The (Parental) Whole Is Greater Than the Sum of Its Parts: A Multifactorial Model of Parent Factors in Pediatric Chronic Pain

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International LicenseParents play a critical role in children's experience of, and recovery from, chronic pain. Although several parental factors have been linked to child pain and functioning, these factors are typically examined in isolation or as moderators or mediators. Structural equation modeling affords the opportunity to examine the extent to which parental factors are interrelated, and if there are differential associations among parental factors and child outcomes. Based on extant literature, a unified model of parental factors, including chronic pain status, physical functioning, responses to child pain, and psychological factors, and their effect on child pain and functioning, was conceptualized. This model was evaluated using structural equation modeling based on data from 146 dyads recruited from a multidisciplinary pain clinic. Modifications to model iterations were made based on theoretical and statistical justification. The final model revealed associations among all parental factors, with significant loadings on child pain and functioning. Findings indicated the conceptual model was supported, with the exception of parent responses to child pain. Findings support the inclusion of parent chronic pain status and physical and psychological functioning as part of a comprehensive assessment of youth with chronic pain and may inform new parental intervention targets to improve child outcomes

East African lake evidence for Pliocene millennial-scale climate variability

Late Cenozoic climate history in Africa was punctuated by episodes of variability, characterized by the appearance and disappearance of large freshwater lakes within the East African Rift Valley. In the Baringo-Bogoria basin, a well-dated sequence of diatomites and fluviolacustrine sediments documents the precessionally forced cycling of an extensive lake system between 2.70 Ma and 2.55 Ma. One diatomite unit was studied, using the oxygen isotope composition of diatom silica combined with X-ray fluorescence spectrometry and taxonomic assemblage changes, to explore the nature of climate variability during this interval. Data reveal a rapid onset and gradual decline of deepwater lake conditions, which exhibit millennial-scale cyclicity of ∼1400–1700 yr, similar to late Quaternary Dansgaard-Oeschger events. These cycles are thought to reflect enhanced precipitation coincident with increased monsoonal strength, suggesting the existence of a teleconnection between the high latitudes and East Africa during this period. Such climatic variability could have affected faunal and floral evolution at the time

Coral larval recruitment in north-western Australia predicted by regional and local conditions

Understanding ecological processes that shape contemporary and future communities facilitates knowledge-based environmental management. In marine ecosystems, one of the most important processes is the supply of new recruits into a population. Here, we investigated spatiotemporal variability in coral recruitment at 15 reefs throughout the Dampier Archipelago, north-western Australia between 2015 and 2017 and identified the best environmental predictors for coral recruitment patterns over this period. Large differences in recruitment were observed among years with the average density of recruits increasing by 375% from 0.017 recruits cm−2 in 2015 to 0.059 recruits cm−2 in 2017. Despite differences in recruitment among years, the rank order of coral recruit density among reefs remained similar among years, suggesting that spatial variation in recruitment within the Dampier Archipelago is partly deterministic and predictable. The density of coral recruits was best explained by percent cover of live corals at both local (within 5 m) and meso-scales (within 15 km), water turbidity and an oceanographic model that predicted larval dispersal. The highest density of coral recruits (~0.13 recruits cm−2 or 37 recruits per tile) occurred on reefs within sub-regions (15 km) with greater than 35% coral cover, low to moderate turbidity (KD490 < 0.2) and moderate to high modelled predictions of larval dispersal. Our results demonstrate that broad-scale larval dispersal models, when combined with local metrics of percent hard coral cover and water turbidity, can reliably predict the relative abundance of coral recruits over large geographical areas and thus can identify hotspots of recruit abundance and potential recovery following environmental disturbances; information that is essential for effective management of coral reefs

Dietary intake in a randomized-controlled pilot of NOURISH: A parent intervention for overweight children

NOURISH is a community-based treatment program for parents of overweight and obese children (ages 6–11, BMI ≥ 85th percentile). This study examined the impact of NOURISH on child and parent dietary intake, secondary trial outcomes

Maternal–fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study

Background: Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant’s neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA. Results: A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a ‘Fetal Stress Index’ (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn’s saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. Conclusions: Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.Fil: Sharma, Ritika. Technische Universitat München; AlemaniaFil: Frasch, Martin Gerbert. University of Washington; Estados UnidosFil: Zelgert, Camila. Technische Universitat München; AlemaniaFil: Zimmermann, Peter. Technische Universitat München; AlemaniaFil: Fabre, Bibiana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; ArgentinaFil: Wilson, Rory. Helmholtz Zentrum Munich; AlemaniaFil: Waldenberger, Melanie. Helmholtz Zentrum Munich; AlemaniaFil: MacDonald, James W.. University of Washington; Estados UnidosFil: Bammler, Theo K.. University of Washington; Estados UnidosFil: Lobmaier, Silvia M.. Technische Universitat München; AlemaniaFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

A robust system for RNA interference in the chicken using a modified microRNA operon

AbstractRNA interference (RNAi) provides an effective method to silence gene expression and investigate gene function. However, RNAi tools for the chicken embryo have largely been adapted from vectors designed for mammalian cells. Here we present plasmid and retroviral RNAi vectors specifically designed for optimal gene silencing in chicken cells. The vectors use a chicken U6 promoter to express RNAs modelled on microRNA30, which are embedded within chicken microRNA operon sequences to ensure optimal Drosha and Dicer processing of transcripts. The chicken U6 promoter works significantly better than promoters of mammalian origin and in combination with a microRNA operon expression cassette (MOEC), achieves up to 90% silencing of target genes. By using a MOEC, we show that it is also possible to simultaneously silence two genes with a single vector. The vectors express either RFP or GFP markers, allowing simple in vivo tracking of vector delivery. Using these plasmids, we demonstrate effective silencing of Pax3, Pax6, Nkx2.1, Nkx2.2, Notch1 and Shh in discrete regions of the chicken embryonic nervous system. The efficiency and ease of use of this RNAi system paves the way for large-scale genetic screens in the chicken embryo

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes:The Anglo–Danish–Dutch Study of Intensive treatment in people with screen-detected diabetes in primary care (ADDITION-Europe) study

Background: Intensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain.  Objective: To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes.  Design: Pragmatic, multicentre, cluster-randomised, parallel-group trial.  Setting: Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK.  Participants: Individuals aged 40–69 years with screen-detected diabetes.  Interventions: Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol.  Main outcome measures: The primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; © Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk/outcomesmodel (accessed 27 January 2016)].  Results: We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient.  Conclusions: Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients