Genetic linkage of beta and gamma subunits of epithelial sodium channel to systolic blood pressure in southern Chinese

published_or_final_versio

Xenoestrogen-Induced ERK-1 and ERK-2 Activation via Multiple Membrane-Initiated Signaling Pathways

Xenoestrogens can mimic or antagonize the activity of physiological estrogens, and the suggested mechanism of xenoestrogen action involves binding to estrogen receptors (ERs). However, the failure of various in vitro or in vivo assays to show strong genomic activity of xenoestrogens compared with estradiol (E(2)) makes it difficult to explain their ability to cause abnormalities in animal (and perhaps human) reproductive functions via this pathway of steroid action. E(2) has also been shown to initiate rapid intracellular signaling, such as changes in levels of intracellular calcium, cAMP, and nitric oxide, and activations of a variety of kinases, via action at the membrane. In this study, we demonstrate that several xenoestrogens can rapidly activate extracellular-regulated kinases (ERKs) in the pituitary tumor cell line GH(3)/B6/F10, which expresses high levels of the membrane receptor for ER-α(mER). We tested a phytoestrogen (coumestrol), organochlorine pesticides or their metabolites (endosulfan, dieldrin, and DDE), and detergent by-products of plastics manufacturing (p-nonylphenol and bisphenol A). These xenoestrogens (except bisphenol A) produced rapid (3–30 min after application), concentration (10(−14)–10(−8) M)-dependent ERK-1/2 phosphorylation but with distinctly different activation patterns. To identify signaling pathways involved in ERK activation, we used specific inhibitors of ERs, epidermal growth factor receptors, Ca(2+) signaling, Src and phosphoinositide-3 kinases, and a membrane structure disruption agent. Multiple inhibitors blocked ERK activation, suggesting simultaneous use of multiple pathways and complex signaling web interactions. However, inhibitors differentially affected each xenoestrogen response examined. These actions may help to explain the distinct abilities of xenoestrogens to disrupt reproductive functions at low concentrations

Association of body mass index, metabolic health status and clinical outcomes in acute myocardial infarction patients: a national registry-based study

INTRODUCTION: Obesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate the risk of short- and long-term all-cause mortality by obesity and metabolic health in AMI patients using data from a multi-ethnic national AMI registry. METHODS: A total of 73,382 AMI patients from the national Singapore Myocardial Infarction Registry (SMIR) were included. These patients were classified into four groups based on the presence or absence of metabolic diseases, diabetes mellitus, hyperlipidaemia, and hypertension, and obesity: (1) metabolically-healthy-normal-weight (MHN); (2) metabolically-healthy-obese (MHO); (3) metabolically-unhealthy-normal-weight (MUN); and (4) metabolically-unhealthy-obese (MUO). RESULTS: MHO patients had reduced unadjusted risk of all-cause in-hospital, 30-day, 1-year, 2-year, and 5-year mortality following the initial MI event. However, after adjusting for potential confounders, the protective effect from MHO on post-AMI mortality was lost. Furthermore, there was no reduced risk of recurrent MI or stroke within 1-year from onset of AMI by the MHO status. However, the risk of 1-year mortality was higher in female and Malay AMI patients with MHO compared to MHN even after adjusting for confounders. CONCLUSION: In AMI patients with or without metabolic diseases, the presence of obesity did not affect mortality. The exception to this finding were female and Malay MHO who had worse long-term AMI mortality outcomes when compared to MHN suggesting that the presence of obesity in female and Malay patients may confer worsened outcomes

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

The validation analysis of the INSHORE system: a precise and efficient coastal survey system

Government and environmental entities are becoming increasingly concerned with qualifying and quantifying the erosion effects that are observed in sandy shores. Correspondingly, survey methodologies that gather data for such erosion studies are increasingly being demanded. The responsible entities are continually broadening their areas of interest, are concerned in the establishment of regular monitoring programmes and are demanding high accuracy from the geo-spatial data that is collected. The budget available for such monitoring activities, however, does not parallel the trend in the increasing demand for quality specifications. Survey methodologies need improvement to meet these requirements. We have developed a new land-based survey system-the INSHORE system-that is ideal for low cost, highly efficient and highly precise coastal surveys. The INSHORE system uses hi-tech hardware that is based on high-grade global positioning system (GPS) receivers and a laser distance sensor combined with advanced software algorithms. This system enables the determination of the ground coordinates of the surveyed areas with a precision of 1 to 2 cm, without having a sensor in contact with the ground surface. The absence of physical contact with the ground makes this system suitable for high-efficiency surveys. The accuracy of the positioning, which is based on advanced differential GPS processing, is enhanced by considering the estimated attitude of the GPS receiver holding structure and eliminates undesirable offsets. This paper describes the INSHORE survey system and presents the results of validation tests that were performed in a sandy shore environment

TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited.</p> <p>Methods</p> <p>Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed.</p> <p>Results</p> <p>High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2 expression was an independent prognostic factor for cancer related survival.</p> <p>Conclusion</p> <p>Histological phenotype and clinical behaviour of colon cancer is not only influenced by mutational incidents in tumour cells but also affected by interaction of tumour tissue with inflammatory cells like macrophages and associated stroma and TGF-beta signalling is one important part of this crosstalk. Further studies are needed to elucidate the exact mechanisms.</p

Enhanced physical health screening for people with severe mental illness in Hong Kong: results from a one-year prospective case series study

Background People with severe mental illness have significantly poorer physical health compared to the general population; previous health screening studies conducted outside Asian countries have demonstrated the potential in addressing this issue. This case series aimed to explore the effects and utility of integrating an enhanced physical health screening programme for community dwelling patients with severe mental illness into routine clinical practice in Hong Kong. Method This study utilises a consecutive prospective case series design. The serious mental illness Health Improvement Profile (HIP) was used as a screening tool at baseline and repeated at 12 months follow-up. Results A total of 148 community-based patients with severe mental illness completed the study. At one year follow-up analysis showed a significant improvement in self-reported levels of exercise and a reduction in the numbers of patients prescribed medications for diabetes However, mean waist circumference increased at follow-up. In addition to the statistically significant results some general trends were observed, including: a lack of deterioration in most areas of cardiovascular risk; a reduction in medicines prescribed for physical health problems; and general improvements in health behaviours over the 12 month period. Conclusions The findings demonstrate that using the HIP is feasible and acceptable in Hong Kong. The results of the enhanced physical health-screening programme are promising, but require further testing using a randomised controlled trial design in order to more confidently attribute the improvements in well-being and health behaviours to the HIP. Trial registration Clinical trial registration number: ISRCTN1258247

Production of π0 and η mesons in Cu+Au collisions at sNN =200 GeV

Production of π0 and η mesons has been measured at midrapidity in Cu+Au collisions at sNN=200GeV. Measurements were performed in π0(η)→γγ decay channel in the 1(2)-20GeV/c transverse momentum range. A strong suppression is observed for π0 and η meson production at high transverse momentum in central Cu+Au collisions relative to the p+p results scaled by the number of nucleon-nucleon collisions. In central collisions the suppression is similar to Au+Au with comparable nuclear overlap. The η/π0 ratio measured as a function of transverse momentum is consistent with mT-scaling parametrization down to pT=2GeV/c, its asymptotic value is constant and consistent with Au+Au and p+p and does not show any significant dependence on collision centrality. Similar results were obtained in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions as well as in e+e- collisions in a range of collision energies sNN=3-1800 GeV. This suggests that the quark-gluon-plasma medium produced in Cu+Cu collisions either does not affect the jet fragmentation into light mesons or it affects the π0 and η the same way

Enhanced physical health screening for people with severe mental illness in Hong Kong: results from a one-year prospective case series study

Background People with severe mental illness have significantly poorer physical health compared to the general population; previous health screening studies conducted outside Asian countries have demonstrated the potential in addressing this issue. This case series aimed to explore the effects and utility of integrating an enhanced physical health screening programme for community dwelling patients with severe mental illness into routine clinical practice in Hong Kong. Method This study utilises a consecutive prospective case series design. The serious mental illness Health Improvement Profile (HIP) was used as a screening tool at baseline and repeated at 12 months follow-up. Results A total of 148 community-based patients with severe mental illness completed the study. At one year follow-up analysis showed a significant improvement in self-reported levels of exercise and a reduction in the numbers of patients prescribed medications for diabetes However, mean waist circumference increased at follow-up. In addition to the statistically significant results some general trends were observed, including: a lack of deterioration in most areas of cardiovascular risk; a reduction in medicines prescribed for physical health problems; and general improvements in health behaviours over the 12 month period. Conclusions The findings demonstrate that using the HIP is feasible and acceptable in Hong Kong. The results of the enhanced physical health-screening programme are promising, but require further testing using a randomised controlled trial design in order to more confidently attribute the improvements in well-being and health behaviours to the HIP. Trial registration Clinical trial registration number: ISRCTN1258247