Telomere length (TL) dynamics in vivo are defined by TL and its age-dependent change, brought about by cell replication. Leukocyte TL (LTL), which reflects TL in hematopoietic stem cells (HSCs), ...becomes shorter with age. In contrast, sperm TL, which reflects TL in the male germ cells, becomes longer with age. Moreover, offspring of older fathers display longer LTL. Thus far, no study has examined LTL and sperm TL relations with age in the same individuals, nor considered their implications for the paternal age at conception (PAC) effect on offspring LTL. We report that in 135 men (mean age: 34.4 years; range: 18-68 years) on average, LTL became shorter by 19 bp/year (r = -0.3; P = 0.0004), while sperm TL became longer by 57 bp/year (r = 0.32; P = 0.0002). Based on previously reported replication rates of HSCs and male germ cells, we estimate that HSCs lose 26 bp per replication. However, male germ cells gain only 2.48 bp per replication. As TL is inherited in an allele-specific manner, the magnitude of the PAC effect on the offspring's LTL should be approximately half of age-dependent sperm-TL elongation. When we compared the PAC effect data from previous studies with sperm-TL data from this study, the result was consistent with this prediction. As older paternal age is largely a feature of contemporary humans, we suggest that there may be progressive elongation of TL in future generations. In this sense, germ cell TL dynamics could be driving the evolution of TL in modern humans and perhaps telomere-related diseases in the general population.
beta-Carboline alkaloids are normal body constituents but are also potent tremor-producing chemicals that are naturally present in the food chain.
To explore the hypothesis that high concentrations ...of beta-carboline alkaloids are associated with essential tremor (ET).
One hundred cases and 100 controls were frequency matched on age, sex, and ethnicity. Blood concentrations of harmane and harmine were quantified by high-performance liquid chromatography, blinded to clinical information.
The mean log blood concentration of harmane was higher in cases than controls (0.72 +/- 0.53 vs 0.51 +/- 0.64 g(-10)/mL; p = 0.01). A nonparametric test on nontransformed data (median harmane = 5.21 g(-10)/mL in cases and 2.28 g(-10)/mL in controls) confirmed this difference (p = 0.005). The mean log blood concentration of harmine was 0.20 +/- 0.48 g(-10)/mL in cases and 0.10 +/- 0.65 g (-10)/mL in controls (p = 0.20). Log harmane concentrations were stratified based on the median value; 62% of cases vs 39% of controls had a high log harmane concentration (p = 0.001). Mean log harmane concentration was similar in the cases with (0.74 +/- 0.58 g(-10)/mL) and without (0.71 +/- 0.50 g(-10)/mL) an affected relative (p = 0.83).
Blood concentrations of harmane were measured in ET cases compared with controls. Concentrations were elevated in cases with and without a family history of ET.
N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be protective for depression during pregnancy. However, there are few data and no consensus regarding this association. In this line, ...we aim to evaluate if the concentration of n-3 and n-6 PUFAs, and their ratio, are associated with depressive symptoms throughout pregnancy.
A prospective cohort of 172 Brazilian women was followed at 5-13th, 20-26th and 30-36th weeks of gestation. The presence of depressive symptoms was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an EPDS score ≥11. The concentrations of n-3 α-linolenic acid; eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and n-6 PUFAs linoleic acid; γ linolenic acid; eicosadienoic acid; eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic acid were expressed as absolute (μg/ml) values. The total n-6/n-3 ratio was calculated. Statistical analyses were performed using univariate and adjusted random intercept logistic model for each fatty acid (FA) considering the longitudinal nature of data. Covariates were selected as potential confounders based on their biological plausibility of having an association with the concentration of FA and depressive symptoms during pregnancy.
The prevalence of depressive symptoms was high in all pregnancy trimesters (1st = 33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA concentrations by depressive symptom classification, for each follow-up visit. The women presented a 5% decrease in the odds of having depressive symptoms for each one-week increase in the gestational age. As individual women progressed through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI: 0.86-0.99), DHA (OR = 0.96; 95% CI: 0.93-0.99), DPA (OR = 0.87; 95% CI: 0.77-0.99) and total n-3 (OR = 0.98; 95% CI: 0.96-0.99) were associated with a lower odds of depressive symptoms, while higher total n-6/n-3 ratio were associated with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09-1.79). We detected a decrease in the probability of depressive symptoms as concentrations of total n-3 FA, α-linolenic acid, DPA, and DHA increased. We also observed a sharper decline for women with initial greater chance of depressive symptoms compared with those with lower chance of having these symptoms.
We found a high prevalence of depressive symptoms in low-income Brazilian pregnant women and no significant associations between n-6 FA and depressive symptoms. Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each pregnancy trimester were associated with higher odds of depressive symptoms throughout pregnancy.
The authors performed a cross-sectional analysis to evaluate the association between arsenic exposure from drinking water and blood pressure using baseline data of 10,910 participants in the Health ...Effects of Arsenic Longitudinal Study in Bangladesh (October 2000–May 2002). A time-weighted well arsenic concentration (TWA) based on current and past use of drinking wells was derived. Odds ratios for high pulse pressure (≥55 mmHg) by increasing TWA quintiles (≤8, 8.1–40.8, 40.9–91.0, 91.1–176.0, and 176.1–864.0 μg/liter) were 1.00 (referent), 1.39 (95% confidence interval (CI): 1.14, 1.71), 1.21 (95% CI: 0.99, 1.49), 1.19 (95% CI: 0.97, 1.45), and 1.19 (95% CI: 0.97, 1.46). Among participants with a lower than average dietary intake level of B vitamins and folate, the odds ratios for high pulse pressure by increasing TWA quintiles were 1.00 (referent), 1.84 (95% CI: 1.07, 3.16), 1.89 (95% CI: 1.11, 3.20), 1.83 (95% CI: 1.09, 3.07), and 1.89 (95% CI: 1.12, 3.20). The odds ratios for systolic hypertension suggest a similar but weaker association. No apparent associations were observed between TWA and general or diastolic hypertension. These findings indicate that the effect of low-level arsenic exposure on blood pressure is nonlinear and may be more pronounced in persons with lower intake of nutrients related to arsenic metabolism and cardiovascular health. Future research is needed to evaluate the effect of low-level arsenic exposure on specific cardiovascular outcomes.
Beta-carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood ...harmane concentrations were elevated in patients with essential tremor (ET) vs controls. Whether this difference is due to greater animal protein consumption by patients or their failure to metabolize harmane is unknown.
The aim of this study was to determine whether patients with ET and controls differ with regard to 1) daily animal protein consumption and 2) the correlation between animal protein consumption and blood harmane concentration.
Data on current diet were collected with a semiquantitative food frequency questionnaire and daily calories and consumption of animal protein and other food types was calculated. Blood harmane concentrations were log-transformed (logHA).
The mean logHA was higher in 106 patients than 161 controls (0.61 +/- 0.67 vs 0.43 +/- 0.72 g(-10)/mL, p = 0.035). Patients and controls consumed similar amounts of animal protein (50.2 +/- 19.6 vs 49.4 +/- 19.1 g/day, p = 0.74) and other food types (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In controls, logHA was correlated with daily consumption of animal protein (r = 0.24, p = 0.003); in patients, there was no such correlation (r = -0.003, p = 0.98).
The similarity between patients and controls in daily animal protein consumption and the absence of the normal correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect) may be increasing blood harmane concentration in patients.
We are studying participants selected from the Child Health and Development Studies (CHDS), a longitudinal birth cohort of over 20,000 California pregnancies between 1959 and 1967, for associations ...between maternal body burden of organochlorine contaminants and thyroid function. We designed a pilot study using 30 samples selected among samples with high and low PCB concentrations to evaluate the feasibility of measuring OH-PCBs in the larger study population. GC-ECD and GC-NCI/MS were used to determine PCBs and OH-PCBs as methyl derivatives, respectively. Maternal serum levels of Σ
11PCBs and Σ
8OH-PCB metabolites varied from 0.74 to 7.99 ng/mL wet wt. with a median of 3.05 ng/mL, and from 0.12 to 0.98 ng/mL wet wt. with a median of 0.39 ng/mL, respectively. Average concentrations of Σ
8OH-PCB metabolites in the high PCB group were significantly higher than those in the low PCB group (
p
<
0.05). The levels of OH-PCB metabolites were dependent on PCB levels (
r
=
0.58,
p
<
0.05) but approximately an order of magnitude lower (
p
<
0.05). The average ratio of Σ
8OH-PCBs to Σ
11PCBs was 0.14
±
0.08. The primary metabolite was 4-OH-CB187 followed by 4-OH-CB107. Both of these metabolites interfere with the thyroid system in
in vitro, animal, and human studies. OH-PCBs were detectable in all archived sera analyzed, supporting the feasibility to measure OH-PCB metabolites in the entire cohort.
At present, it is unclear which treatment strategy is best for couples with unexplained or mild male subfertility. We hypothesized that the prognostic profile influences the effectiveness of assisted ...conception. We addressed this issue by analysing individual patient data (IPD) from randomized controlled trials (RCTs).
We performed an IPD analysis of published RCTs on treatment strategies for subfertile couples. Eligible studies were identified from Cochrane systematic reviews and we also searched Medline and EMBASE. The authors of RCTs that compared expectant management (EM), intracervical insemination (ICI), intrauterine insemination (IUI), all three with or without controlled ovarian stimulation (COS) and IVF in couples with unexplained or male subfertility, and had reported live birth or ongoing pregnancy as an outcome measure, were invited to share their data. For each individual patient the chance of natural conception was calculated with a validated prognostic model. We constructed prognosis-by-treatment curves and tested whether there was a significant interaction between treatment and prognosis.
We acquired data from 8 RCTs, including 2550 couples. In three studies (n = 954) the more invasive treatment strategies tended to be less effective in couples with a high chance of natural conception but this difference did not reach statistical significance (P-value for interaction between prognosis and treatment outcome were 0.71, 0.31 and 0.19). In one study (n = 932 couples) the strategies with COS (ICI and IUI) led to higher pregnancy rates than unstimulated strategies (ICI 8% versus 15%, IUI 13% versus 22%), regardless of prognosis (P-value for interaction in all comparisons >0.5), but at the expense of a high twin rate in the COS strategies (ICI 6% versus 23% and IUI 3% versus 30%, respectively). In two studies (n = 373 couples), the more invasive treatment strategies tended to be more effective in couples with a good prognosis but this difference did not reach statistical significance (P-value for interaction: 0.38 and 0.68). In one study (n = 253 couples) the differential effect of prognosis on treatment effect was limited (P-value for interaction 0.52), perhaps because prognosis was incorporated in the inclusion criteria. The only study that compared EM with IVF included 38 couples, too small for a precise estimate.
In this IPD analysis of couples with unexplained or male subfertility, we did not find a large differential effect of prognosis on the effectiveness of fertility treatment with IUI, COS or IVF.
Exposure to manganese via inhalation has long been known to elicit neurotoxicity in adults, but little is known about possible consequences of exposure via drinking water. In this study, we report ...results of a cross-sectional investigation of intellectual function in 142 10-year-old children in Araihazar, Bangladesh, who had been consuming tube-well water with an average concentration of 793 μg Mn/L and 3 μg arsenic/L. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children's intellectual function was assessed on tests drawn from the Wechsler Intelligence Scale for Children, version III, by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead, As, Mn, and hemoglobin concentrations. After adjustment for sociodemographic covariates, water Mn was associated with reduced Full-Scale, Performance, and Verbal raw scores, in a dose-response fashion; the low level of As in water had no effect. In the United States, roughly 6% of domestic household wells have Mn concentrations that exceed 300 μg Mn/L, the current U.S. Environmental Protection Agency lifetime health advisory level. We conclude that in both Bangladesh and the United States, some children are at risk for Mn-induced neurotoxicity.
Background: We recently reported results of a cross-sectional investigation of intellectual function in 10-year-olds in Bangladesh, who had been exposed to arsenic from drinking water in their home ...wells. Objectives: We present results of a similar investigation of 301 randomly selected 6-year-olds whose parents participated in our ongoing prospective study of the health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Methods: Water As and manganese concentrations of tube wells at each home were obtained by surveying all study region wells. Children and mothers were first visited at home, where the quality of home stimulation was measured, and then seen in our field clinic, where children received a medical examination wherein weight, height, and head circumference were assessed. We assessed children's intellectual function using subtests drawn from the Wechsler Preschool and Primary Scale of Intelligence, version III, by summing weighted items across domains to create Verbal, Performance, Processing Speed, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and were asked to provide blood samples for blood lead measurements. Results: Exposure to As from drinking water was associated with reduced intellectual function before and after adjusting for water Mn, for blood lead levels, and for sociodemographic features known to contribute to intellectual function. With covariate adjustment, water As remained significantly negatively associated with both Performance and Processing Speed raw scores; associations were less strong than in our previously studied 10-year-olds. Conclusion: This second cross-sectional study of As exposure expands our concerns about As neurotoxicity to a younger age group.
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