The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Aid conditionalities, international Good Manufacturing Practice standards and local production rights: a case study of local production in Nepal

© 2015 Brhlikova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This work was supported by the Economic and Social Research Council and the Department for International Development [RES-167-25-0110] through the collaborative research project Tracing Pharmaceuticals in South Asia (2006 – 2009). In addition to the authors of this paper, the project team included: Soumita Basu, Gitanjali Priti Bhatia, Erin Court, Abhijit Das, Stefan Ecks, Patricia Jeffery, Roger Jeffery, Rachel Manners, and Liz Richardson. Martin Chautari (Kathmandu) and the Centre for Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper but are not responsible for the views expressed, nor are ESRC or DFID. Ethical review was provided by the School of Social and Political Science at the University of Edinburgh, and ethical approval in Nepal for the study granted by the Nepal Health Research Council (NHRC)

Fatores de risco para fratura por osteoporose e baixa densidade óssea em mulheres na pré e pós-menopausa

OBJECTIVE: To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women. METHODS: Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05. RESULTS: The prevalence of osteoporosis and osteoporotic fractures was 33% and 11.5%, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95% CI: 1.06;1.08), time since menopause (OR=2.16; 95% CI: 1.49;3.14), previous fracture (OR=2.62; 95% CI: 2.08;3.29) and current smoking (OR=1.45; 95% CI: 1.13;1.85). BMI (OR=0.88; 95% CI: 0.86;0.89), regular physical activity (OR=0.78; 95% CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95% CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95% CI: 1.04;1.06), time since menopause (OR=4.12; 95% CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95% CI: 2.88;4.47) and low BMD (OR=2.28; 95% CI: 1.85;2.82). CONCLUSIONS: Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for fractures might be a reasonable strategy to improve the management of osteoporosis.OBJETIVO: Estimar la prevalencia y analizar los factores de riesgo asociados con osteoporosis y fractura por bajo impacto entre mujeres. MÉTODOS: Estudio transversal realizado con 4.332 mujeres encima de 40 años de edad provenientes de atención primaria de salud en el área metropolitana de la gran São Paulo, SP, entre 2004 2007. Datos antropométricos y ginecológico y relativos a hábitos de vida, fractura previa, antecedentes personales, ingestión alimentaria y actividad física fueron evaluados por medio de entrevista individual y cuantitativa. Fractura por bajo impacto fue definida como decurrente de caída de la propia altura o menos en individuos con más de 50 años de edad. Modelos de regresión multivariada y logística analizaron, respectivamente, la densidad ósea y la fractura por osteoporosis, como variables dependientes y todas las otras como independientes. El nivel de significancia estadística establecido fue p<0,05. RESULTADOS: La prevalencia de osteoporosis y de fracturas por fragilidad ósea fue de 33% y 11,5%, respectivamente. Los principales factores de riesgo asociados con baja densidad ósea fueron edad (OR=1,07; IC 95%: 1,06;1,08), menopausia (OR=2,16; IC 95%: 1,49;3,14), fractura previa (OR=2,62; IC 95%: 2,08;3,29) y tabaquismo actual (OR=1,45; IC 95%: 1,13;1,85). Por otro lado, elevado IMC (OR=0,88; IC 95%: 0,86;0,89), actividad física regular (OR=0,78; IC 95%: 0,65;0,94) y terapia hormonal actual (OR=0,43; IC 95%: 0,33;0,56) desempeñaron papel protector. Los factores de riesgo significantemente relacionados con fractura por osteoporosis fueron edad (OR=1,05; IC 95%: 1,04;1,06), menopausia (OR=4,12; IC 95%: 1,79;9,48), historia familiar de fractura de cuadril (OR=3,59; IC 95%: 2,88;4,47) y baja densidad ósea (OR=2,28; IC 95%: 1,85;2,82). CONCLUSIONES: Edad avanzada, menopausia, fractura previa por bajo impacto y tabaquismo actual son los principales factores de riesgo asociados con baja densidad ósea y esta, con las fracturas por fragilidad ósea. El uso clínico de estos parámetros para identificar mujeres de mayor riesgo para fracturas puede ser una estrategia interesante para mejorar el abordaje de la osteoporosis.OBJETIVO: Estimar a prevalência e analisar os fatores de risco associados com osteoporose e fratura por baixo impacto entre mulheres. MÉTODOS: Estudo transversal realizado com 4.332 mulheres acima de 40 anos de idade provenientes de atendimento primário de saúde na área metropolitana da Grande São Paulo, SP, entre 2004 e 2007. Dados antropométricos e ginecológicos e relativos a hábitos de vida, fratura prévia, antecedentes pessoais, ingestão alimentar e atividade física foram avaliados por meio de entrevista individual e quantitativa. Fratura por baixo impacto foi definida como decorrente de queda da própria altura ou menos em indivíduos com mais de 50 anos de idade. Modelos de regressão multivariada e logística analisaram, respectivamente, a densidade óssea e a fratura por osteoporose como variáveis dependentes e todas as outras como independentes. O nível de significância estatística estabelecido foi p < 0,05. RESULTADOS: A prevalência de osteoporose e de fraturas por fragilidade óssea foi de 33% e 11,5%, respectivamente. Os principais fatores de risco associados com baixa densidade óssea foram idade (OR = 1,07; IC 95%: 1,06;1,08), menopausa (OR = 2,16; IC 95%: 1,49;3,14), fratura prévia (OR = 2,62; IC 95%: 2,08;3,29) e tabagismo atual (OR = 1,45; IC 95%: 1,13;1,85). Por outro lado, elevado IMC (OR = 0,88; IC 95%: 0,86;0,89), atividade física regular (OR = 0,78; IC 95%: 0,65;0,94) e terapia hormonal atual (OR = 0,43; IC 95%: 0,33;0,56) desempenharam papel protetor. Os fatores de risco significativamente relacionados com fratura por osteoporose foram idade (OR = 1,05; IC 95%: 1,04;1,06), menopausa (OR = 4,12; IC 95%: 1,79;9,48), história familiar de fratura de quadril (OR = 3,59; IC 95%: 2,88;4,47) e baixa densidade óssea (OR = 2,28; IC 95%: 1,85;2,82). CONCLUSÕES: Idade avançada, menopausa, fratura prévia por baixo impacto e tabagismo atual são os principais fatores de risco associados com baixa densidade óssea, a qual se associa com as fraturas por fragilidade óssea. O uso clínico desses parâmetros para identificar mulheres de maior risco para fraturas pode ser uma estratégia interessante para melhorar a abordagem da osteoporose.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP-EPM Instituto de Diagnóstico por ImagemUNIFESP-EPM Programa de Pós-Graduação em ReumatologiaUNIFESP-EPM Departamento de RadiologiaUNIFESP, EPM, Instituto de Diagnóstico por ImagemUNIFESP, EPM Programa de Pós-Graduação em ReumatologiaUNIFESP, EPM Depto. de RadiologiaSciEL

Expression of emotional arousal in two different piglet call types

Humans as well as many animal species reveal their emotional state in their voice. Vocal features show strikingly similar correlation patterns with emotional states across mammalian species, suggesting that the vocal expression of emotion follows highly conserved signalling rules. To fully understand the principles of emotional signalling in mammals it is, however, necessary to also account for any inconsistencies in the way that they are acoustically encoded. Here we investigate whether the expression of emotions differs between call types produced by the same species. We compare the acoustic structure of two common piglet calls—the scream (a distress call) and the grunt (a contact call)—across three levels of arousal in a negative situation. We find that while the central frequency of calls increases with arousal in both call types, the amplitude and tonal quality (harmonic-to-noise ratio) show contrasting patterns: as arousal increased, the intensity also increased in screams, but not in grunts, while the harmonicity increased in screams but decreased in grunts. Our results suggest that the expression of arousal depends on the function and acoustic specificity of the call type. The fact that more vocal features varied with arousal in scream calls than in grunts is consistent with the idea that distress calls have evolved to convey information about emotional arousal

High morbid-mortability and reduced level of osteoporosis diagnosis among elderly people who had hip fractures in São Paulo City

OBJECTIVE: To know the morbid-mortality following an osteoporotic hip fracture in elderly patients living in São Paulo. PATIENTS AND METHODS: This study evaluated prospectively all patient over 60 years admitted in 2 school-hospitals in the city of São Paulo in a following 6-month period due to a osteoporotic proximal femur fracture. All of them filled up the Health Assessment Questionnaire (HAQ) and had their chart reviewed. After 6 months they were re-interviewed. Linear regression analysis was utilized to determine the factors related to functional ability. RESULTS: 56 patients were included (mean age 80.7 ± 7.9 years old, 80.4% females). After the 6-month follow up the mortality rate was 23.2%. Only 30% of the patients returned to their previous activities, and 11.6% became totally dependent. Factors related to worse functional ability after fracture were HAQ before fracture, institutionalization after fracture and age (r² 0.482). The diagnosis of osteoporosis was informed only by 13.9% of them, and just 11.6% received any treatment for that. CONCLUSION: Our results showed the great impact of these fractures on mortality and in the functional ability of these patients. Nevertheless, many of our physicians do not inform the patients about the diagnosis of osteoporosis and, consequently, the treatment of this condition is jeopardized.As fraturas osteoporóticas de fêmur proximal trazem graves conseqüências quanto à morbimortalidade e à qualidade de vida, mas desconhece-se este impacto no Brasil. OBJETIVO: Conhecer a morbimortalidade decorrente deste tipo de fraturas em idosos na cidade de São Paulo. MÉTODOS: Foram incluídos todos os pacientes com mais de 60 anos internados por fraturas de fêmur proximal durante seis meses, em dois hospitais de São Paulo. Os pacientes preencheram o questionário de capacidade funcional (HAQ), tiveram seu prontuário examinado e foram reavaliados após seis meses. Utilizou-se a análise de regressão linear para determinar os fatores relacionados à capacidade funcional. RESULTADOS: Cinqüenta e seis pacientes foram incluídos no estudo (80,7 ± 7,9 anos; 80,4% mulheres). A mortalidade em seis meses foi de 23,2%. Apenas 30% retornaram plenamente às suas atividades prévias e 11,6% tornaram-se completamente dependentes. Os fatores que mais bem conseguiram prever pior capacidade funcional após a fratura foram HAQ pré-fratura, institucionalização pós-fratura e idade (r² 0,482). Somente 13,9% receberam o diagnóstico de osteoporose e 11,6% iniciaram algum tratamento. CONCLUSÕES: Os resultados do presente estudo demonstram o impacto deste tipo de fraturas sobre a mortalidade e a capacidade funcional. Entretanto, a falha médica no diagnóstico e na orientação de tratamento da osteoporose permanece elevada.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaSanta Casa de Misericórdia de São Paulo Departamento de OrtopediaUNIFESP-EPM EPMUNIFESP, EPM, EPMSciEL

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Sleep duration and the risk of breast cancer: the Ohsaki Cohort Study

In a prospective study of 23 995 Japanese women, short sleep duration was associated with higher risk of breast cancer (143 cases), compared with women who slept 7 h per day, the multivariate hazard ratio of those who slept ⩽6 h per day was 1.62 (95% confidence interval: 1.05–2.50; P for trend=0.03)

Cutaneous and visceral leishmaniasis co-infection in dogs from Rio de Janeiro, Brazil: evaluation by specific PCR and RFLP-PCR assays

Introduction: During a diagnostic evaluation of canine visceral leishmaniasis (VL), two of seventeen dogs were found to be co-infected by Leishmania (Viannia) braziliensis and Leishmania (Leishmania) chagasi. Methods: Specifi c polymerase chain reaction (PCR) and restriction fragment length polymorphism-PCR (RFLP-PCR) assays were performed. Results: PCR assays for Leishmania subgenus identifi cation followed by RFLP-PCR analysis in biopsies from cutaneous lesions and the spleen confi rmed the presence of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) chagasi in those fragments. Conclusions: This report reinforces the importance of using serological and molecular techniques in the epidemiological surveillance of canine populations in endemic areas in which both diseases are known to co-exist. In such cases, a reassessment of the control measures is required