Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immunemediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Observational studies suggest there are clinical benefits to moderate red wine (RW) consumption. However, the effects on coronary vasculature and overall lifestyle are unclear. We investigated whether a lifestyle of regular long-term RW consumption is associated with changes in coronary plaque burden, calcium score, carotid intima/media thickness, endothelial function, and metabolic variables, compared with alcohol abstinence. Healthy volunteers were evaluated by coronary computed tomography angiography (CTA) as well as carotid and brachial artery ultrasound. Nutritional status, psychological status, and metabolic variables were assessed. The study included 101 drinkers [aged 58.9±7.3 years (means±SD)], from wine brotherhoods, and 104 abstainers, from Anglican, Evangelical and Catholic churches both in the city of São Paulo, Brazil. No significant differences in demographics were noted. Lesion prevalence per patient assessed by coronary CTA and classified as absent (0), 1-25, 26-49, and ≥50% stenosis was similar between groups. When analyzed by individual arteries, i.e., left anterior descending, circumflex, and right coronary, prevalence was also not different. On the other hand, calcium scores were higher among drinkers than abstainers (144.4±362.2 vs 122.0±370.3; P<0.01). However, drinkers reported less history of diabetes and exercised more. RW drinkers consumed 2127.9±387.7 kcal/day while abstainers consumed 1836.0±305.0 (P<0.0001). HDL cholesterol was significantly higher among drinkers compared to abstainers (46.9±10.9 vs 39.5±9.0 mg/dL; P<0.001), while fasting plasma glucose was lower (97.6±18.2 vs 118.4±29.6 mg/dL; P<0.02). Liver enzymes were normal in both groups. In conclusion, long-term wine drinkers displayed a similar plaque burden but greater calcium score than abstainers, despite a more atherogenic diet, and the mechanisms for the increased calcium scores in the former remain speculative.

Objetivo. El presente estudio tuvo como objetivo investigar la presencia de vibrios en el hepatopáncreas del camarón de cultivo. Material y métodos. En este estudio, fueron aislados, identificados y cuantificados los vibrios del hepatopáncreas de 75 camarones blancos del Pacífico (Litopenaeus vannamei), aparentemente sanos, oriundos de un cultivo en la región nordeste de Brasil. Quince muestras, cada una consta de cinco camarones, se pusieron a prueba. Resultados. La densidad de Vibrio varió de 430 a 2.400 NMP g-1 (r s NMP cm-1 = -0.114; r s NMP g-1 = 0.211). Treinta aislamientos fueron obtenidos, la mayoría de los cuales pertenecían a la especie V. cholerae (n=11) y V. parahaemolyticus (n=7). Conclusiones. Los hallazgos del presente estudio sugieren que, incluso en ausencia de síntomas de la vibriosis, la microbiota de lo hepatopáncreas del camarón de cultivo puede incluir vibrios sacarosa positivos y negativos.

Objective. The present study aimed to investigate the presence of vibrios in the hepatopancreas of cultured shrimp. Materials and methods. Vibrios from the hepatopancreas of fifteen samples of five specimens each, of apparently healthy Pacific white shrimp (Litopenaeus vannamei) were isolated, identified and quantified. Results. The vibrio density ranged from 430 to 2,400 MPN g-1 (r s MPN cm-1=-0.114; r s MPN g-1 = 0.211). Thirty isolations were obtained, most of which belonged to the species V. cholerae (n=11) and V. parahaemolyticus (n=7). Conclusions. The outcomes of the present study suggest that, even in the absence of symptoms of vibriosis, the microbiota of the hepatopancreas of cultured shrimp may include sucrose positive and negative vibrios.

The objective of this work was to investigate, on a flask scale, the production of bioemulsifiers by Yarrowia lipolytica in the presence of sea water, supplemented with nitrogen and phosphate sources, using diesel oil as substrate. A full 2(4) factorial design was conducted to investigate the effects and interactions of the nutrient concentrations (diesel oil, urea, ammonium sulfate and monobasic potassium phosphate) on the response variables: emulsification activity and surface tension of the cell-free cultures. High emulsification activities (> 5,4 UEA) were determined after 168 h in all the experiments. The interactions among diesel oil, urea and monobasic potassium phosphate favored the emulsification with statistical significance. A correlation between the increase of emulsification activity and the reduction of surface tension was not identified.

Introdução: A Síndroma de Lynch (SL) confere um risco elevado para carcinoma do cólon e recto, mas também para outros tumores. Não é consensual se o carcinoma gástrico (CG) deve ser incluído no seu espectro, sobretudo em países com incidência elevada para esta neoplasia. Objectivos: Em famílias com diagnóstico ou suspeita de SL e na presença de CG, caracterizar estes tumores e comparálos com um grupo de CG esporádicos. Métodos: Foram incluídos 25 doentes pertencentes a 20 famílias com diagnóstico ou suspeita de SL, nos quais se obteve confirmação histológica do CG. As famílias cumpriam: Critérios de Amesterdão (n=12); Critérios de Bethesda (n=2) ou Critérios de Amesterdão apenas se considerado o CG (SL atípica; n=6). No grupo dos esporádicos, incluíram-se 58 doentes consecutivos com CG. Analisaram-se: sexo, idade de diagnóstico, localização, tipo histológico, grau de diferenciação, estádio e tratamento cirúrgico do CG. No grupo com SL, efectuou-se análise mutacional para os genes MLH1 e MSH2 por DGGE/MLPA e sequenciação directa. Resultados: Os doentes com CG em SL eram mais jovens, tendo os CG sido mais frequentemente detectados em fase precoce e submetidos a cirurgia de intenção curativa (p=0,045). O carcinoma mucocelular foi mais frequente nos CG esporádicos e o mucinoso nos associados à SL (p=0,014). O diagnóstico genético foi inconclusivo em todas as famílias com SL atípica testadas e positivo em 73% das famílias com SL clássica (p=0,02). Registaram-se mais frequentemente outros tumores do espectro nos doentes com CG pertencentes a famílias com mutação identificada (p=0,002) e nenhum ocorreu nos casos de SL atípica (p=0,009). Conclusões: Um subgrupo de doentes com CG pertencentes a famílias com SL apresentou características que favorecem, de forma significativa, a inclusão desta neoplasia no seu espectro tumoral. Nas famílias com SL atípica, a presença de CG não parece contribuir para a confirmação do diagnóstico desta entidade. Seria útil identificar marcadores que indicassem quais os CG que com maior probabilidade pertencerão ao espectro tumoral da SL.

Background: Lynch Syndrome (LS) is associated with an increased risk of colorectal cancer, but also of other tumours. It remains unsettled if gastric carcinoma (GC) should be included in this spectrum, especially when high-incidence countries for this tumour are considered. Aims: To study GC characteristics in LS families and to compare them with a group of sporadic GC. Methods: 25 patients with histological confirmation of GC, belonging to 20 LS families, were included in the present study. The families fulfilled: Amsterdam criteria (n=12); Bethesda criteria (n=2); Amsterdam criteria only if GC was considered (atypical LS - n=6). In the sporadic group, 58 consecutive patients with GC were included. Sex, age at GC diagnosis, tumour localization, histological type, differentiation and type of surgery were analyzed. In the LS group, mutational analysis for MLH1 and MSH2 was performed by DDGE/MLPA and direct sequencing. Results: GC patients in LS were younger and in these cases GC was more frequently detected at earlier stages, and more frequently submitted to curative surgery (p=0.045). Signet-ring cell carcinoma was more common in sporadic GC, while mucinous carcinoma was more frequent in LS (p=0.014). Genetic diagnosis was inconclusive in all atypical LS families studied and positive in 73% of the classical LS families tested (p=0.02). Other tumours of the LS spectrum were more commonly found in patients from families with identified mutations (p=0.002) and in no cases from atypical LS families (p=0.009). Conclusions: A subgroup of patients with GC and LS presented characteristics that strongly suggest GC inclusion in the LS tumour spectrum. In atypical LS families, the presence of GC does not seem to contribute for the diagnosis of this entity. It would be useful to find markers that could distinguish GC cases more likely to be associated with LS.

Timpanometria avalia condições funcionais da orelha média. Quando realizada em neonatos abaixo de quatro meses de idade pode gerar dúvidas. Sondas de alta freqüência têm sido investigadas na busca por resultados mais confiáveis. OBJETIVO: Descrever e analisar interpretações de características e medidas obtidas na timpanometria em neonatos com freqüências de 226, 678 e 1000Hz. MATERIAL E MÉTODO: Os 110 neonatos avaliados tinham idade entre 6 e 30 dias, não apresentaram fatores de risco e tinham emissões otoacústicas presentes. A timpanometria foi realizada com o analisador GSI-33-II, na Divisão de Educação e Reabilitação dos Distúrbios da Comunicação, São Paulo, em 2004. FORMA DE ESTUDO: Clínico prospectivo. RESULTADOS: Observou-se equilíbrio nas curvas pico único e pico duplo em 226Hz, maior ocorrência de assimétrica em 678Hz e de pico único em 1000 Hz. Houve significância de gênero na medida volume equivalente do meato acústico externo, em 226Hz, e na medida admitância acústica estática de pico compensado, em 1000Hz. O protocolo inglês apresentou quase 100% de normalidade em 678 e 1000Hz. CONCLUSÃO: A sonda de 1000Hz apresentou melhores resultados na caracterização da normalidade. O protocolo inglês mostrou-se eficiente em diminuir variabilidades das medidas. Os resultados podem ser usados como guia no diagnóstico da timpanometria.

Tympanometry is used in evaluating middle ear functional conditions. Before six months of age its results may be misleading. High frequency studies aim to provide more valid procedures. AIM: To describe and discuss tympanometric measurements and the interpretation in normal hearing neonates at 226, 678 and 1000Hz. METHOD: 110 neonates that were analyzed had normal otoacoustic emissions and no risk for hearing impairment. The age range was 6 to 30 days. Curves were obtained using the GSI-33-II, at the Divisão de Educação e Reabilitação dos Distúrbios da Comunicação, São Paulo, in 2004. STUDY DESIGN: Clinical prospective. RESULTS: There was a balance between single and double peak curves at 226Hz. Most of the curves were asymmetric at 678Hz, and single-peaked at 1000Hz. quantitative measurements showed a significant gender difference in the Equivalent Ear Canal Volume at 226Hz and on the Peak Compensated Static Acoustic Admittance at 1000Hz. The English protocol showed that almost 100% of ears were normal at 678 and 1000Hz. CONCLUSION: 1000Hz yielded superior results for characterizing normality. The English protocol was efficient to reduce the variability of tympanometric measurements. Data from this study may be used as a guide for diagnosis using tympanometry in neonates.

Introdução: A instabilidade de microssatélites, marcador da via mutadora, é detectada em 15% dos carcinomas do cólon ou recto esporádicos e numa percentagem mais elevada em doentes jovens (idade < 45 anos). Aceita-se que a maioria dos restantes carcinomas do cólon ou recto siga a via supressora. Objectivos: Em doentes com carcinoma do cólon ou recto em idade inferior a 45 anos: 1) Avaliar a prevalência das vias mutadora e supressora; 2) Correlacionar as características clínico-patológicas e a sobrevivência com a via seguida. Doentes e Métodos: Incluíram-se 42 doentes (19 homens/23 mulheres, média de idades: 35,5±6,0 anos). A via mutadora foi caracterizada com os marcadores de Bethesda, considerando-se ser a via seguida pelo tumor na presença instabilidade de alto grau. A via supressora foi avaliada através da análise das perdas de heterozigotia (genes APC, p53, DCC e SMAD4); considerou-se que o tumor seguia a via supressora quando existiam alterações em pelo menos 2 (50%) desses genes. Analisaram-se ainda: localização, diferenciação, produção de muco, estádio, ocorrência de recidiva do carcinoma do cólon ou recto e sobrevivência. Resultados: 14/42 (33%) carcinomas do cólon ou recto seguiram a via mutadora e 16/42 (38%) a via supressora. Em 12/42 (29%) carcinomas do cólon ou recto terá sido seguida uma via alternativa. No entanto, considerando dois grupos, com idade inferior ou igual e superior a 35 anos, nos mais jovens os carcinomas do cólon ou recto seguiram a via mutadora em 53,3%, a via supressora em 13,3% e a via alternativa em 33,3% (p=0,03). Registou-se uma localização preferencial dos carcinomas do cólon ou recto que seguiram a via mutadora ao nível do cólon proximal e dos que seguiram a via alternativa no recto (p<0,001). Os carcinomas do cólon ou recto da via supressora apresentaram menor produção de muco (p=0,03). A probabilidade cumulativa de sobrevivência aos 8 anos foi: 70% na via mutadora, 69% na via alternativa e 50% na via supressora. Conclusões: 1) A via mutadora só foi preferencialmente seguida nos casos com carcinoma do cólon ou recto em idade inferior a 35 anos; 2) Uma percentagem importante dos carcinomas do cólon ou recto em jovens seguiu uma via alternativa, ainda não caracterizada; 3) Nestes últimos casos, verificou-se uma localização predominante dos carcinomas no recto e uma sobrevivência elevada, semelhante à da via mutadora; 4) Admitimos a existência de uma via alternativa em jovens com carcinoma do cólon ou recto, com características próprias e associada a eventos genéticos ainda não esclarecidos.

Background: Microsatellite instability, a hallmark of the mutator pathway in colorectal carcinogenesis, is present in 15% of sporadic colorectal cancers and in a higher percentage of young patients (< 45 years). The majority of the remaining colorectal cancers may follow the classic suppressor pathway. Aims: In patients with colorectal cancers diagnosed at an age < 45 years: 1) to evaluate the prevalence of the mutator and suppressor pathways; 2) to analyse the clinic and pathological characteristics and survival of the two pathways. Patients and Methods: Forty-two patients (19 male and 23 female, mean age: 35.5 ± 6.0 yrs) were included. The mutator pathway was analysed using the Bethesda markers. Colorectal cancers presenting microsatellite instabilityhigh were classified as following the mutator pathway. To study the involvement of the suppressor pathway, loss of heterozigoty was evaluated at the following loci: APC, p53, DCC and SMAD4 genes. When loss of heterozigoty was detected in 2 (50%) or more loci, suppressor pathways was assumed. The cancer location, pathological characteristics, stage and recurrence were also recorded. Results: 14/42 (33%) and 16/42 (38%) of colorectal cancers followed the mutator and the suppressor pathway, respectively. In 12/42 (29%) an alternative pathway of carcinogenesis may have been followed. However, if we divide the patients into two groups according to whether the age at time of diagnosis was before or after 35 years, in the younger group the mutator pathway was observed in 53.3%, the suppressor pathway in 13.3% and an alternative pathway in 33.3% of colorectal cancers (p=0.03). Colorectal cancers following the mutator pathway tended to be located at the proximal colon, while those following the alternative pathway tended to be at the rectum (p<0.001). Colorectal cancers following the suppressor pathway showed less mucous production (p=0.03). The cumulative survival rate at 8 years was: 70% for mutator, 69% for alternative and 50% for suppressor pathways. Conclusions: 1) The mutator pathway was preferentially followed only in colorectal cancer patients under the age of 35; 2) A significant number of cases followed an alternative pathway yet to be described; 3) In the latter cases, colorectal cancers were predominantly located at the rectum and patients had a high survival rate, similar to that of the mutator pathway; 4) Our results suggest that there might be an alternative pathway for colorectal cancers in young patients that presents specific characteristics and is associated with genetic events not yet known.

Snake venom is characterized by hemorrhagic, coagulant, proteolytic and myotoxic activities which in Bothrops jaracussu venom are related to intraspecific variations. In the present study, female Swiss mice were divided into two groups: treated with 25µg or 50µg venom. These were subdivided into three groups of six animals each, according to blood collection: 2, 4 or 24h after venom injection. Animals were anesthetized using diethyl-ether inhalation and 1ml of blood was collected by heart puncture. Then, the following organs were removed: spleen, skeletal muscle, kidneys, liver and lungs; histological sections were obtained and stained with hematoxylin-eosin (HE). The following biochemical parameters were analyzed: aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), total lactate dehydrogenase (LDH), glucose, creatinine and urea levels, and total protein content. Results showed significant alterations in AST, LDH, glucose and urea levels, and total protein content, as well as important tissue alterations in the liver, kidneys and lungs. It could be concluded that, even using sublethal doses of venom, there were significant changes in almost all the tested biochemical parameters as well as tissue alterations in the kidneys and lungs.

Introdução: O diagnóstico clínico da Síndroma de Lynch (SL) baseia-se nos critérios de Amesterdão (CA); adicionalmente, algumas famílias são identificadas com base nos critérios de Bethesda (CB). A SL resulta de mutações germinais em genes de reparação do ADN, sobretudo no MLH1 e MSH2, mas também no MSH6, PMS1 e PMS2. Não foram ainda identificadas localizações preferenciais das mutações nestes genes que permitam orientar o diagnóstico genético. Objectivos: Em doentes de famílias com SL com mutações identificadas nos genes MLH1, MSH2 ou MSH6, correlacionar as características clínicas com a localização das mutações. Doentes e Métodos: Incluíram-se 58 doentes (21 H/37 M) pertencentes a 33 famílias com CA e 7 famílias com CB, todos com mutação germinal identificada num dos genes de reparação do ADN. Registou-se o tipo de tumor desenvolvido, a idade de diagnóstico e as características patológicas dos carcinomas do cólon e recto (CCR). A análise mutacional nos genes MLH1, MSH2 e MSH6 foi efectuada por DGGE, seguida de sequenciação directa a partir do produto de PCR. Nas famílias cujo diagnóstico genético foi inconclusivo por DGGE, procedeu-se a MLPApara identificação de grandes delecções. Resultados: Desenvolveram CCR 48/58 (83%) doentes, com uma média de idades de 45 anos (25-74). Os restantes 10 doentes apresentaram outros tumores do espectro da SL (6 endométrio, 2 ovário, 1 urotélio e 1 estômago). Foram identificadas 22 famílias com mutações no gene MLH1, 17 no gene MSH2 e uma no gene MSH6. A maioria (76%) das mutações patogénicas no gene MLH1 encontrava-se entre os exões 10 e 19, sendo neste grupo a média de idades de desenvolvimento do CCR mais tardia, 49,8 versus 32,5 anos (p=0,01) e mais frequente a presença de tumores extra-cólicos. No gene MSH2, 71% das mutações patogénicas encontravam-se entre os exões 1 e 8, tendo também estas predominado em famílias com tumores extra-cólicos. Conclusões: Os resultados observados sugerem que, de acordo com as características das famílias, se deva iniciar o diagnóstico genético pelos exões mais frequentemente mutados em cada gene.

Background: HNPCC diagnosis is based on the Amsterdam criteria (AC), although some families are also identified using the Bethesda guidelines (BG). HNPCC is associated with germline mutations in the DNA mismatch repair genes, particularly MLH1 and MSH2, but also MSH6, PMS1 and PMS2. At present, no "hot-spots" have been identified that could direct genetic diagnosis. Aims: In patients belonging to HNPCC families with identified mutations in MLH1, MSH2 or MSH6 genes, to correlate tumor characteristics with the location of the mutation. Patients and Methods: We studied 58 patients (21M/37F) belonging to 33 families with AC and 7 families with BG, all with an identified germline mutation. Age of diagnosis and pathological characteristics of the colorectal cancer (CRC) were recorded, as well as the presence of HNPCC extracolonic cancers. Mutational analysis in MLH1, MSH2 and MSH6 genes was performed by DGGE and direct sequencing. In families with no identified point mutations, we also performed MLPA for detection of large deletions. Results: A total of 48/58 (83%) of the patients had CRC, with a mean age at diagnosis of 45 years (25-74). The remaining 10 patients had an HNPCC-associated cancer other than CRC (6 endometrial, 2 ovarian, 1 urinary tract and 1 stomach). We identified 22 families with MLH1 mutations, 17 with MSH2 mutations and one with a MSH6 mutation. Most (76%) of the pathogenic mutations in MLH1 gene were located between exons 10 and 19. In this location mean age of CRC diagnosis was higher, 49.8 versus 32.5 years (p=0.01) and more associated HNPCC extracolonic tumors were found. In MSH2, 71% of the mutations were located between exons 1 and 8 and, in this group, more extra-colonic tumors belonging to HNPCC spectrum were identified. Conclusions: Our results suggest that based on family characteristics, genetic diagnosis should be started by the more frequently mutated exons in each gene.

The stylohyoid chain has caught the attention due to the big incidence of the elongated styloid process of temporal bone with characterizes the Eagle's Syndrome, rating 28% of the population. The purpose of this work is to describe the method of approach by the macroscopic dissection of the stylohyoid chain. Using 15 neck regions of male sex dead bodies, the method has brought a result of 30 stylohyoid chains and verified that the approach from both edges of the chain, prevents the risk of lesion the styloid ligament and preserves the entirety of the stylohyoid chain

La cadena estilohioídea está mereciendo considerable atención debido a la gran incidencia del alargue de uno de sus elementos llamado proceso estiloide del hueso temporal, que caracteriza al Síndrome de Eagle, llegando a alcanzar el 28% de la población. Nuestro trabajo tiene como objetivo describir un método de disección macroscópica para un abordaje de la cadena estilohioídea. Utilizando 15 regiones del cuello de cadáveres humanos, de sexo masculino se obtuvieron 30 cadenas estilohioídeas a través del método de disección macroscópica, observándose que el método de acceso por etapas, a partir de ambas extremidades de la cadena, es el que ofrece menor riesgo de lesión del ligamento estiloihíodeo preservándose, de esta manera, la integridad de la cadena estilohioídea