Small chromosomes among Danish Candida glabrata isolates originated through different mechanisms

We analyzed 192 strains of the pathogenic yeast Candida glabrata from patients, mainly suffering from systemic infection, at Danish hospitals during 1985-1999. Our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. Nine strains contained small chromosomes, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, these C. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to each other (i.e. they contained different sets of genes). We suggest that at least two mechanisms could participate in their origin: (i) through a segmental duplication which covered the centromeric region, or (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of small chromosomes carrying duplicated genes exhibited mitotic instability, while the second type, which contained the corresponding genes in only one copy in the genome, was mitotically stable. Apparently, in patients C. glabrata chromosomes are frequently reshuffled resulting in new genetic configurations, including appearance of small chromosomes, and some of these resulting "mutant" strains can have increased fitness in a certain patient "environment"

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway

Background: reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. Methods: to test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. Results: correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. Conclusions: in summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue

Towards system-wide implementation of the International Classification of Functioning, Disability and Health (ICF) in routine practice: Developing simple, intuitive descriptions of ICF categories in the ICF Generic and Rehabilitation Set

Objective: A national, multi-phase, consensus process to develop simple, intuitive descriptions of International Classification of Functioning, Disability and Health (ICF) categories contained in the ICF Generic and Rehabilitation Sets, with the aim of enhancing the utility of the ICF in routine clinical practice, is presented in this study.Methods: A multi-stage, national, consensus process was conducted. The consensus process involved 3 expert groups and consisted of a preparatory phase, a consensus conference with consecutive working groups and 3 voting rounds (votes A, B and C), followed by an implementation phase. In the consensus conference, participants first voted on whether they agreed that an initially developed proposal for simple, intuitive descriptions of an ICF category was in fact simple and intuitive.Results: The consensus conference was held in August 2014 in mainland China. Twenty-one people with a background in physical medicine and rehabilitation participated in the consensus process. Four ICF categories achieved consensus in vote A, 16 in vote B, and 8 in vote C.Discussion: This process can be seen as part of a larger effort towards the system-wide implementation of the ICF in routine clinical and rehabilitation practice to allow for the regular and comprehensive evaluation of health outcomes most relevant for the monitoring of quality of care.Chinese Mainland Affairs Offic

Erratum: Prolonged monitoring of cerebral blood flow and autoregulation with diffuse correlation spectroscopy in neurocritical care patients

Corrected disclosures for the article “Prolonged monitoring of cerebral blood flow and autoregulation with diffuse correlation spectroscopy in neurocritical care patients.” DOI: 10.1117/1.NPh.5.4.045005.Published versio

Towards the system-wide implementation of the International Classification of Functioning, Disability, and Health in routine clinical practice: Empirical findings of a pilot study from Mainland China

Objective: The aims of this study were to evaluate the feasibility of using the International Classification of Functioning, Disability and Health (ICF) Generic Set in routine clinical practice, and of creating a functioning score based on it, and, subsequently, to examine its sensitivity to change.Methods: In this prospective cohort study, data from 761 adult inpatients from 21 Chinese hospitals were analysed. Each patient was assessed at admission and discharge. Feasibility was evaluated by analysing mean assessment time. The Rasch model was used to create a metric of functioning. Sensitivity to change was analysed with mixed-effects regression and by calculating standardized effect size based on Cohen's f2.Results: Mean duration of assessment was 5.3 min, with a significant decrease between admission and discharge. After removal of the item remunerative employment, the remaining ICF Generic Set categories fitted the Rasch model well. With a mean improvement in functioning of 12.1(95% confidence interval (95% CI):11.5-12.6), this metric proved sensitive to change, both in terms of statistical significance (p < 0.001) and standardized effect size (Cohen's f2=2.35).Discussion: The ICF Generic Set is feasible for use in routine clinical practice and is promising to serve as the basis for the development of a functioning score that is sensitive to change.Chinese Mainland Affairs Offic

Developing additional competition classes for athletes with intellectual impairments: Conceptual approach and efficacy of an ICF derived measure

The purpose of para sport classification systems is to minimise the impact of impairment on competition outcome. Currently, athletes with intellectual impairment (II) compete in one class, regardless of the extent of activity limitation resulting from their impairment. Consequently, athletes with II that cause relatively minor difficulty in sport have a competitive advantage over athletes who have intellectual impairments that cause more significant advantage. This research investigated the efficacy of a measure of health-related functional impairment, derived from the World Health Organisation International Classification of Functioning, Disability, and Health (ICF), as a tool to classify athletes with intellectual impairments (II) into groups with impairments that cause similar activity limitation. The first study used a Delphi technique to identify the most relevant codes within the ICF from which a measure of impairment presence and severity was derived. The second study investigated whether the measure could discriminate between groups of II athletes organised into three competition groups, and whether these groups could be predicted by ICF score. The ICF based questionnaire shows promise as a conceptual approach and as a tool in this context, but this is a preliminary step before establishing a sport-specific approach to classification

Coherent Random Lasing Realized in Polymer Vesicles

We have demonstrated the realization of a coherent vesicle random lasing (VRL) from the dye doped azobenzene polymer vesicles self-assembled in the tetrahydrofuran-water system, which contains a double-walled structure: a hydrophilic and hydrophobic part. The effect of the dye and azobenzene polymer concentration on the threshold of random laser has been researched. The threshold of random laser decreases with an increase in the concentration of the pyrromethene 597 (PM597) laser and azobenzene polymer. Moreover, the scattering of small size group vesicles is attributed to providing a loop to boost the coherent random laser through the Fourier transform analysis. Due to the vesicles having the similar structure with the cell, the generation of coherent random lasers from vesicles expand random lasers to the biomedicine filed

Factors impacting employment for people with autism spectrum disorder: A scoping review

The aim of this study is to holistically synthesise the extent and range of literature relating to the employment of individuals with autism spectrum disorder. Database searches of Medline, CINAHL, PsychINFO, Scopus, ERIC, Web of Science and EMBASE were conducted. Studies describing adults with autism spectrum disorder employed in competitive, supported or sheltered employment were included. Content analysis was used to identify the strengths and abilities in the workplace of employees with autism spectrum disorder. Finally, meaningful concepts relating to employment interventions were extracted and linked to the International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder. The search identified 134 studies for inclusion with methodological quality ranging from limited to strong. Of these studies, only 36 evaluated employment interventions that were coded and linked to the International Classification of Functioning, Disability and Health, primarily focusing on modifying autism spectrum disorder characteristics for improved job performance, with little consideration of the impact of contextual factors on work participation. The International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder are a useful tool in holistically examining the employment literature for individuals with autism spectrum disorder. This review highlighted the key role that environmental factors play as barriers and facilitators in the employment of people with autism spectrum disorder and the critical need for interventions which target contextual factors if employment outcomes are to be improved