The history and rationale of the development of new drugs for migraine treatment / A história e os fundamentos do desenvolvimento de novos medicamentos para o tratamento da migrânea

Abstract Migraine is one of the most prevalent and disabling diseases in the world. Migraine attack treatments and prophylactic treatments of this disease are essential to lessen its individual, social, and economic impact. This is a narrative review of the main drugs used for treating migraine, as well as the experimental models and the theoretical frameworks that led to their development. Ergot derivatives, triptans, non-steroid anti-inflammatory drugs, tricyclic antidepressants, beta-blockers, flunarizine, valproic acid, topiramate, onabotulinumtoxin A, ditans, monoclonal antibodies against CGRP and its receptor, and gepants are discussed. Possible therapeutic targets for the development of new drugs that are under development are also addressed. Many of the drugs currently in use for treating migraine were developed for the treatment of other diseases, but have proven effective for the treatment of migraine, expanding knowledge about the disease. With a better understanding of the pathophysiology of migraine, new drugs have been and continue to be developed specifically for the treatment of this disease.

Resumo A migrânea é uma das doenças mais prevalentes e incapacitantes do mundo. O tratamento da crise de migrânea e o tratamento profilático da doença são essenciais para diminuir o seu impacto individual, social e econômico. Este é um artigo de revisão narrativa. Revisamos as principais drogas usadas para a migrânea e os modelos experimentais e referenciais teóricos que levaram ao seu desenvolvimento. Foram abordados os derivados do ergot, triptanas, anti-inflamatórios não hormonais, antidepressivos tricíclicos, betabloqueadores, flunarizina, ácido valproico, topiramato, toxina onabotulínica do tipo A, os ditans, anticorpos monoclonais contra o CGRP e seu receptor e os gepants. Também foram abordados possíveis alvos terapêuticos para o desenvolvimento de novas drogas e drogas que estão em desenvolvimento para o tratamento da migrânea. Muitas das drogas usadas atualmente foram desenvolvidas para o tratamento de outras doenças e se mostraram efetivas para o tratamento da migrânea. Essas ajudaram a ampliar o conhecimento sobre a doença. Com o melhor entendimento da fisiopatologia da migrânea, novas drogas foram e estão sendo desenvolvidas especificamente para o tratamento dessa doença.

Caracterización de los aspectos etiológicos, fisiopatológicos, clínicos y terapéuticos de la sepsis y shock séptico / Characterization of the etiological, physiopathological, clinical and therapeutic aspects of sepsis and septic shock

La sepsis es un síndrome clínico basado en una compleja y dinámica interacción entre patógeno y huésped. La identificación de diferentes fenotipos y la heterogeneidad de la sepsis obligan a cambiar paradigmas en el diagnóstico-tratamiento. El shock séptico o septicémico se define como la hipotensión inducida por sepsis que persiste a pesar de la reanimación adecuada con fluidos, acompañada de alteraciones de la perfusión o disfunción de órganos. O la necesidad de fármacos vasoactivos para corregir la presión arterial. Es un tipo de shock distributivo, con reducción de las resistencias vasculares sistémicas y generalmente aumento del gasto cardíaco. En los últimos años, ha evolucionado la atención de la sepsis con especial enfoque shock séptico (SS) por su gravedad y su mayor morbimortalidad. En consideración a lo anterior, esta revisión tiene el propósito de realizar la caracterización de esta patología en los aspectos etiológicos, fisiopatológicos, clínicos y terapéuticos más importantes

Sepsis is a clinical syndrome based on a complex and dynamic interaction between pathogen and host. The identification of different phenotypes and the heterogeneity of sepsis requires a paradigm shift in its diagnosis and treatment. Septic shock is defined as a sepsis-induced hypotension that persists despite adequate fluid resuscitation, accompanied by perfusion abnormalities or organ dysfunction. It may also involve the need for vasopressor drugs to correct blood pressure. It is a type of distributive shock, characterized by reduced systemic vascular resistance and typically increased cardiac output. In recent years, the management of sepsis has evolved with a special focus on septic shock (SS) due to its severity and higher morbidity and mortality. Considering the above, this review aims to characterize this condition in terms of its etiological, pathophysiological, clinical, and therapeutic aspects

Case-problem-based learning of pathophysiology based on inquiry-based learning and process management / 中华医学教育探索杂志

Based on the teaching concept of constructivism, this study aims to promote independent inquiry-based learning and clinical thinking among students and establish the guiding ideology of "full participation, process control, in-depth discussion, and expansion of thinking". A blending learning model was adopted with offline inquiry-based group learning and in-class defense and comment, as well as online teacher-student interaction and supervision to promote learning. Case-problem-based learning (CPBL) of pathophysiology was carried out among the medical students in the class of 2017, and process management was strengthened to effectively manage the two key links of data retrieval and group discussion. The analysis of 176 teaching evaluations collected at the end of the semester show that in terms of the overall evaluation of CPBL teaching, 162 students (92.05%) had high evaluation on teaching objectives, organization, cases, and personal gains and held a very or relatively favorable attitude. There were more negative feedbacks on "appropriate time allocation"; 21 students (11.93%) held a relatively or very disapproving attitude, and 149 students (84.66%) "felt very tired". In terms of teaching effect evaluation, 150 students (85.23%) strongly or relatively agreed that CPBL teaching may help to understand professional knowledge, stimulate learning enthusiasm and initiative, improve problem solving ability, emphasize clinical practice to cultivate clinical thinking, supervise and promote learning, and enhance team cooperation and teacher-student communication. In terms of the evaluation of teachers, 167 students (94.89%) thought that teachers were rigorous, responsible, and enthusiastic in teaching, attached importance to process management, and did well in effective guidance and thinking inspiration (strongly or relatively agree). The above results suggest that the CPBL teaching reform of pathophysiology based on process management can effectively promote in-depth inquiry-based independent learning and the cultivation of clinical thinking and improve teaching effectiveness, but further improvement is needed for teaching arrangement and time allocation.

Case-based learning method combined with mind mapping in pathophysiology teaching / 中华医学教育探索杂志

Objective:To explore the effect of case-based learning (CBL) combined with mind mapping on pathophysiology teaching.Methods:Totally 124 undergraduate students from Batch 2017 of Yanjing Medical College of Capital Medical University were selected as research subjects, and they were divided into experimental group ( n=60) and control group ( n=64). The traditional teaching method was used in the control group, while the experimental group adopted CBL combined with mind mapping teaching method. At the end of the course, the teaching effectiveness was evaluated by the usual grades from Mosoteach online teaching platform and test performances. SPSS 17.0 was used to perform Wilcoxon rank sum test and the Welch's correction t test. Results:The initiative of students in the experimental group was significantly improved than that in the control group ( P<0.001), and the understanding ability was also better in the experimental group than the control group ( P=0.020). The average theoretical scores of the experimental group were significantly better than those of the control group ( P=0.036), with the main manifestations that the scores of objective questions were higher than those of the control group ( P<0.001), and the scores of short answer and discussion questions were higher than those of the control group ( P=0.006). There was no significant difference in noun interpretation scores between the two groups ( P=0.302). Conclusion:The CBL combined with mind mapping can significantly improve the teaching quality of pathophysiology.

Advances in application of optical coherence tomography angiography for quantitative analysis in central serous chorioretinopathy / 中华眼底病杂志

Central serous chorioretinopathy (CSC) is one of the representative pachychoroid spectrum disease. Although fundus fluorescein angiography and indocyanine green angiography can be used as the gold standard for the diagnosis of CSC, they are invasive examinations, which may bring certain risks in clinical application and cannot help us obtain quantitative parameters. Optical coherence tomography angiography (OCTA), as a non-invasive and quantitative examination, is an important imaging tool for understanding the pathogenesis, diagnosis and treatment of CSC. With the advancement of OCTA, the swept-source OCTA has a satisfying scanning depth, a wider scanning range and a higher resolution. The development of OCTA broadens the horizons of the pathogenesis of CSC, promotes the understanding of the pathophysiology of CSC, and sheds new light for its clinical diagnosis and treatment. Based on OCTA, the choroid and retina in eyes with CSC are presented with qualitative and quantitative changes in vascular system. OCTA-guided CSC treatment and the discovery of prognostic markers based on OCTA challenge the application of traditional imaging techniques in CSC. With the continuous improvement and progress of OCTA technology, traditional angiography combined with OCTA will bring great benefits to the diagnosis and treatment of CSC. This review summarizes the quantitative application of OCTA in the pathogenesis, diagnosis and treatment of CSC.

Mechanisms of the acute kidney injury to chronic kidney disease transition / 中华老年医学杂志

Acute kidney injury(AKI)is a common clinical pathophysiological phenomenon, which is characterized by high morbidity, ICU hospitalization rate and mortality.In addition, AKI is an independent risk factor for chronic kidney disease(CKD)and end-stage renal disease.A number of studies have revealed various mechanisms involved in the transition of AKI to CKD, but there is still no breakthrough in effective prevention and treatment.This article reviews the mechanisms of transition from AKI to CKD, and expects to provide potential targets for further intervention.

Infarto agudo de miocardio tipo 2: desafíos en la práctica clínica

El infarto de miocardio tipo 2 se produce como consecuencia del desequilibrio entre la relación aporte/consumo de oxígeno miocárdico, que puede ser secundario a la isquemia, debida a mayor demanda de oxígeno del miocardio o como consecuencia de la disminución del aporte en él. Se realiza una revisión actualizada de la literatura acerca del infarto de miocardio tipo 2. Se revisaron aspectos relacionados con los criterios diagnósticos, la fisiopatología, las características clínicas y el tratamiento, para lo cual se realizó una revisión de los principales artículos publicados de enero del 2017 a enero del 2022, en idiomas inglés y español, se consultaron las bases de datos: Pubmed, Scielo y el buscador Google Scholar. Se escogieron 51 artículos. Las evidencias demuestran que existen deficiencias en el conocimiento del infarto agudo de miocardio tipo 2, que dificultan su adecuado diagnóstico, tratamiento y pronóstico. Se recomienda la realización de estudios prospectivos para una mayor evaluación de la prevalencia, la fisiopatología y el manejo de esta entidad.

Type 2 myocardial infarction occurs as a consequence of the imbalance between the myocardial oxygen supply/consumption ratio, which may be secondary to ischemia, due to increased myocardial oxygen demand or as a consequence of decreased oxygen supply. An updated review of the literature on type 2 myocardial infarction is carried out. Aspects related to diagnostic criteria, pathophysiology, clinical characteristics and treatment were reviewed, for which a review of the main articles published in January from 2017 to January 2022, in English and Spanish, the databases were consulted: Pubmed, Scielo and the Google Scholar search engine. 51 articles were chosen. The evidence shows that there are deficiencies in the knowledge of type 2 acute myocardial infarction, which hinder its proper diagnosis, treatment and prognosis. Prospective studies are recommended for further evaluation of the prevalence, pathophysiology, and management of this entity.

Hígado graso (parte 1): aspectos generales, epidemiología, fisiopatología e historia natural / Non-alcoholic fatty liver disease part 1: general aspects, epidemiology. pathophysiology and natural history

Resumen El hígado graso no alcohólico (NAFLD) se define por la presencia de grasa o esteatosis en los hepatocitos y abarca un espectro que va desde la esteatosis simple, pasa por la esteatohepatitis no alcohólica (NASH) con inflamación y fibrosis, y finaliza en la cirrosis. Se considera una prevalencia mundial global cercana al 25% en la población general y se diagnóstica entre los 40 y 50 años, con variaciones respecto al sexo predominante y con diferencias étnicas (la población hispana es la más afectada). El hígado graso está asociado al síndrome metabólico (SM), y la obesidad se considera el principal factor de riesgo con su presencia y con su progresión. El hígado graso es un trastorno complejo y muy heterogéneo en su fisiopatología, que resulta de la interacción de múltiples elementos: factores genéticos, epigenéticos, ambientales, culturales, entre otros. Todo ello en conjunto lleva a incremento paulatino de grasa hepática, resistencia a la insulina y alteraciones hormonales y de la microbiota intestinal, lo que genera un daño hepatocelular a través de la formación de radicales libres de oxígeno y activación de la fibrogénesis hepática. La historia natural del hígado graso es dinámica: los pacientes con esteatosis simple tienen bajo riesgo de progresión a cirrosis, mientras que en los pacientes con NASH este riesgo se aumenta; sin embargo, el proceso puede ser reversible y algunas personas tendrán una mejoría espontánea. La fibrosis parece ser el determinante de la mortalidad global y de los desenlaces asociados a la enfermedad hepática; se considera que en todos los pacientes la fibrosis empeora una etapa cada 14 años y en NASH empeora en una etapa cada 7 años. Estudios previos concluyen que aproximadamente 20% de los casos de esteatosis simple progresan a NASH y que, de ellos, aproximadamente el 20% progresan a cirrosis, con presencia de hepatocarcinoma (HCC) en el 5% a 10% de ellos.

Abstract Fatty liver or NAFLD is defined by the presence of fat or steatosis in hepatocytes and covers a spectrum that goes from simple steatosis, through steatohepatitis (NASH), with inflammation and fibrosis and ending in cirrhosis. It is considered a global world prevalence close to 25% in the general population and is diagnosed between 40 and 50 years, with variations regarding the predominant sex and with ethnic differences, affecting more the Hispanic population. Fatty liver is associated with metabolic syndrome (MS), and obesity is considered the main risk factor for its presence and progression. Fatty liver is a complex and very heterogeneous disorder in its pathophysiology, resulting from the interaction of multiple elements, genetic, epigenetic, environmental, cultural factors, etc. All this together leads to an accumulation of hepatic fat, insulin resistance, hormonal and intestinal microbiota alterations, generating hepatocellular damage through the formation of free oxygen radicals and activation of hepatic fibrogenesis. The natural history of fatty liver is dynamic, patients with simple steatosis have a low risk of progression to cirrhosis, in patients with NASH this risk is increased, however, the process may be reversible, and some people will have spontaneous improvement. Fibrosis seems to be the determinant of overall mortality and outcomes associated with liver disease, it is considered that in all patients fibrosis worsens one stage every 14 years, in NASH it worsens one stage every seven years. Previous studies conclude that approximately 20% of cases of simple steatosis progress to NASH and that approximately 20% of them progress to cirrhosis, with the presence of hepatocellular carcinoma (HCC) in 5 to 10% of them.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 1: definições, farmacologia, epidemiologia, fisiopatologia e fatores genéticos / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 1: definitions, pharmacology, epidemiology, pathophysiology, and genetics

Os anti-inflamatórios não esteroidais (AINE) estão entre os medicamentos mais utilizados no mundo e são os fármacos mais frequentemente associados à ocorrência de reações de hipersensibilidade na América Latina. As reações têm grande variabilidade de apresentações clínicas e, consequentemente, com abordagem terapêutica difícil. Nesta revisão, abordamos aspectos farmacológicos dos AINE, bem como as definições, epidemiologia e fisiopatologia das reações de hipersensibilidade aos AINE. Por fim, discutimos aspectos genéticos associados à intolerância e alergia a esses fármacos.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide and the drugs most frequently associated with the occurrence of hypersensitivity reactions in Latin America. The clinical presentation of the reactions varies widely, which makes them difficult to treat. In this review, we address pharmacological aspects of NSAIDs, as well as the definitions, epidemiology, and pathophysiology of hypersensitivity reactions to NSAIDs. Finally, we discuss genetic factors associated with intolerance and allergy to these drugs.

Fisiopatología del síndrome de ovario poliquístico / Pathophysiology of polycystic ovary syndrome

Introducción: En la génesis del síndrome de ovario poliquístico intervienen múltiples factores sistémicos y locales que tienen una relación multidireccional sobre los que persisten muchas cuestiones aún sin dilucidar y cierta confusión e incertidumbre. Objetivo: Describir el enfoque actual sobre las causas y los mecanismos involucrados en el origen y desarrollo del síndrome de ovario poliquístico. Métodos: Se realizó una revisión bibliográfica tipo estado del arte. Se revisaron alrededor de 250 artículos, que se obtuvieron de las bases PubMed, Medline, SciELO y Google Académico. Se describen los factores y las vías que se proponen para explicar la etiopatogenia y fisiopatología de alteraciones genéticas, ambientales, endocrinas y metabólicas asociadas al síndrome y su expresión clínica. Conclusiones: La fisiopatología del síndrome de ovario poliquístico es compleja. Muchos aspectos permanecen sin esclarecerse, pero se tiene cada vez más conocimiento que aporta luz a los enigmas que aún persisten y a la comprensión de fenómenos previamente desconocidos. Existe el convencimiento creciente de que la alteración central es a nivel ovárico, que el síndrome es heterogéneo en todos sus elementos y que conocer la gran diversidad de factores y mecanismos que intervienen en su etiología y patogenia es fundamental no sólo desde lo científico, sino también por su utilidad práctica(AU)

Introduction: Multiple systemic and local factors are involved in the genesis of polycystic ovary syndrome that have a multidirectional relationship about which many there are questions yet to be clarified and some confusion and uncertainty persist. Objective: To describe the current approach to the causes and mechanisms involved in the origin and development of polycystic ovary syndrome. Methods: A state-of-the-art literature review was performed. The factors and pathways proposed to explain the etiopathogenesis and pathophysiology of genetic, environmental, endocrine and metabolic alterations associated with the syndrome and its clinical expression are described. Conclusions: The pathophysiology of polycystic ovary syndrome is complex. Many aspects remain unclear, but there is increasing knowledge that sheds light on the enigmas that still persist and on the understanding of previously unknown phenomena. There is a growing conviction that the central alteration is at the ovarian level, that the syndrome is heterogeneous in all its elements and that knowledge of the great diversity of factors and mechanisms involved is fundamental, not only from the scientific point of view but also for its practical utility(AU)

Particularidades de la resistencia a la insulina en el síndrome de ovario poliquístico / Particularities of insulin resistance in polycystic ovary syndrome

Introducción: La resistencia a la insulina e hiperinsulinemia son frecuentes en las mujeres con síndrome de ovario poliquístico. Una condición que resulta relevante como factor patogénico principal de las alteraciones metabólicas que acompañan al síndrome y porque condiciona fenotipos con mayor riesgo metabólico y reproductivo. Objetivo: Realizar una revisión bibliográfica sobre la resistencia a la insulina en el síndrome de ovario poliquístico. Métodos: Se realizó una revisión bibliográfica tipo estado del arte. Se consultaron 229 artículos obtenidos de las bases PubMed, Medline, SciELO y Google Académico. Conclusiones: La resistencia a la insulina tiene importancia capital en el síndrome de ovario poliquístico, no sólo por su frecuencia, sino también por el amplio espectro de alteraciones metabólicas y reproductivas que se le asocian. Como en otros trastornos que caracterizan al síndrome, los mecanismos fisiopatogénicos específicos no están del todo claros, pero existe la posibilidad de diagnosticarla y tratarla oportunamente, con lo que pueden prevenirse complicaciones, algunas de importancia vital. Por esto, la educación para la salud desde edades tempranas, que propicie estilos de vida saludable, prevención del sobrepeso corporal y control de otros factores que agravan la resistencia a la insulina, así como la evaluación temprana de la resistencia a la insulina, deben entenderse como cruciales en el manejo de las mujeres con síndrome de ovario poliquístico, con independencia de su peso corporal(AU)

Introduction: Insulin resistance and hyperinsulinemia are frequent in women with polycystic ovary syndrome. This condition is relevant as the main pathogenic factor of the metabolic alterations that accompany the syndrome and because it conditions phenotypes with higher metabolic and reproductive risk. Objective: To perform a literature review on insulin resistance in polycystic ovary syndrome. Methods: A state-of-the-art literature review was performed. The particularities of insulin resistance associated with the syndrome and its clinical expression are described. Conclusions: Insulin resistance is of paramount importance in polycystic ovary syndrome, not only because of its frequency, but also because of the wide spectrum of metabolic and reproductive alterations associated with it. As in other disorders that characterize the syndrome, the specific pathophysiological mechanisms are not entirely clear. However, it is possible to diagnose and treat it in a timely manner, thus preventing complications, some of which are of vital importance. Therefore, and regardless of their body weight, health education from an early age to promote healthy lifestyles, prevention of body overweight and control of other factors that aggravate insulin resistance, including early evaluation of insulin resistance, should be understood as crucial in the management of women with polycystic ovary syndrome(AU)

Aneurisma aórtico torácico com trombose associada em Bugio-preto (Alouatta caraya) / Thoracic aortic aneurysm with associated thrombosis in black-and-gold howler monkey (Alouatta caraya)

O aneurisma é uma dilatação anormal e permanente das artérias, resultante do enfraquecimento da parede do vaso adelgaçamento da camada média e enfraquecimento da camada elástica. Em animais, a maioria dos casos de aneurisma tem origem idiopática e são detectados acidentalmente durante a necropsia. O objetivo deste trabalho é relatar um caso de aneurisma aórtico com trombose associada em Bugio-preto(Alouatta caraya), bem como seus aspectos patológicos. O animal era adulto, macho, pertencente ao Centro Nacional de Primatas (CENP), na cidade de Ananindeua-PA, foi encaminhado para exame necroscópico para investigação da causa mortis. No histórico do animal, não constava qualquer enfermidade. O animal apresentava bom escore de condição corporal com preservação da topografia anatômica dos órgãos. Entretanto, observou-se presença de aumento de volume localizado em aorta torácica, a 1,4 cm da base do coração. Na abertura aórtica foi observado dilatações de tamanhos variados e, no interior da maior dilatação, notou-se uma estrutura de coloração vermelho escuro, aderida, de aspecto seco e superfície áspera, medindo 1,5 cm. Aneurismas aórticos em primatas não humanos não são comuns, porém já foram reportados na literatura. O diagnóstico precoce utilizando exames complementares é importante, porém, ainda há recursos não empregados na rotina veterinária tornando ainda mais difícil o diagnóstico e prevenção. Por isso, na medicina veterinária, os aneurismas são detectados acidentalmente durante a necropsia. Com base nos achados anatomopatológicos, concluiu-se que o animal veio a óbito por trombose associada a aneurisma aórtico.

An aneurysm is an abnormal and permanent dilation of the arteries, resulting from the weakening of the vessel wall.thinning of the middle layer and weakening of the elastic layer. In animals, most cases of aneurysm are idiopathic. This paper aimed to report a case of aortic aneurysm with associated thrombosis in a black-and-gold howler monkey(Alouatta caraya), as well as its pathological aspects. The animal was an adult, male, belonging to the National Primate Center (CENP), in the city of Ananindeua-PA, that was referred for necroscopic examination to investigate the causa mortis. In the animal's history, there was no disease. The animal had a good body condition score with preservation of the anatomical topography of the organs. However, there was an increase in volume located in the thoracic aorta, 1.4 cm from the base of the heart. In the aortic opening, dilations of different sizes were observed, and inside the largest dilatation, a structure of dark red color, adhered, with a dry appearance and rough surface, measuring 1.5 cm was noted in addition to dilations of different sizes. Inside the largest cavitation, a dark red structure was observed, adhered, with a dry appearance and rough surface, measuring 1.5 cm. Aortic aneurysms in non-human primates are incommon, but have been reported in the literature. Early diagnosis using complementary exams is important, however, there are still resources not used in the veterinary routine, making diagnosis and prevention even more difficult. Therefore, in veterinary medicine, aneurysms are accidentally detected during necropsy. Based on the anatomopathological findings, it was concluded that the animal died due to thrombosis associated with an aortic aneurysm.

Current theories of pathophysiology and potential therapeutic targets of COVID-19: What we know so far

In 2019, a new variant of coronavirus emerged that put the whole world on a standstill due to its unprecedented spread and morbidity. Since then, scientists have been working on several theories to explain the origin and pathogenesis of the virus. Over this period of time, it has been observed clinically that individual variation exists in the way this virus infects people, its symptomatology and sequelae. The pathophysiology is still unclear. This review was taken up to consolidate all the available information until date about current theories of etiopathogenesis with an understanding of potential therapeutic targets on the mechanisms. This review also highlights the gray areas that need to be addressed in the future. Research papers published up to December 7, 2020 were included based on a search on PubMed, Google Scholar, etc., to get the latest relevant literature on this topic. Coronavirus expresses differently in different individuals, affecting different organ systems, and having variable severity. However, the underlying pathogenic mechanisms are not completely understood. Due to the lack of definite curative therapy, it is essential to explore the basic pathophysiology so as to develop more effective and target-based therapies in the future.

Afecciones, manifestaciones y repercusiones neurológicas del COVID-19 / COVID-19 conditions, manifestations, and neurological repercussions

Resumen Inetroducción: El Síndrome Respiratorio Agudo Severo (SARS-CoV-2) es la entidad patológica responsable de la actual pandemia que no solo genera un cuadro respiratorio distintivo sino que también se ha asociado con múltiples mecanismos de invasión al sistema nervioso central (SNC). Objetivo: Determinar las afecciones, manifestaciones y repercusiones neurológicas que puede generar la infección por SARS-CoV-2. Métodos: Revisión de la literatura científica de pacientes con infección por SARS-CoV-2, en quienes se evaluó desarrollo de afecciones, manifestaciones y repercusiones neurológicas, desenlace seleccionado en los estudios, presencia de afecciones micro y macroscópicas del SNC y periférico (SNP). Resultados: Se estudiaron 40 artículos que analizaban la familia y estructura del SARS-CoV-2, mecanismos fisiopatológicos, manifestaciones clínicas neurológicas y las posibles repercusiones a nivel sistema nervioso central. Conclusiones: El SARS-CoV-2 es una entidad patológica que se asocia a distintos mecanismos de intervención neurológica, por medio de infección directa al SNC, secundario a un proceso parainfeccioso y postinfeccioso, relacionado con el síndrome de tormenta de citoquinas, daño endotelial, trastornos trombóticos, adicionalmente de secundario a hipoxia, hipoxemia y fallo multiorgánico.

Abstract Introduction: Severe Acute Respiratory Syndrome (SARS-CoV-2) is the pathological entity responsible for the current pandemic that not only generates a distinctive respiratory pattern but has also been associated with multiple mechanisms of invasion of the central nervous system (CNS). Objective: To determine the affections, manifestations and neurological repercussions that SARS-CoV-2 infection can generate. Methods: Review of the scientific literature of patients with SARS-CoV-2 infection, in whom the development of conditions, manifestations and neurological repercussions, selected outcome in the studies, presence of micro and macroscopic conditions of the CNS and peripheral (PNS) were evaluated. Results: 40 articles were included where the family and structure of SARS-CoV-2, pathophysiological mechanisms, neurological clinical manifestations, and possible repercussions at the central nervous system level were analyzed. Conclusions: SARS-CoV-2 is a pathological entity that is associated with different mechanisms of neurological intervention, through direct infection to the CNS, secondary to a parainfectious and postinfectious process, related to cytokine storm syndrome, endothelial damage, thrombotic disorders, in addition to secondary to hypoxia, hypoxemia and multiple organ failure.

Signos radiológicos en la neuroimagen de pacientes pediátricos con trastorno por estrés postraumático / Radiological signs in neuroimaging of pediatric patients with posttraumatic stress disorder

RESUMEN Introducción: El trastorno por estrés postraumático afectan la salud mental de los pacientes pediátricos, se considera muy común en estos pacientes. Estudios científicos apoyados en la resonancia magnética han fundamentado una estrecha relación entre el estrés postraumático y cambios estructurales en el cerebro. Se realizó una revisión bibliográfica en el periodo de abril a mayo de 2021, en los recursos disponibles en MEDLINE, SciELO, Pubmed y Elsevier. Del total de consultas se citaron 25 referencias. Objetivo: Describir los signos radiológicos en la neuroimagen de pacientes pediátricos con estrés postraumático. Desarrollo: Los estudios de neuroimagen en niños y adolescentes con trastorno por estrés postraumático se han centrado en estructuras anormales y la funcionalidad de algunas regiones individuales del cerebro; estas implican las regiones cerebrales asociadas con la fisiopatología, ellas son: la corteza prefrontal medial y dorsolateral; la corteza orbitofrontal; ínsula; núcleo lentiforme; amígdala; hipocampo y el parahipocampo; la corteza cingulada anterior y posterior; el precúneo; cúneo; el giro fusiforme y lingual y los tractos de materia blanca que conectan estas regiones cerebrales. Conclusiones: Los signos radiológicos en la neuroimagen de pacientes pediátricos con trastorno por estrés postraumático son: reducción de los volúmenes del hipocampo; del volumen cerebral e intracraneal y del volumen de la amígdala, así como una disminución del área total del cuerpo calloso. Además se observa que el volumen hipofisario y los volúmenes de materia gris cerebral fueron menores en los pacientes con estrés postraumático.

ABSTRACT Introduction: Post-traumatic stress disorder affects the mental health of pediatric patients; it is considered very common in these patients. Scientific studies supported by magnetic resonance imaging have established a close relationship between post-traumatic stress and structural changes in the brain. A bibliographic review was carried out in the period from April to May 2021, in the resources available in MEDLINE, SciELO, Pubmed and Elsevier. Of the total of consultations, 25 references were cited. Objective: To describe the radiological signs in the neuroimaging of pediatric patients with post-traumatic stress disorder. Development: Neuroimaging studies in children and adolescents with post-traumatic stress disorder have focused on abnormal structures and the functionality of some individual brain regions; these involve the brain regions associated with pathophysiology, they are: the medial and dorsolateral prefrontal cortex; the orbitofrontal cortex; insula; lentiform nucleus; amygdala; hippocampus and parahippocampus; the anterior and posterior cingulate cortex; the precuneus; cuneus; the fusiform and lingual gyrus and the white matter tracts that connect these brain regions. Conclusions: The radiological signs in the neuroimaging of pediatric patients with post-traumatic stress disorder are: reduction of the volumes of the hippocampus; brain and intracranial volume and amygdala volume, as well as a decrease in the total area of ​​the corpus callosum. In addition, it is observed that the pituitary volume and the volumes of cerebral gray matter were lower in patients with post-traumatic stress.

Periodic limb movements during sleep vs seizures and epileptiform discharges: some supposedly shared pathomechanisms / Movimentos periódicos dos membros durante o sono vs crises e descargas epileptiformes: alguns patomecanismos supostamente compartilhados

This is a narrative review that assesses some possible underlying abnormal mechanisms shared between periodic limb movements during sleep (PLMS) and interictal epileptiform discharges (IEDs) or epileptic seizures. The underlying abnormal mechanisms of PLMS are not clearly defined, but the hypotheses raised include a pure motor mechanism originating in the brainstem, spinal cord or a cortico-subcortical interaction, influenced by predisposing factors, through neural networks. PLMS rhythmicity appears to be closely linked to sleep microarchitecture, and also to cortical arousals, as with some types of epilepsy, which involve both the underlying sleep rhythms and their intrinsic functions as well as the so-called central pattern generators that produce rhythmic motor patterns. However, the relationship between PLMS and epilepsy has not yet been fully clarified. Rhythmicity and sleep fragmentation appear to be common denominators between them, at least more closely in sleep-related hypermotor epilepsy. To some extent, the electroencephalographic changes of PLMS would express an epiphenomenon of the involvement of some underlying brain networks common to epileptic seizures and IEDs.

Esta é uma revisão narrativa que avalia alguns possíveis mecanismos anormais subjacentes compartilhados entre os movimentos periódicos dos membros durante o sono (MPMS) e as descargas epileptiformes interictais (DEIs) ou crises epilépticas. Os mecanismos anormais subjacentes dos MPMS não estão claramente definidos, mas as hipóteses levantadas incluem mecanismo motor puro originado no tronco cerebral, medula espinhal ou uma interação córtico-subcortical, por influência de fatores predisponentes, através das redes neurais. A ritmicidade dos MPMS aparece estar intimamente ligada à microarquitetura do sono, e também aos despertares corticais, como acontece com alguns tipos de epilepsia, o que envolve tanto os ritmos subjacentes do sono e suas funções intrínsecas quanto os chamados geradores de padrões centrais que produzem padrões motores rítmicos. No entanto, a relação entre PLMS e epilepsia ainda não foi totalmente esclarecida. Ritmicidade e fragmentação do sono parecem ser denominadores comuns entre eles, pelo menos mais intimamente na epilepsia hipermotora relacionada ao sono. Em certa medida, as alterações eletroencefalográficas de PLMS expressariam um epifenômeno do envolvimento de algumas redes cerebrais subjacentes comuns a crises epilépticas e IEDs.

Teaching and practice in Homeopathy via pharmacobotany and pathophysiology

Semiology, Clinical Pathophysiology, Phytotherapy and Homeopathy were taught through active methodology by the Moodle platform (HL) also using apps for monitoring injuries through SAPB site, building rationality for the external topic use of homeopathic and herbal medicines.At the 7th Infirmary of General Hospital Santa Casa de Misericordia in Rio de Janeiro, the clinical medical team of the Benoit Mure Nucleus of Assistance Teaching and Research,made a medicinal plant gardenwith the agricultural/environmental educator, and communityethnicalleaders. Undergraduate students from UNIFASE/FMP Academic League of Physiology and Pathophysiology plantedCalendula Officinalis seedlings, destined to research in pharmacobotany and to be in touch with pharmacotechnical prepares. Aims: To follow-up the study since from seedling of Calendula Officinalistill to prepare of HUD. Methodology: To prepare medicinal garden: plant seedlings of Calendula offin accordance with good agricultural techniques. At first: Three seeds in ten pots, made in triplicate (N = 90), to obtain explants of quality analyzed whose evaluation was about plant development (explants percentual: weight, size, viability, morphology). To visit pharmacy-school to learn how to preparematrix extracts and High Ultra-Diluted Solutions (HUD) of Calendula off 6DH. Results and Discussion: The stages of teaching semiology and practice in pharmacobotany, besides cultive plant have been completed.Viability was impaired because of lack of irrigation during 4 months (50%). Weight, sizewere minor than usual but with no statistical significance (p>0.05). Morphology was maintained. Unfortunately, the visit to pharmacy-school couldn't be performed at this period. Conclusion: Through hybrid learning and face-to-face activities completely realized, students had qualitative perception of the relevance about morphology and quality of plant development, chemistry plant production, aiming for resolutive actions based upon pathophysiology of chronic diseases. Because of pandemic, it was described just a preliminary experience. After returning to normal activities the experiment will be repeated.

Practical teaching of pathophysiology to LAFFH at the IPD outpatient clinic of FMP/FASE: Historical Repor

Undergraduate students of UNIFASE/FMP, through the Academic League of Human Physiology and Pathophysiology (Liga Acadêmica de Fisiologia e FisiopatologiaHumana -LAFFH), participate in a supervised internship to outpatient at the Infectious and Parasitic DiseasesService of FMP/FASE, authorized by Clinical Direction (October 2018). Patients received conventional therapy in addition to complementary therapy with Homeopathy, for external use for cleaning skin lesions and modulating inflammatory responses, whose mechanisms of action are already described in the scientific literature and authorized by ANVISA. Aims: Make approach of undergraduate students to Homeopathic pathophysiology. Methodology: The supervised clinical internship of LAFFH students is in two service rooms with 6 students in each, based on prior appointment due to spontaneous demand, with medical records registered by the IPD outpatient service secretary. Outpatient clinical care addresses the pathophysiology and miasms of the symptoms and signs of neglected chronic parasitic diseases prevalent in our country, identified by anamnesis and physical examination. They are correlated to biological activities in plant chemistry classes, besides official homeopathic pharmacopoeia. So, it was adopted the external use of HUD Ledum palustre 6ch for the cleansing of skin lesions with torpid evolution at IPD. Results and discussion: Two patients with edemaand varicose ulcers were treated with the ointment offered. Edema extension which was +++/4+ to both patients diminished to +/4+ in 30 days of interval. Indeed, ulcers remained at the same shape and size, but their bases were cleaned, without purulence. Novel clinical sessions did not occur because of social distancing needed. Conclusion: It has been developed a positive perception among patients and students about the action of homeopathic remedies. The practical teaching activity initiated encourages students in clinical reasoning about complementary therapeutic association with Homeopathy for patients whose evolution is below the expected prognosis with conventional therapy. Project of clinical observation will be elaborated to research ethics committee.

Evidence of dengue virus in eviscerated specimens of panophthalmitis secondary to dengue fever: A possible cause-effect phenomenon

Purpose: To report a retrospective series of three cases of infectious panophthalmitis post?dengue fever with ex vivo confirmation of dengue virus ribonucleic acid (RNA) in the tissues of the eye. Methods: Four eyes of three patients, who were diagnosed with panophthalmitis following dengue fever and who underwent evisceration, were included. All demographic and clinical data were recorded. The eviscerated samples were subjected to direct microscopy, culture for bacteria, fungi, and parasites, and molecular virology (dengue virus [DENV] NS1?specific reverse transcription loop?mediated isothermal amplification (RT?LAMP) assay). Results: The time from the development of dengue fever to the occurrence of ocular symptoms was 4.33 ± 1.15 (median 5) days. DENV NS1 RNA, suggestive of the presence of the dengue virus, was confirmed in all evisceration specimens (uveal tissue, cornea). All the patients recovered completely from dengue fever and on follow?up had healthy eviscerated sockets. Conclusion: Demonstration of the DENV RNA in the eviscerated specimens of panophthalmitis following dengue fever implicates the DENV in the pathophysiology of the ocular infection.

Generalised Myoclonus and Cerebellar Ataxia Associated with COVID-19 : A Case Report

COVID-19 pandemic is a Global burden to Public Health. An array of Neurological Manifestations have been reported to be associated with COVID-19 like Anosmia, Cerebrovascular accident, Meningitis, Encephalitis, Seizures, Guillain-Barré Syndrome (GBS), Acute Disseminated Encephalomyelitis (ADEM) etc. Generalised Myoclonus and Cerebellar Ataxia, is a less common Neurological Manifestation when compared to others. Here, we report a case of Generalized Myoclonus and Cerebellar Ataxia following COVID-19 infection. The possible mechanisms of Myoclonus and Ataxia following COVID-19 are also discussed