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Transfer and intra-articular expression of the IL-1Ra cDNA in human rheumatoid joints
Impaired decisional impulsivity in pathological videogamers
Abstract
Background
Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort.
Methods
Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment.
Results
In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time.
Conclusions
We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management
Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites
Midline fascial plication under continuous digital transrectal control: which factors determine anatomic outcome?
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88897.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The aim of the study was to report anatomic and functional outcome of midline fascial plication under continuous digital transrectal control and to identify predictors of anatomic failure. METHODS: Prospective observational cohort. Anatomic success defined as POP-Q stage or= II underwent midline fascial plication under continuous digital transrectal control. Median follow-up was 14 months (12-35 months), and anatomic success was 80.3% (95% CI 75-86). Independent predictors of failure were posterior compartment POP stage >or= III [OR 8.7 (95% CI 2.7-28.1)] and prior colposuspension [OR 5.6 (95% CI 1.1-27.8)]. Sixty-three percent of patients bothered by obstructed defaecation experienced relief after surgery. CONCLUSIONS: Anatomic and functional outcomes were good. Risk factors for anatomic failure were initial size of posterior POP (stage >or= III) and prior colposuspension.1 juni 201
Concomitant Active Tuberculosis Prolongs Survival in Non-Small Cell Lung Cancer: A Study in a Tuberculosis-Endemic Country
BACKGROUND: Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC) shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC) resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. METHODS: Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. RESULTS: A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01). Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48 ~ 0.97). Squamous cell carcinoma (SCC) (55.8 vs. 31.7%, p<0.01) is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05). Active tuberculosis in SCC increases the expression of CD3 (46.4 ± 24.8 vs. 24.0 ± 16.0, p<0.05), CXCR3 (35.1 ± 16.4 vs. 19.2 ± 13.3, p<0.01) and IP-10 (63.5 ± 21.9 vs. 35.5 ± 21.0, p<0.01), while expression of FOXP3 is decreased (3.5 ± 0.5 vs. 13.3 ± 3.7 p<0.05, p<0.05). Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05) and CXCR3 (12.1 vs. 4.4 month, p<0.05) is longer than that with low expression. CONCLUSIONS: Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches
Reacquisition of the lower temporal bar in sexually dimorphic fossil lizards provides a rare case of convergent evolution
Temporal fenestration has long been considered a key character to understand relationships amongst reptiles. In particular, the absence of the lower temporal bar (LTB) is considered one of the defining features of squamates (lizards and snakes). In a re-assessment of the borioteiioid lizard Polyglyphanodon sternbergi (Cretaceous, North America), we detected a heretofore unrecognized ontogenetic series, sexual dimorphism (a rare instance for Mesozoic reptiles), and a complete LTB, a feature only recently recognized for another borioteiioid, Tianyusaurus zhengi (Cretaceous, China). A new phylogenetic analysis (with updates on a quarter of the scorings for P. sternbergi) indicates not only that the LTB was reacquired in squamates, but it happened independently at least twice. An analysis of the functional significance of the LTB using proxies indicates that, unlike for T. zhengi, this structure had no apparent functional advantage in P. sternbergi, and it is better explained as the result of structural constraint release. The observed canalization against a LTB in squamates was broken at some point in the evolution of borioteiioids, whereas never re-occuring in other squamate lineages. This case of convergent evolution involves a mix of both adaptationist and structuralist causes, which is unusual for both living and extinct vertebrates
Abordagem da artroplastia total do joelho no Brasil: estudo transversal
CONTEXT AND OBJECTIVE: Total knee arthroplasty (TKA) has evolved particularly since the 1970s, with improvements in implants and surgical instruments, and has thus become an effective intervention for treating knee arthrosis. Many studies have presented rates of satisfactory clinical and radiological results greater than 90%, from follow-ups of over ten years. Nevertheless, despite scientific evidence showing the efficacy of TKA, the approaches taken present controversies in certain respects. The objective of this study was to evaluate how the Brazilian orthopedists deal with TKA, with investigation of the main aspects of this procedure. DESIGN AND SETTING: Cross-sectional survey conducted during the 39th Brazilian Congress of Orthopedics and Traumatology, in São Paulo, Brazil, in November 2007. METHODS: We applied a questionnaire to orthopedists registered at the congress. The questionnaire was randomly distributed and participation was voluntary; 858 completed questionnaires were included in the analysis. RESULTS: Most of the Brazilian orthopedists were members of SBOT and worked in the southeastern region. They used imported cemented implants through an anterior access route centered on the patella, with replacement of the joint surface of the patella and preservation of the posterior cruciate ligament. They did not have experience with simultaneous bilateral TKA. Postoperatively, they used antibiotics and suction drains for 48 hours. There was no consensus regarding prophylaxis for venous thromboembolism or the frequency of the main complications. CONCLUSION: The majority of Brazilian orthopedists work in the southeastern region of the country and agree about the main aspects of the approaches towards TKA.CONTEXTO E OBJETIVO: A artroplastia total do joelho (ATJ) evoluiu sobremaneira desde os anos 70, com melhora dos implantes e do instrumental cirúrgico, tornando-se uma intervenção efetiva para o tratamento da artrose do joelho. Muitos estudos apresentam resultados clÃnicos e radiológicos satisfatórios superiores a 90% no acompanhamento acima de 10 anos. Apesar das evidências cientÃficas sobre sua eficácia da ATJ, a sua abordagem apresenta controvérsias em alguns aspectos. O objetivo do estudo foi avaliar como o ortopedista brasileiro aborda a ATJ e os principais aspectos técnicos na realização deste procedimento. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado durante o 39º Congresso Brasileiro de Ortopedia e Traumatologia em São Paulo, Brasil, em novembro de 2007. MÉTODOS: Aplicamos um questionário aos ortopedistas inscritos no congresso. A distribuição foi aleatória com adesão voluntária. Foram incluÃdos 858 questionários para análise. RESULTADOS: A maioria dos Ortopedistas Brasileiros são membros da SBOT e atua na região sudeste. Usam o implante importado, cimentado, por via de acesso anterior centrada na patela, com substituição da superfÃcie articular da patela e preservação do ligamento cruzado posterior e não tem experiência com a artroplastia total bilateral simultânea. No pós-operatório utilizam antibióticos e dreno de sucção por 48 horas. Não houve consenso quanto à profilaxia para tromboembolismo venoso e frequência das principais complicações. CONCLUSÃO: A maioria dos ortopedistas brasileiros trabalha na região sudeste e concorda quanto aos principais aspectos da abordagem da ATJ.Universidade Federal de São Paulo (UNIFESP) Department of Orthopedics and TraumatologyUniversidade Federal de São Paulo (UNIFESP) Department of Orthopedics and Traumatology Orthopedist and Head of the Knee GroupUNIFESP, Department of Orthopedics and TraumatologyUNIFESP, Department of Orthopedics and Traumatology Orthopedist and Head of the Knee GroupSciEL
Computer Analysis of User Interfaces Based on Repetition in Transcripts of User Sessions
It is generally acknowledged that the production of quality user interfaces requires a thorough understanding of the user and that this involves evaluating the interface by observing the user working with the system, or by performing human factors experiments. Such methods traditionally involve the use of video tape, protocol analysis, critical incident analysis, etc. These methods require time consuming analyses and may be invasive. In addition, the data obtained through such methods represent a relatively small portion of the use of a system. An alternative approach is to record all user input and systems output, i.e., log the user session. Such transcripts can be collected automatically and non-invasively over a long period of time. Unfortunately, this produces voluminous amounts of data. There is, therefore, a need for tools and techniques that allow an evaluator to identify potential performance and usability problems from such data. It is hypothesized that repetition of user actions is an important indicator of potential user interface problems
Risk-taking, delay discounting, and time perspective in adolescent gamblers: an experimental study
Previous research has demonstrated that adult pathological gamblers (compared to controls) show risk-proneness, foreshortened time horizon, and preference for immediate rewards. No study has ever examined the interplay of these factors in adolescent gambling. A total of 104 adolescents took part in the research. Two equal-number groups of adolescent non-problem and problem gamblers, defined using the South Oaks Gambling Screen-Revised for Adolescents (SOGS-RA), were administered the Balloon Analogue Risk Task (BART), the Consideration of Future Consequences (CFC-14) Scale, and the Monetary Choice Questionnaire (MCQ). Adolescent problem gamblers were found to be more risk-prone, more oriented to the present, and to discount delay rewards more steeply than adolescent non-problem gamblers. Results of logistic regression analysis revealed that BART, MCQ, and CFC scores predicted gambling severity. These novel finding provides the first evidence of an association among problematic gambling, high risk-taking proneness, steep delay discounting, and foreshortened time horizon among adolescents. It may be that excessive gambling induces shortsighted behaviors that, in turn, facilitate gambling involvement
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