Hyperglycaemia-induced resistance to Docetaxel is negated by metformin:a role for IGFBP-2

The incidence of many common cancers varies between different populations and appears to be affected by a Western lifestyle. Highly proliferative malignant cells require sufficient levels of nutrients for their anabolic activity. Therefore, targeting genes and pathways involved in metabolic pathways could yield future therapeutics. A common pathway implicated in energetic and nutritional requirements of a cell is the LKB1/AMPK pathway. Metformin is a widely studied anti-diabetic drug, which improves glycaemia in patients with type 2 diabetes by targeting this pathway. We investigated the effect of metformin on prostate cancer cell lines and evaluated its mechanism of action using DU145, LNCaP, PC3 and VCaP prostate cancer cell lines. Trypan blue dye-exclusion assay was used to assess levels of cell death. Western immunoblotting was used to determine the abundance of proteins. Insulin-like growth factor-binding protein-2 (IGFBP-2) andAMPKgenes were silenced using siRNA. Effects on cell morphology were visualised using microscopy.IGFBP-2gene expression was assessed using real-time RT-PCR. With DU145 and LNCaP cells metformin alone induced cell death, but this was reduced in hyperglycaemic conditions. Hyperglycaemia also reduced the sensitivity to Docetaxel, but this was countered by co-treatment with metformin. LKB1 was required for the activation of AMPK but was not essential to mediate the induction of cell death. An alternative pathway by which metformin exerted its action was through downregulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK. This finding could have important implications in relation to therapeutic strategies in prostate cancer patients presenting with diabetes.</jats:p

Nanotechnology and the Developing World

How nanotechnology can be harnessed to address some of the world's most critical development problem

Supportive care for men with prostate cancer:why are the trials not working? A systematic review and recommendations for future trials

Men with prostate cancer are likely to have a long illness and experience psychological distress for which supportive care may be helpful. This systematic review describes the evidence for effectiveness and cost-effectiveness of supportive care for men with prostate cancer, taking into account treatment pathway and components of interventions. MEDLINE, EMBASE, CINAHL, CENTRAL, and Psychinfo were searched from inception--July 2013 for randomized controlled trials and controlled trials. Two authors independently assessed risk of bias and extracted data. Twenty-six studies were included (2740 participants). Interventions were delivered pre and during (n = 12), short-term (n = 8), and longer term (18 months) (n = 5) after primary treatment. No interventions were delivered beyond this time. Few trials recruited ethnic minorities and none recruited men in same sex relationships. Intervention components included information, education, health professional discussion, homework, peer discussion, buddy support, cognitive behavioral therapy, cognitive restructuring, psychoeducation, Reiki and relaxation. Most interventions were delivered for 5-10 weeks. Risk of bias of trials was assessed as unclear for most domains due to lack of information. The majority of trials measuring quality of life and depression found no effect. Relatively few trials measured anxiety, coping skills and self-efficacy, and the majority found no effect. No cost data were available. Trials of supportive care for men with prostate cancer cover a range of interventions but are limited by population diversity, inconsistent measurement and reporting of outcomes, and inability to assess risk of bias. Recommendations on design and conduct of future trials are presented

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT):Study protocol for a randomised controlled feasibility trial

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.10 page(s

COVID-19 Vaccine Refusal and Fair Allocation of Scarce Medical Resources

When hospitals face surges of patients with COVID-19, fair allocation of scarce medical resources remains a challenge. Scarcity has at times encompassed not only hospital and intensive care unit beds—often reflecting staffing shortages—but also therapies and intensive treatments. Safe, highly effective COVID-19 vaccines have been free and widely available since mid-2021, yet many Americans remain unvaccinated by choice. Should their decision to forgo vaccination be considered when allocating scarce resources? Some have suggested it should,while others disagree. We offer a framework for evaluating when it is ethical and briefly discuss its legality in American law

Frequency of Toxoplasmosis in Water Buffalo (Bubalus bubalis) in Trinidad

Toxoplasmosis has been reported to occur in several animals and humans causing different clinical manifestations. The study was conducted to determine the frequency of Toxoplasma gondii antibodies (IgG) in water buffalo (Bubalus bubalis) across farms in Trinidad using a latex agglutination test. Of a total of 333 water buffalo tested, 26 (7.8%) were seropositive for T. gondii antibodies. Seropositivity for toxoplasmosis was statistically significantly (P < 0.05; χ2) higher in adult water buffalo, 12.4% (14 of 113) compared with young water buffalo, 4.2% (6 of 143). Seropositivity for toxoplasmosis across the seven farms ranged from 0.0% (0 of 20) in Farm G compared with 20.0% (10 of 50) detected in Farm B. The differences in seropositivity by management system, free-ranging 6.7% (14 of 213) and semi-intensive 10.0% (12 of 120) and by sex, in male 6.7% (7 of 104) and female 8.3% (19 of 229) water buffalo, were not statistically significant (P > 0.05; χ2). This is the first documentation of toxoplasmosis in water buffalo in Trinidad

Reproductive Behavior of the Emu

Members of a flock of male and female emus were observed in an ethological experiment designed to investigate trends in reproductive behavior exhibited during the North American mating season, which lasts from October to mid-March. Observations were made at dawn, noon, and dusk from December 1999 to mid-March 2000, and the only behaviors that were consistently expressed during these times were pecking, strutting, exclusive, and male and female sexual activities (defined in text). Though statistical significance was found between male strutting behavior and female sexual activity in the December observation period, no overall significance or significance at other observation periods was found between these two behaviors. No statistical significance was found between male pecking and female sexual behavior—overall or at separate observation periods. The emus also showed more incidences of mating activity at dawn and under cool temperature conditions. Exclusive behavior, however, was more prominent during the dusk observation period