Establishing comprehensive oral assessments for children with safeguarding concerns.

The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input

Effectiveness of acupuncture, special dressings and simple, low-adherence dressings for healing venous leg ulcers in primary healthcare: study protocol for a cluster-randomized open-labeled trial

<p>Abstract</p> <p>Background</p> <p>Venous leg ulcers constitute a chronic recurring complaint that affects 1.0–1.3% of the adult population at some time in life, and which corresponds to approximately 75% of all chronic ulcers of the leg. Multilayer compression bandaging is, at present, the only treatment that has been proved to be effective in treating this type of ulcer. There is no consensus, however, about the dressings that may be applied, beneath the compression, to promote the healing of this type of ulcer, as there does not seem to be any added benefit from using special dressings rather than simple, low-adherence ones. As well as analgesia, acupuncture provokes peripheral vasodilation, in skin and muscles – which has been demonstrated both experimentally and in clinical practice – probably due to the axon reflex, among other mechanisms. The aim of the present study is to measure the effectiveness and cost of compression treatment for venous leg ulcers combined with special dressings, in comparison with low-adherence ones and acupuncture.</p> <p>Methods/design</p> <p>Cluster-randomized open-labeled trial, at 15 primary healthcare clinics in the Sevilla-Sur Healthcare District, with a control group treated with compression bandaging and low-adherence dressings; the experiment will consist, on the one hand, of the compression treatment applied in combination with special dressings (Treatment 1), and on the other, the compression treatment applied in association with low-adherence dressings, together with acupuncture (Treatment 2).</p> <p>Discussion</p> <p>The results will be measured and recorded in terms of the median time elapsed until complete healing of the ulcer, and the rate of complete healing at 3 months after beginning the treatment. An economic analysis will also be made.</p> <p>This study, carried out in the context of real clinical practice, will provide information for decision-taking concerning the effectiveness of special dressings. Moreover, for the first time a high-quality study will evaluate the effectiveness of acupuncture in the process of healing venous leg ulcers.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN26438275.</p

Disruption of AP1S1, Causing a Novel Neurocutaneous Syndrome, Perturbs Development of the Skin and Spinal Cord

Adaptor protein (AP) complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. Because disruption of the various subunits of the AP complexes is embryonic lethal in the majority of cases, characterization of their function in vivo is still lacking. Here, we describe the first mutation in the human AP1S1 gene, encoding the small subunit σ1A of the AP-1 complex. This founder splice mutation, which leads to a premature stop codon, was found in four families with a unique syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK). To validate the pathogenic effect of the mutation, we knocked down Ap1s1 expression in zebrafish using selective antisens morpholino oligonucleotides (AMO). The knockdown phenotype consisted of perturbation in skin formation, reduced pigmentation, and severe motility deficits due to impaired neural network development. Both neural and skin defects were rescued by co-injection of AMO with wild-type (WT) human AP1S1 mRNA, but not by co-injecting the truncated form of AP1S1, consistent with a loss-of-function effect of this mutation. Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord

Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer's Disease

With the exception of APOE ε4 allele, the common genetic risk factors for sporadic Alzheimer's Disease (AD) are unknown., which can be considered potential “new” candidate loci to explore in the etiology of sporadic AD. These candidates included EFNA5, CAND1, MAGI2, ARSB, and PRUNE2, genes involved in the regulation of protein degradation, apoptosis, neuronal loss and neurodevelopment. Thus, we identified common genetic variants associated with the increased risk of developing AD in the ADNI cohort, and present publicly available genome-wide data. Supportive evidence based on case-control studies and biological plausibility by gene annotation is provided. Currently no available sample with both imaging and genetic data is available for replication.Using hippocampal atrophy as a quantitative phenotype in a genome-wide scan, we have identified candidate risk genes for sporadic Alzheimer's disease that merit further investigation

Epigenetic Activation of a Subset of mRNAs by eIF4E Explains Its Effects on Cell Proliferation

BACKGROUND: Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5′ cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E. METHODOLOGY/PRINCIPAL FINDINGS: Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Inducible expression of eIF4E resulted in increased translation of defined sets of mRNAs. Many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth-related factors. In addition, there was augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulum-mediated apoptosis. CONCLUSIONS/SIGNIFICANCE: Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a potential therapeutic option for the development of novel anti-cancer drugs

Perspectives on utilization of edible coatings and nano-laminate coatings for extension of postharvest storage of fruits and vegetables

It is known that in developing countries, a large quantity of fruit and vegetable losses results at postharvest and processing stages due to poor or scarce storage technology and mishandling during harvest. The use of new and innovative technologies for reducing postharvest losses is a requirement that has not been fully covered. The use of edible coatings (mainly based on biopolymers) as a postharvest technique for agricultural commodities has offered biodegradable alternatives in order to solve problems (e.g., microbiological growth) during produce storage. However, biopolymer-based coatings can present some disadvantages such as: poor mechanical properties (e.g., lipids) or poor water vapor barrier properties (e.g., polysaccharides), thus requiring the development of new alternatives to solve these drawbacks. Recently, nanotechnology has emerged as a promising tool in the food processing industry, providing new insights about postharvest technologies on produce storage. Nanotechnological approaches can contribute through the design of functional packing materials with lower amounts of bioactive ingredients, better gas and mechanical properties and with reduced impact on the sensorial qualities of the fruits and vegetables. This work reviews some of the main factors involved in postharvest losses and new technologies for extension of postharvest storage of fruits and vegetables, focused on perspective uses of edible coatings and nano-laminate coatings.María L. Flores-López thanks Mexican Science and Technology Council (CONACYT, Mexico) for PhD fellowship support (CONACYT Grant Number: 215499/310847). Miguel A. Cerqueira (SFRH/BPD/72753/2010) is recipient of a fellowship from the Fundação para a Ciência e Tecnologia (FCT, POPH-QREN and FSE Portugal). The authors also thank the FCT Strategic Project of UID/ BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the project ‘‘BioInd Biotechnology and Bioengineering for improved Industrial and AgroFood processes,’’ REF. NORTE-07-0124-FEDER-000028 Co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico – FUNCAP, CE Brazil (CI10080-00055.01.00/13)

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