Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe

Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

<p>Abstract</p> <p>Background</p> <p>Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population.</p> <p>Methods</p> <p>Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-α, (TNF-α), interleukin-1β (IL-1β), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14 and toll-like receptor 4 (TLR4) was done.</p> <p>Results</p> <p>Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-α, IL-1β, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality.</p> <p>Conclusion</p> <p>We did not find any association between TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis.</p

Cellular changes in boric acid-treated DU-145 prostate cancer cells

Epidemiological, animal, and cell culture studies have identified boron as a chemopreventative agent in prostate cancer. The present objective was to identify boron-induced changes in the DU-145 human prostate cancer cell line. We show that prolonged exposure to pharmacologically-relevant levels of boric acid, the naturally occurring form of boron circulating in human plasma, induces the following morphological changes in cells: increases in granularity and intracellular vesicle content, enhanced cell spreading and decreased cell volume. Documented increases in β-galactosidase activity suggest that boric acid induces conversion to a senescent-like cellular phenotype. Boric acid also causes a dose-dependent reduction in cyclins A–E, as well as MAPK proteins, suggesting their contribution to proliferative inhibition. Furthermore, treated cells display reduced adhesion, migration and invasion potential, along with F-actin changes indicative of reduced metastatic potential. Finally, the observation of media acidosis in treated cells correlated with an accumulation of lysosome-associated membrane protein type 2 (LAMP-2)-negative acidic compartments. The challenge of future studies will be to identify the underlying mechanism responsible for the observed cellular responses to this natural blood constituent

Regional differences in multidimensional aspects of health: findings from the MRC cognitive function and ageing study

BACKGROUND: Differences in mortality and health experience across regions are well recognised and UK government policy aims to address this inequality. Methods combining life expectancy and health have concentrated on specific areas, such as self-perceived health and dementia. Few have looked within country or across different areas of health. Self-perceived health, self-perceived functional impairment and cognitive impairment are linked closely to survival, as well as quality of life. This paper aims to describe regional differences in healthy life expectancy using a variety of states of health and wellbeing within the MRC Cognitive Function and Ageing Study (MRC CFAS). METHODS: MRC CFAS is a population based study of health in 13,009 individuals aged 65 years and above in five centres using identical study methodology. The interviews included self-perceived health and measures of functional and cognitive impairment. Sullivan's method was used to combine prevalence rates for cognitive and functional impairment and life expectancy to produce expectation of life in various health states. RESULTS: The prevalence of both cognitive and functional impairment increases with age and was higher in women than men, with marked centre variation in functional impairment (Newcastle and Gwynedd highest impairment). Newcastle had the shortest life expectancy of all the sites, Cambridgeshire and Oxford the longest. Centre differences in self-perceived health tended to mimic differences in life expectancy but this did not hold for cognitive or functional impairment. CONCLUSION: Self-perceived health does not show marked variation with age or sex, but does across centre even after adjustment for impairment burden. There is considerable centre variation in self-reported functional impairment but not cognitive impairment. Only variation in self-perceived health relates to the ranking of life expectancy. These data confirm that quite considerable differences in life experience exist across regions of the UK beyond basic life expectancy

Glycogen Synthase Kinase 3 (GSK3) Inhibitor, SB-216763, Promotes Pluripotency in Mouse Embryonic Stem Cells

Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months

Regeneration of Pancreatic Non-β Endocrine Cells in Adult Mice following a Single Diabetes-Inducing Dose of Streptozotocin

The non-β endocrine cells in pancreatic islets play an essential counterpart and regulatory role to the insulin-producing β-cells in the regulation of blood-glucose homeostasis. While significant progress has been made towards the understanding of β-cell regeneration in adults, very little is known about the regeneration of the non-β endocrine cells such as glucagon-producing α-cells and somatostatin producing δ-cells. Previous studies have noted the increase of α-cell composition in diabetes patients and in animal models. It is thus our hypothesis that non-β-cells such as α-cells and δ-cells in adults can regenerate, and that the regeneration accelerates in diabetic conditions. To test this hypothesis, we examined islet cell composition in a streptozotocin (STZ)-induced diabetes mouse model in detail. Our data showed the number of α-cells in each islet increased following STZ-mediated β-cell destruction, peaked at Day 6, which was about 3 times that of normal islets. In addition, we found δ-cell numbers doubled by Day 6 following STZ treatment. These data suggest α- and δ-cell regeneration occurred rapidly following a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling techniques, we demonstrated α- and δ-cell regeneration involved cell proliferation. Co-staining of the islets with the proliferating cell marker Ki67 showed α- and δ-cells could replicate, suggesting self-duplication played a role in their regeneration. Furthermore, Pdx1+/Insulin− cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. This is further confirmed by the detection of Pdx1+/glucagon+ cells and Pdx1+/somatostatin+ cells following STZ treatment. Taken together, our study demonstrated adult α- and δ-cells could regenerate, and both self-duplication and regeneration from endocrine precursor cells were involved in their regeneration

Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study

<p>Abstract</p> <p>Background</p> <p>The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1) improve nutrition, (2) increase health literacy and, (3) increase physical activity. This study is a response to this call to action.</p> <p>Methods</p> <p>After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1). Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2).</p> <p>Results</p> <p>There were no significant differences between the two groups in baseline bone mineral density (BMD) or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass). In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition.</p> <p>Both groups experienced a significant positive mean annualized percent change (MAPC) in BMD compared to expectation [AlgaeCal 1: 1.15%, <it>p </it>= 0.001; AlgaeCal 2: 2.79%, <it>p </it>= 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, <it>p </it>= 0.14; AlgaeCal 2: 2.18%, <it>p </it>< 0.001]. The MAPC in AlgaeCal 2 was significantly greater than that in AlgaeCal 1 (<it>p </it>= 0.005). The MAPC contrast between compliant and partially compliant subjects was significant for both plans (<it>p </it>= 0.001 and <it>p </it>= 0.003 respectively). No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group.</p> <p>Conclusions</p> <p>Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from baseline was significantly greater than the increase from baseline in AlgaeCal 1. Increased compliance was associated with greater increases in BMD in both groups. No adverse effects were reported in either group.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01114685">NCT01114685</a></p