Antioxidant supplementation and immunoendocrine responses to prolonged exercise

Davison, Glen, et al., 'Antioxidant supplementation and immunoendocrine responses to prolonged exercise', Medicine and Science in Sports and Exercise, (2007) 39(4) pp.645-652 RAE2008

Political Leadership and Public Support In Belarus: Forward to the Past?

Korosteleva-Polglase Elena, White, S., 'Political Leadership and Public Support In Belarus: Forward to the Past?', In: 'The EU and Belarus: Between Moscow and Brussels', (London: Kogan Page), pp.51-71, 2001 RAE2008

Keats and the Holocaust: Notes towards a post-temporalism

Grovier, Kelly, 'Keats and the Holocaust: Notes towards a post-temporalism', Literature and Theology (2003) 17 (4) pp.361-373 RAE2008

Evaluation of microbial adjuncts and their effect on the ripening of cheddar cheese

A bacteriocin-producing strain of Lactobacillus paracasei DPC 4715 was used as an adjunct culture in Cheddar cheese in order to control the growth of “wild” nonstarter lactic acid bacteria. No suppression of growth of the indicator strain was observed in the experimental cheese. The bacteriocin produced by Lactobacillus paracasei DPC 4715 was sensitive to chymosin and cathepsin D and it may have been cleaved by the rennet used for the cheese manufactured or by indigenous milk proteases. A series of studies were performed using various microbial adjuncts to influence cheese ripening. Microbacterium casei DPC 5281, Corynebacterium casei DPC 5293 and Corynebacterium variabile DPC 5305 were added to the cheesemilk at level of 109 cfu/ml resulting in a final concentration of 108 cfu/g in Cheddar cheese. The strains significantly increased the level of pH 4.6-soluble nitrogen, total free amino acids after 60 and 180 d of ripening and some individual free amino acids after 180 d. Yarrowia lipolytica DPC 6266, Yarrowia lipolytica DPC 6268 and Candida intermedia DPC 6271 were used to accelerate the ripening of Cheddar cheese. Strains were grown in YG broth to a final concentration of 107 cfu/ml, microfluidized, freeze-dried and added to the curd during salting at level of 2% w/w. The yeasts positively affected the primary, secondary proteolysis and lipolysis of cheeses and had aminopeptidase, dipeptidase, esterase and 5’ phosphodiestere activities that contributed to accelerate the ripening and improve the flavor of cheese. Hafia alvei was added to Cheddar cheesemilk at levels of 107 cfu/ml and 108 cfu/ml and its contribution during ripening was evaluated. The strain significantly increased the level of pH 4.6-soluble nitrogen, total free amino-acids, and some individual free amino-acids of Cheddar cheese, whereas no differences in the urea-polyacrylamide gel electrophoresis (urea-PAGE) electrophoretograms of the cheeses were detected. Hafia alvei also significantly increased the level of some biogenic amines. A low-fat Cheddar cheese was made with Bifidobacterium animalis subsp. lactis, strain BB-12® at level of 108 cfu/ml, as a probiotic adjunct culture and Hi-Maize® 260 (resistant high amylose maize starch) at level of 2% and 4% w/v, as a prebiotic fiber which also played the role of fat replacer. Bifidobacterium BB-12 decreased by 1 log cycle after 60 d of ripening and remained steady at level of ~107 cfu/g during ripening. The Young’s modulus also increased proportionally with increasing levels of Hi-maize. Hencky strain at fracture decreased over ripening and increased with increasing in fat replacer. A cheese based medium (CBM) was developed with the purpose of mimicking the cheese environment at an early ripening stage. The strains grown in CBM showed aminopeptidase activity against Gly-, Arg-, Pro- and Phe-p-nitroanalide, whereas, when grown in MRS they were active against all the substrates tested. Both Lb. danicus strains grown in MRS and in CBM had aminotransferase activity towards aromatic amino acids (Phe and Trp) and also branched-chain amino acids (Leu and Val). Esterase activity was expressed against p-nitrophenyl-acetate (C2), pnitrophenyl- butyrate (C4) and p-nitrophenyl-palmitate (C16) and was significantly higher in CBM than in MRS.

Citizenship education in Irish secondary schools: the influence of curriculum content, school culture and stakeholder perspectives

This research interrogates the status of citizenship education in Irish secondary schools. The following questions are examined: How does school culture impact on citizenship education? What value is accorded to the subjects, Civic, Social and Political Education (CSPE) and Social, Personal and Health Education (SPHE)? To what extent are the subjects of both the cognitive and non-cognitive curricula affirmed? The importance of these factors in supporting the social, ethical, personal, political and emotional development of students is explored. The concept of citizenship is dynamic and constantly evolving in response to societal change. Society is increasingly concerned with issues such as: globalisation; cosmopolitanism; the threat of global risk; environment sustainability; socio-economic inequality; and recognition/misrecognition of new identities and group rights. The pedagogical philosophy of Paulo Freire which seeks to educate for the conscientisation and humanisation of the student is central to this research. Using a mixed methods approach, data on the insights of students, parents, teachers and school Principals was collected. In relation to Irish secondary school education, the study reached three main conclusions. (1) The educational stakeholders rate the subjects of the non-cognitive curriculum poorly. (2) The subjects Civic, Social and Political education (CSPE), and Social, Personal and Health Education (SPHE) command a low status in the secondary school setting. (3) The day-to-day school climate is influenced by an educational philosophy that is instrumentalist in character. Elements of school culture such as: the ethic of care; the informal curriculum; education for life after school; and affirmation of teachers, are not sufficiently prioritised in supporting education for citizenship. The research concludes that the approach to education for citizenship needs to be more robust within the overall curriculum, and culture and ethos of the Irish education system.

Evaluation of rhizobacterial colonisation and the ability to induce Globodera pallida hatch

Three bacterial isolates, SB13 (Acinetobacter sp.), SB14 (Arthrobacter sp.) and SB15 (Bacillus sp.), were previously isolated from the rhizosphere of sugar beet (Beta vulgaris ssp. vulgaris) plants and shown to increase hatch of potato cyst nematodes in vitro. In this study, the three isolates were assayed for rhizosphere competence. Each isolate was applied to seeds at each of four concentrations (105-108 CFU ml−1) and the inoculated seeds were planted in plastic microcosms containing coarse sand. All three isolates were shown to colonise the rhizosphere, although to differing degrees, with the higher inoculation densities providing significantly better colonisation. The isolates increased sugar beet root and shoot dry weight. Isolates SB14 and SB15 were analysed for their ability to induce in vivo hatch of Globodera pallida in non-sterile soil planted with sugar beet. After 4 and 6 weeks, both isolates had induced significantly greater percentage hatch compared to controls.

A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

3-year results of docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer: a pilot study.

BACKGROUND: Docetaxel has proven efficacy in metastatic breast cancer. In this pilot study, we explored the efficacy/feasibility of docetaxel-based sequential and combination regimens as adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: From March 1996 till March 1998, four consecutive groups of patients with stages II and III breast cancer, aged < or = 70 years, received one of the following regimens: a) sequential Doxorubicin (A) --> Docetaxel (T) --> CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil): A 75 mg/m q 3 wks x 3, followed by T100 mg/m2 q 3 wks x 3, followed by i.v. CMF Days 1+8 q 4 wks x 3; b) sequential accelerated A --> T --> CMF: A and T administered at the same doses q 2 wks with Lenograstin support; c) combination therapy: A 50 mg/m2 + T 75 mg/m2 q 3 wks x 4, followed by CMF x 4; d) sequential T --> A --> CMF: T and A, administered as in group a), with the reverse sequence. When indicated, radiotherapy was administered during or after CMF, and Tamoxifen after CMF. RESULTS: Ninety-three patients were treated. The median age was 48 years (29-66) and the median number of positive axillary nodes was 6 (1-25). Tumors were operable in 94% and locally advanced in 6% of cases. Pathological tumor size was >2 cm in 72% of cases. There were 21 relapses, (18 systemic, 3 locoregional) and 11 patients (12%) have died from disease progression. At median follow-up of 39 months (6-57), overall survival (OS) was 87% (95% CI, 79-94%) and disease-free survival (DFS) was 76% (95% CI, 67%-85%). CONCLUSION: The efficacy of these docetaxel-based regimens, in terms of OS and DFS, appears to be at least as good as standard anthracycline-based adjuvant chemotherapy (CT), in similar high-risk patient populations.

Correlates of poor health among orphans and abandoned children in less wealthy countries: the importance of caregiver health.

BACKGROUND: More than 153 million children worldwide have been orphaned by the loss of one or both parents, and millions more have been abandoned. We investigated relationships between the health of orphaned and abandoned children (OAC) and child, caregiver, and household characteristics among randomly selected OAC in five countries. METHODOLOGY: Using a two-stage random sampling strategy in 6 study areas in Cambodia, Ethiopia, India, Kenya, and Tanzania, the Positive Outcomes for Orphans (POFO) study identified 1,480 community-living OAC ages 6 to 12. Detailed interviews were conducted with 1,305 primary caregivers at baseline and after 6 and 12 months. Multivariable logistic regression models describe associations between the characteristics of children, caregivers, and households and child health outcomes: fair or poor child health; fever, cough, or diarrhea within the past two weeks; illness in the past 6 months; and fair or poor health on at least two assessments. PRINCIPAL FINDINGS: Across the six study areas, 23% of OAC were reported to be in fair or poor health; 19%, 18%, and 2% had fever, cough, or diarrhea, respectively, within the past two weeks; 55% had illnesses within the past 6 months; and 23% were in fair or poor health on at least two assessments. Female gender, suspected HIV infection, experiences of potentially traumatic events, including the loss of both parents, urban residence, eating fewer than 3 meals per day, and low caregiver involvement were associated with poorer child health outcomes. Particularly strong associations were observed between child health measures and the health of their primary caregivers. CONCLUSIONS: Poor caregiver health is a strong signal for poor health of OAC. Strategies to support OAC should target the caregiver-child dyad. Steps to ensure food security, foster gender equality, and prevent and treat traumatic events are needed.

Herbal Dietary Supplements: Safety, Efficacy, and Use by Breast Cancer Survivors

Gemstone Team IMAC (Integrative Medicine and Cancer)

Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy.

Intervertebral disc herniation may contribute to inflammatory processes that associate with radicular pain and motor deficits. Molecular changes at the affected dorsal root ganglion (DRG), spinal cord, and even midbrain, have been documented in rat models of radiculopathy or nerve injury. The objective of this study was to evaluate gait and the expression of key pain receptors in the midbrain in a rodent model of radiculopathy. Radiculopathy was induced by harvesting tail nucleus pulposus (NP) and placing upon the right L5 DRG in rats (NP-treated, n=12). Tail NP was discarded in sham-operated animals (n=12). Mechanical allodynia, weight-bearing, and gait were evaluated in all animals over time. At 1 and 4 weeks after surgery, astrocyte and microglial activation was tested in DRG sections. Midbrain sections were similarly evaluated for immunoreactivity to serotonin (5HT(2B)), mu-opioid (µ-OR), and metabotropic glutamate (mGluR4 and 5) receptor antibodies. NP-treated animals placed less weight on the affected limb 1 week after surgery and experienced mechanical hypersensitivity over the duration of the study. Astroctye activation was observed at DRGs only at 4 weeks after surgery. Findings for pain receptors in the midbrain of NP-treated rats included an increased expression of 5HT(2B) at 1, but not 4 weeks; increased expression of µ-OR and mGluR5 at 1 and 4 weeks (periaqueductal gray region only); and no changes in expression of mGluR4 at any point in this study. These observations provide support for the hypothesis that the midbrain responds to DRG injury with a transient change in receptors regulating pain responses.

In vivo luminescence imaging of NF-κB activity and serum cytokine levels predict pain sensitivities in a rodent model of osteoarthritis.

OBJECTIVE: To investigate the relationship between NF-κB activity, cytokine levels, and pain sensitivities in a rodent model of osteoarthritis (OA). METHODS: OA was induced in transgenic NF-κB-luciferase reporter mice via intraarticular injection of monosodium iodoacetate (MIA). Using luminescence imaging we evaluated the temporal kinetics of NF-κB activity and its relationship to the development of pain sensitivities and serum cytokine levels in this model. RESULTS: MIA induced a transient increase in joint-related NF-κB activity at early time points (day 3 after injection) and an associated biphasic pain response (mechanical allodynia). NF-κB activity, serum interleukin-6 (IL-6), IL-1β, and IL-10 levels accounted for ∼75% of the variability in pain-related mechanical sensitivities in this model. Specifically, NF-κB activity was strongly correlated with mechanical allodynia and serum IL-6 levels in the inflammatory pain phase of this model (day 3), while serum IL-1β was strongly correlated with pain sensitivities in the chronic pain phase of the model (day 28). CONCLUSION: Our findings suggest that NF-κB activity, IL-6, and IL-1β may play distinct roles in pain sensitivity development in this model of arthritis and may distinguish the acute pain phase from the chronic pain phase. This study establishes luminescence imaging of NF-κB activity as a novel imaging biomarker of pain sensitivities in this model of OA.

Enhanced de novo alloantibody and antibody-mediated injury in rhesus macaques.

Chronic allograft rejection is a major impediment to long-term transplant success. Humoral immune responses to alloantigens are a growing clinical problem in transplantation, with mounting evidence associating alloantibodies with the development of chronic rejection. Nearly a third of transplant recipients develop de novo antibodies, for which no established therapies are effective at preventing or eliminating, highlighting the need for a nonhuman primate model of antibody-mediated rejection. In this report, we demonstrate that depletion using anti-CD3 immunotoxin (IT) combined with maintenance immunosuppression that included tacrolimus with or without alefacept reliably prolonged renal allograft survival in rhesus monkeys. In these animals, a preferential skewing toward CD4 repopulation and proliferation was observed, particularly with the addition of alefacept. Furthermore, alefacept-treated animals demonstrated increased alloantibody production (100%) and morphologic features of antibody-mediated injury. In vitro, alefacept was found to enhance CD4 effector memory T cell proliferation. In conclusion, alefacept administration after depletion and with tacrolimus promotes a CD4+memory T cell and alloantibody response, with morphologic changes reflecting antibody-mediated allograft injury. Early and consistent de novo alloantibody production with associated histological changes makes this nonhuman primate model an attractive candidate for evaluating targeted therapeutics.

The Toronto Word Pool: Norms for imagery, concreteness, orthographic variables, and grammatical usage for 1,080 words

Imagery and concreteness norms and percentage noun usage were obtained on the 1,080 verbal items from the Toronto Word Pool. Imagery was defined as the rated ease with which a word aroused a mental image, and concreteness was defined in relation to level of abstraction. The degree to which a word was functionally a noun was estimated in a sentence generation task. The mean and standard deviation of the imagery and concreteness ratings for each item are reported together with letter and printed frequency counts for the words and indications of sex differences in the ratings. Additional data in the norms include a grammatical function code derived from dictionary definitions, a percent noun judgment, indexes of statistical approximation to English, and an orthographic neighbor ratio. Validity estimates for the imagery and concreteness ratings are derived from comparisons with scale values drawn from the Paivio, Yuille, and Madigan (1968) noun pool and the Toglia and Battig (1978) norms. © 1982 Psychonomic Society, Inc.

Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.

Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint.