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Objective Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. Methods Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease’s context. Results None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. Conclusion Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial Resumo Objetivo Anormalidades no endométrio eutópico de mulheres com endometriose podem estar relacionadas à infertilidade associada à doença. Embora a análise prévia de sequenciamento de RNA não tenha evidenciado expressão diferencial em transcritos endometriais de pacientes com endometriose, outras alterações moleculares poderiam afetar a síntese de proteínas e a receptividade endometrial. Nosso objetivo foi rastrear mutações funcionais em transcritos de endométrios eutópicos de mulheres inférteis com endometriose e de controles durante a janela de implantação. Métodos Os dados do sequenciamento de RNA de biópsias endometriais coletados durante a janela de implantação de 17 pacientes (6 mulheres inférteis com endometriose, 6 controles inférteis, 5 controles férteis) foram analisados para a descoberta de variantes e a identificação de mutações funcionais. Um estudo direcionado das alterações encontradas foi realizado para compreender os dados no contexto da doença. Resultados Nenhuma das variantes identificadas foi comuma outras amostras dentro do mesmo grupo, assim como nenhuma mutação se repetiu entre pacientes com endometriose, controles inférteis e férteis. No grupo de endometriose, foram identificadas nove mutações deletérias preditas, mas apenas uma foi previamente associada a uma condição clínica sem impacto endometrial. Ao cruzar os genes mutados com os descritores endometriose e/ou endométrio, o gene CMKLR1 foi associado a resposta inflamatória na endometriose e a processos endometriais para estabelecimento da gravidez. Conclusão Apesar de nenhum padrão de mutação ter sido encontrado, ponderamos o pequeno tamanho da amostra e a análise dos dados de sequenciamento de RNA. Considerando o objetivo do estudo de triagem e a importância do gene CMKLR1 na modulação endometrial, este poderia ser um gene candidato para estudos adicionais que avaliem mutações no endométrio eutópico de pacientes com endometriose.

COVID-19 is a pandemic associated with systemic clinical manifestations. In this study, we aimed to present a narrative review on kidney involvement in COVID-19. Kidney involvement could be derived from direct cytopathic effects, immunological mechanisms, indirect effects on renal tissue through other mediators, and dysfunction or injury of other organs. The evolution of COVID-19 may be complicated with acute kidney injury (AKI) in a significant percentage of patients, and renal dysfunction seems to be associated with worse prognosis. Patients with chronic kidney disease (CKD) seem to be more susceptible to the severe forms of COVID-19. Patients with renal replacement therapy (RRT) are also a vulnerable population as consequence of their advanced age, underlying comorbidities, impaired immune response, and clustering in hemodialysis centers, with requirements for frequent contact with healthcare services. Kidney transplant patients may be at high-risk due to long-term immunosuppression and comorbidities, hence, managing immunosuppression is imperative. Lastly, renal replacement therapy may be required during COVID-19, and different modalities are discussed based on clinical findings and laboratorial aspects. Therefore, COVID-19 seems to affect kidney by different mechanisms, which contributes for AKI development and increases the severity of the disease. Also, patients with CKD and kidney transplant recipients are at higher risk for COVID-19 and mortality.

Introduction Fluorescence guidance with 5-aminolevulinic acid (5-ALA) is a safe and reliable tool in total gross resection of intracranial tumors, especially malignant gliomas and cases of metastasis. In the present retrospective study, we have analyzed 5-ALA-induced fluorescence findings in different central nervous system (CNS) lesions to expand the indications of its use in differential diagnoses. Objectives To describe the indications and results of 5-ALA fluorescence in a series of 255 cases. Methods In 255 consecutive cases, we recorded age, gender, intraoperative 5-ALA fluorescence tumor response, and 5-ALA postresection status, as well the complications related to the method. Postresection was classified as ‘5-ALA free’ or ‘5-ALA residual’. The diagnosis of histopathological tumor was established according to the current classification of the World Health Organization (WHO). Results There were 195 (76.4%) 5-ALA positive cases, 124 (63.5%) of whom underwent the ‘5-ALA free’ resection. The findings in the positive cases were: 135 gliomas of all grades; 19 meningiomas; 4 hemangioblastomas; 1 solitary fibrous tumor; 27 metastases; 2 diffuse large B cell lymphomas; 2 cases of radionecrosis; 1 inflammatory disease; 2 cases of gliosis; 1 cysticercosis; and 1 immunoglobulin G4-related disease. Conclusion Fluorescence with 5-ALA can be observed in lesions other than malignant gliomas or metastases, including meningiomas, hemangioblastomas, pilocytic astrocytomas, and lymphomas. Although there is need for further evidence for the use of 5-ALA beyond high-grade gliomas, it may be a safe and reliable tool to improve resection in positive tumors or to guide the histopathologic analysis in biopsies.

The Wistar audiogenic rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister × brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing is known about its mitochondrial metabolism. Here, we addressed mitochondrial aspects of oxidative phosphorylation, oxidative stress, biogenesis, and dynamics in liver, skeletal muscle, and heart of male WARs and correlating them with physiological aspects of body metabolism. The results showed higher mitochondrial content, respiration rates in phosphorylation and noncoupled states, and H2O2 production in WARs. Liver presented higher content of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) and mammalian target of rapamycin, proteins related to mitochondrial biogenesis. In agreement, isolated liver mitochondria from WARs showed higher respiration rates in phosphorylation state and ADP-to-O ratio, as well as higher content of proteins related to electron transport chain ATP synthase, TCA cycle, and mitochondrial fusion and fission compared with their Wistar counterparts. Mitochondria with higher area and perimeter and more variable shapes were found in liver and soleus from WARs in addition to lower reduced-to-oxidized glutathione ratio. In vivo, WARs demonstrated lower body mass and energy expenditure but higher food and water intake and amino acid oxidation. When exposed to a running test, WARs reached higher speed and resisted for a longer time and distance than their Wistar controls. In conclusion, the WAR strain has mitochondrial changes in liver, skeletal muscle, and heart that improve its mitochondrial capacity of ATP production, making it an excellent rat model to study PGC1α overexpression and mitochondrial function in different physiological conditions or facing pathological challenges.

To present a methodology for the simultaneous setting of quantitative targets that reflect both an improvement in the national average of an indicator for Sustainable Development Goal 3 (SDG3), as well as a reduction in its geographic inequality.A five-step algorithm was developed: (a) calculate the national average annual percent change (AAPC) for an SDG3 indicator; (b) normatively define geographic strata from the subnational distribution of the indicator in a baseline year; (c) apply a proportional progressivity criterion to the AAPC to project the stratum-specific indicator value for the target year; (d) set the national target as the weighted average of the indicator in the subnational territorial units for the target year; and (e) set the inequality reduction targets by calculating the absolute and relative gaps between the bottom and top strata for the target year.The algorithm was applied to SDG indicator 3.1.1 (maternal mortality ratio, MMR), disaggregated by Guatemala's 22 departments at the baseline year 2014 (MMR = 113 per 100,000 live births). By sustaining the AAPC rate attained from 2009 to 2014 (-4.3%) and focalizing its actions with territorial progressivity, by 2030 the country could reduce its MMR to 53 per 100,000 and its absolute and relative inequality gaps by 72% and 48%, respectively.The proposed methodology allows for simultaneously setting targets for overall progress and inequality reduction in health, making explicit the primacy of the equity principle contained in the SDG commitment to leave no one behind, whose urgency takes on renewed relevance in the current pandemic scenario.Presentar una metodología para la formulación simultánea de metas cuantitativas que reflejen tanto la mejoría del promedio nacional de un indicador del tercer Objetivo de Desarrollo Sostenible (ODS3) como la reducción de su desigualdad geográfica.Se definió un algoritmo en cinco pasos: a) cálculo del cambio porcentual anual promedio (CPAP) nacional para un indicador del ODS3; b) definición normativa de estratos geográficos a partir de la distribución subnacional del indicador en un año base; c) aplicación de un criterio de progresividad proporcional del CPAP para proyectar el indicador estrato-específico al año meta; d) establecimiento de la meta nacional como el promedio ponderado del indicador en las unidades territoriales subnacionales al año meta; y e) formulación de metas de reducción de desigualdad mediante el cálculo de las brechas absoluta y relativa entre los estratos extremos al año meta.Se aplicó el algoritmo al indicador ODS 3.1.1 (razón de mortalidad materna, RMM), desagregado por los 22 departamentos de Guatemala para el año base 2014 (RMM = 113 por 100 000 nacidos vivos). Sosteniendo la intensidad promedio de CPAP observada entre 2009 y 2014 (-4,3%) y focalizando sus acciones con progresividad territorial, el país reduciría al 2030 su RMM a 53 por 100 000 nacidos vivos y sus brechas absoluta y relativa en 72% y 48%, respectivamente.La metodología propuesta permite formular simultáneamente metas de reducción de las desigualdades geográficas en salud y hacer explícita la primacía del principio de equidad expresado en el compromiso deApresentar uma metodologia para a formulação simultânea de metas quantitativas que reflitam tanto a melhoria da média nacional de um indicador do terceiro Objetivo de Desenvolvimento Sustentável (ODS3) quanto a redução das desigualdades geográfica nesse indicador.Estabelecemos um algoritmo em cinco etapas: (a) cálculo da variação percentual anual média (VPAM) em um país para um indicador do ODS3, (b) definição normativa de estratos geográficos a partir da distribuição subnacional do indicador em um ano base, (c) aplicação de um critério de progressividade proporcional da VPAM para projetar o indicador específico do estrato para o ano base, (d) estabelecimento da meta nacional como a média ponderada do indicador nas unidades territoriais subnacionais para o ano alvo e (e) estabelecimento de metas para a redução das desigualdades calculando a disparidade absoluta e relativa entre os estratos extremos para o ano alvo.Aplicamos o algoritmo ao indicador ODS 3.1.1 (razão de mortalidade materna, RMM), desagregado pelos 22 departamentos da Guatemala para o ano base de 2014 (RMM = 113 por 100.000 nascidos vivos). Se mantiver a intensidade média da VPAM observada entre 2009 e 2014 (-4,3%) e concentrar as suas ações com progressividade territorial, o país reduzirá, até 2030, a sua RMM para 53 por 100.000 e sua disparidade absoluta e relativa em 72% e 48%, respectivamente.A metodologia proposta permite formular simultaneamente metas para a redução das desigualdades geográficas em saúde e explicitar a primazia do princípio da equidade expresso no compromisso de

The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy, specifically brainstem-dependent tonic-clonic seizures, triggered by acute auditory stimulation. Chronic audiogenic seizures (audiogenic kindling) mimic temporal lobe epilepsy, with significant participation of the hippocampus, amygdala, and cortex. The objective of the present study was to characterize the mitochondrial energy metabolism in hippocampus and cortex of WAR and verify its relationship with seizure severity. Hippocampus of WAR naive (no seizures) presented higher oxygen consumption in respiratory states related to the maximum capacities of phosphorylation and electron transfer system, elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl and lactate contents, compared with their Wistar counterparts. Audiogenic kindling had no adding functional effect in WAR, but in Wistar, it induced the same alterations observed in the audiogenic strain. In the cortex, WAR naive presented elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl levels. Chronic acoustic stimulation in Wistar induced the same alterations in cortex and hippocampus. Mainly in the hippocampus, WAR naive presented elevated mRNA expression of glucose, lactate and excitatory amino acids transporters, several glycolytic enzymes, lactate dehydrogenase, and Na+/K+ ATPase in neurons and in astrocytes. In vivo treatment with mitochondrial uncoupler 2,4-dinitrophenol (DNP) or N-acetylcysteine (NAC) in WAR had no effect on mitochondrial metabolism, but lowered oxidative stress. Unlike DNP, NAC downregulated all enzyme genes involved in glucose and lactate uptake, and metabolism in neurons and astrocytes. Additionally, it was able to reduce brainstem seizure severity in WAR. In conclusion, in WAR naive animals, both cerebral cortex and hippocampus display elevated mitochondrial density and/or activity associated with oxidative damage, glucose and lactate metabolism pathways upregulation, and increased Na+/K+ ATPase mRNA expression. Only in vivo treatment with NAC was able to reduce seizure severity of kindled WARs, possibly via down regulation of glucose/lactate metabolism. Taken together, our results are a clear contribution to the field of mitochondrial metabolism associated to epileptic seizures.

Type 1 diabetes is associated with systemic low grade inflammation (LGI). We have previously shown that LGI in diabetic mice depends on systemic circulation of leukotriene (LTB4) which potentiates the toll-like/IL1β receptors response in macrophages. Impaired wound healing is an important co-morbidity in diabetes, and macrophages play a key role in this process. Here, we investigated the role of leukotrienes on monocytes and macrophages phenotype and in the impaired wound healing in diabetic mice. Type 1 diabetes was induced with streptozotocin in 129SvE wild-type (WT) and leukotrienes-deficient 5LO−/− (5-lipoxygenase knockout) mice. In diabetics, the systemic levels of LTB4, TNF-α, IL-6, IL-10, IL-12 and IFNγ were increased as well as the frequency of pro-inflammatory monocytes (CD11b+Ly6ChighLy6G−) compared to healthy mice. In diabetic 5LO−/− mice, these parameters were similar to those in healthy mice. Resident peritoneal macrophages from diabetic WT mice showed a classically activated M1-like phenotype (high Nos2, Stat and Il12 expression, and nitrite levels). Macrophages from diabetic 5LO−/− mice presented alternatively activated M2-macrophages markers (high Arg1 and Chi3l3 expression and arginase activity) and when stimulated with IL4, enhanced phosphorylated-STAT6. Cutaneous wound healing in diabetic WT mice was impaired, which correlated with the decreased frequency of M2-macrophages (CD45+F4/80+CD206+) in the lesions. In diabetic 5LO−/− mice, the frequency of M2-macrophages in the wound was similar to that in healthy mice, suggesting that the impaired healing of diabetic mice depends on 5LO products. The inhibition of leukotrienes or antagonism of its receptors could be a therapeutic alternative for diabetic patients with impaired healing.

Author(s): Mulligan, Kathleen; Glidden, David V; Anderson, Peter L; Liu, Albert; McMahan, Vanessa; Gonzales, Pedro; Ramirez-Cardich, Maria Esther; Namwongprom, Sirianong; Chodacki, Piotr; de Mendonca, Laura Maria Carvalo; Wang, Furong; Lama, Javier R; Chariyalertsak, Suwat; Guanira, Juan Vicente; Buchbinder, Susan; Bekker, Linda-Gail; Schechter, Mauro; Veloso, Valdilea G; Grant, Robert M; Preexposure Prophylaxis Initiative Study Team | Abstract: BackgroundDaily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women.MethodsDual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF.ResultsIn 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P = .001) and hip (-0.61% [95% CI, -.96% to -.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P l .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD.ConclusionsIn HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.Clinical trials registrationNCT00458393.

Retinoids (vitamin A and derivatives) are recognized as essential factors for central nervous system (CNS) development. Retinol (vitamin A) also was postulated to be a major antioxidant component of diet as it modulates reactive species (RS) production and oxidative stress in biological systems. Oxidative stress plays a major role either in pathogenesis or development of neurodegenerative diseases, or even in both. Here we investigate the role of retinol supplementation to human neuron-derived SH-SY5Y cells over RS production and biochemical markers associated to neurodegenerative diseases expressed at neuronal level in Parkinson’s disease and Alzheimer’s disease: α-synuclein, β-amyloid peptide, tau phosphorylation and RAGE. Retinol treatment (24 h) impaired cell viability and increased intracellular RS production at the highest concentrations (7 up to 20 µM). Antioxidant co-treatment (Trolox 100 µM) rescued cell viability and inhibited RS production. Furthermore, retinol (10 µM) increased the levels of α-synuclein, tau phosphorylation at Ser396, β-amyloid peptide and RAGE. Co-treatment with antioxidant Trolox inhibited the increased in RAGE, but not the effect of retinol on α-synuclein, tau phosphorylation and β-amyloid peptide accumulation. These data indicate that increased availability of retinol to neurons at levels above the cellular physiological concentrations may induce deleterious effects through diverse mechanisms, which include oxidative stress but also include RS-independent modulation of proteins associated to progression of neuronal cell death during the course of neurodegenerative diseases.

OBJETIVO: descrever as prevalências de fatores de risco e proteção para doenças crônicas na população adulta brasileira e analisar as diferenças segundo variáveis sociodemográficas. MÉTODOS: estudo transversal com dados de 2012 do Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (Vigitel), incluindo residentes nas capitais brasileiras com idade ≥18 anos; foram calculadas as prevalências e respectivos intervalos de confiança de 95% (IC95%) segundo sexo, faixa etária e escolaridade. RESULTADOS: entre 45.448 entrevistados, a prevalência de tabagismo foi de 12,1% (IC95%: 11,5%-12,8%), inatividade física, 14,9% (IC95%: 14,2%-15,5%), consumo abusivo de bebidas alcoólicas, 18,4% (IC95%: 17,7%-19,2%), excesso de peso, 51,0°% (IC95%: 50,1%-51,9%) e obesidade, 17,4°% (IC95%: 16,7%-18,1%); os fatores de risco estudados estiveram associados a maior idade, sexo masculino e menor escolaridade. CONCLUSÃO: a prevalência dos fatores de risco e proteção apresenta diferenças segundo características sociodemográficas, a serem consideradas nas estratégias de promoção da saúde.

Jatropha gossypiifoliaL. (Euphorbiaceae), widely known as “bellyache bush,” is a medicinal plant largely used throughout Africa and America. Several human and veterinary uses in traditional medicine are described for different parts and preparations based on this plant. However, critical reviews discussing emphatically its medicinal value are missing. This review aims to provide an up-to-date overview of the traditional uses, as well as the phytochemistry, pharmacology, and toxicity data ofJ. gossypiifoliaspecies, in view of discussing its medicinal value and potential application in complementary and alternative medicine. Pharmacological studies have demonstrated significant action of different extracts and/or isolated compounds as antimicrobial, anti-inflammatory, antidiarrheal, antihypertensive, and anticancer agents, among others, supporting some of its popular uses. No clinical trial has been detected to date. Further studies are necessary to assay important folk uses, as well as to find new bioactive molecules with pharmacological relevance based on the popular claims. Toxicological studies associated with phytochemical analysis are important to understand the eventual toxic effects that could reduce its medicinal value. The present review provides insights for future research aiming for both ethnopharmacological validation of its popular use and its exploration as a new source of herbal drugs and/or bioactive natural products.

A major drawback of radiotherapy is the accelerated growth of the surviving tumor cells. Radiotherapy generates a variety of lipids that bind to the receptor for platelet-activating factor, expressed by cells in the tumor microenvironment. In the present study, using the TC-1 tumor cell line, we found that irradiation induced a twofold increase in receptor expression and generated agonists of receptor. Irradiated cells induced a 20-fold increase in live TC-1 proliferation in vitro. Furthermore, subcutaneous co-injection of irradiated TC-1 cells with TC-1 expressing luciferase (TC-1 fluc+) markedly increased TC-1 fluc+ proliferation in a receptor-dependent way. Moreover we used a human carcinoma cell line not expressing the PAF receptor (KBM) and the same cell transfected with the receptor gene (KBP). Following co-injection of live KBP cells with irradiated KBM in RAG mice, the tumor growth was significantly increased compared with tumor formed following co-injection of live KBM with irradiated KBM. This tumor cell repopulation correlated with increased infiltration of tumor-promoting macrophages (CD206+). We propose that receptor represents a possible target for improving the efficacy of radiotherapy through inhibition of tumor repopulation.

In today’s globalized world, diseases have the potential to transcend geopolitical boundaries through international travel and trade. It is now understood that the economies and livelihoods of the entire international community can be affected by a single health crisis in one country. With this concept in mind, a revised version of the World Health Organization (WHO) International Health Regulations (IHRs) was established in 2005 (effective 15 June 2007) to “help the international community prevent and respond to acute public health risks that have the potential to cross borders and threaten people worldwide” (1). This binding legal instrument covers 194 countries across the globe, including all WHO Member States, and aims to protect public health through the prevention of the spread of diseases. For that purpose and as part of IHR implementation, WHO Member States are committed to strengthening their surveillance of and ability to rapidly detect, assess, notify, and report potential Public Health Emergencies of International Concern (PHEICs) in accordance with these regulations. A PHEIC is an extraordinary event that has been determined, as provided in the IHRs, to 1) “constitute a public health risk to other States through the international spread of disease” and 2) “potentially require a coordinated international response” (1).

Binuclear compounds of the type [Pd(μ-L)(N3)(PPh3)]2 {L = pyrazolate (1); 3,5-dimethylpyrazolate (2); 4-iodopyrazolate (3); PPh3 = triphenylphosphine} were synthesized and characterized by elemental analyses, infrared and 1H and 31P{1H} NMR spectroscopies. The crystal and molecular structures of the complex [Pd(μ-dmPz)(N3)(PPh3)]2 (2) were determined by single-crystal X-ray diffraction techniques. In vitro antimycobacterial evaluation demonstrated that compound [Pd(μ-Pz)(N3)(PPh3)]2 (1) displayed a MIC of 8.16 μM, being more active than some commonly used anti-TB drugs and other Pd(II) complexes.

Oculomotor nerve palsy is frequently caused by an aneurismal compression and diabetes mellitus. Brainstem infarction, cavernous sinus tumors and other intracranial lesions are well known causes of oculomotor palsy also. However, neurovascular conflict causing oculomotor nerve disturbances are rare1-4. After the advent of high quality MRI and neuroimaging improvements, the diagnosis of such atypical neurovascular conflicts in symptomatic patients became quite simple5,6. The case of a patient with bilateral oculomotor disorder with MRI imaging of the head showing a right [...]

Head and neck dermoid cysts are lesions relatively rare, which usually occur during childhood as solitary lesions. They are often identified and surgically removed at birth, being uncommon in adults. A 23-year-old male presented with a congenital tumor of the anterior fontanelle, which histopathological examination revealed a dermoid cyst. Surgical intervention is the treatment of choice to remove this lesion. The objective of this study is to report the case, once this type of lesion is rare in adults.

CONTEXT: The appearance of adenomas and their progression to adenocarcinomas is the result of an accumulation of genetic changes in cells of the intestinal mucosa inherited or acquired during life. Several proteins have been studied in relation to the development and progression of colorectal cancer, including tumor protein p53 (p53) and antigen identified by monoclonal antibody Ki-67 (Ki-67). OBJECTIVE: To evaluate the expression of p53 and Ki-67 in colorectal adenomas and correlate the observed levels with clinical and pathologic findings. METHOD: The sample consisted of 50 adenomatous polyps from patients undergoing colonoscopy. After performing polypectomy, polyps were preserved in a formalin solution with 10% (vol./vol.) phosphate buffer, submitted for routine preparation of sections and slides and stained with hematoxylin and eosin. For each adenoma we then performed immunohistochemistry to detect specific p53 and Ki-67 proteins using a streptavidin-biotin-peroxidase enzyme immunoassay. RESULTS: p53 was detected in 18% of the adenomas. The average Ki-67 protein index (i.Ki-67) was 0.49. A statistically significant difference was observed in p53 (P = 0.0003) and Ki-67 (P = 0.02) expression between adenomas with low- and high-grade dysplasia, particularly for p53. The expression of Ki-67 was greater in rectal adenomas than in colic adenomas (P = 0.02). No relationship was found between the expression of the two proteins in the sample. CONCLUSION: The p53 protein is expressed in a proportion of adenomas, while the Ki-67 protein was expressed in all adenomas. The expression of p53 was higher in adenomas with high-grade dysplasia. The expression of Ki-67 was higher in rectal adenomas and in adenomas with high-grade dysplasia.

FUNDAMENTO: O refluxo de prótese valvar é uma possível complicação da cirurgia de troca valvar. Embora raro, suas consequências podem ser graves. Há poucos estudos que correlacionam o grau do refluxo de prótese valvar com os eventos clínicos dos pacientes. OBJETIVO: Comparar a evolução pós-operatória de pacientes com refluxo de prótese valvar discreto/moderado (D/M) ou importante (Imp). MÉTODOS: Dentre 1.350 pacientes submetidos a cirurgia valvar entre 1999 e 2001, foram selecionados 185 pacientes com refluxo de prótese valvar. Desses pacientes, foram avaliados retrospectivamente dados clínicos, laboratoriais e ecocardiográficos de uma amostra de 58 pacientes (37 homens) com refluxo de prótese valvar no pré e/ou no pós-operatório de troca valvar com dados completos em prontuários, sendo 36 com refluxo D/M versus 22 com refluxo Imp. RESULTADOS: A incidência de reoperação foi de 11,1% no Grupo D/M versus 22,7% no Grupo Imp (odds ratio = 2,35 [IC95% 0,56-9,94]). Endocardite foi a causa de reoperação em 75% dos pacientes do Grupo D/M e em 60% do Grupo Imp. As biopróteses aórticas foram as mais acometidas por refluxo (55,8% no Grupo D/M e 57,7% no Grupo Imp). Evoluíram sem refluxo de prótese valvar no segundo pós-operatório 40% dos pacientes com refluxo prévio D/M versus 21,4% dos pacientes com refluxo de prótese valvar Imp. Não houve diferenças significantes nas variáveis laboratoriais. CONCLUSÕES: (1) Os portadores de refluxo importante têm maior probabilidade de reoperação. (2) Endocardite foi a causa mais frequente de reoperação para qualquer grau de refluxo. (3) O refluxo de prótese valvar importante é de mais difícil resolução completa após tratamento cirúrgico. BACKGROUND: Prosthetic valve leak is a possible complication of surgical valve replacement. Although uncommon, its consequences may be serious. Few studies correlate the degree of prosthetic valve leak with clinical events. OBJECTIVE: To compare the postoperative outcome of patients with mild/moderate (Mi/Mo) or severe (Sev) prosthetic valve leak METHODS: A total of 185 patients with prosthetic valve leak were selected among 1350 patients undergoing heart valve surgery between 1999 and 2001. Of these, a sample of 58 patients (37 men) with prosthetic valve leak (36 with Mi/Mo versus 22 with Sev leak) in the pre and/or postoperative period of heart valve replacement had complete medical record data, so their clinical, laboratory and echocardiographic data could be retrospectively assessed. RESULTS: The incidence of reoperation was 11.1% in the Mi/Mo group, versus 22.7% in the Sev group (odds ratio = 2.35 [95% CI 0.56-9.94]). Endocarditis was the cause of reoperation in 75% of the patients of the Mi/Mo group and in 60% of the Sev group. Aortic bioprostheses were those most frequently related to leak (55.8% in the Mi/Mo group and 57.7% in the Sev group). Forty percent of the patients with previous Mi/Mo leak did not present prosthetic valve leak on postoperative day 2 versus 21.4% of the patients with Sev prosthetic valve leak. No significant differences were found regarding laboratory variables. CONCLUSIONS: (1) Patients with severe leak are more likely to undergo reoperation. (2) Endocarditis was the most frequent cause of reoperation for any leak degree. (3) Severe prosthetic valve leak is more difficult to fully resolve after surgical treatment. FUNDAMENTO: El reflujo de prótesis valvular es una posible complicación de la cirugía de reemplazo valvular. Aunque raras, sus consecuencias pueden resultar severas. Hay pocos estudios que correlacionan el grado del reflujo de prótesis valvular con los eventos clínicos de los pacientes. OBJETIVO: Comparar la evolución postoperatoria de pacientes con reflujo de prótesis valvular leve/moderado (L/M) o severo (S). MÉTODOS: Teniendo en cuenta a los 1.350 pacientes sometidos a la cirugía valvular entre el 1999 y el 2001, se seleccionaron a 185 pacientes con reflujo de prótesis valvular. De ellos, se evaluaron retrospectivamente datos clínicos, laboratoriales y ecocardiográficos de una muestra de 58 pacientes (37 varones) con reflujo de prótesis valvular en el pre y/o en el postoperatorio de reemplazo valvular con datos completos en prontuarios, con 36 presentado reflujo L/M versus 22 con reflujo S. RESULTADOS: La incidencia de reoperación fue del 11,1% en el Grupo L/M versus el 22,7% en el Grupo S (odds ratio = 2,35 [IC95% 0,56-9,94]). La Endocarditis fue la causa de reoperación en el 75% de los pacientes del Grupo L/M y en el 60% del Grupo S. Las bioprótesis aórticas fueron las más afectadas por reflujo (el 55,8% en el Grupo L/M y el 57,7% en el Grupo S). Evolucionaron sin reflujo de prótesis valvular en el segundo postoperatorio el 40% de los pacientes con reflujo previo L/M versus el 21,4% de los pacientes con reflujo de prótesis valvular S. No hubo diferencia significantes en las variables laboratoriales. CONCLUSIÓN: 1) Los portadores de reflujo severo tienen mayor probabilidad de reoperación. 2) Endocarditis fue la causa más frecuente de reoperación para cualquier grado de reflujo. 3) El reflujo de prótesis valvular severo es de más difícil resolución completa tras tratamiento quirúrgico.

Relata-se sobre um homem de 36 anos com passagem quatro anos antes pela selva amazônica. Admitido após seis meses do aparecimento progressivo de tetraparesia, ataxia de marcha, disfagia, disartria, dispnéia e soluço. A ressonância magnética revelou lesão parietoccipital à direita e no bulbo, sendo esta última maior. Investigações para tuberculose e síndrome da imunodeficiência adquirida tiveram resultados negativos. Foi submetido a microcirurgia da lesão do bulbo. O estudo anatomopatológico revelou paracoccidioidomicose. Recebeu tratamento com anfotericina B até 2100 mg, e sulfametoxazol-trimetoprim por três meses, e fisioterapia. Voltou às atividades após seis meses do término do tratamento. Comenta-se sobre a participação do sistema imunológico e das citocinas (interleucinas). We report on a 36 years-old man that had been at the Amazon forest four years before. Six months before the admission he had developed a progressive quadriparesis, gait ataxia, dysphagia, dysarthria, difficulty in breathing and hiccup. The gadolinium-enhanced T1-weighted MRI showed a lesion into the right parietoccipital area and another into the medulla, that was the largest. There was any evidence of tuberculosis or AIDS. The patient was submitted to microsurgical approach to the medulla. Pathological examination revealed paracoccidioidomycosis. Treatment with anphotericin B till 2100mg was administered followed by sulfamethoxazole-trimetoprim for three months plus physical therapy. The patient went back to his activities six months after the end of the treatment. Comments are presented about the participation of the immunological system and of the cytokines (interleukines).

Neurons in the region of dorsomedial hypothalamus are involved in the organization of the physiological responses to emotional stress. We have recently shown that the cardiovascular response evoked by activation of dorsomedial hypothalamus neurons is largely dependent on a synaptic relay with the lateral/dorsolateral periaqueductal gray region. In this study, we aimed to investigate whether excitatory amino acid receptors at the lateral/dorsolateral periaqueductal gray region are involved in mediating the response evoked by activation of dorsomedial hypothalamus neurons. In conscious rats, the cardiovascular effects produced by microinjection of GABAA receptor antagonist, bicuculline methiodide into the dorsomedial hypothalamus were evaluated before and after injection of different excitatory amino acid antagonists into lateral/dorsolateral periaqueductal gray region. Pretreatment of lateral/dorsolateral periaqueductal gray region with the non-selective ionotropic excitatory amino acid receptor antagonist kynurenic acid or with the N-methyl- d -aspartate receptor-selective antagonist, MK-801, largely reduced the tachycardic and pressor effects evoked by activation of dorsomedial hypothalamus neurons by bicuculline methiodide microinjection (heart rate 90 and 74%; blood pressure 81 and 84%, respectively). The non-N-methyl- d -aspartate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, did not alter the cardiovascular response evoked by dorsomedial hypothalamus activation. In an additional series of experiments, microinjection of the N-methyl- d -aspartate receptor agonist, N-methyl- d -aspartate, into the lateral/dorsolateral periaqueductal gray region, evoked an increase in heart rate and a pressor response that was accompanied by an increase in locomotor activity. These effects were not altered by pretreatment of lateral/dorsolateral periaqueductal gray region neurons with 6-cyano-7-nitroquinoxaline-2,3-dione but were completely abolished by MK-801. Altogether, these findings indicate that the cardiovascular response evoked by dorsomedial hypothalamus activation involves a synaptic relay at the lateral/dorsolateral periaqueductal gray region that is mediated at least in large part by excitatory amino acid receptors, possibly N-methyl- d -aspartate receptors.

Entre os tumores intracranianos, e rarissimo o achado de tuberculomas individualizados, nao sendo mesmo referida, em nosso meio, tal eventualidade […] Tuberculoma cerebral: Extirpacao cirurgica

Os AA. apresentam o caso de um paciente portador de neurinoma intrarraqueano, que melhorou extraordinariamente apos a extirpacao do tumor, apesar do tempo relativamente longo de evolucao. Referem-se particularmente a discordância entre os dados clinicos e os mielograficos, manifestando-se favoraveis a obediencia aos dados clinicos, que seriam menos sujeitos a erros […]. Compressao medular por neurinoma gigante. Extirpacao cirurgica

Cardiopulmonary bypass (CPB) is related to inflammatory response and pulmonary dysfunction. The aim of this study was to evaluate the effects of CPB leukocyte filtration on inflammation and lung function after coronary artery bypass grafting (CABG). A prospective randomized study was performed to compare CABG patients undergoing CPB leukocyte filtration (n = 9) or standard CPB (n = 11). Computed tomography, oxygenation, leukocyte count, hemodynamic data, PaO2/FiO2, shunt fraction, interleukins, elastase, and myeloperoxidase were evaluated. Data were analyzed using two-factor ANOVA for repeated measurements. The filtered group showed lower neutrophil counts up to 50 min of CPB, lower shunt fraction up to 6 h after surgery, and lower levels of IL-10 at the end of surgery (p