Patient safety and the ageing physician: a qualitative study of key stakeholder attitudes and experiences

Background Unprecedented numbers of physicians are practicing past age 65. Unlike other safety-conscious industries, such as aviation, medicine lacks robust systems to ensure late-career physician (LCP) competence while promoting career longevity. Objective To describe the attitudes of key stakeholders about the oversight of LCPs and principles that might shape policy development. Design Thematic content analysis of interviews and focus groups. Participants 40 representatives of stakeholder groups including state medical board leaders, institutional chief medical officers, senior physicians (\u3e65 years old), patient advocates (patients or family members in advocacy roles), nurses and junior physicians. Participants represented a balanced sample from all US regions, surgical and non-surgical specialties, and both academic and non-academic institutions. Results Stakeholders describe lax professional self-regulation of LCPs and believe this represents an important unsolved challenge. Patient safety and attention to physician well-being emerged as key organising principles for policy development. Stakeholders believe that healthcare institutions rather than state or certifying boards should lead implementation of policies related to LCPs, yet expressed concerns about resistance by physicians and the ability of institutions to address politically complex medical staff challenges. Respondents recommended a coaching and professional development framework, with environmental changes, to maximise safety and career longevity of physicians as they age. Conclusions Key stakeholders express a desire for wider adoption of LCP standards, but foresee significant culture change and practical challenges ahead. Participants recommended that institutions lead this work, with support from regulatory stakeholders that endorse standards and create frameworks for policy adoption

REPAIRtoire—a database of DNA repair pathways

REPAIRtoire is the first comprehensive database resource for systems biology of DNA damage and repair. The database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases correlated with mutations in genes encoding DNA repair proteins. REPAIRtoire provides also links to publications and external databases. REPAIRtoire contains information about eight main DNA damage checkpoint, repair and tolerance pathways: DNA damage signaling, direct reversal repair, base excision repair, nucleotide excision repair, mismatch repair, homologous recombination repair, nonhomologous end-joining and translesion synthesis. The pathway/protein dataset is currently limited to three model organisms: Escherichia coli, Saccharomyces cerevisiae and Homo sapiens. The DNA repair and tolerance pathways are represented as graphs and in tabular form with descriptions of each repair step and corresponding proteins, and individual entries are cross-referenced to supporting literature and primary databases. REPAIRtoire can be queried by the name of pathway, protein, enzymatic complex, damage and disease. In addition, a tool for drawing custom DNA–protein complexes is available online. REPAIRtoire is freely available and can be accessed at http://repairtoire.genesilico.pl/

TGF- mediates early angiogenesis and latent fibrosis in an Emilin1-deficient mouse model of aortic valve disease

Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1-/-) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1-/- aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1-/- aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD

Whole scalp resting state EEG of oscillatory brain activity shows no parametric relationship with psychoacoustic and psychosocial assessment of tinnitus: a repeated measures study

Tinnitus is a perception of sound that can occur in the absence of an external stimulus. A brief review of electroencephalography (EEG) and magnetoencephalography (MEG) literature demonstrates that there is no clear relationship between tinnitus presence and frequency band power in whole scalp or source oscillatory activity. Yet a preconception persists that such a relationship exists and that resting state EEG could be utilised as an outcome measure for clinical trials of tinnitus interventions, e.g. as a neurophysiological marker of therapeutic benefit. To address this issue, we first examined the test-retest correlation of EEG band power measures in tinnitus patients (n ¼ 42). Second we examined the evidence for a parametric relationship between numerous commonly used tinnitus variables (psychoacoustic and psychosocial) and whole scalp EEG power spectra, directly and after applying factor reduction techniques. Test-retest correlation for both EEG band power measures and tinnitus variables were high. Yet we found no relationship between whole scalp EEG band powers and psychoacoustic or psychosocial variables. We conclude from these data that resting state whole scalp EEG should not be used as a biomarker for tinnitus and that greater caution should be exercised in regard to reporting of findings to avoid confirmation bias. The data was collected during a randomised controlled trial registered at ClinicalTrials.gov (Identifier: NCT01541969)

BIN1 Localizes the L-Type Calcium Channel to Cardiac T-Tubules

Cardiac tubular-like membrane invaginations contain the membrane scaffolding protein BIN1, which tethers dynamic microtubules that deliver calcium channels directly to T-tubule membrane

Characterisation and validation of insertions and deletions in 173 patient exomes.

Recent advances in genomics technologies have spurred unprecedented efforts in genome and exome re-sequencing aiming to unravel the genetic component of rare and complex disorders. While in rare disorders this allowed the identification of novel causal genes, the missing heritability paradox in complex diseases remains so far elusive. Despite rapid advances of next-generation sequencing, both the technology and the analysis of the data it produces are in its infancy. At present there is abundant knowledge pertaining to the role of rare single nucleotide variants (SNVs) in rare disorders and of common SNVs in common disorders. Although the 1,000 genome project has clearly highlighted the prevalence of rare variants and more complex variants (e.g. insertions, deletions), their role in disease is as yet far from elucidated.We set out to analyse the properties of sequence variants identified in a comprehensive collection of exome re-sequencing studies performed on samples from patients affected by a broad range of complex and rare diseases (N = 173). Given the known potential for Loss of Function (LoF) variants to be false positive, we performed an extensive validation of the common, rare and private LoF variants identified, which indicated that most of the private and rare variants identified were indeed true, while common novel variants had a significantly higher false positive rate. Our results indicated a strong enrichment of very low-frequency insertion/deletion variants, so far under-investigated, which might be difficult to capture with low coverage and imputation approaches and for which most of study designs would be under-powered. These insertions and deletions might play a significant role in disease genetics, contributing specifically to the underlining rare and private variation predicted to be discovered through next generation sequencing

Pathological lesions in European bison [Bison bonasus] with infestation by Ashworthius sidemi [Nematoda, Trichostrongylidae]

Asworthius sidemi Schulz, 1933 is a blood sucking gastrointestinal nematode, primarily typical for Asiatic deer. It was found for the first time in Poland in European bison in 1997. To estimate the level of invasion of A. sidemi and histopathological changes connected with the presence of the parasite in the years 2004-2007 parasitological and histopathological examinations of 54 European bison from Białowieża Forest were carried out. Parasitological examination was carried out by the sedimentation method and A. sidemi were diagnosed under a binocular microscope. Samples for histological examination were collected from the abomasum and duodenum walls as well as from regional lymph nodes. Tissue samples were then fixed with 10% buffered formalin, embedded in paraffin, cut in to 5 μm thick sections and stained with hematoxylin and eosin (H&E). Parasitological examinations showed the presence of fourth stage larvae and juvenile forms of A. sidemi. The maximal intensity of invasion rose systematically from 4470 A. sidemi nematodes in 2004/2005 to 44310 in 2006/2007. Histopathological examinations showed infiltrations of inflammatory cells in the walls of abomasa and duodena at various levels of intensity (mainly lymphoid cells and eosinophils), hyperemiae, oedemae and lesions of mucosa and proliferation of lymphatic follicles. In individual cases of dysplasia of epithelial cells, atrophy or hyperplasia of glands and the presence of parasites in the lumen or walls of the abomasum/duodenum were observed. In one case, parasitic nodules were found. In regional lymph nodes proliferation of lymphatic follicles, presence of eosinophils and desolation of reproduction centers were observed. Intensification of histopathological changes was connected to a considerable degree with the developmental stage of A. sidemi as shown by parasitological examination

Determination of limits of ashworthiosis foci in eastern and southern Poland

The task was to establish the foci of ashworthiosis. The locations were: Białowieża Forest and Bieszczady Mountains. The wild cervides including: 52 red deer and 15 roe deer as well as domestic ruminants: 17 cattle and 18 sheep were examined parasitologically. Also, the examination was extended to neighbouring and additional areas. Contents of abomasa after multiple decantation were conserved with 2% formaldehyde. All nematodes were isolated from the contest, cleared in 70% ethanol with 5% glycerol and determinated to the species on the basis of structure of bursa copulatrix. Intensity of invasions of red deer oscillated from 3 to 296 specimens of A. sidemi and of roe deer from 42 to 545 nematodes. There were found none of domestic ruminants infected with this nematode in areas neighbouring with woods in both foci. Examinations showed that relatively new (found in 2000 year) focus of ashworthiosis in Polish part of Białowieża Forest has not dispersed yet beyond the limits of this forest complex. However, focus of ashworthiosis found in Bieszczady Mountains in 1997 year initially in Lutowiska Forest District expanded on the area of neighbouring Bieszczady forest districts: Komańcza, Cisna and Baligród and also on the area of Forest District Krasiczyn lying in Pogórze Przemyskie. So it is necessary further monitoring of status of A. sidemi infection of wild and domestic ruminants in neighbouring of both till now found foci

The Impact of Humic Substances as Remediation Agents to the Speciation Forms of Metals in Soil

AbstractHumic substances (HS) are the most widespread group of organic substances in natural environment and have high stability. The main terrestrial reserves are found in the form of naturally occurring ore, peat or lignite. The aim of this paper is to study possibilities to use HS as agents for remediation of contaminated with heavy metals soil and impacts of HS of metal speciation forms in it. It has been proved that HS are able to bind to metal ions and change their speciation forms in soils. The ability to form complexes with metal ions depends on the type of soil, type of metal, as well as concentrations of HS in soil. The study was carried out in experimental conditions and analytical method to determine availability of metals to living organisms was used for spiked soils. Remediation by using HS has shown good result for diminishing the content of biologically available copper and lead