Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis.

Triclocarban is a phenyl ether that has recently been classified as a contaminant of emerging concern. Evidence shows that triclocarban is present in human tissues, but little is known about the impact of triclocarban on the nervous system, particularly at early developmental stages. This study demonstrated that triclocarban that was used at environmentally relevant concentrations induced apoptosis in mouse embryonic neurons, inhibited sumoylation, and changed the epigenetic status, as evidenced by impaired activities of HDAC, sirtuins, and DNMT, global DNA hypomethylation, and alterations of methylation levels of bax, bcl2, Ahr, and Car genes. The use of selective antagonists and specific siRNAs, which was followed by the co-localization of aryl hydrocarbon receptor (AHR) and constitutive androstane receptor (CAR) in mouse neurons, points to the involvement of AHR and CAR in triclocarban-induced neurotoxicity. A 24-h treatment with triclocarban enhanced protein levels of the receptors which was paralleled by Car hypomethylation and Ahr hypermethylation. Car hypomethylation is in line with global DNA hypomethylation and explains the increased mRNA and protein levels of CAR in response to triclocarban. Ahr hypermethylation could reflect reduced Ahr mRNA expression and corresponds to lowered protein levels after 3- and 6-h exposures to triclocarban that is likely related to proteasomal degradation of activated AHR. We hypothesize that the triclocarban-induced apoptosis in mouse neurons and the disruption of epigenetic status involve both AHR- and CAR-mediated effects, which may substantiate a fetal basis of the adult onset of neurological diseases; however, the expression of the receptors is regulated in different ways.

[Advising Women to Avoid Excessive Gestational Weight Gain: What do Pregnant Women Think?] / Sichtweisen schwangerer Frauen zu ihrem Ernährungs- und Bewegungsverhalten: eine Beratungsgrundlage zur Vermeidung exzessiver Gewichtszunahme.

Gestational weight gain above the IOM recommendations is a risk factor for both pregnancy complications and maternal and childhood overweight. Therefore, pregnant women should be advised about their weight gain. Do these women have special specific needs? A total of 34 pregnant women were interviewed. Using Mayring's frequency analysis, we found that these pregnant women were not aware of health consequences of excessive weight gain. Furthermore, we identified 4 main types of nutritional behavior: (i) women who are informed but do not put into practice their knowledge, (ii) women who adhere strictly to recommendations, (iii) women who are led by their physical feelings and (iv) women mostly indifferent. Women who were physically inactive before pregnancy did not start exercising in pregnancy. There are still information gaps on weight gain and healthy eating that have to be considered for future interventions. According to women's behavioral patterns, interventions might yield varying results. According to women's type of behavior, interventions might yield different success rates. Motivation and providing information on suitable exercise forms during pregnancy are challenging.

[Psychosocial situation of families with chronically ill children: a survey of parent initiatives]. / Psychosoziale Lage von Familien mit chronisch kranken Kindern: Eine Befragung betroffener Eltern in Selbsthilfegruppen.

Children with chronic illness or disabilities and their families require more support than healthy families. The working group "custodial and psychosocial supply" defined 4 theses to figure out deficits and targets of family support: 1) my child is different; 2) my child is not devisable; 3) my child needs strong helpers; and 4) my child needs safety.Based on these theses, a questionnaire for parents was designed of which 20 were sent to 34 parent initiatives in Germany each, for distribution to a random sample of member families.499/680 questionnaires were returned of which 419 could be included in the analysis. Less than 50% of the parents felt adequately and timely informed about their child's condition, and support for coping with the child's diagnosis was rarely given. Less than half of the parents reported to have been informed about the options for support within the German social system, and less than 15% were aware of instructions for clearing houses on care and support. About a third of the parents reported needs for managing family, siblings or household, but only a third of these had been offered organised and structured family support. More than 50% of the families reported restraints in participating in social life: such restraints were associated with problems in partnership and loss of friends. Half of the parents felt restraints of the family income because of their child's condition.There is need for improvement of the psychosocial condition of families with chronically ill or disabled children by better, more and timely information about the child's clinical condition, access to the social support system and availability of support services.

Fruit and vegetable consumption and BMI change in primary school-age children: a cohort study.

BACKGROUND/OBJECTIVES: Healthy eating behaviours, such as increasing fruit and vegetable consumption (FVC), are frequently used as a target or outcome measure in obesity prevention interventions. The goal of this study was to demonstrate replacement of high-caloric foods/drinks by FVC and changes in body mass index (BMI) z-score associated with FVC. SUBJECTS/METHODS: Anthropometric measurements of 1252 children (51.0% girls) were taken before school entrance (age 6 years) and repeated in the fourth grade (age 10 years). At the same time, parents were asked about their children's diet using a questionnaire. RESULTS: In longitudinal analysis, changes in FVC were not significantly correlated with changes of other nutritional habits, such as consumption of sweets and high-caloric drinks. BMI gain tended to be lower (nonsignificant) in children with increasing fruit consumption compared to those with decreasing fruit consumption. An opposite (nonsignificant) tendency was observed for vegetable consumption and BMI gain. CONCLUSIONS: Although beneficial for other health outcomes, the evidence for FVC replacing high-energy foods and thereby reducing BMI gain is weak and could not be substantiated in this study. This might be partially due to the limitation in dietary assessment.

Long-term effects of enteral feeding on growth and mental health in adolescents with anorexia nervosa--results of a retrospective German cohort study.

BACKGROUND/OBJECTIVE: Anorexia nervosa (AN) is a severe eating disorder with a high mortality rate. Treatment regimes show regional and global variation and are sometimes supported by enteral feeding (EF) via nasogastric tube, although risks and benefits are still unclear. We aimed to find out whether EF improves growth and AN recovery and prevents psychiatric comorbidities. SUBJECTS/METHODS: Data were retrospectively collected from medical records and follow-up data were collected via questionnaires. Two hundred and eight female AN patients who were hospitalized below the age of 18 years with a mean follow-up of 6 years were analyzed. We calculated relative risks for the association between EF and suboptimal growth, remission of AN and the occurrence of psychiatric comorbidities, adjusting for potential confounders. RESULTS: A third of the analyzed girls received EF at any time. In the adjusted analyses, we found no significant associations between EF and suboptimal growth, the persistence of AN and the occurrence of psychiatric comorbidities, respectively. CONCLUSION: Our data suggest EF to be neither a risk factor nor beneficial for growth, recovery or persistence of AN and the occurrence of psychiatric comorbidities.

Gestational diabetes predicts the risk of childhood overweight and abdominal circumference independent of maternal obesity.

AIM: Gestational diabetes mellitus is believed to be a risk factor for childhood overweight/obesity. We aimed to assess whether this association is either a reflection or independent of confounding by maternal BMI. METHODS: Data from 7355 mother-child dyads of the German Perinatal Prevention of Obesity cohort with full anthropometric information on mothers and children, gestational diabetes and confounding factors were obtained at school entry health examination. We calculated crude and adjusted logistic regression models for the association of gestational diabetes and childhood overweight/obesity and abdominal adiposity defined by age- and sex-specific percentiles for BMI and waist circumference. RESULTS: Among all children (mean age 5.8 years), 8.1% were overweight, 2.6% were obese and 15.5% had abdominal adiposity. The prevalence of overweight (obesity) was 21% (8.2%) in children of mothers with gestational diabetes and 10.4% (2.4%) in children of healthy mothers. Analyses with adjustment for maternal BMI and other potential confounders yielded an odds ratio of 1.81 (95% CI 1.23-2.65) and 2.80 (95% CI 1.58-4.99) for the impact of gestational diabetes on childhood overweight and obesity, respectively. Similar results were obtained for the risk of childhood abdominal adiposity (odds ratio 1.64, 95% CI 1.16-2.33) by maternal gestational diabetes. CONCLUSIONS: The postulated increased risk of overweight and abdominal adiposity in offspring of mothers with gestational diabetes cannot be explained by maternal BMI alone and may be stronger for childhood obesity than for overweight.

Gestational weight gain in accordance to the IOM/NRC criteria and the risk for childhood overweight: a meta-analysis.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Gestational weight gain is a modifiable risk factor for childhood overweight. WHAT THIS STUDY ADDS: Exceeding the recommended gestational weight gain increases the risk for childhood overweight by about 30%. Interventions to avoid excessive weight gain are needed. BACKGROUND: Overweight and obesity in children are thought to be related to prenatal priming. Gestational weight gain (GWG) might be a potential modifiable risk factor for childhood overweight. OBJECTIVE: To quantify the associations of inadequate and excessive GWG with childhood overweight. METHODS: The electronic literature search in six databases was complemented by a hand search for relevant articles. Papers were selected and quality was assessed. The effect estimates of the individual studies were pooled using a random-effects model. RESULTS: The literature search yielded 1492 results in total, of which seven observational studies met the inclusion criteria. The studies had medium to good quality. The pooled estimate for the association between excessive GWG and childhood overweight yielded an odds ratio (OR) of 1.38 (95% confidence interval [CI]: 1.21-1.57). The association between inadequate GWG and childhood overweight yielded an OR of 0.91 (95% CI: 0.85-0.98). CONCLUSION: These data provide evidence for at least a 21% risk for childhood overweight related to excessive GWG. Therefore, further efforts to design appropriate interventions against excessive GWG may appear warranted.

Gestational diabetes and cardiovascular risk factors in the offspring: results from a cross-sectional study.

BACKGROUND: While the association of gestational diabetes mellitus and abnormal glucose tolerance is beyond doubt, its associations with other cardiovascular disease risk factors in the offspring are less clearly established. Some of these associations, in particular overweight in the offspring, might be confounded by maternal overweight. METHODS: Data on 12,542 children in the age of 3-17 years with full information about gestational diabetes mellitus and maternal BMI were available from the German nationwide KiGGS study. We calculated linear and logistic regression models for measurements of body composition, blood pressure, HbA(1c) and cholesterol values in the offspring with gestational diabetes mellitus as the explanatory variable, with and without adjustment for maternal BMI. RESULTS: The prevalence of gestational diabetes mellitus in the dataset was 2.2%. Unadjusted regression analyses suggested weak positive effects of gestational diabetes mellitus on body composition measurements [e.g. a mean increase in BMI standard deviation scores (SDS) of 0.17 units (95% confidence interval: 0.03, 0.30)]. After adjustment for maternal BMI, the observed associations almost disappeared [e.g. BMI SDS: 0.07 (-0.06, 0.20)]. With respect to blood pressure and cholesterol, no potential effects of gestational diabetes mellitus were observed in both unadjusted and adjusted models. CONCLUSION: Gestational diabetes mellitus does not appear to have a relevant effect on cardiovascular disease correlates such as blood pressure or cholesterol levels in children, and the potential effect of gestational diabetes mellitus on body composition seems to be widely explainable by maternal BMI.

Microvascular fluid filtration capacity (Kf) assessed with cumulative small venous pressure steps and with various degrees of tilt.

UNLABELLED: Orthostatic dysregulation is a frequent phenomenon in pilots experiencing extreme G forces and after prolonged exposures to microgravity in cosmonauts. We used non-invasive venous congestion plethysmography (VCP) to study microcirculatory changes and the ability to activate peripheral and centrally mediated protective mechanisms during various degrees of tilt, which we used as an orthostatic challenge. METHOD: The study, which was approved by the local ethical committee of the Institute of Biomedical Problems, was performed on six healthy 20 - 26 years old male volunteers. We applied 6 - 8 cumulative small venous congestion pressure steps (8 mmHg) to the thigh and determined the fluid filtration capacity (Kf), the linear relationship between cuff pressure (Pcuff) and measured fluid filtration (Jv). We then measured the fluid filtration (Jv) response to varying cumulative degrees of tilt, starting at 0 degrees followed by head down -8 degrees -15 degrees, -30 degrees -15 degrees, -8 degrees, 0 degrees, and then head up 15 degrees, 30 degrees, 70 degrees, 30 degrees, 15 degrees and 0 degrees. Each tilt stage was sustained for 15 minutes. The change in hydrostatic load, at the level of the strain gauge, was determined by measuring the difference in vertical height between the right atrium and mid calf at the level of the gauge. Limb arterial blood flow was measured and lung function tests were performed before and after the small cumulative pressure step protocol, as well as at the end of each tilt step. RESULTS: No significant changes in blood pressure (BP) and heart rate (HR) occurred during the cumulative pressure step protocol. However, an increase in HR was observed during the tilt, but only reached significance at 30 degrees and 70 degrees. The mean Kf value measured with small cumulative pressure steps was 3.25 +/- 0.5 (10(-3) ml.100 ml tissue(-1) mmHg(-1) = KfU), which was significantly (p < 0.005) higher than the value obtained using tilt to increase the hydrostatic load (0.98 +/- 0.2 KfU). One subject had an unchanged Kf value and experienced vaso - vagal syncope following the imposition of 70 degrees tilt, with a heart rate < 35 / min and a systolic blood pressure of 60 mmHg. The measurement of blood flow in the limb showed no significant change during the tilt procedure. The lung function measurements revealed, that only expiratory reserve volume (ERV) did significantly increase during 35 degrees and 70 degrees head up tilt. All other parameters were unchanged. We suggest that the differences in these Kf values can be explained by the activation of both central and peripheral mediated changes in pre- capillary resistance in response to the tilt. We suspect, that the vaso - vagal syncope, experienced by one subject, reflected his inability to activate these protective reflex mechanisms, a situation that could be exacerbated by sub-clinical venous insufficiency. We believe that these results show that VCP is a useful tool for the determination of intolerance to orthostatic stress.

Changes in the arteriolar volume pulse of the finger during various degrees of tilt using near infra-red and red photoplethysmography.

1. Photoplethysmography is a widely used non invasive technique for the measurement of peripheral oxygen saturation. A more detailed analysis of the volume pulse (VP) can indicate alterations in peripheral vascular tone, due to sympathetic stimulation, stress, pain and temperature. - 2. In six healthy male volunteers we investigated changes in the VP resulting from vasoconstriction and vasodilatation induced by varies degrees of tilt. Subjects were subjected 0 degrees tilt followed by head down -8 degrees -15 degrees, -30 degrees -15 degrees, -8 degrees, 0 degrees, 15 degrees, 30 degrees , 70 degrees, 30 degrees, 15 degrees and 0 degrees. Each tilt stage was sustained for 15 minutes. Both VP - and haemodynamic changes were continuously recorded 30s before and then for 210 s after the imposition of each tilt step. We used a new computer driven soft and hardware for the analysis of the VP. 3. The VP signal was obtained with a sensor emitting 840 nm (NIR) and 640 nm (RED) light into finger tip with a sample rate of 128 Hz. All data was normalised to the initial mean value obtained at 0 degrees tilt. The signal strength parameters amplitude, and area under the curve and the first derivative of the amplitude (flux) as well as time discrete parameters, time of first maximum (Tmax), dicrote wave (Td), volume pulse decrease (Tdec) and fundamental arterial oscillation Tag = Td - Tmax were measured. 4. HR increased significantly during 30 degrees and 70 degrees tilt, but no change in the other hemodynamic parameters was observed. Amplitude, area under the curve and flux of both the Red and the NIR signal increased following head down tilt. A significant decrease of those parameters was found during foot down tilt. 5. No significant changes were found in the time discrete values, neither within each tilt step nor when compared to the initial mean value at 0 degrees tilt. 6. This study reveals that signal strength related parameters such as area under the curve, amplitude and flux reflect changes in vascular tone. Time discrete parameters however did not depict these changes and appear unsuitable for data analysis when using this specific hardware applied in the current study.

Microvascular fluid filtration capacity (Kf) assessed with cumulative small venous pressure steps and with various degrees of tilt.

Tilt procedures are frequently used to test central and peripheral cardio-vascular reflexes. We have previously used venous congestion strain gauge plethysmography for measurement of fluid filtration capacity (Kf) in human legs and have shown that, providing small cumulative venous congestion pressure steps are applied, venous congestion pressure can be increased to arterial diastolic pressure without activating peripheral vasoconstrictor mechanisms. We have also studied the effect of passive tilting on Kf and have shown that the procedure does not influence the measured value Kf indicating that passive tilting does not after the total surface area available for fluid filtration, but rather the blood flow in the microvessels of the tissue under study. In the present protocol we compared the fluid filtration (Jv) resulting from small (7-10 mmHg) cumulative pressure steps with those obtained by altering hydrostatic load with progressive increases and decreases of head down tilt of -8 degrees -15 degrees and -30 degrees, followed by a similar pattern of 15 degrees, 30 degrees and 70 degrees of head up tilt. The values of Jv obtained in response to these procedures were compared with those deduced from the relationship between fluid filtration and venous congestion pressure (Pcuff) obtained during the small cumulative pressure step protocol. It was reasoned that reflex activation, by the tilt induced pressure load, would cause a reduction in local blood flow and enhanced microvascular fluid extraction. The resulting local increase in colloid osmotic pressure would give rise to lower values of Jv than those predicted on the basis of the Kf slope.