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A handball is one of two technical skills used to dispose of the ball in Australian Football. Previous research has only considered handball effectiveness in the analysis of team performance and there is a need to understand whether there are other more important characteristics of handball execution that explain effectiveness (i.e., performance). 1342 handballs from Australian Football League matches were analysed. Ten characteristic variables were created that represent the context and execution of each handball included in the analysis. A mixed effects generalised linear model was used to evaluate the effect of the (ten) characteristics on handball outcome. Three out of ten characteristics were associated with handball outcome, and these related to the posture of the handballer and the type of defensive pressure applied to the handballer and the receiver of the handball. These findings explain both how to increase handball effectiveness and how to reduce the handball effectiveness of an opposition team. Given the important role of handballing in passing sequences and maintaining ball possession, the practical application of these findings could enhance overall team performance.
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Desempenho Atlético , Humanos , Austrália , Modelos Lineares , Esportes de EquipeRESUMO
We present data on life history parameters from a long-term study of vervet monkeys in the Eastern Cape, South Africa. Estimates are presented of age at first conception for females and age at natal dispersal for males, along with the probability of survival to adulthood for infants born during the study, female reproductive life-span, reproductive output (including lifetime reproductive success for a subset of females), and inter-birth interval (IBI) duration. We also assess the effect of maternal age and infant survival on length of IBI. We then go on to compare life history parameters for our population with those from two East African populations in Kenya (Amboseli and Laikipia). We find there is broad consensus across the three populations, although mean infant survival was considerably lower for the two East African sites. Such comparisons must be made cautiously, however, as local ecology across the duration of the studies obviously has an impact on the estimates obtained. With this caveat in place, we consider that the concordance between values is sufficient to enable the values reported here to be used in comparative studies of primate life history, although data from habitats with higher rainfall and lower levels of seasonality are needed, and the results presented here should not be seen as canonical.
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This study aimed to determine whether machine learning models based on technical performance and not score margin could be used to predict end-of-match outcome of Australian football matches in real-time. If efficacious, these models could be used to generate insights about team performance and support the decision-making of coaches during matches. A database of 168 team technical performance indicators from 829 Australian Football League matches played between 2017 and 2021 was used. Two feature sets (data-driven and data-informed) were used to train and evaluate six models (generalised linear model, random forest and adaboost) on match outcome prediction (Win/Loss) over 120 epochs (a representation of normalised time during each match). All models performed well (mean classification accuracy = 73.5-75.8%) in comparison with a benchmark score-based model (mean classification accuracy = 77.4%). Data-informed feature sets performed better than data-driven in most cases. Classification accuracy was low at the start of a match (45.7-48.8%) but increased to a peak near the end of a match (87.2-92.7%). These findings suggest that any of the employed models can be used to formulate in-match decision support. The model which is best in practice will depend on factors such as time-cost trade-off, feasibility and the perceived value of its suggestions.
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Desempenho Atlético , Humanos , Austrália , Comportamento Competitivo , Esportes de EquipeRESUMO
BACKGROUND: Long non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (ß-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters. METHODS AND RESULTS: Bioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal-Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p < 0.009, p < 0.014, p < 0.008, respectively). Also, BACE1 over expression was significantly associated with tumour site (p < 0.009), metastasis (p < 0.017) and histological differentiation (p < 0.028) and staging (p < 0.017). Furthermore, ROC curve plotting showed LINC-PINT LNC-BACE1 may distinguish between early and late-stage of CRC, highlighting the value of both BACE1 and PINT as CRC progression biomarkers. CONCLUSION: We investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options.
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Neoplasias Colorretais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação para Baixo/genética , Regulação para Cima , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Irã (Geográfico) , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologiaRESUMO
Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.
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BACKGROUND: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
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Antirreumáticos/uso terapêutico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Aortite/diagnóstico por imagem , Aortite/tratamento farmacológico , Aortite/patologia , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/patologia , Humanos , Metotrexato/uso terapêutico , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/patologiaRESUMO
PURPOSE: To evaluate the association of postoperative fluoroquinolone use following arthroscopic primary rotator cuff repair with failure requiring revision rotator cuff repair. METHODS: An insurance database was queried for patients undergoing rotator cuff repair from 2007 to 2015. These patients were divided into three groups: (1) patients prescribed fluoroquinolones within 6 months postoperatively (divided into 0-2, 2-4, and 4-6 months), (2) a matched negative control cohort of patients not prescribed fluoroquinolones, and (3) a matched positive control cohort of patients prescribed fluoroquinolones between 6 and 18 months following rotator cuff repair. Rates of failure requiring revision rotator cuff repair were compared within 2 years. RESULTS: A total of 1292 patients were prescribed fluoroquinolones within 6 months after rotator cuff repair, including 442 within 2 months, 433 within 2 to 4 months, and 417 within 4 to 6 months, and were compared to 5225 matched negative controls and 1597 matched positive controls. The rate of revision rotator cuff repair was significantly higher in patients prescribed fluoroquinolones within 2 months (6.1 %) compared to matched negative (2.2 %, P = 0.0009) and positive controls (2.4 %, P = 0.0026). There were no significant differences in the rate of revision rotator cuff repair when fluoroquinolones were prescribed >2 months after rotator cuff repair. CONCLUSIONS: Early use of fluoroquinolones following rotator cuff repair was independently associated with significantly increased rates of failure requiring revision rotator cuff repair. This is the first clinical study examining the association of postoperative fluoroquinolone use with failure following arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: III.
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Fluoroquinolonas/farmacologia , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Artroplastia , Artroscopia , Humanos , Masculino , Procedimentos Neurocirúrgicos , Período Pós-Operatório , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the impact that the structure and combination of athlete classification within lineups has on possession outcome in Wheelchair Rugby (WR). DESIGN: Retrospective. METHODS: Analysis was conducted using data from all 18 WR matches from the 2020 Tokyo Paralympic Games. Pearson's chi-squared analysis was conducted to investigate the effect of lineup structures on performance and a nested generalised logistic mixed model (GLMM) was fitted to the data to investigate the association between independent variables and the outcome of possessions. Specifically, the impact of offensive and defensive lineup structures on possession outcome and whether the offensive and defensive lineup structures matching or not impact possession outcome. RESULTS: There was a significant relationship between the offensive lineup structure and possession outcome. Balanced lineups had greater turnovers than expected. Balanced lineups also had fewer tries than expected, whilst high-low lineups had fewer than expected turnovers. There were no significant associations between the defensive lineup structure and possession outcome. Furthermore, no significant associations were found between whether the structure of the offensive and defensive lineup matched (or not) and the possession outcome. CONCLUSIONS: The findings suggest that the offensive team's lineup structure plays a more prominent role in impacting possession outcome, compared to the defensive team's lineup structure. The present results provide valuable insights into WR performance for coaches, practitioners, and researchers.
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Desempenho Atlético , Futebol Americano , Cadeiras de Rodas , Humanos , Estudos Retrospectivos , Desempenho Atlético/classificação , Pessoas com Deficiência/classificação , Esportes para Pessoas com Deficiência/classificaçãoRESUMO
AIMS: To explore the relationship between nutritional intake, fermentable oligo-, di, monosaccharides and polyols, and carbohydrate malabsorption, with gastrointestinal symptoms during a 56 km trail ultramarathon event and identify differences in nutritional intake between runners with severe and non-severe gastrointestinal symptoms. METHODS: Forty-four ultramarathoners recorded and self-reported dietary intake 3 days before, morning of, and during the ultramarathon with gastrointestinal symptoms obtained retrospectively and nutrient analysis via FoodWorks. Carbohydrate malabsorption was determined via breath hydrogen content pre- and post-race. Spearman's rank-order and Mann-Whitney U-tests were used to identify relationships and differences between groups. RESULTS: Total fermentable oligo-, di, monosaccharides and polyols intake were not associated with gastrointestinal symptoms, but weak associations were observed for lower energy (rs = -0.302, p = 0.044) and fat intake (rs = -0.340, p = 0.024) 3 days before with upper gastrointestinal symptoms and higher caffeine intake 3 days before with overall gastrointestinal symptoms (rs = 0.314, p = 0.038). Total fermentable oligo-, di-, monosaccharides and polyols intake and breath hydrogen were not different between those with severe versus non-severe symptoms (p > 0.05). Although those with severe symptoms had higher caffeine (p = 0.032), and total polyols intake (p = 0.031) 3 days before, and higher % energy from fat (p = 0.043) and sorbitol intake (p = 0.026) during the race, and slower ultramarathon finish times (p = 0.042). CONCLUSION: Total fermentable oligo-, di-, and monosaccharides intake and carbohydrate malabsorption were not associated with gastrointestinal symptoms. Additional research on the effect of fat, caffeine, and polyol intake on exercise-associated gastrointestinal symptoms is warranted and presents new nutritional areas for consideration when planning nutritional intake for ultramarathoners.
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Carboidratos da Dieta , Fermentação , Gastroenteropatias , Monossacarídeos , Corrida , Humanos , Masculino , Corrida/fisiologia , Feminino , Pessoa de Meia-Idade , Carboidratos da Dieta/administração & dosagem , Adulto , Monossacarídeos/administração & dosagem , Gastroenteropatias/etiologia , Estudos Retrospectivos , Polímeros , Síndromes de Malabsorção/metabolismo , Testes RespiratóriosRESUMO
Background: Limited data about acute respiratory illness (ARI) and respiratory virus circulation are available in congregate community settings, specifically schools. To better characterize the epidemiology of ARI and respiratory viruses in schools, we developed School Knowledge of Infectious Diseases in Schools (School KIDS). Methods: School KIDS is a prospective, respiratory viral testing program in a large metropolitan school district (pre-kindergarten-12th grade) in Kansas City, Missouri. During the 2022-2023 school year, all students and staff were eligible to participate in surveillance respiratory viral testing at school by submitting observed self-administered nasal swabs monthly. Participants could also submit a nasal swab for on-demand symptomatic testing when experiencing ≥1 ARI symptom, including cough, fever, nasal congestion, runny nose, shortness of breath, sore throat, and/or wheezing. Swabs were tested in a research laboratory using multipathogen respiratory polymerase chain reaction assays. Participants were evaluated for ongoing viral shedding by collecting two weekly nasal swabs (i.e., convalescent), following initial on-demand symptomatic testing. Participants were asked to complete an electronic survey to capture the presence and type of ARI symptom(s) before the collection of respiratory swabs. Results: From 31 October 2022 to 29 June 2023, School KIDS enrolled 978 participants, including 700 students, representing 3.4% of the district student population, and 278 staff members. Participants submitted a median of six surveillance, one symptomatic, and two convalescent specimens during the study period. A total of 6,315 respiratory specimens, including 4,700 surveillance, 721 on-demand symptomatic, and 894 convalescent specimens, were tested. Overall, a virus was detected in 1,168 (24.9%) surveillance and 363 (50.3%) symptomatic specimens. Of the 5,538 symptom surveys sent to participants before scheduled surveillance testing, 4,069 (73.5%) were completed; ARI symptoms were reported on 1,348 (33.1%) surveys. Conclusion: Respiratory surveillance testing in schools is feasible and provides novel information about respiratory virus detections in students and staff attending school. Schools are an important community setting, and better knowledge of respiratory virus circulation in schools may be useful to identify respiratory virus transmission in the community and assess the impact of effective infection prevention measures.
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Infecções Respiratórias , Instituições Acadêmicas , Humanos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Missouri/epidemiologia , Estudos Prospectivos , Adolescente , Criança , Feminino , Masculino , Conhecimentos, Atitudes e Prática em Saúde , Estudantes/estatística & dados numéricos , Pré-Escolar , Viroses/diagnóstico , Viroses/epidemiologiaRESUMO
The ability to make effective decisions is an important function of any football coach, whether during training, team selection, match-day performance or post-match player evaluation. It is not yet known how elite Australian football coaches make decisions during matches, in time-constrained but well-resourced environments. This study is the first to explore the decision-making of elite Australian football coaches during matches, in pursuit of identifying opportunities to improve the translation and implementation of research findings into the competitive match environment. Using semi-structured interviews and thematic analysis, a six-stage framework of the decision-making of elite Australian football coaches during matches was developed. The stages include (1) Opportunity trigger, (2) Understand the opportunity, (3) Determine the need for action, (4) Explore options, (5) Take action and (6) Evaluate the decision. Coaches relied on subjective and objective sources of information and consulted with assistant coaches, performance analysts, and sport scientists. The findings enable researchers to ensure future interventions to improve decision-making during matches are well integrated. They also provide an opportunity for coaches to reflect on their own decision-making process, identifying targeted areas for improvement in their own practice.
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Utensílios Domésticos , Médicos , Humanos , Austrália , Esportes de EquipeRESUMO
This study examines the relationship between religious and spiritual (R/S) struggle and religiosity with depression and anxiety in adolescents admitted to inpatient psychiatric units of a pediatric hospital in the Midwest of the United States. We administered four self-reported scales to 71 adolescents (ages 13-17) to assess religiosity, R/S struggle, depression, and anxiety. The prevalence of R/S struggle among this population was high (88.73%). Significant associations were found between R/S struggle and depression and anxiety, linking greater R/S struggles with more severe depression or anxiety. However, no significant associations between religiosity and depression and anxiety were noted. By examining the prevalence of R/S struggle among this population and its relationship to depression and anxiety, this study contributes to the expanding research on the impact of religion and spirituality on the psychological well-being of adolescents.
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Depressão , Pacientes Internados , Criança , Humanos , Adolescente , Estados Unidos , Depressão/epidemiologia , Depressão/psicologia , Religião , Ansiedade , Transtornos de Ansiedade , Espiritualidade , Adaptação PsicológicaRESUMO
Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a protein kinase A (PKA)-activated epithelial anion channel involved in salt and fluid transport in multiple organs, including the lung. Most CF mutations either reduce the number of CFTR channels at the cell surface (e.g., synthesis or processing mutations) or impair channel function (e.g., gating or conductance mutations) or both. There are currently no approved therapies that target CFTR. Here we describe the in vitro pharmacology of VX-770, an orally bioavailable CFTR potentiator in clinical development for the treatment of CF. In recombinant cells VX-770 increased CFTR channel open probability (P(o)) in both the F508del processing mutation and the G551D gating mutation. VX-770 also increased Cl(-) secretion in cultured human CF bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and the F508del processing mutation on the other allele by approximately 10-fold, to approximately 50% of that observed in HBE isolated from individuals without CF. Furthermore, VX-770 reduced excessive Na(+) and fluid absorption to prevent dehydration of the apical surface and increased cilia beating in these epithelial cultures. These results support the hypothesis that pharmacological agents that restore or increase CFTR function can rescue epithelial cell function in human CF airway.
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Aminofenóis/farmacologia , Brônquios/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/fisiopatologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Quinolinas/farmacologia , Quinolonas/farmacologia , Absorção/efeitos dos fármacos , Substituição de Aminoácidos/efeitos dos fármacos , Aminofenóis/química , Animais , Células Cultivadas , Cloretos/metabolismo , Cílios/efeitos dos fármacos , Cílios/metabolismo , Sinergismo Farmacológico , Canais Epiteliais de Sódio/metabolismo , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Camundongos , Mutação/genética , Células NIH 3T3 , Quinolinas/química , Quinolonas/química , Sódio/metabolismoRESUMO
Long non-coding RNAs have been proposed as biomarkers for the detection, prevention and screening of various malignancies. In this study, two lncRNAs (ANRIL and BANCR) were assessed for biomarker application in the early detection of colorectal cancer (CRC) through stool specimen testing, as a non-invasive and cost-effective methodology. A total of 40 stool samples were collected from patients referred to the hospital with colorectal cancer or adenomatous polyps as pre-cancerous lesions; patients were diagnosed using colonoscopy and pathology reports were available. Twenty control samples were also obtained from healthy subjects for comparison. RNA extraction and cDNA synthesis were followed by real-time PCR to evaluate lncRNA expression. The up-regulation of ANRIL in 20% of samples taken from polyp patients, combined with up-regulation in 65% of patients with CRC, confirmed the potential usefulness of ANRIL as a prognostic biomarker (AUC 0.95; P < 0.0001). BANCR relative expression analysis illustrated significant up-regulation in polyp (P < 0.04) and tumoural participants (P < 0.03) compared with normal control individuals. The expression patterns of ANRIL and BANCR in polyp cases were significantly correlated according to correlation analysis (r = 0.45, P < 0.045). ANRIL expression patterns in stool specimens of polyp and tumour cases supported the use of ANRIL as a prognostic biomarker for screening patients in the early stages of CRC. Up-regulation of BANCR in pre-cancerous lesions as well as down-regulation of ANRIL may also be a specific marker pair for easy, convenient and fast CRC prognosis.
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Neoplasias Colorretais , RNA Longo não Codificante , Biomarcadores , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Functional bracing is often used as an adjunct to nonoperative treatment of anterior shoulder instability, but no study has evaluated the effectiveness of in-season bracing. The purpose of this study was to examine successful return to play in a nonoperative cohort of adolescent athletes with in-season shoulder instability and compare those athletes treated with bracing to those who were not. HYPOTHESIS: The use of functional bracing will improve success rates in a cohort of athletes treated nonoperatively for in-season shoulder instability. STUDY DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 97 athletes with anterior shoulder instability were followed for a minimum of 1 year. The mean age was 15.8 ± 1.4 years (range, 12.0-18.0 years). All athletes were treated with initial nonoperative management. Twenty athletes (21%) were also treated with bracing while 77 (79%) were not. The athlete completing the current season and 1 subsequent season without surgery or time lost from shoulder injury was defined as a successful outcome. RESULTS: There was no statistical difference in nonoperative success rates between the braced and nonbraced athletes (P = 0.33). Braced athletes (n = 20) returned to play 80% of the time, while nonbraced athletes (n = 77) returned at a rate of 88%. Of the braced athletes, 85% were football players (n = 17). A football-only comparison demonstrated no difference between braced failures (26%) and nonbraced failures (16%) (P = 0.47). CONCLUSION: This is the first study to evaluate the utility of functional bracing in returning an athlete to sport and completing a full subsequent season without surgery or time loss due to injury of the shoulder. In adolescent athletes with shoulder instability treated nonoperatively, functional bracing did not result in increased success rates when compared with no bracing. CLINICAL RELEVANCE: The data from this study indicate that functional bracing may not improve success rates for athletes with shoulder instability.
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Braquetes , Instabilidade Articular/terapia , Volta ao Esporte , Lesões do Ombro/terapia , Esportes Juvenis/lesões , Adolescente , Criança , Tratamento Conservador , Humanos , Relesões , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Here, we evaluated the VEGF gene -2578C/A polymorphism as a potential susceptibility factor in colorectal cancer (CRC) occurrence amongst Iranian CRC patients. BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulatory factor in angiogenesis which plays essential roles in the development of malignancy in colorectal cancer (CRC), as the third most prevalent cancer worldwide. METHODS: VEGF -2578C/A polymorphism was evaluated in 200 CRC patients and 200 healthy control subjects via restriction fragment length polymorphism analysis. RESULTS: The frequencies of CC, AC and AA genotypes among CRC patients were 22.5%, 51% and 26.5%, respectively, with their respective genotype frequencies at 16%, 54% and 30% in control cohorts (P=0.247). The A allele frequency among the case group was 52% and for control group, it was 57%. C allele frequency in case and control groups was 48% and 43%, respectively (p=0.156). No significant association was observed (p=0.990) between this polymorphism and CRC stage. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C/A VEGF are associated with increased risk of colorectal cancer in Iranian colorectal cancer patients and suggest instead that meta data studies, which have previously relied upon populations definitions such as 'Asian', should more specifically take into account country of origin when associating prognostic value to a given genotype.
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Aberrant activation of the WNT/CTNNB1 pathway is notorious in colorectal cancer (CRC). Here, we demonstrate that the expression of specific and crucial WNT signaling pathway genes is linked to disease progression in colonic adenomatous (AP) and hyperplastic (HP) polyps in an Iranian patient population. Thus, we highlight potential gene expression profiles as candidate novel biomarkers for the early detection of CRC. From a 12-month study (2016-2017), 44 biopsy samples were collected during colonoscopy from the patients with colorectal polyps and 10 healthy subjects for normalization. Clinical and demographic data were collected in all cases, and mRNA expression of APC, CTNNB1, CDH1, AXIN1, and AXIN2 genes was investigated using real-time polymerase chain reaction (PCR). CTNNB1 and CDH1 expression levels were unaltered in AP and HP subjects, whereas mRNA expression of APC was decreased in AP contrasted with HP subjects, with a significant association between APC downregulation and polyp size. Although AXIN1 showed no changes between AP and HP groups, a significant association between AXIN1 and dysplasia grade was found. Also, significant upregulation of AXIN2 in both AP and HP subjects was detected. In summary, we have shown increased expression of AXIN2 and decreased expression of APC correlating with grade of dysplasia and polyp size. Hence, AXIN2 and APC should be explored as biomarker candidates for early detection of AP and HP polyps in CRC.
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Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.
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Neoplasias Colorretais/genética , Metilação de DNA , MicroRNAs/genética , Adolescente , Adulto , Fatores Etários , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Ilhas de CpG , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Fatores Sexuais , Adulto JovemRESUMO
Participants (aged 5-6 yrs, 9-10 yrs and adults) rated (using a five-point scale) grammatical (intransitive) and overgeneralized (transitive causative)(1) uses of a high frequency, low frequency and novel intransitive verb from each of three semantic classes [Pinker, S. (1989a). Learnability and cognition: The acquisition of argument structure. Cambridge, MA: MIT Press]: "directed motion" (fall, tumble), "going out of existence" (disappear, vanish) and "semivoluntary expression of emotion" (laugh, giggle). In support of Pinker's semantic verb class hypothesis, participants' preference for grammatical over overgeneralized uses of novel (and English) verbs increased between 5-6 yrs and 9-10 yrs, and was greatest for the latter class, which is associated with the lowest degree of direct external causation (the prototypical meaning of the transitive causative construction). In support of Braine and Brooks's [Braine, M.D.S., & Brooks, P.J. (1995). Verb argument strucure and the problem of avoiding an overgeneral grammar. In M. Tomasello & W. E. Merriman (Eds.), Beyond names for things: Young children's acquisition of verbs (pp. 352-376). Hillsdale, NJ: Erlbaum] entrenchment hypothesis, all participants showed the greatest preference for grammatical over ungrammatical uses of high frequency verbs, with this preference smaller for low frequency verbs, and smaller again for novel verbs. We conclude that both the formation of semantic verb classes and entrenchment play a role in children's retreat from argument-structure overgeneralization errors.
Assuntos
Generalização Psicológica , Julgamento , Desenvolvimento da Linguagem , Semântica , Vocabulário , Adulto , Criança , Pré-Escolar , Comportamento de Escolha , Compreensão , Feminino , Humanos , Masculino , Psicolinguística , Aprendizagem VerbalRESUMO
The P2RX7 receptor is a unique member of a family of extracellular ATP (eATP)-gated ion channels expressed in immune cells, where its activation triggers the inflammatory cascade. Therefore, P2RX7 has been long investigated as a target in the treatment of infectious and inflammatory diseases. Subsequently, P2RX7 signaling has been documented in other physiological and pathological processes including pain, CNS and psychiatric disorders and cancer. As a result, a range of P2RX7 antagonists have been developed and trialed. Interestingly, the recent crystallization of mammalian and chicken receptors revealed that most widely-used antagonists may bind a unique allosteric site. The availability of crystal structures allows rational design of improved antagonists and modeling of binding sites of the known or presumed inhibitors. However, several unanswered questions limit the cogent development of P2RX7 therapies. Firstly, this receptor functions as an ion channel, but its chronic stimulation by high eATP causes opening of the non-selective large pore (LP), which can trigger cell death. Not only the molecular mechanism of LP opening is still not fully understood but its function(s) are also unclear. Furthermore, how can tumor cells take advantage of P2RX7 for growth and spread and yet survive overexpression of potentially cytotoxic LP in the eATP-rich environment? The recent discovery of the feedback loop, wherein the LP-evoked release of active MMP-2 triggers the receptor cleavage, provided one explanation. Another mechanism might be that of cancer cells expressing a structurally altered P2RX7 receptor, devoid of the LP function. Exploiting such mechanisms should lead to the development of new, less toxic anticancer treatments. Notably, targeted inhibition of P2RX7 is crucial as its global blockade reduces the immune and inflammatory responses, which have important anti-tumor effects in some types of malignancies. Therefore, another novel approach is the synthesis of tissue/cell specific P2RX7 antagonists. Progress has been aided by the development of p2rx7 knockout mice and new conditional knock-in and knock-out models are being created. In this review, we seek to summarize the recent advances in our understanding of molecular mechanisms of receptor activation and inhibition, which cause its re-emergence as an important therapeutic target. We also highlight the key difficulties affecting this development.