Hydrogen bonding heterogeneity correlates with protein folding transition state passage time as revealed by data sonification.

Protein-protein and protein-water hydrogen bonding interactions play essential roles in the way a protein passes through the transition state during folding or unfolding, but the large number of these interactions in molecular dynamics (MD) simulations makes them difficult to analyze. Here, we introduce a state space representation and associated "rarity" measure to identify and quantify transition state passage (transit) events. Applying this representation to a long MD simulation trajectory that captured multiple folding and unfolding events of the GTT WW domain, a small protein often used as a model for the folding process, we identified three transition categories: Highway (faster), Meander (slower), and Ambiguous (intermediate). We developed data sonification and visualization tools to analyze hydrogen bond dynamics before, during, and after these transition events. By means of these tools, we were able to identify characteristic hydrogen bonding patterns associated with "Highway" versus "Meander" versus "Ambiguous" transitions and to design algorithms that can identify these same folding pathways and critical protein-water interactions directly from the data. Highly cooperative hydrogen bonding can either slow down or speed up transit. Furthermore, an analysis of protein-water hydrogen bond dynamics at the surface of WW domain shows an increase in hydrogen bond lifetime from folded to unfolded conformations with Ambiguous transitions as an outlier. In summary, hydrogen bond dynamics provide a direct window into the heterogeneity of transits, which can vary widely in duration (by a factor of 10) due to a complex energy landscape.

Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy.

PURPOSE: Infection after transrectal prostate biopsy has become an increasing concern due to fluoroquinolone resistant bacteria. We determined whether colonization identified by rectal culture can identify men at high risk for post-transrectal prostate biopsy infection. MATERIALS AND METHODS: Six institutions provided retrospective data through a standardized, web based data entry form on patients undergoing transrectal prostate biopsy who had rectal culture performed. The primary outcome was any post-transrectal prostate biopsy infection and the secondary outcome was hospital admission 30 days after transrectal prostate biopsy. We used chi-square and logistic regression statistical analysis. RESULTS: A total of 2,673 men underwent rectal culture before transrectal prostate biopsy from January 1, 2007 to September 12, 2013. The prevalence of fluoroquinolone resistance was 20.5% (549 of 2,673). Fluoroquinolone resistant positive rectal cultures were associated with post-biopsy infection (6.6% vs 1.6%, p <0.001) and hospitalization (4.4% vs 0.9%, p <0.001). Fluoroquinolone resistant positive rectal culture increased the risk of infection (OR 3.98, 95% CI 2.37-6.71, p <0.001) and subsequent hospital admission (OR 4.77, 95% CI 2.50-9.10, p <0.001). If men only received fluoroquinolone prophylaxis, the infection and hospitalization proportion increased to 8.2% (28 of 343) and 6.1% (21 of 343), with OR 4.77 (95% CI 2.50-9.10, p <0.001) and 5.67 (95% CI 3.00-10.90, p <0.001), respectively. The most common fluoroquinolone resistant bacteria isolates were Escherichia coli (83.7%). Limitations include the retrospective study design, nonstandardized culture and interpretation of resistance methods. CONCLUSIONS: Colonization of fluoroquinolone resistant organisms in the rectum identifies men at high risk for infection and subsequent hospitalization from prostate biopsy, especially in those with fluoroquinolone prophylaxis only.

A prospective randomized trial of povidone-iodine prophylactic cleansing of the rectum before transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided prostate biopsy can lead to urinary tract infections in 3% to 11% and sepsis in 0.1% to 5% of patients. We investigated the efficacy of rectal cleansing with povidone-iodine before transrectal ultrasound guided prostate biopsy to reduce infectious complications. MATERIALS AND METHODS: Between 2009 and 2011, 865 men were prospectively randomized to rectal cleansing (421) or no cleansing (444) before transrectal ultrasound guided prostate biopsy. Patients received ciprofloxacin prophylaxis and rectal swab cultures were obtained before transrectal ultrasound guided prostate biopsy. Patients completed a telephone interview 7 days after undergoing the biopsy. The primary end point was the rate of infectious complications, a composite end point of 1 or more of 1) fever greater than 38.0C, 2) urinary tract infection or 3) sepsis (standardized definition). Chi-square significance testing was performed for differences between groups and a multivariate analysis was performed to assess risk factors for infectious complications. RESULTS: Infectious complications were observed in 31 (3.5%) patients, including 11 (2.6%) treated and 20 (4.5%) control patients (p = 0.15). Sepsis was observed in 4 (1.0%) treated and 7 (1.6%) control patients (p = 0.55). On multivariate analysis resistance to ciprofloxacin in the rectal swab culture (p = 0.002) and a history of taking ciprofloxacin in the 3 months preceding transrectal ultrasound guided prostate biopsy (p = 0.009) predicted infectious complications. CONCLUSIONS: Rectal cleansing with povidone-iodine before transrectal ultrasound guided prostate biopsy was safe, but the 42% relative risk reduction of infectious complications was not statistically significant. Patients who have received ciprofloxacin within 3 months of transrectal ultrasound guided prostate biopsy should be considered for alternate prophylaxis or possibly a delay of biopsy beyond 3 months.

The influence of diet on fatty acids in the egg yolk of green sea turtles, Chelonia mydas.

Fatty acid concentrations found in the yolk of green sea turtles reflect differences in the diet of the mothers. All of the 12 fatty acids measured in yolk samples were significantly different between eggs produced from the pellet and wild-type diets. However, the relative pattern of yolk fatty acids in the green turtle mirrored those of other reptiles. Yolk samples contained mostly (63-67%) 14:0. 16:0, 16:1n-7 and 18:1n-9. Yolks from captive animals on pellet diet contained an additional 17.64% of the total yolk lipid as 12:0 and 18:2n-6. Wild yolks contained an extra 11.41% of lipid as 18:0 and 18:1n-7. Selection of fatty acids for the yolk should balance the energetic and anabolic needs of the embryo. Eggs are provisioned based on maternal metabolism of available nutrients and subtle differences between natural foods and those available in captivity could affect the viability of future eggs.