Endotoxaemia and acute pancreatitis: correlation between the severity of the disease and the anti-enterobacterial common antigen antibody titre

Enterobacterial common antigen is a highly immunogenic component of the Gram negative bacterial cell wall that is common to all enteric bacteria. In the present study, the humoral antibody response against enteric bacteria was investigated by measuring antibodies to enterobacterial common antigen in paired serum samples in 38 patients with acute pancreatitis and in 31 healthy subjects. In mild pancreatitis (11 patients), no changes in anti-enterobacterial common antigen titres were observed as compared with healthy controls. Nine of the 10 patients had a significant increase (greater than or equal to 8 times) in anti-enterobacterial common antigen titres during the disease. Similarly, in patients with fulminant (haemorrhagic) pancreatitis who survived, a significant increase in anti-enterobacterial common antigen titres occurred during the course of the disease (in nine of the 11 patients). Paradoxically, only one of the six patients with fulminant pancreatitis with fatal outcome showed a significant increase in his anti-enterobacterial common antigen titre. The results suggest that Gram negative bacterial components escape into the systemic circulation in acute pancreatitis. This may have pathophysiologic significance in this disease.     

Plasma Levels of Nitrites/Nitrates in Patients with Chronic Atrial Fibrillation are Increased after Electrical Restoration of Sinus Rhythm

Introduction: Patients with persistent atrial fibrillation (AF) have hemodynamic changes, which impair endothelial cell function resulting in decreased nitric oxide (NO) production. The aim of this work was to assess endothelial function in AF patients before and at various time points after cardioversion. Methods: Forty-two patients with AF and 21 normal and age-adjusted healthy controls were studied. Nitrites and nitrates (NO _x ) and von Willebrand factor (vWf) concentrations were measured on blood samples taken just before cardioversion and over a 30 day period after the procedure. Results: Plasma levels of NO _x in AF were significantly lower compared to healthy controls (p < 0.001), but after cardioversion gradually increased to approach to those of the healthy controls by the end of the first month of sustained sinus rhythm (p = 0.004). Interestingly plasma levels of NO _x were negatively correlated to left atrial volume measured by ultrasonography (r = –0.34, p < 0.05). Plasma levels of vWf in AF patients were significantly higher compared to the healthy controls (p < 0.01) but with sustained sinus rhythm decreased (p = 0.02). Conclusion: The parallel normalization of the NO _x titers and vWf levels suggests that vascular endothelial function improves after 30 days of normal sinus rhythm.     

The Relationship between Subjective Cognitive Impairment and Activity Participation: A Systematic Review

ABSTRACT

This systematic review synthesizes current evidence to determine how subjective cognitive impairment (SCI) relates to physical, cognitive, and social activity participation in older adults. Nine peer-reviewed articles were reviewed and appraised for evidence quality. Most were cross-sectional and had high methodological quality. Higher levels of SCI were almost universally associated with lower levels of physical and social activity participation. These findings suggest that older adults who report higher SCI engage in fewer activities. Examining these relationships longitudinally is an important next step to determine whether SCI precedes withdrawing from activities in older adults.     

ASIC proteins regulate smooth muscle cell migration

The purpose of the present study was to investigate Acid Sensing Ion Channel (ASIC) protein expression and importance in cellular migration. We recently demonstrated that Epithelial Na(+)Channel (ENaC) proteins are required for vascular smooth muscle cell (VSMC) migration; however, the role of the closely related ASIC proteins has not been addressed. We used RT-PCR and immunolabeling to determine expression of ASIC1, ASIC2, ASIC3 and ASIC4 in A10 cells. We used small interference RNA to silence individual ASIC expression and determine the importance of ASIC proteins in wound healing and chemotaxis (PDGF-bb)-initiated migration. We found ASIC1, ASIC2, and ASIC3, but not ASIC4, expression in A10 cells. ASIC1, ASIC2, and ASIC3 siRNA molecules significantly suppressed expression of their respective proteins compared to non-targeting siRNA (RISC) transfected controls by 63%, 44%, and 55%, respectively. Wound healing was inhibited by 10, 20, and 26% compared to RISC controls following suppression of ASIC1, ASIC2, and ASIC3, respectively. Chemotactic migration was inhibited by 30% and 45%, respectively, following suppression of ASIC1 and ASIC3. ASIC2 suppression produced a small, but significant, increase in chemotactic migration (4%). Our data indicate that ASIC expression is required for normal migration and may suggest a novel role for ASIC proteins in cellular migration.     

Action capability constrains visuo-motor complexity during planning and performance in on-sight climbing

The capability to adapt to changing conditions is crucial for safe and successful performance in physical activities and sports. According to the affordance-based control perspective, individuals act in such a way as to take into account the limits of their capability to act. However, it is not clear how strength interacts with skill in shaping performer-environment interactions. We, therefore, determined whether fingertip strength influences patterns of gaze and climbing behavior on new routes of ever-increasing difficulty. We expected that comparatively weaker climbers would show less complex behavior because of an inability to perceive and act. Stronger climbers would show more complex visuo-motor behavior because more opportunities for action remain, even as route difficulty increases. For very strong climbers the route would not be challenging enough, and less complex patterns suffice. Twenty climbers, ranging from lower grade to elite level participated. Maximum fingertip strength was obtained. Participants previewed and then climbed two separate 3 m long traverses, gradually decreasing in edge depth. Gaze and hip positions were collected for subsequent computation of gaze transition entropy (during preview) and hip displacement entropy (during climbing). Data revealed statistically significant curvilinear relationships between both fingertip strength and gaze transition entropy, and fingertip strength, and hip displacement entropy. Visuo-motor complexity is scaled by how close the individual must act relative to boundaries of what the environment affords and does not afford for action given the individual constraints. Future research should examine in greater detail relationships between action capabilities and functional movement variability.     

‘Your whole life is lived through your teeth’: biographical disruption and experiences of tooth loss and replacement

The experience and meaning of tooth loss and replacement has varied historically and culturally but has received relatively little attention from social scientists. Our study set out to understand these experiences in the context of the arrival of newer, dental implant treatments. Semi‐structured qualitative interviews were carried out with 39 men and women who had experienced tooth loss and replacement. A thematic analysis was sensitised by previous sociological work on chronic illness, particularly Bury's notion of biographical disruption. We found that while for some individuals the loss of a tooth was relatively insignificant, for others it was devastating and disruptive. In seeking to understand this difference, the concept of biographical disruption was a helpful analytical tool. Our analysis identified two forms of disruption. The first related to the meanings of tooth loss (the neglected mouth) and denture wearing (a marker of old age). The second, embodied, disruption concerned the relationship between the self and mouth in those wearing dentures (the invaded, unreliable mouth) and could occur even where tooth loss and denture wearing had been biographically anticipated.     

A high‐throughput LC‐MS/MS screen for GHRP in equine and human urine,featuring peptide derivatization for improved chromatography

The growth hormone releasing peptides (GHRPs) hexarelin, ipamorelin, alexamorelin, GHRP‐1, GHRP‐2, GHRP‐4, GHRP‐5, and GHRP‐6 are all synthetic met‐enkephalin analogues that include unnatural D‐amino acids. They were designed specifically for their ability to stimulate growth hormone release and may serve as performance enhancing drugs. To regulate the use of these peptides within the horse racing industry and by human athletes, a method is presented for the extraction, derivatization, and detection of GHRPs from equine and human urine. This method takes advantage of a highly specific solid‐phase extraction combined with a novel derivatization method to improve the chromatography of basic peptides. The method was validated with respect to linearity, repeatability, intermediate precision, specificity, limits of detection, limits of confirmation, ion suppression, and stability. As proof of principle, all eight GHRPs or their metabolites could be detected in urine collected from rats after intravenous administration. Copyright © 2014 John Wiley & Sons, Ltd.     

Genetic interaction between the non-homologous end-joining factors during B and T lymphocyte development: In vivo mouse models

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double-strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, MRI) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.     

Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†

Relapse‐enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet‐based polymerase chain reaction to establish whether relapse‐enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.