Remote control of transgene expression using noninvasive near-infrared irradiation.

This study investigated whether noninvasive near-infrared (NIR) energy could be transduced into heat in deep-seated organs in which adenovirus type-5 vectors tend to accumulate, thereby activating heat shock protein (HSP) promoter-mediated transgene expression, without local administration of photothermal agents. NIR irradiation of the subdiaphragmatic and left dorsocranial part of the abdominal cavity of adult immunocompetent C3H/HeNRj mice with an 808-nm laser effectively increased the temperature of the irradiated regions of the liver and spleen, respectively, resulting in the accumulation of the heat-inducible HSP70 protein. Spatial control of transgene expression was achieved in the NIR-irradiated regions of the mice administered an adenoviral vector carrying a firefly luciferase (fLuc) coding sequence controlled by a human HSP70B promoter, as assessed by bioluminescence and immunohistochemistry analyses. Levels of reporter gene expression were modulated by controlling NIR power density. Spatial control of transgene expression through NIR-focused activation of the HSP70B promoter, as well as temporal regulation by administering rapamycin was achieved in the spleens of mice inoculated with an adenoviral vector encoding a rapamycin-dependent transactivator driven by the HSP70B promoter and an adenoviral vector carrying a fLuc coding sequence controlled by the rapamycin-activated transactivator. Mice that were administered rapamycin and exposed to NIR light expressed fLuc activity in the splenic region, whereas no activity was detected in mice that were only administered rapamycin or vehicle or only NIR-irradiated. Thus, in the absence of any exogenously supplied photothermal material, remote control of heat-induced transgene expression can be achieved in the liver and spleen by means of noninvasive NIR irradiation.

Trans-cutaneous electrical nerve stimulation to treat dry mouth (xerostomia) following radiotherapy for head and neck cancer. A systematic review.

BACKGROUND: A dry mouth or xerostomia is one of the most common long-term complications following radiotherapy for head and neck cancer and has a negative impact on quality of life in cancer survivors. Transcutaneous electrical nerve stimulation (TENS) is a novel approach to improving saliva flow in these patients. OBJECTIVE: To perform a systematic review of studies evaluating TENS in the treatment of radiotherapy induced xerostomia in head and neck cancer patients. DATA COLLECTION AND ANALYSIS: A comprehensive electronic search was performed in PubMed/MEDLINE, the Cochrane Library, and Google Scholar databases for appropriate published studies. The last search was conducted in January 2020. Two review authors assessed all studies identified by the search strategy and carried out data extraction. RESULTS: Five studies were included in the systematic review which analysed a total of 280 patients with head and neck cancer. Methodological quality and outcomes were evaluated in every study included. The outcome measure was either subjectively assessed or objectively measured. Three studies used conventional TENS therapy to stimulate parotid glands which produced a significant increase in saliva production following therapy. Two studies used acupunctured TENS type to electrically stimulate acupuncture points scattered in the body and they reported improvement in saliva production at the same level as medical treatment. No reported adverse effect of TENS was identified. CONCLUSIONS: This systematic review confirms the safety and feasibility of TENS in the treatment of xerostomia. It is established that commencing daily TENS therapy simultaneously with radiotherapy has the most efficacy. Given the nonspecific parameters used in the included studies, further evidence is needed in order to establish optimal settings and parameters of TENS for treatment of xerostomia.

JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability.

BACKGROUND: Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. Following their synthesis, histones undergo a series of maturation steps to prepare them for deposition onto chromatin. RESULTS: Here, we identify the lysine demethylase JMJD1B as a novel player in the maturation cascade that contributes to regulate histone provision. We find that depletion of JMJD1B increases the protein levels of the histone chaperone tNASP leading to an accumulation of newly synthesized histones H3 and H4 at early steps of the histone maturation cascade, which perturbs chromatin assembly. Furthermore, we find a high rate of JMJD1B mutations in cancer patients, and a correlation with genomic instability. CONCLUSIONS: Our data support a role for JMJD1B in fine-tuning histone supply to maintain genome integrity, opening novel avenues for cancer therapeutics.

Efeito do Treinamento Resistido e do Pilates na Qualidade de vida de Idosas: um ensaio clínico randomizado / Effect of Resistance Training and Pilates on the Quality of Life of Elderly Women: A Randomized Clinical Trial

Resumo Objetivo comparar os efeitos do treinamento resistido (TR) e Pilates na qualidade de vida (QV) de idosas. Foi realizado um estudo de delineamento experimental com intervenção de 12 semanas. Métodos Foram avaliadas mulheres idosas (≥60 anos) que não praticavam nenhum tipo de exercício físico regularmente há pelo menos 3 meses. Participaram do estudo 41 idosas que foram aleatoriamente divididas em três grupos:1- grupo Pilates (GP), 2- grupo treinamento resistido (GTR) e 3- grupo controle (GC). Para avaliar a QV, foram utilizados os questionários WHOQOL-OLD, WHOQOL-BREF e SF-36. Foi utilizado o teste de Wilcoxon-Mann-Whitney para analisar a evolução das variáveis intragrupo e o teste de Kruskal-Wallis com post hoc de Dunn para as análises intergrupos. Para a comparação das variáveis de caracterização da amostra entre os grupos foi utilizado o teste qui-quadrado. Resultados Observou-se melhora do domínio Participação Social para o GP (p=0,016). No GTR, foi encontrada diferença significativa para o domínio Saúde Mental (p=0,019). No GC, observou-se melhora do domínio Participação Social (p=0,044) e Escore Total do WHOQOL-OLD (p=0,044). Nas comparações intergrupos, observou-se diferença do Escore Total do WHOQOL-BREF do GP e GTR, com o GP apresentando uma melhor QV no início do estudo (p=0,039). A Vitalidade (p=0,010) e Saúde Mental (p=0,024) do GTR melhorou em relação ao GP. Conclusão Os grupos analisados melhoraram sua QV após o período de intervenção.

Abstract Objective The objective of the study was to compare the effects of resistance training (RT) and Pilates on the quality of life (QOL) of elderly women. An experimental design study was carried out with a 12-week intervention. Methods Elderly women (≥60 years) who did not practice any type of physical exercise regularly for at least 3 months were evaluated. The study included 41 elderly women who were randomly divided into three groups: 1- Pilates group (PG), 2- Resistance training group (RTG) and 3- Control group (CG). To assess QOL, the WHOQOL-OLD, WHOQOL-BREF and SF-36 questionnaires were used. The Wilcoxon-Mann-Whitney Test was used to analyze the evolution of intragroup variables and the Kruskal-Wallis test with Dunn's post hoc for intergroup analyzes. To compare the sample characterization variables between the groups, the chi-square test was used. Results There was an improvement in the Social Participation domain for the PG (p=0.016). In the RTG, a significant difference was found for the Mental Health domain (p=0,019). In the CG, there was an improvement in the Social Participation domain (p=0.044) and Total WHOQOL-OLD Score (p=0.044). In the intergroup comparisons, there was a difference in the WHOQOL-BREF Total Score of the PG and RTG, with the PG presenting a better QOL at the beginning of the study (p=0.039). The Vitality (p=0,010) and Mental Health (p=0,024) of the RTG improved in relation to the PG. Conclusion The groups analyzed improved their QOL after the intervention period.

Effect of pilates method on physical fitness related to health in the elderly: a systematic review / Efeito do método pilates na aptidão física relacionada à saúde de idosos: uma revisão sistemática / Efecto del método pilates en la aptitud física relacionada a la salud de individuos de la tercera edad: una revisión sistemática

ABSTRACT The objective of this review was to analyze the evidence of Pilates in physical fitness related to health in the elderly. The article indexing databases (Pubmed, Medline, Science Direct, Scielo, Lilacs, and Cochrane) were reviewed along with the Pilates, elderly and aging descriptors. A total of 41 studies with a randomized experimental and quasi-experimental design met the inclusion criteria. The selection of the studies was carried out by two researchers and the quality of the articles was assessed using the PEDro scale. Interventions ranged from 4-24 weeks with 1-3 sessions/week, and balance was the most investigated variable. The studies included in this review indicate that Pilates improves health status in the elderly, promoting gains in balance, muscle strength, flexibility, functional autonomy, muscular endurance, body composition and aerobic endurance. Despite these findings, some variables need to be further investigated. Level of Evidence II; Systematic review.

RESUMO O objetivo desta revisão foi analisar as evidências do Pilates na aptidão física relacionada com a saúde de idosos. Foram revisadas as bases de indexação de artigos (Pubmed, Medline, Science Direct, Scielo, Lilacs e Cochrane), com os descritores "Método pilates, idosos e envelhecimento". Atenderam os critérios de inclusão 41 estudos com delineamento randomizado experimental e "quase experimental". A seleção dos estudos foi realizada por dois pesquisadores e a qualidade dos artigos foi avaliada pela escala PEDro. As intervenções variaram entre 4 e 24 semanas, de 1 a 3 sessões/semana e a variável mais investigada foi o equilíbrio. Os estudos incluídos nesta revisão indicam que a prática de Pilates melhora as condições de saúde dos idosos, promovendo ganhos de equilíbrio, força muscular, flexibilidade, autonomia funcional, resistência muscular, composição corporal e resistência aeróbica. Apesar destes achados, algumas variáveis precisam ser mais investigadas. Nível de Evidência II; Revisão sistemática.

RESUMEN El objetivo de esta revisión fue analizar las evidencias del Pilates en la aptitud física relacionada a la salud de individuos de la tercera edad. Se revisaron las bases indexadoras de artículos (Pubmed, Medline, Science Direct, Scielo, Lilacs, y Cochrane), con los descriptores "Método pilates, ancianos y envejecimiento". Se cumplieron los criterios de inclusión 41 estudios con delineación experimental aleatorizada y "casi experimental". La selección de los estudios fue realizada por dos investigadores y la calidad de los artículos fue evaluada a través de la escala PEDro. Las intervenciones variaron entre 4-24 semanas, de 1-3 sesiones/semana y la variable más investigada fue el equilibrio. Los estudios incluidos en esta revisión indican que la práctica del Pilates mejora las condiciones de salud de los individuos de la tercera edad, promoviendo aumentos de equilibrio, fuerza muscular, flexibilidad, autonomía funcional, resistencia muscular, composición corporal y resistencia aeróbica. A pesar de estos hallazgos, algunas variables necesitan ser más investigadas. Nível de Evidencia II; Revision sistemática.

Characterization of Posttranslational Modifications on Histone Variants.

The study of histone variants and histone posttranslational modifications (PTMs) is a trending topic in different fields including developmental biology, neurobiology, and immunology; as well as in the understanding of molecular mechanisms leading to diverse diseases, such as cancer. Since the establishment of histone PTMs starts immediately after their synthesis and it continues once they are assembled into chromatin, here we describe a classic protocol of subcellular fractionation aiming to study histones at different stages of maturation. This includes newly synthesized histones enriched in cytosolic fractions; a pool of newly synthesized, evicted, and stored histones enriched in nuclear soluble fractions; and chromatin-associated histones enriched in chromatin pellet. To study specific histone variants and the establishment of their PTMs, we describe a protocol for obtaining histone variants expressed in bacteria. In addition, we describe a Triton-Acetic acid-Urea (TAU) gel electrophoresis protocol adapted to work on mini-gels, which can be coupled to Western blot to analyze PTMs on histone variants. Finally, we describe a Chromatin immunoprecipitation (ChIP) assay for studying histone PTMs, or tagged histone variants, on specific DNA sequences.

Substrate Microarchitecture Shapes the Paracrine Crosstalk of Stem Cells with Endothelial Cells and Osteoblasts.

We examined the hypothesis that substrate microarchitecture regulates the crosstalk between human mesenchymal stem cells (hMSC) and cell types involved in bone regeneration. Compared with polyester flat substrates having uniformly distributed homogenous pores (2D), three-dimensional polystyrene substrates with randomly oriented and interconnected pores of heterogeneous size (3D) stimulated the stromal secretion of IGF-1 while lessened the production of VEGFR-1, MCP-1 and IL-6. The medium conditioned by hMSC cultured in 3D substrates stimulated tube formation by human endothelial cells (hEC) to a higher extent than medium from 2D cultures. 3D co-cultures of hMSC and hEC contained higher secreted levels of IGF-1, EGF and FGF-2 than 2D co-cultures, resulting in increased hEC proliferation and migration. Substrate microarchitecture influenced the secretion of factors related to bone remodeling as the ratio RANKL to OPG, and the levels of M-CSF and IL-6 were higher in 3D co-cultures of hMSC and human osteoblasts (hOB) than in 2D co-cultures. Cytokine microenvironment in 3D co-cultures stimulated osteoblast matrix reorganization while demoted the late steps of osteoblastic maturation. Altogether, data in this study may unveil a new role of scaffold microarchitecture during bone regeneration, as modulator of the paracrine relationships that hMSC establish with hEC and hOB.

Avaliação da aptidão física e funcional de idosos com prática de atividade física diferenciada / Evaluation of physical and functional fitness of older people with practice of differentiated physical activity / Evaluación de la aptitud física y funcional de los ancianos con práctica de actividad física diferenciada

O objetivo foi verificar e comparar o efeito da prática de exercício físico na aptidão física em idosos, com prática de atividades físicas diferenciadas e específicas. Como metodologia, foram formados 3 grupos de idosos e realizados testes por meio de protocolos e anamnese. Os resultados nos mostram que a atividade física regular nos grupos ativos apresenta diferença significativa no desempenho global quando comparado com o grupo sedentário. Concluiu-se que a prática de atividade física ou lúdica regular melhora o desempenho global dos idosos.

The objective was to verify and compare the effect of physical exercise practice on physical fitness in the elderly, with practice of differentiated and specific physical activities. As a methodology, 3 groups of elderly were formed and performed tests through protocols and anamnesis. The results show that regular physical activity in the active groups presents a significant difference in overall performance when compared to the sedentary group. It was concluded that the practice of regular physical activity or play improves the overall performance of the elderly.

El objetivo fue verificar y comparar el efecto de la práctica de ejercicio físico en la aptitud física en ancianos, con práctica de actividades físicas diferenciadas y específicas. Como metodología, se formaron 3 grupos de ancianos y se realizaron pruebas a través de protocolos y anamnesis. Los resultados nos muestran que la actividad física regular en los grupos activos presenta una diferencia significativa en el desempeño global en comparación con el grupo sedentario. Se concluyó que la práctica de actividad física o lúdica regular mejora el desempeño global de los ancianos.

Lipogels responsive to near-infrared light for the triggered release of therapeutic agents.

Here we report a composite system based on fibrin hydrogels that incorporate in their structure near-infrared (NIR) responsive nanomaterials and thermosensitive liposomes (TSL). Polymerized fibrin networks entrap simultaneously gold-based nanoparticles (NPs) capable of transducing NIR photon energy into heat, and lysolipid-incorporated TSL (LTSL) loaded with doxorubicin hydrochloride (DOX). NIR irradiation of the resulting hydrogels (referred to as "lipogels") with 808nm laser light increased the temperature of the illuminated areas, leading to the release of the liposomal cargo. Levels of DOX that release from the "smart" composites were dependent on the concentration of NIR nanotransducers loaded in the lipogel, the intensity of the electromagnetic energy deposited and the irradiation regime. Released DOX retained its bioactivity, as shown in cultures of epithelial carcinoma cells. Finally, the developed drug delivery platform was refined by using NIR-photoabsorbers based on copper sulfide NPs to generate completely biodegradable composites as well as through the incorporation of cholesterol (Ch) in LTSL formulation, which lessens leakiness of the liposomal cargo at physiological temperature. This remotely controlled system may suit well for those therapies that require precise control over the dose of delivered drug in a defined spatiotemporal framework. STATEMENT OF SIGNIFICANCE: Hydrogels composed of fibrin embedding nanoparticles responsive to near infrared (NIR) energy and thermosensitive liposomes loaded with doxorubicin hydrochloride (DOX), were prepared by in situ polymerization. NIR-light irradiation of these constructs, referred to as "NIR responsive lipogels", results in the controlled release of DOX to the surrounding medium. This technology may use fully degradable components and can preserve the bioactivity of liposomal cargo after remote triggering to finely regulate the dose and bioavailability of delivered payloads. NIR responsive lipogels technology overcomes the limitations of drug release systems based on the combination of liposomes and degradable polymeric materials, which in many cases lead to insufficient release at therapy onset or to overdose during high degradation period.

Photothermal and photodynamic activity of polymeric nanoparticles based on α-tocopheryl succinate-RAFT block copolymers conjugated to IR-780.

The aim of this work was the generation of a multifunctional nanopolymeric system that incorporates IR-780 dye, a near-infrared (NIR) imaging probe that exhibits photothermal and photodynamic properties; and a derivate of α-tocopheryl succinate (α-TOS), a mitochondria-targeted anticancer compound. IR-780 was conjugated to the hydrophilic segment of copolymer PEG-b-polyMTOS, based on poly(ethylene glycol) (PEG) and a methacrylic derivative of α-tocopheryl succinate (MTOS), to generate IR-NP, self-assembled nanoparticles (NPs) in aqueous media which exhibit a hydrophilic shell and a hydrophobic core. During assembly, the hydrophobic core of IR-NP could encapsulate additional IR-780 to generate derived subspecies carrying different amount of probe (IR-NP-eIR). Evaluation of photo-inducible properties of IR-NP and IR-NP-eIR were thoroughly assessed in vitro. Developed nanotheranostic particles showed distinct fluorescence and photothermal behavior after excitation by a laser light emitting at 808nm. Treatment of MDA-MB-453 cells with IR-NP or IR-NP-eIR resulted in an efficient internalization of the IR-780 dye, while subsequent NIR-laser irradiation led to a severe decrease in cell viability. Photocytoxicity conducted by IR-NP, which could not be attributed to the generation of lethal hyperthermia, responded to an increase in the levels of intracellular reactive oxygen species (ROS). Therefore, the fluorescence imaging and inducible phototoxicity capabilities of NPs derived from IR-780-PEG-b-polyMTOS copolymer confer high value to these nanotheranostics tools in clinical cancer research. STATEMENT OF SIGNIFICANCE: Multifunctional polymeric nanoparticles (NPs) that combine imaging and therapeutic properties are highly valuable in cancer treatment. In this paper we describe the development of NPs that are fluorescent in the near-infrared (NIR). This is important for their visualization in living tissues that present low absorption and low autofluorescence in this wavelength region (between 700 and 1000nm). Moreover, NPs present photothermal and photodynamic properties when NIR irradiated: the NPs produce an efficient increment of temperature and increase the intracellular reactive oxygen species (ROS) when laser irradiated at 808nm. These tuneable photoinduced properties make the NPs highly cytotoxic after NIR irradiation and provide a new tool for highly precise cancer treatment.

New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival.

Comparative modeling of the DNA-binding domain of human HSF1 facilitated the prediction of possible binding pockets for small molecules and definition of corresponding pharmacophores. In silico screening of a large library of lead-like compounds identified a set of compounds that satisfied the pharmacophoric criteria, a selection of which compounds was purchased to populate a biased sublibrary. A discriminating cell-based screening assay identified compound 001, which was subjected to systematic analysis of structure-activity relationships, resulting in the development of compound 115 (IHSF115). IHSF115 bound to an isolated HSF1 DNA-binding domain fragment. The compound did not affect heat-induced oligomerization, nuclear localization and specific DNA binding but inhibited the transcriptional activity of human HSF1, interfering with the assembly of ATF1-containing transcription complexes. IHSF115 was employed to probe the human heat shock response at the transcriptome level. In contrast to earlier studies of differential regulation in HSF1-naïve and -depleted cells, our results suggest that a large majority of heat-induced genes is positively regulated by HSF1. That IHSF115 effectively countermanded repression in a significant fraction of heat-repressed genes suggests that repression of these genes is mediated by transcriptionally active HSF1. IHSF115 is cytotoxic for a variety of human cancer cell lines, multiple myeloma lines consistently exhibiting high sensitivity.

Profile of practitioners of supervised physical exercise in the southern region of Brazil / Perfil dos praticantes de exercício físico supervisionado da região sul do Brasil

With 23,398 fitness academies, catering for around seven million users, Brazil ranks second behind the United States in the number of units. The objective of this study is to delineate the profile of supervised physical activity practitioners in the three most southern states of Brazil (Paraná, Santa Catarina, and Rio Grande do Sul), analyzing the reasons which lead them to choose a fitness service. Fitness academy clients were also surveyed in relation to their alcohol, tobacco and food supplement usage. Seven hundred and ninety-seven (797) people were evaluated by means of a questionnaire. Data was collected in 24 fitness academies (eight in each state) in the three most southern states of Brazil. It was observed that those who practiced exercise regularly at fitness academies smoked little, consumed few food supplements, and with (50.44%) of those surveyed stating that they consumed only moderate amounts of alcohol. The majority, (34.13%) of exercise practitioners in southern Brazil chose to go to the gym five times a week, (40.99%) went at night, with (40.56%) giving as their reason for practicing exercise as being a way to improve their health. The distance between their home and the gym was the most important reason in choosing a place to conduct training. Intense individual activities were the most practiced type of exercise, there being no statistical difference between the percentages in the three states.

O Brasil ocupa o segundo lugar do mundo em número de academias, totalizando 23.398 unidades com cerca de sete milhões de frequentadores, ficando atrás apenas dos EUA. Neste sentido, o objetivo desse estudo foi delinear o perfil dos praticantes de atividade física supervisionada, analisando os motivos que os levam a escolher um serviço de fitness, bem como traçar o perfil de consumo de álcool, tabaco e suplementos alimentares dos habitantes da Região Sul do Brasil. Foram avaliadas 797 pessoas através de um questionário próprio. A coleta foi realizada em 24 academias divididas em oito para cada um dos três estados do Sul do Brasil. Observou-se que os frequentadores de academias da área de abrangência da pesquisa fumam pouco, consomem poucos suplementos alimentares e apenas 50,44% dessa população consome bebidas alcoólicas de maneira moderada. A maior parte (34,13%) dos praticantes de exercício físico do Sul do Brasil optam por frequentar a academia cinco vezes por semana, no período noturno (40,99%), com o intuito de melhorar a saúde (40,56%). A distância entre a residência e a academia se mostrou o motivo mais relevante para escolher um locar para realizar o treinamento. O tipo de exercício mais praticado são as atividades individuais mais intensas e não houve diferença estatística entre os percentuais nos três estados estudados.

Remote Patterning of Transgene Expression Using Near Infrared-Responsive Plasmonic Hydrogels.

The development of noninvasive technologies for remote control of gene expression has received increased attention for their therapeutic potential in clinical scenarios, including cancer, neurological disorders, immunology, tissue engineering, as well as developmental biology research. Near-infrared (NIR) light is a suitable source of energy that can be employed to pattern transgene expression in plasmonic cell constructs. Gold nanoparticles tailored to exhibit a plasmon surface band absorption peaking at NIR wavelengths within the so called tissue optical window (TOW) can be used as fillers in fibrin-based hydrogels. These biocompatible composites can be loaded with cells harboring heat-inducible gene switches. NIR laser irradiation of the resulting plasmonic cell constructs causes the local conversion of NIR photon energy into heat, achieving spatially restricted patterns of transgene expression that faithfully match the illuminated areas of the hydrogels. In combination with cells genetically engineered to harbor gene switches activated by heat and dependent on a small-molecule regulator (SMR), NIR-responsive hydrogels allow reliable and safe control of the spatiotemporal availability of therapeutic biomolecules in target tissues.

Efeito agudo de diferentes volumes do treinamento de força na flexibilidade / Acute effect of different strength training volume in flexibility

Introdução: O volume em uma sessão de treinamento de força (TF) pode alterar a flexibilidade. Objetivo: Verificar o efeito agudo de uma sessão de TF com diferentes volumes na flexibilidade, imediatamente após o término da sessão e 24 e 48 horas após. Métodos: Sessenta e um voluntários (24,31±0,81anos) do sexo masculino distribuídos aleatoriamente em três grupos: grupo controle (GC), duas série (G2S) e três séries (G3S). Todos os grupos foram avaliados pré e pós-treinamento no teste de sentar e alcançar, Goniometria (ombro, cotovelo, quadril, joelho e coluna) e teste de 10 Repetições Máximas (RM). O treinamento foi composto por nove exercícios que envolviam todas as articulações avaliadas e executado 10 repetições. Resultados: Houve aumento dos níveis de flexibilidade para maioria dos movimentos do ombro; quadril (extensão) e tronco (flexão e extensão) quando comparadas as situações pré e pós-treinamento para todos os grupos submetidos ao treinamento (p < 0,05). Conclusão: Uma sessão de ER com diferentes volumes é capaz de modificar a flexibilidade de articulações triaxiais.

Introduction: The volume in a resistance exercise (RE) session can change flexibility. Objective: The aim of the study was to investigate the acute effect of a training session with different volumes flexibility, immediately after the session and 24 and 48 hours after the training session. Methods: Study participants were 61 volunteers (24.31 ± 0,81 year) males randomly assigned to three groups: control group (CG), two series (G2S) and three series (G3S). All groups were assessed before and after training in the sit and reach test, Goniometry (shoulder, elbow, hip, knee and spine) and test 10 Maximum Repetitions (RM). The training was composed of nine exercises that involved all tested joints and was run 10 repetitions of each exercise with moderate intensity. Results: There was an increase of the flexibility levels for most shoulder movements; hip (extension) and trunk (flexion and extension) when comparing before and after training for all undergoing training groups (p <0.05). Conclusion: A RE session with different volumes is able to modify the flexibility of triaxial joints.

Achievement goals and sportsmanlike attitudes in young soccer players and its association with perceived pressure from significant social agents / Orientações motivacionais e atitudes desportivas em jovens futebolistas e suas associações com as pressões percebidas de agentes sociais significativos

The purposes of this study were to characterize the achievement goals and sportsmanlike attitudes in young soccer players and their association with perceived pressure from different significant social agents (parents/family, coaches, teammates and friends). The sample of the study was comprised of 118 young soccer players, aged between 11 and 19 years (M= 14.68, SD= 2.16). Athletes had 5.40 ± 2.39 years of sport experience and 71 (60.2%) of the athletes had competed at a regional level, while 47 (39.8%) had participated in national competitions. Participants completed a socio-demographic survey, the Task and Ego Orientation in Sports Questionnaire and the Sports Values Questionnaire. The statistical analyses involved univariate normality and descriptive, comparative and correlational analyses. Results revealed that task orientation was positively correlated with sportsmanlike attitudes (r= 0.47, p<0.01) and negatively associated with unsportsmanlike attitudes (r= −0.46, p<0.01), whereas ego orientation effects were contrary (sportsmanlike attitudes: r= −0.33, p<0.01 and unsportsmanlike attitudes: r= 0.42, p<0.01). Perceived pressures from all significant social agents were positively and significantly associated with unsportsmanlike attitudes (p<0.05), with perceived pressure from coaches also being associated with higher ego orientation scores and with lower task orientation and sportsmanlike attitudes in young soccer players. In summary, these results indicate the need for coaches and other social agents to promote a competition climate that reinforces self-referenced improvements and the expression of positive social attitudes in sports contexts. .

- Os objetivos do estudo foram caracterizar as orientações motivacionais e as atitudes (anti)desportivas de jovens futebolistas e suas associações com as pressões percebidas de distintos agentes sociais (pais/família, treinadores, colegas de equipa e amigos). A amostra foi constituída por um total de 118 futebolistas masculinos, com idades entre os 11 e os 19 anos (M= 14.68, DP= 2.16). Os atletas tinham 5.40 ± 2.39 anos de experiência federada, sendo que 71 (60.2%) atletas competiam em nível regional e 47 (39.8%) em competições nacionais. Os participantes responderam a um questionário sociodemográfico, ao Questionário de Orientação Motivacional no Desporto e ao Questionário de Valores no Desporto. A análise estatística envolveu procedimentos de normalidade univariada e análise descritiva, comparativa e correlacional. Os resultados indicaram que a orientação para a tarefa correlacionou-se positivamente com as atitudes desportivas (r= 0.47, p<0.01) e negativamente com as atitudes antidesportivas (r= −0.46, p<0.01), enquanto a orientação para o ego exerceu um efeito contrário (atitudes desportivas: r= −0.33, p<0.01 e atitudes antidesportivas: r= 0.42, p<0.01). As pressões percebidas por parte de todos os agentes de socialização associaram-se positiva e significativamente com as atitudes antidesportivas (p<0.05), sendo os treinadores as principais fontes de pressão promotoras de níveis superiores de orientação para o ego e menores níveis de orientação para a tarefa e atitudes desportivas nos atletas. Em suma, estes resultados indicam a necessidade dos treinadores e outros agentes sociais promoverem um clima de competição orientado para o autoaperfeiçoamento e para a expressão de atitudes socialmente positivas ...

Temporal and spatial patterning of transgene expression by near-infrared irradiation.

We investigated whether near-infrared (NIR) light could be employed for patterning transgene expression in plasmonic cell constructs. Hollow gold nanoparticles with a plasmon surface band absorption peaking at ∼750 nm, a wavelength within the so called "tissue optical window", were used as fillers in fibrin-based hydrogels. These composites, which efficiently transduce NIR photon energy into heat, were loaded with genetically-modified cells that harbor a heat-activated and ligand-dependent gene switch for regulating transgene expression. NIR laser irradiation in the presence of ligand triggered 3-dimensional patterns of transgene expression faithfully matching the illuminated areas of plasmonic cell constructs. This non-invasive technology was proven useful for remotely controlling in vivo the spatiotemporal bioavailability of transgenic vascular endothelial growth factor. The combination of spatial control by means of NIR irradiation along with safe and timed transgene induction presents a high application potential for engineering tissues in regenerative medicine scenarios.

Patterning expression of regenerative growth factors using high intensity focused ultrasound.

Temporal and spatial control of growth factor gradients is critical for tissue patterning and differentiation. Reinitiation of this developmental program is also required for regeneration of tissues during wound healing and tissue regeneration. Devising methods for reconstituting growth factor gradients remains a central challenge in regenerative medicine. In the current study we develop a novel gene therapy approach for temporal and spatial control of two important growth factors in bone regeneration, vascular endothelial growth factor, and bone morphogenetic protein 2, which involves application of high intensity focused ultrasound to cells engineered with a heat-activated- and ligand-inducible gene switch. Induction of transgene expression was tightly localized within cell-scaffold constructs to subvolumes of ∼30 mm³, and the amplitude and projected area of transgene expression was tuned by the intensity and duration of ultrasound exposure. Conditions for ultrasound-activated transgene expression resulted in minimal cytotoxicity and scaffold damage. Localized regions of growth factor expression also established gradients in signaling activity, suggesting that patterns of growth factor expression generated by this method will have utility in basic and applied studies on tissue development and regeneration.

The influence of positional release therapy on the myofascial tension of the upper trapezius muscle / A influencia da terapia de libertacao posicional sobre a tensao miofascial do musculo trapezio

The objective of this study was to analyze the influence of positional release therapy (PRT) on the myofascial tension of the upper trapezius muscle with an active myofascial trigger point (TrP). We studied 30 subjects (18 men and 12 women), mean age 34.5 ± 9.4 years, with an active TrP in the upper trapezius muscle on one side. A search for TrPs was performed bilaterally and the points were considered to be active when both local and referred pain evoked by manual palpation reproduced a deep aching and burning pain. The patients were evaluated under three conditions: (a) resting baseline, (b) concentric contraction and (c) isometric contraction, before and after treatment with PRT, regarding the following parameters: (i) pain intensity during manual palpation (visual analogue pain scale) and (ii) upper trapezius muscle electromyographic (EMG) signals. A significant decrease in painful symptoms from 5.3 ± 1.9 to 2.8 ± 1.8 (p < 0.001) was observed after treatment. There were no significant differences in EMG signals during resting baseline and in the presence of concentric contraction after the PRT session. It was concluded that PRT may be an effective treatment for pain relief and to reduce resting baseline EMG signals in the upper trapezius muscle with a TrP, suggesting that its use as an alternative or an adjunct to other therapies. The effectiveness of this type of treatment should be confirmed by further clinical studies.

O objetivo deste estudo foi analisar a influência da Terapia de Libertação Posicional (TLP) sobre a tensão miofascial do músculo trapézio superior, com presença de ponto gatilho (PG) miofascial ativo. Foram estudados 30 indivíduos (18 homens e 12 mulheres), idade média 34,5 + 9,4 anos, com presença de PG ativo, no músculo trapézio superior, de um dos lados. Os PG foram avaliados em ambos os lados e foram considerados ativos quando era evocada uma dor local, disseminada e persistente, por palpação manual. Os indivíduos foram avaliados em três condições: (a) repouso basal, (b) contração concêntrica e (c) contração isométrica, antes e após da aplicação da TLP, nos seguintes parâmetros: (i) intensidade da dor durante a palpação (escala visual analógica de dor) e (ii) sinais eletromiográficos (EMG) do músculo trapézio superior. Houve uma redução significativa do sintoma doloroso 5,3 ± 1,9 para 2,8 ± 1,8 (p < 0,001). Quanto à atividade electromiográfica, em repouso basal e na contração concêntrica, não se observaram diferenças significativas nos sinais EMGs, após a utilização da TLP. Os resultados sugerem que a TLP diminui o sintoma doloroso e reduz os sinais da electromiografia, em repouso basal, do músculo trapézio superior com PG. Isto sugere que a técnica de TLP pode ser utilizada como uma alternativa ou em concomitância com outras terapias. A eficácia desta forma de tratamento deve ser confirmada por outros estudos clínicos.

Spatiotemporal control of vascular endothelial growth factor expression using a heat-shock-activated, rapamycin-dependent gene switch.

A major challenge in regenerative medicine is to develop methods for delivering growth and differentiation factors in specific spatial and temporal patterns, thereby mimicking the natural processes of development and tissue repair. Heat shock (HS)-inducible gene expression systems can respond to spatial information provided by localized heating, but are by themselves incapable of sustained expression. Conversely, gene switches activated by small molecules provide tight temporal control and sustained expression, but lack mechanisms for spatial targeting. Here we combine the advantages of HS and ligand-activated systems by developing a novel rapamycin-regulated, HS-inducible gene switch that provides spatial and temporal control and sustained expression of transgenes such as firefly luciferase and vascular endothelial growth factor (VEGF). This gene circuit exhibits very low background in the uninduced state and can be repeatedly activated up to 1 month. Furthermore, dual regulation of VEGF induction in vivo is shown to stimulate localized vascularization, thereby providing a route for temporal and spatial control of angiogenesis.

Simvastatin prevents the induction of interleukin-6 gene expression by titanium particles in human osteoblastic cells.

One of the most important complications of total joint arthroplasty is failure associated with periprosthetic osteolysis, a process mainly initiated by the biological response to wear-derived products from the biomaterials in service. The inflammatory mediator interleukin-6 (IL-6) plays a key role in the establishment and progression of aseptic loosening. Metal particles specifically up-regulate IL-6 production in bone-forming cells and implant-bone interfacial tissues. The use of statins has been recently associated with a significantly reduced risk of revision in patients that undergo total hip arthroplasty. We hypothesized that simvastatin (Simv) could modulate the osteoblastic response to titanium particles (Ti) by attenuating the production of IL-6. Pre-treatment of human osteoblastic cells with Simv down-regulated Ti particle-induced IL-6 gene expression at mRNA and protein levels. The effect of Simv on Ti-induced IL-6 production in osteoblastic cells could not be explained by inhibition of the internalization of metal particles. The mechanism involved in this down-regulation is based in the inhibition of the HMG-CoA/GGPP/RhoA/ROCK pathway, independently of Simv effects in the cholesterol synthesis. The cytokine-lowering property of Simv has been observed in Saos-2 cells and human primary osteoblasts (hOBs) exposed to Ti particles, and was further enhanced when hOBs were co-cultured with macrophages.