22 research outputs found

    Determination of horizon size in state-based peridynamics

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    Peridynamics is based on integro-differential equations and has a length scale parameter called horizon which gives peridynamics a non-local character. Currently, there are three main peridynamic formulations available in the literature including bond-based peridynamics, ordinary state-based peridynamics and non-ordinary state-based peridynamics. In this study, the optimum horizon size is determined for ordinary state-based peridynamics and non-ordinary state-based peridynamics formulations by using uniform and non-uniform discretisation under dynamic and static conditions. It is shown that the horizon sizes selected as optimum sizes for uniform discretisation can also be used for non-uniform discretisation without introducing significant error to the system. Moreover, a smaller horizon size can be selected for non-ordinary state-based formulation which can yield significant computational advantage. It is also shown that same horizon size can be used for both static and dynamic problems

    Selective attrition and bias in a longitudinal health survey among survivors of a disaster

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    BACKGROUND: Little is known about the response mechanisms among survivors of disasters. We studied the selective attrition and possible bias in a longitudinal study among survivors of a fireworks disaster. METHODS: Survivors completed a questionnaire three weeks (wave 1), 18 months (wave 2) and four years post-disaster (wave 3). Demographic characteristics, disaster-related factors and health problems at wave 1 were compared between respondents and non-respondents at the follow-up surveys. Possible bias as a result of selective response was examined by comparing prevalence estimates resulting from multiple imputation and from complete case analysis. Analysis were stratified according to ethnic background (native Dutch and immigrant survivors). RESULTS: Among both native Dutch and immigrant survivors, female survivors and survivors in the age categories 25–44 and 45–64 years old were more likely to respond to the follow-up surveys. In general, disasters exposure did not differ between respondents and non-respondents at follow-up. Response at follow-up differed between native Dutch and non-western immigrant survivors. For example, native Dutch who responded only to wave 1 reported more depressive feelings at wave 1 (59.7%; 95% CI 51.2–68.2) than Dutch survivors who responded to all three waves (45.4%; 95% CI 41.6–49.2, p < 0.05). Immigrants who responded only to wave 1 had fewer health problems three weeks post-disaster such as depressive feelings (M = 69.3%; 95% CI 60.9–77.6) and intrusions and avoidance reactions (82.7%; 95% CI 75.8–89.5) than immigrants who responded to all three waves (respectively 89.9%; 95% CI 83.4–96.9 and 96.3%; 95% CI 92.3–100, p < .01). Among Dutch survivors, the imputed prevalence estimates of wave 3 health problems tended to be higher than the complete case estimates. The imputed prevalence estimates of wave 3 health problems among immigrants were either unaffected or somewhat lower than the complete case estimates. CONCLUSION: Our results indicate that despite selective response, the complete case prevalence estimates were only somewhat biased. Future studies, both among survivors of disasters and among the general population, should not only examine selective response, but should also investigate whether selective response has biased the complete case prevalence estimates of health problems by using statistical techniques such as multiple imputation

    In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization

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    Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention

    Regeneração do fígado de ratos após oclusão parcial da drenagem venosa hepática Hepatic regeneration after parcial oclusion of hepatic vein drainage in rats

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    INTRODUÇÃO: A regeneração hepática é um mecanismo para superar a perda de tecido funcional do fígado. Este processo é estudado através de diferentes métodos. OBJETIVO: Avaliar o efeito da oclusão parcial da drenagem venosa hepática sobre a regeneração do fígado remanescente de ratos submetidos à hepatectomia parcial. MÉTODO: Foram colhidas biópsias de fígado em 30 ratos Wistar machos, e a seguir realizada hepatectomia a dois terços. Os animais foram divididos em três grupos: um grupo controle e dois grupos de estudo, submetidos a diferentes graus de estenose da veia hepática direita. Após 96 horas do estímulo para regeneração hepática, todos submeteram-se à outra biópsia hepática. Analisaram-se os fragmentos por imunoistoquímica para os marcadores Ki-67 e fator de von Willebrand. Para a leitura das amostras utilizou-se o sistema SAMBA 4000. A deposição de colágeno foi avaliada pela coloração tricrômico de Masson. RESULTADOS: A proliferação celular dos animais submetidos à hepatectomia parcial e estenose moderada ou severa da veia hepática direita persistiu mais elevada quando comparada ao grupo controle. O Índice de Marcação para o Ki-67 foi significativamente mais elevado após a hepatectomia nos grupos submetidos à oclusão parcial da veia hepática, tanto moderada quanto severa. A expressão de fator de von Willebrand estava diminuída após a hepatectomia parcial nos três grupos. Houve pouco depósito de colágeno no tecido hepático nos animais dos dois grupos com estenose da veia hepática direita. CONCLUSÃO: A oclusão parcial da drenagem venosa hepática em ratos submetidos à hepatectomia parcial prolonga o tempo de proliferação de células hepáticas quando comparado aos animais com veias de calibre normal. Como consequência, também houve atraso na restauração da matriz extracelular e na formação de novos vasos sinusoidais.<br>BACKGROUND: Hepatic regeneration is a mechanism to overcome the loss of liver functional tissue. This process has been studied through different methods. AIM: To evaluate the effect of the partial occlusion of the hepatic venous drainage on the regeneration of the remainder livers in rats submitted to partial hepatectomy. METHOD: Liver biopsies from 30 male Wistar rats were collected, and after they were submitted two-third hepatectomy. The animals were divided in three groups: a control group and two study groups, which were submitted to different degrees of the right hepatic vein stenosis. After 96 hours of the stimulation for regeneration all rats were submitted to another hepatic biopsy. The analysis of the fragments was performed by immunohistochemistry for the Ki-67 and von Willebrand factor markers. The reading of the samples was done using the SAMBA 4000 system. Collagen deposition was evaluated by the trichromic Masson's staining. RESULT: The cellular proliferation of the animals submitted to partial hepatectomy and stenosis of the right hepatic vein persists higher when compared to control group. The Label Index for Ki-67 was significantly higher post-hepatectomy in groups submitted to hepatic vein partial occlusion. The expression of von Willebrand factor was strongly decreased after the hepatectomy in all groups. There was little deposit of collagen in the hepatic tissue of animals with hepatic vein stenosis. CONCLUSION: Partial occlusion of the hepatic venous drainage in rats submitted to partial hepatectomy prolongs the time of hepatic cells proliferation when compared to the animals with vein of normal caliber. Consequently, there will be also a delay in the restoration of the extracellular matrix and in the formation of new sinusoidal vessels

    Is there an association between obstructive sleep apnea syndrome and periodontal inflammation?

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    WOS: 000374562300003PubMed ID: 26232894Objectives The aim of this study is to assess salivary, serum biomarkers, and subgingival bacteria as putative candidates in the potential association between obstructive sleep apnea syndrome (OSAS) and periodontal disease. Materials and methods Fifty-two patients were grouped according to the severity of OSAS: 13 participants served as controls, 17 patients had mild-to-moderate OSAS, and 22 severe OSAS. Serum, saliva, and subgingival plaque samples were collected, and clinical periodontal parameters were recorded. Salivary, serum concentrations of interleukin-6 (IL-6), tumour necrosis factor (TNF-alpha), osteoprotegerin, soluble Receptor activator of nuclear factor kappa B ligand (sRANKL), and apelin were analysed by enzyme-linked immunosorbent assay. Bacterial counts were determined by real-time QPCR on plaque microbial DNA preparations. Results There was a significant change in the composition of microbes in plaque particularly in severe OSAS samples (p < 0.01). Statistical analyses indicated significantly higher salivary IL-6 levels in both OSAS groups compared to controls (p < 0.05). Salivary apelin levels were significantly higher in the severe OSAS group compared to the control group. Serum levels of these biomarkers and salivary osteoprotegerin, sRANKL levels were similar in the study groups. The incidence and duration of apnea positively correlated with clinical periodontal parameters (p < 0.05). Conclusion OSAS appeared to alter the tested bacteria in plaque, correlate with increasing periodontal disease severity, have additive effect on salivary IL-6
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