Project description:The longitudinal relationship between smoking status and risk of developing visual impairment (VI) remains unclear. We examined the relationship of smoking status and urinary cotinine level, an objective measure of smoking, with incidence of VI. This cohort study included 279,069 individuals free of VI who were followed for up to 8.8 years (median 4.8 years). VI was defined as when bilateral visual acuity was worse than 0.5 (cutoffs of 0.3 Logarithm of the Minimum Angle of Resolution). During 1,324,429.8 person-years of follow-up, 7852 participants developed new-onset bilateral VI. Self-reported current smoking status was associated with increased risk of developing VI in both men and women, with a stronger association in women (P for interaction = 0.01). Multivariable adjusted hazard ratios (95% confidence intervals) for incident VI comparing current smokers to never-smokers were 1.14 (1.04-1.25) in men and 1.52 (1.28-1.80) in women. Urinary cotinine levels of ≥ 100 ng/ml were significantly associated with increased risk of incident VI, and these associations remained when introducing changes in urinary cotinine and other confounders during follow-up as time-varying covariates. Cigarette smoking assessed based on self-report and urinary cotinine level was associated with increased incidence of VI. Our findings identify smoking as an independent risk factor for VI.
Project description:Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method for cotinine analysis by combining micellar electrokinetic chromatography with enrichment techniques. We employed the method to measure cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12 or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed to room air for the same period. Further, we investigated the morphological changes in lungs of mice and observed tobacco smoke induced emphysema. Our results indicate that the method can be used to measure cotinine and there is an association between the serum cotinine concentration and tobacco smoke-induced emphysema in mice.
Project description:IntroductionSmoking status based solely on self-reporting is unreliable and might be inaccurate, particularly among women. This study investigated the association between urinary cotinine-verified smoking status and hyperuricemia in a nationwide Korean population.MethodsThis study included 5329 participants aged ≥19 years with information on smoking status, urine cotinine levels and serum uric acid. We determined smoking status according to self-reports and urinary cotinine levels. Multivariate linear regression analysis was used to measure the association between smoking exposure and serum uric acid levels. The effects of smoking on hyperuricemia were evaluated by multivariate logistic regression analysis.ResultsBiochemically verified active and passive smokers comprised 22% (38.7% of men and 8.8% of women) and 12.3% (11.9% of men and 12.6% of women) of the study population, respectively. While reclassification rate of active smokers was 1.4% in men, 31.8% of cotinine-verified female active smokers were self-reported never smokers. Higher uric acid levels were observed with increased tobacco exposure among women (p-trend=0.007) but not among men. After adjusting for confounders, the risk of hyperuricemia increased with tobacco exposure only in women (p-trend=0.016).ConclusionsCotinine-verified smoking status was associated with increased serum uric acid and hyperuricemia in a dose-response manner only in women. This study might provide evidence to support the importance of smoking cessation in women with gout and further studies are necessary to elucidate the underlying mechanism of the observed association.
Project description:The formative work of Jane Jacobs underscores the combination of "eyes on the street" and trust between residents in deterring crime. Nevertheless, little research has assessed the effects of residential street monitoring on crime due partly to a lack of data measuring this process. We argue that neighborhood-level rates of households with dogs captures part of the residential street monitoring process core to Jacobs' hypotheses and test whether this measure is inversely associated with property and violent crime rates. Data from a large-scale marketing survey of Columbus, OH, USA residents (2013; n = 43,078) are used to measure census block group-level (n = 595) rates of households with dogs. Data from the Adolescent Health and Development in Context study are used to measure neighborhood-level rates of trust. Consistent with Jacobs' hypotheses, results indicate that neighborhood concentration of households with dogs is inversely associated with robbery, homicide, and, to a less consistent degree, aggravated assault rates within neighborhoods high in trust. In contrast, results for property crime suggest that the inverse association of dog concentration is independent of levels of neighborhood trust. These associations are observed net of controls for neighborhood sociodemographic characteristics, temporally lagged crime, and spatial lags of trust and dog concentration. This study offers suggestive evidence of crime deterrent benefits of local street monitoring and dog presence and calls attention to the contribution of pets to other facets of neighborhood social organization.
Project description:ObjectivesCotinine is the most widely used biomarker to distinguish active versus passive smoking. However, there is an overlap in cotinine levels when comparing light or occasional smokers versus heavily exposed passive smokers. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. The aim of the study was to determine optimal cutoff points to discriminate active versus passive smokers and to compare sensitivity and specificity for the use of cotinine, NNAL, and the ratio of the NNAL/cotinine in urine.MethodsCotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers.ResultsGeometric mean cotinine levels were 2.03 ng/ml (interquartile interval: 0.43-8.60) and 1,043 ng/ml (658-2,251) and NNAL levels were 5.80 pg/ml (2.28-15.4) and 165 pg/ml (90.8-360) pg/ml in passive and active smokers, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 vs. 0.16, p < .01). The receiver operating characteristics analysis determined optimal cutoff points to discriminate passive versus active smokers: 31.5 ng/ml for cotinine (sensitivity: 97.1% and specificity: 93.9%), 47.3 pg/ml for NNAL (87.4% and 96.5%), and 0.74 x 10?³ for NNAL/cotinine ratio (97.3% and 87.3%).ConclusionsBoth urine cotinine and NNAL are sensitive and specific biomarkers for discriminating the source of tobacco smoke exposure. Cotinine is the best overall discriminator when biomarkers are measured while a person has ongoing exposure to tobacco smoke. NNAL because of its long half-life would be particularly useful when there is a delay between exposure and biomarker measurement. The NNAL/cotinine ratio provides similar sensitivity but poorer specificity at discriminating passive versus active smokers when compared with NNAL alone.
Project description:IntroductionCotinine, the primary proximate metabolite of nicotine, is commonly measured as an index of exposure to tobacco in both active users of tobacco and nonsmokers with possible exposure to secondhand smoke (SHS). A number of laboratories have implemented analyses for measuring serum cotinine in recent years, but there have been few interlaboratory comparisons of the results. Among nonsmokers exposed to SHS, the concentration of cotinine in blood can be quite low, and extensive variability in these measurements has been reported in the past.MethodsIn this study, a group of seven laboratories, all experienced in serum cotinine analysis, measured eight coded serum pools with concentrations ranging from background levels of about 0.05 ng/ml to relatively high concentrations in the active smokers range. All laboratories used either gas-liquid chromatography with nitrogen-phosphorus detection or liquid chromatography with mass spectrometric detection.ResultsAll seven laboratories reliably measured the cotinine concentrations in samples that were within the range of their methods. In each case, the results for the pools were correctly ranked in order, and no significant interlaboratory bias was observed at the 5% level of significance for results from any of the pools.DiscussionWe conclude that present methods of chromatographic analysis of serum cotinine, as used by these experienced laboratories, are capable of providing accurate and precise results in both the smoker and the nonsmoker concentration range.
Project description:Antibody-drug conjugates (ADCs) can selectively deliver cytotoxic agents to tumor cells and are frequently more potent than naked antibodies. However, optimization of the conjugation process between antibodies and cytotoxic agents and characterization of ADCs are laborious and time-consuming processes. Here, we describe a novel ADC platform using a tetravalent bispecific antibody that simultaneously binds to the tumor-associated antigen and a hapten conjugated to a cytotoxic agent. We selected cotinine as the hapten because it is not present in biological systems and is inert and nontoxic. We prepared an anti-epidermal growth factor receptor (EGFR) × cotinine bispecific antibody and mixed it with an equimolar amount of cotinine-conjugated duocarmycin to form the ADC. This ADC showed significant in vitro and in vivo antitumor activity against EGFR-positive, cetuximab-refractory lung adenocarcinoma cells with KRAS mutations.
Project description:IntroductionOur aim was to understand the strength of association between parental smoking and child environmental tobacco smoke (ETS) exposure in order to inform the development of future tobacco control policies. ETS was measured using child cotinine levels below the active smoking threshold.MethodsParticipants were drawn from the Avon Longitudinal Study of Parents and Children and included 3,128 participants at age 7 years and 1,868 participants at age 15 years. The primary outcome was cotinine levels of nonsmoking children, to investigate the relationship between maternal smoking and child cotinine levels. The secondary outcome was cotinine levels of all individuals to investigate the relationship between child smoking and child cotinine levels. Maternal and child smoking behavior was assessed by self-report questionnaire. We adjusted for several sociodemographic variables.ResultsWe found an association between maternal smoking and child cotinine at age 7 years (mean cotinine = 1.16ng/ml serum, ratio of geometric means = 3.94, 95% CI = 2.86-5.42) and at age 15 years (mean cotinine = 0.94ng/ml serum, ratio of geometric means = 5.26, 95% CI = 3.06-9.03), after adjustment for potential confounders.ConclusionsThe magnitude of this association for children whose mothers were heavy smokers was comparable with the quantity of half the levels of cotinine observed among children who were irregular (i.e., nonweekly) active smokers, and it was greater than five times higher than that seen in nonsmoking children whose mothers didn't smoke. This provides further evidence for the importance of public health interventions to reduce smoking exposure in the home.
Project description:BackgroundDiabetic kidney disease (DKD) is a common and potentially fatal consequence of diabetes. Chronic renal failure or end-stage renal disease may result over time. Numerous studies have demonstrated the function of the microbiota in health and disease. The use of advanced urine culture techniques revealed the presence of resident microbiota in the urinary tract, undermining the idea of urine sterility. Studies have demonstrated that the urine microbiota is related with urological illnesses; nevertheless, the fundamental mechanisms by which the urinary microbiota influences the incidence and progression of DKD remain unclear. The purpose of this research was to describe key characteristics of the patients with DKD urinary microbiota in order to facilitate the development of diagnostic and therapeutic for DKD.MethodsWe evaluated the structure and composition of the microbiota extracted from urine samples taken from DKD patients (n = 19) and matched healthy controls (n = 15) using 16S rRNA gene sequencing. Meanwhile, serum metabolite profiles were compared using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Associations between clinical characteristics, urine microbiota, and serum metabolites were also examined. Finally, the interaction between urine microbiota and serum metabolites was clarified based on differential metabolite abundance analysis.ResultsThe findings indicated that the DKD had a distinct urinary microbiota from the healthy controls (HC). Taxonomic investigations indicated that the DKD microbiome had less alpha diversity than a control group. Proteobacteria and Acidobacteria phyla increased in the DKD, while Firmicutes and Bacteroidetes decreased significantly (P < 0.05). Acidobacteria was the most prevalent microbiota in the DKD, as determined by the Linear discriminant analysis Effect Size (LEfSe) plot. Changes in the urinary microbiota of DKD also had an effect on the makeup of metabolites. Short-chain fatty acids (SCFAs) and protein-bound uremic toxins (PBUTs) were shown to be specific. Then we discovered that arginine and proline metabolism was the primary mechanism involved in the regulation of diabetic kidney disease.ConclusionsThis study placed the urinary microbiota and serum metabolite of DKD patients into a functional framework and identified the most abundant microbiota in DKD (Proteobacteria and Acidobacteria). Arginine metabolites may have a major effect on DKD patients, which correlated with the progression of DKD.
Project description:2-Hydroxypropylmercapturic acid (2-HPMA) is a urinary biomarker of exposure to propylene oxide, a mutagen and carcinogen to which humans are exposed through inhalation of cigarette smoke as well as in certain environmental and occupational settings. 2-HPMA is the final product of a detoxification pathway in which propylene oxide is conjugated with glutathione, and the resulting conjugate is further metabolized and excreted. We have developed and validated a liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS/MS) method for the rapid quantitation of 2-HPMA in human urine. The method was applied to an analysis of urine samples from 40 smokers and 40 nonsmokers as well as from a group of 15 subjects who quit smoking. The results demonstrate that smokers have significantly (P<0.001) higher levels of urinary 2-HPMA (median=480pmol/mg creatinine) than do nonsmokers (208pmol/mg). Similarly, subjects who quit smoking for four weeks exhibited a significant (P<0.001) 52% median decrease in urinary 2-HPMA upon cessation. Approximately 5% of all urine samples had unusually high levels of 2-HPMA (>10 times higher than the median), apparently unrelated to tobacco smoke exposure or available demographic data. The method presented here can be used to rapidly quantify an individual's exposure to propylene oxide via tobacco smoke or other sources.