278 research outputs found

    Effect of mechanical loading on the metabolic activity of cells in the temporomandibular joint: a systematic review

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    Objectives: The purpose of this systematic review was to elucidate how different modalities and intensities of mechanical loading affect the metabolic activity of cells within the fibro-cartilage of the temporomandibular joint (TMJ). Materials and methods: A systematic review was conducted according to PRISMA guidelines using PubMed, Embase, and Web of Science databases. The articles were selected following a priori formulated inclusion criteria (viz., in vivo and in vitro studies, mechanical loading experiments on TMJ, and the response of the TMJ). A total of 254 records were identified. After removal of duplicates, 234 records were screened by assessing eligibility criteria for inclusion. Forty-nine articles were selected for full-text assessment. Of those, 23 were excluded because they presented high risk of bias or were reviews. Twenty-six experimental studies were included in this systematic review: 15 in vivo studies and 11 in vitro ones. Conclusion: The studies showed that dynamic mechanical loading is an important stimulus for mandibular growth and for the homeostasis of TMJ cartilage. When this loading is applied at a low intensity, it prevents breakdown of inflamed cartilage. Yet, frequent overloading at excessive levels induces accelerated cell death and an increased cartilage degradation

    Sociodemographic factors and delays in the diagnosis of six cancers: analysis of data from the ‘National Survey of NHS Patients: Cancer'

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    This paper aims to explore the relationship between sociodemographic factors and the components of diagnostic delay (total, patient and primary care, referral, secondary care) for these six cancers (breast, colorectal, lung, ovarian, prostate, or non-Hodgkin's lymphoma). Secondary analysis of patient-reported data from the ‘National Survey of NHS patients: Cancer' was undertaken (65 192 patients). Data were analysed using univariate analysis and Generalised Linear Modelling. With regard to total delay, the findings from the GLM showed that for colorectal cancer, the significant factors were marital status and age, for lung and ovarian cancer none of the factors were significant, for prostate cancer the only significant factor was social class, for non-Hodgkin's lymphoma the only significant factor was age, and for breast cancer the significant factors were marital status and ethnic group. Where associations between any of the component delays were found, the direction of the association was always in the same direction (female subjects had longer delays than male subjects, younger people had longer delays than older people, single and separated/divorced people had longer delays than married people, lower social class groups had longer delays than higher social class groups, and Black and south Asian people had longer delays than white people). These findings should influence the design of interventions aimed at reducing diagnostic delays with the aim of improving morbidity, mortality, and psychological outcomes through earlier stage diagnosis

    Seismic behaviour of traditional timber frame walls: experimental results on unreinforced walls

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    Timber frame buildings are well known as an efficient seismic resistant structure and they are used worldwide. Moreover, they have been specifically adopted in codes and regulations during the XVIII and XIX centuries in the Mediterranean area. These structures generally consist of exterior masonry walls with timber elements embedded which tie the walls together and internal walls which have a timber frame with masonry infill and act as shearwalls. In order to preserve these structureswhich characterizemany cities in theworld it is important to better understand their behaviour under seismic actions. Furthermore, historic technologies could be used even in modern constructions to build seismic resistant buildings using more natural materials with lesser costs. Generally, different types of infill could be applied to timber frame walls depending on the country, among which brick masonry, rubble masonry, hay and mud. The focus of this paper is to study the seismic behaviour of the walls considering different types of infill, specifically: masonry infill, lath and plaster and timber frame with no infill. Static cyclic tests have been performed on unreinforced timber frame walls in order to study their seismic capacity in terms of strength, stiffness, ductility and energy dissipation. The tests showed how in the unreinforced condition, the infill is able to guarantee a greater stiffness, ductility and ultimate capacity of the wall.The authors would like to acknowledge Eng. Filipe Ferreira and A.O.F. (Augusto Oliveira Ferreira & C Lda.) for their expertise and collaboration in the construction of the wall specimens. The first author would also like to acknowledge the Portuguese Science and Technology Foundation (FCT) for its financial support through grant SFRH / BD / 61908 / 2009

    Nanogrooved microdiscs for bottom-up modulation of osteogenic differentiation

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    Grooved topographical features have effectively modulated cell differentiation on two-dimensional substrates. To transpose patterning into a 3D environmment, nanogrooved microdiscs, "topodiscs", are produced as cell carriers for bottom-up cell-mediated assembly. While enhancing cell proliferation, topodiscs led to the formation of bone-like aggregates, even in culture medium lacking osteoinductive factors.publishe

    Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration

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    AbstractCyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type. The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated to homozygous mutant males produce few live offspring. COX-1-deficient mice provide a useful model to distinguish the physiological roles of COX-1 and COX-2

    Do diagnostic delays in cancer matter?

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    background: The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis. methods: Scoping review of the published studies, with a focus on methodological issues. results: Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings. conclusion: While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods

    PECAM-Independent Thioglycollate Peritonitis Is Associated With a Locus on Murine Chromosome 2

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    Background: Previous studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background. Methodology/Principal Findings: We have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM. Conclusions/Significance: These data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation

    Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

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    <p>Abstract</p> <p>Background</p> <p>Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.</p> <p>Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC.</p> <p>Methods</p> <p>Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis.</p> <p>Results</p> <p>In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (<it>p </it>= 0.27).</p> <p>In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank <it>p </it>= 0.93).</p> <p>In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank <it>p </it>= 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay (≀median) was 1.8 (95% confidence interval (CI) 1.1 to 3.0; <it>p </it>= 0.01). Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors.</p> <p>Conclusion</p> <p>In symptomatic CRC patients, a longer diagnostic and therapeutic delay in routine clinical practice was not associated with an adverse effect on survival. The time to CRC diagnosis and initiation of treatment did not differ between early stage and late stage colorectal cancer.</p

    Dystroglycan versatility in cell adhesion: a tale of multiple motifs

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    Dystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular a-subunit makes connections with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular matrix and the transmembrane b-subunit makes connections to the actin filament network via cytoskeletal linkers including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatiotemporal regulation
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