Attitudes toward integrative paediatrics: a national survey among youth health are physicians in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Integrative Medicine (IM) is an emerging field in paediatrics, especially in the USA. The purpose of the present study was to assess the attitudes and beliefs of Youth Health Care (YHC) physicians in the Netherlands toward IM in paediatrics.</p> <p>Methods</p> <p>In October 2010, a link to an anonymous, self-reporting, 30-item web-based questionnaire was mailed to all members of the Dutch Organisation of YHC physicians. The questionnaire included questions on familiarity with IM, attitudes towards Integrative Paediatrics (IP), use and knowledge of Complementary and Alternative Medicine (CAM), demographic and practice characteristics.</p> <p>Results</p> <p>A total of 276 YHC physicians (response rate of 27%) responded to the survey. Of the respondents, 52% was familiar with IM and 56% had used some kind of CAM therapy during the past 2 years, of which self-medicated herbal and/or homeopathic remedies (61%) and supplements (50%) were most frequently mentioned. Most of the YHC physicians (62%) seldom asked parents of clients about CAM use. One third of the YHC physicians recommended CAM to their clients. In general, about 50% or more of the respondents had little knowledge of CAM therapies. Predictors for a positive attitude towards IP were familiarity with IM, own CAM use, asking their clients about CAM use and practising one or more forms of CAM therapy. Logistic regression analysis showed that the following factors were associated with a higher recommendation to CAM therapies: own CAM use (odds ratio (OR) = 3.8; 95% confidence interval (CI) = 2.1-6.9, <it>p </it>= 0.001) and practising CAM (OR 4.4; 95% CI = 1.6-11.7, <it>p </it>= 0.003).</p> <p>Conclusions</p> <p>In general Dutch YHC physicians have a relative positive attitude towards IP; more than half of the respondents used one or more forms of CAM and one third recommended CAM therapies. However, the majority of YHC physicians did not ask their clients about CAM use and seemed to have a lack of knowledge regarding CAM.</p

Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease

OBJECTIVES: Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). METHODS: Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-term mouse IBD model (anti-CD40 Rag2(-/-)) treated preventively with monoclonal antibodies (mAbs) to the IL-23 receptor (IL-23R). The biomarkers were then measured in an IBD T-cell transfer model treated therapeutically with a mAb to IL-23 (p19), confirming their association with IBD. To assess the clinical relevance of these markers, we assessed their concentrations in clinical serum, colon tissue, and feces from CD patients. RESULTS: We identified 57 proteins up or downregulated in diseased animals that returned to control values when the mice were treated with mAbs to IL-23R. Among those, S100A8, S100A9, regenerating protein 3β (REG), REG3γ, lipocalin 2 (LCN2), deleted in malignant tumor 1 (DMBT1), and macrophage migration inhibitory factor (MIF) mRNA levels correlated with disease score and dose titration of mAbs to IL-23R or IL-23(p19). All biomarkers, except DMBT1, were also downregulated after therapeutic administration of mAbs to IL-23(p19) in a T-cell transfer IBD mouse model. In sera from CD patients, we confirmed a significant upregulation of S100A8/A9 (43%), MIF (138%), pancreatitis-associated protein (PAP, human homolog of REG3β/γ; 49%), LCN2 (520%), and CCL20 (1280%), compared with control samples, as well as a significant upregulation of S100A8/A9 (887%), PAP (401%), and LCN2 (783%) in human feces from CD patients compared with normal controls. CONCLUSIONS: These studies identify multiple protein biomarkers downstream of IL-23 that could be valuable tools to assess the efficacy of this new therapeutic agent.Clinical and Translational Gastroenterology (2012) 3, e10; doi:10.1038/ctg.2012.2; published online 16 February 2012

Contribution of isoprene to chemical budgets:A model tracer study with the NCAR CTM MOZART-4

We present a study of the sensitivity of isoprene emission calculations in a global chemistry transport model (CTM) to input land cover characteristics and analyze the impacts of changes in isoprene on the tropospheric budgets of atmospheric key species. The CTM Model for Ozone and Related Chemical Species, version 4 (MOZART-4) includes the online calculation of isoprene emissions based on the Model of Emissions of Gases and Aerosols from Nature (MEGAN), which is driven by three different land parameter inputs. We also included a tagging scheme in the CTM, which keeps track of the production of carbon containing species from isoprene oxidation. It is found that the amount of tropospheric carbon monoxide (CO), formaldehyde (HCHO) and peroxyacetylnitrate (PAN) explained by isoprene oxidation ranges from 9-16%, 15-27%, and 22-32%, depending on the isoprene emissions scenario. Changes in the global tropospheric burden with different land cover inputs can reach up to 10% for CO, 15% for HCHO, and 20% for PAN. Changes for ozone are small on a global scale, but regionally differences are as large as 3DU in the tropospheric column and as large as 5 ppbv in the surface concentrations. Our results demonstrate that a careful integration of isoprene emissions and chemistry in CTMs is very important for simulating the budgets of a number of atmospheric trace gases. We further demonstrate that the model tagging scheme has the capability of improving conventional methods of constraining isoprene emissions from space-borne HCHO column observations, especially in regions where a considerable part of the variability in the HCHO column is not related to isoprene. Copyright 2008 by the American Geophysical Union

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field