Final report of the Construction Industry Institute, Hong Kong research project on reinventing the Hong Kong construction industry for its sustainable development

Author name used in this publication: Andrew N. BaldwinAuthor name used in this publication: Y. H. ChiangAuthor name used in this publication: Joyce W. S. CheungAuthor name used in this publication: Joanne W. S. NgConstruction Industry Institute-Hong Kong Report, no. 132008-2009 > Academic research: not refereed > Research book or monograph (author)Other Versio

Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St John’s College, Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals (CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm

Examining the variability of neurocognitive functioning in individuals at clinical high risk for psychosis: a meta-analysis

This study aims to meta-analytically characterize the presence and magnitude of within-group variability across neurocognitive functioning in young people at Clinical High-Risk for psychosis (CHR-P) and comparison groups. Multistep, PRISMA/MOOSE-compliant systematic review (PROSPERO-CRD42020192826) of the Web of Science database, Cochrane Central Register of Reviews and Ovid/PsycINFO and trial registries up to July 1, 2020. The risk of bias was assessed using a modified version of the NOS for cohort and cross-sectional studies. Original studies reporting neurocognitive functioning in individuals at CHR-P compared to healthy controls (HC) or first-episode psychosis (FEP) patients were included. The primary outcome was the random-effect meta-analytic variability ratios (VR). Secondary outcomes included the coefficient of variation ratios (CVR). Seventy-eight studies were included, relating to 5162 CHR-P individuals, 2865 HC and 486 FEP. The CHR-P group demonstrated higher variability compared to HC (in descending order of magnitude) in visual memory (VR: 1.41, 95% CI 1.02-1.94), executive functioning (VR: 1.31, 95% CI 1.18-1.45), verbal learning (VR: 1.29, 95% CI 1.15-1.45), premorbid IQ (VR: 1.27, 95% CI 1.09-1.49), processing speed (VR: 1.26, 95% CI 1.07-1.48), visual learning (VR: 1.20, 95% CI 1.07-1.34), and reasoning and problem solving (VR: 1.17, 95% CI 1.03-1.34). In the CVR analyses the variability in CHR-P population remains in the previous neurocognitive domains and emerged in attention/vigilance, working memory, social cognition, and visuospatial ability. The CHR-P group transitioning to psychosis showed greater VR in executive functioning compared to those not developing psychosis and compared to FEP groups. Clinical high risk for psychosis subjects shows increased variability in neurocognitive performance compared to HC. The main limitation of this study is the validity of the VR and CVR as an index of variability which has received debate. This finding should be explored by further individual-participant data research and support precision medicine approaches

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects

PublishedResearch Support, Non-U.S. Gov'tBACKGROUND: Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established. OBJECTIVES: We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent). METHODS: Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17 alpha-ethinyl-estradiol (EE2)], and to EE2 alone. RESULTS: In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes. CONCLUSION: These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures.This work was funded by the Environment Agency to C.R.T. (project no. SC040078). T.N. was supported by a Fundação para a Ciência ea Tecnologia (FCT) fellowship (BPD/18192/04)

Knockout mice: Is it just genetics? Effect of enriched housing on fibulin-4+/- mice

Background. Fibulin-4 is an extracellular matrix protein expressed by vascular smooth muscle cells that is essential for maintaining arterial integrity. Fibulin-4-/- mice die just before birth due to arterial hemorrhage, but fibulin-4+/- mice appear to be outwardly normal. Experiments were therefore performed to determine whether fibulin-4+/- mice display arterial pathologies on a microscopic scale. After preliminary experiments were performed, a second purpose developed, which was to test the hypothesis that any observed pathologies would be ameliorated by housing the animals in enriched cages. Methodology. Fibulin-4+/- and wild-type mice were housed either four/cage in standard cages or two per cage in larger cages, each cage containing a tunnel and a wheel. After three weeks the mice were sacrificed, and the aortas perfusion-fixed and excised for light and electron microscopy. Principle Findings. When the mice were in standard cages, localized regions of disorganized extracellular matrix and collagen fibers consistently appeared between some of the medial smooth muscle cells in the fibulin-4+/- mice. In the wild-type mice, the smooth muscle cells were closely connected to each other and the media was more compact. The number of disorganized regions per square mm was significantly greater for fibulin-4+/- mice (172±43 (SEM)) than for wild-type mice (15±8) (p<0.01, n = 8). When the mice were in enriched cages, the fibulin-4+/- mice showed significantly fewer disorganized regions than those in standard cages (35±12) (p<0.05, n = 8). The wild type mice also showed fewer disorganized regions (3±2), but this difference was not significant. Conclusions. These results indicate that arterial pathologies manifested in fibulin-4+/- mice can be reduced by enriching the housing conditions, and imply that appropriate environments may counteract the effects of some genetic deficiencies

Identification of a Siglec-F+ granulocyte-macrophage progenitor

In recent years multi-parameter flow cytometry has enabled identification of cells at major stages in myeloid development; from pluripotent hematopoietic stem cells, through populations with increasingly limited developmental potential (common myeloid progenitors and granulocyte-macrophage progenitors), to terminally differentiated mature cells. Myeloid progenitors are heterogeneous, and the surface markers that define transition states from progenitors to mature cells are poorly characterized. Siglec-F is a surface glycoprotein frequently used in combination with IL-5 receptor alpha (IL5Rα) for the identification of murine eosinophils. Here, we describe a CD11b+ Siglec-F+ IL5Rα- myeloid population in the bone marrow of C57BL/6 mice. The CD11b+ Siglec-F+ IL5Rα- cells are retained in eosinophil deficient PHIL mice, and are not expanded upon overexpression of IL-5, indicating that they are upstream or independent of the eosinophil lineage. We show these cells to have GMP-like developmental potential in vitro and in vivo, and to be transcriptionally distinct from the classically described GMP population. The CD11b+ Siglec-F+ IL5Rα- population expands in the bone marrow of Myb mutant mice, which is potentially due to negative transcriptional regulation of Siglec-F by Myb. Lastly, we show that the role of Siglec-F may be, at least in part, to regulate GMP viability

Self-rated health of primary care house officers and its relationship to psychological and spiritual well-being

<p/> <p>Background</p> <p>The stress associated with residency training may place house officers at risk for poorer health. We sought to determine the level of self-reported health among resident physicians and to ascertain factors that are associated with their reported health.</p> <p>Methods</p> <p>A questionnaire was administered to house officers in 4 residency programs at a large Midwestern medical center. Self-rated health was determined by using a health rating scale (ranging from 0 = death to 100 = perfect health) and a Likert scale (ranging from "poor" health to "excellent" health). Independent variables included demographics, residency program type, post-graduate year level, current rotation, depressive symptoms, religious affiliation, religiosity, religious coping, and spirituality.</p> <p>Results</p> <p>We collected data from 227 subjects (92% response rate). The overall mean (SD) health rating score was 87 (10; range, 40–100), with only 4 (2%) subjects reporting a score of 100; on the Likert scale, only 88 (39%) reported excellent health. Lower health rating scores were significantly associated (P < 0.05) with internal medicine residency program, post-graduate year level, depressive symptoms, and poorer spiritual well-being. In multivariable analyses, lower health rating scores were associated with internal medicine residency program, depressive symptoms, and poorer spiritual well-being.</p> <p>Conclusion</p> <p>Residents' self-rated health was poorer than might be expected in a cohort of relatively young physicians and was related to program type, depressive symptoms, and spiritual well-being. Future studies should examine whether treating depressive symptoms and attending to spiritual needs can improve the overall health and well-being of primary care house officers.</p