Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

Isokinetic muscle function comparison of lower limbs among elderly fallers and non-fallers

O objetivo deste estudo foi identificar se há diferenças entre o desempenho muscular de tornozelo, joelho e quadril em idosos com e sem relato de queda nos últimos seis meses. Foram incluídos 81 idosos com 65 anos ou mais: 56 negaram quedas (G1) e 25 relataram quedas (G2). Utilizou-se o questionário perfil de atividade humana para medir o nível de atividade física, e o dinamômetro isocinético para mensurar os parâmetros físicos da função muscular. Os grupos não diferiram entre si em relação à idade (p=0,925), duração (p=0,065) e frequência (p=0,302) da prática do exercício físico, índice de massa corpórea (p=0,995) e nível de atividade física (p=0,561). O G2 apresentou menor desempenho para as variáveis pico de torque de flexão e extensão de joelho esquerdo (p=0,027 e p=0,030, respectivamente) e trabalho por peso corporal (p=0,040) de flexão de joelho esquerdo a 60°/s; pico de torque e trabalho por peso corporal de flexão e extensão de joelho a 180°/s bilateralmente (p<0,050); e potência média de flexão de joelhos direito e esquerdo (p=0,030). A maioria das variáveis do tornozelo e quadril não apresentou diferenças entre os grupos. Apenas a variável pico de torque de extensão de quadril esquerdo foi significativamente maior no G1 (p=0,035). É importante considerar a função muscular do joelho na avaliação clínica de idosos para direcionar a intervenção terapêutica e a prevenção de quedas.The aim of this study was to identify whether there are differences between the performance of muscular groups of ankle, knee and hip among elderly people who didn't have falls and individuals who reported falls in the last six months. The study included 81 elderly aged 65 or older: 56 non-faller subjects (G1) and 25 faaller subjects (G2). To obtain the level of physical activity, the questionnaire Human Activity Profile was used, and the muscle function of the lower limbs was assessed using isokinetic dynamometer. The groups did not differ regarding age (p=0.925), duration (p=0.065) and frequency (p=0.302) of the practice of physical exercise, body mass index (BMI) (p=0.995) and level of physical activity (p=0.561). The G2 showed a lower performance of peak torque of left knee flexion and extension (p=0.027 and p=0.030, respectively) and work proportional to body weight (p=0.040) of left knee flexion at 60°/s; peak torque and work proportional to body weight of bilaterally knee flexion and extension at 180°/s (p<0.05) and average power of right and left knee extension (p=0.03). Most variables of ankle and hip joints did not differ between groups. Only peak torque of left hip extension was significantly higher in the non-faller group (p=0.035). It is important to consider knee muscle function in the clinical evaluation of elderly in order to make the intervention more assertive and thus to prevent falls

Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer

PURPOSE: Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC) treated with hypofractionation. MATERIALS AND METHODS: Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients. RESULTS: Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV) volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1) acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS) are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively. CONCLUSION: 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy

Complementarity of Spike- and Rate-Based Dynamics of Neural Systems

Relationships between spiking-neuron and rate-based approaches to the dynamics of neural assemblies are explored by analyzing a model system that can be treated by both methods, with the rate-based method further averaged over multiple neurons to give a neural-field approach. The system consists of a chain of neurons, each with simple spiking dynamics that has a known rate-based equivalent. The neurons are linked by propagating activity that is described in terms of a spatial interaction strength with temporal delays that reflect distances between neurons; feedback via a separate delay loop is also included because such loops also exist in real brains. These interactions are described using a spatiotemporal coupling function that can carry either spikes or rates to provide coupling between neurons. Numerical simulation of corresponding spike- and rate-based methods with these compatible couplings then allows direct comparison between the dynamics arising from these approaches. The rate-based dynamics can reproduce two different forms of oscillation that are present in the spike-based model: spiking rates of individual neurons and network-induced modulations of spiking rate that occur if network interactions are sufficiently strong. Depending on conditions either mode of oscillation can dominate the spike-based dynamics and in some situations, particularly when the ratio of the frequencies of these two modes is integer or half-integer, the two can both be present and interact with each other

Impact of the Health Gym Program on hospital admissions for stroke in the state of Pernambuco, Brazil

This study aimed to evaluate the impact of the Health Gym Program (HGP) on hospital admissions for stroke in the state of Pernambuco, Brazil. This policy impact evaluation used a quasi-experimental approach consisting of a difference-in-differences estimator, weighted by propensity score matching to deal with potential confounding variables. The study comprised socioeconomic, demographic, and epidemiological data from official Brazilian databases from 2010 to 2019. The treatment group was composed of the 134 municipalities that implemented the HGP since 2011. The 51 municipalities that did not were allocated to the comparison group. The nearest neighbor algorithm (N5) was used to pair treatment and comparison group municipalities and create the weights to evaluate the average treatment effect on the treated (ATT) in the difference-in-differences estimator. In 2010, 2,771 people were hospitalized for stroke (0.51% of all hospitalizations) and in 2019, 11,542 (2%). Municipalities that implemented the HGP had 18.37% fewer hospitalizations than their counterparts in the comparison group. The program’s impact in reducing hospitalization rates was incrementally greater among men (ATT: -0.1932) and those aged 71 to 80 years (ATT: -0.1911). All results were statistically significant at the 5% level. The HGP reduced hospitalization for stroke in several population groups, but primarily in those whose underlying prevalence of stroke is highest, reinforcing the importance of public investments in health promotion policies designed to encourage lifestyle changes.Resumo: O estudo teve como objetivo avaliar o impacto do Programa Academia da Saúde (PAS) nas internações hospitalares por acidente vascular cerebral (AVC) no Estado de Pernambuco, Brasil. Esta avaliação de impacto das políticas utilizou uma abordagem quase-experimental que consiste em um estimador de diferença-em-diferenças, ponderado pelo pareamento por escore de propensão para lidar com possíveis fatores de confusão. O estudo foi composto por dados socioeconômicos, demográficos e epidemiológicos de bases de dados oficiais brasileiras entre os anos de 2010 e 2019. O grupo de tratamento foi composto pelos 134 municípios que implantaram o PAS a partir de 2011, e os 51 municípios que não implantaram foram alocados no grupo de comparação. O algoritmo do vizinho mais próximo (N5) foi utilizado para emparelhar os municípios tratados e comparar aos municípios do grupo controle, criando os pesos que foram utilizados para avaliar o efeito médio do tratamento sobre o tratado (ATT) no estimador de diferença- -em-diferenças. Houve 2.771 internações por AVC em 2010 (0,51% de todas as internações) e 11.542 (2%) em 2019. Os municípios que implementaram o PAS tiveram 18,37% menos internações em comparação com seus homólogos no grupo de comparação. O impacto do programa na redução das taxas de internação foi maior entre os homens (ATT: -0,1932) e naqueles com idade entre 71 e 80 anos (ATT: -0,1911). Todos os resultados foram estatisticamente significativos em um nível de 5%. O PAS reduziu a hospitalização por AVC em vários grupos populacionais, mas principalmente naqueles em que a prevalência subjacente de AVC é mais alta, reforçando a importância dos investimentos públicos em políticas de promoção da saúde destinadas a estimular mudanças nos estilos de vida. Avaliação de Programas e Projetos de Saúde; Doença Crônica; Promoção da Saúde; Pontuação de Propensão; Acidente Vascular CerebralResumen: El objetivo de este trabajo es evaluar el impacto del Programa Academia de la Salud (PAS) en los ingresos hospitalarios por accidente cerebrovascular (ACV) en el estado de Pernambuco, Brasil. Esta evaluación del impacto de la política utilizó un enfoque cuasi-experimental que consiste en un estimador de diferencias en diferencias, ponderado por el emparejamiento de puntuación de propensión para hacer frente a posibles factores de confusión. El estudio incluyó datos socioeconómicos, demográficos y epidemiológicos de bases de datos oficiales brasileñas de 2010 a 2019. El grupo de tratamiento se compuso de los 134 municipios que implementaron el PAS a partir de 2011 y los 51 municipios que no lo hicieron se asignaron al grupo de comparación. Se utilizó el algoritmo del vecino más próximo (N5) para emparejar los municipios tratados y los del grupo de comparación y crear las ponderaciones que se emplearon para evaluar el efecto medio del tratamiento sobre los tratados (ATT) en el estimador de diferencias en diferencias. Hubo 2.771 hospitalizaciones por ACV en 2010 (0,51% de todas las hospitalizaciones) y 11.542 (2%) en 2019. Los municipios que aplicaron el PAS tuvieron un 18,37% menos de hospitalizaciones en comparación con sus homólogos del grupo de comparación. El impacto del programa en la reducción de las tasas de hospitalización fue gradualmente mayor entre los hombres (ATT: -0,1932) y entre las personas de 71 a 80 años (ATT: -0,1911). Todos los resultados fueron estadísticamente significativos al nivel del 5%. El PAS redujo la hospitalización por ACV en varios grupos de población, pero principalmente en aquellos en los que la prevalencia subyacente de ACV es mayor, lo que refuerza la importancia de las inversiones públicas en políticas de promoción de la salud diseñadas para impulsar cambios en los estilos de vida. Evaluación de Programas y Proyectos de Salud; Enfermedad Crónica; Promoción de la Salud; Puntaje de Propensión; Accidente CerebrovascularPernambuco State Foundation for the Support of Science and Technology (FACEPE), and the Brazilian National Research Council (CNPq)

Higher incidence of perineal community acquired MRSA infections among toddlers

<p>Abstract</p> <p>Background</p> <p>A six-fold increase in pediatric MRSA infections, prompted us to examine the clinical profile of children with MRSA infections seen at Mercy Children's Hospital, Toledo, Ohio and to characterize the responsible strains.</p> <p>Methods</p> <p>Records were reviewed of pediatric patients who cultured positive for MRSA from June 1 to December 31, 2007. Strain typing by pulsed field gel electrophoresis (PFT) and DiversiLab, SCC<it>mec </it>typing, and PCR-based <it>lukSF-PV </it>gene (encodes Panton-Valentine leukocidin), arginine catabolic mobile element (ACME) and <it>cap</it>5 gene detection was performed.</p> <p>Results</p> <p>Chart review of 63 patients with MRSA infections revealed that 58(92%) were community acquired MRSA (CAMRSA). All CAMRSA were skin and soft tissue infections (SSTI). Twenty five (43%) patients were aged < 3 yrs, 19(33%) aged 4-12 and 14(24%) aged 13-18. Nineteen (76%) of those aged < 3 yrs had higher incidence of perineal infections compared to only 2(11%) of the 4-12 yrs and none of the 13-18 yrs of age. Infections in the extremities were more common in the older youth compared to the youngest children. Overall, there was a significant association between site of the infection and age group (Fisher's Exact p-value < 0.001). All CAMRSA were USA300 PFT, clindamycin susceptible, SCC<it>mec </it>type IVa and <it>lukSF-PV gene </it>positive. Nearly all contained ACME and about 80% were <it>cap</it>5 positive. Of the 58 USA300 strains by PFT, 55(95%) were also identified as USA300 via the automated repetitive sequence-based PCR method from DiversiLab.</p> <p>Conclusions</p> <p>CAMRSA SSTI of the perineum was significantly more common among toddlers and that of the extremities in older children. The infecting strains were all USA300 PFT. Further studies are needed to identify the unique virulence and colonization characteristics of USA300 strains in these infections.</p