The prevalence of vitamin supplementation in ultraendurance athletes

Ultraendurance exercise training places large energy demands on athletes and causes a high turnover of vitamins through sweat losses, metabolism, and the musculoskeletal repair process. Ultraendurance athletes may not consume sufficient quantities or quality of food in their diet to meet these needs. Consequently, they may use oral vitamin and mineral supplements to maintain their health and performance. We assessed the vitamin and mineral intake of ultraendurance athletes in their regular diet, in addition to oral vitamin and mineral supplements. Thirty-seven ultraendurance triathletes (24 men and 13 women) completed a 7-day nutrition diary including a questionnaire to determine nutrition adequacy and supplement intake. Compared with dietary reference intakes for the general population, both male and female triathletes met or exceeded all except for vitamin D. In addition, female athletes consumed slightly less than the recommended daily intake for folate and potassium; however, the difference was trivial. Over 60% of the athletes reported using vitamin supplements, of which vitamin C (97.5%), vitamin E (78.3%), and multivitamins (52.2%) were the most commonly used supplements. Almost half (47.8%) the athletes who used supplements did so to prevent or reduce cold symptoms. Only 1 athlete used supplements on formal medical advice. Vitamin C and E supplementation was common in ultraendurance triathletes, despite no evidence of dietary deficiency in these 2 vitamins.

Tocotrienol as potential anticancer agent

Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as an effective anticancer therapeutic agent. With most of the previous clinical studies on TP producing disappointing results, research has now focused on testing T3 as the next generation vitamin E for chemoprevention and cancer treatment. This review will summarize recent developments in the understanding of the anticancer effects of T3. We will also discuss current progress in clinical trials involving T3 as an adjuvant to conventional cancer therapy.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa : a cross-sectional study

Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

Training program impact on thermoplastic immobilization for head and neck radiation therapy

Purpose: To determine whether uniform guidelines and training in the stabilization and formation of thermoplastic shells can improve the reproducibility of set-up for Head and Neck cancer patients. Methods and materials: Image based measurements of the planning and treatment positions for 35 head and neck cancer patients undergoing radical radiotherapy were analysed to provide a baseline of the reproducibility of thermoplastic immobilization. Radiation therapists (RT) were surveyed to establish a perception of their confidence in thermoplastic procedures. An evidence based staff training program was created and implemented. Set-up reproduction and staff perception were reviewed to measure the impact of the training program. Results: The mean (SD) 3D vectors of anatomical displacement, measured on the patient images, improved from 4.64 (2.03) for the baseline group compared to 3.02 (1.65) following training (p < 0.01). The proportion of 3D displacements of patient data exceeding 5 mm 3D vector was decreased from 37.1% to 5.7% (p < 0.001) and the 3 mm vector from 85.7% to 42.9% (p < 0.001). The post-training survey scores demonstrated improved confidence in reproducibility of set-up for head and neck patients. Conclusion: The Thermoplastic Shells Training Program has been found to improve the treatment reproducibility for head and neck radiation therapy patients. Uniform guidelines have increased RT confidence in thermoplastic procedures.

Vitamin D intake, sun exposure and 25-hydroxy vitamin D status in Peritoneal dialysis (PD) and Haemodialysis (HD) patients

Inadequate vitamin D levels have been linked to bone disease but more recently have been associated with wider health implications. Limited studies suggest a high prevalence of Vitamin D deficiency in dialysis patients, although evidence is lacking on whether this is due to dietary restrictions, limited mobility and time outdoors or a combination of these. The aim of this study was to assess the contributions of diet, supplements and sunlight exposure to serum Vitamin D (25(OH)D) levels in dialysis patients. Cross-sectional data were obtained from 30 PD (Mean±SD age 56.9±16.2 y; n=13 male) and 22 HD (Mean±SD age 65.4±14.0 y; n=18 male) patients between 2009 and 2010. Serum 25(OH)D was measured and oral vitamin D intake estimated through a food-frequency-questionnaire and quantifying inactive supplementation. Sunlight exposure was assessed using a validated questionnaire. Prevalence of inadequate/insufficient vitamin D differed between dialysis modality (31% and 43% insufficient (<50nmol/L); 4% and 34% deficient (<25nmol/L) in HD and PD patients respectively (p=0.002)). In HD patients, there was a significant correlation between diet plus supplemental vitamin D intake and 25(OH)D (ρ=0.84, p<0.001). Results suggest a higher frequency of 25(OH)D inadequacy/deficiency in PD compared to HD patients. No other relationships between intake, sun exposure and 25(OH)D were seen. This could reflect limitations of the study design or the importance of other factors such as age, ethnicity and sun protection as interactions in the analysis. Understanding these factors is important given Vitamin D’s emerging status as a biomarker of systemic ill health.

Serine protease inhibition and mitochondrial dysfunction associated with cisplatin resistance in human tumor cell lines : targets for therapy

Indicators of mitochondrial function were studied in two different cell culture models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa-S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor—plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell line HeLa. In both models, CDDP resistance was associated with sensitivity to killing by adriamycin, etoposide, auranofin, bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride {[Au(DPPE)2]Cl}, CdCl2 and the mitochondrial inhibitors rhodamine-123 (Rhl23), dequalinium chloride (DeCH), tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate dehydrogenase activities. Total platinum uptake and DNA-bound platinum were slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by HeLa-S1a was similar to HeLa, but DNA-bound platinum was much lower than for the parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered morphology and were fewer in number than those of JAM and HeLa. In both models, CDDP resistance was associated with less platinum accumulation and with mitochondrial and membrane defects, brought about one case with expression of a protease inhibitor which is implicated in tumor progression. Such markers may identify tumors suitable for treatment with gold phosphine complexes or other mitochondrial inhibitors.

Productivity and time use during occupational therapy and nutrition/dietetics clinical education : a cohort study

Background: Currently in the Australian higher education sector higher productivity from allied health clinical education placements are a contested issue. This paper will report results of a study that investigated output changes associated with occupational therapy and nutrition/dietetics clinical education placements in Queensland, Australia. Supervisors’ and students’ time use during placements and how this changes for supervisors compared to when students are not present in the workplace is also presented. Methodology/Principal Findings: A cohort design was used with students from four Queensland universities, and their supervisors employed by Queensland Health. There was an increasing trend in the number of occasions of service delivered when the students were present, and a statistically significant increase in the daily mean length of occasions of service delivered during the placement compared to pre-placement levels. For project-based placements that were not directly involved in patient care, supervisors’ project activity time decreased during placements, with students undertaking considerably more time in project activities. Conclusions/Significance: A novel method for estimating productivity and time use changes during clinical education programs for allied health disciplines has been applied. During clinical education placements there was a net increase in outputs, suggesting supervisors engage in longer consultations with patients for the purpose of training students, while maintaining patient numbers. Other activities are reduced. This paper is the first time these data have been shown and form a good basis for future assessments of the economic impact of student placements for allied health disciplines.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Prenatal Vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation

In a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin d deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin d-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin d deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin d status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

Does the addition of integrated cognitive behaviour therapy and motivational interviewing improve the outcomes of standard care for young people with comorbid depression and substance misuse?

Background: The high rates of comorbid depression and substance use in young people have been associated with a range of adverse outcomes. Yet, few treatment studies have been conducted with this population. Objective: To determine if the addition of Motivational Interviewing and Cognitive Behaviour Therapy (MI/CBT) to standard alcohol and other drug (AOD) care improves the outcomes of young people with comorbid depression and substance use. Participants and Setting: Participants comprised 88 young people with comorbid depression (Kessler 10 score of > 17) and substance use (mainly alcohol/cannabis) seeking treatment at two youth AOD services in Melbourne, Australia. Sixty young people received MI/CBT in addition to standard care (SC) and 28 received SC alone. Outcomes Measures: Primary outcome measures were depressive symptoms and drug and alcohol use in the past month. Assessments were conducted at baseline, 3 and 6 months follow up. Results and Conclusions: The addition of MI/CBT to SC was associated with a significantly greater rate of change in depression, cannabis use, motivation to change substance use and social contact in the first 3 months. However, those who received SC had achieved similar improvements on these variables by 6 months follow up. All young people achieved significant improvements in functioning and quality of life variables over time, regardless of the treatment group. No changes in alcohol or other drug use were found in either group. The delivery of MI/CBT in addition to standard AOD care may offer accelerated treatment gains in the short-term.