Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders

Stress responses in alfalfa (Medicago sativa L.) XIX. Transcriptional activation of oxidative pentose phosphate pathway genes at the onset of the isoflavonoid phytoalexin response

Article on stress responses in alfalfa (Medicago sativa L.) XIX and transcriptional activation of oxidative pentose phosphate pathway genes at the onset of the isoflavonoid phytoalexin response

Novel Formative Approach of the ESAP-ITE Provides Strong Predictive Value for ABIM Certification Outcomes

AbstractBackgroundThe Endocrine Self-Assessment Program In-Training Examination (ESAP-ITE) has the novel formative approach of allowing open access to all questions and answers after secure examination administration is complete, resulting in the creation of an entirely new in-training examination annually.ObjectiveTo determine whether scores on the novel ESAP-ITE predict pass/fail outcomes on the American Board of Internal Medicine Endocrinology, Diabetes, and Metabolism Certification Examination (ABIM-ECE).MethodsAll endocrine fellows-in-training who took the ESAP-ITE between 2016 and 2019 and then subsequently attempted the ABIM-ECE within the same calendar year were included (n = 982). Primary analyses used the ESAP-ITE score from the final year of fellowship training. Covariates included sex, age on date of ABIM-ECE, medical school country, fellowship program region, pass/fail outcomes on the ABIM Internal Medicine Certification Examination, and ESAP-ITE score. All variables were analyzed using multivariable logistic regression.ResultsESAP-ITE score (P &amp;lt; 0.001), ABIM Internal Medicine Certification Examination outcome (P &amp;lt; 0.001), and age (P = 0.005) were each significant predictors of passing the ABIM-ECE on the first attempt. ESAP-ITE score was the strongest predictor of passing the ABIM-ECE, and this relationship was such that a score of 75% correct yielded a 97% probability of passing the ABIM-ECE, whereas a score of 50% correct generated only a 70% probability of doing so. Sex, fellowship program region, and medical school country were not significant predictors of ABIM-ECE outcomes.ConclusionsIn addition to serving as an important learning instrument for endocrine fellowship programs, ESAP-ITE is a robust predictive tool for pass/fail outcomes on the ABIM-ECE.</jats:sec

What’s in a Realist Configuration? Deciding Which Causal Configurations to Use, How, and Why

Background: Realist studies represent an increasingly popular approach for exploring complex interventions’ successes and failures. The theory-driven approach seeks to explain “what works, how, why, in which contexts, for whom, and to what extent” using context–mechanism–outcome (CMO) configurations. When the approach was first developed, CMO configurations were the method for expressing causal explanations. Increasingly, realist studies have been conducted using different variations of the heuristic such as strategy–context–mechanism–outcome (SCMO) configurations or intervention–context–actor–mechanism–outcome (ICAMO) configurations. Researchers have highlighted a lack of methodological guidance regarding which additional explanatory factors can be included in configurations (e.g., strategies, interventions, actors). This article aims to clarify and further develop the concept of configurations by discussing how explanatory factors could be robustly added to the original CMO configuration as put forward by Pawson and Tilley. Comparing the use of different types of configurations: We draw on two of our own studies, one which formulated CMO configurations and one which formulated SCMO configurations, and on an evidence scan of realist studies. We explored the effects these different configurations had on studies’ findings and highlight why researchers chose CMOs or SCMOs. Finally, we provide recommendations regarding the use of configurations. These are as follows: Using additional explanatory factors is possible but consider the research scope to select the configuration appropriate for the study; Be transparent about the choice in configuration and include examples of configurations; Further studies about the use of additional explanatory factors are needed to better understand the effects on each step in the realist evaluation cycle; and New ways of disseminating realist findings are needed to balance transparency regarding the use of configurations. Conclusions: Adding explanatory factors is possible and can be insightful depending on the study’s scope and aims; however, any configuration type must adhere to the rule of generative causation. </jats:sec

On-target activity of neoadjuvant cixutumumab and combined androgen deprivation therapy for high-risk prostate cancer: A phase II trial.

153 Background: IMC-A12 (cixutumumab) is a fully human monoclonal antibody which targets the insulin-like growth factor receptor 1. Preclinical data suggests that the combination of androgen deprivation and IMC-A12 is much more effective than either treatment alone. This clinical trial tests the effectiveness of the combined treatment in a neoadjuvant fashion before radical prostatectomy. We have assayed serum samples from the first 18 patients to identify signs of on-target activity in this setting. Methods: Eligible men with high risk localized prostate cancer are defined by one of the following: Gleason score ≥ 8, PSA ≥ 20, Clinical Stage T2c-T3, or a risk for relapse exceeding 50% as defined by the Kattan nomogram. Men are treated for 3 months with goserelin, bicalutamide, and biweekly IMC-A12 infusions (10 mg/kg). The primary objective of the trial is to determine the rate of pathological complete response with an accrual goal of 28 men. Using samples from the first 18 patients on study, serum protein markers were assayed by ELISA and serum PSA and glucose levels were determined by clinical laboratory analysis. Results: Significant increases in c-peptide (1.7-fold, p&lt;0.01), IGF-I (4.1-fold, p&lt;0.01), IGF-II (1.32-fold, p&lt;0.001), IGFBP-3 (1.9-fold, p&lt;0.01), growth hormone (8-fold, p&lt;0.01) were noted after initiation of ADT+IMC-A12, compared to pre-treatment levels. Non-significant increases of insulin (1.9-fold), IGFBP-1 (2-fold), and glucose (1.24-fold) levels were seen. Stratification of patients by nadir PSA levels correlated with residual tumor volume, likelihood of positive surgical margins and likelihood of lymph node metastases. Interestingly, patients with lower nadir PSA levels had smaller increases in c-peptide (50%, p&lt;0.01), insulin (66%, p&lt;0.02) and blood sugar (21%, P&lt;0.01) compared to the patients with higher nadir PSA levels. Conclusions: Combined with ADT in the neoadjuvant setting, IMC-A12 effectively targets the IGF-1R axis in prostate cancer patients. Metabolic differences between patients may alter the efficacy of IMC-A12 in this setting. [Table: see text] </jats:p