Premalignant Oral Lesion Immunobiology: Immune Modulation and Vaccination

While studies have indicated that squamous cell carcinoma of the head and neck (HNSCC) is associated with immune suppression, these studies did not analyze the immune response at the dysplastic stage. This study utilized a mouse model of 4-nitroquinoline 1-oxide (4NQO)-induced oral carcinogenesis to examine the alterations in immune phenotype at the premalignant and malignant stages of HNSCC. Cervical lymph nodes of HNSCC-bearing mice were found to contain a greater number of cells, including a greater number of conventional (Tconv) and regulatory (Treg) T cells, compared to lymph nodes of control and premalignant lesion-bearing mice. Premalignant lesion-bearing mouse lymph nodes consist of a greater percentage of Tconv cells expressing markers for activation, memory, and exhaustion compared to both control and HNSCC-bearing mice. Lymph nodes from both premalignant lesion-bearing and HNSCC-bearing mice include increased numbers of Th1, Tc1 and Th17 cells compared to control mice. The data show that while there is the expected increase in Tregs in lymph nodes when HNSCC is present, there is also an unexpected increase in immune populations usually associated with a beneficial anti-tumor response. In addition, the results demonstrate that the premalignant stage of HNSCC development is associated with a robust immune response involving an increase in inflammatory cells. The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by the immune evasion tactics often employed by carcinomas such as HNSCC. This study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Bone marrow-derived DCs were pulsed with premalignant lesion lysate (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions. Endoscopic examination revealed that DCpm vaccination and control vaccination with dendritic cells pulsed with normal tongue epithelium lysate (DCnt) significantly decreased lesion burden. Analysis of lymph node cells revealed that while DCnt vaccination resulted in a rapid increase in total lymphocyte count, levels of activated Tconv cells, and Th1, Tel, Th17, Te17, and Th2 cells, DCpm vaccination results in a delayed, yet substantial, increase in these immune effector mechanisms. This suggests that dendritic cell vaccination may have a beneficial effect on clinical outcome regardless of type of antigenic stimulation, and DCs pulsed with premalignant lysate rather than normal tongue epithelium lysate result in a delayed immune effector response upon vaccination of premalignant lesion-bearing mice

Seizure progression is slowed by enhancing neurosteroid availability in the brain of epileptic rats

Trilostane is a 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase inhibitor able to produce a manyfold increase in brain levels of various neurosteroids, including allopregnanolone. We previously found that treatment with trilostane can slow down epileptogenesis in the kainic acid (KA) model of temporal lobe epilepsy. It is unknown whether trilostane may have a similar effect on the progression of epilepsy severity, as observed in KA-treated rats. Consequently, we investigated the effects of trilostane (50 mg/kg/day, 1 week) in epileptic rats, given 64 days after KA administration. Seizures were monitored by video-electrocorticographic recordings before and during the treatment with trilostane or vehicle (sesame oil), and neurosteroid levels were measured in serum and cerebral tissue using liquid chromatography–electrospray tandem mass spectrometry after treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone peripheral levels were massively increased by trilostane. With the only exception of hippocampal pregnenolone sulfate, the other neurosteroids augmented in both the neocortex and hippocampus. Only pregnanolone levels were not upregulated by trilostane. As expected, a significant increase in the seizure occurrence was observed in rats receiving the vehicle, but not in the trilostane group. This suggests that the increased availability of neurosteroids produced a disease-modifying effect in the brain of epileptic rats

Transtorno afetivo bipolar: carga da doença e custos relacionados

BACKGROUND: Bipolar disorder (BD) is a recurrent, chronic and severe disease. Mental and physical comorbidities, risk of suicide, health services use and impairment of social and professional domains significantly worsen the burden and increase the costs of illness. OBJECTIVES: Review clinical aspects, burden of disease, and consequent financial outcomes of BD. METHODS: MEDLINE/PubMed database search using the terms bipolar disorder, epidemiology, burden of disease, comorbidity, cost of illness, outcomes e financial consequences, published in MEDLINE from 1980 to 2006. RESULTS: BD has a high rate of comorbidities, which worsen the prognosis and increase costs with health services. Subjects with BD have more cardiovascular risk factors than the general population, and therefore a higher risk of death by cardiovascular event. Delay of diagnosis and misdiagnosis increase the costs of illness. DISCUSSION: Comorbidities, risk of suicide, social and professional impairment and low adherence to treatment increase the cost of illness. The search of comorbidities may help clinicians to adjust treatment strategies, taking into account all associated risk factors and costs, which may be considered also by professionals involved in health care management, either private or public.CONTEXTO: O transtorno afetivo bipolar (TAB) é uma doença recorrente, crônica e grave. Comorbidades psiquiátricas e físicas, aumento do risco de suicídio, maior utilização de serviços de saúde e prejuízo na esfera social/profissional aumentam significativamente a carga e custos relacionados à doença. OBJETIVOS: Revisar aspectos clínicos, de carga da doença e conseqüentes desfechos financeiros do TAB. MÉTODOS: Pesquisa de base de dados MEDLINE/PubMed utilizando os termos bipolar disorder, epidemiology, burden of disease, comorbidity, cost of illness, outcomes e financial consequences, publicados entre 1980 e 2006. RESULTADOS: O TAB apresenta alta comorbidade com outros transtornos, o que agrava seu prognóstico e eleva os custos com os serviços de saúde. Os indivíduos com TAB apresentam mais fatores de risco cardiovascular e, conseqüentemente, maior risco de morte por evento cardíaco. O atraso e o erro diagnóstico no TAB elevam consideravelmente a carga e os custos da doença. CONCLUSÕES: As comorbidades, o risco de suicídio, o prejuízo social/profissional e a baixa adesão ao tratamento contribuem para a alta carga e os custos associados à doença. A pesquisa de comorbidades pode ajudar os médicos a ajustarem suas estratégias de tratamento, considerando cuidadosamente todos os fatores de risco e custos associados, fatores estes que devem ser levados em conta também pelos profissionais que trabalham com gestão de saúde, tanto no setor privado quanto público

Status epilepticus dynamics predicts latency to spontaneous seizures in the kainic acid model

(TLE), a common neurologic disorder characterized by spontaneous recurrent seizures (SRSs). However, the relationship between SE and TLE is still incompletely characterized. For this reason, in a model of TLE we evaluated the lesion extent and the onset of SRSs to determine if they were influenced by the SE dynamics. Methods: Sixty-two adult male Sprague-Dawley rats were implanted for video-electrocorticographic (v-ECoG) monitoring and intraperitoneally treated with saline or kainic acid (KA, 15 mg/kg) at 8 weeks of age. v-ECoG recordings were obtained during SE, in the following 9 weeks, and assessed by amplitude or power band spectrum. Rats were euthanized 3 or 64 days after SE to evaluate the lesion. Results: SE lasted about 10 h during which the mean duration of convulsive seizures (CSs) increased from 39 s, at 30 min, to 603 s at 4 h. The gamma power peaked 30 min after the SE onset and its peak was correlated (r²=0.13, p=0.042) with the overall SE duration. Subsequently, the gamma power was reduced under the baseline until the end of SE. The theta power increased at approximately 150% of basal levels 3 h after KA injection, but it went back to basal levels with the full development of CSs. Interestingly, the timing of the first SRS in chronic epilepsy was correlated with the latency to develop the first CS with loss of posture during SE (r²=0.60, p<0.001). Additionally, the overall duration of CSs observed during SE was related to the number of damaged brain regions (r²=0.60, p=0.005), but it did not influence the timing of the first SRS in chronic epilepsy. Conclusion: Overall, our results show that the onset of chronic epilepsy is modulated by SE dynamics, whereas brain damage is related to prolonged convulsions in SE

Real-time dry matter content of corn silage by a microwave sensor

Daily dry matter (DM) intake in dairy cow is a central point to meet nutritional requirements and optimal performance, reducing the incidence of metabolic diseases. DM content of some forages, such as silages, can undergo huge variations during storing, affecting the total daily DM consumed. Reference laboratory method is time consuming and cannot be applied to daily changes in diet composition. Currently, new promising real-time technologies are available to monitor the DM content of feeds. The aim of the study was to test and calibrate a portable microwave sensor (MS) for DM content in corn silage samples. Twenty-two samples were collected from a corn silage front; sampling procedure was optimized to collect as much as DM content variability as possible within the samples. MS readings were performed with 3 different methods for each samples: 1) directly on the silage front, 2) with the MS over the collected sample and 3) with MS placed under the sample. After the first MS reading, a correspondent silage sample was obtained by a silage corer for readings 2 and 3 and the laboratory DM content assay. A simple regression analysis was performed (JMP, SAS Institute, Cary, NC, 2015) over obtained data. Results evidences as the best MS reading method is represented by the probe burdening on the sample (R2=0.75) with respect to the other methods. The obtained results outlined as, with a correct reading method, MS can be valuable tool to determine DM content of corn silage directly at farm level

ISOS: Sistema de valoración de puestos de trabajo para llevar a la práctica el principio de igualdad retributiva

A fair pay structure is an essential element of the personnel policy of a firm. If the pay structure is perceived as arbitrary by the members of the staff, it becomes a cause of disturbance of the labor relations. Particularly, a pay structure is unfair if it discriminates against women. Job evaluation is a traditional tool used by companies to assist in the process of determining pay structures that can be also useful to detect and combat wage discrimination, since allow determining whether two jobs are of comparable worth or not. Although there are many kinds of systems, authors agree when defining point factor methods as the most appropriate and fair job evaluation systems. However, even being well defined from a technical point of view, most existing systems give discriminatory results regarding to gender. ISOS, a new job evaluation system which is described in this paper, has been designed, with the aim to define a neutral system with regard to gender, based on present jobs characteristics, existing job evaluation systems and job description questionnaires, international experts’ knowledge and a wide body of literature on gender discrimination and its relation with job evaluation. Using ISOS can contribute to detect, combat and eliminate part of the existing wage discrimination in general and, in particular, against women. ISOS includes all aspects of the work so no characteristics are omitted. The system can be applied in any company and to evaluate any job, and offers flexibility to be adapted to the specific characteristics of an organization. ISOS can also be used to detect and combat wage discrimination. Furthermore, characteristics of present jobs, such as cross-training or flexible working time, are also included so the system can be considered innovative in a very traditional field of industrial engineering.Una estructura salarial justa debe ser un elemento esencial de la política de personal de cualquier empresa. Cuando ésta es percibida como arbitraria, se convierte entonces en una causa de disturbio de las relaciones laborales. En particular, una estructura salarial es injusta si es discriminatoria en relación con el género. La valoración de puestos de trabajo (VPT) es una herramienta tradicional utilizada en el proceso de diseño de las estructuras salariales. Pero estas herramientas pueden ser utilizadas también para detectar y combatir la discriminación salarial, ya que permiten determinar si dos trabajos tienen o no un valor equivalente. Aunque existen muchos tipos de sistemas, existe un amplio consenso al definir los procedimientos de asignación de puntos por factor como lo más adecuados y justos. Sin embargo, aún estando bien definidos desde un punto de vista técnico, la mayoría de los sistemas existentes proporcionan resultados que son discriminatorios en relación con el género. ISOS es un nuevo sistema de VPT que ha sido diseñado con el objetivo de definir un sistema neutro con respecto al género. El sistema se basa en las características de los puestos de trabajo actuales (se han incluido aspectos relacionados con la polivalencia o la distribución flexible del tiempo de trabajo, entre otros), en sistemas de valoración y cuestionarios para la descripción de puestos, en el conocimiento de expertos internacionales y en la amplia literatura existente sobre discriminación de género y su relación con la VPT. ISOS, que incluye todos los aspectos del trabajo sin omitir ninguna característica relevante, puede ser implementado en cualquier tipo de empresa y para valorar cualquier tipo de trabajo, y ofrece flexibilidad para ser adaptado a las características específicas de cada organización. Utilizar ISOS puede contribuir a detectar, combatir y eliminar parte de la discriminación salarial existente (general y de la mujer)

Aldeia Sowante: exploração, colonialismo e reconquista territorial

O recente ordenamento territorial dos índios Nambiquara da Serra do Norte que se identificaram durante os trabalhos de campo como Sabanê, Kolimisí, Idalamarê, Lakondê, Niyahlosu, Siwaihsu e Hinkatesu consite no objeto deste estudo. O que se quer evidenciar é a dinâmica cultural desses grupos que há mais de uma década decidiram retornar ao seu antigo território de ocupação tradicional. O contato dos índios com os não índios encontra-se enlaçado em dimensões culturais e políticas, resultantes de uma distribuição desigual de poder. Com base na pesquisa etnográfica, este artigo pretende lançar luz ao retorno de famílias pertencentes aos grupos Nambiquara da Serra do Norte, anteriormente localizadas na Terra Indígena Pyreneus de Souza, município de Comodoro, Mato Grosso. Daí retornaram ao seu território tradicional, à margem direita do rio Roosevelt, no Sul da Terra Indígena Parque do Aripuanã. Afora a pesquisa etnográfica adotada para resolver a problemática indicada, a metodologia utilizada consistiu também na pesquisa documental, quando foram analisados documentos do SPI e os poucos produzidos pelas lideranças indígenas que conduziram o processo de retorno ao Sul do Parque do Aripuanã. O percurso teórico seguiu especialmente as trilhas de Junqueira (2002), Boaventura de Sousa Santos e Maria Paula Meneses (2010), Anibal Quijano (2005), Georges Balandier (1976 e 1997) para investigar outras lógicas de produção de conhecimento e ideias, com padrões próprios de expressão intelectual indígena

Aldeia Sowante: exploração, colonialismo e reconquista territorial

O recente ordenamento territorial dos índios Nambiquara da Serra do Norte que se identificaram durante os trabalhos de campo como Sabanê, Kolimisí, Idalamarê, Lakondê, Niyahlosu, Siwaihsu e Hinkatesu consite no objeto deste estudo. O que se quer evidenciar é a dinâmica cultural desses grupos que há mais de uma década decidiram retornar ao seu antigo território de ocupação tradicional. O contato dos índios com os não índios encontra-se enlaçado em dimensões culturais e políticas, resultantes de uma distribuição desigual de poder. Com base na pesquisa etnográfica, este artigo pretende lançar luz ao retorno de famílias pertencentes aos grupos Nambiquara da Serra do Norte, anteriormente localizadas na Terra Indígena Pyreneus de Souza, município de Comodoro, Mato Grosso. Daí retornaram ao seu território tradicional, à margem direita do rio Roosevelt, no Sul da Terra Indígena Parque do Aripuanã. Afora a pesquisa etnográfica adotada para resolver a problemática indicada, a metodologia utilizada consistiu também na pesquisa documental, quando foram analisados documentos do SPI e os poucos produzidos pelas lideranças indígenas que conduziram o processo de retorno ao Sul do Parque do Aripuanã. O percurso teórico seguiu especialmente as trilhas de Junqueira (2002), Boaventura de Sousa Santos e Maria Paula Meneses (2010), Anibal Quijano (2005), Georges Balandier (1976 e 1997) para investigar outras lógicas de produção de conhecimento e ideias, com padrões próprios de expressão intelectual indígena

A temática indígena em sala da aula

Resenha de: A temática indígena em sala da aula: reflexões para o ensino a partir da Lei 11.645/2008. SILVA, Edson; Silva, Maria da Penha da (Orgs.). Recife: Ed. Universitária da UFPE, 2013

A temática indígena em sala da aula

Resenha de: A temática indígena em sala da aula: reflexões para o ensino a partir da Lei 11.645/2008. SILVA, Edson; Silva, Maria da Penha da (Orgs.). Recife: Ed. Universitária da UFPE, 2013