Search

Objective: Endovascular treatment of complex vascular pathologies in the pediatric population is often performed by nonpediatric subspecialists with adaptation of equipment and techniques developed for adult patients. We aimed to report our center's experience with safety and outcomes of endovascular treatments for pediatric vascular pathologies., Methods: We performed a retrospective review of our endovascular database. All patients ≤18 years who underwent endovascular treatment between January 1, 2004 and December 1, 2022 were included., Results: During the study time frame, 118 cerebral angiograms were performed for interventional purposes in 55 patients. Of these patients, 8(14.5%) had intracranial aneurysms, 21(38.2%) had intracranial arteriovenous malformations, 6(10.9%) had tumors, 5(9.1%) had arterial occlusions (n = 3) or dissections (n = 2), 8(14.5%) had vein of Galen malformations, and 7(12.7%) had other cerebrovascular conditions. Of the total 118 procedures, access-site complications occurred in 2(1.7%), intraprocedural complications occurred in 3(2.5%), and transient neurological deficits were observed after 2(1.7%). Treatment-related mortality occurred in 1(1.8%) patient., Conclusions: Neurointervention in pediatric patients was safe and effective in our experience., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Promoting minorities within medical specialties has been postulated to be crucial to patient care and recruitment of diverse candidates. This concept has been suspected but not formally studied in the minority of women faculty and trainees in neurosurgery. We aimed to quantitatively investigate the postulated correlation relative to female representation in neurosurgery., Methods: Data obtained from accredited neurosurgery residency programs were reviewed. Data describing the percentage of female residents and 6 demographic and 14 program-specific variables were collected. All program websites were reviewed to assess percentages of female faculty and visible commitment to diversity in applicants, evident through communicated policies, statements, or initiatives. Included programs were defined as "low" or "high" percentage of female residents or faculty relative to the grouped median value for both categories; groups were assessed for significant differences. Percentages of female faculty and residents and program-communicated diversity initiatives were investigated for significant correlation., Results: Female faculty and diversity data were available at 117 program sites; 81 programs reported female resident percentages. Analysis revealed a significant positive correlation between female faculty and female resident percentages. Programs with higher female resident percentages had higher levels of diversity in terms of race and ethnicity. No significant correlation was found between the percentage of female faculty or residents and a communicated diversity initiative., Conclusion: This study of current female representation in neurosurgery revealed a previously undocumented positive correlation between percentages of female faculty and female trainees. These data suggest a modifiable barrier to female entry into neurosurgical residency programs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Earlier pubertal timing is associated with higher rates of depressive disorders in adolescence. Neuroimaging studies report brain structural associations with both pubertal timing and depression. However, whether brain structure mediates the relationship between pubertal timing and depression remains unclear., Methods: The current registered report examined associations between pubertal timing (indexed via perceived pubertal development), brain structure (cortical and subcortical metrics, and white matter microstructure) and depressive symptoms in a large sample (N = ∼5000) of adolescents (aged 9-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We used three waves of follow-up data when the youth were aged 10-11 years, 11-12 years, and 12-13 years, respectively. We used generalised linear-mixed models (H1) and structural equation modelling (H2 & H3) to test our hypotheses., Hypotheses: We hypothesised that earlier pubertal timing at Year 1 would be associated with increased depressive symptoms at Year 3 (H1), and that this relationship would be mediated by global (H2a-b) and regional (H3a-g) brain structural measures at Year 2. Global measures included reduced cortical volume, thickness, surface area and sulcal depth. Regional measures included reduced cortical thickness and volume in temporal and fronto-parietal areas, increased cortical volume in the ventral diencephalon, increased sulcal depth in the pars orbitalis, and reduced fractional anisotropy in the cortico-striatal tract and corpus callosum. These regions of interest were informed by our pilot analyses using baseline ABCD data when the youth were aged 9-10 years., Results: Earlier pubertal timing was associated with increased depressive symptoms two years later. The magnitude of effect was stronger in female youth and the association remained significant when controlling for parental depression, family income, and BMI in females but not in male youth. Our hypothesised brain structural measures did not however mediate the association between earlier pubertal timing and later depressive symptoms., Conclusion: The present results demonstrate that youth, particularly females, who begin puberty ahead of their peers are at an increased risk for adolescent-onset depression. Future work should explore additional biological and socio-environmental factors that may affect this association so that we can identify targets for intervention to help these at-risk youth., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Intrameningeal cysts are rare lesions without definitive etiologies that can involve the dura or arachnoid mater. Spinal arachnoid cysts have been described, and several different etiologies have been hypothesized. This includes one-way valve mechanisms, traumatic herniation of arachnoid through the dura, and abnormal arachnoid membrane proliferation. To the authors' knowledge, no such descriptions exist regarding purely dural-based cystic lesions; however, the authors hypothesize similar mechanisms may be involved. Most notably, a traumatic injury to the dura leading to a one-way valve mechanism may allow for egress of cerebrospinal fluid between the dural layers, splitting them open. This progressive enlargement can lead to displacement of neural elements and subsequent neurological compromise., Methods: We describe a 17-year-old girl who presented with progressive neck and back pain, left upper-extremity numbness, bilateral lower-extremity weakness, paresthesias, and numbness without obvious etiology despite an extensive neurologic investigation. She had undergone conservative management options including multiple medications, physical and chiropractic therapy, and epidural steroid injections. Computed tomography myelography revealed a cerebrospinal fluid leak into the lumbar epidural space for which surgical exploration was performed. Despite utilizing fluoroscopy and intrathecal fluorescein, no leak source was identified. Fluid collection was found contained within the dural layers rather than the epidural space., Results: An intracystic blood patch was performed with near-complete resolution of the lesion by 6-week follow-up and near-complete return of neurologic function., Conclusions: Ventral panspinal cysts are an exceedingly rare cause of radiculopathy and myelopathy that can be resolved by an intracystic blood patch., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised., Methods: We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9)., Results: After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA., Discussion: There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass., Objectives: A study is presented of the association between FFM and physical activity in relation to age., Methods: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution., Results: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively., Conclusions: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Currently, there are only 3 reported cases of central nervous system malignancies in patients with Noonan syndrome in the literature, all of which are intracranial pathologies. To our knowledge, there are no cases of spinal cord glioblastoma multiforme reported in the literature., Case Description: We describe the case of a 12-year-old girl with Noonan syndrome who presented with back pain and new onset neurological deficits and was found to have a spinal cord lesion. T10-L1 laminoplasty with safe maximal resection was done. Postoperative pathological analysis identified this lesion as a high-grade astrocytoma consistent with glioblastoma multiforme., Conclusions: Spinal cord glioblastoma multiforme is a rare occurrence in the general population, particularly in a patient with an underlying diagnosis of Noonan syndrome. Patients with spinal cord tumors can present with a multitude of clinical signs and symptoms and treatment should not be delayed., (Published by Elsevier B.V.)

Introduction: Class III obesity (BMI ≥ 40 kg/m 2 ) during pregnancy predisposes mother and offspring to a range of adverse pregnancy complications and outcomes. Risk profiles vary between pregnancies and are affected by interpregnancy weight gain. We evaluated the risk of adverse outcomes in women with BMI ≥ 40 kg/m 2 in first and second pregnancies, and the impact of interpregnancy weight change on this risk., Materials and Methods: Data were extracted for all women with BMI ≥ 40 kg/m 2 at first antenatal visit, who completed antenatal and delivery care for first and second pregnancies in NHS Lothian between 1/1/2009-31/12/2018. Multiple pregnancies and recipients of bariatric surgery were excluded., Results: 442 pregnancies among 221 women were included. In first pregnancy, median (interquartile range) weight was 117 kg (108.5-126.7), age 28 years (24-31) and BMI 42 kg/m 2 (41.0-44.5), 14.4% had gestational diabetes (GDM), 11.3% had pregnancy-induced hypertension and 44.6% had a post-partum haemorrhage (PPH). 20.8% of babies were large for gestational age (LGA, ≥97% centile at birth). In second pregnancy, women were heavier with a median weight of 119.9 kg (109.0-130.0, p = 0.00) with 19.9% gaining over 10 kg. Women were more likely to develop GDM (21.6%, p = 0.02). Babies were heavier with 40% of babies LGA (p < 0.0001). Interpregnancy weight change had no significant impact on GDM, pregnancy induced hypertension, PPH, perinatal mortality or LGA., Conclusions: In a population of women with BMI ≥ 40 kg/m 2 , pregnancy complications are common and risk is higher in second pregnancy. The interpregnancy period is a critical time to engage women in health improvement and weight loss strategies to maximise outcomes for mother and offspring., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

There is an ever-increasing number of opioid users among chronic pain patients and safely managing them can be challenging for surgeons, anesthesiologists, pain experts, and addiction specialists. Healthcare providers must be familiar with phenomena typical of opioid users and abusers, including tolerance, physical dependence, hyperalgesia, and addiction. Insufficient pain management is very common in these patients. Patient-centered preoperative communication is integral to setting realistic expectations for postoperative pain, developing successful nonopioid analgesic regimens, minimizing opioid consumption during the postoperative period, and decreasing the number of opioid pills at the risk of diversion. Preoperative evaluation should identify comorbidities and identify risk factors for substance abuse and withdrawal. Intraoperative and postoperative strategies can ensure safe and effective pain management and minimize the potential for morbidity and mortality in this high-risk patient population., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Ltd.)

Background: Prenatal exposure to environmental adversities, including maternal overweight/obesity, diabetes/hypertensive disorders, or mood/anxiety disorders, increases the risk for adverse neurodevelopmental outcomes in children. However, the underlying biological mechanisms remain elusive. We tested whether maternal antenatal inflammation was associated with the number of neurodevelopmental delay areas in children and whether it mediated the association between exposure to any prenatal environmental adversity and child neurodevelopmental delay., Methods: Mother-child dyads (N = 418) from the PREDO (Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction) study were followed up to 10.8 years. We analyzed maternal plasma high-sensitivity C-reactive protein and glycoprotein acetyls at 3 consecutive antenatal time points, measured maternal body mass index in early pregnancy, extracted data on diabetes/hypertensive disorders in pregnancy from medical records, and extracted data on mood/anxiety disorders until childbirth from the Care Register for Health Care. To estimate the number of neurodevelopmental delay areas in children across cognitive, motor, and social functioning, we pooled data from the Care Register for Health Care on psychological development disorders with mother-reported Ages and Stages Questionnaire data on developmental milestones., Results: Higher levels of maternal high-sensitivity C-reactive protein and glycoprotein acetyls at and across all 3 antenatal time points were associated with 1.30- to 2.36-fold (p values < .02) increased relative risk for higher number of areas of child neurodevelopmental delay. Higher maternal inflammation across the 3 time points also mediated the effect of any prenatal environmental adversity on child neurodevelopmental delay., Conclusions: Higher levels of maternal inflammation, especially when persisting throughout pregnancy, increase a child's risk of neurodevelopmental delay and mediate the effect of prenatal environmental adversity on child neurodevelopmental delay., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Maternal obesity is the most common metabolic disturbance in pregnancy affecting >1 in 5 women in some countries. Babies born to obese women are heavier with more adiposity at birth, and are vulnerable to obesity and metabolic disease across the lifespan suggesting offspring health is 'programmed' by fetal exposure to an obese intra-uterine environment. The placenta plays a major role in dictating the impact of maternal health on prenatal development. Maternal obesity impacts the function of integral placental receptors and transporters for glucocorticoids and nutrients, key drivers of fetal growth, though mechanisms remain poorly understood. This review aims to summarise current knowledge in this area, and considers the impact of obesity on the epigenetic machinery of the placenta at this vital juncture in offspring development. Further research is required to advance understanding of these areas in the hope that the trans-generational cycle of obesity can be alleviated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Heat illness (HI) is a growing global concern; its incidence has risen dramatically across the world in recent years. The individual factors whereby elevated core temperature produces HI are not well-understood. Given known physiological differences between men and women pertaining to temperature regulation, we hypothesized that women would be at increased risk of HI than men., Objectives: We aimed to determine the relative risk of HI in women compared with men through an exhaustive literature review and meta-analysis., Methods: We search PubMed and Ovid Medline databases from inception to Apr 2017. Search terms included all permutations of sex and heat illness (including heatstroke and exertional heat illness) with no language restrictions. We included adult or adolescent human data reporting comparable male and female HI rates. One reviewer identified and screened titles and abstracts. Two independent reviewers applied eligibility criteria. Disagreements were resolved with a third reviewer., Results: Of 5888 articles identified by searches, 36 were included in the systematic review and 22 in the meta-analysis. The mean (standard deviation) quality score was 3.31(1.25)/5. Overall the rate among women was consistently lower than men across the lifespan. The male: female pooled IRR was 2.28 (p < 0.001, 95% CI: 1.66-3.16). There was modest heterogeneity (between-studies variance (τ 2 ) = 0.02). The rates did not differ significantly when corrected for severity or occupation., Discussion: The rate of HI was significantly increased in men compared with women. Risk for HI might be conferred by psychological and behavioral factors rather than physiological ones. Further research is required to delineate which groups are at greatest risk, leading to the development of mitigation strategies against HI., Other: No funding was received. The authors acknowledge the support of the UK Women in Ground Close Combat Review. The Study was registered with PROSPREO CRD42017064739., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems., Method: A total of 694 mothers from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) Study provided information on history of depression diagnosed before pregnancy; 581 completed the Center for Epidemiological Studies Depression Scale throughout pregnancy, and 407 completed the Child Behavior Checklist at child's age 3.7 years (SD = 0.75 year). DNA methylation (DNAm) GA of fetal cord blood DNA was based on the methylation profile of 148 selected cytosine linked to guanine by phosphate (CpG) sites. Epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA., Results: Maternal history of depression diagnosed before pregnancy (mean difference = -0.25 SD units, 95% CI = -0.46 to -0.03) and greater antenatal depressive symptoms (-0.08 SD unit per 1-SD unit increase, 95% CI = -0.16 to -0.004) were associated with child's lower epigenetic GA. Child's lower epigenetic GA, in turn, prospectively predicted total and internalizing problems and partially mediated the effects of maternal antenatal depression on internalizing problems in boys., Conclusion: Maternal antenatal depression is associated with lower epigenetic GA in offspring. This lower epigenetic GA seems to be associated with a developmental disadvantage for boys, who, in early childhood, show greater psychiatric problems., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Increasing evidence supports fetal glucocorticoid exposure with associated altered offspring hypothalamic-pituitary-adrenal (HPA) axis activity as a key mechanism linking early life events with later life disease. Alterations in HPA axis activity are linked to a range of cardiometabolic and psychiatric diseases. As many of these diseases manifest sex differences in presentation we review the evidence for programmed sex-differences in the HPA axis. Available literature suggests vulnerability of the female HPA axis to prenatal stressors with female offspring demonstrating increased HPA axis reactivity. This may be due to changes in placental glucocorticoid metabolism leading to increased fetal glucocorticoid exposure. We discuss the potential consequences of increased vulnerability of the female HPA axis for later life health and consider the underlying mechanisms. Further studies are needed to determine whether sex-differences in early-life programming of the HPA axis represent a pathway underpinning the sex-differences in common cardiometabolic and psychiatric diseases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Maternal depressive symptoms during pregnancy are associated with increased risk of psychiatric problems in children. A more precise understanding of the timing of the symptoms during pregnancy and their independence of other prenatal and postnatal factors in predicting child psychopathology risk is needed. We examined whether maternal depressive symptoms during pregnancy predict child psychiatric problems, whether these associations are trimester- or gestational-week-specific and/or independent of pregnancy disorders, and whether maternal depressive symptoms after pregnancy mediate or add to the prenatal effects., Method: The study sample comprised 2,296 women and their children born in Finland between 2006-2010, participating in the prospective pregnancy cohort study Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) and followed up from 1.9 to 5.9 years of age. The women completed the Center for Epidemiologic Studies Depression Scale biweekly between gestational weeks+days 12+0/13+6 and 38+0/39+6 or delivery. In the follow-up, they completed the Beck Depression Inventory-II and Child Behavior Checklist 1½-5., Results: Maternal depressive symptoms during pregnancy predicted significantly higher internalizing (0.28 SD unit per SD unit increase [95% CI = 0.24-0.32]), externalizing (0.26 [0.23-0.30]), and total problems (0.31 [0.27-0.35]) in children. These associations were nonspecific to gestational week and hence pregnancy trimester, independent of pregnancy disorders, and independent of, although partially mediated by, maternal depressive symptoms after pregnancy. Psychiatric problems were greatest in children whose mothers reported clinically significant depressive symptoms across pregnancy trimesters and during and after pregnancy., Conclusion: Maternal depressive symptoms during pregnancy predict increased psychiatric problems in young children. Preventive interventions from early pregnancy onward may benefit offspring mental health., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Increased fetal exposure to glucocorticoids is a key mechanism thought to underlie the early life programming of later life disease. There is substantial experimental data in animal models in support of this hypothesis. Emerging evidence suggests glucocorticoid programming may also occur in humans with some studies now linking maternal endogenous cortisol levels with size at birth and gestation at delivery. The dramatic changes to the maternal hypothalamic-pituitary-adrenal axis during pregnancy mean that large-scale studies in humans are challenging to conduct. One of the key regulators of fetal glucocorticoid exposure is the activity of placental "barrier" enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which converts active cortisol to inactive cortisone. In animal models, this enzyme is down-regulated by various influences including maternal malnutrition, inflammation or stress but it is not known whether this is a major factor in regulation of human fetal glucocorticoid exposure. More studies are needed to understand the mechanisms whereby altered fetal glucocorticoid exposure may alter fetal growth trajectories and whether changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy could be suitable as a biomarker to identify those pregnancies most at risk., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Preterm infants are at increased risk of cardiometabolic disease in later life. Extrauterine growth restriction, catch-up growth, altered adiposity, and abnormal hypothalamic-pituitary-adrenal axis activity could be predisposing factors. Altered DNA methylation (5-methylcytosine, 5mC) might be one underlying mechanism. We hypothesised that preterm infants have altered 5mC at the linked differentially methylated region 2 (DMR2) of IGF2 and the H19 imprinting control region (H19 ICR) compared with term infants over the first year of life., Methods: We recruited 46 preterm (range 25 weeks + 2 days' gestation to 31 + 5, mean 28 + 6) and 40 term infants (38 + 3 to 42 + 2 weeks' gestation, mean 40 + 2). Anthropometric variables including body composition were measured at term age and 3 months corrected age with air displacement plethysmography and at 1-year-corrected age with skin-fold thickness. Salivary cortisol was measured at 3 months corrected age after the physical examination. Percentage methylation (%5mC) was analysed with pyrosequencing on buccal DNA. Statistical analysis used Student's t test and multivariate linear regression., Findings: Preterm infants demonstrated growth deficit early in postnatal life but had greater percentage body fat at term age (β=5·73, p<0·001), but not at 3 months (β=-0·28, p=0·82). Compared with term infants, preterm infants had a blunted cortisol response to physical examination (mean difference 0·38 μg/dL, p=0·024). At birth, preterm infants had a significant decrease in %5mC at DMR2 compared with term infants at birth (β=-11·48, p<0·001) and compared with preterm infants at term-corrected age (t=3·13, p=0·01). By term-corrected age, preterm infants had decreased %5mC at both DMR2 (β=-2·84, p=0·013) and the H19 ICR (β=-2·31, p=0·048) compared with term infants at birth, although this difference disappeared at 1 year. Social deprivation was independently associated with decreased %5mC at DMR2 at birth (β=-1·73, p=0·006) and term-corrected age (β=-0·86, p=0·016) but not at 1 year (β=-0·89, p=0·07)., Interpretation: Our results show that decreased %5mC accompanies the early growth deficit in preterm infants. The marked reduction in %5mC at IGF2 DMR2 in preterm infants at birth compared with term-age supports existing evidence that imprinting at secondary regions is established after fertilisation, whereas imprinting is established during gametogenesis at primary regions (H19 ICR). Both regions might be susceptible to early life stressors such as preterm birth and social deprivation., Funding: Chief Scientist Office of the Scottish Government., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The hypothalamic-pituitary-adrenal (HPA) axis is important for fetal growth and timing of parturition. Maternal obesity is associated with macrosomia (birthweight ⩾4000g) and prolonged pregnancy (⩾41weeks). We aimed to characterise HPA axis hormones in obese pregnancy and to test associations with these pregnancy outcomes., Method: Fasting cortisol was measured by radioimmunoassay in venous blood at 16, 28 and 36 weeks of gestation in 286 obese (BMI 44.05±3.98kg/m(2)) and 137 lean (BMI 22.71±1.66kg/m(2)) pregnant women. In subsets (n=20 obese, 20 lean) we measured corticosteroid binding globulin (CBG) and CRH by radioimmunoassay; progesterone, estradiol (E2), estriol (E3) and sex-hormone-binding-globulin (SHBG) by ELISA; and albumin by bromocresol green binding. Free cortisol levels were calculated using Coolen's equation., Results: Cortisol, CBG, calculated free cortisol, CRH, E2, E3, progesterone and SHBG levels rose similarly during pregnancy in obese and lean, but were significantly lower in obese (p<0.05). In obese, lower free cortisol at 16 weeks was associated with higher birthweight (r=-0.46, p<0.05). Cortisol was not associated with labour onset. CRH was significantly lower at 36 weeks in women who delivered at ⩾41weeks and in women with macrosomic babies (p<0.05); and correlated negatively with gestation at delivery in obese (r=-0.557, p<0.05)., Conclusion: Our findings suggest that decreased HPA axis activity in obese pregnancy may be a mechanism underlying macrosomia and prolonged pregnancy., (Copyright © 2014.)

People with obesity and type 2 diabetes are at increased risk of cognitive impairment. We aimed to investigate the association of leptin with cognitive abilities in an elderly population with type 2 diabetes. We performed a cross-sectional study of 1057 men and women aged 60-75 years with type 2 diabetes living in Lothian (Scotland). A cognitive battery was administered. Prior intelligence was estimated from vocabulary testing and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning leptin levels and cognitive ability and estimated cognitive change were tested. Higher leptin levels were associated with significantly poorer estimated overall cognitive decline, and poorer performance in 2 cognitive domains assessing mental flexibility and executive function, only amongst men (p < 0.05). High morning leptin levels in elderly men with type 2 diabetes are associated with estimated age-related cognitive change., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Pre-gravid obesity is associated with increased morbidity and mortality for both mother and offspring. Recent studies have demonstrated a heightened inflammatory response both systemically and locally within the adipose and placental tissue in women with pre-gravid obesity, which may play a role in mediating the adverse pregnancy outcomes. The aim of this study was to characterise the maternal and placental inflammatory status and investigate associated changes in placental structure in obese women., Methods: The pro-inflammatory status of a cohort of 47 non-obese (BMI 20-25 kg/m(2)) and 33 obese (≥30 kg/m(2)) women was characterised by measuring maternal circulating levels and placental gene expression of pro-inflammatory cytokines, and quantifying immune cell populations within the placenta. The effect of pre-gravid obesity on placental structure was investigated by examining placental maturity, vessel density, the formation of syncytial knots and sprouts, and the degree of fibrin deposition, chorangiosis and muscularisation of vessel walls., Results: Maternal obesity was associated with significantly greater IL-1β (p < 0.05), IL-8 (p < 0.05), MCP-1 (p < 0.001) and CXCR2 (p < 0.05) mRNA expression within the placenta and higher circulating maternal levels of IL-6 (3.30 ± 0.38 vs. 1.77 ± 0.15 pg/ml) (p < 0.001) compared with non-obese women. There were no differences in the number of CD14(+), CD68(+) cells or neutrophils within the placental villi of non-obese and obese women. However there were significantly higher numbers of neutrophils within the interstitial space (p < 0.05). Greater muscularity of placental vessel walls was associated with maternal obesity (p = 0.03), however no other associated structural changes were observed., Conclusions: Our findings show that although pre-gravid obesity was associated with greater expression of placental pro-inflammatory cytokines and higher circulating IL-6 in pregnancy, there were no major differences in immune cell populations within the placental villi and only a greater degree of muscularity in the vessel walls., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background & Aims: Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase., Methods: The effect of bile acids on glucocorticoid metabolism was studied in vitro in hepatic subcellular fractions and hepatoma cells, allowing quantitation of the kinetics and transcript abundance of 5beta-reductase. Metabolism was subsequently examined in vivo in rats following dietary manipulation or bile duct ligation. Finally, glucocorticoid metabolism was assessed in humans with obstructive jaundice., Results: In rat hepatic cytosol, chenodeoxycholic acid competitively inhibited 5beta-reductase (K(i) 9.19+/-0.40 microM) and reduced its transcript abundance (in H4iiE cells) and promoter activity (reporter system, HepG2 cells). In Wistar rats, dietary chenodeoxycholic acid (1% w/w chow) inhibited hepatic 5beta-reductase activity, reduced urinary excretion of 3alpha,5beta-tetrahydrocorticosterone and reduced adrenal weight. Conversely, a fat-free diet suppressed bile acid levels and increased hepatic 5beta-reductase activity, supplementation of the fat-free diet with CDCA reduced 5beta-reductase activity, and urinary 3alpha,5beta-reduced corticosterone. Cholestasis in rats suppressed hepatic 5beta-reductase activity and transcript abundance. In eight women with obstructive jaundice, relative urinary excretion of 3alpha,5beta-tetrahydrocortisol was significantly lower than in healthy controls., Conclusion: These data suggest a novel role for bile acids in inhibiting hepatic glucocorticoid clearance, of sufficient magnitude to suppress hypothalamic-pituitary-adrenal axis activity. Elevated hepatic bile acids may account for adrenal insufficiency in liver disease., (Crown Copyright (c) 2010. Published by Elsevier B.V. All rights reserved.)

A sensitive liquid chromatography-mass spectrometric method was validated for the quantification of RU38486 (mifepristone) in human and murine plasma. The analyte and internal standard (alfaxolone) were extracted by liquid-liquid extraction with diethyl ether, resolved on a C18 column using gradient elution with methanol and ammonium acetate and detected after positive electrospray ionization (m/z 430-->372; m/z 333-->297, respectively). Quantification was linear over the range 0.5-500ng (r(2)>0.997), precise and accurate (intra-assay RSD< or =7.2%, RME< or =8.2%; inter-assay RSD< or =15.7% RME< or =10.2%). The limit of quantification (LOQ) was 50pg injected on column, permitting reproducible analysis of RU38486 in small volumes of plasma.

There are many unresolved issues regarding how to feed the extremely-low-birth-weight (ELBW) infant. Trophic feedings of small volumes of breast milk or formula do not appear to increase the incidence of necrotizing enterocolitis (NEC). For prevention of NEC, breast milk, antenatal steroids and fluid restriction each confers a benefit. Because the incidence of NEC is relatively low, to determine if a particular prevention strategy is effective, large numbers of infants would need to be enrolled in a prospective, randomized controlled trial, and such trials are rare. Candidate therapies for NEC prevention that warrant further study include oral immunoglobulins, probiotics, long-chain polyunsaturated fatty acids and arginine. Suboptimal nutrition in ELBW infants is common in the early postnatal period. This is also the most critical time for the development of bronchopulmonary dysplasia, when even brief periods of malnutrition have significant effects on lung development and growth.