Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment

<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

Investigation of finger reflectance photoplethysmography in volunteers undergoing a local sympathetic stimulation

Optical sensors used in clinical applications have gained great popularity over the last few decades, especially the photoplethysmographic (PPG) technique used in estimating arterial blood oxygen saturation in the well-known medical devices called pulse oximeters. In this study we investigate the photoplethysmogram further in an effort to understand its origin better, as there is a significant void in the current knowledge on the PPG quantitative measurement. The photoplethysmographic signal provides a heart rhythm pulsating AC component, and a non-pulsating DC component. The signal is commonly believed to originate from tissue volume changes only and hasn't been investigated intensively. This in vivo study examines the source of the PPG signal in relation to pulse amplitude and pulse rhythm while volunteers undergo a right hand ice immersion. It was found that the PPG signal is sensitive in detecting the sympathetic stimulation which corresponds to volumetric and heart rate changes. During the immersion, AC pulse amplitudes (PA) from both hands decreased significantly, while DC levels increased significantly in the right hand and non-significantly in the left hand. Also, a significant decrease in the pulse repetition time (PRT) was observed. Using blood pressure-flow theories, these results suggest that there are possibly other factors in the blood flow regulation that alter the blood optical density which contributes to the detected signal. Further studies need to investigate PPGs in relation to blood optical density and the dynamics of the pulsatile flow effects besides volumetric changes. Such investigations might explore further applications of the PPG in medicine

Population-Level Associations between Preschool Vulnerability and Grade-Four Basic Skills

Background: This is a predictive validity study examining the extent to which developmental vulnerability at kindergarten entry (as measured by the Early Development Instrument, EDI) is associated with children’s basic skills in 4th grade (as measured by the Foundation Skills Assessment, FSA). Methodology/Principal Findings: Relative risk analysis was performed on a large database linking individual-level EDI ratings to the scores the same children obtained on a provincial assessment of academic skills (FSA – Foundation Skills Assessment) four years later. We found that early vulnerability in kindergarten is associated with the basic skills that underlie populations of children’s academic achievement in reading, writing and math, indicating that the Early Development Instrument permits to predict achievement-related skills four years in advance. Conclusions/Significance: The EDI can be used to predict children’s educational trends at the population level and can help select early prevention and intervention programs targeting pre-school populations at minimum cost

Stainless Steel Alloys from First-principles Theory

Gaining an accurate description of materials obviously requires the most advanced atomic-scale techniques fromboth experimental and theoretical areas. In spite of the vast number of available techniques, however, theexperimental study of the atomic-scale properties and phenomena even in simple solids is rather difficult. Insteels the challenges become more complex due to the interplay between the structural, chemical and magneticeffects. On the other hand, advanced computational methods based on density functional theory ensure a properplatform for studying the fundamental properties of steel materials from first-principles. Our group at the RoyalInstitute of Technology in Stockholm has an international position in developing and applying computationalcodes for such applications. Using our ab initio tools, we have presented an insight to the electronic andmagnetic structure, and micromechanical properties of austenitic stainless steel alloys. In the presentcontribution, we review the most important developments within the ab initio quantum-mechanics-aided steeldesign with special emphasis on the role of magnetism on the fundamental properties of alloy steels

Jurisdictional, socioeconomic and gender inequalities in child health and development: analysis of a national census of 5-year-olds in Australia

OBJECTIVES: Early child development may have important consequences for inequalities in health and well-being. This paper explores population level patterns of child development across Australian jurisdictions, considering socioeconomic and demographic characteristics. DESIGN: Census of child development across Australia. SETTING AND PARTICIPANTS: Teachers complete a developmental checklist, the Australian Early Development Index (AEDI), for all children in their first year of full-time schooling. Between May and July 2009, the AEDI was collected by 14 628 teachers in primary schools (government and non-government) across Australia, providing information on 261 147 children (approximately 97.5% of the estimated 5-year-old population). OUTCOME MEASURES: Level of developmental vulnerability in Australian children for five developmental domains: physical well-being, social competence, emotional maturity, language and cognitive skills and communication skills and general knowledge. RESULTS: The results show demographic and socioeconomic inequalities in child development as well as within and between jurisdiction inequalities. The magnitude of the overall level of inequality in child development and the impact of covariates varies considerably both between and within jurisdiction by sex. For example, the difference in overall developmental vulnerability between the bestperforming and worst-performing jurisdiction is 12.5% for males and 7.1% for females. Levels of absolute social inequality within jurisdictions range from 8.2% for females to 12.7% for males. CONCLUSIONS: The different mix of universal and targeted services provided within jurisdictions from pregnancy to age 5 may contribute to inequality across the country. These results illustrate the potential utility of a developmental census to shed light on the impact of differences in universal and targeted services to support child development by school entry.Sally A. Brinkman, Angela Gialamas, Azizur Rahman, Murthy N. Mittinty, Tess A. Gregory, Sven Silburn, Sharon Goldfeld, Stephen R. Zubrick, Vaughan Carr, Magdalena Janus, Clyde Hertzman and John W. Lync

Symptomatic reactions, clinical outcomes and patient satisfaction associated with upper cervical chiropractic care: A prospective, multicenter, cohort study

<p>Abstract</p> <p>Background</p> <p>Observational studies have previously shown that adverse events following manipulation to the neck and/or back are relatively common, although these reactions tend to be mild in intensity and self-limiting. However, no prospective study has examined the incidence of adverse reactions following spinal adjustments using upper cervical techniques, and the impact of this care on clinical outcomes.</p> <p>Methods</p> <p>Consecutive new patients from the offices of 83 chiropractors were recruited for this practice-based study. Clinical outcome measures included 1) Neck pain disability index (100-point scale), 2) Oswestry back pain index (100-point scale), 3) 11-point numerical rating scale (NRS) for neck, headache, midback, and low back pain, 4) treatment satisfaction, and 5) Symptomatic Reactions (SR). Data were collected at baseline, and after approximately 2 weeks of care. A patient reaching sub-clinical status for pain and disability was defined as a follow-up score <3 NRS and <10%, respectively. A SR is defined as a new complaint not present at baseline or a worsening of the presenting complaint by >30% based on an 11-point numeric rating scale occurring <24 hours after any upper cervical procedure.</p> <p>Results</p> <p>A total of 1,090 patients completed the study having 4,920 (4.5 per patient) office visits requiring 2,653 (2.4 per patient) upper cervical adjustments over 17 days. Three hundred thirty- eight (31.0%) patients had SRs meeting the accepted definition. Intense SR (NRS ≥8) occurred in 56 patients (5.1%). Outcome assessments were significantly improved for neck pain and disability, headache, mid-back pain, as well as lower back pain and disability (<it>p </it><0.001) following care with a high level (mean = 9.1/10) of patient satisfaction. The 83 chiropractors administered >5 million career upper cervical adjustments without a reported incidence of serious adverse event.</p> <p>Conclusions</p> <p>Upper cervical chiropractic care may have a fairly common occurrence of mild intensity SRs short in duration (<24 hours), and rarely severe in intensity; however, outcome assessments were significantly improved with less than 3 weeks of care with a high level of patient satisfaction. Although our findings need to be confirmed in subsequent randomized studies for definitive risk-benefit assessment, the preliminary data shows that the benefits of upper cervical chiropractic care may outweigh the potential risks.</p