Cytologic features of nipple aspirate fluid using an automated non-invasive collection device: a prospective observational study

BACKGROUND: Detection of cytologic atypia in nipple aspirate fluid (NAF) has been shown to be a predictor of risk for development of breast carcinoma. Manual collection of NAF for cytologic evaluation varies widely in terms of efficacy, ease of use, and patient acceptance. We investigated a new automated device for the non-invasive collection of NAF in the office setting. METHODS: A multi-center prospective observational clinical trial involving asymptomatic women designed to assess fluid production, adequacy, safety and patient acceptance of the HALO NAF Collection System (NeoMatrix, Irvine, CA). Cytologic evaluation of all NAF samples was performed using previously described classification categories. RESULTS: 500 healthy women were successfully enrolled. Thirty-eight percent (190/500) produced fluid and 187 were available for cytologic analysis. Cytologic classification of fluid producers showed 50% (93/187) Category 0 (insufficient cellular material), 38% (71/187) Category I (benign non-hyperplastic ductal epithelial cells), 10% (18/187) Category II (benign hyperplastic ductal epithelial cells), 3% (5/187) Category III (atypical ductal epithelial cells) and none were Category IV (unequivocal malignancy). Overall, 19% of the subjects produced NAF with adequate cellularity and 1% were found to have cytologic atypia. CONCLUSION: The HALO system is a simple, safe, rapid, automated method for standardized collection of NAF which is acceptable to patients. Cytologic assessment of HALO-collected NAF showed the ability to detect benign and pre-neoplastic ductal epithelial cells from asymptomatic volunteers

The FlbA-regulated predicted transcription factor Fum21 of <i>Aspergillus niger</i> is involved in fumonisin production

Aspergillus niger secretes proteins throughout the colony except for the zone that forms asexual spores called conidia. Inactivation of flbA that encodes a regulator of G-protein signaling results in colonies that are unable to reproduce asexually and that secrete proteins throughout the mycelium. In addition, the ΔflbA strain shows cell lysis and has thinner cell walls. Expression analysis showed that 38 predicted transcription factor genes are differentially expressed in strain ΔflbA. Here, the most down-regulated predicted transcription factor gene, called fum21, was inactivated. Growth, conidiation, and protein secretion were not affected in strain Δfum21. Whole genome expression analysis revealed that 63 and 11 genes were down- and up-regulated in Δfum21, respectively, when compared to the wild-type strain. Notably, 24 genes predicted to be involved in secondary metabolism were down-regulated in Δfum21, including 10 out of 12 genes of the fumonisin cluster. This was accompanied by absence of fumonisin production in the deletion strain and a 25% reduction in production of pyranonigrin A. Together, these results link FlbA-mediated sporulation-inhibited secretion with mycotoxin production

Characterization of a modular enzyme of exo-1,5-α-l-arabinofuranosidase and arabinan binding module from Streptomyces avermitilis NBRC14893

A gene encoding an α-l-arabinofuranosidase, designated SaAraf43A, was cloned from Streptomyces avermitilis. The deduced amino acid sequence implies a modular structure consisting of an N-terminal glycoside hydrolase family 43 module and a C-terminal family 42 carbohydrate-binding module (CBM42). The recombinant enzyme showed optimal activity at pH 6.0 and 45°C and was stable over the pH range of 5.0–6.5 at 30°C. The enzyme hydrolyzed p-nitrophenol (PNP)-α-l-arabinofuranoside but did not hydrolyze PNP-α-l-arabinopyranoside, PNP-β-d-xylopyranoside, or PNP-β-d-galactopyranoside. Debranched 1,5-arabinan was hydrolyzed by the enzyme but arabinoxylan, arabinogalactan, gum arabic, and arabinan were not. Among the synthetic regioisomers of arabinofuranobiosides, only methyl 5-O-α-l-arabinofuranosyl-α-l-arabinofuranoside was hydrolyzed by the enzyme, while methyl 2-O-α-l-arabinofuranosyl-α-l-arabinofuranoside and methyl 3-O-α-l-arabinofuranosyl-α-l-arabinofuranoside were not. These data suggested that the enzyme only cleaves α-1,5-linked arabinofuranosyl linkages. The analysis of the hydrolysis product of arabinofuranopentaose suggested that the enzyme releases arabinose in exo-acting manner. These results indicate that the enzyme is definitely an exo-1,5-α-l-arabinofuranosidase. The C-terminal CBM42 did not show any affinity for arabinogalactan and debranched arabinan, although it bound arabinan and arabinoxylan, suggesting that the CBM42 bound to branched arabinofuranosyl residues. Removal of the module decreased the activity of the enzyme with regard to debranched arabinan. The CBM42 plays a role in enhancing the debranched arabinan hydrolytic action of the catalytic module in spite of its preference for binding arabinofuranosyl side chains

Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons

Background. The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health. Methods. A longitudinal, non-controlled design was used. The programme consisted of two weekly exercise sessions and one weekly cognitive session during 12 weeks. The main outcome measures were body mass index, blood pressure, cardiorespiratory fitness, abd

Qualitative study on the implementation of professional pharmacy services in Australian community pharmacies using framework analysis

Abbreviations: BCT, Behavioural change techniques taxonomy; BCW, Behavioural change wheel; CFIR, Consolidated framework for implementation research; EPOC, Cochrane effective practice and organisation of care; FISpH, Framework for the implementation of services in pharmacy; GIF, Generic implementation framework; KPI, Key performance indicator; TDF, Theoretical domains frameworkBackground: Multiple studies have explored the implementation process and influences, however it appears there is no study investigating these influences across the stages of implementation. Community pharmacy is attempting to implement professional services (pharmaceutical care and other health services). The use of implementation theory may assist the achievement of widespread provision, support and integration. The objective was to investigate professional service implementation in community pharmacy to contextualise and advance the concepts of a generic implementation framework previously published. Methods: Purposeful sampling was used to investigate implementation across a range of levels of implementation in community pharmacies in Australia. Twenty-five semi-structured interviews were conducted and analysed using a framework methodology. Data was charted using implementation stages as overarching themes and each stage was thematically analysed, to investigate the implementation process, the influences and their relationships. Secondary analyses were performed of the factors (barriers and facilitators) using an adapted version of the Consolidated Framework for Implementation Research (CFIR), and implementation strategies and interventions, using the Expert Recommendations for Implementing Change (ERIC) discrete implementation strategy compilation. Results: Six stages emerged, labelled as development or discovery, exploration, preparation, testing, operation and sustainability. Within the stages, a range of implementation activities/steps and five overarching influences (pharmacys' direction and impetus, internal communication, staffing, community fit and support) were identified. The stages and activities were not applied strictly in a linear fashion. There was a trend towards the greater the number of activities considered, the greater the apparent integration into the pharmacy organization. Implementation factors varied over the implementation stages, and additional factors were added to the CFIR list and definitions modified/contextualised for pharmacy. Implementation strategies employed by pharmacies varied widely. Evaluations were lacking. Conclusions: The process of implementation and five overarching influences of professional services implementation in community pharmacy have been outlined. Framework analysis revealed, outside of the five overarching influences, factors influencing implementation varied across the implementation stages. It is proposed at each stage, for each domain, the factors, strategies and evaluations should be considered. The Framework for the Implementation of Services in Pharmacy incorporates the contextualisation of implementation science for pharmacy.The study was funded as part of a University of Technology Sydney (UTS) Research Excellence Scholarship (RES), comprising of an Australian Postgraduate Award (APA) Scholarship funded by the Australian Government, plus a Top-up funded by the University of Technology Sydney, received from the primary author (JCM)

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal speciesFilamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.National Science Foundation (grant number DEB-1442113). Received by AR. U.S. National Library of Medicine training grant (grant number 2T15LM007450). Received by ALL. Conselho Nacional de Desenvolvimento Cientı´fico e 573 Tecnológico. Northern Portugal Regional Operational Programme (grant number NORTE-01- 0145-FEDER-000013). Received by FR. Fundação de Amparo à Pesquisa do 572 Estado de São Paulo. Received by GHG. National Institutes of Health (grant number R01 AI065728-01). Received by NPK. National Science Foundation (grant number IOS-1401682). Received by JHW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio