Comparative evaluation of 11 in silico models for the prediction of small molecule mutagenicity: role of steric hindrance and electron-withdrawing groups.

The goal of this investigation was to perform a comparative analysis on how accurately 11 routinely-used in silico programs correctly predicted the mutagenicity of test compounds that contained either bulky or electron-withdrawing substituents. To our knowledge this is the first study of its kind in the literature. Such substituents are common in many pharmaceutical agents so there is a significant need for reliable in silico programs to predict precisely whether they truly pose a risk for mutagenicity. The predictions from each program were compared to experimental data derived from the Ames II test, a rapid reverse mutagenicity assay with a high degree of agreement with the traditional Ames assay. Eleven in silico programs were evaluated and compared: Derek for Windows, Derek Nexus, Leadscope Model Applier (LSMA), LSMA featuring the in vitro microbial Escherichia coli-Salmonella typhimurium TA102 A-T Suite (LSMA+), TOPKAT, CAESAR, TEST, ChemSilico (±S9 suites), MC4PC and a novel DNA docking model. The presence of bulky or electron-withdrawing functional groups in the vicinity of a mutagenic toxicophore in the test compounds clearly affected the ability of each in silico model to predict non-mutagenicity correctly. This was because of an over reliance on the part of the programs to provide mutagenicity alerts when a particular toxicophore is present irrespective of the structural environment surrounding the toxicophore. From this investigation it can be concluded that these models provide a high degree of specificity (ranging from 71% to 100%) and are generally conservative in their predictions in terms of sensitivity (ranging from 5% t o 78%). These values are in general agreement with most other comparative studies in the literature. Interestingly, the DNA docking model was the most sensitive model evaluated, suggesting a potentially useful new mode of screening for mutagens. Another important finding was that the combination of a quantitative structure-activity relationship and an expert rules system appeared to offer little advantage in terms of sensitivity, despite of the requirement for such a screening paradigm under the ICH M7 regulatory guideline.

Women with fibromyalgia (ACR criteria) compared with women diagnosed by doctors and women with osteoarthritis: Cross-sectional study using functional and clinical variables.

PURPOSE: To compare functional and clinical variables of women with fibromyalgia (American College of Rheumatology [ACR] criteria) vs women diagnosed by doctors and women with knee osteoarthritis (KOA). METHODS: This is a cross-sectional study. We used clinical measures, namely, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Fibromyalgia Impact Questionnaire-Revised (FIQ-R), Numerical Pain Rating Scale (NPRS), Central Sensitization Inventory (CSI), Pain-Related Catastrophizing Thoughts Scale (PCTS), and functional measures, such as Sit-to-Stand (STS) test, and Timed Up and Go (TUG) test. RESULTS: The sample consisted of 91 participants divided into 3 groups: participants with KOA (n = 30), fibromyalgia diagnosed according to the ACR (FM-ACR, n = 31), and fibromyalgia according to the medical diagnosis (FM-Med, n = 30). In the comparisons, we observed a significant difference (P < 0.05) and a large effect size (d ≥ 0.8), between all groups, in the WPI, WPI + SSS, FIQ-R domains, CSI, and PCTS. We did not observe significant values in the correlations between the clinical variables, SST, and TUG test. CONCLUSION: People with fibromyalgia according, to the ACR, have higher levels of widespread pain, symptom severity, global impact on quality of life, central sensitization, and catastrophizing compared with people with knee OA and people with clinical fibromyalgia diagnosis not confirmed by the ACR diagnostic criteria.

Kinase Inhibition in Multiple Myeloma: Current Scenario and Clinical Perspectives.

Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.

Structural validity of the Brazilian version of the Western Ontario and McMaster Universities Osteoarthritis Index among patients with knee osteoarthritis.

BACKGROUND: The original structure of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been contested in several languages. OBJECTIVE: To assess the structural validity of the Brazilian version of WOMAC among patients with knee osteoarthritis. DESIGN AND SETTING: Structural validity study conducted at physiotherapy clinics and primary healthcare units. METHODS: The study included males and females aged 40 to 80 years who were all native Brazilian Portuguese speakers, with knee pain in the previous six months and a diagnosis of knee osteoarthritis. We used exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA) with implementation of a polychoric matrix and the robust diagonally weighted least squares (RDWLS) extraction method. The adequacy of the model was assessed using the following fit indices: root mean square error of approximation (RMSEA), comparative fit index (CFI), Tucker-Lewis index (TLI), standardized root mean square residual (SRMR) and chi-square/degree of freedom (DF). RESULTS: 203 patients with knee osteoarthritis were included. The model proposed in this study with two factors, i.e. "pain" (items 1, 2, 3 and 4) and "physical function" (items 10, 11, 16, 17, 18, 19, 21 and 22), showed adequate fit indices in CFA: chi-square/DF = 1.30; CFI = 0.976; TLI = 0.970; RMSEA = 0.039; and SRMR = 0.070. The factorial loads ranged from 0.68 to 0.76 for the "pain" domain and 0.44 to 0.62 for the "physical function" domain. CONCLUSION: The Brazilian version of WOMAC with two domains, i.e. "pain" (four items) and "physical function" (eight items), presents the best structure.

New species and records of Paliphora from the Brazilian semi-arid region.

In the course of studies about conidial fungi that grow on plant debris in the semi-arid region of Brazil, four species of Paliphora were found on unidentified dicotyledonous plants. Paliphora intermedia and P. porosa are recorded for the first time for South America and the neotropics respectively. Paliphora inflata and P. multiseptata are proposed as new species. A key and synoptic table of characters of the five known species of Paliphora are provided.

Structural validity of the Brazilian version of the Western Ontario and McMaster Universities Osteoarthritis Index among patients with knee osteoarthritis

BACKGROUND: The original structure of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been contested in several languages. OBJECTIVE: To assess the structural validity of the Brazilian version of WOMAC among patients with knee osteoarthritis. DESIGN AND SETTING: Structural validity study conducted at physiotherapy clinics and primary healthcare units. METHODS: The study included males and females aged 40 to 80 years who were all native Brazilian Portuguese speakers, with knee pain in the previous six months and a diagnosis of knee osteoarthritis. We used exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA) with implementation of a polychoric matrix and the robust diagonally weighted least squares (RDWLS) extraction method. The adequacy of the model was assessed using the following fit indices: root mean square error of approximation (RMSEA), comparative fit index (CFI), Tucker-Lewis index (TLI), standardized root mean square residual (SRMR) and chi-square/degree of freedom (DF). RESULTS: 203 patients with knee osteoarthritis were included. The model proposed in this study with two factors, i.e. "pain" (items 1, 2, 3 and 4) and "physical function" (items 10, 11, 16, 17, 18, 19, 21 and 22), showed adequate fit indices in CFA: chi-square/DF = 1.30; CFI = 0.976; TLI = 0.970; RMSEA = 0.039; and SRMR = 0.070. The factorial loads ranged from 0.68 to 0.76 for the "pain" domain and 0.44 to 0.62 for the "physical function" domain. CONCLUSION: The Brazilian version of WOMAC with two domains, i.e. "pain" (four items) and "physical function" (eight items), presents the best structure.

Assessment of microbiological contamination of fresh, minimally processed, and ready-to-eat lettuces (Lactuca sativa), Rio de Janeiro State, Brazil.

UNLABELLED: This study aimed to assess the microbiological contamination of lettuces commercialized in Rio de Janeiro, Brazil, in order to investigate detection of norovirus genogroup II (NoV GII), Salmonella spp., total and fecal coliforms, such as Escherichia coli. For NoV detection samples were processed using the adsorption-elution concentration method associated to real-time quantitative polymerase chain reaction (qPCR). A total of 90 samples of lettuce including 30 whole fresh lettuces, 30 minimally processed (MP) lettuces, and 30 raw ready-to-eat (RTE) lettuce salads were randomly collected from different supermarkets (fresh and MP lettuce samples), food services, and self-service restaurants (RTE lettuce salads), all located in Rio de Janeiro, Brazil, from October 2010 to December 2011. NoV GII was not detected and PP7 bacteriophage used as internal control process (ICP) was recovered in 40.0%, 86.7%, and 76.7% of those samples, respectively. Salmonella spp. was not detected although fecal contamination has been observed by fecal coliform concentrations higher than 10(2) most probable number/g. E. coli was detected in 70.0%, 6.7%, and 30.0% of fresh, MP, and RTE samples, respectively. This study highlights the need to improve hygiene procedures at all stages of vegetable production and to show PP7 bacteriophage as an ICP for recovering RNA viruses' methods from MP and RTE lettuce samples, encouraging the evaluation of new protocols that facilitate the establishment of methodologies for NoV detection in a greater number of food microbiology laboratories. PRACTICAL APPLICATION: The PP7 bacteriophage can be used as an internal control process in methods for recovering RNA viruses from minimally processed and ready-to-eat lettuce samples.

Listeria monocytogenes em hortaliças: isolamento e sorotipagem / Listeria monocytogenes in green vegetables: isolation and serotyping

A ingestão de alimentos contaminados com Listeria monocytogenes representa um risco à saúde humana.A pesquisa de L. monocytogenes por meio de técnica de enriquecimento seletivo foi efetuada em 97amostras de hortaliças, comercializadas no Estado do Rio de Janeiro. Foram analisadas 35 hortaliças innatura, 32 minimamente processadas e 30 pratos de saladas cruas prontas para consumo. Os isoladosforam sorotipados por soroaglutinação clássica utilizando-se antissoro policlonal flagelar e somático.Sete amostras (7,2 %) apresentaram L. monocytogenes, sendo duas hortaliças in natura e cinco emforma de salada. Todos os isolados foram identificados como sorovar 1/2a. Em virtude da ocorrência decontaminação de hortaliças in natura com L. monocytogenes, é fundamental que os consumidores estejamesclarecidos quanto à possível presença deste patógeno nesse tipo de alimento, e ficarem cientes quantoà realização de corretos procedimentos de sanitização e de cuidados para evitar a contaminação cruzadacom outros alimentos. A presença de L. monocytogenes em saladas prontas para consumo representa umrisco à saúde dos consumidores, principalmente para indivíduos pertencentes ao grupo de risco.

Celulite associada às lesões na bolsa de Fabrício de frangos de corte ao abate, sob inspeção sanitária / Cellulitis associated with lesions of bursa of Fabricius from broilers under sanitary inspection

Foi realizado um estudo epidemiológico de caso controle, onde foram avaliados 128 frangos de corte, entre 40 e 48 dias deidade, sob inspeção sanitária, vacinados contra a Doença Infecciosa da Bolsa de Fabrício (DIB) no 14o dia de vida (via água debebida). O grupo caso foi constituído por 68 aves portadoras de celulite e o grupo controle, por 60 aves sem a doença. Asbolsas de Fabrício foram medidas em bursômetro e registradas de acordo com sua escala. Após o exame macroscópicoforam coletados fragmentos de pele, lesada e íntegra, e de bolsa de Fabrício, fixados em formol a 10%, para a realização dahistopatologia. Foi criado o seguinte escore para análise histológica das lesões: escore 0 – sem lesão; escore 1 – discretashiperplasia e rarefação linfóide de folículos; 2 – edema, infiltrado inflamatório, necrose de folículos, rarefação linfóide severa eatrofia discreta de folículos; escore 3 – presença de cistos foliculares e epiteliais, atrofia severa de folículos e fibrose. A análiseestatística constou dos testes de qui-quadrado Kruskall-Wallys e Regressão Linear. A mensuração do bursômetro mostrou,no grupo caso 28 frangos com bolsas de diâmetro 10mm (tamanho 3); 37, com diâmetro 13mm (tamanho 4); três, comdiâmetro 16mm (tamanho 5); e no grupo controle 26 frangos com bolsas de diâmetro 10mm (tamanho 3); 31, com diâmetro13mm (tamanho 4); três, de diâmetro 16mm (tamanho 5). Macroscopicamente não foram observadas alterações.Microscopicamente foram registrados uma bolsa com escore 0; três, com escore 1; 25, com escore 2; e 99, com escore 3.Houve diferença estatística (p< 0,05) entre os grupos caso e controle em relação ao diâmetro e aos escores de lesão de bolsade Fabrício obtidos. Conclui-se que lesões amareladas em placas no subcutâneo de frangos de corte devem ser consideradascomo celulite, e critério para julgamento da carcaça, e são favorecidas pelas lesões mais graves na bolsa de Fabrício

This work is an epidemiological study of case control, evaluating 128 broiler chickens, between 40 and 48 days old, undersanitary inspection, vaccinated against the DIB in the 14th day of age (through drinking water). The case group consists of 68broiler chickens with celulitis and the control group consists of 60 healthy animals. The bursals, when collected, were measuredin bursometer and registered in accordance with its scale. After the macroscospic examination were collected skin fragments,both injured and not injured, as well as bursal fragments, fixed with 10% phormol, in order to finish the histopathology, and alsofor the and processing by the established techniques, as well as included in paraffin and stained with hematoxilin and eosin, atthe Pathological Anatomy Service Professor Jéfferson Andrade dos Santos (UFF). A score has been created for the histophatologicalanalysis of the injuries with the following criteria: score 0 - without injury; score 1 - discrete hyperplasia and lymphoid folliclesrarefaction; score 2 - edema, inflammatory infiltrate, follicle necrosis, severe lymphoid rarefaction and follicle discrete atrophy;3 - presence of epithelial and follicle cysts, severe follicle atrophy and fibrosis. The statistical analysis was made with the Qui-square Kruskall-Wallys tests and Linear Regression. The bursometer analysis has demonstrated that: in case group- 28broiler chickens with burse the diameter 10 mm (size 3); 37, with diameter 13 mm (size 4); three, with diameter 16 mm (size 5);and in control group – 26 broiler chickens with burse the diameter 10 mm (size 3); 31, with diameter 13 mm (size 4); três, threewith diameter 16 mm (size 5). Through microscopical analysis we registered 1 bursal with score 0; 3 with score 1; 25 with score2; and 99 with score 3. There was statistical difference (p£ 0.05) between the case and control groups in relation to the diameterand to the scores of bursal injuries that...

Aspectos anatomopatológicos da miopatia peitoral profunda em frangos de corte abatidos sob inspeção sanitária

A miopatia peitoral profunda é uma enfermidade poligênica, caracterizada pela necrose do músculo supracoracóideo defrangos de corte e perus comerciais. A lesão é causada pela isquemia local, resultado do intenso melhoramento genéticodessas aves, na tentativa de selecionar animais com musculatura peitoral bem desenvolvida. Neste estudo foram realizadasdescrições macroscópicas e microscópicas de lesões consideradas típicas de miopatia peitoral profunda. Foram colhidosfragmentos do músculo supracoracóideo de 17 frangos de corte e do músculo peitoral de um frango. Macroscopicamente, amusculatura afetada apresentava coloração variada, sendo observadas as cores vermelho-púrpura, amarelo-claro ou verde,e ainda, atrofia acentuada. Nestes últimos, a textura era ressecada e friável, enquanto nos casos em que a coloração eravermelho-púrpura, notava-se uma aparência edematosa da musculatura. Microscopicamente, as alterações eram representadaspor extensas áreas de necrose de fibras, com mineralização e fragmentação de miofibras. Em duas amostras eram evidentesa calcificação de paredes vasculares e a degeneração de nervos. Em uma amostra era marcante o processo inflamatóriogranulomatoso, rico em células gigantes multinucleadas. De acordo com os resultados obtidos, pode-se afirmar que,independentemente dos aspectos apresentados ao exame externo, as alterações microscópicas foram constantes, t

Relação entre o diâmetro e histopatologia de bolsas de Fabrício de frangos de corte sob inspeção sanitária no estado de Santa Catarina

Foram estudadas 128 bolsas de Fabrício de frangos de corte com idade entre 40 e 48 dias, vacinados contra a doençainfecciosa da bolsa de Fabrício no décimo quarto dia de vida. As bolsas foram coletadas em um matadouro sob inspeçãosanitária, e após mensuradas no bursômetro, foram acondicionadas em formol a 10% para o processamento pela técnicahabitual de histologia para inclusão em parafina e coloração pela hematoxilina-eosina, para exame histológico. Foram obtidosos seguintes resultados na escala do bursômetro, convertida em milímetros: 54 (42,19%) frangos com bolsas de diâmetro10mm (tamanho 3); 68 (53,12%), com diâmetro 13mm (tamanho 4) e seis (4,69%), com diâmetro 16mm (tamanho 5). Asbolsas de Fabrício apresentaram os seguintes escores de lesões histológicas: escore 0, um caso; escore 1, três casos;escore 2, 25 casos e escore 3, 99 casos. As bolsas com os diâmetros 10 e 13mm, registraram grau de lesão mais grave,escore 3 (p 0,001). Das bolsas de maior diâmetro, apenas um caso foi classificado com escore 3. A maioria dos frangos decorte ao abate apresentou os menores tamanhos das bolsas de Fabrício, justificados pela observação das lesõesmicroscópicas mais graves que promoveram a atrofia do órgão, o que pode comprometer a higidez da ave.

Cistercose bovina em matadouro-frigorífico dob inspeção sanitária no município de Teixeira de Freitas-BA: prevalência da enfermidade e análise anatomopatológica de diagnósticos sugestivos de cisticercose / Bovine cysticercosis in slaughterhouse under sanitary inspection in Teixeira de Freitas-Brazil: prevalence and anatomy pathological analysis of suspected cysticercosis

Foram diagnosticados, nas linhas de inspeção e registrados nos mapas de condenação, 115 (4,20) casos de cisticercose bovina, 108 (92,17).