Oncolytic Viruses Partner With T-Cell Therapy for Solid Tumor Treatment

Adoptive T-cell immunotherapies, including chimeric antigen receptor-modified T-cells (CAR-T cells), have revolutionized cancer treatment, especially for hematologic malignancies. Clinical success of CAR-T cell monotherapy in solid tumors however, has been only modest. Oncolytic viruses provide direct cancer cell lysis, stimulate systemic immune responses, and have the capacity to provide therapeutic transgenes. Oncolytic virotherapy has shown great promise in many preclinical solid tumor models and the first oncolytic virus has been approved by the FDA for the treatment of advanced melanoma. As monotherapies for solid tumors, oncolytic virotherapy provides only moderate anti-tumor effects. However, due to their complementary modes of action, oncolytic virus and T-cell therapies can be combined to overcome the inherent limitations of each agent. This review focuses on the aspects of oncolytic viruses that enable them to synergize with adoptive T-cell immunotherapies to enhance anti-tumor effects for solid tumors

Acessibilidade e Mediação Cultural: uma reflexão e aproximação entre concepções

O presente artigo realiza uma reflexão conceitual crítica acerca dos termos “mediação cultural” e “acessibilidade”, objetivando ampliar compreensões sobre concepções e visões de mundo ativadas a partir do sentido dado aos termos, visando complexificar o modo de atuação na área. Fundamentada numa abordagem teórica, a investigação teve início com um levantamento bibliográfico que constatou uma escassez na literatura nacional frente à conceitualização da articulação temática “mediação cultural e acessibilidade”. O estudo desenvolvido baseia-se em marcos regulatórios internacionais e em legislação e publicações nacionais que apresentam o posicionamento brasileiro relacionado ao tema. Num primeiro momento os termos são analisados de maneira independente entre si, para depois serem revistos quando aplicados conjuntamente no contexto brasileiro. O levantamento de concepções acerca da “mediação cultural” chegou à compreensão do mediador cultural como um agente que potencializa a construção de interpretações e trocas sociais, revendo-se criticamente por meio da metamediação. Por sua vez, as transformações conceituais do termo “acessibilidade”, evidenciadas no texto, direcionaram-nos para a promoção da inclusão de todas as pessoas. Por fim, constatou-se que nas instituições culturais nacionais a “mediação cultural” e a “acessibilidade” necessitam extravasar a delimitação dos setores educativos, de modo a efetivar-se uma inclusão sociocultural plena de indivíduos e comunidades

The impact of control strategies and behavioural changes on the elimination of Ebola from Lofa County, Liberia.

The Ebola epidemic in West Africa was stopped by an enormous concerted effort of local communities and national and international organizations. It is not clear, however, how much the public health response and behavioural changes in affected communities, respectively, contributed to ending the outbreak. Here, we analyse the epidemic in Lofa County, Liberia, lasting from March to November 2014, by reporting a comprehensive time line of events and estimating the time-varying transmission intensity using a mathematical model of Ebola transmission. Model fits to the epidemic show an alternation of peaks and troughs in transmission, consistent with highly heterogeneous spread. This is combined with an overall decline in the reproduction number of Ebola transmission from early August, coinciding with an expansion of the local Ebola treatment centre. We estimate that healthcare seeking approximately doubled over the course of the outbreak, and that isolation of those seeking healthcare reduced their reproduction number by 62% (mean estimate, 95% credible interval (CI) 59-66). Both expansion of bed availability and improved healthcare seeking contributed to ending the epidemic, highlighting the importance of community engagement alongside clinical intervention.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'

Combined CO2 laser and intense pulsed light therapy in the treatment of vascular lesions

Congenital vascular lesions can be subdivided into tumors and malformations. Hemangiomas are benign vascular tumors resulting from the abnormal proliferation of endothelial cells, whereas port-wine stains are vascular malformations of a possible autosomal dominant inheritance. To date, there are no studies associating the use of intense pulsed light and CO2 laser as a therapeutic form for these pathologies. We present a series of 10 cases of vascular injuries treated with the combination of these forms of irradiation. This combined therapy can be effective in reducing the thickness of the lesions or in attenuating the color

Cutaneous infection by Mycobacterium haemophilum and kansasii in an IgA-deficient man

<p>Abstract</p> <p>Background</p> <p>The prevalence of infections by nontuberculous mycobacteria (NTM) has steadily increased over the past decades, especially in immunocompromised patients.</p> <p>Case presentation</p> <p>We present a patient with IgA-deficiency and mixed cutaneous infection by two slowly growing mycobacteria, <it>Mycobacterium </it>(<it>M.</it>) <it>haemophilum </it>and <it>M. kansasii.</it></p> <p>Conclusions</p> <p>Cutaneous <it>M. haemophilum </it>infections most often result from HIV or transplantation-associated immunosuppression. Rarely, <it>M. haemophilum </it>may also infect healthy patients or iatrogenically immunosuppressed patients without transplantation. <it>M. kansasii </it>is one of the most frequent NTM and large awareness exists about its involvement in human diseases. Mycobacterial diagnosis of cutaneous infections should be considered in long-lasting skin lesions.</p

INTERVENÇÃO EM GRUPO PARA ENSINO DE PRÁTICAS PARENTAIS A MÃES DE CRIANÇAS COM PROBLEMAS DE COMPORTAMENTO

The present study evaluated the effects of an intervention program to teach parenting skills to eight mothers of children with behavioral problems. The program is a replication of a previous study, comprising ten intervention sessions to access adherence and effects in different population. We used the Child Behavior Checklist (CBCL), interview with mothers, and Parenting Skills Inventory (IEP). Several subjects were accessed as limits establishment, rules and functional analysis of inadequate children behaviors. Data were compared to earlier study that this one was based, that had six sessions with same subjects, plus two evaluation instruments (Depression Inventory and Self-Esteem Scale) and applied to young offenders’ mothers. Among the eight participants, only three finished the program, indicating low adherence. Results indicated decrease on problems dealing with children (average 76.8 on CBCL pretest and 66.3 on posttest; average –1.57 on IEP pretest and 5.33 on posttest). Results are close to those found previously (pretest of 67.4 on CBCL and posttest of 52.2; –21 on IEP pretest and –11.5 on posttest).Keywords: parenting skills, group intervention, behavior problems.O presente estudo avaliou os efeitos de um programa de intervenção com o objetivo de ensinar práticas parentais a oito mães de crianças com queixa clínica de problemas de comportamento. O programa é uma replicação de estudo anterior, consistindo de 10 sessões de intervenção para avaliar adesão e resultados em população diferente. Foram utilizados Child Behavior Checklist (CBCL), entrevista com as mães e Inventário de Estilos Parentais (IEP). Vários temas foram trabalhados, como o estabelecimento de limites, regras e análise funcional dos comportamentos inadequados dos filhos. Os dados foram comparados com o estudo anterior no qual foram baseados, que consistiu em seis sessões com os mesmos temas, acrescidos de dois instrumentos de avaliação (Inventário de Depressão e Escala de Autoestima), e foi conduzido com mães de adolescentes infratores. Das oito participantes, somente três terminaram o programa, indicando baixa adesão. Os resultados indicaram diminuição nos problemas de relacionamento com os filhos (pré-teste médio no CBCL de 76,8 e pós-teste de 66,3; pontuação média pré-teste no IEP de –1,57 e pós-teste de 5,33). Esses resultados são próximos aos encontrados anteriormente (pré-teste médio no CBCL de 67,4 e pós-teste de 52,2; pontuação média pré-teste no IEP de –21 e pós-teste de –11,5).Palavras-chave: práticas parentais, intervenção em grupo, problemas de comportamento

Geochemistry and geobiology of a present-day serpentinization site in California: The Cedars

Ultra-basic (pH 11–12) reducing (−656 to −585 mV) groundwater springs discharging from serpentinized peridotite of The Cedars, CA, were investigated for their geochemistry and geobiology. The spring waters investigated were of meteoric origin; however, geochemical modeling suggests that there were two sources of groundwater, a shallow source with sufficient contact with The Cedars’ peridotite body to be altered geochemically by serpentinization, and a deeper groundwater source that not only flows through the peridotite body but was also in contact with the marine sediments of the Franciscan Subduction Complex (FSC) below the peridotite body. We propose that the groundwater discharging from lower elevations (GPS1 and CS1) reflect the geochemistry of the deeper groundwater in contact with FSC, while groundwaters discharging from springs at higher elevations (NS1 and BSC) were a mixture of the shallow peridotite-only groundwater and the deeper groundwater that has been in contact with the FSC. Cell densities of suspended microbes within these waters were extremely low. In the NS1 and BSC spring fluids, cell densities ranged from 10^2 to 10^3 cells/ml, while suspended cells at GPS were lower than 10 cells/mL. However, glass slides incubated in the BSC and GPS1 springs for 2–3 weeks were colonized by cells with densities ranging from 10^6 to 10^7 cells/cm^2 attached to their surfaces. All of the springs were very low (⩽1 μM) in several essential elements and electron acceptors (e.g. nitrate/ammonium, sulfate, and phosphate) required for (microbial) growth, which is not uncommon at sites of continental serpentinization. Gases rich in N_2, H_2, and CH_4 were exsolving from the springs. The stable carbon isotope value (δ^(13)C_(CH4) = −68 ± 0.6‰) and the CH_4/C_(2+) (>10^3) of methane and other gaseous hydrocarbons exsolving from NS1 were typical of microbially sourced methane, whereas the isotope values and the CH_4/C_(2+) of BSC and CS1 springs were more enriched in ^(13)C and had CH_4/C_(2+) < 10^3, suggesting a mixture of microbial and non-microbial methane. The concentrations of aromatic compounds, and ethane, propane, iso- and n-butane were well described by simple physical mixing between the aromatic- and alkane-poor, shallow groundwater and the relatively aromatic, and alkane-rich groundwater that flows through both the peridotite and the FSC suggesting that these aromatic and alkane compounds originated in the deeper FSC groundwater and are not produced in the shallow peridotite-only groundwater. The aromatic compounds most probably originated from the diagenesis/degradation of organic matter in the marine sediments below the peridotite body, while the gaseous alkanes may have multiple sources including thermal degradation of the organic matter in the marine sediments below the peridotite body and possibly by abiogenic reactions occurring within the peridotite body. This geochemical study demonstrates the complexity of The Cedars, and the possible sources of hydrocarbons at continental sites of serpentinization

Caracterización de los incidentes de caídas de pacientes adultos internados en un hospital universitario

Objetivo: Avaliar as notificações e caracterizar os incidentes de quedas dos pacientes adultos internados em unidades clínicas e cirúrgicas de um hospital universitário na região sul do país, no período de 2011 a 2014. Método: Estudo descritivo, transversal e retrospectivo, realizado no período de dezembro de 2016 a dezembro de 2017. A amostra foi de 1112 notificações, abrangendo todos os pacientes internados que foram notificados com ocorrência de quedas no período estudado. Os dados foram analisados por meio de estatística descritiva e analítica. Resultados: Foram predominantes na amostra os pacientes do sexo feminino e idosos, onde 69,4% dos incidentes não apresentaram dano. A ocorrência de quedas foi significativamente maior no período noturno. Limitação para deambular e estar desacompa- nhado foram os fatores mais prevalentes nas condições do paciente antes da queda. Conclusão: Queda é um evento multifatorial que necessita avaliação periódica dos fatores de risco pela equipe para planejar sua prevenção.Objective: To evaluate the occurrences and to characterize the falling incidents of adult patients hospitalized in clinical and surgical units of a university hospital in the southern region of the country, in the period from 2011 to 2014. Method: Descriptive, cross-sectional and retrospective study, carried out from December 2016 to December 2017. The sample consisted of 1112 reports, covering all hospitalized patients who were notified with falls occurring in the studied period. Data were analyzed using descriptive and analytical statistics. Results: Female and elderly patients were predominant in the sample, in which 69.4% of the incidents did not present any damage. The occurrence of falls was significantly higher at night. Limitation to walking and being unaccompanied were the most prevalent factors in the patient’s conditions before the fall. Conclusion: The fall is a multifactorial event that requires periodic evaluation of the risk factors by the team to plan their prevention.Objetivo: Evaluar las notificaciones y caracterizar los incidentes de caídas de los pacientes adultos internados en unidades clínicas y quirúrgicas de un hospital universitario en la región sur del país, en el período 2011 a 2014. Método: Estudio descriptivo, transversal y retrospectivo, realizado en el período de diciembre de 2016 a diciembre de 2017. La muestra fue de 1112 notificaciones, abarcando a todos los pacientes internados que fueron notificados con ocurrencia de caídas en el periodo estudado. Los datos fueron analizados por medio de estadística descriptiva y analítica. Resultados: Fueron predominantes en la muestra los pacientes del sexo femenino y ancianos, donde el 69,4% de los incidentes no presentaron daño. La ocurrencia de caídas fue significativamente mayor en el período nocturno. La limitación para deambular y estar desatendido fueron los factores más prevalentes en las condiciones del paciente antes de la caída. Conclusión: La caída es un evento multifactorial que necesita evaluación periódica de los factores de riesgo por el equipo para planificar su prevención

Variation in ligand responses of the bitter taste receptors TAS2R1 and TAS2R4 among New World monkeys

Background New World monkeys (NWMs) are unique in that they exhibit remarkable interspecific variation in color vision and feeding behavior, making them an excellent model for studying sensory ecology. However, it is largely unknown whether non-visual senses co-vary with feeding ecology, especially gustation, which is expected to be indispensable in food selection. Bitter taste, which is mediated by bitter taste receptors (TAS2Rs) in the tongue, helps organisms avoid ingesting potentially toxic substances in food. In this study, we compared the ligand sensitivities of the TAS2Rs of five species of NWMs by heterologous expression in HEK293T cells and calcium imaging. Results We found that TAS2R1 and TAS2R4 orthologs differ in sensitivity among the NWM species for colchicine and camphor, respectively. We then reconstructed the ancestral receptors of NWM TAS2R1 and TAS2R4, measured the evolutionary shift in ligand sensitivity, and identified the amino acid replacement at residue 62 as responsible for the high sensitivity of marmoset TAS2R4 to colchicine. Conclusions Our results provide a basis for understanding the differences in feeding ecology among NWMs with respect to bitter taste

Myelin Basic Protein as a Novel Genetic Risk Factor in Rheumatoid Arthritis—A Genome-Wide Study Combined with Immunological Analyses

Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and a typical complex trait. Although several genetic determinants have been identified, they account for only a part of the genetic susceptibility. We conducted a genome-wide association study of RA in Japanese using 225,079 SNPs genotyped in 990 cases and 1,236 controls from two independent collections (658 cases and 934 controls in collection1; 332 cases and 302 controls in collection2), followed by replication studies in two additional collections (874 cases and 855 controls in collection3; 1,264 cases and 948 controls in collection4). SNPs showing p<0.005 in the first two collections and p<10−4 by meta-analysis were further genotyped in the latter two collections. A novel risk variant, rs2000811, in intron2 of the myelin basic protein (MBP) at chromosome 18q23 showed strong association with RA (p = 2.7×10−8, OR 1.23, 95% CI: 1.14–1.32). The transcription of MBP was significantly elevated with the risk allele compared to the alternative allele (p<0.001). We also established by immunohistochemistry that MBP was expressed in the synovial lining layer of RA patients, the main target of inflammation in the disease. Circulating autoantibody against MBP derived from human brain was quantified by ELISA between patients with RA, other connective tissue diseases and healthy controls. As a result, the titer of anti-MBP antibody was markedly higher in plasma of RA patients compared to healthy controls (p<0.001) and patients with other connective tissue disorders (p<0.001). ELISA experiment using citrullinated recombinant MBP revealed that a large fraction of anti-MBP antibody in RA patients recognized citrullinated MBP. This is the first report of a genetic study in RA implicating MBP as a potential autoantigen and its involvement in pathogenesis of the disease