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Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP) and 1,2,dibromo-3-chloropropane (DBCP) on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS) formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format., (Copyright © 2015. Published by Elsevier B.V.)

Background: Persons with higher blood pressure have emotional dampening in some contexts. This may reflect interactive changes in central nervous system control of affect and autonomic function in the early stages of hypertension development., Purpose: The purpose of this study is to determine the independence of cardiovascular emotional dampening from alexithymia to better understand the role of affect dysregulation in blood pressure elevations., Methods: Ninety-six normotensives were assessed for resting systolic and diastolic (DBP) blood pressure, recognition of emotions in faces and sentences using the Perception of Affect Task (PAT), alexithymia, anxiety, and defensiveness., Results: Resting DBP significantly predicted PAT emotion recognition accuracy in men after adjustment for age, self-reported affect, and alexithymia., Conclusions: Cardiovascular emotional dampening is independent of alexithymia and affect in men. Dampened emotion recognition could potentially influence interpersonal communication and psychosocial distress, thereby further contributing to BP dysregulation and increased cardiovascular risk.

Background: A range of nonpharmacological interventions (e.g., meditation) have positive effects on blood pressure (BP) but tend to have poor adherence. These interventions may lower BP partly by absorbing and directing attention away from one's negative thoughts. We hypothesized that recurring self-selected activities (SSAs) that are attentionally absorbing may similarly lower BP. We examined the effect of reported engagement in SSAs during the previous month prior to participation on ambulatory BP (ABP) and whether those prone to rumination were less likely to show these effects., Methods: Participants (n = 38) reported engagement in SSAs and how absorbing they were, responded to trait rumination and perceived stress questionnaires, wore an ABP monitor for 24 hours, and at each ABP measurement answered electronic diary questions assessing activity levels, affect, social interactions, and caffeine and tobacco use., Results: Regression analyses tested whether the reported absorption of SSAs, trait rumination, and their interaction predicted daytime and nighttime systolic and diastolic ABP. Greater absorption predicted lower daytime and nighttime ABP (bs = -18.83 to -8.79; Ps < .05), but this relationship was moderated by trait rumination (bs = 3.72 to 9.97; Ps < .05). Follow-up analyses revealed that absorption was unrelated to ABP for those with high trait rumination but that more absorption predicted lower ABP for those less prone to rumination., Conclusions: Our results suggest that regular engagement in absorbing SSAs is related to lower ABP. These findings have implications for the development of nonpharmacological interventions and suggest SSAs may serve as an adjuvant intervention strategy to lower BP., (© American Journal of Hypertension, Ltd 2013. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Religious coping arguably prevents negative health outcomes for stressed persons. This study examined the moderating role of religious coping (positive, negative, and combined) in the connection of care recipient functional status with diurnal salivary cortisol patterns among dementia family caregivers., Methods: Thirty African American (AA) female dementia caregivers and 48 AA noncaregivers completed the Religious Coping (RCOPE) scale, the Activities of Daily Living scale, and the Revised Memory and Behavior Problem Checklist (RMBPC) and collected five saliva samples daily (at awakening, 9 A.M., 12 P.M., 5 P.M., and 9 P.M.) for 2 straight days., Results: Hierarchical regression tests with mean diurnal cortisol slope as the outcome illustrated surprisingly that higher combined and positive (but not negative) RCOPE scores were associated with increasingly flatter or worse cortisol slope scores for caregivers (but not noncaregivers). Of note, the RCOPE by RMBPC interaction was significant. Among caregivers who reported higher RMBPC scores, higher combined and positive (but not negative) RCOPE scores were unexpectedly associated with increasingly flatter cortisol slopes., Conclusions: These results extend current findings by showing that being AA, a caregiver, and high in positive religious coping may predict increased daily stress responses, mainly for those with higher patient behavioral problems. Because religious coping is a central coping strategy for AA caregivers, it is vital that epidemiologic assessments of religious coping in health and aging as well as tailored interventions focus on the unique reasons for this disparity., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: The John Henryism active coping (JHAC) hypothesis suggests that striving with life challenges predicts increased risk for cardiovascular disease for those with scarce coping resources. This study examined the moderating role of JHAC in the associations of 1) caregiver status and 2) care recipient functional status with diurnal salivary cortisol patterns among 30 African Americans (AAs) and 24 white female dementia caregivers and 63 noncaregivers (48 AAs)., Methods: Caregiver participants completed the JHAC-12 scale, Activities of Daily Living (ADL) scale, and Revised Memory and Behavior Problem checklist (RMBPC) and collected five saliva samples daily (at awakening, 9 A.M., 12 P.M., 5 P.M., and 9 P.M.) for 2 successive days., Results: Univariate analysis of variance tests with mean diurnal cortisol slope as the outcome illustrated that among AA caregivers, higher JHAC scores were related to flatter (or more dysregulated) cortisol slopes. The JHAC by ADL and JHAC by RMBPC interactions were each significant for AA caregivers. Among AA caregivers who reported higher ADL and RMBPC scores, higher JHAC scores were associated with flatter cortisol slopes., Conclusions: These findings extend recent studies by showing that being AA, a caregiver, and high in JHAC may elevate the risk for chronic disease, especially for those with higher patient ADL and behavioral problems. Thus, it is imperative that interventions appreciate the pernicious role of high-effort coping style, especially for AA caregivers, to minimize the stressful side effects of patient ADL and memory and behavioral problems for the caregiver.

Work is central to well-being but working is problematic when people experience workplace bullying, which includes psychological, physical, and sexual abuse or harassment. The purpose of the present grounded theory study was to extend current understanding, from the perspective of women, of how workplace bullying affects their work and how they engage in the workforce. The study was conducted in eastern Canada with 36 English-speaking women who had been bullied in the workplace. They reported mainly psychological bullying. The central problem for women is they cannot continue working as they had before the workplace bullying. The authors named a four-stage process of how women address this problem as "Doing Work Differently." The four stages are Being Conciliatory, Reconsidering, Reducing Interference, and Redeveloping Balance. The process is influenced by women's support systems, the effects on their health, and financial circumstances. There are implications for public education, workplace policies, and health care workers.

Our purpose in this grounded theory study was to explore the impact of workplace bullying (WPB) on women working in health care. We analyzed interviews with 21 women, professionals and nonprofessionals. The women experienced a change in their meaning of work (MOW) when they had experienced WPB, and they addressed this change through a process we called the shifting meaning of work. This process has three stages. The first, developing insight, involves recognizing causes of changed MOW as external. In the second stage, resisting, women defend against changed MOW by sustaining acceptable MOW and work performances, and by confronting causes. In the final stage, rebuilding, women try to adapt and modify approaches to work by coming to terms, adjusting work attitudes, and investing in self. We identified implications of this process for managing health and work issues with women, health care providers, and employers.

Study Design: Clinical Measurement., Introduction: Thumb carpometacarpal (CMC) osteoarthritis is a frequent cause of thumb pain., Purpose of the Study: To evaluate the interrater reliability and the criterion validity of the grind test for thumb CMC osteoarthritis., Methods: Radiological evaluation was used as the gold standard. Seventy thumbs of 54 persons with various hand disorders were included in the study. The grind test was performed by two physical therapists, and radiographs were evaluated by a certified hand surgeon, all blinded to the participants' diagnosis and other test results. Interrater reliability was compared with a kappa statistic, and the sensitivity, specificity, likelihood ratios, and predictive values were calculated from a 232 table., Results: A kappa value of 0.48 was calculated as the interrater reliability. The sensitivity of the grind test was 42% and 53%, depending on tester. The specificity of the grind test was 80% and 93%, depending on tester. The positive likelihood ratio was 2.65 and 6.00, and the negative likelihood ratio was 0.59 and 0.62. The positive predictive value was 91% and 96%, depending on tester. The negative predictive value was 68% and 70%, depending on tester., Conclusion: The grind test has moderate reliability and accurately confirms the diagnosis of CMC osteoarthritis and identifies those who do not have CMC osteoarthritis. However, a negative grind test does not necessarily reflect negative radiographic evidence of thumb CMC osteoarthritis., Level of Evidence: n/a., (Copyright © 2010 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

This study evaluated cardiovascular responses (CVR) to an active speech task with blatantly discriminatory (BRC) versus neutral (NRC) stimuli and an anger recall task in a sample of Black men (N = 73; age 18 to 47). Diastolic blood pressure scores were higher for NRC versus BRC stimuli during anger recall (p = .05). Moreover, persons in the NRC group who perceived high levels of racism (vs. no racism or BRC group) during active speech showed larger increases in blood pressure across postspeech rest, anger recall, and subsequent rest (p = .03). The notable elevation in CVR in response to an ambiguous event extends current models of racism suggesting that subtle racism is a psychosocial stressor that erodes health through chronically elevated CVR., (2006 APA, all rights reserved)

Reduced arterial compliance has been implicated as a risk factor for future cardiovascular events in hypertensive patients. Recently, several non-invasive techniques have been used to access arterial compliance. However, comparisons of these techniques with older individuals and African-Americans have not been done. In the present study, beat-to-beat blood pressure was examined in 75 males and females (n = 24 old Caucasian; n = 24 young Caucasian; n = 27 African-Americans) who were part of the Baltimore Longitudinal Study of Aging (BLSA). Resting beat-to-beat blood pressure (5 minutes) was assessed using the PORTAPRES Ambulatory Blood Pressure Device. Results indicated that the three-element windkessel and the stroke volume-pulse pressure ratio measures of arterial compliance provide comparable estimates. Specifically, arterial compliance is reduced in the oldest individuals in our sample with young and African-Americans showing higher compliance. These results indicate that the simpler stroke volume-pulse pressure ratio provides reliable estimates of arterial compliance in both older adults and African-Americans. This technique is an excellent means to assess arterial compliance and is a useful measure to determine risk for adverse cardiovascular events.

Typically, blood pressure variability has been calculated by taking the simple mathematical standard deviations of a collection of discrete blood pressure (BP) measurements. Recently, spectral analytic techniques have been employed to examine beat-to-beat blood pressure variability and the underlying autonomic adjustments associated with the performance of various tasks. In the present study, beat-to-beat blood pressure was examined in 104 older African-Americans males and females who were part of the Healthy Aging in Nationally Diverse Longitudinal Samples (HANDLS) Study. Participants evaluated faces and sentences depicting emotional content and rested before (Baseline) and after (Recovery) the tasks. There were no significant gender effects in any analyses. In addition, there were no significant task effects. However, there was a trend for both low and high frequency systolic blood pressure variability to decrease linearly from baseline, through faces and sentences to recovery. Interestingly, both systolic and diastolic high frequency blood pressure variability was greater in older as compared to younger adults. Increased blood pressure variability has been associated with greater sheer stress and greater end organ damage. These results will explicate the effects of aging on cardiovascular disease risk. Overall, these data indicate that blood pressure variability derived via spectral analytic techniques is a useful tool for understanding cardiodynamics and may provide a more in-depth analysis of blood pressure response.

Objective: To explore the associations among ethnicity, educational attainment, and cortisol secretion., Design: Participants include 63 white (n = 31) and African-American (n = 32) adult men and women. Subjects provided salivary cortisol samples immediately upon awakening and again, 30 minutes later., Results: Analyses adjusted for relevant covariates revealed a steeper awakening response among whites with higher education compared to other groups. Cortisol levels were significantly lower among African-American participants with lower levels of education. All effects were independent of perceived stress., Conclusions: These preliminary findings demonstrate significant ethnic and education-related differences in awakening cortisol secretion responses. Our data highlight the importance of considering ethnicity and the moderating effects of social class when examining the associations among social contextual factors and cortisol secretion.

Power spectral analysis of beat-to-beat heart rate variability (HRV) has provided a useful means of understanding the interplay between autonomic and cardiovascular functionality. Despite their utility, commonly employed frequency-domain techniques are limited in their prerequisite for stationary signals and their inability to account for temporal changes in the power spectral and/or frequency properties of signals. The purpose of this study is to develop an algorithm that utilizes continuous wavelet transform (CWT) parameters as inputs to a Kohonen self-organizing map (SOM), providing a method of clustering subjects with similar wavelet transform signatures. Continuous interbeat-intervals were recorded (Portapres monitor at 200 Hz) during a perception of affect test in 79 African-American volunteers (ages 21-83), where after a 5-min baseline, participants evaluated emotional expressions in sentences and pictures of faces, followed by a 5-min recovery. Individual HRV biosignals from each session were pre-processed (artifact replacement and signal resampling at 2 Hz) and a CWT was applied (db9 wavelet basis function over 32 scales). Standard deviations of resulting wavelet coefficients at each scale were calculated, normalized, and used as inputs into a SOM with Kullback-Leibler divergence as the dissimilarity measure used for clustering. Differences in subject demographics between two final clusters were assessed via two-independent-groups t-tests or chi-square or Fisher's exact tests of contingency tables. Significant differences were found for age, initial systolic blood pressure, smoking status, and mean s.d. of coefficients in the high frequency band (0.15-0.4 Hz). These findings may have clinical significance and the developed algorithm provides an alternative means of analyzing HRV data originating from populations with complex covariates.

Seventy-nine African-American participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) pilot study were genotyped for the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and had spectral power of their high-frequency (HF) heart rate variability (HRV) determined by fast-Fourier transformation. HF HRV was highest in II, intermediate in ID, and lowest in DD (II vs DD, p <0.043) genotypes, thus making an association of the ACE I/D DD genotype with decreased HF HRV that is consistent with the hypothesis that the DD genotype confers susceptibility to increased cardiovascular risk. The urban African-American population we studied had a particularly high cardiovascular risk, and these findings suggest that ACE I/D genotypes may modify that risk.

Traditionally baroreflex sensitivity (BRS) has been assessed with pharmacological approaches such as phenylephrine infusion. Recently, non-invasive approaches using spectral analytic techniques have been employed to combine heart rate and blood pressure variability parameters to estimate BRS (the alpha index). Some authors have argued that BRS assessed at different frequencies of cardiovascular variabilities provide identical information and they should be combined into a single index of BRS based on total variability. The present study examined the relationship between BRS assessed using low, high, and total heart rate and blood pressure variabilities, and indices of cardiac vagal control assessed by standard spectral measures. Participants were 105 older male and female African-Americans who were part of the Healthy Aging In Nationally Diverse Longitudinal Samples (HANDLS) Study. Heart rate and blood pressure variabilities (HRV and BPV) were assessed using the Fast-Fourier Transform (FFT). The alpha index was computed as the square root of the ratio of low, high, or the mean of low and high frequency heart rate variability and the corresponding frequency ranges for systolic blood pressure variability. Correlations examining the relationships among BRS and various (e.g. log, normalized) indices of high frequency heart period variability (HF) were calculated for the total sample and by gender. Results indicated that the different BRS indices do not have the same relationship to all indices of HF. The results suggest that an aggregation of the power across bands is problematic at best, and indicates the need to examine the various frequency components separately.

Recently, time-frequency analysis has become very popular for examining non-stationary time series and for researching fast changing phenomena. We used the smoothed-pseudo Wigner-Ville distribution to model the underlying dynamic autonomic nervous system changes during the intracarotid sodium amobarbital (ISA) or so-called Wada test. The Wada test involves injecting sodium amobarbitol into the internal carotid artery that results in inactivation of cerebral structures supplied by the ipsilateral anterior and middle cerebral arteries. Electrocardiogram (EKG) data were recorded during the entire procedure and the 10 minutes prior to each injection were used as baseline values for that hemisphere. Interbeat-interval time series were created from these data for a 13 year old patient and were examined using a smoothed-pseudo Wigner-Ville distribution. Inspection of these data indicated that sodium amobarbitol injection to either side produced decreased power in the vagally mediated high frequency band (.14-.40 Hz). Importantly, this decrease was greater when the right hemisphere was inactivated as compared to the left. These results are consistent with the known lateralized innervation of the heart such that right-sided autonomic inputs have greater influence on cardiac chronotropy. The present results also revealed the very rapid changes in autonomic control that characterized the inactivation and subsequent recovery of the cerebral hemispheres. These findings confirm the utility of time-frequency analysis in the investigation of cardiac time series.

Lactoferrin (LF) binding to the surface of human neutrophils was shown to be dependent upon the presence of cell surface DNA by (i) an abrogation of LF binding after treatment of whole cells with DNAse; (ii) an abrogation of LF binding to a purified cell membrane suspension after DNAse digestion, (iii) a restoration of LF binding, after initial treatment of cells with DNAse, by the addition of exogenous DNA. Using a biotinylated LF probe, no other binding molecules were found after SDS PAGE of neutrophil cell membrane proteins. Further evidence of a DNA-LF interaction was obtained by the co-isolation of LF with DNA by both gel chromatography and affinity chromatography using Heparin Sepharose CL 6B. The interaction of LF with neutrophils was a saturable phenomenon with a Kd of 6.2 X 10(-6) M and a maximum binding of 9.2 X 10(6) molecules per cell. These results suggest that cell membrane DNA may have a novel role as a receptor for LF, and indicates the need for further experiments to determine whether the functional effects of LF are modified by the DNAse treatment of LF responsive cells.

The receptor for DNA was functionally defective in the majority of patients with systemic lupus erythematosus (SLE; 91% of 35 studied) and allied rheumatic disorders. This functional defect was manifest by impaired binding of exogenous DNA to the cell surface of peripheral blood mononuclear cells and an inability of cells to internalise and degrade DNA. The receptor defect was not constitutive, since it could be reversed by overnight incubation of cells; this process was sensitive to cycloheximide, suggesting a requirement for active receptor regeneration. The DNA-receptor defect could be induced in healthy controls, by incubating their cells with the serum of patients with SLE. The humoral factor inducing the defect was an autoantibody.

Previous studies have indicated that white blood cells possess DNA on their outer membranes. In this study we set out to determine whether exogenous DNA bound to cells in a fashion compatible with a ligand receptor union. Purified populations of white blood cells; neutrophils (polymorphonuclear leukocytes, PMN), adherent mononuclear cells (ADMC), rosetting lymphocytes (E+ cells), and nonrosetting lymphocytes (E- cells) were incubated with radiolabeled lambda phage DNA in increasing concentrations. Binding of [3H]DNA was a saturable process and was inhibited by excess cold DNA and prior trypsinization of the cells. Rate zonal density centrifugation of purified cell membrane preparations confirmed that DNA was binding to the outer cell surface. The dissociation constant for all four cell types was approximately 10(-9) M, and from 0.81 X 10(3) to 2.6 X 10(3) molecules of lambda phage DNA bound to each cell depending upon cell type. Binding was not competitively inhibited by RNA, polydeoxyadenylic acid-polydeoxythymidylic acid (poly [d(A).d(T)]), or mononucleotides. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE)-separated proteins from PMN, ADMC, E+, and E- cells were electrophoretically blotted onto nitrocellulose sheets; a probe of biotin-labeled DNA indicated a single species of DNA-binding molecule migrating in a position consistent with a molecular weight of 30,000. Isotopic and immunofluorescent studies indicate that DNA is internalized and degraded to oligonucleotides; this process is inhibited by cycloheximide. These results support the notion that there is a common binding site for DNA on white blood cells, that the stoichiometry of the association is compatible with a ligand receptor relationship, and that this apparent receptor is responsible for the endocytosis and degradation of exogenous DNA.