In multistep reactions, stability of intermediates is critical to the rate of product formation and a significant factor in generating kinetic traps. The capsid protein of cowpea chlorotic mottle virus (CCMV) can be induced to assemble into spherical particles of 30, 60, and 90 dimers. Based on examining assembly kinetics and reaction end points, we find that formation of uniform, ordered structures is not always a result of reactions that reach equilibrium. Equilibration or, alternatively, kinetic trapping can be identified by a straightforward analysis. Altering the assembly path of "spherical" particles is a means of controlling the distribution of products, which has broad applicability to self-assembly reactions.

Purpose The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with abnormal PSA and/or digital rectal examination. Experimental Design Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, age 40-79, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer (PCa), Gleason score, and tumor stage. Results Among European American (EA) men, there was an association of 25-OH D < 12 ng/ml with higher Gleason score ≥ 4+4 (OR = 3.66 [1.41, 9.50], p = 0.008) and tumor stage (stage ≥ cT2b vs. ≤ cT2a, OR = 2.42 [1.14, 5.10], p = 0.008). In African American (AA) men, we find increased odds of PCa diagnosis on biopsy with 25-OH D < 20 ng/ml (OR = 2.43 [1.20, 4.94], p = 0.01). AA men demonstrated an association between 25-OH D < 12ng/ml and Gleason ≥ 4+4 (OR = 4.89 [1.59, 15.07]; p = 0.006). There was an association with tumor stage ≥ cT2b vs. ≤ cT2a (OR: 4.22, [1.52 – 11.74], p = 0.003). Conclusions In AA men, vitamin D deficiency was associated with increased odds of PCa diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage.

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Vitamin D deficiency is epidemiologically linked to prostate, breast, and colon cancer. When compared with European American (EA) men, African American (AA) men have increased risk of prostate cancer, but few studies evaluate vitamin D status in AA men. The authors evaluate the biological and environmental predictors of vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet radiation environment. Blood samples were collected from 492 men, aged between 40 and 79 years, from urology clinics at three hospitals in Chicago, along with demographic and medical information, body mass index, and skin melanin content using a portable narrow-band reflectometer. Vitamin D intake and ultraviolet radiation exposure were assessed using validated questionnaires. The results demonstrated that Black race, cold season of blood draw, elevated body mass index, and lack of vitamin D supplementation increase the risk of vitamin D deficiency. Supplementation is a high-impact, modifiable risk factor. Race and sunlight exposure should be taken into account for recommended daily allowances for vitamin D intake.

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Background Among men with localized high‐risk prostate cancer (PCa), patients who meet very high‐risk (VHR) criteria have been shown to experience worse outcomes after radical prostatectomy (RP) in a previous study. Variations of VHR criteria have been suggested to be prognostic in other single‐center cohorts, but multicenter outcomes validating VHR criteria have not been described. This study was designed to validate VHR criteria for identifying which PCa patients are at greatest risk for cancer progression. Methods Patients with high‐risk PCa undergoing RP (2005‐2015) at 3 tertiary centers were pooled. The outcomes of men with VHR PCa were compared with the outcomes of those who did not meet VHR criteria. The high‐risk criteria were a clinical stage of T3 to T4, a prostate‐specific antigen level > 20 ng/mL, or a biopsy Gleason grade sum of 8 to 10. The VHR criteria were multiple high‐risk features, >4 biopsy cores with a Gleason grade sum of 8 to 10, or primary Gleason grade pattern 5. Biochemical recurrence, metastasis (METS), and cancer‐specific mortality (CSM) were assessed with competing risks regressions. Overall mortality was assessed with Cox survival models. Results Among 1981 patients with high‐risk PCa, men with VHR PCa (n = 602) had adverse pathologic outcomes: 37% versus 25% for positive margins and 37% versus 15% for positive lymph nodes (P <  .001 for both comparisons). Patients with VHR PCa also had higher adjusted hazard ratios for METS (2.78; 95% confidence interval [CI], 2.08‐3.72), CSM (6.77; 95% CI, 2.91‐15.7), and overall mortality (2.44; 95% CI, 1.56‐3.80; P <  .001 for all comparisons). Conclusions In a validation study of patients who underwent treatment for high‐risk PCa, VHR criteria were strongly associated with adverse pathologic and oncologic outcomes.

BACKGROUND Prostate cancer (PCa) and smoking-related morbidity disproportionately burdens African American (AA) men. Smoking is associated with high-grade PCa and incidence, but few studies have focused on AA men. This study aims to determine the effect of tobacco-use on odds of PCa and of high-grade PCa in a population of predominantly AA men. METHODS This is a cross-sectional study evaluating smoking and PCa status in men with incident PCa and screened healthy controls. Altogether, 1,085 men (527 cases and 558 controls), age ≥ 40 years were enrolled through outpatient urology clinics in two US cities from 2001 to 2012. Validated questionnaires were used to gather clinical and socioeconomic data. RESULTS The cases and controls were predominantly AA (79.9% and 71.3%, respectively, P = 0.01). AA men smoked more frequently (53.4% vs. 47.9%, P < 0.001) and quit less frequently than European American (EA) men (31.5% vs. 40.4%, P = 0.01). AA heavy smokers had increased odds of PCa diagnosis (OR 2.57, 95% CI 1.09, 6.10) and high-grade cancer (OR 1.89, 95% CI 1.03, 3.48) relative to never smokers and light smokers. Among AAs, heavy smokers had lower odds of NCCN low PCa recurrence risk stratification. AA former smokers had a trend for increased odds of high-grade cancer compared to never smokers. The associations between smokings, cancer diagnosis and cancer grade did not reach statistical significance in EA men. CONCLUSION We found ethnic differences in smoking behavior. Heavy smoking is associated with increased odds of PCa and of higher Gleason grade in AA men.

Purpose Lower serum Vitamin D levels has demonstrated associations with increased risk of aggressive prostate cancer. Among men with localized prostate cancer, especially with low- or intermediate risk disease, vitamin D may serve as an important biomarker of disease aggression. The aim of this study is to assess the relationship between adverse pathology at the time of radical prostatectomy and serum 25-hydroxyvitamin (25-OH D) levels. Patients and Methods This is a cross-sectional study from 2009 to 2014, nested within a large epidemiologic study of 1,760 healthy controls and men undergoing prostate cancer. In total, 190 men underwent radical prostatectomy in the cohort. Adverse pathology was defined as the presence of primary Gleason 4 or any Gleason 5 disease, or extra-prostatic extension. Descriptive and multivariate analyses were performed to assess the relationship between 25-OH D and adverse pathology at the time of prostatectomy. Results 45.8 % (87/190) of men in this cohort demonstrated adverse pathology at radical prostatectomy. The median age in the cohort was 64.0 years (IQR 59.0–67.0). On univariate analysis men with adverse pathology at radical prostatectomy demonstrated lower median serum 25-OH D (22.7 vs 27.0 ng/ml, p = 0.007) when compared to their counterparts. On multivariate analysis controlling for age, serum PSA, and suspicious digital rectal examination, serum 25-OH D < 30 ng/mL was associated with increased odds of adverse pathology (OR 2.64, 95% CI 1.25, 5.59, p = 0.01). Conclusion Insufficiency/Deficiency in serum 25-OH D is associated with increased odds of adverse pathology in men with localized disease undergoing radical prostatectomy. Serum 25-OH D may serve as a useful biomarker in prostate cancer aggressiveness, which deserves continued study.