Association between early life antibiotic use and childhood overweight and obesity: a narrative review.

Background: Recent research implicates antibiotic use as a potential contributor to child obesity risk. In this narrative review, we examine current observational evidence on the relation between antibiotic use in early childhood and subsequent measures of child body mass. Methods: We searched PubMed, Web of Science and the Cochrane Library to identify studies that assessed antibiotic exposure before 3 years of age and subsequent measures of body mass or risk of overweight or obesity in childhood. Results: We identified 13 studies published before October 2017, based on a total of 6 81 332 individuals, which examined the relation between early life antibiotic exposure and measures of child body mass. Most studies did not appropriately account for confounding by indication for antibiotic use. Overall, we found no consistent and conclusive evidence of associations between early life antibiotic use and later child body mass [minimum overall adjusted odds ratio (aOR) reported: 1.01, 95% confidence interval (95% CI) 0.98-1.04, N = 2 60 556; maximum overall aOR reported: 2.56, 95% CI 1.36-4.79, N = 616], with no clinically meaningful increases in weight reported (maximum increase: 1.50 kg at 15 years of age). Notable methodological differences between studies, including variable measures of association and inclusion of confounders, limited more comprehensive interpretations. Conclusions: Evidence to date is insufficient to indicate that antibiotic use is an important risk factor for child obesity, or leads to clinically important differences in weight. Further comparable studies using routine clinical data may help clarify this association.This work was supported by the Wellcome Trust (grant number 206194), the African Partnership for Chronic Disease Research (Medical Research Council UK partnership grant number MR/K013491/1) and the National Institute for Health Research Cambridge Biomedical Research Centre (UK). EP is supported by the Gates Cambridge Trust

Combinatorial localized dissolution analysis : application to acid-induced dissolution of dental enamel and the effect of surface treatments

A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1 mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca2+ flux (jCa2+), is first order with respect to the interfacial proton concentration and given by the following rate law: jCa2+=k0[H+], with k0=0.099±0.008 cm s−1. Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10–20 nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

The Wnt Receptor Ryk Reduces Neuronal and Cell Survival Capacity by Repressing FOXO Activity During the Early Phases of Mutant Huntingtin Pathogenicity

The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD. © 2014 Tourette et al

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

"I don't eat a hamburger and large chips every day!" A qualitative study of the impact of public health messages about obesity on obese adults

BackgroundWe are a society that is fixated on the health consequences of \u27being fat\u27. Public health agencies play an important role in \u27alerting\u27 people about the risks that obesity poses both to individuals and to the broader society. Quantitative studies suggest people comprehend the physical health risks involved but underestimate their own risk because they do not recognise that they are obese.MethodsThis qualitative study seeks to expand on existing research by exploring obese individuals\u27 perceptions of public health messages about risk, how they apply these messages to themselves and how their personal and social contexts and experiences may influence these perceptions. The study uses in depth interviews with a community sample of 142 obese individuals. A constant comparative method was employed to analyse the data.ResultsPersonal and contextual factors influenced the ways in which individuals interpreted and applied public health messages, including their own health and wellbeing and perceptions of stigma. Individuals felt that messages were overly focused on the physical rather than emotional health consequences of obesity. Many described feeling stigmatised and blamed by the simplicity of messages and the lack of realistic solutions. Participants described the need for messages that convey the risks associated with obesity while minimising possible stigmatisation of obese individuals. This included ensuring that messages recognise the complexity of obesity and focus on encouraging healthy behaviours for individuals of all sizes.ConclusionThis study is the first step in exploring the ways in which we understand how public health messages about obesity resonate with obese individuals in Australia. However, much more research - both qualitative and quantitative - is needed to enhance understanding of the impact of obesity messages on individuals

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Patient-directed self-management of pain (PaDSMaP) compared to treatment as usual following total knee replacement; a randomised controlled trial

Background Self-administration of medicines by patients whilst in hospital is being increasingly promoted despite little evidence to show the risks and benefits. Pain control after total knee replacement (TKR) is known to be poor. The aim of the study was to determine if patients operated on with a TKR who self-medicate their oral analgesics in the immediate post-operative period have better pain control than those who receive their pain control by nurse-led drug rounds (Treatment as Usual (TAU)). Methods A prospective, parallel design, open-label, randomised controlled trial comparing pain control in patient-directed self-management of pain (PaDSMaP) with nurse control of oral analgesia (TAU) after a TKR. Between July 2011 and March 2013, 144 self-medicating adults were recruited at a secondary care teaching hospital in the UK. TAU patients (n = 71) were given medications by a nurse after their TKR. PaDSMaP patients (n = 73) took oral medications for analgesia and co-morbidities after two 20 min training sessions reinforced with four booklets. Primary outcome was pain (100 mm visual analogue scale (VAS)) at 3 days following TKR surgery or at discharge (whichever came soonest). Seven patients did not undergo surgery for reasons unrelated to the study and were excluded from the intention-to-treat (ITT) analysis. Results ITT analysis did not detect any significant differences between the two groups’ pain scores. A per protocol (but underpowered) analysis of the 60% of patients able to self-medicate found reduced pain compared to the TAU group at day 3/discharge, (VAS -9.9 mm, 95% CI -18.7, − 1.1). One patient in the self-medicating group over-medicated but suffered no harm. Conclusion Self-medicating patients did not have better (lower) pain scores compared to the nurse-managed patients following TKR. This cohort of patients were elderly with multiple co-morbidities and may not be the ideal target group for self-medication