Heterologous hybridization to a complementary DNA microarray reveals the effect of thermal acclimation in the endothermic bluefin tuna (Thunnus orientalis).

The temperature stress that pelagic fishes experience can induce physiological and behavioural changes that leave a signature in gene expression profiles. We used a functional genomics approach to identify genes that were up- or down-regulated following thermal stress in the Pacific bluefin tuna. Following the acclimation period, 113, 81 and 196 genes were found to be differentially expressed between the control (20 degrees C) and cold (15 degrees) treatment groups, in ventricle, red muscle and white muscle, respectively.

Highly enantioselective total synthesis of (-)-(3'S)-Lomatin and (+)-(3'S,4'R)-trans-khellactone.

Concise highly enantioselective three-step syntheses are described for (-)-(3'S)-lomatin and (+)-(3'S,4'R)-trans-khellactone from 7-hydroxycoumarin in 97% ee and in 57% and 58% overall yields, respectively, using nonaqueous enantioselective epoxidation by an iminium salt as the key step.

Measuring outcomes of importance to women with stress urinary incontinence.

Objective: To provide evidence on outcomes of importance to women who have stress urinary incontinence (SUI). The secondary aim was to identify additional outcomes that ought to be collected in future primary studies or in systematic reviews of the literature.

Design: Questionnaire survey of a cohort of women with SUI.

Impact of an express admit unit on emergency department length of stay.

Background: Express admit units (EAUs) have been proposed as a way to expedite patient flow through the Emergency Department (ED).

Objectives: We sought to determine the effect of opening a five-bed EAU unit for temporary placement of admitted patients on our ED length of stay (LOS) and waiting room times (WT).

Method: This was a before-and-after interventional study of the 3-month period immediately before (pre-EAU) and after opening (post-EAU) of the EAU.

Prevalence of urinary and faecal incontinence and nocturnal enuresis and attitudes to treatment and help-seeking amongst a community-based representative sample of adults in the United Kingdom.

Aim: To determine relative prevalence in the same population of urinary incontinence (UI), faecal incontinence (FI) and nocturnal enuresis (NE). To explore attitudes and behaviours relating to help-seeking and beliefs about incontinence prevalence, impact, causes and treatments.

Design: Online survey.

Reduced glomerular filtration rate and its association with clinical outcome in older patients at risk of vascular events: secondary analysis.

Background: Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity.

Numerous preclinical, epidemiologic, and clinical studies have suggested the benefits of vitamin D and its analogues for the prevention and treatment of cancer. However, the hypercalcemic effects have limited the use of 1alpha,25(OH)(2)D(3), the hormonally active form of vitamin D. To identify vitamin D analogues with better efficacy and low toxicity, we have tested >60 novel Gemini vitamin D analogues with a unique structure of two side chains for growth inhibition of breast cancer cells.

Does low to moderate alcohol intake protect against cognitive decline in older people?

Objectives: To determine whether low to moderate alcohol intake is protective against cognitive decline in older people.

Design: Prospective cohort study.

Setting: Community-based study in Ireland, the Netherlands, and Scotland.

Toxicokinetics and toxicodynamics of paraquat accumulation in mouse brain.

Paraquat (PQ) is a potential human neurotoxicant and is used in models of oxidative stress. We determined the toxicokinetics (TK) and toxicodynamics (TD) of PQ in adult mouse brain following repeated or prolonged PQ exposure. PQ accumulated in different brain regions and reached a plateau after approximately 18 i.

Are elevated circulating intercellular adhesion molecule 1 levels more strongly predictive of diabetes than vascular risk? Outcome of a prospective study in the elderly.

Aims/hypothesis: The aim of this prospective study was to determine whether circulating intercellular adhesion molecule (ICAM) 1, as a potential surrogate of 'endothelial activation', is more strongly associated with risk of vascular events than with incident diabetes.

Methods: We related baseline ICAM-1 levels to vascular events (866 CHD and stroke events in 5,685 participants) and incident diabetes (292 in 4,945 without baseline diabetes) in the elderly over 3.2 years of follow-up.

Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population.

Objective: To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women.

Research Design And Methods: We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up.

Phase I combination study of trabectedin and doxorubicin in patients with soft-tissue sarcoma.

Purpose: To determine the dose of trabectedin plus doxorubicin with granulocyte colony-stimulating factor support associated with manageable neutropenia and acceptable dose-limiting toxicities (DLT) in patients with recurrent or persistent soft-tissue sarcoma.

Methods: In this phase I, open-label, multicenter trial, patients previously treated with 0-1 prior chemotherapy regimens excluding doxorubicin, an Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function received a 10- to 15-min i.v.

Analytical method developed for measurement of dialkylphosphate metabolites in urine collected from children non-occupationally exposed to organophosphate pesticides in an agricultural community in Thailand.

There has been increasing concern in regards to organophosphate (OP) pesticide exposure among farm workers and their families in Thailand's agricultural areas. Therefore, the development of an analytical method for estimating OP pesticide exposure is necessary to allow for monitoring of OP pesticide exposures within these populations. This paper describes an analytical method developed to measure dialkylphosphate (DAP) metabolites in urine.

Do patients with angina alone have a more benign prognosis than patients with a history of acute myocardial infarction, revascularisation or both? Findings from a community cohort study.

Aim: To compare prognosis for patients with a diagnosis of angina alone to patients postacute myocardial infarction (AMI) and/or revascularisation and/or angina.

Design: Community-based retrospective cohort study.

Setting: A random selection of 37 Irish general practices.

Multimorbidity and risk among patients with established cardiovascular disease: a cohort study.

Background: Most patients managed in primary care have more than one condition. Multimorbidity presents challenges for the patient and the clinician, not only in terms of the process of care, but also in terms of management and risk assessment.

Aim: To examine the effect of the presence of chronic kidney disease and diabetes on mortality and morbidity among patients with established cardiovascular disease.

An Endogenous TNF-α Antagonist Induced by Splice-switching Oligonucleotides Reduces Inflammation in Hepatitis and Arthritis Mouse Models.

Tumor necrosis factor-α (TNF-α) is a key mediator of inflammatory diseases, including rheumatoid arthritis (RA), and anti-TNF-α drugs such as etanercept are effective treatments. Splice-switching oligonucleotides (SSOs) are a new class of drugs designed to induce therapeutically favorable splice variants of targeted genes. In this work, we used locked nucleic acid (LNA)-based SSOs to modulate splicing of TNF receptor 2 (TNFR2) pre-mRNA.

Interpretation of biomonitoring data in clinical medicine and the exposure sciences.

Biomonitoring has become a fundamental tool in both exposure science and clinical medicine. Despite significant analytical advances, the clinical use of environmental biomarkers remains in its infancy. Clinical use of environmental biomarkers poses some complex scientific and ethical challenges.

Identifying uncertainties to prioritise research.

Brian Buckley describes a project by the James Lind Alliance to identify treatment uncertainties in the care of people with urinary incontinence and prioritise these to influence and inform publicly funded research.

Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice.

Cell-penetrating peptides (CPPs), containing arginine (R), 6-aminohexanoic acid (X), and/or beta-alanine (B) conjugated to phosphorodiamidate morpholino oligomers (PMOs), enhance their delivery in cell culture. In this study, the potency, functional biodistribution, and toxicity of these conjugates were evaluated in vivo, in EGFP-654 transgenic mice that ubiquitously express the aberrantly spliced EGFP-654 pre-mRNA reporter. Correct splicing and enhanced green fluorescence protein (EGFP) upregulation serve as a positive readout for peptide-PMO (PPMO) entry into cells and access to EGFP-654 pre-mRNA in the nucleus.

Lymphotoxin-alpha C804A polymorphism is a risk factor for stroke. The PROSPER study.

Inflammation plays a prominent role in the development of atherosclerosis, which is the most important risk factor for vascular events. Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine and is found to be expressed in atherosclerotic lesions. We investigated the association between the C804A polymorphism within the LTA gene and coronary and cerebrovascular events in 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).