Systematic review and meta-analyses of the relationship between short sleep and incidence of obesity and effectiveness of sleep interventions on weight gain in preschool children

The aim of this study is to determine (a) whether short sleep is associated with the incidence of obesity and (b) whether interventions beneficial for sleep reduce weight gain in preschool children. We systematically searched PubMed, Embase, Web of Science and Cochrane up to 12/09/2019. (a) Studies that were included were prospective, had follow‐up ≥1 year, with sleep duration at baseline and required outcome measures. (b) Intervention trials with sleep intervention and measures of overweight or obesity were included. Data were extracted according to PRISMA guidelines. (a) The risk of developing overweight/obesity was greater in short sleeping children (13 studies, 42 878 participants, RR: 1.54; 95% CI, 1.33 to 1.77; p < 0.001). Sleep duration was associated with a significant change in BMI z‐score (10 studies, 11 cohorts and 29 553 participants) (mean difference: −0.02 unit per hour sleep; −0.03 to −0.01; p < 0.001). (b) Four of the five intervention studies reported improved outcomes: for BMI (−0.27 kg/m2; −0.50 to −0.03; p = 0.03); for BMI z‐score (−0.07 unit; −0.12 to −0.02; p = 0.006). Short sleep duration is a risk factor or marker of the development of obesity in preschool children. Intervention studies suggest that improved sleep may be beneficially associated with a reduced weight gain in these children

Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.

BACKGROUND: There is evidence of under-detection and poor management of pain in patients with dementia, in both long-term and acute care. Accurate assessment of pain in people with dementia is challenging and pain assessment tools have received considerable attention over the years, with an increasing number of tools made available. Systematic reviews on the evidence of their validity and utility mostly compare different sets of tools. This review of systematic reviews analyses and summarises evidence concerning the psychometric properties and clinical utility of pain assessment tools in adults with dementia or cognitive impairment. METHODS: We searched for systematic reviews of pain assessment tools providing evidence of reliability, validity and clinical utility. Two reviewers independently assessed each review and extracted data from them, with a third reviewer mediating when consensus was not reached. Analysis of the data was carried out collaboratively. The reviews were synthesised using a narrative synthesis approach. RESULTS: We retrieved 441 potentially eligible reviews, 23 met the criteria for inclusion and 8 provided data for extraction. Each review evaluated between 8 and 13 tools, in aggregate providing evidence on a total of 28 tools. The quality of the reviews varied and the reporting often lacked sufficient methodological detail for quality assessment. The 28 tools appear to have been studied in a variety of settings and with varied types of patients. The reviews identified several methodological limitations across the original studies. The lack of a 'gold standard' significantly hinders the evaluation of tools' validity. Most importantly, the samples were small providing limited evidence for use of any of the tools across settings or populations. CONCLUSIONS: There are a considerable number of pain assessment tools available for use with the elderly cognitive impaired population. However there is limited evidence about their reliability, validity and clinical utility. On the basis of this review no one tool can be recommended given the existing evidence

Deep Sequencing of Pyrethroid-Resistant Bed Bugs Reveals Multiple Mechanisms of Resistance within a Single Population

A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD50 bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance

Usefulness of NT-pro BNP monitoring to identify echocardiographic responders following cardiac resynchronization therapy

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization therapy (CRT) improves left ventricular (LV) volumes, mitral regurgitation (MR) severity and symptoms of patients with heart failure (HF). However, ≥ 30% of patients have no significant clinical or echocardiographic improvement following CRT. Reverse remodeling after CRT correlates with improved clinical outcomes. We hypothesized that in NT-pro BNP monitoring is accurate to identify responders following CRT.</p> <p>Methods</p> <p>42 consecutive patients (mean age 66 ± 12 years, male 68%) with HF undergoing CRT were prospectively enrolled. Responders at follow-up were defined by echocardiography (decrease in LV end systolic volume ≥ 15%). Echocardiography and NT-pro BNP measurement were performed at baseline and repeated 3 to 6 month after CRT.</p> <p>Results</p> <p>There was no significant difference between responders (n = 29, 69%) and non-responders (n = 13, 31%) regarding baseline NT-pro BNP level. Responders had significantly higher decrease in NT-pro BNP levels during follow-up than non-responders (absolute: -1428 ± 1333 pg.ml^-1vs. -61 ± 959 pg.ml^-1, p = 0.002; relative: -45 ± 28% vs. 2 ± 28%, p < 0.0001). A decrease of ≥ 15% in NT-pro BNP 3–6 months after CRT identifies echocardiographic responders with a sensitivity of 90% and a specificity of 77%.</p> <p>Conclusion</p> <p>NT-pro BNP monitoring can accurately identify echocardiographic responders after CRT.</p

Drug education in victorian schools (DEVS): the study protocol for a harm reduction focused school drug education trial

<p>Abstract</p> <p>Background</p> <p>This study seeks to extend earlier Australian school drug education research by developing and measuring the effectiveness of a comprehensive, evidence-based, harm reduction focused school drug education program for junior secondary students aged 13 to 15 years. The intervention draws on the recent literature as to the common elements in effective school curriculum. It seeks to incorporate the social influence of parents through home activities. It also emphasises the use of appropriate pedagogy in the delivery of classroom lessons.</p> <p>Methods/Design</p> <p>A cluster randomised school drug education trial will be conducted with 1746 junior high school students in 21 Victorian secondary schools over a period of three years. Both the schools and students have actively consented to participate in the study. The education program comprises ten lessons in year eight (13-14 year olds) and eight in year nine (14-15 year olds) that address issues around the use of alcohol, tobacco, cannabis and other illicit drugs. Control students will receive the drug education normally provided in their schools. Students will be tested at baseline, at the end of each intervention year and also at the end of year ten. A self completion questionnaire will be used to collect information on knowledge, patterns and context of use, attitudes and harms experienced in relation to alcohol, tobacco, cannabis and other illicit drug use. Multi-level modelling will be the method of analysis because it can best accommodate hierarchically structured data. All analyses will be conducted on an Intent-to-Treat basis. In addition, focus groups will be conducted with teachers and students in five of the 14 intervention schools, subsequent to delivery of the year eight and nine programs. This will provide qualitative data about the effectiveness of the lessons and the relevance of the materials.</p> <p>Discussion</p> <p>The benefits of this drug education study derive both from the knowledge gained by trialling an optimum combination of innovative, harm reduction approaches with a large, student sample, and the resultant product. The research will provide better understanding of what benefits can be achieved by harm reduction education. It will also produce an intervention, dealing with both licit and illicit drug use that has been thoroughly evaluated in terms of its efficacy, and informed by teacher and student feedback. This makes available to schools a comprehensive drug education package with prevention characteristics and useability that are well understood.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12612000079842.aspx">ACTRN12612000079842</a></p

The role of conversation in health care interventions: enabling sensemaking and learning

<p>Abstract</p> <p>Background</p> <p>Those attempting to implement changes in health care settings often find that intervention efforts do not progress as expected. Unexpected outcomes are often attributed to variation and/or error in implementation processes. We argue that some unanticipated variation in intervention outcomes arises because unexpected conversations emerge during intervention attempts. The purpose of this paper is to discuss the role of conversation in shaping interventions and to explain why conversation is important in intervention efforts in health care organizations. We draw on literature from sociolinguistics and complex adaptive systems theory to create an interpretive framework and develop our theory. We use insights from a fourteen-year program of research, including both descriptive and intervention studies undertaken to understand and assist primary care practices in making sustainable changes. We enfold these literatures and these insights to articulate a common failure of overlooking the role of conversation in intervention success, and to develop a theoretical argument for the importance of paying attention to the role of conversation in health care interventions.</p> <p>Discussion</p> <p>Conversation between organizational members plays an important role in the success of interventions aimed at improving health care delivery. Conversation can facilitate intervention success because interventions often rely on new sensemaking and learning, and these are accomplished through conversation. Conversely, conversation can block the success of an intervention by inhibiting sensemaking and learning. Furthermore, the existing relationship contexts of an organization can influence these conversational possibilities. We argue that the likelihood of intervention success will increase if the role of conversation is considered in the intervention process.</p> <p>Summary</p> <p>The generation of productive conversation should be considered as one of the foundations of intervention efforts. We suggest that intervention facilitators consider the following actions as strategies for reducing the barriers that conversation can present and for using conversation to leverage improvement change: evaluate existing conversation and relationship systems, look for and leverage unexpected conversation, create time and space where conversation can unfold, use conversation to help people manage uncertainty, use conversation to help reorganize relationships, and build social interaction competence.</p

ALDH1A2 (RALDH2) genetic variation in human congenital heart disease

Abstract\ud \ud \ud \ud Background\ud \ud Signaling by the vitamin A-derived morphogen retinoic acid (RA) is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2) is critical for cardiac development, we screened patients with congenital heart disease (CHDs) for genetic variation at the ALDH1A2 locus.\ud \ud \ud \ud Methods\ud \ud One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430) at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM) simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay.\ud \ud \ud \ud Results\ud \ud We describe in Tetralogy of Fallot (TOF) the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT) design using single marker genotype, or haplotype information do not show differences between cases and controls.\ud \ud \ud \ud Conclusion\ud \ud In summary, our screen indicates that ALDH1A2 genetic variation is present in TOF patients, suggesting a possible causal role for this gene in rare cases of human CHD, but does not support the hypothesis that variation at the ALDH1A2 locus is a significant modifier of the risk for CHD in humans.Work supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 01/000090; 00/030722; 01/142381; 02/113402; 03/099982; 04/116068; 04/157044 and Conselho Nacional de Desenvolvimento Científico e Tecnológico 481872/20078. We would like to thank the careful work and thoughtful suggestions of the two reviewers responsible for the reviewing editorial process.Work supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 01/00009-0; 00/03072-2; 01/14238-1; 02/11340-2; 03/09998-2; 04/11606-8; 04/15704-4 and Conselho Nacional de Desenvolvimento Científico e Tecnológico 481872/2007-8. We would like to thank the careful work and thoughtful suggestions of the two reviewers responsible for the reviewing editorial process

Family Businesses and Adaptation: A Dynamic Capabilities Approach

The main objective of this research was to propose a framework centred on the dynamic capabilities approach, and to be applied in the context of family businesses’ adaption to their changing business environment. Data were gathered through interviews with ten FBs operating in Western Australia. Based on the findings, the clusters of activities, sensing, seizing, and transforming emerged as key factors for firms’ adaptation, and were reinforced by firms’ open culture, signature processes, idiosyncratic knowledge, and valuable, rare, inimitable and non-substitutable attributes. Thus, the usefulness of the proposed framework was confirmed. Implications and future research opportunities are presented. © 2018, The Author(s)

Selective Release of MicroRNA Species from Normal and Malignant Mammary Epithelial Cells

MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease

Computed tomography myocardial perfusion vs (15)O-water positron emission tomography and fractional flow reserve

Objectives: Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with ¹⁵O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). Methods: 51 patients (63 (61–65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by “snapshot” adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. Results: PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32–2.20) vs 3.11 (2.44–3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32–2.20) vs 3.12 (2.44–3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71–76) vs 86 (84–88) HU, P < 0.001 and 101 (96–106) vs 111 (107–114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. Conclusion: CT myocardial attenuation density correlates with ¹⁵O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. Key Points: •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from “snapshot” imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with ¹⁵O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve