An assessment of potential cancer risk following occupational exposure to ethanol.

Recognition of the carcinogenic properties of ethanol has resulted from comprehensive evidence regarding the effect of consumption of alcohol; indeed, ethanol in alcoholic beverages is now considered a Group 1 carcinogen by the International Agency for Research on Cancer. However, there is little information on the effects of ethanol following exposure via the occupationally relevant routes of inhalation and dermal exposure. This review therefore focuses on these exposure routes, to assess potential carcinogenic risk associated with occupational exposure to ethanol.

TNF, LTA and TGFB1 genotype distributions among acute graft-vs-host disease subsets after HLA-matched unrelated hematopoietic stem cell transplantation: a pilot study.

Cytokine single nucleotide polymorphisms and consequent production levels have been associated with acute graft-vs-host disease (aGVHD) development. The aim of this pilot study was to determine whether polymorphisms in tumor necrosis factor (TNF), lymphotoxin alpha (LTA) and transforming growth factor beta 1 (TGFB1) showed any association with aGVHD severity. Novel alleles and polymorphisms were identified for each cytokine locus.

Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis.

Purpose: Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials.

E2F4 is required for early eye patterning.

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.

Evaluation of Patient Navigation in a Community Radiation Oncology Center Involved in Disparities Studies: A Time-to-Completion-of-Treatment Study.

PURPOSE: To evaluate whether data on length of time from patient referral to treatment completion, collected routinely as part of a quality improvement program, can be used to measure the effectiveness of a patient navigator program. PATIENTS AND METHODS: During a calendar year, 72 disparities patients, 38 of whom received navigator services, and a group of 157 nondisparate, un-navigated patients received external beam radiation therapy at a community center. Data from referral time through completion of treatment, which had been collected routinely under an existing continuous quality improvement program, were compared retrospectively, as well as missed treatments and the percentage of planned treatments completed, for three patient groups.

Isotope tracing enhancement of chemiluminescence assays for nitric oxide research.

Chemiluminescence assays are used widely for the detection of nitric oxide (NO)-derived species in biological fluids and tissues. Here, we demonstrate that these assays can be interfaced with mass-sensitive detectors for parallel determination of isotopic abundance. Results obtained with tri-iodide and ascorbic acid-based reductive assays indicate that mass spectrometric detection enables NO isotope-tracing experiments to be carried out to a limit of detectability of a few picomoles, a sensitivity similar to that of standard gas phase chemiluminescence methods.

Irinotecan and uridine diphosphate glucuronosyltransferase 1A1 pharmacogenetics: to test or not to test, that is the question.

Pharmacogenetic research indicates a relationship between a polymorphism in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and irinotecan inactivation, in that degradation of SN-38, the active metabolite of irinotecan, correlates inversely with the number of TA repeats in the TATA element of the UGT1A1 promoter region. Individuals who are homozygous for the UGT1A1*28 allele (7 repeats) may exhibit reduced degradation of SN-38 and increased probability of severe toxicities. Clinical study results, as reported in the literature, have not been uniform, however, in showing a relation between genotype and the development of toxicities.

Drug-eluting stents versus bare-metal stents for off-label indications: a propensity score-matched outcome study.

Background: The US Food and Drug Administration recently concluded that data on off-label drug-eluting stent (DES) safety are limited. However, in actual clinical practice, DES are often used for off-label indications, and observational studies demonstrate that complications are higher when compared with on-label use. We aimed to determine whether clinical outcomes differ after DES and bare-metal stent implantation in a patient cohort defined by DES off-label indications.

Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage.

Despite the importance of Mcl-1, an anti-apoptotic Bcl-2 family member, in the regulation of apoptosis, little is known regarding its role in nervous system development and injury-induced neuronal cell death. Because germline deletion of Mcl-1 results in peri-implantation lethality, we address the function of Mcl-1 in the nervous system using two different conditional Mcl-1 mouse mutants in the developing nervous system. Here, we show for the first time that Mcl-1 is required for neuronal development.

HES1 regulates 5-HT1A receptor gene transcription at a functional polymorphism: essential role in developmental expression.

Mammalian HES1 and HES5 are abundant in developing CNS and inhibit neurogenesis, while HES6 promotes neurogenesis. An early serotonergic differentiation marker, the 5-HT1A receptor, is repressed by HES5 and DEAF1 which recognize the C(-1019), but not G(-1019) allele of a human 5-HT1A promoter polymorphism associated with mood disorders. We tested whether HES1 and HES6 regulate transcriptional activity at this element.

CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage.

DNA damage is an important initiator of neuronal apoptosis and activates signaling events not yet fully defined. Using the camptothecin-induced DNA damage model in neurons, we previously showed that cyclin D1-associated cell cycle cyclin-dependent kinases (Cdks) (Cdk4/6) and p53 activation are two major events leading to activation of the mitochondrial apoptotic pathway. With gene array analyses, we detected upregulation of Cited2, a CBP (cAMP response element-binding protein-binding protein)/p300 interacting transactivator, in response to DNA damage.

The management of household hazardous waste in the United Kingdom.

Waste legislation in the United Kingdom (UK) implements European Union (EU) Directives and Regulations. However, the term used to refer to hazardous waste generated in household or municipal situations, household hazardous waste (HHW), does not occur in UK, or EU, legislation. The EU's Hazardous Waste Directive and European Waste Catalogue are the principal legislation influencing HHW, although the waste categories described are difficult to interpret.

Hospital and operator variations in drug-eluting stent use: a multi-level analysis of 5967 consecutive patients in Scotland.

Objective: To determine whether drug-eluting stent (DES) use varies among Scottish hospitals, and the extent to which any variations are explained by differences between operators, patients and lesions.

Methods: Multi-level analysis of consecutive patients treated with percutaneous coronary intervention (PCI) between April 2005 and March 2006 in Scotland, using the Scottish Coronary Revascularization Registry.

Results: A total of 38 operators performed 5967 PCI procedures on 8489 lesions.

Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP.

PTEN-induced putative kinase 1 (Pink1) is a recently identified gene linked to a recessive form of familial Parkinson's disease (PD). The kinase contains a mitochondrial localization sequence and is reported to reside, at least in part, in mitochondria. However, neither the manner by which the loss of Pink1 contributes to dopamine neuron loss nor its impact on mitochondrial function and relevance to death is clear.

Delayed combinatorial treatment with flavopiridol and minocycline provides longer term protection for neuronal soma but not dendrites following global ischemia.

We previously reported that delayed administration of the general cyclin-dependent kinase inhibitor flavopiridol following global ischemia provided transient neuroprotection and improved behavioral performance. However, it failed to provide longer term protection. In the present study, we investigate the ability of delayed flavopiridol in combination with delayed minocycline, another neuroprotectant to provide sustained protection following global ischemia.

The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.

Recent evidence has indicated that common mechanisms play roles among multiple neurological diseases. However, the specifics of these pathways are not completely understood. Stroke is caused by the interruption of blood flow to the brain, and cumulative evidence supports the critical role of oxidative stress in the ensuing neuronal death process.

Specific in vivo roles for E2Fs in differentiation and development.

E2Fs have been historically considered as key interacting factors for the retinoblastoma (Rb) family of pocket proteins, acting as universal regulators of cell cycle progression. Often exhibiting overlapping function, deregulated E2F activity is thought to cancer or cell death. While early reports hypothesized that E2Fs may be capable of regulating distinct functions beyond proliferation, several recent reports have characterized increasingly diverse, context dependent functions for different E2Fs in vivo, often in what appears to a manner beyond traditional cell cycle regulation.

Required roles of Bax and JNKs in central and peripheral nervous system death of retinoblastoma-deficient mice.

Retinoblastoma-deficient mice show massive neuronal damage and deficits in both CNS and PNS tissue. Previous work in the field has shown that death is regulated through distinct processes where CNS tissue undergoes death regulated by the tumor suppressor p53 and the apoptosome component, APAF1. Death in the PNS, however, is independent of p53 and reliant on the death protease, caspase 3.

Synthesis and in vitro protozoocidal evaluation of novel diazabicyclic tropolone derivatives.

The synthesis and in vitro antiparasitic activity of twenty-seven novel diazabicycles based on tropolone ethers is presented. The compounds can be readily prepared by means of a high-yielding hetero Diels-Alder reaction using simple and readily available starting materials. Several of the new diazabicycles have in vitro activities against Trypanosoma cruzi, Leishmania donovani, Trypanosoma brucei rhodesiense, and chloroquine-resistant Plasmodium falciparum that are comparable or superior to those of currently employed protozoocidal agents.

The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict?

Objectives: The Lund-Mackay score is widely used in assessment of chronic rhinosinusitis. We aimed to describe its relationship to other measures of pre- and post-treatment health status.

Study Design: Multicenter prospective study of 1840 patients undergoing surgery for chronic rhinosinusitis in the UK.

Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease.

We reported previously that calpain-mediated Cdk5 activation is critical for mitochondrial toxin-induced dopaminergic death. Here, we report a target that mediates this loss. Prx2, an antioxidant enzyme, binds Cdk5/p35.