Definitions and clinical guidance on the enteral dependence component of the avoidant/restrictive food intake disorder diagnostic criteria in children

The aim of the current paper is to offer definitive guidance on weaning children who are reliant on nasogastric/gastrostomy feeding tubes. To date, no internationally recognised definitions or principles for interventions exist and clinics have been reliant on creating their own unique intervention criteria. To achieve the aim, two goals are set out within the current paper. The first goal was to definitively define the process of tube weaning. In order to achieve this, both tube dependency and oral eating also required definitions. It is necessary for these two additional definitions to fully understand the process of tube weaning and the transition that the child is making within these clinical interventions. The second goal of this paper was to propose a set of minimum measurement criteria within a tube weaning protocol so that different clinical practices and perspectives may be measured accurately. This would then allow outcomes from different clinical services to be compared for efficacy. The culmination of this paper is a set of five core principles that should govern clinics that adhere to the auspices of evidence-based practice. These principles, if adopted, will provide the basis of a set of internationally recognised criteria within this field of paediatric gastroenterology

Phosphate regulates expression of SIBLINGs and MMPs in cementoblasts

Introduction: Cementoblasts, the cells responsible for tooth root cementum formation, are especially sensitive to local phosphate and pyrophosphate during development, as evidenced by cementum phenotypes resulting from altered phosphate/pyrophosphate distribution. SIBLING family members BSP, OPN, and DMP-1 are regulated by phosphate in cementoblasts and have been shown to activate three specific matrix metalloproteinase (MMP) partners: MMP2, MMP3, and MMP9, respectively, in vitro. The aim of this study was to examine regulatory effects of phosphate on SIBLING and MMP expression in cementoblasts, in vitro. Materials & Methods: Immortalized murine cementoblasts were treated with inorganic phosphate, in vitro, and effects on gene expression (by real time RT-PCR and mouse total genome microarray) were observed. Dose-response 80.1-10 mM phosphate) and time-course (1-48hr) assays were performed. A sodium-phosphate uptake inhibitor, foscarnet, was used to better define phosphate-mediated effects on cells. Results: Three SIBLING family members were regulated by phosphate: OPN (increased over 3000f control), DMP-1 (increased over 3,00027777701060f control), and BSP (decreased). MMP3 was dramatically increased (4,00026651125000f control), paralleling regulation of its partner OPN. Both MMP2 and MMP9 were slightly down-regulated. Time-course experiments indicated a response for SIBLING and MMP genes within 24 hr. Use of foscarnet demonstrated that phosphate uptake was required for observed changes in gene expression. Discussion: These results indicate an effect of phosphate on cementoblast SIBLING and MMP expression in vitro. During cementum formation, phosphate may be an important regulator of cementoblast activity, including modulation of biomineralization, attachment, and matrix modification

An early Cambrian agglutinated tubular lophophorate with brachiopod characters.

The morphological disparity of lophotrochozoan phyla makes it difficult to predict the morphology of the last common ancestor. Only fossils of stem groups can help discover the morphological transitions that occurred along the roots of these phyla. Here, we describe a tubular fossil Yuganotheca elegans gen. et sp. nov. from the Cambrian (Stage 3) Chengjiang Lagerstätte (Yunnan, China) that exhibits an unusual combination of phoronid, brachiopod and tommotiid (Cambrian problematica) characters, notably a pair of agglutinated valves, enclosing a horseshoe-shaped lophophore, supported by a lower bipartite tubular attachment structure with a long pedicle with coelomic space. The terminal bulb of the pedicle provided anchorage in soft sediment. The discovery has important implications for the early evolution of lophotrochozoans, suggesting rooting of brachiopods into the sessile lophotrochozoans and the origination of their bivalved bauplan preceding the biomineralization of shell valves in crown brachiopods

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Measuring measurement

Measurement connects the world of quantum phenomena to the world of classical events. It plays both a passive role, observing quantum systems, and an active one, preparing quantum states and controlling them. Surprisingly - in the light of the central status of measurement in quantum mechanics - there is no general recipe for designing a detector that measures a given observable. Compounding this, the characterization of existing detectors is typically based on partial calibrations or elaborate models. Thus, experimental specification (i.e. tomography) of a detector is of fundamental and practical importance. Here, we present the realization of quantum detector tomography: we identify the optimal positive-operator-valued measure describing the detector, with no ancillary assumptions. This result completes the triad, state, process, and detector tomography, required to fully specify an experiment. We characterize an avalanche photodiode and a photon number resolving detector capable of detecting up to eight photons. This creates a new set of tools for accurately detecting and preparing non-classical light.Comment: 6 pages, 4 figures,see video abstract at http://www.quantiki.org/video_abstracts/0807244

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development

<p>Abstract</p> <p>Background</p> <p>Most human cancers show inactivation of both pRB- and p53-pathways. While retinoblastomas are initiated by loss of the <it>RB1 </it>tumor suppressor gene, <it>TP53 </it>mutations have not been found. High expression of the p53-antagonist MDM2 in human retinoblastomas may compromise p53 tumor surveillance so that <it>TP53 </it>mutations are not selected for in retinoblastoma tumorigenesis. We previously showed that p14^ARFprotein, which activates p53 by inhibiting MDM2, is low in retinoblastomas despite high mRNA expression.</p> <p>Methods</p> <p>In human fetal retinas, adult retinas, and retinoblastoma cells, we determined endogenous <it>p14^ARF</it>mRNA, ARF protein, and miR-24 expression, while integrity of p53 signalling in WERI-Rb1 cells was tested using an adenovirus vector expressing p14^ARF. To study p14^ARFbiogenesis, retinoblastoma cells were treated with the proteasome inhibitor, MG132, and siRNA against miR-24.</p> <p>Results</p> <p>In human retinoblastoma cell lines, <it>p14^ARF</it>mRNA was disproportionally high relative to the level of p14^ARFprotein expression, suggesting a perturbation of p14^ARFregulation. When p14^ARFwas over-expressed by an adenovirus vector, expression of p53 and downstream targets increased and cell growth was inhibited indicating an intact p14^ARF-p53 axis. To investigate the discrepancy between <it>p14^ARF</it>mRNA and protein in retinoblastoma, we examined p14^ARFbiogenesis. The proteasome inhibitor, MG132, did not cause p14^ARFaccumulation, although p14^ARFnormally is degraded by proteasomes. miR-24, a microRNA that represses p14^ARFexpression, is expressed in retinoblastoma cell lines and correlates with lower protein expression when compared to other cell lines with high <it>p14^ARF</it>mRNA. Transient over-expression of siRNA against miR-24 led to elevated p14^ARFprotein in retinoblastoma cells.</p> <p>Conclusions</p> <p>In retinoblastoma cells where high levels of <it>p14^ARF</it>mRNA are not accompanied by high p14^ARFprotein, we found a correlation between miR-24 expression and low p14^ARFprotein. p14^ARFprotein levels were restored without change in mRNA abundance upon miR-24 inhibition suggesting that miR-24 could functionally repress expression, effectively blocking p53 tumor surveillance. During retinal tumorigenesis, miR-24 may intrinsically compromise the p53 response to <it>RB1 </it>loss.</p

A process evaluation of a "physical activity pathway" in the primary care setting

<p>Abstract</p> <p>Background</p> <p>Let's Get Moving (LGM) is a systematic approach to integrating physical activity promotion into the primary care setting. LGM combines a number of recommended strategies to support behavior change including brief interventions, goal-setting, written resources, and follow-up support. This study involved a process evaluation of implementing LGM in UK general practice.</p> <p>Methods</p> <p>The LGM intervention was implemented in six general practices in London. Practices recruited patients either 'opportunistically' in routine consultations or by letter of invitation sent to patients on the hypertension disease register. A key component of the intervention was the delivery of a brief counselling session aimed at facilitating physical activity behaviour change. Data collection methods included electronic patient records, a practice survey and focus groups and interviews with practitioners.</p> <p>Results</p> <p>A total of 526 patients were considered for LGM, 378 via the 'opportunistic' recruitment method and 148 using the disease register approach. Patient interest in the brief counselling session was high although the actual delivery style and content varied between practitioners. Patients were directed towards a variety of physical activity opportunities including local leisure services and walking schemes.</p> <p>Conclusion</p> <p>The learning from this pilot should inform a revised update of the LGM protocols before the planned dissemination of the intervention which is outlined in the Governments 'Be Active, Be Healthy' physical activity strategy. A robust assessment of effectiveness involving an experimental design and behaviour change measures is also warranted prior to wider dissemination.</p

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U