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.

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.

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES: Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Mineralogy, chemistry and biological contingents of an early-middle Miocene Antarctic paleosol and its relevance as a Martian analogue

Fossil mesofauna and bacteria recovered from a paleosol in a moraine situated adjacent to the inland ice, Antarctica, and dating to the earliest glacial event in the Antarctic Dry Valleys opens several questions. The most important relates to understanding of the mineralogy and chemistry of the weathered substrate habitat in which Coleoptera apparently thrived at some point in the Early/Middle Miocene and perhaps earlier. Here, Coleoptera remains are only located in one of six horizons in a paleosol formed in moraine deposited during the alpine glacial event (> 15 Ma). A tendency for quartz to decrease upward in the section may be a detrital effect or a product of dissolution in the early stage of profile morphogenesis when climate was presumably milder and the depositing glacier of temperate type. Discontinuous distributions of smectite, laumontite, and hexahydrite may have provided nutrients and water to mesofauna and bacteria during the early stage of biotic colonization of the profile. Because the mesofauna were members of burrowing Coleoptera species, future work should assess the degree to which the organisms occupied other sites in the Dry Valleys in the past. Whereas there is no reasonable expectations of finding Coleoptera/insect remains on Mars, the chemistry and mineralogy of the paleosol is within a life expectancy window for the presence of microorganisms, principally bacteria and fungi. Thus, parameters discussed here within this Antarctic paleosol could provide an analogue to identifying similar fossil or life-bearing weathered regolith on Mars.

Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis

OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations.

METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline.

RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses.

CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.

Estudo da variabilidade genética de marcadores moleculares ligados ao gene da MGP e sua aplicação para paternidades em Sparus aurata

Dissertação de Mestrado, Biologia Marinha, Especialização em Biotecnologia Marinha, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2008

Genetic characterization of the South Portugal population with GlobalFilerTM Express kit - internal validation and forensic applications

Tese de mestrado. Biologia (Biologia Humana e Ambiente). Universidade de Lisboa, Faculdade de Ciências, 2014

What Is Known: Prose Pieces

Thesis (Master's)--University of Washington, 2013

No association between ApoE polymorphism and febrile seizures.

Seizures associated with fever are a common pediatric problem, affecting about 2-7 % of children between 3 months and 5 years of age. Differentiation of febrile seizures from acute symptomatic seizures secondary to central nervous system infections or seizures associated with fever in children with epilepsy is essential to provide appropriate treatment and follow-up care. Here, we tested the hypothesis that children who exhibit simple febrile seizures during early childhood, but do not develop epileptic seizures later in life, might preferentially carry the ApoE2 allele of the gene coding for the apolipoprotein E. We did not find any differences in the distribution of ApoE alleles or genotypes between individuals who exhibited simple febrile seizures (n = 93) and age-matched, typically developing subjects (n = 80). We found that the observed allele and genotype frequencies did not deviate from Hardy-Weinberg equilibrium, which suggests that the frequencies of ApoE alleles and genotypes are stable in the Swiss population from which our samples were derived. Across both groups of subjects (n = 173), we found an ApoE2 allele frequency of 0.064, an ApoE3 frequency of 0.829 and an ApoE4 frequency of 0.107. Our findings are consistent with previous reports of the distribution of ApoE polymorphism for European subjects free of any neurological disorders, and show that the different alleles of the gene coding for the apolipoprotein E are not associated with the occurrence of simple febrile seizures.

Resilience factors of university and college students with learning disabilities as revealed through retrospective interviews /

This qualitative study examined resilience factors of eight university and college students with learning disabilities as revealed through retrospective interviews. This study has added to the existing literature surrounding resilience especially as it relates to individuals with learning disabilities. This study may provide additional insight into the emotional impacts of repeated and chronic risks on students with learning disabilities. The major themes that emerged using the interpretive phenomenological analysis method (Smith & Osborn, 2003) were organized under these four major headings: Challenges and Obstacles, Surviving Challenges, Supportive Conditions, and A Journey of Discovery and Hope. An adaptation of the listening guide analytical method (Gilligan, Spencer, Weinberg, & Bertsch, 2003) was also utilized and offered a more personal depiction of the participants and an exploration of the unique contributions their stories made to this study. Specifically, a theme of feeling trapped/wanting to escape emerged as a reaction to adversity faced during elementary school years. Furthennore, this study has demonstrated that for several of the participants, the benefits of positive outlets extended beyond nurturing areas of strength and self-esteem to also include the provision of a short respite from their challenges and enhanced feelings of overall well-being. Additionally, this study may add to the existing literature surrounding character traits evident in resilient students, specifically highlighting the significance of optimism and selfacceptance.

Demographic and genetic attributes of dispersing and resident individuals of an enclosed Microtus pennsylvanicus population

A dispersal polymorphism may exist in emigrants from cyclic populations of Microtus '~nnsylvanicus biasing trap-revealed movements of unenclosed animals in favour of sedentary or colonizing individuals. The dispersal tendency of emigrants from an enclosed population was investigated by releasing animals via tubes into one of two adjacent enclosures, one vacant and one inhabited. Individuals from the enclosed population were monitored for age, sex, weight and electrophoretically detectable serum transferrin genotype in an intensive live-trapping program. In 1973 the minimum number alive in the introduced enclosed study population reached approximately l67/ha when breeding stopped in October. In 1974 intensive breeding increased the population density to 333/ha by mid-July when a long decline in numbers and breeding intensity began without an intervening plateau. An adjacent unenclosed area had a much lower density and longer breeding season in 1974. The growth rate of young males in the enclosed population tended to be lowest during the decline period in 1974. Survival of the enclosed population was high throughout but was lowest during the decline phase in both sexes, especially males. Low transferrin heterozygote survival during the decline coincided with a significant heterozygote deficiency in females whereas in males genotype frequencies did not depart from Hardy-Weinberg equilibrium values throughout th.e study. Twenty-nine suitable ani.mals were released during the decline in five periods from July to November 1974. The proportions of males and transferrin heterozygotes in the released graun were generally greater than in the source population~ In the test enclosures 21% of the released animals continued their movement through the vacant area while 41% (no significant difference) moved through the inhabited enclosure. In the vacant test area, females had a greater tendency than males to continue dispersal whereas no difference was noted in the inhabited area. Low frequency of captures in the tubes, predator disturbances and cold weather forced the termination of the study. The role of dispersal as a population regulating mechanism was further substantiated. The genetic differences between emigrant and resident animals lend support to Howard's hypothesis that a genetic polymorphism influences the tendency to disperse. Support is also given to Myers' and Krebs' contention that among dispersers an additional density dependent polymorphism influences the distance dispersed.

Exploring Gifted Adults' Perception of Giftedness in their Pursuit of Graduate Education

This qualitative study explores 8 gifted adults' perceptions of their own giftedness and how those perceptions influenced their pursuit of graduate education as revealed by retrospective interviews. This study serves to inform the existing literature surrounding giftedness especially as it relates to gifted individuals across the lifespan and their experiences and perceptions of education at all levels. This study also provides insight into the emotional impact being labeled gifted has on an individual's self-concept and academic identity. The major themes that emerged using the interpretive phenomenological analysis method (Smith & Osborn, 2003) were discussed under five main headings: Evolution of Giftedness, Success and Failure, Expectations, Effort, and Doubt and Proof. An adaptation of the listening guide method (Gilligan, Spencer, Weinberg, & Bertsch, 2003) was used to provide a unique and personal perspective of the phenomenon of giftedness and revealed the feelings behind the themes that emerged in the interpretive phenomenological analysis method. Specifically; this study illuminates the lack of evolution that an individual's understanding and perception of giftedness undergoes across the lifespan, and the impact such a static and school-bound understanding has on gifted adults' self-concept. It also reveals the influence that gifted individuals' innate need to achieve has on their academic aspirations and their perceptions of themselves as gifted. Furthermore, it reveals how important the understanding and internalization of failure can be on the self-concept of gifted individuals, and that this issue needs immediate attention at all levels of education.

Investigating the role of potential genetic markers that can predict risk for steroid refractory inflammatory bowel disease

Contexte - La variation interindividuelle de la réponse aux corticostéroïdes (CS) est un problème important chez les patients atteints de maladies inflammatoires d’intestin. Ce problème est bien plus accentué chez les enfants avec la prévalence de la corticodépendance extrêmement (~40 %) élevée. La maladie réfractaire au CS a des répercussions sur le développement et le bien-être physique et psychologique des patients et impose des coûts médicaux élevés, particulièrement avec la maladie active comparativement à la maladie en rémission, le coût étant 2-3 fois plus élevé en ambulatoire et 20 fois plus élevé en hôpital. Il est ainsi primordial de déterminer les marqueurs prédictifs de la réponse aux CS. Les efforts précédents de découvrir les marqueurs cliniques et démographiques ont été équivoques, ce qui souligne davantage le besoin de marqueurs moléculaires. L'action des CS se base sur des processus complexes déterminés génétiquement. Deux gènes, le ABCB1, appartenant à la famille des transporteurs transmembraneaux, et le NR3C1, encodant le récepteur glucocorticoïde, sont des éléments importants des voies métaboliques. Nous avons postulé que les variations dans ces gènes ont un rôle dans la variabilité observée de la réponse aux CS et pourraient servir en tant que les marqueurs prédictifs. Objectifs - Nous avons visé à: (1) examiner le fardeau de la maladie réfractaire aux CS chez les enfants avec la maladie de Crohn (MC) et le rôle des caractéristiques cliniques et démographiques potentiellement liés à la réponse; (2) étudier l'association entre les variantes d'ADN de gène ABCB1 et la réponse aux CS; (3) étudier les associations entre les variantes d'ADN de gène NR3C1 et la réponse aux CS. Méthodes - Afin d’atteindre ces objectifs, nous avons mené une étude de cohorte des patients recrutés dans deux cliniques pédiatriques tertiaires de gastroentérologie à l’Ottawa (CHEO) et à Montréal (HSJ). Les patients avec la MC ont été diagnostiqués avant l'âge de 18 ans selon les critères standard radiologiques, endoscopiques et histopathologiques. La corticorésistance et la corticodépendance ont été définies en adaptant les critères reconnus. L’ADN, acquise soit du sang ou de la salive, était génotypée pour des variations à travers de gènes ABCB1 et NR3C1 sélectionnées à l’aide de la méthodologie de tag-SNP. La fréquence de la corticorésistance et la corticodépendance a été estimée assumant une distribution binomiale. Les associations entre les variables cliniques/démographiques et la réponse aux CS ont été examinées en utilisant la régression logistique en ajustant pour des variables potentielles de confusion. Les associations entre variantes génétiques de ABCB1 et NR3C1 et la réponse aux CS ont été examinées en utilisant la régression logistique assumant différents modèles de la transmission. Les associations multimarqueurs ont été examinées en utilisant l'analyse de haplotypes. Les variantes nongénotypées ont été imputées en utilisant les données de HAPMAP et les associations avec SNPs imputés ont été examinées en utilisant des méthodes standard. Résultats - Parmi 645 patients avec la MC, 364 (56.2%) ont reçu CS. La majorité de patients étaient des hommes (54.9 %); présentaient la maladie de l’iléocôlon (51.7%) ou la maladie inflammatoire (84.6%) au diagnostic et étaient les Caucasiens (95.6 %). Huit pourcents de patients étaient corticorésistants et 40.9% - corticodépendants. Le plus bas âge au diagnostic (OR=1.34, 95% CI: 1.03-3.01, p=0.040), la maladie cœxistante de la région digestive supérieure (OR=1.35, 95% CI: 95% CI: 1.06-3.07, p=0.031) et l’usage simultané des immunomodulateurs (OR=0.35, 95% CI: 0.16-0.75, p=0.007) ont été associés avec la corticodépendance. Un total de 27 marqueurs génotypés à travers de ABCB1 (n=14) et NR3C1 (n=13) ont été en l'Équilibre de Hardy-Weinberg, à l’exception d’un dans le gène NR3C1 (rs258751, exclu). Dans ABCB1, l'allèle rare de rs2032583 (OR=0.56, 95% CI: 0.34-0.95, p=0.029) et génotype hétérozygote (OR=0.52, 95% CI: 0.28-0.95 p=0.035) ont été négativement associes avec la dépendance de CS. Un haplotype à 3 marqueurs, comprenant le SNP fonctionnel rs1045642 a été associé avec la dépendance de CS (p empirique=0.004). 24 SNPs imputés introniques et six haplotypes ont été significativement associés avec la dépendance de CS. Aucune de ces associations n'a cependant maintenu la signification après des corrections pour des comparaisons multiples. Dans NR3C1, trois SNPs: rs10482682 (OR=1.43, 95% CI: 0.99-2.08, p=0.047), rs6196 (OR=0.55, 95% CI: 0.31-0.95, p=0.024), et rs2963155 (OR=0.64, 95% CI: 0.42-0.98, p=0.039), ont été associés sous un modèle additif, tandis que rs4912911 (OR=0.37, 95% CI: 0.13-1.00, p=0.03) et rs2963156 (OR=0.32, 95% CI: 0.07-1.12, p=0.047) - sous un modèle récessif. Deux haplotypes incluant ces 5 SNPs (AAACA et GGGCG) ont été significativement (p=0.006 et 0.01 empiriques) associés avec la corticodépendance. 19 SNPs imputés ont été associés avec la dépendance de CS. Deux haplotypes multimarqueurs (p=0.001), incluant les SNPs génotypés et imputés, ont été associés avec la dépendance de CS. Conclusion - Nos études suggèrent que le fardeau de la corticodépendance est élevé parmi les enfants avec le CD. Les enfants plus jeunes au diagnostic et ceux avec la maladie coexistante de la région supérieure ainsi que ceux avec des variations dans les gènes ABCB1 et NR3C1 étaient plus susceptibles de devenir corticodépendants.