Aspergillus mastoiditis, presenting with unexplained progressive otalgia, in an immunocompetent (older) patient

Aspergillus mastoidits and skull-base osteomyelitis are extremely rare, even in immunocompromised patients. We report a case of an 81-year-old immunocompetent man, who underwent a mastoidectomy because of unexplained, progressive otalgia in spite of a noninflamed and air-containing middle-ear space. Histopathology yielded Aspergillus fumigatus. When confronted with otitis with an unexpected clinical course a high index of suspicion is required to facilitate early diagnosis and appropriate therapy of a potential lethal Aspergillus infection, even in immunocompetent patients. This seems to be more so in older patients with an open middle-ear cavity and/or when there is facial nerve involvement

Health-related characteristics and preferred methods of receiving health education according to dominant language among Latinos Aged 25 to 64 in a large Northern California health plan

<p>Abstract</p> <p>Background</p> <p>Latinos are a fast growing segment of the U.S. health care population. Acculturation factors, including English fluency, result in an ethnic group heterogeneous with regard to SES, health practices, and health education needs. This study examined how demographic and health-related characteristics of Spanish-dominant (SD), Bilingual (BIL), and English-dominant (ED) Latino men and women aged 25–64 differed among members of a large Northern California health plan.</p> <p>Methods</p> <p>This observational study was based on data from cohorts of 171 SD (requiring an interpreter), 181 BIL, and 734 ED Latinos aged 25–64 who responded to random sample health plan member surveys conducted 2005–2006. Language groups were compared separately by gender on education, income, behavioral health risks (smoking, obesity, exercise frequency, dietary practices, health beliefs), health status (overall health and emotional health, diabetes, hypertension, high cholesterol, heartburn/acid reflux, back pain, depression), computer and Internet access, and health education modality preferences.</p> <p>Results</p> <p>Compared with ED Latinos, higher percentages of the SD and BIL groups had very low educational attainment and low income. While groups were similar in prevalence of diabetes, hypertension, and high cholesterol, SD were less likely than ED Latinos to rate overall health and emotional well-being as good, very good, or excellent and more likely to report heartburn and back pain (women only). The groups were similar with regard to smoking and obesity, but among women, SD were more likely to be physically inactive than ED, and BIL were less likely than SD and ED groups to eat <3 servings of fruit/vegetables per day. SD and BIL of both genders were significantly less likely than ED Latinos to believe that health practices had a large impact on health. Compared to ED men and women, SD and BIL Latinos had significantly lower Internet and computer access. As a result, SD Latinos had a greater preference for lower technology health education modalities such as videos and taped phone messages.</p> <p>Conclusion</p> <p>There are important differences among Latinos of different English language proficiency with regard to education, income, health status, health behaviors, IT access, and health education modality preferences that ought to be considered when planning and implementing health programs for this growing segment of the U.S. population.</p

Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma

Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaig

O2‐08‐05: Neuronal Injury and Degeneration Evaluated with Imaging and CSF Biomarkers in Autosomal Dominant Alzheimer’s Disease: Results from the Dian Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152556/1/alzjjalz201606440.pd

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Mechanical and kinetic effects of shortened tropomyosin reconstituted into myofibrils

The effects of tropomyosin on muscle mechanics and kinetics were examined in skeletal myofibrils using a novel method to remove tropomyosin (Tm) and troponin (Tn) and then replace these proteins with altered versions. Extraction employed a low ionic strength rigor solution, followed by sequential reconstitution at physiological ionic strength with Tm then Tn. SDS-PAGE analysis was consistent with full reconstitution, and fluorescence imaging after reconstitution using Oregon-green-labeled Tm indicated the expected localization. Myofibrils remained mechanically viable: maximum isometric forces of myofibrils after sTm/sTn reconstitution (control) were comparable (~84%) to the forces generated by non-reconstituted preparations, and the reconstitution minimally affected the rate of isometric activation (kact), calcium sensitivity (pCa50), and cooperativity (nH). Reconstitutions using various combinations of cardiac and skeletal Tm and Tn indicated that isoforms of both Tm and Tn influence calcium sensitivity of force development in opposite directions, but the isoforms do not otherwise alter cross-bridge kinetics. Myofibrils reconstituted with Δ23Tm, a deletion mutant lacking the second and third of Tm’s seven quasi-repeats, exhibited greatly depressed maximal force, moderately slower kact rates and reduced nH. Δ23Tm similarly decreased the cooperativity of calcium binding to the troponin regulatory sites of isolated thin filaments in solution. The mechanisms behind these effects of Δ23Tm also were investigated using Pi and ADP jumps. Pi and ADP kinetics were indistinguishable in Δ23Tm myofibrils compared to controls. The results suggest that the deleted region of tropomyosin is important for cooperative thin filament activation by calcium

Creating Creative Technologists: playing with(in) education

Since the industrial revolution, the organization of knowledge into distinct scientific, technical or creative categories has resulted in educational systems designed to produce and validate particular occupations. The methods by which students are exposed to different kinds of knowledge are critical in creating and reproducing individual, professional or cultural identities. (“I am an Engineer. You are an Artist”). The emergence of more open, creative and socialised technologies generates challenges for discipline-based education. At the same time, the term “Creative Technologies” also suggests a new occupational category (“I am a Creative Technologist”). This chapter presents a case-study of an evolving ‘anti-disciplinary’ project-based degree that challenges traditional degree structures to stimulate new forms of connective, imaginative and explorative learning, and to equip students to respond to a changing world. Learning is conceived as an emergent process; self-managed by students through critique and open peer review. We focus on ‘playfulness’ as a methodology for achieving multi-modal learning across the boundaries of art, design, computer science, engineering, games and entrepreneurship. In this new cultural moment, playfulness also re-frames the institutional identities of teacher and learner in response to new expectations for learning