Consequences In Later Life Research Articles

7A.03

Objective: Early postnatal life is considered as a critical time window for determination of long-term metabolic states and organ functions. Extrauterine growth restriction (EUGR) causes the development of adult onset chronic diseases, including pulmonary hypertension (PH). However, the mechanisms involved and the possibilities of transgenerational transmission on pulmonary vascular consequences in later life are still unclear. Epigenetic information can be inherited and represents a plausible transgenerational carrier of environmental information. Our study was designed to test whether epigenetics dysregulation mediates the cellular memory of this early postnatal event.Design and method: To test this hypothesis, the EUGR pups were established by undernutritional until weaning. We isolated pulmonary vascular endothelial cells (PVEC) by magnetic-activated cell sorting (MACS) from EUGR and control rats. MeDIP-chip (Methyl-DNA immune precipitation chip), genome-scale mapping studies to search for differentially methylated loci. A postnatal insult, nutritional restriction-induced EUGR caused development of an increased PH at 9-week of age in male rats (First-generation of EUGR, F1-EUGR male). We intercrossed female adult control and F1-EUGR-male rats to obtain the second-generation (F2) offspring in two groups: C male-C female, EUGR-male -C-female. Results: We found that significantly decreased pulmonary artery pressure in F2 female offspring in EUGR-male-C-female group (F2-EUGR-female), compared with controls to some degrees. we carried out genome-wide DNA methylation profiles screen for genes in rats between F1-EUGR-male and F2-EUGR-female. The EUGR and control group comparisons revealed consistently and distinctively methylated loci, with 74.8% F1-EUGR-male group and 84.5% F2-EUGR-female group changes in hyper-methylation loci enriched for highly significant group differences. Gene ontology (GO) analysis on no consistent differentially methylated genes (approximately 37%) between F1-EUGR-male and F2-EUGR-female groups showed that are lipid metabolic process, calcium signaling, methylation and PH-associated genes. We validated candidate dysregulated loci with quantitative assays of cytosine methylation and gene expressions. Conclusions: These results, in conjunction with recent human epidemiological data, demonstrate that DNA methylation is a strong mechanism for propagating the cellular memory of early postnatal events, causing changes in expression of genes and transgenerational transmission on pulmonary vascular consequences in later life.

Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice

Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual’s response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3–5) and a late window (postnatal day 14–16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders.

The association of adverse childhood experiences with mid-life depressive symptoms and quality of life among incarcerated males: exploring multiple mediation

Objectives: To explore the association of experiencing death, trauma, and abuse during childhood with depressive symptoms and quality of life at mid-life among incarcerated men and to understand how current social support and coping strategies mediate the impact of childhood trauma histories on mental health.Methods: Study participants were 192 male inmates in a maximum security prison. Participants completed measures of adverse childhood experiences related to death, trauma, and abuse, and depressive symptoms and quality of life. Data were analyzed using multiple mediation modeling.Results: Men who reported having experienced adverse childhood experiences reported more depressive symptoms and lower quality of life than their counterparts. The results showed that in models both unadjusted and adjusted for age, race, education, number of years served, and whether the inmate had a life sentence, the association between adverse childhood experiences and quality of life were partially explained by the total of the indirect effects (point estimate = −.5052; CI.95 = −1.0364, −.0429 and point estimate = −.7792; CI.95 = −1.6369, −.0381), primarily via social support. However, the associations between adverse childhood experiences and depressive symptoms were not explained by social support and coping.Conclusion: Adverse childhood experiences are associated with deleterious mental health effects in later life. Social support and coping partially mediate the association between adverse childhood experiences and quality of life. The high prevalence of childhood trauma among aging prison inmates warrants attention to increasing social support mechanisms to improve mental health.

Treatment of Severe Childhood Aggression (TOSCA) Studies.

[Author Affiliation]Michael G. Aman. Department of Psychiatry, Ohio State University, Columbus, Ohio.Address correspondence to: Michael G. Aman, PhD, Professor Emeritus of Psychology, The Nisonger Center (OCEDD) Ohio State University, 1581 Dodd Drive, Columbus, Ohio 43210, E-mail: Aman.1@osu.eduFor decades we have known that physical aggression in youth often has dire consequences in later life. The Treatment of Severe Childhood Aggression or TOSCA study was a departure from earlier monotherapy studies of medication treatment for aggression because it entailed an attempt to normalize behavioral outcomes through the use of combined treatment, if needed. The impetus for TOSCA was a series of risperidone studies conducted by Janssen Pharmaceutica and others (e.g., Findling et al., 2000) published in the early 2000s. When designing TOSCA, we were especially interested in risperidone's potential to dampen aggression and other disruptive behaviors. Initially, our focus was comparison of psychostimulant vs. risperidone monotherapy, both with an adjunctive parent training (PT) program. However, using the best data available, power analyses indicated that over 2,000 participants would be needed to have sufficient sensitivity to separate treatments! Eventually, we settled on a combined treatment design not only because it dealt with the statistical-power issue but also because it was ecologically valid (i.e., it followed a common clinical practice; see Farmer et al. 2011 for methodological details).TOSCA is important because it has mapped uncharted territory insofar as pediatric drug research design is concerned. To satisfy the statistical-power issues, we advocated for the complex add-on design (i.e., combined therapy) despite the fact that we, like most practitioners, were trained that simpler is better. The TOSCA design not only called for the use of combined treatments, but one of those treatments was an antipsychotic. Such agents often provoke concern because of their reputation as powerful drugs, because they can cause possible long-term movement disorders, and because of their association with metabolic syndrome. Eventually, the NIMH funded TOSCA and, in so doing, acknowledged the importance of aggression in today's society and the reality that combined pharmacotherapy has become a common practice in child and adolescent psychiatry.The TOSCA participants were 168 children with severe physical aggression (to others, to self, and/or to property) and presence of attention-deficit/hyperactivity disorder (ADHD); psychotic and bipolar disorders were excluded. All study participants received psychostimulant medication and PT in behavior management. If disruptive behavior was not normalized by 3 weeks, then either placebo or risperidone was added as co-therapy from weeks 4 through 9. Psychostimulant+PT+placebo were termed basic treatment, whereas psychostimulant+PT+risperidone were termed augmented treatment. Our earliest reports indicated that augmented treatment was more effective than basic treatment in reducing parent ratings of disruptive behavior (moderate effect size) but not clinician global ratings.Three TOSCA studies appear in this issue. Arnold et al. (2015) examined domains other than disruptive behavior as rated by parents and teachers. They found that augmented treatment resulted in a reduction to teacher-rated anxiety and further that these reductions mediated improvements in parent-rated disruptive behavior. …

G409(P) An evaluation of the transition to adult care for young patients with sickle cell disease

Aims More than 95% of children with sickle cell disease (SCD) survive into adulthood, making a successful transition from child to adult care an essential process. Poor management of this transition may result in reduced compliance, high non-attendance rates and adverse effects in later life. This study aimed to investigate the views of young patients in the process of transitioning with the long-term goal of improving previously poor engagement within the adolescent population. Methods A questionnaire was given to all SCD patients between the ages of 13 and 21 who attended out-patient clinics over a four-month period. Results 31 questionnaire responses were collected (response rate 94%). Overall satisfaction with the transition process varied with age. The mean score was 7.4/10 among 16–21 year olds, but only 4/10 among 13–15 year olds. Praise was given for transition services such as a previously organised tour of the adult department, a peer discussion day and an information pack. 48.4% were interested in speaking to peers about their experiences. 41.9% reported receiving a transition information pack of which 81% found it useful. Adolescents recounted that the topic of transitioning had been first broached at a wide range of ages (see Figure 1). Conclusion There are discrepancies between the planned transition programme and reported patient experience. The tour of adult department and peer discussion day were praised, however not every adolescent recounted experiencing these services. Feedback from clinicians suggests that even though adolescents like the idea of these transition services they still fail to attend. A focus group has been initiated to improve adolescent participation. The information pack was introduced in 2010 which may explain why under half reported receiving it. Notably the majority of those that received it found it useful, suggesting that it is an important component of transition. The age that the topic of transition is introduced could be optimised and standardised, as it is widely thought that beginning the transition process early is an essential element for successful transfer to adult care.

Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh.

BackgroundEarly life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine.MethodsBetween March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation.ResultsArsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 μg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 μg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant’s urine increased non-significantly by 0.13 μg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant’s urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine.ConclusionsWe observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization’s maximum permissible limit (WHO Permissible Limit 15 μg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.

Extrauterine growth restriction on pulmonary vascular endothelial dysfunction in adult male rats: the role of epigenetic mechanisms.

Objective:Early postnatal life is considered as a critical time window for the determination of long-term metabolic states and organ functions. Extrauterine growth restriction (EUGR) causes the development of adult-onset chronic diseases, including pulmonary hypertension. However, the effects of nutritional disadvantages during the early postnatal period on pulmonary vascular consequences in later life are not fully understood. Our study was designed to test whether epigenetics dysregulation mediates the cellular memory of this early postnatal event.Methods and results:To test this hypothesis, we isolated pulmonary vascular endothelial cells by magnetic-activated cell sorting from EUGR and control rats. A postnatal insult, nutritional restriction-induced EUGR caused development of an increased pulmonary artery pressure at 9 weeks of age in male Sprague–Dawley rats. Methyl-DNA immune precipitation chip, genome-scale mapping studies to search for differentially methylated loci between control and EUGR rats, revealed significant difference in cytosine methylation between EUGR and control rats. EUGR changes the cytosine methylation at approximately 500 loci in male rats at 9 weeks of age, preceding the development of pulmonary hypertension and these represent the candidate loci for mediating the pathogenesis of pulmonary vascular disease that occurs later in life. Gene ontology analysis on differentially methylated genes showed that hypermethylated genes in EUGR are vascular development-associated genes and hypomethylated genes in EUGR are late-differentiation-associated and signal transduction genes. We validated candidate dysregulated loci with the quantitative assays of cytosine methylation and gene expressions.Conclusion:These results demonstrate that epigenetics dysregulation is a strong mechanism for propagating the cellular memory of early postnatal events, causing changes in the expression of genes and long-term susceptibility to pulmonary hypertension, and further providing a new insight into the prevention and treatment of EUGR-related pulmonary hypertension.

Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier.

Blood cholesterol levels are not consistently elevated in subjects with age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased long-term risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood-brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life.

Diverse specificities, phenotypes, and antiviral activities of cytomegalovirus-specific CD8+ T cells.

CD8(+) T cells specific for pp65, IE1, and IE2 are present at high frequencies in human cytomegalovirus (HCMV)-seropositive individuals, and these have been shown to have phenotypes associated with terminal differentiation, as well as both cytokine and proliferative dysfunctions, especially in the elderly. However, more recently, T cell responses to many other HCMV proteins have been described, but little is known about their phenotypes and functions. Consequently, in this study, we chose to determine the diversity of HCMV-specific CD8(+) T cell responses to the products of 11 HCMV open reading frames (ORFs) in a cohort of donors aged 20 to 80 years old as well as the ability of the T cells to secrete gamma interferon (IFN-γ). Finally, we also tested their functional antiviral capacity using a novel viral dissemination assay. We identified substantial CD8(+) T cell responses by IFN-γ enzyme-linked immunospot (ELISPOT) assays to all 11 of these HCMV proteins, and across the cohort, individuals displayed a range of responses, from tightly focused to highly diverse, which were stable over time. CD8(+) T cell responses to the HCMV ORFs were highly differentiated and predominantly CD45RA(+), CD57(+), and CD28(-), across the cohort. These highly differentiated cells had the ability to inhibit viral spread even following direct ex vivo isolation. Taken together, our data argue that HCMV-specific CD8(+) T cells have effective antiviral activity irrespective of the viral protein recognized across the whole cohort and despite viral immune evasion. Human cytomegalovirus (HCMV) is normally carried without clinical symptoms and is widely prevalent in the population; however, it often causes severe clinical disease in individuals with compromised immune responses. HCMV is never cleared after primary infection but persists in the host for life. In HCMV carriers, the immune response to HCMV includes large numbers of virus-specific immune cells, and the virus has evolved many mechanisms to evade the immune response. While this immune response seems to protect healthy people from subsequent disease, the virus is never eliminated. It has been suggested that this continuous surveillance by the immune system may have deleterious effects in later life. The study presented in this paper examined immune responses from a cohort of donors and shows that these immune cells are effective at controlling the virus and can overcome the virus' lytic cycle immune evasion mechanisms.

Children with Down's syndrome display high rates of hyperuricaemia.

Several studies show that hyperuricaemia, abnormally high levels of uric acid in the blood, frequently occurs in adult Down's syndrome patients, but paediatric research is scarce. We aimed to clarify its prevalence in paediatric Down's syndrome patients and its association with lifestyle-related laboratory variables and nutritional intake, to consider possible effects in later life. We compared 52 Down's syndrome patients, from one to 15 years of age, with age-matched controls. Hyperuricaemia was defined using reference values established for children, as uric acid z-scores of more than 2.0. Nutritional intake was estimated using 3-day dietary records. Hyperuricaemia occurred in 17 Down's patients (32.7%) and was significantly higher in Down's patients than the controls. The prevalence was also significantly higher in males. There were no significant differences between hyperuricaemia-positive and hyperuricaemia-negative patients in terms of age, body mass index standard deviation scores, fasting blood glucose, insulin, homeostasis model assessment-insulin resistance and triglyceride, and purine body intake was similar. There were differences in high-density lipoprotein cholesterol. We found high rates of hyperuricaemia from early childhood in Down's syndrome patients. This suggests careful management of Down's syndrome patients, as hyperuricaemia is an independent risk factor for lifestyle-related diseases in adulthood.

Risk behaviors related to violence and injury among school-going adolescents in Karnataka, Southern India

Adolescence is a crucial stage of life. The development and practice of various risk behaviors predisposes the risk of getting injured and consequences in later life. This cross-sectional study was conducted among 381 adolescents (15-19 years) studying in different schools and colleges of Udupi. The Youth Risk Behavior Survey (YRBS), Center for Disease Control (CDC) Questionnaire and the Atlanta Questionnaire and Guidelines was adopted for data collection. Behaviors such as poor obeying traffic rules while driving, violence at school premises, and suicidal thoughts of the participants were explored. Univariate analysis followed by multivariate logistic regression was done to estimate the predictors of violence-related behavior using the Statistical Packages for Social Sciences (SPSS) v. 20. In our study, 27.03% of students (total=381) had knowledge of traffic rules in detail, where 65% drove a motorized vehicle. Nearly 75% of students did not use a helmet or seatbelt while driving and 17% used a mobile phone for either talking or texting while driving. Considering all violence risk behaviors, 33.07% of students had at least and 18% had at least two violence-related risk behaviors. Nearly 21.78% thought of hitting somebody, 16.34% of boys and 9.5% of girls carried sharp objects to school, 18.81% of boys and 10.39% of girls damaged or stole other students' property, 18.37% bullied others in the past month at the school campus, and 11.32% were involved in serious fights. Out of 381 students, 114 (30.32%) were bullied, 10% had been slapped intentionally, and 18% of girls felt unsafe to go out of their home because of threat compared with 15% of boys. In total, 71 (18.93%) students thought of suicide and 22 of them attempted it. Logistic regression showed that boys [odds ratio (OR): 1.72, 95% confidence interval (CI): 1.02-2.93) and students of 16 years of age (OR: 3.02, 95% CI: 1.06-9.02) affected or victimized by violent activities at school (OR: 3.23, 95% CI: 1.76-5.93) and bullied by others (OR: 2.6, 95% CI: 1.55-4.36) were determining factors for violence-related behaviors after adjusting for other variables. There is a need to identify students at risk and for intervention addressing the risk factors. Further qualitative studies could provide more insight.

Differential Regulation of Brain-Derived Neurotrophic Factor in Term and Preterm Preeclampsia

Our earlier studies in preeclampsia (PE) suggest a causal relationship between altered angiogenic factors and birth outcomes. Recent studies suggest that brain-derived neurotrophic factor (BDNF) can stimulate angiogenesis. The present study examines the levels of maternal and cord BDNF in women with PE (n = 106; full term [n = 60] and preterm [n = 46]) and normotensive women (n = 95; control) delivering at term. Maternal BDNF levels were lower (P < .05) in women with PE when compared to normotensive women. Cord BDNF levels were higher (P < .01) in women with PE delivering at term, while it was lower (P < .01) in women delivering preterm. Maternal BDNF levels were negatively associated with systolic and diastolic blood pressure (P < .01 for both). Our data for the first time suggest a possible role for BDNF in the pathophysiology of PE. Differential regulation of cord BDNF levels in preterm PE suggests a need to follow-up children to assess the neurodevelopmental effects in later life.

Late-Life Effects of Chronic Methamphetamine Exposure during Puberty on Behaviour and Corticostriatal Mono-Amines in Social Isolation-Reared Rats

Chronic methamphetamine (MA) abuse results in an acute psychosis indistinguishable from paranoid schizophrenia. However, less is known of the interaction between MA use and environmental insults, and how this contributes to late-onset psychopathology. Using social isolation rearing (SIR), a neurodevelopmental animal model of schizophrenia, we investigated the association between changes in corticostriatal mono-amines and putative behaviours related to MA-induced psychosis in isolation and group-housed rats following chronic MA or saline exposure. Weaned male offspring of MA-naive female Wistar rats, either group- or isolation-housed from postnatal day (PND) +21, received saline (2 ml/kg s.c. b.i.d.) or an escalating dose of MA (0.2-6 mg/kg s.c. b.i.d.) for 16 days from PND +35 to +50. On PND +78, offspring were tested for deficits in social interactive behaviour (SIB) and prepulse inhibition (PPI) of startle, with frontal cortex and striatum harvested for the assessment of mono-amine concentrations. SIR significantly reduced rearing time, staying together, approaching and anogenital sniffing (outward-directed SIB), but increased self-grooming and locomotor activity (self-directed SIB), and also induced profound deficits in PPI. Pubertal MA exposure in group-housed animals also induced similar alterations in outward- and self-directed SIB and reduced PPI. Combined MA + SIR exposure evoked a similarly intense behavioural response as SIR or MA separately, with no exacerbation evident. Neither treatment separately nor together affected corticostriatal serotonin or noradrenaline levels, although frontal cortical dopamine (DA) levels were significantly increased in SIR and MA + group-housed animals. A trend towards further elevated frontal cortical DA was noted in the MA + SIR treatment group. Striatal DA was unaltered by all treatments. This study provides the first evidence that chronic pubertal MA exposure evokes postpubertal psychosis-like behaviours in rats of similar intensity to that induced by a neurodevelopmental animal model of schizophrenia (SIR). Moreover, the study is unique in that these behavioural changes occur together with associated changes in frontal cortical but not striatal DA, without affecting other mono-amines, and strongly implicates frontal cortical DA changes in the psychotogenic effects of early-life MA exposure or environmental insult. Although MA exposure in animals with a history of environmental insult (i.e. MA + SIR) has similar effects, combined exposure was not additive with regard to behavioural or neurochemical changes. We conclude that a ceiling effect or compensatory mechanisms prevent more pronounced neurobehavioural deficits occurring following MA + SIR treatment, at least under the current study conditions.

Psychiatric Nursing Care for Adult Survivors of Child Maltreatment: A Systematic Review of the Literature

To determine what is known from the literature about nursing care of psychiatric patients with a history of child maltreatment. Psychiatric nurses underline the importance of a routine inquiry of child abuse on admission of patients to psychiatric care, but are reluctant to ask about child abuse. They often feel insufficiently competent to respond effectively to patients with a history of child maltreatment. Psychiatric nurses need training in how to assess a history of child abuse and the late-life consequences of abuse in adult psychiatric patients. They also need to be trained to respond effectively to these patients.

Neuropsychological factors related to college ice hockey concussions.

We analyzed data from 74 male collegiate hockey players. Each athlete's season began with a baseline administration of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) neuropsychology test battery. Fourteen athletes sustained a sport-related head injury and were readministered the test to assess the impact of the injury. A significant decrease in performance (compared to baseline) on immediate and delayed word recall and designs followed the first concussion. Following a second sport-related concussion, the 4 affected athletes showed significant decrease in visual motor speed. Performance improved on 2 response speed measures (Ps < .01). More errors occurred during a visual processing/discrimination task and immediate recall of designs declined (Ps < .05). We discuss the results in light of recent work related to the impact of early-life concussions and head injury on late-life consequences, such as chronic traumatic encephalopathy, and more immediate issues such as return-to-play decisions for athletes.

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

This study examined late-life effects of perinatal exposure of rats to a mixture of endocrine-disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, u.v.-filters, bisphenol A, parabens, and the drug paracetamol. The groups received vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or 450-times (TotalMix450) high-end human exposure, or 450-times a mixture of nine predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous cyclicity at 9 and 12 months of age were assessed. Few female offspring showed significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared with controls. In 19-month-old male offspring, epididymal sperm counts were lower than controls, and in ventral prostate an overrepresentation of findings related to hyperplasia was observed in exposed groups compared with controls, particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450 group. Developmental exposure of rats to the highest dose of a human-relevant mixture of endocrine disrupters induced adverse effects late in life, manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia, and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.

Maternal dietary fat affects the LT muscle fatty acid composition of progeny at weaning and finishing stages in pigs

The present study was conducted to investigate whether maternal dietary fat affects the fatty acid composition of the longissimus thoracis (LT) muscle in offspring pigs at weaning and finishing stages. Fourteen sows were randomly assigned to a control or a high fat (HF) group. The HF sows received a diet containing 8% corn oil starting seven days before farrowing until weaning. The results showed that a high-fat diet significantly increased the contents of serum-lipid-related indexes in the sows. Although the triglyceride content did not change, the C18:2n−6 content was higher in the colostrum and in the LT muscle of offspring pigs at both investigated stages. The total n−6 content and the n−6/n−3 ratio generally increased. This study demonstrated that maternal dietary fat during lactation affects the fatty acid composition of the LT muscle of progeny at weaning, and can have persistent effects in later life.

Gewalt in Wiener Heimen zwischen 1945 und 1990 – eine retrospektive Studie aus psychotraumatologischer Perspektive

Commissioned by the victims-organisation 'Weißer Ring', we conducted 130 interviews (34% female, 66% male, medium age of 53.6 years) during a period of 12 months (March 2011-March 2012). All of them reported that they had been traumatised children in residential care (1946-1975: 70%, 1976-1990: 25%). The interviews primarily aimed at providing expert estimates of the consequences of individual traumas in order to establish a valid basis for compensation. The later evaluation of the interviews allows insight in to forms and quantity of subjective experiences of trauma and of their consequences for later life; although-due to the sampling procedures-no reliable generalisations about the entire system of Social Pedagogy of the City of Vienna are possible. All 130 one-hour long, clinical-biographic interviews were conducted by the same expert (who has qualifications in general and in adolescent psychiatry). 98.5% report experiences of psychic, 96.2% of bodily and 46.9% of sexual violence. 45.5% also report some positive experiences (independent of the form of experienced violence). There are significantly more reports about the frequency of physical violence during 1946-1975, however not about other forms of violence than from the later years. Problems in later life emerge more frequently after experiences of sexual violence, such as instable career trajectories, instable partnerships, psychopathological symptoms and severe turbulences in one's life history. The experiences of physical violence correlate significantly higher with instable career trajectories and (not significantly) with criminal tendencies. The frequency of later psychiatric care is related to the length of time spent in residential care (but not significantly).

Cognitive Risks of Anticholinergics in the Elderly

Many drugs commonly prescribed to the elderly have anticholinergic properties. Due to the current clinical use of drugs with mild-to-modest anticholinergic activity, the clinical manifestations of anticholinergic toxicity are likely to be nonspecific (e.g., cognitive impairment) and reflect the effects of cumulative anticholinergic burden. Age-associated physiological and pharmacokinetic changes increase anticholinergic drug effects in later life. Those with cognitive impairment and neurodegeneration are particularly susceptible to anticholinergic toxicity. Recent findings suggest that chronic anticholinergic burden may hasten or contribute to a neurodegenerative process. APOE ε4 carrier status may be a genetic risk factor for vulnerability to negative anticholinergic effects. There is no clinically available laboratory test to assess anticholinergic levels. Clinicians need to be cognizant of anticholinergic risks in later life. The use of clinical scales (e.g., Anticholinergic Drug Scale) and consensus guidelines (e.g., Revised Beers Criteria) may be helpful.

English

Spinal anomalies are commonly encountered in radiology practice. Spinal dysraphism is defined as a defect in the development and closure of the germ layers of the developing spine. It can manifest as a soft tissue mass in the spinal region or may remain occult without any visual mass. Sacral spina bifida usually presents as a globular soft tissue mass over the back. Its presentation as a tail like projection is rare and infrequently reported. Because of its rarity, such a case may be regarded as an anatomical variant resulting in neurological consequences in later life. The objective of this article is to sensitize the clinicians to the rare manifestation of sacral lipomyelocele as human tail.