Altered basal cortisol levels at 3, 6, 8 and 18 months in infants born at extremely low gestational age

Little is known about the developmental trajectory of cortisol levels in preterm infants after hospital discharge.

Relationships between adrenocorticotropic hormone and cortisol are altered during clustered nursing care in preterm infants born at extremely low gestational age

Little is known about the effects of clustered nursing care on hypothalamic pituitary axis (HPA) responses in preterm infants in the neonatal intensive care unit.

Cortisol, contingency learning, and memory in preterm and full-term infants

Cortisol plays an important role in learning and memory. An inverted-U shaped function has been proposed to account for the positive and negative effects of cortisol on cognitive performance and memory in adults, such that too little or too much impair but moderate amounts facilitate performance. Whether such relationships between cortisol and mental function apply to early infancy, when cortisol secretion, learning, and memory undergo rapid developmental changes, is unknown. We compared relationships between learning/memory and cortisol in preterm and full-term infants and examined whether a greater risk for adrenal insufficiency associated with prematurity produces differential cortisol-memory relationships. Learning in three-month old (corrected for gestational age) preterm and full-term infants was evaluated using a conjugate reinforcement mobile task. Memory was tested by repeating the same task 24h later. Salivary cortisol samples were collected before and 20 min after the presentation of the mobile. We found that preterm infants had lower cortisol levels and smaller cortisol responses than full-term infants. This is consistent with relative adrenal insufficiency reported in the neonatal period. Infants who showed increased cortisol levels from 0 to 20 min on Day 1 had significantly better memory, regardless of prematurity, than infants who showed decreased cortisol levels.

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty-seven preterm infants were studied at 32 (+/-1 week) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born

Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months

Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; <or =28 weeks), very low gestational age (VLGA; 29-32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit.

Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

In animal models, variations in early maternal care are associated with differences in hypothalamic-pituitary-adrenal(HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression.

Stomatal proxy record of CO2 concentrations from the last termination suggests an important role for CO2 at climate change transitions

A new stomatal proxy-based record of CO₂ concentrations ([CO₂]), based on Betula nana (dwarf birch) leaves from the Hässeldala Port sedimentary sequence in south-eastern Sweden, is presented. The record is of high chronological resolution and spans most of Greenland Interstadial 1 (GI-1a to 1c, Allerød pollen zone), Greenland Stadial 1 (GS-1, Younger Dryas pollen zone) and the very beginning of the Holocene (Preboreal pollen zone). The record clearly demonstrates that i) [CO₂] were significantly higher than usually reported for the Last Termination and ii) the overall pattern of CO₂ evolution through the studied time period is fairly dynamic, with significant abrupt fluctuations in [CO₂] when the climate moved from interstadial to stadial state and vice versa. A new loss-on-ignition chemical record (used here as a proxy for temperature) lends independent support to the Hässeldala Port [CO₂] record. The large-amplitude fluctuations around the climate change transitions may indicate unstable climates and that " tipping-point" situations were involved in Last Termination climate evolution. The scenario presented here is in contrast to [CO₂] records reconstructed from air bubbles trapped in ice, which indicate lower concentrations and a gradual, linear increase of [CO₂] through time. The prevalent explanation for the main climate forcer during the Last Termination being ocean circulation patterns needs to re-examined, and a larger role for atmospheric [CO₂] considered.

High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes

To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes.

Apolipoprotein C-III protein concentrations and gene polymorphisms in Type 1 diabetes:associations with microvascular disease complications in the DCCT/EDIC cohort

We investigated the associations of apolipoprotein C-III (apoCIII) protein and apoCIII gene variation with microvascular disease complications in Type 1 diabetes.

Apolipoprotein C-III protein concentrations and gene polymorphisms in type 1 diabetes:associations with lipoprotein subclasses

Serum apolipoprotein C-III (apoCIII) concentration and apoCIII gene polymorphisms have been shown to be a risk factor for cardiovascular disease; however, the underlying mechanisms remain unclear. In addition, no studies have been performed that address these issues in type 1 diabetes. The current study investigated apoCIII protein and apoCIII gene variation in a normotriglyceridemic (82 +/- 57 mg/dL) population of patients with type 1 diabetes, the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort. Blood samples were obtained in 409 patients after an overnight fast. Serum apoCIII concentration was highly correlated with multiple changes in lipids and lipoproteins that resulted in an adverse cardiovascular disease risk profile. Higher apoCIII concentrations were associated (P <.0001) with increased triglycerides (r = 0.78), total (r = 0.61) and low-density lipoprotein (LDL) (r = 0.40) cholesterol, apoA-I (r = 0.26), and apoB (r = 0.50), and these relationships persisted after controlling for age, gender, body mass index (BMI), and hemoglobin A1c (HbA1c). Nuclear magnetic resonance (NMR) lipoprotein subclass analyses demonstrated that apoCIII was correlated with an increase in very-low-density lipoprotein (VLDL) subclasses (P = .0001). There also was a highly significant positive relationship between serum apoCIII concentration and the LDL particle concentration in both men (r = 0.49, P = .001) and women (r = 0.40, P = .001), and a highly significant negative relationship between serum apoCIII levels and average LDL particle size in both men (r = -0.37, P = .001) and women (r = -0.22, P = .001) due primarily to an augmentation in the small L1 subclass (r = 0.42, P = .0001). Neither the T(-455) --> C polymorphism affecting an insulin response element in the apoCIII gene promoter nor a SacI polymorphism in the 3'UTR were associated with any alterations in circulating apoCIII concentrations, serum lipids, apolipoprotein concentrations, lipoprotein composition, or parameters measured by NMR lipoprotein subclass analyses. In summary, elevated apoCIII concentration was associated with risk factors for cardiovascular disease in normolipidemic type 1 diabetic patients through associated changes in lipoprotein subfraction distributions, which were independent of apoCIII genotype.

3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes

3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as N epsilon-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 +/- 0.189 vs. 0.494 +/- 0.072 microM, P <0.001, and 69.9 +/- 44.2 vs. 38.7 +/- 16.1 nmol/mg creatinine, P <0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c (P <0.005 in all cases), and with urinary FL (P <0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.

Total arsenic, inorganic arsenic, and other elements concentrations in Italian rice grain varies with origin and type

Rice is comparatively efficient at assimilating inorganic arsenic (As _i), a class-one, non-threshold carcinogen, into its grain, being the dominant source of this element to mankind. Here it was investigated how the total arsenic (As_t) and As_i content of Italian rice grain sourced from market outlets varied by geographical origin and type. Total Cr, Cd Se, Mg, K, Zn, Ni were also quantified. As_t concentration on a variety basis ranged from means of 0.18 mg kg^-1 to 0.28 mg kg ^-1, and from 0.11 mg kg^-1 to 0.28 mg kg^-1 by production region. For As_i concentration, means ranged from 0.08 mg kg^-1 to 0.11 mg kg^-1 by variety and 0.10 mg kg ^-1 to 0.06 mg kg^-1 by region. There was significant geographical variation for both As_t and As_i; total Se and Ni concentration; while the total concentration of Zn, Cr, Ni and K were strongly influenced by the type of rice.

Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age

Objective

To examine whether early inflammation is related to cortisol levels at 18 months corrected age (CA) in children born very preterm.

Study Design

Infants born ≤ 32 weeks gestational age were recruited in the NICU, and placental histopathology, MRI, and chart review were obtained. At 18 months CA developmental assessment and collection of 3 salivary cortisol samples were carried out. Generalized least squares was used to analyze data from 85 infants providing 222 cortisol samples.

Results

Infants exposed to chorioamnionitis with funisitis had a significantly different pattern of cortisol across the samples compared to infants with chorioamnionitis alone or no prenatal inflammation (F[4,139] = 7.3996, P <.0001). Postnatal infections, necrotizing enterocolitis and chronic lung disease were not significantly associated with the cortisol pattern at 18 months CA.

Conclusion

In children born very preterm, prenatal inflammatory stress may contribute to altered programming of the HPA axis.

Keywords: preterm, chorioamnionitis, funisitis, premature infants, hypothalamic-pituitary-adrenal axis, infection, cortisol, stress

Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age

Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm =32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-?B, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm. © 2013 Grunau et al.

Chlorophyll-a concentrations and macroinvertebrate declines coincide with the collapse of overwintering diving duck populations in a large eutrophic lake

1. Lough Neagh is one of the most important non-estuarine sites in the British Isles for overwinteringwildfowl. A change in the waterbird assemblage following the winter of 2000/2001 was drivenmainly by a rapid decline in the population of overwintering diving ducks. Sudden and discretechanges in resident as well as migratory waterbirds may suggest an intrinsic cause.
2. We compared the density and biomass of benthic macroinvertebrates, the food of overwinteringdiving ducks, in 2010 (following the diving duck population decline) with values from a baselinesurvey conducted in 1997/1998 (before the decline in diving ducks).
3. The mean total density of macroinvertebrates declined significantly by c. 65% from 15 300 m2in1997/1998 to 5136 m2in 2010. There was a concomitant c. 70% decline in mean macroinvertebratebiomass from 15 667 mg m2to 5112 mg m2. In terms of taxonomic composition, the relativecontribution of Tanypodinae, Glyptotendipes spp . and Tanytarsini declined, while the relativecontribution of Chironomus spp. increased.
4. We describe a shift in chlorophyll-a concentration, a proxy of phytoplankton biomass, in thelargest freshwater lake in the British Isles coincident with a significant reduction in macroinverte-brate density and biomass, with potential implications for ecosystem processes and ecologically andeconomically important consumer populations, including waterbirds and fishes