Associations of vigorous physical activity with all-cause, cardiovascular and cancer mortality among 64 913 adults

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Background Physical activity recommendations state that for the same energy expenditure, moderate-to-vigorous physical activities (MVPAs) produce similar health benefits. However, few epidemiological studies have tested this hypothesis. Design We examined whether, compared with moderate, vigorous activity was associated with larger mortality risk reductions. Methods Data from 11 cohorts of the Health Survey for England and the Scottish Health Survey, collected from 1994 to 2011 (mean (SD) follow-up, 9.0 (3.6) years). Adults aged ≥30 years reported MVPA and linkage to mortality records. Exposure was the proportion of self-reported weighted MVPA through vigorous activity. Outcomes were all-cause, cardiovascular disease (CVD) and cancer mortality. Results Among 64 913 adult respondents (44% men, 56% women, mean (SD) age, 49.8 (13.6) years), there were 5064 deaths from all-causes, 1393 from CVD and 1602 from cancer during 435 743 person-years of follow-up. Compared with those who reported no vigorous physical activity, and holding constant the volume of weighted MVPA, vigorous activity was associated with additional reductions in mortality risk. For all-cause mortality, the adjusted HR was HR=0.84 (95% CI 0.71, 0.99) and HR=0.84 (95% CI 0.76, 0.94) among those who reported between >0% and<30%, or ≥30% of their activity as vigorous, respectively. For CVD and cancer mortality, point estimates showed similar beneficial associations yet CIs were wider and crossed unity. Conclusion Vigorous activities were associated with larger reductions in mortality risk than activities of moderate intensity, but no evidence of dose-response effects was found

A Prospective Evaluation of Quick Intraoperative Parathyroid Hormone Assay at the Time of Skin Closure in Predicting Clinically Relevant Hypocalcemia after Thyroidectomy

BACKGROUND: Post-thyroidectomy hypocalcemia is a major contributing factor in delayed hospital discharge and dissuading surgeons from ambulatory thyroidectomy. We prospectively evaluated the accuracy and reliability of quick parathyroid hormone level measurement at skin closure (PTH-SC) in predicting clinically relevant hypocalcemia (i.e., patients requiring calcium +/- calcitriol supplements on hospital discharge). METHODS: Of the 117 patients who underwent a total or completion total thyroidectomy and PTH-SC, 17 (14.5 %) had hypocalcemic symptoms or adjusted calcium 1 pmol/L) had a higher specificity (95.0 %) and AUC (0.887) than serial calcium monitoring or PTH-D1 alone. Although 3/98 of patients with PTH-SC >1 pmol/L required calcium supplements on discharge, they required only the minimum amount to maintain normocalcemia. CONCLUSION: PTH-SC is an accurate and reliable means of predicting clinically relevant hypocalcemia. It would be reasonable to discharge those with PTH-SC >1 pmol/L on the same operative day as the risk of life-threatening hypocalcemia would seem unlikely.published_or_final_versio

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

Epidemiology and outcomes of community-onset methicillin-susceptible Staphylococcus aureus bacteraemia in a university hospital in Singapore

10.1186/1471-2334-8-14BMC infectious diseases81

Do Asian breast cancer patients have poorer survival than their western counterparts? A comparison between Singapore and Stockholm

10.1186/bcr2219Breast Cancer Research111-BCRR

Assessment of motor functioning in the preschool period

The assessment of motor functioning in young children has become increasingly important in recent years with the acknowledgement that motor impairment is linked with cognitive, language, social and emotional difficulties. However, there is no one gold standard assessment tool to investigate motor ability in children. The aim of the current paper was to discuss the issues related to the assessment of motor ability in young pre-school children and to provide guidelines on the best approach for motor assessment. The paper discusses the maturational changes in brain development at the preschool level in relation to motor ability. Other issues include sex differences in motor ability at this young age, and evidence for this in relation to sociological versus biological influences. From the previous literature it is unclear what needs to be assessed in relation to motor functioning. Should the focus be underlying motor processes or movement skill assessment? Several key assessment tools are discussed that produce a general measure of motor performance followed by a description of tools that assess specific skills, such as fine and gross motor, ball and graphomotor skills. The paper concludes with recommendations on the best approach in assessing motor function in pre-school children

Thrombospondin-4 is a putative tumour-suppressor gene in colorectal cancer that exhibits age-related methylation

<p>Abstract</p> <p>Background</p> <p><it>Thrombospondin-4 </it>(<it>THBS4</it>) is a member of the extracellular calcium-binding protein family and is involved in cell adhesion and migration. The aim of this study was to evaluate the potential role of deregulation of <it>THBS4 </it>expression in colorectal carcinogenesis. Of particular interest was the possible silencing of expression by methylation of the CpG island in the gene promoter.</p> <p>Methods</p> <p>Fifty-five sporadic colorectal tumours stratified for the CpG Island Methylator Phenotype (CIMP) were studied. Immunohistochemical staining of THBS4 protein was assessed in normal and tumour specimens. Relative levels of <it>THBS4 </it>transcript expression in matched tumours and normal mucosa were also determined by quantitative RT-PCR. Colony forming ability was examined in 8 cell lines made to overexpress THBS4. Aberrant promoter hypermethylation was investigated as a possible mechanism of gene disruption using MethyLight. Methylation was also assessed in the normal colonic tissue of 99 patients, with samples biopsied from four regions along the length of the colon.</p> <p>Results</p> <p><it>THBS4 </it>expression was significantly lower in tumour tissue than in matched normal tissue. Immunohistochemical examination demonstrated that THBS4 protein was generally absent from normal epithelial cells and tumours, but was occasionally expressed at low levels in the cytoplasm towards the luminal surface in vesicular structures. Forced THBS4 over-expression caused a 50-60% repression of tumour colony growth in all eight cell lines examined compared to control cell lines. Tumours exhibited significantly higher levels of methylation than matched normal mucosa, and <it>THBS4 </it>methylation correlated with the CpG island methylator phenotype. There was a trend towards decreased gene expression in tumours exhibiting high <it>THBS4 </it>methylation, but the correlation was not significant. <it>THBS4 </it>methylation was detectable in normal mucosal biopsies where it correlated with increasing patient age and negatively with the occurrence of adenomas elsewhere in the colon.</p> <p>Conclusions</p> <p><it>THBS4 </it>shows increased methylation in colorectal cancer, but this is not strongly associated with altered gene expression, either because methylation has not always reached a critical level or because other factors influence <it>THBS4 </it>expression. <it>THBS4 </it>may act as a tumour suppressor gene, demonstrated by its suppression of tumour colony formation <it>in vitro</it>. <it>THBS4 </it>methylation is detectable in normal colonic mucosa and its level may be a biomarker for the occurrence of adenomas and carcinoma.</p