Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

From error bounds to the complexity of first-order descent methods for convex functions

This paper shows that error bounds can be used as effective tools for deriving complexity results for first-order descent methods in convex minimization. In a first stage, this objective led us to revisit the interplay between error bounds and the Kurdyka-\L ojasiewicz (KL) inequality. One can show the equivalence between the two concepts for convex functions having a moderately flat profile near the set of minimizers (as those of functions with H\"olderian growth). A counterexample shows that the equivalence is no longer true for extremely flat functions. This fact reveals the relevance of an approach based on KL inequality. In a second stage, we show how KL inequalities can in turn be employed to compute new complexity bounds for a wealth of descent methods for convex problems. Our approach is completely original and makes use of a one-dimensional worst-case proximal sequence in the spirit of the famous majorant method of Kantorovich. Our result applies to a very simple abstract scheme that covers a wide class of descent methods. As a byproduct of our study, we also provide new results for the globalization of KL inequalities in the convex framework. Our main results inaugurate a simple methodology: derive an error bound, compute the desingularizing function whenever possible, identify essential constants in the descent method and finally compute the complexity using the one-dimensional worst case proximal sequence. Our method is illustrated through projection methods for feasibility problems, and through the famous iterative shrinkage thresholding algorithm (ISTA), for which we show that the complexity bound is of the form $O(q^{k})$ where the constituents of the bound only depend on error bound constants obtained for an arbitrary least squares objective with $\ell^1$ regularization

Clinical significance of cardiovascular dysmetabolic syndrome

Although diabetes mellitus is predominantly a metabolic disorder, recent data suggest that it is as much a vascular disorder. Cardiovascular complications are the leading cause of death and disability in patients with diabetes mellitus. A number of recent reports have emphasized that many patients already have atherosclerosis in progression by the time they are diagnosed with clinical evidence of diabetes mellitus. The increased risk of atherosclerosis and cardiovascular complications in diabetic patients is related to the frequently associated dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, and endothelial dysfunction. The evolving knowledge regarding the variety of metabolic, hormonal, and hemodynamic abnormalities in patients with diabetes mellitus has led to efforts designed for early identification of individuals at risk of subsequent disease. It has been suggested that insulin resistance, the key abnormality in type II diabetes, often precedes clinical features of diabetes by 5–6 years. Careful attention to the criteria described for the cardiovascular dysmetabolic syndrome should help identify those at risk at an early stage. The application of nonpharmacologic as well as newer emerging pharmacologic therapies can have beneficial effects in individuals with cardiovascular dysmetabolic syndrome and/or diabetes mellitus by improving insulin sensitivity and related abnormalities. Early identification and implementation of appropriate therapeutic strategies would be necessary to contain the emerging new epidemic of cardiovascular disease related to diabetes

Depurated fish as an alternative reference for field-based biomarker monitoring

The whole of the Swan-Canning Estuary, in the south-west of Australia, is impacted by human activity, and the selection of a local reference site to assess the impact of environmental contamination on the health of biota is not possible. To determine whether fish depurated under laboratory conditions could be used as an alternative to a reference site; adult black bream (Acanthopagrus butcheri) were collected from the estuary and maintained in clean water (S24) for 3 months. A suite of biomarkers of fish health were assessed, and the results were compared with field-captured black bream from three sites within the estuary (Ascot, Claisebrook, and Riverton). Comparisons of a subset of biomarkers were also made between hatchery-bred juvenile fish and the depurated fish. Biomarker levels were up to 3.8 times higher in field captured fish compared with depurated fish, while DNA integrity was lower. EROD activity was comparable in the hatchery-bred black bream to the depurated fish while s-SDH levels were two times higher in the hatchery fish. From the results obtained, field-captured black bream depurated for 3 months are suitable to determine reference/baseline levels for biomarker of health studies in estuarine environments

Perceived barriers to integrated care in rheumatoid arthritis: views of recipients and providers of care in an inner-city setting

<p>Abstract</p> <p>Background</p> <p>A number of recent reports published in the UK have put the quality of care of adults with Rheumatoid Arthritis (RA) centre stage. These documents set high standards for health care professionals and commissioning bodies that need to be implemented into routine clinical practice. We therefore have obtained the views of recipients and providers of care in inner city settings as to what they perceive are the barriers to providing integrated care.</p> <p>Methods</p> <p>We conducted focus groups and face to face interviews between 2005-8 with 79 participants (patients, carers, specialist medical and nursing outpatient staff and general practitioners (GPs)) working in or attending three hospitals and three primary care trusts (PCT).</p> <p>Results</p> <p>Three barriers were identified that stood in the way of seamless integrated care in RA from the perspective of patients, carers, specialists and GPs: (i) early referral (e.g. 'gate keeper's role of GPs); (ii) limitations of ongoing care for established RA (e.g. lack of consultation time in secondary care) and (iii) management of acute flares (e.g. pressure on overbooked clinics).</p> <p>Conclusion</p> <p>This timely study of the multi-perspective views of recipients and providers of care was conducted during the time of publications of many important reports in the United Kingdom (UK) that highlighted key components in the provision of high quality care for adults with RA. To achieve seamless care across primary and secondary care requires organisational changes, greater personal and professional collaboration and GP education about RA.</p

Microglia and Microglia-Like Cell Differentiated from DC Inhibit CD4 T Cell Proliferation

The central nervous system (CNS) is generally regarded as a site of immune privilege, whether the antigen presenting cells (APCs) are involved in the immune homeostasis of the CNS is largely unknown. Microglia and DCs are major APCs in physiological and pathological conditions, respectively. In this work, primary microglia and microglia-like cells obtained by co-culturing mature dendritic cells with CNS endothelial cells in vitro were functional evaluated. We found that microglia not only cannot prime CD4 T cells but also inhibit mature DCs (maDCs) initiated CD4 T cells proliferation. More importantly, endothelia from the CNS can differentiate maDCs into microglia-like cells (MLCs), which possess similar phenotype and immune inhibitory function as microglia. Soluble factors including NO lie behind the suppression of CD4 T cell proliferation induced by both microglia and MLCs. All the data indicate that under physiological conditions, microglia play important roles in maintaining immune homeostasis of the CNS, whereas in a pathological situation, the infiltrated DCs can be educated by the local microenvironment and differentiate into MLCs with inhibitory function

Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution

During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

Relation of DNA Methylation of 5′-CpG Island of ACSL3 to Transplacental Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Childhood Asthma

In a longitudinal cohort of ∼700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5′-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5′-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m3 (OR = 13.8; p<0.001; sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9; p<0.05). Thus, if validated, methylated ACSL3 5′CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposure-disease relationships in birth cohorts. The results support the emerging theory of early origins of later life disease development