To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.

Using a case-control design, we evaluated differences in risk factors for colorectal polyps according to histological type, anatomical site, and severity. Participants were enrollees in the Group Health Cooperative aged 20-79 years who underwent colonoscopy in Seattle, Washington, between 1998 and 2007 and comprised 628 adenoma cases, 594 serrated polyp cases, 247 cases with both types of polyps, and 1,037 polyp-free controls. Participants completed a structured interview, and polyps were evaluated via standardized pathology review. We used multivariable polytomous logistic regression to compare case groups with controls and with the other case groups. Factors for which the strength of the association varied significantly between adenomas and serrated polyps were sex (P < 0.001), use of estrogen-only postmenopausal hormone therapy (P = 0.01), and smoking status (P < 0.001). For lesion severity, prior endoscopy (P < 0.001) and age (P = 0.05) had significantly stronger associations with advanced adenomas than with nonadvanced adenomas; and higher education was positively correlated with sessile serrated polyps but not with other serrated polyps (P = 0.02). Statistically significant, site-specific associations were observed for current cigarette smoking (P = 0.05 among adenomas and P < 0.001 among serrated polyps), postmenopausal estrogen-only therapy (P = 0.01 among adenomas), and obesity (P = 0.01 among serrated polyps). These findings further illustrate the epidemiologic heterogeneity of colorectal neoplasia and may help elucidate carcinogenic mechanisms for distinct pathways.

Exposure to cadmium, a heavy metal present in cigarettes, can be assessed in both urine and blood. Few studies have compared the properties of concurrent measurements of urine cadmium (uCd) and blood cadmium (bCd) in relation to the duration and timing of a known exposure. In this study, bCd and uCd were modeled with data from the National Health and Nutrition Examination Survey (1999–2010). Adjusted geometric mean bCd and uCd were estimated from regression results. Each 1% higher geometric mean uCd was associated with 0.50% (95% CI: 0.47%–0.54%; R2=0.30) higher bCd. In male never-smokers, bCd was 69% (59%–81%) and uCd was 200%(166%–234%) higher at age ≥70y versus 20–29y. Ten pack-years (py) of smoking were associated with 13.7%(10.0%–17.4%) higher bCd and 16.8% (12.6%–21.1%) higher uCd in male smokers. The first year after smoking cessation was associated with 53% (48%–58%) lower bCd and 23%(14%–33%) lower uCd in representative males age 55y with 20py smoking. Smoking in the previous 5 days was associated with 55%(40%–71%) higher bCd and 7%(−3%–18%) higher uCd. Results were similar for women. uCd mainly measures long-term exposure and bCd recent exposure, but with noticeable overlap. Epidemiological studies should base the choice of uCd or bCd on the timing of cadmium exposure relevant to the disease under study.

Objective This study examined prospective data from the Third National Health and Nutrition Examination Survey (NHANES III) cohort to investigate the relationship between cadmium exposure and cancer mortality, and the specific cancers associated with cadmium exposure, in the general population. Methods Vital status and cause of death through December 31, 2006 were obtained by the National Center for Health Statistics for NHANES III participants. Cadmium concentration of spot urine samples was measured, and corrected for urine creatinine. Weighted Cox proportional hazards regression with age as the time metric was applied to estimate sex-specific adjusted hazard ratios (aHRs) of mortality associated with uCd for all cancers and the cancers responsible for the most deaths in the US. Estimates were stratified by smoking history and adjusted education, body mass index, and race. Results uCd was associated with cancer mortality (aHR per 2-fold higher uCd (95%CI), men: 1.26 (1.07–1.48)); women: 1.21 (1.04–1.42)). In men, mortality from lung, pancreatic cancer and non-Hodgkin lymphoma was associated with uCd; an association with leukemia mortality was suggested. In women, associations were suggested with mortality due to lung cancer, leukemia, ovarian, and uterine cancer, but evidence was weaker than in men. Conclusions Cadmium appears to be associated with overall cancer mortality in men and women, but the specific cancers associated differ between men and women, suggesting avenues for future research. Limitations of the study include the possibility of uncontrolled confounding by cigarette smoking or other factors, and the limited number of deaths due to some cancers.

Background and objectives Although a peritoneal equilibration test yields data on three parameters (4-hour dialysate/plasma creatinine, 4-to 0-hour dialysate glucose, and 4-hour ultrafiltration volume), all studies have focused on the prognostic value of dialysate/plasma creatinine for patients undergoing peritoneal dialysis. Because dialysate 4-to 0-hour glucose and ultrafiltration volume may be superior in predicting daily ultrafiltration, the likely mechanism for the association of peritoneal equilibration test results with outcomes, we hypothesized that they are superior to dialysate/plasma creatinine for risk prediction.Design, setting, participants, & measurements We examined unadjusted and adjusted associations of three peritoneal equilibration test parameters with all-cause mortality, technique failure, and hospitalization rate in 10,142 patients on peritoneal dialysis treated between January 1, 2007 and December 31, 2011 in 764 dialysis facilities operated by a single large dialysis organization in the United States, with a median follow-up period of 15.8 months; 87% were treated with automated peritoneal dialysis.Results Demographic and clinical parameters explained only 8% of the variability in dialysate/plasma creatinine. There was a linear association between dialysate/plasma creatinine and mortality (adjusted hazards ratio per 0.1 unit higher, 1.07; 95% confidence interval, 1.02 to 1.13) and hospitalization rate (adjusted incidence rate ratio per 0.1 unit higher, 1.05; 95% confidence interval, 1.03 to 1.06). Dialysate/plasma creatinine and dialysate glucose were highly correlated (r=20.84) and yielded similar risk prediction. Ultrafiltration volume was inversely related with hospitalization rate but not with all-cause mortality. None of the parameters were associated with technique failure. Adding 4-to 0-hour dialysate glucose, ultrafiltration volume, or both did not result in any improvement in risk prediction with dialysate/plasma creatinine alone.Conclusions This analysis from a large contemporary cohort treated primarily with automated peritoneal dialysis validates dialysate/plasma creatinine as a robust predictor of outcomes in patients treated with peritoneal dialysis.