Wendie A. Robbins

Risk factors for hepatitis C virus infection among homeless adults

OBJECTIVE: To describe the prevalence of hepatitis C virus (HCV) infection in a sample of homeless and impoverished adults and examine risk factors for HCV infection in the overall sample and as a function of injection drug use.DESIGN: Assays were conducted on stored sera. Socio-demographic characteristics and risky sexual activity were measured by content-specific items. Substance use was measured by a structured questionnaire. HCV antibodies were tested by enzyme-linked immunosorbent assay; a confirmatory level was defined by recombinant immunoblot assay.SETTINGS: Shelters (N=36) and outdoor locations in Los Angeles.PARTICIPANTS: Eight hundred eighty-four homeless women and/or partners or friends.RESULTS: Among this sample of 884 homeless and impoverished adults, 22% were found to be HCV infected. Lifetime injection drug users (IDUs) (cocaine, crack, and methamphetamine) and recent daily users of crack were more likely than nonusers or less-frequent users of these drugs to be HCV-infected. Similar results were found for those who had been hospitalized for a mental health problem. Among non-injection drug users and persons in the total sample, those who reported lifetime alcohol abuse were more likely than those who did not to be HCV infected. Controlling for socio-demographic characteristics, multiple logistic regression analyses revealed IDUs have over 25 times greater odds of having HCV infection than non-IDUs. HCV infection was also predicted by older age, having started living on one’s own before the age of 18, and recent chronic alcohol use. Males and recent crack users had about one and a half times greater odds of HCV infection when compared to females and non-chronic crack users.CONCLUSIONS: Targeted outreach for homeless women and their partners, including HCV testing coupled with referrals to HCV and substance abuse treatments, may be helpful.

Integrating new tests of sperm genetic integrity into semen analysis: breakout group discussion.

The First International Conference on Male-Mediated Developmental Toxicity, held in September 1992, reported that the spermatozoon can bring genetic damage into the oocyte at fertilization and thereby contribute to subsequent abnormal pregnancy outcomes (Olshan and Mattison, 1994). At that time, laboratory tests for genetic defects in sperm were at an early stage of development and were relatively untested in the clinic and the field. A breakout group at that meeting discussed the need for improved sperm biomarkers of adverse reproductive effects and concluded that sensitive, reliable, and practical methods

Effect of lifestyle exposures on sperm aneuploidy

Lifestyle exposures including cigarette smoke, alcohol, and caffeine have all been studied in relationship to male reproductive health. Over the years the focus has primarily been on semen quality and/or fertility. More recently, literature evaluating direct adverse effects of lifestyle exposures on sperm chromosomes and chromatin has grown due to concern that induced damage could be transmitted to offspring causing transgenerational health effects. In this paper we present a new analysis that summarizes published studies of smoking effects on sperm chromosome number and demonstrates a statistically significant increase in sperm disomy among smokers compared to nonsmokers (P < 0.001). In addition, new data on the effect of alcohol intake on sperm chromosome number are presented showing a rate ratio of 1.38 (95% CI 1.2, 1.6) for XY frequency in sperm of alcohol drinkers compared to nondrinkers.

Stable Variants of Sperm Aneuploidy among Healthy Men Show Associations between Germinal and Somatic Aneuploidy

Repeated semen specimens from healthy men were analyzed by sperm fluorescence in situ hybridization (FISH), to identify men who consistently produced elevated frequencies of aneuploid sperm and to determine whether men who were identified as stable variants of sperm aneuploidy also exhibited higher frequencies of aneuploidy in their peripheral blood lymphocytes. Seven semen specimens were provided by each of 15 men over a 2-year period and were evaluated by the X-Y-8 multicolor sperm FISH method (i.e., approximately 1,050,000 sperm were analyzed from 105 specimens). Three men were identified as stable aneuploidy variants producing significantly higher frequencies of XY, disomy X, disomy Y, disomy 8, and/or diploid sperm over time. In addition, one man and three men were identified as sperm-morphology and sperm-motility variants, respectively. Strong correlations were found between the frequencies of sperm with autosomal and sex-chromosome aneuploidies and between the two types of meiosis II diploidy; but not between sperm aneuploidy and semen quality. A significant association was found between the frequencies of sex-chromosome aneuploidies in sperm and lymphocytes in a subset of 10 men (r2=0.67, P=.004), especially between XY sperm and sex-chromosome aneuploidy in lymphocytes (r2=0.70, P=.003). These findings suggest that certain apparently healthy men can produce significantly higher frequencies of both aneuploid sperm and lymphocytes. Serious long-term somatic and reproductive health consequences may include increased risks of aneuploidy-related somatic diseases and of having children with paternally transmitted aneuploidies, such as Klinefelter, Turner, triple-X, and XYY syndromes.

Chronic boron exposure and human semen parameters.

Boron found as borates in soil, food, and water has important industrial and medical applications. A panel reviewing NTP reproductive toxicants identified boric acid as high priority for occupational studies to determine safe versus adverse reproductive effects. To address this, we collected boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood, semen, and urine from boron workers and two comparison worker groups (n=192) over three months and determined correlations between boron and semen parameters (total sperm count, sperm concentration, motility, morphology, DNA breakage, apoptosis and aneuploidy). Blood boron averaged 499.2 ppb for boron workers, 96.1 and 47.9 ppb for workers from high and low environmental boron areas (p<0.0001). Boron concentrated in seminal fluid. No significant correlations were found between blood or urine boron and adverse semen parameters. Exposures did not reach those causing adverse effects published in animal toxicology work but exceeded those previously published for boron occupational groups.

Presence and Predictors of Hepatitis C Virus RNA in the Semen of Homeless Men

Although the possibility of sexual transmission of the hepatitis C virus (HCV) remains controversial, little is known of the associations of positive semen specimens with potential demographic and behavioral risk factors. Knowledge of these predictors may suggest factors that increase risk of HCV RNA in the semen. Semen and blood from 80 HCV-infected homeless men were evaluated for the presence ofHCVRNA by means of branch DNA and transcription-mediated amplification analyses. Associations of selected demographic and behavioral characteristics of the participants with presence or absence of HCV in their semen were also assessed. HCV RNA was detected in the semen of 36% of the sample. Associations were found with HCV RNA in semen and older age, higher viral loads of HCV in blood, current alcohol and lifetime methamphetamine use, and having been vaccinated for the hepatitis B virus. Findings suggest that sexual transmission of HCV is plausible and shed light on the need to conduct more in-depth investigations.

Biomarkers of Environmental and Workplace Boron Exposure

The purpose of this work was to identify an accurate, noninvasive biomarker of boron exposure that could be used in worker populations. Occupational exposure to boron is of concern due to high numbers of workers exposed, animal toxicity data suggesting reproductive effects, and lack of human studies. Total daily boron exposure was determined from duplicate samples of 24-hr food and fluid intake, plus workplace personal air monitoring in boron workers and comparison groups in northern China during 2003 and 2004. Boron was also measured in blood, semen, creatinine-corrected postshift urine, and 24-hr urine. Total daily boron exposure (mg/day) averaged 41.2 for men working in the boron industry and 2.3 for the comparison group. Boron concentration in postshift urine was correlated with 24-hr urine boron concentration (Pearson correlation coefficient = 0.85, p < 0.0001). Boron concentration in postshift urine was correlated with total daily boron exposure measured through food, fluid, and personal air monitoring (Pearson correlation coefficient = 0.83, p < 0.0001). Boron concentration in postshift urine was also correlated with internal dose measures of boron in blood and semen (Pearson correlation coefficient = 0.85, 0.80 respectively, p < 0.0001). This work suggests that creatinine-corrected, postshift urine boron concentration can be used as a biomarker of human boron exposure in worker populations.

A hierarchical zero-inflated log-normal model for skewed responses

Although considerable attention has been given to zero-inflated count data, research on zero-inflated lognormal data is limited. In this article, we consider a study to examine human sperm cell DNA damage obtained from single-cell electrophoresis (COMET assay) experiment in which the outcome measures present a typical example of log-normal data with excess zeros. The problem is further complicated by the fact that each study subject has multiple outcomes at each of up to three visits separated by six-week intervals. Previous methods for zero-inflated log-normal data are based on either simple experimental designs, where comparison of means of zero-inflated log-normal data across different experiment groups is of primary interest, or longitudinal measurements, where only one observation is available for each subject at each visit. Their methods cannot be applied when multiple observations per visit are possible and both inter- and intra-subject variations are present. Our zero-inflated model extends the previous methods by incorporating a hierarchical structure using latent random variables to take into account both inter- and intra-subject variations in zero-inflated log-normal data. An EM algorithm has been developed to obtain the Maximum likelihood estimates of the parameters and their standard errors can be estimated by parametric bootstrap. The model is illustrated using the COMET assay data.

Evaluation of aneuploidy and DNA damage in human spermatozoa: applications in field studies

With the goal of incorporating measures of sperm nuclear integrity in an epidemiology study, semen samples from young Czech men were analysed for sperm aneuploidy and sperm chromatin structure in addition to routine measures of sperm production and quality. The exposure in question was to high seasonal air pollution containing reactive polyaromatic hydrocarbons potentially capable of affecting spermatogenesis and damaging sperm DNA. The sperm aneuploidy assay uses fluorescence in situ hybridization to label selected sperm chromosomes; as applied in this study, the sex chromosomes (X,Y) and chromosome 8 were targeted. The sperm chromatin structure assay detects sperm nuclei with increased susceptibility to denaturation, a feature that is associated with DNA damage. Logistically, these assays were relatively easy to incorporate into the study design. The aneuploidy assay provided information suggesting that exposure to high levels of air pollution may increase the risk of sperm aneuploidy and that it is important to control for exposure to cigarette smoke and/or alcohol in such studies. The sperm chromatin structure assay provided valuable baseline information about Czech semen donors and data suggestive of an adverse effect of smoking and air pollution on spermatozoa that merits further investigation.

Walnuts Improve Semen Quality in Men Consuming a Western-Style Diet: Randomized Control Dietary Intervention Trial

ABSTRACT We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21–35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, −0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.