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Purpose: Anastomotic leakage (AL) is associated with increased morbidity and mortality after colorectal surgery. Calcification of the arteries has been identified as a risk factor for cardiovascular events and can be reliably measured on computed tomography using software assistance. The aim of this prospective study was to prove the value of calcium scoring of the iliac arteries as a predictor of AL after rectal anastomosis. Methods: Consecutive patients who underwent colorectal resection with rectal anastomosis were analyzed. Diagnostic computed tomography images were used to detect calcification of the arteries supplying the rectal anastomosis. Logistic regression analysis was used to determine the relationship between vascular calcification and AL. Results: Of 139 included and analyzed patients, AL occurred in 15 (11%). The volume and calcium scores were significantly higher in the infrarenal aorta, the left and right common iliac artery, and the left internal iliac artery. In univariate analysis, calcification of the left internal iliac artery and both internal iliac arteries combined correlated with the occurrence of the primary endpoint. A receiver operating curve analysis led to the cut-off values of 30 and 6 for the volume score and calcium score, respectively. They provide a negative predictive value of 0.97 and a positive predictive value of 0.19. Conclusions: Calcification in the iliac arteries appears to be a good marker for the risk of leakage after rectal anastomosis. The calcification scoring system is easy to calculate after computed tomography and may aid in patient selection to create a protective ileostomy. [ABSTRACT FROM AUTHOR]

ABSTRACT Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen-induced arthritis (AIA) mouse model with methylated bovine serum albumin (mBSA) as well as a modified model with mutated citrullinated vimentin (MCV) alone or in combination with mBSA. Periarticular bone loss, subchondral osteoclastogenesis, as well as local expression of cytokines, osteoclast genes, and peptidyl-arginine deiminase (PAD) enzymes were assessed after arthritis induction. Immune cell and osteoclast precursor infiltration were detected in the periarticular bone marrow and local lymph nodes. In addition, periarticular bone loss was assessed upon challenge of mice with purified anti-MCV antibody. Despite inducing a milder form of arthritis than mBSA, MCV triggered significant periarticular bone loss associated with an increased infiltration of osteoclast precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced the expression of the osteoclast inducers RANKL and M-CSF, the cytokines IL-8, IL-1, IL-6, and TNF-α, as well as PAD2 and PAD4 enzymes in the periarticular bone marrow. Furthermore, also anti-MCV antibody challenge induced significant periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity against citrullinated vimentin triggers periarticular bone loss by osteoclast activation in the bone marrow. These findings may explain why periarticular bone loss is already found very early in the disease course of patients with rheumatoid arthritis. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The prevalence of neurodegenerative disease and arthritis increases with age. Despite both processes being associated with immune activation and inflammation, little is known about the mechanistic interactions between neurodegenerative disease and arthritis. In this article, we show that tau-transgenic (tau-tg) mice that develop neurodegenerative disease characterized by deposition of tau tangles in the brain are highly susceptible to developing arthritis. Already at steady-state conditions, tau-tg mice exhibit peripheral immune activation that is manifested by higher numbers of granulocytes, plasmablasts, and inflammatory Ly6Chi CCR2+ monocytes, as well as increased levels of proinflammatory cytokines, such as TNF-α and IL-17. Upon induction of collagen-induced arthritis (CIA), tau-tg mice displayed an increased incidence and an earlier onset of CIA that was associated with a more pronounced inflammatory cytokine response. Furthermore, induction of CIA led to significantly elevated numbers of Iba-1-expressing cells in the brain, indicative of microglia activation, and the formation of anti-tau Abs in tau-tg mice. These changes were accompanied by the resolution of tau tangles and significantly decreased neurodegenerative pathology. In summary, these data show that neurodegenerative disease enhances the development of arthritis. In addition, arthritis, once induced, triggers innate immune responses in the brain, leading to resolution of neurodegenerative changes. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to assess the use of continuous epidural analgesia in pediatric patients undergoing major abdominal tumor surgery. Methods: Children undergoing major abdominal tumor surgery at our institution between 2008 and 2012 (n=40) received continuous epidural analgesia via an epidural catheter. Surgical trauma scores, pain scores, and clinical data of the children were compared to a pair-matched historical control group operated on between 2002 and 2007 without epidural analgesia. Results: Pain levels in the study group on day 1 and 3 after surgery were lower compared to the control group. The differences did, however, not reach statistical significance (p =0.15 and 0.09). Children in the study group received significantly fewer additional doses of piritramide or morphine (45% versus 82%, p <0.001). Despite significantly higher surgical trauma scores in the study group (p=0.018), there were no statistical differences regarding clinical parameters, such as mechanical ventilation time, time on intensive care unit, and total hospital stay. There were no catheter-related complications. Conclusions: Continuous epidural analgesia is beneficial for children undergoing complex abdominal tumor surgery with regard to pain levels, postoperative recovery, and general clinical course. Expertise of the managing team, a careful patient selection, and a continuous quality assessment are essential for success. [Copyright &y& Elsevier]

Objective: To determine if B cell activating factor of the tumor necrosis factor family (BAFF) acts as an acute phase reactant and predicts severity of acute pancreatitis. Methods:40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III) and the clinical course of the patient (treatment, duration of stay, duration ICU) were recorded. Results: Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03) similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 ). Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948) and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843) serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes. Conclusion:This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response. [ABSTRACT FROM AUTHOR]

Data from captive animals indicated that browsing (BR) ruminants have larger fecal particles-indicative of lesser chewing efficiency-than grazers (GR). To answer whether this reflects fundamental differences between the animal groups, or different reactions of basically similar organisms to diets fed in captivity, we compared mean fecal particle size (MPS) in a GR and a BR ruminant (aurox Bos primigenius taurus, giraffe Giraffa camelopardalis) and a GR and a BR hindgut fermenter (Przewalski's horse Equus ferus przewalskii, lowland tapir Tapirus terrestris), both from captivity and from the wild. As would be expected owing to a proportion of finely ground, pelleted feeds in captive diets, MPS was smaller in captive than free-ranging GR. In contrast, MPS was drastically higher in captive than in free-ranging BR of either digestion type. Thus, the difference in MPS between GR and BR was much more pronounced among captive than free-ranging animals. The results indicate that BR teeth have adapted to their natural diet so that in the wild, they achieve a particle size reduction similar to that of GR. However, although GR teeth seem equally adapted to food ingested in captivity, the BR teeth seem less well suited to efficiently chew captive diets. In the case of ruminants, less efficient particle size reduction could contribute to potential clinical problems like 'rumen blockage' and bezoar formation. Comparisons of MPS between free-ranging and captive animals might offer indications for the physical suitability of zoo diets. Zoo Biol 27:70-77, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

VB17+ TCR dominate in Ni-driven T cell cultures from highly Ni-sensitized patients. Using transfection of TCR from three CD4+, VB17+, Ni-specific human T cell clones, we studied their Ni–MHC contacts by site-directed TCR mutation and combination of α and β chains between different TCR. All three TCR exhibited N-nucleotide-determined Arg–Asp motifs in their CDR3-β sequences. Two of them were specifically restricted to HLA-DR13, while the third one accepted a variety of HLA-DR alleles. The highly similar α or β chains of the DR13-restricted TCR were interchangable without loss of specificity, but α or β chains of other TCR were not tolerated. Mutations of their Arg–Asp motif revealed loss of reactivity upon exchanging Asp for Glu or Ala and of Arg for Ala but not of Arg for Lys or the Ni binding His. Reactivity was also destroyed by mutation of α chain position 51, proposed as a general contact site for MHC. Hence, in these two TCR the Arg–Asp motif is clearly involved in contacting Ni–MHC complexes, and close cooperation between α and β chain is required. In contrast, the third TCR retained Ni reactivity upon mutation of α chain position 51 or of its β chain Arg–Asp motif, which rather affected the pattern of DR cross-restriction. Moreover, its α chain paired with various β chains from other, even mouse TCR, irrespective of their specificity, retaining Ni reactivity as well as promiscuous HLA-DR restriction. This preponderance of an α chain in defining specificity indicates fundamental differences in Ni interactions of individual TCR and implies that β chain similarities may not necessarily result from antigen selection. [ABSTRACT FROM PUBLISHER]

Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor. [ABSTRACT FROM AUTHOR]

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation. [ABSTRACT FROM AUTHOR]

A correction to the article "Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against Citrullinated Vimentin" is presented.

Several health promoting effects have been reported for maqui berry, rich in anthocyanins. Direct effects of anthocyanins as well as bioactive metabolites might be involved. Within the study, bioavailability of a proprietary standardized maqui berry extract Delphinol® was investigated based on two selected anthocyanins (delphinidin-3-O-glucoside (DS) + cyanidin-3-O-sambubioside (CS)) and two breakdown products (protocatechuic acid (PCA) + gallic acid (GA)) after a single-dose supplementation in humans. Pharmacokinetic parameters were calculated from individual concentration time curves. In all 12 subjects a significant increase was noted in plasma values of DG and CS after intake of maqui berry extract. Maximum concentration of DG was observed after 1.0 ± 0.3 h and CS after 2.0 ± 1.1 h. Within 8 h, concentrations nearly returned to baseline levels. The results confirm a fast uptake and metabolism of the two selected key substances. Additionally, the phenolic acids GA and PCA were observed as breakdown products of anthocyanins. In summary, the study clearly confirms the bioavailability of maqui berry extract and its specific anthocyanin compounds and related breakdown products in healthy subjects. [ABSTRACT FROM AUTHOR]

Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarization of microglia. In steady-state microglia, ubiquitous neuronal-derived stress signals such as ATP induced expression of this NR, which contributed to the maintenance of a resting and noninflammatory microglia phenotype. Global and microglia-specific deletion of Nr4a1 triggered the spontaneous and overwhelming activation of microglia and resulted in increased cytokine and NO production as well as in an accelerated and exacerbated form of experimental autoimmune encephalomyelitis. Ligand-induced activation of Nr4a1 accordingly ameliorated the course of this disease. Our current data thus identify Nr4a1 as regulator of microglia activation and potentially new target for the treatment of inflammatory CNS diseases such as multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background/aims: The objective of this study was to assess the outcome in a large unselected population of patients with acute pancreatitis treated at a single university center., Methodology: We performed a retrospective analysis of 364 patients with acute pancreatitis and evaluated outcome, morbidity and mortality in relation to different treatment modalities., Results: 238 patients suffered from interstitial-edematous pancreatitis, 126 patients from the necrotizing form. ICU treatment was necessary for 174 patients (48%). Minimally-invasive CT guided drainage techniques were used in 73 patients (20%) with pancreatic necroses but also in seven patients with edematous pancreatitis (2%), which showed extrapancreatic tissue necrosis. The overall hospital mortality was 14% (5.5% for patients with edematous pancreatitis vs. 30% for patients with necrotizing pancreatitis)., Conclusions: In patients with the edematous form a small subpopulation showed peripancreatic tissue necrosis without necrosis of the pancreas itself, which was related to higher mortality rates than expected for patients with edematous pancreatitis. Regarding therapeutic procedures interventional treatment modalities should be considered as alternative treatment modalities.