Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity

Background: Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.<p></p> Results: Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.<p></p> Conclusions: Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.<p></p&gt

Dissociation of Subjectively Reported and Behaviorally Indexed Mind Wandering by EEG Rhythmic Activity

Inattention to current activity is ubiquitous in everyday situations. Mind wandering is an example of such a state, and its related brain areas have been examined in the literature. However, there is no clear evidence regarding neural rhythmic activities linked to mind wandering. Using a vigilance task with thought sampling and electroencephalography recording, the current study simultaneously examined neural oscillatory activities related to subjectively reported and behaviorally indexed mind wandering. By implementing time-frequency analysis, we found that subjectively reported mind wandering, relative to behaviorally indexed, showed increased gamma band activity at bilateral frontal-central areas. By means of beamformer source imaging, we found subjectively reported mind wandering within the gamma band to be characterized by increased activation in bilateral frontal cortices, supplemental motor area, paracentral cortex and right inferior temporal cortex in comparison to behaviorally indexed mind wandering. These findings dissociate subjectively reported and behaviorally indexed mind wandering and suggest that a higher degree of executive control processes are engaged in subjectively reported mind wandering

Ectopic thyroid presenting as a submental mass: A case report

Thyroid ectopia affects roughly 1/100,000 people, with the majority of patients having hypofunctional thyroid tissue and an absent orthotopic gland. If not recognized early, thyroid ectopia may cause diagnostic dilemmas and result in unnecessary workup. Through the use of basic radiographic and histologic analyses, these lesions can be properly identified while also ruling out more common clinical entities. Conservative management remains a legitimate option for many patients, with surgical intervention reserved for severe symptoms or malignancy. We describe the case of a woman with an impressive sublingual ectopic thyroid gland who was managed successfully with conservative strategies

Preconditioning of mesenchymal stem cells for improved transplantation efficacy in recessive dystrophic epidermolysis bullosa

INTRODUCTION: The use of hematopoietic cell transplantation (HCT) has previously been shown to ameliorate cutaneous blistering in pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB), an inherited skin disorder that results from loss-of-function mutations in COL7A1 and manifests as deficient or absent type VII collagen protein (C7) within the epidermal basement membrane. Mesenchymal stem cells (MSCs) found within the HCT graft are believed to be partially responsible for this amelioration, in part due to their intrinsic immunomodulatory and trophic properties and also because they have been shown to restore C7 protein following intradermal injections in models of RDEB. However, MSCs have not yet been demonstrated to improve disease severity as a stand-alone systemic infusion therapy. Improving the efficacy and functional utility of MSCs via a pre-transplant conditioning regimen may bring systemic MSC infusions closer to clinical practice. METHODS: MSCs were isolated from 2- to 4-week-old mice and treated with varying concentrations of transforming growth factor-β (TGFβ; 5-20 ng/mL), tumor necrosis factor- α (TNFα; 10-40 ng/mL), and stromal cell-derived factor 1-α (SDF-1α; 30 ng/mL) for 24-72 hours. RESULTS: We demonstrate that treating murine MSCs with exogenous TGFβ (15 ng/mL) and TNFα (30 ng/mL) for 48 hours induces an 8-fold increase in Col7a1 expression and a significant increase in secretion of C7 protein, and that the effects of these cytokines are both time and concentration dependent. This cytokine treatment also promotes a 4-fold increase in Tsg-6 expression, a gene whose product is associated with improved wound-healing and immunosuppressive features. Finally, the addition of exogenous SDF-1α to this regimen induces a simultaneous upregulation of Col7a1, Tsg-6, and Cxcr4 expression. CONCLUSIONS: These data suggest that preconditioning represents a feasible method for improving the functional utility of MSCs in the context of RDEB stem cell transplantation, and also highlight the applicability of preconditioning principles toward other cell-based therapies aimed at treating RDEB patients

Gamma band beamformer analysis showed increased neural activity associated with subjective reported mind wandering relative to behavioral indexed mind wandering.

<p>The results were superimposed on a group-averaged T1 MRI image. X/Y/Z are MNI coordinates. MFC = middle frontal cortex; IFC = inferior frontal cortex; SMA = supplemental motor area; ParaCC = paracentral cortex; ITC = inferior temporal cortex.</p

Topographical distributions of the enhanced gamma band activity associated with subjectively reported mind wandering relative to behavioral indexed mind wandering.

<p>The values are the statistical results of the differences. The ‘X’ marks the significant clusters of electrodes in the topographies.</p

Behavioral results.

<p>(a) Trial number under each condition, error bars indicate standard errors of the mean; (b) Positive correlation between trial number of off-task and trial number of missed target, and positive correlation between trial number of on-task and trial number of hit target. The data of each subject is indicated by a triangle or circle. The lines represent the linear best fit.</p

Clinical and functional outcomes after total laryngectomy and laryngopharyngectomy: Analysis by tumor subsite, salvage status, and extent of resection

Background: Outcomes following surgical intervention for laryngeal and hypopharyngeal tumors are dependent on several factors. In the present study, we sought to determine whether tumor subsite, salvage status, and extent of resection influenced postoperative outcomes. Methods: Retrospective review of 107 patients at a single institution who underwent total laryngectomy or partial/total laryngopharyngectomy. Results: Hypopharyngeal subsite and total laryngopharyngectomy subgroups had inferior speech and swallow outcomes compared to their respective cohorts (P \u3c.05). Salvage patients had inferior 3-year overall survival (P \u3c.05) and swallow outcomes (P \u3c.001). Previously radiated patients had increased fistula rates (29.9% vs 10%, P =.02), and the use of tissue coverage in salvage total laryngectomy had a protective effect on fistula formation (10% vs 37%, P =.04). Conclusions: By stratifying patients across multiple subgroups, we provide a detailed narrative in surgical outcomes that can be incorporated into treatment planning. Further prospective studies are needed to compare surgical outcomes to those of organ preservation therapy

Clinical and functional outcomes after total laryngectomy and laryngopharyngectomy: Analysis by tumor subsite, salvage status, and extent of resection

Background: Outcomes following surgical intervention for laryngeal and hypopharyngeal tumors are dependent on several factors. In the present study, we sought to determine whether tumor subsite, salvage status, and extent of resection influenced postoperative outcomes. Methods: Retrospective review of 107 patients at a single institution who underwent total laryngectomy or partial/total laryngopharyngectomy. Results: Hypopharyngeal subsite and total laryngopharyngectomy subgroups had inferior speech and swallow outcomes compared to their respective cohorts (P \u3c.05). Salvage patients had inferior 3-year overall survival (P \u3c.05) and swallow outcomes (P \u3c.001). Previously radiated patients had increased fistula rates (29.9% vs 10%, P =.02), and the use of tissue coverage in salvage total laryngectomy had a protective effect on fistula formation (10% vs 37%, P =.04). Conclusions: By stratifying patients across multiple subgroups, we provide a detailed narrative in surgical outcomes that can be incorporated into treatment planning. Further prospective studies are needed to compare surgical outcomes to those of organ preservation therapy

Randomized Controlled Pilot Study of Video Self-assessment for Resident Mastoidectomy Training

A prospective randomized controlled pilot study was performed to determine if video self-assessment improves competency in mastoidectomy and to assess interrater agreement between expert and resident evaluations of recorded mastoidectomy. Sixteen otolaryngology residents were recorded while performing cadaveric mastoidectomy and randomized into video self-assessment and control groups. All residents performed a second recorded mastoidectomy. Performance was evaluated by blinded experts with a validated assessment scale. Video self-assessment did not lead to greater skill improvement between the first and second mastoidectomy. Interrater agreement was fair to substantial between the expert evaluators and between resident self-evaluations by recall and video review. Agreement between experts and residents was only slight to fair; residents consistently rated their performance higher than experts ( P < .05). In conclusion, 1 session of video self-review did not lead to improved competence in mastoidectomy over standard practice. While experts agree on assessments, residents may overestimate their competency in performing cadaveric mastoidectomy