Maternal smoking during pregnancy and the risk of childhood brain tumors: Results from a Swedish cohort study

BackgroundTobacco metabolites and carcinogens can be found in placental and umbilical cord tissues of fetuses exposed to maternal smoking. However, studies regarding maternal smoking during pregnancy and childhood brain tumor (CBT) have shown inconsistent results.MethodsAll children born in Sweden between 1983 and 2010 and with information about maternal smoking during pregnancy, obtained from the Swedish Medical Birth Register, were included in this population based cohort study (n = 2,577,305). CBT cases were identified from the National Cancer Register. Cox regression models were used to estimate the effect of maternal smoking during pregnancy on the risk of CBTs.ResultsWe identified 1039 cases of CBT in the cohort. Overall, there was little or no effect of maternal smoking during pregnancy on the risk of CBTs. However, in analyses stratified by age at diagnosis and child’s sex, positive associations were found among 5–9 years old children. In this age interval, maternal smoking during pregnancy was associated with an increased risk of all CBTs combined only among male children (RR = 1.50, 95% CI 0.96–2.34), while for astrocytoma there was a positive association in both male (RR = 2.00, 95% CI 1.02–3.91) and female children (RR = 1.80, 95% CI 0.85–3.82).ConclusionResults from this large Swedish cohort study suggest that even though maternal smoking during pregnancy has a limited overall effect on CBTs, it may increase the risk of astrocytomas.     

Domoic acid exposure and associated clinical signs and histopathology in Pacific harbor seals (Phoca vitulina richardii)

Domoic acid (DA) is a potent neurotoxin that has caused strandings and mortality of seabirds and marine mammals off the California coast. Pacific harbor seals (Phoca vitulina richardii) are an abundant, nearshore species in California; however, DA exposure and toxicosis have not been documented for harbor seals in this region. To investigate DA exposure in harbor seals, samples were collected from free-ranging and stranded seals off California to assess exposure, clinical signs of toxicosis, and brain lesions in harbor seals exposed to DA. Domoic acid was detected in 65% (17/26) of urine samples collected from apparently healthy free-ranging seals, with concentrations of 0.4–11.7 ng/ml. Domoic acid also was detected in feces (2.4–2887 ng/g), stomach contents (1.4 ng/g; stranded only), milk (2.2 ng/ml; stranded only), amniotic fluid (9.7 ng/ml; free-ranging only), fetal meconium (14.6–39.8 ng/g), and fetal urine (2.0–10.2 ng/ml). Clinical signs indicative of DA toxicosis were observed in two live-stranded seals, and included disorientation, seizures, and uncoordinated movements. Histopathology revealed the presence of brain lesions consistent with DA toxicosis in two live-stranded seals, and one free-ranging seal that died during capture. Results indicated that harbor seals were exposed to DA, exhibited clinical signs and histological lesions associated with DA exposure, and that pups were exposed to DA in utero and during lactation via milk. Future investigation is required to determine the magnitude of impact that DA has on the health and mortality of harbor seals.     

Prepubertal octylphenol exposure up-regulate BRCA1 expression,down-regulate ERα expression and reduce rat mammary tumorigenesis

Background: Endogenous estrogens play an important role in the development of breast cancer. Octylphenol (OP) and genistein (GEN) are estrogen-like chemicals. Prepubertal estradiol and genistein exposure can up-regulate BRCA1 mRNA in mammary gland and reduce futuer breast cancer risk. In the present study, the effects of prepubertal exposure to high-dose OP and GEN on mammary carcinogenesis and the association with the expression of BRCA1 and ERα were investigated. Methods: Prepubertal female Sprague–Dawley rats were exposed to 20, 40, 80 mg/kg OP daily from postnatal day (PND) 22–28, subsequently, the rats were given a single dose of 100 mg/kg 7,12-dimethylbenz [a] anthracene (DMBA) on PND42 to induce mammary tumor. Results: The incidence of DMBA-induced mammary tumors significantly decreased when rats were treated with 40 mg/kg OP. BRCA1 mRNA and protein expression were found up-regulated and ERα expression was down-regulated in the mammary tumor when rats were exposed to 40 mg/kg octylphenol. Conclusion: Exposure 40 mg/kg octylphenol can reduce later breast cancer risk in prepubertal Sprague–Dawley rats, the protective effect of OP is associated with persistent up-regulation of BRCA1 and down-regulation of ERα in the mammary tumor.     

Case-control study of birth characteristics and the risk of hepatoblastoma

Background: Hepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology. Methods: We matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n = 218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates. Results: We observed increased risks for hepatoblastoma among children with low [1500–2499 g, Odds Ratio (OR) = 2.02, 95% confidence interval (CI) 1.29–3.15] and very low birthweight (<1500 g, OR = 15.4, 95% CI 10.7–22.3), preterm birth <33 weeks (OR = 7.27, 95% CI 5.00, 10.6), small size for gestational age (OR = 1.75, 95% CI 1.25–2.45), and with multiple birth pregnancies (OR = 2.52, 95% CI 1.54–4.14). We observed a number of pregnancy and labor complications to be related to hepatoblastoma, including preeclampsia, premature labor, fetal distress, and congenital anomalies. Conclusion: These findings confirm previously reported associations with low birthweight and preeclampsia. The relation with multiple birth pregnancies has been previously reported and may indicate a relation to infertility treatments.     

Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep

Glucocorticoids including betamethasone (BM) are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious long term consequences. In a sheep model of fetal programming, BM-exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of age associated with changes in the circulating and renal renin-angiotensin systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen (Aogen), and receptor expression in this brain region of exposed and control offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1 receptor expression was not changed. BMX offspring exhibited a higher ratio of Ang II to Ang-(1-7) (2.30 ± 0.36 versus 0.99 ± 0.28; p < 0.01) and Ang II to Ang I at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in 0.5-year BMX animals (0.78 ± 0.06 vs. 1.94 ± 0.41; p < 0.05) suggesting a greater degree of enzymatic processing of the precursor protein in exposed animals. We conclude that in utero BM exposure promotes an imbalance in the central RAS pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and lower BRS in this model.     

Risk of neuroblastoma,maternal characteristics and perinatal exposures: The SETIL study

PurposeNeuroblastoma (NB) is the most common extra-cranial paediatric solid tumour. Incidence peaks in infancy, suggesting a role of in-utero and neonatal exposures but its aetiology is largely unknown. The aim of the present study is to evaluate the association between maternal characteristics and perinatal factors with the risk of NB, using data from the SETIL database.MethodsSETIL is a large Italian population-based case-control study established to evaluate several potential cancer risk factors in 0–10 year olds. Information about maternal characteristics, reproductive history, environmental and occupational exposures during pregnancy, as well as newborns’ characteristics were obtained using a structured questionnaire. Extremely low frequency magnetic field (ELF-MF) home exposure was measured. The study included 1044 healthy controls and 153 NB cases, diagnosed between 1998 and 2001.ResultsA twofold risk was associated to exposure in pregnancy to chemical products for domestic work and to hair dye. The risk associated with the latter was higher among 0–17 month old children (OR = 5.5, 95%CI: 1.0–29.3). Risk was increased for children whose mothers had suffered work related exposure in the preconception period to solvents (OR = 2.0 95%CI: 1.0–4.1) and in particular to aromatic hydrocarbons (OR = 9.2, 95%CI: 2.4–34.3). No association was observed with ELF-MF exposure. A higher risk was found among children with congenital malformations (OR = 4.9, 95%CI: 1.8–13.6) or neurofibromatosis (2 cases and 0 controls, p = 0.016).ConclusionsOur study suggests maternal exposure to hair dyes and aromatic hydrocarbons plays a role and deserves further investigation. The association with congenital malformations might also be explained by over-diagnosis.External exposure, in particular during and before pregnancy might contribute to NB occurrence.     

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR) = 1.48, 95% CI: 1.14–1.91, P < 0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR = 1.70, 95% CI: 1.28–2.27, P < 0.01). However, differences in SCE frequency were not observed (FR = 1.14, 95% CI: 0.81–1.61, P > 0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR = 1.35, 95% CI: 1.02–1.80, P < 0.05); age, older workers exhibited higher MN frequencies than younger workers (FR = 1.45, 95% CI: 1.14–1.84, P < 0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR = 1.40, 95% CI: 1.10–1.77, P < 0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (?) (FR = 1.48, 95% CI: 1.14–1.92) or GSTT1 (?) (FR = 1.42, 95% CI: 1.10–1.83) genotypes, and especially those who carried both (FR = 2.10, 95% CI: 1.43–3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P > 0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.     

Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde

DNA and chromosome damages in peripheral blood lymphocytes were evaluated in 151 workers occupationally exposed to formaldehyde (FA) and 112 non-FA exposed controls. The effects of polymorphisms in three glutathione-S-transferase (GSTs) genes on the DNA and chromosome damages were assessed as well. Alkaline comet assay and cytokinesis-block micronucleus (CBMN) assay were used to determine DNA and chromosome damages, respectively. The genotypes of GSTP1 (Ile105Val), GSTT1, and GSTM1 were assayed. The mean 8-h time-weighted average (TWA) concentrations of FA in two plywood factories were 0.83 ppm (range: 0.08–6.30 ppm). FA-exposed workers had higher olive tail moment (TM) and CBMN frequency compared with controls (Olive TM, 3.54, 95%CI = 3.19–3.93 vs. 0.93, 95%CI = 0.78–1.10, P < 0.01; CBMN frequency, 5.51 ± 3.37 vs. 2.67 ± 1.32, P < 0.01). Olive TM and the CBMN frequency also had a dose-dependent relation with the personal FA exposure. Significant association between FA exposure history and olive TM and CBMN frequency were also identified. The level of olive TM was slightly higher in FA-exposed workers with GSTM1 null genotype than those with non-null genotype (3.86, 95%CI = 3.31–4.50 vs. 3.27, 95%CI = 2.83–3.78, P = 0.07) with adjustment of covariates. We also found that FA-exposed workers carrying GSTP1 Val allele had a slightly higher CBMN frequency compared with workers carrying only the wild-type allele (6.32 ± 3.78 vs. 5.01 ± 2.98, P = 0.05). Our results suggest that the FA exposure in this occupational population increased DNA and chromosome damages and polymorphisms in GSTs genes may modulate the genotoxic effects of FA exposure.     

The relationship between fetal and maternal selenium concentrations in sheep and goats

In this study, biological samples (slaughterhouse material) were collected from 30 sheep and 36 goats and classified according to gestational stage into either early or late gestation. Samples consisted of allantoic fluid, amniotic fluid, fetal liver, fetal kidney, fetal thyroid gland, maternal plasma and liver to determine selenium (Se) concentrations throughout gestation. The Se concentrations in the allantoic fluid, fetal liver and kidney increased significantly (p < 0.01) during late gestation. Concurrently, the Se concentrations in amniotic fluid, maternal plasma and liver decreased significantly (p < 0.01) over time. Significant (p < 0.01) positive relationships were recorded between the age of the fetus and Se concentrations in the allantoic fluid (r = 0.57–0.75), fetal liver (r = 0.43–0.59) and kidney (r = 0.80–0.81) in both sheep and goats. A significant (p < 0.05) positive relationships were also recorded between the Se concentrations in the allantoic fluid and fetal liver (r = 0.35–0.37), the maternal plasma and liver Se concentrations (r = 0.37–0.57) between sheep and goats. A significant (p < 0.05) negative correlation was recorded between the Se concentrations in the allantoic fluid with maternal plasma of sheep (r = −0.41) as well as between the fetal liver and maternal liver Se (r = −0.22 to 0.50) and a negative correlation (r = −0.42 to 0.43) (p < 0.01) between Se concentrations in the fetal liver and amniotic fluid in both sheep and goats, respectively. Se concentration in the fetal liver was significantly (p < 0.01) higher than that of the kidney and thyroid. In the thyroid gland no morphological differences were noted. Strong fetal–maternal relationships in Se concentration were evident throughout the gestational period and dams seem to sacrifice Se levels in order to maintain that in the fetus. Se concentrations in the amniotic and allantoic fluids could be used as a possible indicator of the Se status of the fetus throughout gestation.     

Multiple myeloma and occupation: A pooled analysis by the International Multiple Myeloma Consortium

Objective: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case–control studies. Methods: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). Results: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50, 95% CI 0.9–2.3), while other farming jobs did not. Metal processors (OR = 1.55, 95% CI 0.9–2.3), female cleaners (OR = 1.32, 95% CI 1.0–1.8), and high level exposure to organic solvents (OR = 1.38, 95% CI 0.96–1.8) also showed moderately increased risks. Conclusions: Additional case–control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.     

Cotyledonary responses to maternal selenium and dietary restriction may influence alterations in fetal weight and fetal liver glycogen in sheep

To examine the effects of maternal supranutritional selenium (Se) and nutrient restriction during mid and late gestation on placental characteristics and fetal liver glycogen, ewes received either adequate Se (ASe) or high Se (HSe) prior to breeding. On d 64 of gestation, ASe and HSe ewes remained at 100% of requirements (controls; CON) or were restricted (RES; 60% of requirements). On d 135 of gestation, fetal weight (P ≤ 0.08) was greatest in both HSe and CON ewes. Placentome number, mass, and caruncular and cotyledonary weight were not different (P ≥ 0.17) among treatments. Fetal mass:placental mass ratio was less (P = 0.06) in RES compared to CON ewes. Compared to ASe, HSe exhibited increased (P ≤ 0.08) cellular proliferation and DNA concentration and decreased (P = 0.07) cellular size in cotyledonary tissue. Nutritional restriction decreased (P ≤ 0.08) cotyledonary protein concentration and cellular size. VEGF receptor 1 (Flt) mRNA in cotyledonary tissue was greater in HSe compared with ASe ewes (P = 0.06) and in RES compared with CON ewes (P = 0.08). There was no effect of diet on caruncular growth variables (P ≥ 0.13) or on placental vascularity (P ≥ 0.11). Progesterone was greater (P ≤ 0.08) in ASe–RES ewes compared to all groups at d 90 and ASe–CON and HSe–CON at d 104. Although fetal glucose and cortisol concentrations were not affected by diet, fetal liver glycogen was greater (P = 0.04) in ASe–RES compared to ASe–CON and HSe–RES ewes with HSe–CON being intermediate. Both Se and nutritional plane may impact placental function and fetal growth, as fetal weight and liver glycogen are altered despite similar placental vascularity measurements.     

Long-term risk of receiving a total hip replacement in cancer patients

Aim: To investigate whether cancer patients have an increased risk of receiving a total hip replacement compared to the standard population of Norway. Materials and methods: By linking of The Cancer Register of Norway and The Norwegian Arthroplasty Register we obtained information on cancer diagnoses (type, date of diagnosis), total hip arthroplasties and date of death for all patients living in Norway. This includes 741,901 patients categorized into three groups: 652,197 patients with at least one cancer diagnosis but no hip arthroplasties, 72,469 patients with at least one hip arthroplasty but no cancer diagnosis and 17,235 patients who have at least one cancer diagnosis and at least one hip arthroplasty. Within this latter group, 8563 individuals had been diagnosed with cancer prior to a total hip arthroplasty. Statistical methods applied in this study were Cox interval censored regression models and standardized incidence ratios (SIR). Results: Cancer patients had a slightly increased risk of receiving a total hip arthroplasty compared to the Norwegian population (SIR = 1.15 (95% CI, 1.12–1.17)). For primary tumours located cranially to the pelvic area there was no significant increase in risk for hip arthroplasty. An exception was breast cancer (SIR = 1.13 (95% CI 1.08–1.18)). Cancer located in the pelvic region (SIR = 1.20 (95% CI 1.16–1.24)), malignant lymphoma (SIR = 1.30 (95% CI 1.15–1.46)) and leukaemia (SIR = 1.17 (95% CI 1.01–1.34)) had an increased risk for receiving a total hip arthroplasty. Conclusion: Cancer survivors, mainly those with pelvic and lympho-hematological malignancies, have a small statistically significant increase in risk for receiving total hip arthroplasty.     

Postpartum resumption of ovarian cycling activity in first-calf suckled beef cows exposed to familiar or unfamiliar bulls

The objective of this experiment was to determine if the proportion of first-calf suckled beef cows that resumed ovulatory cycles and the interval to resumption of ovarian cycling activity differ after exposure to either “unfamiliar” bulls or cows on d 35 postpartum, after exposure to either “familiar” bulls or cows for the first 30–32 d after calving. Fifty Angus × Hereford cows were stratified by calving date, calf BW, and calf sex by d 3 postpartum, and assigned to be exposed to familiar epididectomized bulls (BEF; n = 25) or familiar mature ovariectomized (OVX) cows (CEF; n = 25). On d 35 after calving, 12 BEF cows were assigned to be exposed to unfamiliar bulls (BEU); likewise, 12 CEF cows were assigned to be exposed to unfamiliar OVX cows (CEU). Cows were in their treatments for either 95 d (BEF and CEF) or 60 d (BEU and CEU) during the experiment. Blood samples were collected every third d from the beginning to the end of the experiment. A rise in progesterone concentration of >0.5 ng/mL in consecutive samples was used as the criterion for resumption of ovulatory cycles. Exposing cows to bulls on d 5 after calving and then switching a subset of these cows to be exposed to unfamiliar bulls 30–32 d later did not (P > 0.10) alter: (1) the proportion of cows that resumed cycling activity; and (2) postpartum interval to resumption of ovarian cycling activity compared to cows exposed to familiar bulls. However, 32% more (P < 0.05) cows exposed to bulls (BEF and BEU) resumed cycling activity by approximately 14.8 d before cows that were exposed to OVX cows (CEF and CEU). We conclude that the familiarity of first-calf cows to either bulls or ovariectomized cows, did not affect the postpartum occurrence of cycling activity or the interval from calving to resumption of ovulatory cycles. However, bull exposure, whether familiar or unfamiliar, stimulates first-calf cows to resume ovulatory cycles sooner after calving than if they are not exposed to bulls.     

Plasma copeptin concentration and outcome after pediatric traumatic brain injury

Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 126 healthy children and 126 children with acute severe TBI were measured by enzyme-linked immunosorbent assay. Twenty-one patients (16.7%) died and 38 patients (30.2%) had an unfavorable outcome (Glasgow Outcome Scale score of 1–3) at 6 months. Plasma copeptin level was obviously higher in patients than in healthy children (46.2 ± 20.8 pmol/L vs. 9.6 ± 3.0 pmol/L, P < 0.001). Plasma copeptin level was identified as an independent predictor for 6-month mortality [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112–1.538, P = 0.005] and unfavorable outcome (OR 1.313, 95% CI 1.146–1.659, P = 0.003). The predictive value of copeptin was similar to that of Glasgow Coma Scale (GCS) score for 6-month mortality [area under curve (AUC) 0.832, 95% CI 0.755–0.892 vs. AUC 0.873, 95% CI 0.802–0.926, P = 0.412] and unfavorable outcome (AUC 0.863, 95% CI 0.790–0.918 vs. AUC 0.885, 95% CI 0.816–0.935, P = 0.596). Copeptin improved the AUC of GCS score for 6-month unfavorable outcome (AUC 0.929, 95% CI 0.869–0.967, P = 0.013), but not for 6-month mortality (AUC 0.887, 95% CI 0.818–0.936, P = 0.600). Thus, plasma copeptin level represents a novel biomarker for predicting 6-month clinical outcome in children with TBI.     

Stature,body mass,and brain size: A two-million-year odyssey

Physical size has been critical in the evolutionary success of the genus Homo over the past 2.4 million-years. An acceleration in the expansion of savannah grasslands in Africa from 1.6 Ma to 1.2 Ma witnessed concomitant increases in physical stature (150–170 cm), weight (50–70 kg), and brain size (750–900 cm³). With the onset of 100,000 year Middle Pleistocene glacial cycles (“ice ages”) some 780,000 years ago, large-bodied Homo groups had reached modern size and had successfully dispersed from equatorial Africa, Central, and Southeast Asia to high-latitude localities in Atlantic Europe and North East Asia. While there is support for incursions of multiple Homo lineages to West Asia and Continental Europe at this time, data does not favour a persistence of Homo erectus beyond ～400,000 years ago in Africa, west and Central Asia, and Europe. Novel Middle Pleistocene Homo forms (780,000–400,000 years) may not have been substantially taller (150–170 cm) than earlier Homo (1.6 Ma–800,000 years), yet brain size exceeded 1000 cm³ and body mass approached 80 kg in some males. Later Pleistocene Homo (400,000–138,000 years) were ‘massive’ in their height (160–190 cm) and mass (70–90 kg) and consistently exceed recent humans. Relative brain size exceeds earlier Homo, yet is substantially lower than in final glacial H. sapiens and Homo neanderthalensis. A final leap in absolute and relative brain size in Homo (300,000–138,000 years) occurred independent of any observed increase in body mass and implies a different selective mediator to that operating on brain size increases observed in earlier Homo.     

Assessment of alterations in X-ray irradiation-induced DNA damage of glioma cells by using proton nuclear magnetic resonance spectroscopy

Glioma is one of the most common types of brain tumors. DNA damage is closely associated with glioma cell apoptosis induced by X-ray irradiation. Alterations of metabolites in glioma can be detected noninvasively by proton nuclear magnetic resonance (1H NMR) spectroscopy. To noninvasively explore the micro mechanism in X-ray irradiation-induced apoptosis, the relationship between metabolites and DNA damage in glioma cells was investigated. Three glioma cell lines (C6, U87 and U251) were randomly designated as control (0 Gy) and treatment groups (1, 5, 10, 15 Gy). After X-ray exposure, each group was separated into four parts: (i) to detect metabolites by 1H NMR spectroscopy; (ii) to make cell colonies; (iii) to detect cell cycle distribution and apoptosis rate by flow cytometry; and (iv) to measure DNA damage by comet assay. The metabolite ratios of lactate/creatine and succinate/creatine decreased (lactate/creatine: C6, 22.17–66.27%; U87, 15.93–44.56%; U251, 26.27–74.48%. succinate/creatine: C6, 14.41–48.35%; U87, 22.03–70.62%; U251, 17.33–60.06%) and choline/creatine increased (C6, 52.22–389.68%; U87, 56.15–82.36%; U251, 31.87–278.62%) in the treatment groups compared with the control group (each P < 0.05), which linearly depended on DNA damage. An increasing dose of X-ray irradiation increased numbers of apoptotic cells (P < 0.01), and the DNA damage parameters were dose-dependent (P < 0.05). The colony-forming rate declined (P < 0.01) and the percentage of cells at G1 stage increased when exposed to 1 Gy X-ray (three cell lines, P < 0.05). Metabolite alterations detected by 1H NMR spectroscopy can be used to determine DNA damage induced by X-ray irradiation. 1H NMR spectroscopy is a noninvasive method to predict DNA damage of glioma cell at the micro level.     

Techniques for in utero,longitudinal MRI of fetal brain development in baboons at 3 T

Magnetic Resonance Imaging (MRI) is a promising tool for the noninvasive, longitudinal study of developing primate brains. We developed a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. This protocol includes procedures for animal preparation, anesthesia, MRI scanning, and post-scan animal care. We applied this protocol to scan 5 baboons multiple times across the latter 70% of gestation—from as early as 56 days post-conceptional age to as late as 185 days (term ～180 days). We successfully acquired high-resolution anatomical images and maps of relaxation times (T₁ and T₂) of the fetal brains at multiple time points across gestation. These images and maps demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the convergence of contrast is a consequence of the continuous change in relaxation times during fetal brain development. We estimated the rates of decrease of T₁ and T₂ in white matter and gray matter, respectively. In addition, we measured the volumes of fetal brain at different gestational ages and calculated the growth rates of whole brain (0.91 ± 0.08 cm³/day) and cortical gray matter (0.40 ± 0.04 cm³/day). We also measured the mean diffusivity in white matter and deep gray matter using diffusion tensor imaging. In conclusion, in utero MRI of fetal baboon brains greatly enhances the use of nonhuman primate models to study fetal brain development longitudinally.     

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

Introduction: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Methods: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Results: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI = 0.77–1.34)]; esophagus [1.17 (95% CI = 0.90–1.51)]; stomach [1.09 (95% CI = 0.93–1.28)]; colon [0.89 (95% CI = 0.70–1.12)]; and rectum [1.17 (95% CI = 0.98–1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR = 1.49 (95% CI = 1.06–2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Discussion: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.     

Behavioral and mortality responses of the bivalves Scrobicularia plana and Cerastoderma edule to temperature,as indicator of climate change's potential impacts

Temperature is one of the most important abiotic factors affected by climate change. It determines physiological processes, ecological patterns and establishes the limits of geographic distribution of species. The induced thermal stress frequently results in physiological and behavioral responses and, in extreme cases, may lead to mortality episodes. Scrobicularia plana and Cerastoderma edule behavioral and mortality responses to temperature were evaluated. Specimens were sampled in the Mondego estuary (Portugal), acclimated and exposed to different temperature treatments (5–35 °C). Individual activity and mortality were registered during 120 h laboratory assays. Both species showed a thermal optimum for their activity (S. plana: 15–23 °C; C. edule: 20–23 °C), and survival was mainly affected by high temperature (S. plana: LC50_120 h = 28.86 °C; C. edule: LC50_120 h = 28.01 °C), with 100% mortality above critical values (≥32 °C). Results further indicated that both species are more affected the higher the temperature and the longer the exposure time. This study indicates that the occurrence of extreme climatic events, especially heat waves, may be particularly impairing for these species.     

Effect of Zinc nanoparticles on oxidative stress-related genes and antioxidant enzymes activity in the brain of Oreochromis niloticus and Tilapia zillii

This study was carried out to determine the median lethal concentrations (LC₅₀) of Zinc nanoparticles (ZnNPs) on Oreochromis niloticus and Tilapia zillii. The biochemical and molecular potential effects of ZnNPs (500 and 2000 μg L⁻¹) on the antioxidant system in the brain tissue of O. niloticus and T. zillii were investigated. Four hundred fish were used for acute and sub-acute studies. ZnNP LC₅₀ concentrations were investigated in O. niloticus and T. zillii. The effect of 500 and 2000 μg L⁻¹ ZnNPs on brain antioxidants of O. niloticus and T. zillii was investigated. The result indicated that 69 h LC₅₀ was 5.5 ± 0.6 and 5.6 ± 0.4 for O. nilotica and T. zillii, respectively. Fish exposed to 500 μg L⁻¹ ZnNPs showed a significant increase in reduced glutathione (GSH), total glutathione (tGSH) levels, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity and gene expression. On the contrary, malondialdehyde (MDA) levels significantly decreased. Meanwhile, fish exposed to 2000 μg L⁻¹ ZnNPs showed a significant decrease of GSH, tGSH levels, SOD, CAT, GR, GPx and GST activity and gene expression. On the contrary, MDA levels significantly increased. It was concluded that, the 96 h LC₅₀ of ZnNPs was 5.5 ± 0.6 and 5.6 ± 0.4 for O. nilotica and T. zillii, respectively. ZnNPs in exposure concentrations of 2000 μg/L induced a deleterious effect on the brain antioxidant system of O. nilotica and T. zillii. In contrast, ZnNPs in exposure concentrations of 500 μg L⁻¹ produced an inductive effect on the brain antioxidant system of O. nilotica and T. zillii.