystectomy is the ideal treatment option, the persistence of postoperative symptoms, even in the passing of the years it is frequent, in this context, it is necessary to mention the post-cholecystectomy syndrome that is little reported in the locality. We present the case of a 71-year-old male patient with a history of open cholecystectomy 13 years ago, who consulted for abdominal bloating, dyspepsia, and mild pain in the right hypochondrium. In the complementary imaging tests, by abdominal ultrasound, cholelithiasis is evidenced in the remaining gallbladder stump, a diagnosis certified by magnetic resonance, previously indicated by the physician to control his comorbidities, in which the incidental finding of gallbladder lithiasis occurs. Surgical management is performed, laparoscopic cholecystectomy, without any complications. The patient showed adequate postoperative evolution, being discharged with analgesia and antibiotic therapy.
Os cálculos biliares estão entre os motivos de consulta mais frequentes em todo o mundo, a entidade cirúrgica emergente é a colecistite em 90-95% dos casos, a colecistectomia laparoscópica é a opção de tratamento ideal, a persistência dos sintomas pós-operatórios, mesmo com o passar dos anos é frequente, nesse contexto, é necessário citar a síndrome pós-colecistectomia que é pouco relatada na localidade. Apresentamos o caso de um paciente do sexo masculino de 71 anos com história de colecistectomia aberta há 13 anos, que consultou por dispepsia, dispepsia e dor leve no hipocôndrio direito. Nos exames complementares de imagem, por ultrassonografia abdominal, evidencia-se colelitíase no coto vesicular remanescente, diagnóstico certificado por ressonância magnética, previamente indicado pelo médico para controle de suas comorbidades, em que ocorre o achado incidental de litíase vesicular. O manejo cirúrgico é realizado, colecistectomia laparoscópica, sem complicações. A paciente apresentou evolução pós-operatória adequada, recebendo alta com analgesia e antibioticoterapia.
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Humanos , Masculino , Anciano , Colecistectomía Laparoscópica , ColecistitisRESUMEN
SUMMARY Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that result in the uncontrolled release of catecholamines and secondary hypertension. They usually manifest with episodic blood pressure fluctuations, headaches and palpitations. In some cases PPGLs may be asymptomatic until they are detected as a diagnostic approach to other diseases. There have been reports that have associated PPGLs with arterial thrombosis, some with the additional finding of intracardiac thrombi. We present the case of a 21-year-old male Hispanic patient with a recurrent para-aortic paraganglioma detected by persistent hypertension, bilateral lower limb artery thrombosis and an intracardiac thrombus.
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Humanos , Masculino , Adulto , Adulto Joven , Paraganglioma/complicaciones , Feocromocitoma , Trombosis/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales , Recurrencia Local de NeoplasiaRESUMEN
Abstract The Colombian government, through Law 1787 of 2016, has created a regulatory framework that allows its citizens to have a safe and informed access to cannabis and its derivatives for medical and scientific purposes. Our country joins others in their efforts to legalize cannabis-derived substances for therapeutic purposes, as many jurisdictions have recognized the potential these products have in the treatment of certain medical conditions. This paper describes the current medical cannabis outlook in Colombia, compares the different medical cannabis supply systems in other parts of the world, summarizes the evidence related to the potential therapeutic benefits and potential risks of using cannabis for medical purposes.
Resumen Mediante la Ley 1787 de 2016, el Gobierno colombiano creó el marco regulatorio que permite el acceso seguro e informado al uso médico y científico del cannabis y sus derivados en nuestro territorio. Este movimiento hacia la legalización de sustancias derivadas de cannabis con fines terapéuticos se suma a otros instaurados en otros países que han reconocido el posible potencial que tienen estos productos en el tratamiento de ciertas condiciones clínicas. Este artículo describe la situación actual del cannabis medicinal en Colombia, compara los diferentes sistemas de provisión de cannabis con fines médicos en otras jurisdicciones, resume la evidencia alrededor de su utilización con fines médicos que justifica la legalización, y los potenciales riesgos que existen con el uso del cannabis.
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Humanos , Terapéutica , Cannabis , Marihuana Medicinal , Riesgo , Colombia , Gobierno , JurisprudenciaRESUMEN
Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that result in the uncontrolled release of catecholamines and secondary hypertension. They usually manifest with episodic blood pressure fluctuations, headaches and palpitations. In some cases PPGLs may be asymptomatic until they are detected as a diagnostic approach to other diseases. There have been reports that have associated PPGLs with arterial thrombosis, some with the additional finding of intracardiac thrombi. We present the case of a 21-year-old male Hispanic patient with a recurrent para-aortic paraganglioma detected by persistent hypertension, bilateral lower limb artery thrombosis and an intracardiac thrombus.
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Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Trombosis , Adulto , Humanos , Masculino , Recurrencia Local de Neoplasia , Paraganglioma/complicaciones , Trombosis/diagnóstico por imagen , Adulto JovenRESUMEN
Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) are toxic and bioaccumulative, included in the Stockholm Convention's list as persistent organic pollutants. Due to their toxicity, worldwide distribution, and lack of information in spermatozoa physiology during pre-fertilization processes, the present study seeks to analyze the toxic effects and possible alterations caused by the presence of these compounds in boar sperm during the in vitro capacitation. The spermatozoa capacitation was performed in supplemented TALP-Hepes media and mean lethal concentration values of 460.55 µM for PFOS, and 1930.60 µM for PFHxS were obtained. Results by chlortetracycline staining showed that intracellular Ca2+ patterns bound to membrane proteins were scarcely affected by PFOS. The spontaneous acrosome reaction determined by FITC-PNA was significantly reduced by PFOS and slightly increased by PFHxS. Both toxic compounds significantly alter the normal capacitation process from 30 min of exposure. An increase in ROS production was observed by flow cytometry and considerable DNA fragmentation by the comet assay. The immunocytochemistry showed a decrease of tyrosine phosphorylation in proteins of the equatorial and acrosomal zone of the spermatozoa head. In conclusion, PFOS and PFHxS have toxic effects on the sperm, causing mortality and altering vital parameters for proper sperm capacitation.
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BACKGROUND: Although a significant amount of literature has explored peer sexual harassment in higher education, little is known about peer sexual harassment in primary and middle school. Among existing studies, most have examined individual student characteristics that predict peer sexual harassment without considering the importance of the classroom and school context, which may prevent or promote such harassment. OBJECTIVE: The purpose of this study was to identify individual and school-related factors predicting sexual harassment victimization. METHODS: A sample of 17,364 Chilean students from Grades 5 through 8 in 405 schools with low socioeconomic status answered instruments concerning peer sexual harassment, other types of peer victimization and discrimination, and perceptions of classroom and school climate and norms against sexual harassment. Data were analyzed through hierarchical multivariate regression. RESULTS: Experiences of being sexual harassed by other students were reported by 13.5 % of students, with higher frequencies in male students, students from Grades 5 and 6, and students with lower individual socioeconomic status. School-related experiences of being discriminated against due to sexual orientation, ethnic origin, and disability were the strongest predictors of sexual harassment victimization. CONCLUSION: We discuss how peer sexual harassment might be understood as a consequence of peer social discrimination based on sexism, racism, and ableism. We also discuss the need to provide inclusive school climate policies that allow all students to feel safe and included.
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Grupo Paritario , Instituciones Académicas , Acoso Sexual/psicología , Acoso Sexual/estadística & datos numéricos , Adolescente , Niño , Chile/epidemiología , Niños con Discapacidad , Etnicidad , Femenino , Humanos , Masculino , Conducta Sexual , Clase SocialRESUMEN
Background: Previous studies of migraine classification have focused on the analysis of brain waves, leading to the development of complex tests that are not accessible to the majority of the population. In the early stages of this pathology, patients tend to go to the emergency services or outpatient department, where timely identification largely depends on the expertise of the physician and continuous monitoring of the patient. However, owing to the lack of time to make a proper diagnosis or the inexperience of the physician, migraines are often misdiagnosed either because they are wrongly classified or because the disease severity is underestimated or disparaged. Both cases can lead to inappropriate, unnecessary, or imprecise therapies, which can result in damage to patients' health. Methods: This study focuses on designing and testing an early classification system capable of distinguishing between seven types of migraines based on the patient's symptoms. The methodology proposed comprises four steps: data collection based on symptoms and diagnosis by the treating physician, selection of the most relevant variables, use of artificial neural network models for automatic classification, and selection of the best model based on the accuracy and precision of the diagnosis. Results: The artificial neural network models used provide an excellent classification performance, with accuracy and precision levels >97% and which exceed the classifications made using other model, such as logistic regression, support vector machines, nearest neighbor, and decision trees. Conclusions: The implementation of migraine classification through artificial neural networks is a powerful tool that reduces the time to obtain accurate, reliable, and timely clinical diagnoses.
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Algoritmos , Trastornos Migrañosos , Humanos , Modelos Logísticos , Trastornos Migrañosos/diagnóstico , Redes Neurales de la Computación , Máquina de Vectores de SoporteRESUMEN
Infection with Toxoplasma gondii is very common in humans throughout the world, the intake of raw or undercooked meat with tissue cysts and fruits, vegetables and water contaminated with parasite oocysts being the main routes of infection. Here, we analyzed the seroprevalence of anti-T. gondii antibodies in pregnant females (age 13-44 years; nâ¯=â¯920) between April 2014 and December 2017 from Chascomús (Argentina), a city immersed in a rural area. Altogether 320 tested positive for immunoglobulin G antibodies, yielding an overall seroprevalence of 34.8% (CI 95%: 31.7-37.9). No association was observed between seropositivity and age. In addition, by using the QGIS 3.2.1 software we analyzed the geographical distribution of 769 (83.6%) pregnant females in two main areas of the city: Urban (nâ¯=â¯157) and Peri-urban (nâ¯=â¯612) with a seroprevalence of 26.8% (CI 95%: 19.8-33.7) and 36.4% (CI 95%: 32.6-40.3) respectively, and this difference was statistically significant (pâ¯=â¯0.023). Furthermore, we assessed through a questionnaire survey, between April 2016 to December 2017, possible risk factors such as activity (urban and rural), home water supply, animal husbandry, presence of cats as pets, gardening and consumption of meat and its derivatives (pork, sheep meat and sausages) and their frequencies (consumption per week), not finding significant association with seropositivity. Significant differences was found when the seroprevalence was analyzed between the urban and peri-urban neighborhoods of the city of Chascomús. The higher seroprevalence in peri-urban neighborhoods could be due to an unfavorable socioeconomic situation and/or to undeveloped peri-urban environments, which is a risk factor that should be taken into account when planning the health care of pregnant females.
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BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. METHODS: We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. RESULTS: Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. CONCLUSION: IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA.
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Accurate and detailed species distribution maps are fundamental for documenting and interpreting biological diversity. For snakes, an ecologically diverse group of reptiles, syntheses and detailed data on distribution patterns remain scarce. We present the first comprehensive collection of detailed, voucher-based, point-locality, range maps for all described and documented Brazilian snakes, with the major aim of mitigating the Wallacean shortfall and as a contribution towards a better understanding of this rich, threatened, and poorly studied megadiverse fauna. We recorded a total of 412 snake species in Brazil on the basis of an extensive and verified point-locality database of 163,498 entries and 75,681 unique records (available here as Online Supporting Information). Our results reveal previously undocumented patterns of distribution, sampling effort, richness, and endemism levels, resulting in a more objective view of snake diversity in the Neotropics. Apart from these achievements, we understand that the most relevant and enduring contribution of the present atlas is to stimulate researchers to publish corrections, additions, and new discoveries.