Plos One
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Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questions remain as to the timing and sequence of therapies and the role of radiotherapy for unresectable PDAC. ⋯ We found that a smaller LAI leads to a larger metastatic burden. Furthermore, our analyses ascertain that i) radiotherapy after induction chemotherapy improves survival in cases receiving induction FFX or with larger LAI, ii) neoadjuvant chemotherapy improves survival in cases with resectable PDAC, and iii) temporary cessations of chemotherapies do not impact overall survival, which supports the feasibility of treatment holidays for patients with FFX-associated adverse effects. Our findings inform clinical decision-making for PDAC patients and allow for the rational design of clinical strategies using FFX, GEM, GEM+nab-paclitaxel, neoadjuvant chemotherapy, and radiation.
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We investigated whether supplementation with the barley line BARLEYmax (Tantangara; BM), which contains three fermentable fibers (fructan, β-glucan, and resistant starch), modifies the microbiota in cecal and distal colonic digesta in addition to short-chain fatty acids (SCFAs) production more favorably than supplementation with a high-β-glucan barley line (BG012; BG). Male Sprague-Dawley rats were randomly divided into 3 groups that were fed an AIN-93G-based diet that contained 5% fiber provided by cellulose (control), BM or BG. Four weeks after starting the respective diets, the animals were sacrificed and digesta from the cecum, proximal colon and distal colon were collected and the SCFA concentrations were quantified. ⋯ These results indicated that BM increased the concentration of total SCFAs in the distal colonic digesta. These changes might have been caused by fructan and resistant starch in addition to β-glucan. In conclusion, fermentable fibers in BM reached the distal colon and modified the microbiota, leading to an increase in the concentration of total SCFAs in the distal colonic digesta, more effectively compared with the high-β-glucan barley line (BG).
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Chronic pain is among the most burdensome conditions. Its prevalence ranges between 12% and 30% in Europe, with an estimated 21% among Austrian adults. The economic impact of chronic pain from a societal perspective, however, has not been sufficiently researched. This study aims to provide an estimate of the societal costs for working-age adults with chronic pain in Austria. It explores the impact of sex, number of pain sites, self-reported pain severity, health literacy and private health insurance on costs associated with chronic pain. ⋯ This study is the first to provide a comprehensive assessment of the individual and societal burden of chronic pain in Austria. It highlights that chronic pain is associated with substantial direct medical costs and productivity losses. Patient costs may show systematic differences by health insurance status, implying a need for future research in this area.
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The endothelial glycocalyx constitutes part of the endothelial barrier but its degradation leaves endothelial cells exposed to transmigrating cells and circulating mediators that can damage the barrier or promote intercellular gaps. Syndecan proteins are key components of the endothelial glycocalyx and are shed during disease states where expression and activity of proteases such as thrombin are elevated. We tested the ability of thrombin to cleave the ectodomains of syndecans and whether the products could act directly on endothelial cells to alter barrier function. ⋯ We suggest that thrombin can cleave syndecan-3/4 ectodomain into fragments which interact with endothelial cells causing paracellular hyperpermeability. This may have important implications in the pathogenesis of vascular dysfunction during sepsis or thrombotic disease states where thrombin is activated.
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To assess the association between salivary ultrasonography (sUS) findings and disease activity and damage in patients with primary Sjogren's syndrome (pSS). We investigated the potential prognostic role of sUS as a tool in the assessment of disease activity. ⋯ Pathological salivary gland ultrasonography is associated with high disease activity and damage in pSS. Consequently, sUS abnormalities might be surrogate items for glandular domains in the assessment of disease activity and damage. Thus, ultrasonography of the salivary gland combined with clinical and serological markers might be part of the next prognostic and therapeutic algorithm in the near future.