Detection and measurement of Hypercholesterolaemia in South Africans attending general practitioners in private practice - The cholesterol monitor

Background. 1bis paper reports data on the detection and management of hypercholesterolaemia in patients attending general practitioners in private practice in South Africa.Methods. The frequency of cholesterol testing and the level at which active therapeutic intervention occurred at medical practices were monitored over a 2-year period. A sample of 200 medical practitioners was selected from private practices in major citie;. Data on patients seen by the selected doctors during a 5-day monitoring period were recorded on a standardised form.Results. 12842 patients were seen by the 200 private practice· GPs. More men (18.7%) than women (10.4%) had coronary heart disease (CHD), and their mean total cholesterol (TC) levels were 5.9 mmol/l and 6.0 mmol/l, respectively. Only 3.1% of the patients were reported to have familial hypercholesterolaemia (FH) and 12.8% were reported to have a family history of CHD. Reported smoking rates were exceptionally high (77.5% of women and 64.4% of men). The most commonly prescribed group of lipid-lowering agents was HMG-CoA reductase inhibitors.Conclusions. Inadequate management of hypercholesterol-· aemia leaves many patients with a high risk of CHD mortality in South Africa. Appropriately investigated patients with hypercholesterolaemia should receive treatment to reduce cardiovascular disease using more effective TC control programmes than are currently used in South Africa

Land-use and vegetation in Western Australia : project DAW27 : National Land and Water Resources Audit

This report details a project to compile detailed land-use data for Western Australia, on pre-European and present vegetation types, and aspects of disturbance of or threats to the present vegetation. Metadata on botanical surveys throughout the state were also compiled

Effects of Photobiomodulation Therapy on Regulation of Myogenic Regulatory Factor mRNA Expression In Vivo: A Systematic Review

Non-invasive promotion of myogenic regulatory factors (MRFs), through photobiomodulation therapy (PBMT), may be a viable method of facilitating skeletal muscle regeneration post-injury, given the importance of MRF in skeletal muscle regeneration. The aim of this systematic review was to collate current evidence, identifying key themes and changes in expression of MRF in in vivo models. Web of Science, PubMed, Scopus and Cochrane databases were systematically searched and identified 1459 studies, of which 10 met the inclusion criteria. Myogenic determination factor was most consistently regulated in response to PBMT treatment, and the expression of remaining MRFs was heterogenous. All studies exhibited a high risk of bias, primarily due to lack of blinding in PBMT application and MRF analysis. Our review suggests that the current evidence base for MRF expression from PBMT is highly variable. Future research should focus on developing a robust methodology for determining the effect of laser therapy on MRF expression, as well as long-term assessment of skeletal muscle regeneration

Megapolitan Political Ecology and Urban Metabolism in Southern Appalachia

Drawing on megapolitan geographies, urban political ecology, and urban metabolism as theoretical frameworks, this article theoretically and empirically explores megapolitan political ecology. First, we elucidate a theoretical framework in the context of southern Appalachia and, in particular, the Piedmont megapolitan region, suggesting that the megapolitan region is a useful scale through which to understand urban metabolic connections that constitute this rapidly urbanizing area. We also push the environmental history and geography literature of the U.S. South and southern Appalachia to consider the central role urban metabolic connections play in the region's pressing social and environmental crises. Second, we empirically illuminate these human and nonhuman urban metabolisms across the Piedmont megapolitan region using data from the Coweeta Long-Term Ecological Research (LTER) program, especially highlighting a growing “ring of asphalt” that epitomizes several developing changes to patterns of metabolism. The conclusion suggests that changing urban metabolisms indicated by Coweeta LTER data, ranging from flows of people to flows of water, pose a complicated problem for regional governance and vitality in the future

The design-by-adaptation approach to universal access: learning from videogame technology

This paper proposes an alternative approach to the design of universally accessible interfaces to that provided by formal design frameworks applied ab initio to the development of new software. This approach, design-byadaptation, involves the transfer of interface technology and/or design principles from one application domain to another, in situations where the recipient domain is similar to the host domain in terms of modelled systems, tasks and users. Using the example of interaction in 3D virtual environments, the paper explores how principles underlying the design of videogame interfaces may be applied to a broad family of visualization and analysis software which handles geographical data (virtual geographic environments, or VGEs). One of the motivations behind the current study is that VGE technology lags some way behind videogame technology in the modelling of 3D environments, and has a less-developed track record in providing the variety of interaction methods needed to undertake varied tasks in 3D virtual worlds by users with varied levels of experience. The current analysis extracted a set of interaction principles from videogames which were used to devise a set of 3D task interfaces that have been implemented in a prototype VGE for formal evaluation

Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults.

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

Risks, Health Consequences, and Response Challenges for Small-Island-Based Populations: Observations From the 2017 Atlantic Hurricane Season

The intensely active 2017 Atlantic basin hurricane season provided an opportunity to examine how climate drivers, including warming oceans and rising seas, exacerbated tropical cyclone hazards. The season also highlighted the unique vulnerabilities of populations residing on Small Island Developing States (SIDS) to the catastrophic potential of these storms. During 2017, 22 of the 29 Caribbean SIDS were affected by at least one named storm, and multiple SIDS experienced extreme damage. This paper aims to review the multiplicity of storm impacts on Caribbean SIDS throughout the 2017 season, to explicate the influences of climate drivers on storm formation and intensity, to explore the propensity of SIDS to sustain severe damage and prolonged disruption of essential services, to document the spectrum of public health consequences, and to delineate the daunting hurdles that challenged emergency response and recovery operations for island-based, disaster-affected populations