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Cultural values are crucial to the practice and impact of patient and public involvement (PPI) in research.
To understand different PPI cultures among research teams and the impacts of PPI associated with each culture type.
A participatory action research design.
The setting was 10 palliative care research projects. Seventeen patients and members of the public and 31 researchers participated.
A programme consisting of four components (1) training and coaching of patients and the public to prepare them for participation in research, (2) tailored coaching of the 10 research teams over 12-18months, (3) a community of practice, and (4) a qualitative evaluation.
We identified three cultures types relationship cultures, task cultures, and control cultures. We identified four areas of impact the project aim became more relevant to the target audience, methodological reliability increased, the research products were better able to reach the public, and the awareness increased, associated with behavioural changes, among researchers regarding PPI.
A relationship culture appears to be long-lasting due to impacting the behaviours of the researchers during future projects. Different cultural types require different types of patients and researcher participants, assigned to different tasks.
Further research remains necessary to investigate the support required by researchers to enable relationship- and task-oriented PPI cultures.
Patient advocates and representatives contributed to our research team throughout the entire research process, as well as within the 10 implementation projects.
Patient advocates and representatives contributed to our research team throughout the entire research process, as well as within the 10 implementation projects.Human purine nucleoside phosphorylase (HsPNP) belongs to the purine salvage pathway of nucleic acids. Genetic deficiency of this enzyme triggers apoptosis of activated T-cells due to the accumulation of deoxyguanosine triphosphate (dGTP). Therefore, potential chemotherapeutic applications of human PNP inhibitors include the treatment of T-cell leukemia, autoimmune diseases and transplant tissue rejection. In this report, we present the discovery of novel HsPNP inhibitors by coupling experimental and computational tools. A simple, inexpensive, direct and non-radioactive enzymatic assay coupled to hydrophilic interaction liquid chromatography and UV detection (LC-UV using HILIC as elution mode) was developed for screening HsPNP inhibitors. Enzymatic activity was assessed by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx) by LC-UV. A small library of 6- and 8-substituted nucleosides was synthesized and screened. The inhibition potency of the most promising compound, 8-aminoinosine (4), was quantified through Ki and IC50 determinations. The effect of HsPNP inhibition was also evaluated in vitro through the study of cytotoxicity on human T-cell leukemia cells (CCRF-CEM). Docking studies were also carried out for the most potent compound, allowing further insights into the inhibitor interaction at the HsPNP active site. This study provides both new tools and a new lead for developing novel HsPNP inhibitors.We describe the clinical, electrodiagnostic, and genetic findings of three homozygous FIG4-c.122T>C patients suffering from Charcot-Marie-Tooth disease type 4J (AR-CMT-FIG4). see more This syndrome usually involves compound heterozygosity associating FIG4-c.122T>C, a hypomorphic allele coding an unstable FIG4-p.Ile41Thr protein, and a null allele. While the compound heterozygous patients presenting with early onset usually show rapid progression, the homozygous patients described here show the signs of relative clinical stability. As FIG4 activity is known to be dose dependent, these patients' observations could suggest that the therapeutic perspective of increasing levels of the protein to improve the phenotype of AR-CMT-FIG4-patients might be efficient.
Due to the chemical and morphological differences between primary vs. permanent teeth, the time reduction of the acid etching or acidic primer can result in higher values of bond strength.
To assess through a systematic review and meta-analysis the influence of the reducing etching (acid etching or acidic primer) time on the bond strength of adhesive systems to primary dentin.
A systematic search was carried out in 3 databases PubMed, Web of Science and Scopus. Studies that evaluated the effect of reducing the etching time on the bond strength of adhesive systems to primary dentin were included. Meta-analyses were performed using a random-effects model, with subgroups for etch-and-rinse and self-etching adhesives, with a significance level of P<.05. The risk of bias and heterogeneity between studies (Cochrane and I2 tests) were assessed.
Eight studies were included in the systematic review and seven in the meta-analyses. The shortening etching time did not influence the immediate dentin bond strength for etch-and-rinse (Z=0.07, P=.95) and self-etching adhesives (Z=0.41, P=.69). After ageing, however, the shorting etching time improved the bond strength for etch-and-rinse adhesives (Z=2.01, P=.04). All studies presented high bias risk.
Reducing the acid-etching time to primary dentin improves the long-term bond strength to this substrate.
Reducing the acid-etching time to primary dentin improves the long-term bond strength to this substrate.Iron (Fe) deficient plants employ multiple strategies to increase root uptake and root-to-shoot translocation of Fe. The identification of genes that are responsible for these processes, and a comprehensive understanding of the regulatory effects of transcriptional networks on their expression, including transcription factors (TFs), is underway in Arabidopsis thaliana. Here, we show that a Histone- or heme-associated proteins (HAP) transcription factor (TF), HAP5A, is necessary for the response to Fe deficiency in Arabidopsis. Its expression was induced under Fe deficiency, and the lack of HAP5A significantly decreased Fe translocation from the root to the shoot, resulting in substantial chlorosis of the newly expanded leaves, compared with the wild-type (WT, Col-0). Further analysis found that the expression of a gene encoding nicotianamine (NA) synthase (NAS1) was dramatically decreased in the hap5a mutant, regardless of the Fe status. Yeast-one-hybrid and ChIP analyses suggested that HAP5A directly binds to the promoter region of NAS1.