Fast cholesterol flip-flop and lack of swelling in skin lipid multilayers

Atomistic simulations were performed on hydrated model lipid multilayers that are representative of the lipid matrix in the outer skin (stratum corneum). We find that cholesterol transfers easily between adjacent leaflets belonging to the same bilayer via fast orientational diffusion (tumbling) in the inter-leaflet disordered region, while at the same time there is a large free energy cost against swelling. This fast flip-flop may play an important role in accommodating the variety of curvatures that would be required in the three dimensional arrangement of the lipid multilayers in skin, and for enabling mechanical or hydration induced strains without large curvature elastic costs

Memory rehabilitation for people with multiple sclerosis

Background: This is an update of the Cochrane review ‘Memory rehabilitation for people with multiple sclerosis’ (first published in the Cochrane Library 14 March 2012, Issue 3). Impairments in cognitive function, particularly memory, are common in people with multiple sclerosis (MS) and can potentially affect their ability to complete functional activities. There is evidence from single-case or small group studies that memory rehabilitation can be beneficial for people with MS, but findings from randomised controlled trials (RCTs) and systematic reviews have been inconclusive. Objectives: To determine whether people with MS who received memory rehabilitation showed: 1. better outcomes in their memory functions compared to those given no treatment or receiving a placebo control; and 2. better functional abilities, in terms of activities of daily living, mood, and quality of life, than those who received no treatment or a placebo. Search methods: We searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (2 June 2015) and the following electronic databases: The NIHR Clinical Research Network Portfolio database (NIHR CRN) (from 2010 to June 2015), The Allied and Complementary Medicine Database (AMED) (2010 to June 2015), British Nursing Index (BNI) (2010 to June 2015), PsycINFO (2011 to June 2015), and CAB Abstracts (2010 to June 2015). Start dates for the electronic databases coincided with the last search for the previous review. We handsearched relevant journals and reference lists. Selection criteria: We selected RCTs or quasi-randomised trials ofmemory rehabilitation or cognitive rehabilitation for people with MS in which a memory rehabilitation treatment group was compared to a control group. Selection was conducted independently first and then confirmed through group discussion. We excluded studies that included participants whose memory deficits were the result of conditions other than MS unless we could identify a subgroup of participants with MS with separate results. Data collection and analysis: Three review authors were involved in this update in terms of study selection, quality assessment, and data extraction. We contacted investigators of primary studies for further information where required. We conducted data analysis and synthesis in accordance with the Cochrane Handbook for Systematic Reviews ofInterventions (Higgins 2011). We performed a ’best evidence’ synthesis based on the methodological quality of the primary studies included. Main results: We added seven studies during this update, bringing the total to 15 studies, involving 989 participants. The interventions involved various memory retraining techniques, such as computerised programmes and training on internal and external memory aids. Control groups varied in format from assessment-only groups, discussion and games, non-specific cognitive retraining, and attention or visuospatial training. The risk of bias of the included studies was generally low, but we found eight studies to have high risk of bias related to certain aspects of their methodology. We found significant effect of intervention on objective assessments of memory in both the immediate and long-term follow-ups: standardised mean difference (SMD) 0.23 (95% confidence interval (CI) 0.05 to 0.41) and SMD 0.26 (95% CI 0.03 to 0.49), respectively. We also found significant effect of intervention for quality of life in the immediate follow-up (SMD 0.23 (95% CI 0.05 to 0.41)). These findings showed that the intervention group performed significantly better than the control group. We also found a significant difference for activities of daily living (ADL) in the long-term follow-up (SMD -0.33 (95% CI -0.63 to -0.03)), showing that the control groups had significantly less difficulty completing ADLs than the intervention groups. We found no significant effects, either immediate or long-term, on subjective reports of memory problems (SMD 0.04 (95% CI -0.19 to 0.27) and SMD 0.04 (95% CI -0.19 to 0.27)); on mood (SMD 0.02 (95% CI -0.16 to 0.20) and SMD -0.01 (95% CI -0.21 to 0.20)); and on immediate follow-up for ADL (SMD -0.13 (95% CI -0.60 to 0.33)) and in the long term for quality of life (SMD 0.16 (95% CI -0.03 to 0.36)). We could not complete a sensitivity analysis of intention-to-treat in comparison with per-protocol analysis, due to insufficient information from the included papers. However, a sensitivity analysis of high- versus low-risk studies suggested that while quality of the trials did not affect most outcomes, differences were seen in the objective memory outcomes (both at immediate and long term) and quality of life (immediate) outcome, with studies with higher risk of bias inflating the overall effect size estimates for these outcomes, and the test of overall effect changing from being statistically significant to not significant when studies at high risk of bias were excluded. This suggests that lower-quality studies may have positively influenced the outcomes. Authors’ conclusions: There is some evidence to support the effectiveness of memory rehabilitation on memory function, as well as on quality of life. However, the evidence is limited and does not extend to subjective reports of memory functioning or mood. Furthermore, the objective measures used are not ecologically valid measures, and thus potentially limit generalisability of these findings into daily life. Further robust RCTs of high methodological quality and better quality of reporting, using ecologically valid outcome assessments, are still needed

Monomeric and Dimeric CXCL8 Are Both Essential for In Vivo Neutrophil Recruitment

Rapid mobilization of neutrophils from vasculature to the site of bacterial/viral infections and tissue injury is a critical step in successful resolution of inflammation. The chemokine CXCL8 plays a central role in recruiting neutrophils. A characteristic feature of CXCL8 is its ability to reversibly exist as both monomers and dimers, but whether both forms exist in vivo, and if so, the relevance of each form for in vivo function is not known. In this study, using a ‘trapped’ non-associating monomer and a non-dissociating dimer, we show that (i) wild type (WT) CXCL8 exists as both monomers and dimers, (ii) the in vivo recruitment profiles of the monomer, dimer, and WT are distinctly different, and (iii) the dimer is essential for initial robust recruitment and the WT is most active for sustained recruitment. Using a microfluidic device, we also observe that recruitment is not only dependent on the total amount of CXCL8 but also on the steepness of the gradient, and the gradients created by different CXCL8 variants elicit different neutrophil migratory responses. CXCL8 mediates its function by binding to CXCR2 receptor on neutrophils and glycosaminoglycans (GAGs) on endothelial cells. On the basis of our data, we propose that dynamic equilibrium between CXCL8 monomers and dimers and their differential binding to CXCR2 and GAGs mediates and regulates in vivo neutrophil recruitment. Our finding that both CXCL8 monomer and dimer are functional in vivo is novel, and indicates that the CXCL8 monomer-dimer equilibrium and neutrophil recruitment are intimately linked in health and disease

An Overview of Recent Development in Composite Catalysts from Porous Materials for Various Reactions and Processes

Catalysts are important to the chemical industry and environmental remediation due to their effective conversion of one chemical into another. Among them, composite catalysts have attracted continuous attention during the past decades. Nowadays, composite catalysts are being used more and more to meet the practical catalytic performance requirements in the chemical industry of high activity, high selectivity and good stability. In this paper, we reviewed our recent work on development of composite catalysts, mainly focusing on the composite catalysts obtained from porous materials such as zeolites, mesoporous materials, carbon nanotubes (CNT), etc. Six types of porous composite catalysts are discussed, including amorphous oxide modified zeolite composite catalysts, zeolite composites prepared by co-crystallization or overgrowth, hierarchical porous catalysts, host-guest porous composites, inorganic and organic mesoporous composite catalysts, and polymer/CNT composite catalysts

Observation of Top Quark Production in Proton-Nucleus Collisions

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