How does blood regulate cerebral temperatures during hypothermia?

Macro-modeling of cerebral blood flow can help determine the impact of thermal intervention during instances of head trauma to mitigate tissue damage. This work presents a bioheat model using a 3D fluid-porous domain coupled with intersecting 1D arterial and venous vessel trees. This combined vascular porous (VaPor) model resolves both cerebral blood flow and energy equations, including heat generated by metabolism, using vasculature extracted from MRI data and is extended using a tree generation algorithm.

Germline mutations in MAP3K6 are associated with familial gastric cancer.

Gastric cancer is among the leading causes of cancer-related deaths worldwide. While heritable forms of gastric cancer are relatively rare, identifying the genes responsible for such cases can inform diagnosis and treatment for both hereditary and sporadic cases of gastric cancer. Mutations in the E-cadherin gene, CDH1, account for 40% of the most common form of familial gastric cancer (FGC), hereditary diffuse gastric cancer (HDGC).

The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists.

The identification and subsequent optimisation of a selective non-peptidic NPY Y2 antagonist series is described. This led to the development of amine 2, a selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure.

The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure.

The identification of a highly selective D(2) partial agonist, D(3) antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described.

Novel mutations in the sacsin gene in ataxia patients from Maritime Canada.

We ascertained two families in Eastern Canada segregating a form of ataxia consistent with a recessive mode of inheritance. We performed a whole genome scan using dense SNP genotyping, and despite an absence of shared homozygosity in the families we defined linkage to a small region on chromosome 13. Direct DNA resequencing was employed to screen biologically relevant candidate genes in the interval, and two presumptive pathogenic mutations were found in the gene encoding sacsin.

The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists.

A novel small molecule NPY Y2 antagonist (3) identified from high throughput screening is described. A subsequent SAR study and optimisation programme based around this molecule is also described, leading to the identification of potent and soluble pyridyl analogue 36.

The NURSE Center: A peer mentor-tutor project for disadvantaged nursing students in Appalachia.

To assist disadvantaged Appalachian nursing students, a grant-supported peer mentor-tutor project was initiated in a regional university. Located in the NURSE Center (Nursing Undergraduate Resource for Successful Education), the goals of the project were to improve participants'academic achievement, increase retention, encourage timely academic progression, and improve NCLEX-RN passing rates. The authors describe the project, the first year of operation, and future directions.

Community partnerships for an LPN to BSN career mobility project.

Based on a 6-year, learn and earn curriculum, the authors report on a year-old project that assists licensed practical nurses (LPNs) to obtain a baccalaureate degree in nursing (BSN). Partnerships with 4 area healthcare agencies employing LPNs were developed to support students with full or partial tuition reimbursement and work schedules to accommodate classes. Key university staff in the offices of admissions, financial aid, adult programs and services, and nursing advisement are assigned to this student group to provide individualized assistance.

Patterns of peer tutoring in nursing.

Peer tutoring in higher education is an effective strategy for promoting academic gains. Within nursing, peer tutoring has been used in the clinical setting, but little information is available regarding its use across the nursing curriculum. A peer tutoring program was created at a regional Appalachian university to meet the needs of students with poor academic backgrounds and multiple risk factors for failure.

An in vitro and an in vivo unscheduled DNA synthesis assay with a zinc oxide/hexachloroethane (Zn/HCE) smoke.

1. Since Zn/HCE smoke has been shown previously to be weakly positive in the Ames test, and negative in the bone marrow micronucleus assay, other assays including a second in vivo assay examining unscheduled DNA synthesis (UDS) in rat hepatocytes has been carried out, as recommended by the UK Department of Health guidelines. 2.

The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays.

Antioxidants are thought to be important in protecting against damage from active oxygen species. The effects of the antioxidant nutrients vitamins C and E have been investigated after bleomycin treatment in the Salmonella typhimurium bacterial mutation assay, in the human peripheral lymphocyte chromosome aberration assay, and in the mouse micronucleus assay in peripheral blood and bone marrow cells. There were no protective effects from vitamins C and E in the bacterial mutation assay, but vitamin C and not vitamin E abolished chromosome damaging responses in human peripheral lymphocytes, and both vitamins reduced responses in micronuclei from peripheral blood cells in mice.

Use of precision-cut liver slices for studies of unscheduled DNA synthesis.

Precision-cut liver slices were prepared from untreated and Aroclor 1254 (ARO)-treated male Sprague-Dawley rats with a Krumdieck tissue slicer. Liver slices were cultured for 24 hr in medium containing [3H]thymidine and 0-0.1 mM 2-acetylaminofluorene (2-AAF) using a dynamic organ culture system and processed for autoradiographic evaluation of unscheduled DNA synthesis (UDS).

A method for the detection of protein-bound mutagens in food.

To investigate the possible presence of protein-bound mutagens in food an analytical procedure has been devised in which the sample is enzymically hydrolysed, fractionated by HPLC and examined by a modified liquid incubation Ames assay. To validate the method MeIQx was added, as a model compound, to beefburger and a recovery of 82% obtained. The limit of detection for protein-bound mutagens was 1 microgram/kg, expressed as equivalents of MeIQx.

Mutagenicity testing of imidazole and related compounds.

Ames tests have been performed with imidazole and its principal metabolites, hydantoin and hydantoic acid. N-Acetyl-imidazole, a potential metabolite resulting from the action of intestinal bacteria, and histamine, a structurally related compound which is widely distributed in mammalian tissues, have also been tested. Imidazole and histamine were also tested in the UDS assay in primary rat hepatocytes, while imidazole alone was tested in the M2-C3H mouse fibroblast malignant transformation assay.

Studies on the mutagenicity of a zinc oxide-hexachloroethane smoke.

1. A suitable method has been developed for generating atmospheres of zinc oxide/hexachloroethane smoke (ZnHCE). 2.

Effects of the nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine on Salmonella typhimurium TA100 in the host-mediated assay in mice.

The N-nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine (APNG) was examined for mutagenicity in the mouse host-mediated assay using Salmonella typhimurium strain TA100. Administration of APNG orally or as a single ip injection was shown to produce an increase in revertants. This study provides the first evidence that APNG is absorbed after oral administration in mice and demonstrates that the mutagenic product of APNG is short-lived in vivo.

Genotoxic effects in peripheral blood and urine of workers exposed to low level benzene.

Blood samples were obtained from a population of refinery workers representing different age groups. Sixty six men with low average exposure to benzene and 33 male controls were investigated. An examination of cell cycle kinetics and sister chromatid exchange was carried out on control and exposed individuals.

The in vivo genotoxic properties of the nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine.

The N-nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine (APNG) was investigated for in vivo genotoxicity using the dominant lethal assay and the micronucleus test in mice, and the bone marrow test in rats. APNG was shown to cause definite genetic effects in the mouse but a much lesser effect in the rat, indicating that APNG is a genotoxic agent in vivo.

Chromosomal aberrations and sister chromatid exchanges in lymphocytes and urine mutagenicity of migraine patients: a comparison of chronic feverfew users and matched non-users.

1. Thirty migraine patients who had taken the leaves, tablets or capsules of feverfew daily for more than 11 consecutive months were compared to 30 feverfew non-user migraine patients who had been individually age- and sex-matched. 2.

Mutagenic effect of amniotic fluid from smoking women at term.

Concentrated term amniotic fluid samples from 44 women smokers and 44 controls were investigated with respect to mutagenic effect in the Salmonella/mammalian-microsome mutagenicity test, using tester strains TA98 and TA100. Tests with freeze-dried specimens of term amniotic fluid showed increases in the number of revertant colonies over background values, regardless of smoking status. However, samples from heavy smokers produced a higher number of revertants than did samples from nonsmokers in several experiments with tester strain TA98.

Study of the amniotic fluid from smokers and non-smokers in the Ames test.

Amniotic fluid from smokers and non-smokers was tested by the Salmonella/mammalian microsome test. Concentrated amniotic fluid from heavy smokers at term showed an increase in the number of revertants with increasing exposure to tar. However, some of the non-smokers had a higher number of revertants than the smokers.