The consent process: enabling or disabling patients’ active participation?

Standards expected by doctors’ regulatory bodies in respect of the process of consent to treatment have arguably sought to restructure the nature of the doctor-patient relationship from one of paternalism to that of shared decision-making. Yet, few studies have explored empirically, from patients’ perspectives, the extent to which the process of consent to treatment enables or disables patients’ participation in medical decision-making. Our paper examines patients’ attitudes towards the consent process, exploring how and why these attitudes influence patients’ active participation in decision-making and considering possible consequent medico-legal issues. Data were collected longitudinally using semi-structured interviews and field observations involving 35 patients and 19 of their caregivers, in an English hospital between February and November 2014. These indicate that generally patients defer to the doctor in respect of treatment decision-making. Although most patients and their caregivers wanted detailed information and discussion, they did not necessarily expect that this would be provided. Further, patients perceived that signing the consent form was an obligatory routine principally to protect doctors from legal action should something go wrong. Our study suggests that patients’ predominantly paternalistic perceptions of the consent process can not only undermine attempts by doctors to involve them in decision-making but, as patients are now considered in law as informed actors, their perceptions of the consent form as not being in their interests could be a self-fulfilling prophecy if signing is undertaken without due consideration to the content

ORMDL3 expression in ASM regulates hypertrophy, hyperplasia via TPM1 and TPM4, and contractility

ORM1-like 3 (ORMDL3) has strong genetic linkage to childhood onset asthma. To determine whether ORMDL3 selective expression in airway smooth muscle (ASM) influences ASM function, we used Cre-loxP techniques to generate transgenic mice (hORMDL3Myh11eGFP-cre), which express human ORMDL3 selectively in smooth muscle cells. In vitro studies of ASM cells isolated from the bronchi of hORMDL3Myh11eGFP-cre mice demonstrated that they developed hypertrophy (quantitated by FACS and image analysis), developed hyperplasia (assessed by BrdU incorporation), and expressed increased levels of tropomysin proteins TPM1 and TPM4. siRNA knockdown of TPM1 or TPM4 demonstrated their importance to ORMDL3-mediated ASM proliferation but not hypertrophy. In addition, ASM derived from hORMDL3Myh11eGFP-cre mice had increased contractility to histamine in vitro, which was associated with increased levels of intracellular Ca2+; increased cell surface membrane Orai1 Ca2+ channels, which mediate influx of Ca2+ into the cytoplasm; and increased expression of ASM contractile genes sarco/endoplasmic reticulum Ca2+ ATPase 2b and smooth muscle 22. In vivo studies of hORMDL3Myh11eGFP-cre mice demonstrated that they had a spontaneous increase in ASM and airway hyperreactivity (AHR). ORMDL3 expression in ASM thus induces changes in ASM (hypertrophy, hyperplasia, increased contractility), which may explain the contribution of ORMDL3 to the development of AHR in childhood onset asthma, which is highly linked to ORMDL3 on chromosome 17q12-21

Portuguese validation of FACES-IV in adult children caregivers facing parental cancer

The purpose of the present study was to examine the psychometric properties of the FACES-IV in Portuguese caregivers of cancer patients. In this cross-sectional study, a sample of 214 adult children caregivers of cancer patients receiving chemotherapy, completed FACES-IV, Family Communication Scale (FCS), Family Satisfaction Scale (FSS), and Satisfaction with Social Support Scale (SSSS). Internal consistencies above .70 were found for all FACES-IV scales, except for Enmeshed and Rigid scales, as well as for the FCS, FSS, and SSSS (except for Intimacy). Strong correlations between FACES-IV and the validation scales FCS and FSS were found except for the Enmeshed and Rigid scales. Confirmatory analysis yielded an acceptable model for the six theoretical subscales. The discriminant analysis between problematic and non-problematic family systems showed results similar to the original study. These findings suggest that FACES-IV is a valid measure of family functioning in oncological family caregiving’s contexts.Acknowledgments This study was funded by a grant from the Portuguese Foundation for Science and Technology (reference SFRH/BD/43275/2008)

Development and psychometric testing of the online Adolescent Diabetes Needs Assessment Tool (ADNAT)

Supplementary information published since the original article was published.This document is the Accepted Manuscript version of a published work that appeared in final form in World Biomedical Frontiers. To access the final edited and published work see http://biomedfrontiers.org/diabetes-obesity-2015-1-21/.World Biomedical Frontiers provides a platform for the exchange of the latest research progress, including strategic and emerging research areas such as diabetes. Their aim is to accelerate understanding of human health and improvetreatment of a variety of human diseases. Our article, published in the Journal of Advanced Nursing, was selected for their web based publication. It provides an abstract plus supplementary information on the research work associated with ADNAT

A combined prediction strategy increases identification of peptides bound with high affinity and stability to porcine MHC class I molecules SLA-1*04:01, SLA-2*04:01, and SLA-3*04:01

Affinity and stability of peptides bound by major histocompatibility complex (MHC) class I molecules are important factors in presentation of peptides to cytotoxic T lymphocytes (CTLs). In silico prediction methods of peptide-MHC binding followed by experimental analysis of peptide-MHC interactions constitute an attractive protocol to select target peptides from the vast pool of viral proteome peptides. We have earlier reported the peptide binding motif of the porcine MHC-I molecules SLA-1*04:01 and SLA-2*04:01, identified by an ELISA affinity-based positional scanning combinatorial peptide library (PSCPL) approach. Here, we report the peptide binding motif of SLA-3*04:01 and combine two prediction methods and analysis of both peptide binding affinity and stability of peptide-MHC complexes to improve rational peptide selection. Using a peptide prediction strategy combining PSCPL binding matrices and in silico prediction algorithms (NetMHCpan), peptide ligands from a repository of 8900 peptides were predicted for binding to SLA-1*04:01, SLA-2*04:01, and SLA-3*04:01 and validated by affinity and stability assays. From the pool of predicted peptides for SLA-1*04:01, SLA-2*04:01, and SLA-3*04:01, a total of 71, 28, and 38 % were binders with affinities below 500 nM, respectively. Comparison of peptide-SLA binding affinity and complex stability showed that peptides of high affinity generally, but not always, produce complexes of high stability. In conclusion, we demonstrate how state-of-the-art prediction and in vitro immunology tools in combination can be used for accurate selection of peptides for MHC class I binding, hence providing an expansion of the field of peptide-MHC analysis also to include pigs as a livestock experimental model.Fil: Pedersen, Lasse Eggers. Technical University of Denmark; DinamarcaFil: Rasmussen, Michael. Universidad de Copenhagen; DinamarcaFil: Harndahl, Mikkel. Universidad de Copenhagen; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas (subsede Chascomús) | Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas (subsede Chascomús); ArgentinaFil: Buus, Søren. Universidad de Copenhagen; DinamarcaFil: Jungersen, Gregers. Technical University of Denmark; Dinamarc

DNA Fingerprinting of Pearls to Determine Their Origins

We report the first successful extraction of oyster DNA from a pearl and use it to identify the source oyster species for the three major pearl-producing oyster species Pinctada margaritifera, P. maxima and P. radiata. Both mitochondrial and nuclear gene fragments could be PCR-amplified and sequenced. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in the internal transcribed spacer (ITS) region was developed and used to identify 18 pearls of unknown origin. A micro-drilling technique was developed to obtain small amounts of DNA while maintaining the commercial value of the pearls. This DNA fingerprinting method could be used to document the source of historic pearls and will provide more transparency for traders and consumers within the pearl industry

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported. We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected. The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated

Template-Directed Ligation of Tethered Mononucleotides by T4 DNA Ligase for Kinase Ribozyme Selection

Background: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 59 or 29 OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. Methodology/Principal Findings: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 59 phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxy)ribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A2.A1.A3.A4.A0.A6.A8.A10 and T2.T3.T4.T6<T1.T8.T10. Bridging T’s generally gave higher yield of ligated product than bridging A’s. ATP concentrations above 33 mM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (.90%) joined a correctly paired, or T:G wobble-paired, substrate on the 39 side of the ligation junction while discriminating approximately 100-fold against most mispaire

Temporal Dynamics of Visual Attention Allocation

We often temporally prepare our attention for an upcoming event such as a starter pistol. In such cases, our attention should be properly allocated around the expected moment of the event to process relevant sensory input efficiently. In this study, we examined the dynamic changes of attention levels near the expected moment by measuring contrast sensitivity to a target that was temporally cued by a five-second countdown. We found that the overall attention level decreased rapidly after the expected moment, while it stayed relatively constant before it. Results were not consistent with the predictions of existing explanations of temporal attention such as the hazard rate or the stimulus-driven oscillations. A control experiment ruled out the possibility that the observed pattern was due to biased time perception. In a further experiment with a wider range of cue-stimulus-intervals, we observed that attention level increased until the last 500 ms of the interval range, and thereafter, started to decrease. Based on the performances of a generative computational model, we suggest that our results reflect the nature of temporal attention that takes into account the subjectively estimated hazard rate and the probability of relevant events occurring in the near future