Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso).

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Is Evening Carbohydrate Intake in Healthy Individuals Associated with Higher Postprandial Glycemia and Insulinemia When Compared to Morning Intake? A Systematic Review and Meta-Analysis of Randomized Crossover Studies.

This systematic review aimed to summarize randomized clinical trials that compared the postprandial glycemic and insulinemic metabolic response after eating isocaloric and standardized carbohydrate meals consumed at two moments: morning versus night, in healthy individuals who were not shift workers. The search strategy consisted of an electronic search using the following electronic databases: MEDLINE (via PubMed), EMBASE (via Elsevier), LILACs (Virtual Health Library - VHL), Cochrane Registers of Clinical Trials (CENTRAL, via Wiley) and gray literature (Opengray.eu). The PICO strategy was used to define the search terms (P: healthy adults, I: nocturnal intake, C: morning intake, O: area under the curve (AUC) of the postprandial glucose and insulin response). This review was reported according to the PRISMA statement. From the 3757 articles found, 412 were duplicates and excluded, totaling 3345 that had their titles and abstracts read. A total of 42 articles met the inclusion criteria and were read in full, and eight studies were included in the systematic review. The certainty of the evidence was assessed using GRADE. The results showed, with moderate quality of evidence, a postprandial response with higher glycemic values in the evening compared to the morning (SMD = 1.30; 95% CI, 1.01 to 1.59; I2 = 0%; p < 0.00001; 8 studies and 116 participants). No differences were found between insulin values at night and in the morning (SMD = 0.19; 95% CI, -0.10 to 0.49; 6 studies and 90 participants). We concluded that the intake of carbohydrates at night leads to higher glycemic, but not insulinemic, postprandial values. Revision Record: PROSPERO number CRD42019137862 available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019137862 Key teaching points and nutritional relevanceThis systematic review summarized randomized clinical trials that compared the postprandial glycemic and insulinemic response after eating carbohydrate meals in the morning versus at night.A total of eight studies were included in the systematic review; the results showed a postprandial response with higher glycemic values in the evening compared to the morning.No differences were found between insulin values at night and in the morning;• The intake of carbohydrates at night leads to higher glycemic, but not insulinemic, postprandial values.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

The blockade of µ­opioid receptors in the lateral hypothalamus enhances panic attack­like behaviour and diminishes defensive antinociception.

The lateral hypothalamus (LH) sends neural pathways to structures involved on predator­related defensive behaviours, escape and antinociception. The aim of this study was to investigate the role played by µ-opioid receptors located on LH neurons in defensive behaviour and unconditioned fear­induced antinociception elicited by electric stimulation of LH. To achieve the goals, the µ1-opioid receptor selective antagonist naloxonazine was administered at different concentrations in the LH, and the defensive behaviour and fear­induced antinociception elicited by electrical stimulation of LH were evaluated. The electrical stimulation of LH caused escape behaviour followed by defensive antinociception. Microinjections of naloxonazine in a concentration of 5.0 µg/0.2 µL in the LH decreased the aversive stimulus­induced escape behaviour thresholds, but diminished defensive antinociception. These findings suggest that µ-opioid receptors of LH can be critical to panic attack­related symptoms and facilitate the unconditioned fear­induced antinociception produced by LH neurons activation.

Is self-reported short sleep duration associated with obesity? A systematic review and meta-analysis of cohort studies.

CONTEXT: A possible association between self-reported short sleep duration and risk of obesity has been studied. OBJECTIVE: To analyze the association between sleep duration and obesity. METHODS: The LILACS, Medline, Central, Embase, and OpenGrey databases were searched from inception until July 2020. Two authors screened the studies independently according to the PECO strategy, as follows: participants: > 18 years old; exposure: short sleep duration; control: regular sleep; outcome: obesity). Only cohort studies were included. A total of 3286 studies were retrieved with the search strategy, but only 36 were included. Disagreements were resolved by a third author. The quality of studies was assessed with Newcastle-Ottawa Quality Assessment Form for Cohort Studies. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Thirty-six studies were included, and 22 contributed quantitative data. Most of the studies (n = 27) assessed sleep by self-report. The meta-analysis showed a significant association between self-reported short sleep and development of obesity, and the chances of developing obesity increased when self-reported sleep duration decreased. CONCLUSIONS: Self-reported short sleep was significantly associated with a higher incidence of obesity, with moderate quality of evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019130143.

Cattle and goats' humoral response to vaccination with Clostridium perfringens type D purified epsilon toxoids.

Herd vaccination is an important preventive measure against enterotoxemia in ruminants. Vaccination in goats should be performed every four months, and recent studies have shown that immunity in cattle lasts for less than one year. One of the mechanisms for increasing the duration of the immune response is to use purified toxoids as immunogens. The aim of the present study was to evaluate the humoral response in cattle and goats after vaccination with purified and semi-purified Clostridium perfringens type D epsilon toxoid. The following three different vaccines were used: vaccine 1 (V1), a semi-purified toxoid adsorbed to aluminum hydroxide; vaccine 2 (V2), a purified toxoid adsorbed to aluminum hydroxide; and vaccine (V3), a purified toxoid adsorbed on chitosan microparticles. Groups of cattle (n = 6-7) and goats (n = 6-7) were vaccinated on days 0 and 30, and serum samples for antitoxin titration were collected every 30 days for one-year post-vaccination. Goats were revaccinated on day 360, and their serum was evaluated on days 367 and 374. The antibody peaks ranged between 6.90 and 11.47 IU/mL in cattle and from 1.11 to 4.40 IU/mL in goats. In cattle administered with the V1 and V2 vaccines, we observed that the antibody titers were maintained above 0.2 IU/mL until the end of the experiment. In goats, V2 elicited long-lasting antibodies, and all animals maintained the protective titers for 210 days after the first dose. In conclusion, the purified toxoid vaccine with aluminum hydroxide adjuvant was able to induce strong and long-lasting humoral responses in both species and could be an alternative for improving the immunization schedule against enterotoxemia in goats and cattle.

Methodological quality and redundancy of systematic reviews that compare endarterectomy versus stenting for carotid stenosis.

A review of systematic reviews (SRs) and a critical appraisal study was conducted at Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp). The objectives of this review are (1) to identify all published SRs comparing the effectiveness and safety of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) for carotid artery stenosis, (2) to assess their methodological quality and (3) to compare the primary studies contained in each SR. We included 17 SRs published between 2005 and 2017. None of the SRs fulfilled all items of AMSTAR-2. The overall confidence in the results was graded as critically low for 16 SRs (94%) and low for 1 SR (6%). Five items were judged inadequate in all SRs: reference to a published protocol, explanation to the selection of study design, comprehensive search of the literature, methods for statistical combination of findings and consideration of the risk of bias on the results of meta-analysis. In total, 15 randomised clinical trials (RCTs) were included at least in one SR. The number of included RCTs in each SR was inconsistent (4 to 15) and was not related to the year of publication of the SR. Our study found redundant and low methodological quality SR comparing CAS versus CEA for carotid stenosis.

[Effect of palonosetron, ondansetron and dexamethasone in the prevention of postoperative nausea and vomiting in video cholecystectomy with total venous anesthesia with propofol-remifentanil - randomized clinical trial]. / Efeito da palonosetrona, ondansetrona e dexametasona na prevenção de náusea e vômito pós­operatório em videocolecistectomia com anestesia venosa total com propofol­remifentanil ­ ensaio clínico randomizado duplo cego.

INTRODUCTION AND OBJECTIVES: The incidence of Postoperative Nausea and Vomiting (PONV) after video cholecystectomy is high. Progress in pharmacological PONV prophylaxis includes a new generation of 5-HT3 antagonists. This study aims to assess the effect of the 5-HT3 antagonist in postanesthetic antiemetic management of patients submitted to laparoscopic cholecystectomy with total intravenous anesthesia. METHODS: Sixty individuals who underwent video cholecystectomy were randomized into three groups of 20 individuals according to the treatment administered: 0.125 mg of palonosetron (Group 1); 4 mg of ondansetron associated with 4 mg of dexamethasone (Group 2); 4 mg of dexamethasone (Group 3). General intravenous anesthesia was performed with propofol, remifentanil and rocuronium. The group to which the participant belonged was concealed from the investigator who assessed drug effect. PONV was assessed using the Rhodes Scale at 12 and 24 hours after surgery. Rescue medication was 0.655 to 1.5 mg of droperidol. RESULTS: Group 1 presented a lower incidence of PONV and required less rescue medication in the first postoperative hour. There was no significant difference among the three groups regarding PONV incidence in the first 12 postoperative hours. Groups 1 and 2 were superior to Group 3 regarding the control of PONV from 12 to 24 hours, and after rescue medication from 12 to 24 hours. Group 1 showed significantly superior nausea control in the first 12 postoperative hours. CONCLUSIONS: The present study showed evidence that palonosetron is superior to the drugs compared regarding a protracted antiemetic effect and less requirement of rescue drugs, mainly related to its ability to completely inhibit the uncomfortable symptom of nausea.

Effect of palonosetron, ondansetron and dexamethasone in the prevention of postoperative nausea and vomiting in video cholecystectomy with total venous anesthesia with propofol-remifentanil - randomized clinical trial / Efeito da palonosetrona, ondansetrona e dexametasona na prevenção de náusea e vômito pós-operatório em videocolecistectomia com anestesia venosa total com propofol-remifentanil - ensaio clínico randomizado duplo cego

Abstract Introduction and objectives: The incidence of Postoperative Nausea and Vomiting (PONV) after video cholecystectomy is high. Progress in pharmacological PONV prophylaxis includes a new generation of 5-HT3 antagonists. This study aims to assess the effect of the 5-HT3 antagonist in postanesthetic antiemetic management of patients submitted to laparoscopic cholecystectomy with total intravenous anesthesia. Methods: Sixty individuals who underwent video cholecystectomy were randomized into three groups of 20 individuals according to the treatment administered: 0.125 mg of palonosetron (Group 1); 4 mg of ondansetron associated with 4 mg of dexamethasone (Group 2); 4 mg of dexamethasone (Group 3). General intravenous anesthesia was performed with propofol, remifentanil and rocuronium. The group to which the participant belonged was concealed from the investigator who assessed drug effect. PONV was assessed using the Rhodes Scale at 12 and 24 hours after surgery. Rescue medication was 0.655 to 1.5 mg of droperidol. Results: Group 1 presented a lower incidence of PONV and required less rescue medication in the first postoperative hour. There was no significant difference among the three groups regarding PONV incidence in the first 12 postoperative hours. Groups 1 and 2 were superior to Group 3 regarding the control of PONV from 12 to 24 hours, and after rescue medication from 12 to 24 hours. Group 1 showed significantly superior nausea control in the first 12 postoperative hours. Conclusions: The present study showed evidence that palonosetron is superior to the drugs compared regarding a protracted antiemetic effect and less requirement of rescue drugs, mainly related to its ability to completely inhibit the uncomfortable symptom of nausea.

Resumo Justificativa e objetivo: Náuseas e Vômitos no Pós-Operatório (NVPO) têm alta incidência após videocolecistectomia. Avanços na profilaxia farmacológica de NVPO incluem a nova geração de antagonista 5-HT3. O objetivo deste estudo foi avaliar o efeito do antagonista 5-HT3 no controle antiemético pós-anestésico em videocolecistectomia com anestesia venosa total. Método: Estudo realizado no HC-UFU (Hospital Terciário). Sessenta indivíduos submetidos a videocolecistectomia foram randomizados em três grupos de igual número, sendo administrados 0,125 mg de palonosetrona (Grupo 1); 4 mg de ondasetrona e 4 mg de dexametasona (Grupo 2); ou 4 mg de dexametasona (Grupo 3). A anestesia geral venosa foi realizada com propofol, remifentanil e rocurônio. O avaliador do efeito da droga desconhecia o grupo ao qual o indivíduo pertencia. NVPO foi avaliada aplicando a Escala de Rhodes após 12 e 24 horas do término da cirurgia. Para resgate terapêutico, foi estabelecido 0,655−1,5 mg de droperidol. Resultado: Observou-se no Grupo 1 menor incidência de NVPO e de resgate terapêutico na primeira hora de PO. Não foi observada diferença significativa entre os três grupos com relação a ocorrência de NVPO nas primeiras 12 horas de pós-operatório. Os grupos 1 e 2 foram superiores ao Grupo 3 no que se refere ao controle de NVPO de 12 a 24 horas e após o resgate de 12−24 horas. Observou-se que o controle de náuseas nas primeiras 12 horas de pós-operatório do Grupo 1 foi significantemente superior. Conclusão: O presente estudo mostrou evidências da superioridade da palonosetrona às demais drogas empregadas no que se refere ao efeito antiemético prolongado e menor necessidade de resgate, principalmente na capacidade de inibir completamente o desconfortável sintoma de náusea.

Effectiveness and safety of structured exercise vs. no exercise for asymptomatic aortic aneurysm: systematic review and meta-analysis.

We conducted a systematic review to compare the effectiveness and safety of exercise versus no exercise for patients with asymptomatic aortic aneurysm. We followed the guidelines set out in the Cochrane systematic review handbook. We searched Medline, Embase, CENTRAL, LILACS, PeDRO, CINAHL, clinicaltrials.gov, ICTRP, and OpenGrey using the MeSH terms "aortic aneurysm" and "exercise". 1189 references were identified. Five clinical trials were included. No exercise-related deaths or aortic ruptures occurred in these trials. Exercise did not reduce the aneurysm expansion rate at 12 weeks to 12 months (mean difference [MD], -0.05; 95% confidence interval [CI], -0.13 to 0.03). Six weeks of preoperative exercise reduced severe renal and cardiac complications (risk ratio, 0.54; 95% CI, 0.31-0.93) and the length of intensive care unit stay (MD, -1.00; 95% CI, -1.26 to -0.74). Preoperative and postoperative forward walking reduced the length of hospital stay (MD, -0.69; 95% CI, -1.24 to -0.14). The evidence was graded as 'very low' level.

Foi realizada revisão sistemática para comparar a efetividade e a segurança de exercícios versus não exercícios em pacientes assintomáticos com aneurisma de aorta. Usamos os termos MeSH aortic aneurysm e exercise para as bases MEDLINE, Embase, CENTRAL, LILACS, PeDRO, CINAHL, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) e OpenGrey. Foram obtidas 1.189 referências. Cinco ensaios clínicos foram incluídos. Não houve morte ou rotura associada ao exercício. Além disso, este não reduziu a velocidade de crescimento do aneurisma em 12 semanas a 12 meses [diferença de médias (DM) −0,05; intervalo de confiança de 95% (IC95%) −0,13 a 0,03]. Seis semanas de exercícios pré-operatórios reduziram complicações clínicas renais e cardíacas (razão de risco 0,54; IC95% 0,31­0,93) e a permanência em unidade de terapia intensiva (DM −1,00; IC95% −1,26 a −0,74). Caminhadas nos períodos pré e pós-operatório reduziram a permanência hospitalar. A evidência foi classificada como de muito baixa qualidade.

Effectiveness and safety of structured exercise vs. no exercise for asymptomatic aortic aneurysm: systematic review and meta-analysis / Efetividade e segurança de exercícios estruturados versus sem exercício em pacientes assintomáticos com aneurisma de aorta: revisão sistemática e metanálise

Abstract We conducted a systematic review to compare the effectiveness and safety of exercise versus no exercise for patients with asymptomatic aortic aneurysm. We followed the guidelines set out in the Cochrane systematic review handbook. We searched Medline, Embase, CENTRAL, LILACS, PeDRO, CINAHL, clinicaltrials.gov, ICTRP, and OpenGrey using the MeSH terms "aortic aneurysm" and "exercise". 1189 references were identified. Five clinical trials were included. No exercise-related deaths or aortic ruptures occurred in these trials. Exercise did not reduce the aneurysm expansion rate at 12 weeks to 12 months (mean difference [MD], −0.05; 95% confidence interval [CI], −0.13 to 0.03). Six weeks of preoperative exercise reduced severe renal and cardiac complications (risk ratio, 0.54; 95% CI, 0.31-0.93) and the length of intensive care unit stay (MD, −1.00; 95% CI, −1.26 to −0.74). Preoperative and postoperative forward walking reduced the length of hospital stay (MD, −0.69; 95% CI, −1.24 to −0.14). The evidence was graded as 'very low' level.

Resumo Foi realizada revisão sistemática para comparar a efetividade e a segurança de exercícios versus não exercícios em pacientes assintomáticos com aneurisma de aorta. Usamos os termos MeSH aortic aneurysm e exercise para as bases MEDLINE, Embase, CENTRAL, LILACS, PeDRO, CINAHL, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) e OpenGrey. Foram obtidas 1.189 referências. Cinco ensaios clínicos foram incluídos. Não houve morte ou rotura associada ao exercício. Além disso, este não reduziu a velocidade de crescimento do aneurisma em 12 semanas a 12 meses [diferença de médias (DM) −0,05; intervalo de confiança de 95% (IC95%) −0,13 a 0,03]. Seis semanas de exercícios pré-operatórios reduziram complicações clínicas renais e cardíacas (razão de risco 0,54; IC95% 0,31-0,93) e a permanência em unidade de terapia intensiva (DM −1,00; IC95% −1,26 a −0,74). Caminhadas nos períodos pré e pós-operatório reduziram a permanência hospitalar. A evidência foi classificada como de muito baixa qualidade.

Evidence for varicose vein treatment: an overview of systematic reviews

ABSTRACT BACKGROUND: Varicose veins affect nearly 30% of the world's population. This condition is a social problem and needs interventions to improve quality of life and reduce risks. Recently, new and less invasive methods for varicose vein treatment have emerged. There is a need to define the best treatment options and to reduce the risks and costs. Since there are cosmetic implications, treatments for which effectiveness remains unproven present risks to consumers and higher costs for stakeholders. These risks and costs justify conducting an overview of systematic reviews to summarize the evidence. DESIGN AND SETTING: Overview of systematic reviews within the Discipline of Evidence-Based Health, at Universidade Federal de São Paulo (UNIFESP). METHODS: Systematic reviews on clinical or surgical treatments for varicose veins were included, with no restrictions on language or publication date. RESULTS: 51 reviews fulfilled the inclusion criteria. Outcomes and comparators were described, and a narrative review was conducted. Overall, there was no evidence that compression stockings should be recommended for patients as the initial treatment or after surgical interventions. There was low to moderate evidence that minimally invasive therapies (endovenous laser therapy, radiofrequency ablation or foam sclerotherapy) are as safe and effective as conventional surgery (ligation and stripping). Among these systematic reviews, only 18 were judged to present high quality. CONCLUSIONS: There was evidence of low to moderate quality that minimally invasive treatments, including foam sclerotherapy, laser and radiofrequency therapy are comparable to conventional surgery, regarding effectiveness and safety for treatment of varicose veins.

Evidence for varicose vein treatment: an overview of systematic reviews.

BACKGROUND: Varicose veins affect nearly 30% of the world's population. This condition is a social problem and needs interventions to improve quality of life and reduce risks. Recently, new and less invasive methods for varicose vein treatment have emerged. There is a need to define the best treatment options and to reduce the risks and costs. Since there are cosmetic implications, treatments for which effectiveness remains unproven present risks to consumers and higher costs for stakeholders. These risks and costs justify conducting an overview of systematic reviews to summarize the evidence. DESIGN AND SETTING: Overview of systematic reviews within the Discipline of Evidence-Based Health, at Universidade Federal de São Paulo (UNIFESP). METHODS: Systematic reviews on clinical or surgical treatments for varicose veins were included, with no restrictions on language or publication date. RESULTS: 51 reviews fulfilled the inclusion criteria. Outcomes and comparators were described, and a narrative review was conducted. Overall, there was no evidence that compression stockings should be recommended for patients as the initial treatment or after surgical interventions. There was low to moderate evidence that minimally invasive therapies (endovenous laser therapy, radiofrequency ablation or foam sclerotherapy) are as safe and effective as conventional surgery (ligation and stripping). Among these systematic reviews, only 18 were judged to present high quality. CONCLUSIONS: There was evidence of low to moderate quality that minimally invasive treatments, including foam sclerotherapy, laser and radiofrequency therapy are comparable to conventional surgery, regarding effectiveness and safety for treatment of varicose veins.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.

The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour. The chemical stimulation of the VMH with 9nmol of N-methyl-d-aspartic acid (NMDA) elicited oriented and non-oriented escape behaviours. The pretreatment of the dPAG with a non-selective blocker of synaptic contacts, cobalt chloride (CoCl2), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9nmol of NMDA, abolished the non-oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl2 was followed by stimulation of the dPAG with 6nmol of NMDA, no effect was observed either on the non-oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein-labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA-labelled neural fibres with terminal boutons surrounding Fos-labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic-like behavioural responses. The current data suggest that the dPAG is the key structure that organises non-oriented/explosive escape reactions associated with panic attack-like behaviours.

ADAPTE: uma ferramenta para adaptação de diretrizes na área da saúde. Revisão e avaliação crítica da literatura / ADAPT: a tool for adaptation of guidelines in health care. Review and critical appraisal of the literature

Contexto: O desenvolvimento de diretrizes na área da saúde é fundamental para tomadas de decisões clínicas e de gestão em saúde. O seu custo é elevado e demanda pessoal especializado. A ferramenta ADAPTE se propõe a adaptar diretrizes clínicas existentes para um diferente contexto ou situação, resultando em melhores práticas clínicas e de gestão em saúde para realidades locais. Objetivos: Descrever a ferramenta, mapear a literatura sobre os estudos publicados sobre o ADAPTE e avaliar as vantagens e desvantagens da utilização da ferramenta de acordo com a opinião dos autores que a utilizaram. Métodos: Revisão narrativa com busca sistematizada nas bases de dados eletrônicas MEDLINE, TRIP e LILACS, utilizando os termos ?ADAPTE working group? OR ?ADAPTE collaboration? OR ?ADAPTE?. Foram incluídos todos os estudos que aplicaram, descreveram ou avaliaram o ADAPTE. As características dos estudos que aplicaram o ADAPTE foram detalhadas. Resultados: A ferramenta ADAPTE foi desenvolvida pelo ADAPTE Working Group Collaboration, é validada e procura melhorar a eficiência de diretrizes existentes, estendendo o seu uso a realidades diferentes dos locais de origem. Utiliza metodologia consistentecom as fontes primárias, abordagem participativa e flexibilidade para acomodar necessidades locais. Conclusões: Com base na opinião dos autores que aplicaram o ADAPTE para adaptar diretrizes existentes à sua realidade, não foi observada redução de custos, esforços, tempo e infraestrutura necessária. São necessários estudos prospectivos comparando a aplicação do ADAPTE com o desenvolvimento de uma diretriz de novo para estabelecer a efetividade e a utilidade dessa ferramenta na prática da gestão em saúde.

Evaluation of epicardial adipose tissue in familial partial lipodystrophy.

BACKGROUND: Dunnigan type Familial Partial Lipodystrophy (FPLD) is characterized by loss of subcutaneous fat from the limbs and excessive accumulation on the visceral adipose tissue (VAT). Affected individuals have insulin resistance (IR), diabetes, dyslipidemia and early cardiovascular (CV) events, due to their imbalanced distribution of total body fat (TBF). Epicardial adipose tissue (EAT) is correlated with VAT. Hence, EAT could be a new index of cardiac and visceral adiposity with great potential as a marker of CV risk in FPLD. OBJECTIVE: Compare EAT in FPLD patients versus healthy controls. Moreover, we aimed to verify if EFT is related to anthropometrical (ATPM) and Dual-Energy X-ray Absorptiometry (DEXA) measures, as well as laboratory blood findings. We postulated that FPLD patients have enlarged EAT. METHODS: This is an observational, cross-sectional study. Six patients with a confirmed mutation in the LMNA gene for FPLD were enrolled in the study. Six sex, age and BMI-matched healthy controls were also selected. EFT was measured by transthoracic echocardiography (ECHO). All participants had body fat distribution evaluated by ATPM and by DEXA measures. Fasting blood samples were obtained for biochemical profiles and also for leptin measurements. RESULTS: Median EFT was significantly higher in the FPLD group than in matched controls (6.0 ± 3.6 mm vs. 0.0 ± 2.04 mm; p = 0.0306). Additionally, FPLD patients had lower leptin values. There was no significant correlation between EAT and ATPM and DEXA measurements, nor laboratory findings. CONCLUSIONS: This study demonstrates, for the first time, that EAT measured by ECHO is increased in FPLD patients, compared to healthy controls. However, it failed to prove a significant relation neither between EAT and DEXA, ATPM or laboratory variables analyzed.

Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a case-control study.

OBJECTIVE: To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease. METHODS: Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations. RESULTS: Serum levels of CA125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups. CONCLUSION: The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a case-control study / Avaliação do CA-125 e CD-23 solúvel em pacientes com endometriose pélvica: estudo de caso-controle

OBJECTIVE: To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease. METHODS: Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations. RESULTS: Serum levels of CA125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups. CONCLUSION: The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

OBJETIVO: Avaliar as concentrações séricas de CA-125 e CD-23 solúvel e correlacioná-los com sintomas clínicos, localização e estádio da endometriose pélvica e classificação histológica da doença. MÉTODOS: Amostras de sangue foram coletadas de 44 mulheres com endometriose e 58 sem endometriose durante os primeiros três dias (1ª amostra) e durante o sétimo, o oitavo e o nono dia (2ª amostra) do ciclo menstrual. As dosagens de CA-125 e CD-23 solúvel foram realizadas por ELISA. O teste U de Mann-Whitney foi usado para idade, avaliação de dor (escala analógica visual) e para a concentração dos biomarcadores. RESULTADOS: Os níveis séricos de CA-125 foram mais altos nas pacientes com endometriose do que no grupo-controle quando avaliados em ambos os períodos do ciclo menstrual, assim como apresentaram-se elevados nessas mulheres quando referiam dor pélvica crônica, dispareunia de profundidade (coleta na 2ª amostra), dismenorreia (ambas as amostras) e dor ao evacuar durante o fluxomenstrual (coleta na 2ª amostra). A concentração de CA-125 foi mais alta no estádio avançado em ambas as amostras, assim como em mulheres com endometriomas ovarianos. Em relação ao CD-23 solúvel, nenhuma diferença estatisticamente significativa foi observada entre os grupos. CONCLUSÃO: As concentrações de CA-125 foram mais altas em pacientes com endometriose do que em pacientes sem a doença. Nenhuma diferença estatisticamente significativa foi observada para CD-23 solúvel entre os grupos.

A variabilidade hemodinâmica venosa detectada pelos parâmetros da pletismografia a ar nas classes clínicas da classificação CEAP / Variability of venous hemodynamics detected by air plethysmography in CEAP clinical classes / Variability of venous hemodynamics detected by air plethysmography in CEAP clinical classes

CONTEXTO: A variabilidade hemodinâmica da pletismografia a ar é conhecida, mas o exato papel dessa variabilidade no cotidiano clínico não foi investigado, podendo ter algum significado clínico ainda não explorado. Sabe-se que há sobreposição entre as classes clínicas (C0 a C6) da classificação CEAP e mesmo entre membros inferiores de uma mesma classe clínica. OBJETIVO: Avaliar a variabilidade hemodinâmica dos parâmetros da pletismografia a ar nas classes clínicas da classificação CEAP. MÉTODO: Este estudo retrospectivo confronta a doença varicosa de membros inferiores classificada de C0 a C6 pela classificação CEAP com os parâmetros hemodinâmicos venosos obtidos pela pletismografia a ar. Os dados obtidos foram tabulados e analisados em suas classes clínicas pelos testes de variância de Kruskal-Wallys e Barllett. RESULTADOS: Foram realizados 310 exames em 230 pacientes cujas idades variaram entre 19 a 81 anos, com uma média de 46,2 anos. Os parâmetros índice de enchimento venoso e volume venoso funcional mostraram aumento da variabilidade hemodinâmica quando analisados na classe clínica C0 do CEAP, demonstrada por meio do coeficiente de variabilidade que, para o índice de enchimento venoso foi de 28,12 por cento na classe clínica C0 e se manteve acima de 57 por cento nas classes de C2 a C6. A fração de ejeção e a fração de volume residual não aumentaram a variabilidade quando comparados com a classe clínica C0 do CEAP. CONCLUSÃO: O índice de enchimento venoso foi o melhor parâmetro para avaliação e triagem de pacientes com insuficiência venosa crônica, mas tem grande variabilidade nas classes clínicas C2 a C6 do CEAP.

BACKGROUND: The hemodynamic variability of air plethysmography is known in the literature, but the clinical significance of this event has not been investigated yet, and there may be some unexplored clinical meaning. There is known superpositioning of CEAP clinical classes (C0-C6) and even in lower limbs of the same clinical classes. OBJECTIVE: To evaluate hemodynamic variability of air plethysmography parameters in CEAP clinical classes. METHODS: This retrospective study compares lower limb varicose disease between C0 and C6 CEAP clinical classes with venous hemodynamic parameters obtained by air plethysmography. Data were tabled and analyzed according to their clinical classes by Kruskal-Wallys and Barllet variance tests. RESULTS: A total of 310 examinations were performed in 230 patients, aged between 19-81 years (mean = 46.2 years). Venous filling index and functional venous volume increased hemodynamic variability when compared with CEAP C0. This was demonstrated by the variability coefficient, which was 28.12 percent for venous filling index in C0 and higher than 57 percent between clinical classes C2 and C6. Ejection fraction and residual venous fraction had no increase in variability when compared with CEAP C0. CONCLUSION: Venous filling index is the best parameter for assessment and screening patients with chronic venous insufficiency, but has great variability in C2 to C6 CEAP clinical classes.

Envolvimento de receptores 5-HT2A/2C do núcleo magno da rafe e do complexo gigantocelular na analgesia induzida pelo medo evocado por estimulação elétrica das camadas profundas do colículo superior e da substancia cinzenta periaquedutal dorsal

O teto mesencefálico é responsável pela elaboração de comportamentos defensivos, que por sua vez são caracterizados por alterações autonômicas e locomotoras, tais como o aumento da freqüência cardíaca, o aumento do fluxo sanguíneo para os músculos, piloereção, exoftalmia, alerta, congelamento, saltos, corrida, giros e vocalizações, que aumentam as chances de sobrevivência de um animal em risco iminente de vida. Além de todas essas alterações, após o comportamento de defesa, ocorre uma potente antinocicepção. Esta analgesia é devida à ativação de um sistema responsável pela modulação de impulsos nociceptivos em situações críticas para o animal confrontado com estímulos aversivos. Este sistema é comumente chamado de sistema endógeno de inibição de dor. O estímulo elétrico de estruturas que fazem parte deste sistema tais como a SCP, NMgR, NDR e NRpg promovem analgesia. O objetivo do nosso trabalho foi verificar o envolvimento do NMgR, do complexo gigantocelular e de receptores 5-'HT IND.2' na analgesia induzida pelo medo evocado pelo estímulo elétrico das CPCS e da SCPd. Para isso, foi microinjetada ritanserina, um antagonista para receptores 5-'HT IND.2A/2C', no NMgR e complexo gigantocelular, em animais que receberam implantes de eletrodos nas CPCS e SCPd que permitiam o estímulo elétrico local, e cânulas-guia direcionadas aos núcleos monoaminérgicos do sistema endógeno de inibição de dor (onde o bloqueio farmacológico era localmente efetuado). A ritanserina foi capaz de reverter a analgesia induzida pelo medo após o estímulo elétrico do mesencéfalo dorsal, sugerindo, assim, que este processo antinociceptivo está sob controle serotoninérgico, sendo especificamente recrutados receptores 5-'HT IND.2A/2c' localizados no NMgR e no complexo gigantocelular durante a elaboração da analgesia induzida pelo medo (AU)