Revision Bronchoscopy After Endobronchial Valve Treatment for Emphysema:Indications, Findings and Outcomes

Background: Endobronchial valve (EBV) treatment is an effective treatment for patients with severe emphysema. Revision bronchoscopies after endobronchial valve treatment can be essential to prolong the effect of treatment or address long-term complications. Purpose: To evaluate the indications, endoscopic findings and outcomes of revision bronchoscopies and investigate if any predictors for granulation tissue formation, after EBV treatment, can be identified. Patients and Methods: Patients who underwent EBV treatment between 2016 and 2019 in our hospital, as routine care, were included. If a patient underwent a revision bronchoscopy, data regarding revision bronchoscopies, including indication, finding, intervention and pulmonary function testing (PFT) after revision bronchoscopy were analysed. Results: One hundred seventy-nine patients were included of which 41% required at least one revision bronchoscopy. In 43% of the revision bronchoscopy patients, the indication was loss of initial treatment effect. In 53% of the revision bronchoscopy patients, granulation tissue was found to be the underlying cause. Valve replacement(s) were performed in 51% of the revision bronchoscopy cases. Permanent valve removal was required in 13% of all patients. Overall, revision bronchoscopies led to improvements in PFT outcomes for patients experiencing no or a loss of initial treatment effect. No clinically relevant predictors for granulation tissue formation were identified. Conclusion: Performing a revision bronchoscopy after EBV treatment is a useful procedure leading to an improved treatment effect in most patients. Granulation tissue formation, causing valve dysfunction, is the most common cause of longer term problems

Sex and the Cinema: What American Pie Teaches the Young

This paper focuses upon the wildly successful blockbuster American Pie teenpics, especially American Pie 3 – the Wedding. I argue that these films, which are sited so securely within the visual and pedagogical machinery of Hollywood culture, are specifically designed to appeal to teenage male audiences, and to provide lessons in sex and romance. Movies like this are especially important as they are experienced by far more teenagers than, for example, instructional films or other classroom materials; indeed, as Henry Giroux has observed, "teens and youth learn how to define themselves outside of the traditional sites of instruction, such as the home and the school… Learning in the postmodern age is located elsewhere – in popular spheres that shape their identities, through forms of knowledge and desires that appear absent from what is taught in schools" (Giroux, 1997, p.49). In this paper I discuss whether the American Pie series is actually a "new age" effort which, via insubordinate performances of gender, contests the hegemonic field of signification which regulates the production of sex, gender and desire, or whether it is more accurately described as a retrogressive hetero-conservative opus with a veneer of sexual radicalism. In short, I intend to probe whether this filmic vector for sex education is all about the shaping of responsible, caring, vulnerable men, or is it guiding them to become just like their heterosexual, middle-class fathers? And whether, despite its riotous and raunchy advertising, American Pie really dishes up something spicy or something terribly wholesome instead

A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities

In recent years, various endogenous compounds have been proposed as putative biomarkers for the hepatic uptake transporters OATP1B1 and OATP1B3 that have the potential to predict transporter-mediated drug-drug interactions (DDIs). However, these compounds have often been identified from top-down strategies and have not been fully utilized as a substitute for traditional DDI studies. In an attempt to eliminate observer bias in biomarker selection, we applied a bottom-up, untargeted metabolomics screening approach in mice and found that plasma levels of the conjugated bile acid chenodeoxycholate-24-glucuronide (CDCA-24G) are particularly sensitive to deletion of the orthologous murine transporter Oatp1b2 (31-fold increase vs. wild type) or the entire Oatp1a/1b(-/-)cluster (83-fold increased), whereas the humanized transgenic overexpression of hepatic OATP1B1 or OATP1B3 resulted in the partial restoration of transport function. Validation studies with the OATP1B1/OATP1B3 inhibitors rifampin and paclitaxel in vitro as well as in mice and human subjects confirmed that CDCA-24G is a sensitive and rapid response biomarker to dose-dependent transporter inhibition. Collectively, our study confirmed the ability of CDCA-24G to serve as a sensitive and selective endogenous biomarker of OATP1B-type transport function and suggests a template for the future development of biomarkers for other clinically important xenobiotic transporters.</p

Factors influencing the consumption of seafood among young children in Perth: a qualitative study

<p>Abstract</p> <p>Background</p> <p>This formative study sought to explore the factors that influence the consumption of fish and seafood among 4–6 year old children in the Perth metropolitan area. Focus groups were conducted with mothers of young children to gain insights into the enablers and barriers to regular seafood consumption in children, and the knowledge, attitudes and perceptions of their mothers to including seafood as a regular part of their children's diet.</p> <p>Methods</p> <p>Purposive sampling techniques were used to select and recruit mothers of children aged between four and six years from within the Perth metropolitan area. A total of seven focus groups were conducted. Thematic content analysis was employed to code data generated and to extract major themes.</p> <p>Results</p> <p>Findings indicated that all children of study participants had tried fish and seafood products, with some being exposed to a wide variety from an early age. Across focus groups, several dominant factors were apparent in influencing the frequency and type of seafood purchased and consumed. Perceived cost, freshness, availability/accessibility, and the level of confidence to prepare a meal to suit all family members were significant determinants of whether seafood featured regularly on the household menu. The influence of others in the family (particularly the husband or partner) also tended to impact upon the likelihood of serving fish and seafood, and the types of products mothers were willing to serve.</p> <p>Conclusion</p> <p>Findings from this qualitative study indicate that interventions seeking to promote seafood (particularly fish) as an integral part of a healthy diet should address existing negative attitudes and beliefs around the storage and preparation of seafood. The influence of dominant male influences within the family unit should also be considered. Strategies directed at parents and children should include experimental 'hands-on' components to encourage experimentation, particularly focussing on ease of preparation and the variety of lower cost seafood available.</p

Sleep-disordered breathing was associated with lower health-related quality of life and cognitive function in a cross-sectional study of older adults

BACKGROUND AND OBJECTIVE: The clinical significance of sleep‐disordered breathing (SDB) in older age is uncertain. This study determined the prevalence and associations of SDB with mood, daytime sleepiness, quality of life (QOL) and cognition in a relatively healthy older Australian cohort. METHODS: A cross‐sectional analysis was conducted from the Study of Neurocognitive Outcomes, Radiological and retinal Effects of Aspirin in Sleep Apnoea. Participants completed an unattended limited channel sleep study to measure the oxygen desaturation index (ODI) to define mild (ODI 5–15) and moderate/severe (ODI ≥ 15) SDB, the Centre for Epidemiological Studies Scale, the Epworth Sleepiness Scale, the 12‐item Short‐Form for QOL and neuropsychological tests. RESULTS: Of the 1399 participants (mean age 74.0 years), 36% (273 of 753) of men and 25% (164 of 646) of women had moderate/severe SDB. SDB was associated with lower physical health‐related QOL (mild SDB: beta coefficient [β] −2.5, 95% CI −3.6 to −1.3, p < 0.001; moderate/severe SDB: β −1.8, 95% CI −3.0 to −0.6, p = 0.005) and with lower global composite cognition (mild SDB: β −0.1, 95% CI −0.2 to 0.0, p = 0.022; moderate/severe SDB: β −0.1, 95% CI −0.2 to 0.0, p = 0.032) compared to no SDB. SDB was not associated with daytime sleepiness nor depression. CONCLUSION: SDB was associated with lower physical health‐related quality of life and cognitive function. Given the high prevalence of SDB in older age, assessing QOL and cognition may better delineate subgroups requiring further management, and provide useful treatment target measures for this age group

A Multi-Proxy Assessment of the Impact of Environmental Instability on Late Holocene (4500-3800 BP) Native American Villages of the Georgia Coast

Circular shell rings along the South Atlantic Coast of North America are the remnants of some of the earliest villages that emerged during the Late Archaic (5000-3000 BP). Many of these villages, however, were abandoned during the Terminal Late Archaic (ca 3800-3000 BP). We combine Bayesian chronological modeling with mollusk shell geochemistry and oyster paleobiology to understand the nature and timing of environmental change associated with the emergence and abandonment of circular shell ring villages on Sapelo Island, Georgia. Our Bayesian models indicate that Native Americans occupied the three Sapelo shell rings at varying times with some generational overlap. By the end of the complex\u27s occupation, only Ring III was occupied before abandonment ca. 3845 BP. Ring III also consists of statistically smaller oysters harvested from less saline estuaries compared to earlier occupations. Integrating shell biochemical and paleobiological data with recent tree ring analyses shows a clear pattern of environmental fluctuations throughout the period in which the rings were occupied. We argue that as the environment became unstable around 4300 BP, aggregation at villages provided a way to effectively manage fisheries that are highly sensitive to environmental change. However, with the eventual collapse of oyster fisheries and subsequent rebound in environmental conditions ca. post-3800 BP, people dispersed from shell rings, and shifted to non-marine subsistence economies and other types of settlements. This study provides the most comprehensive evidence for correlations between large-scale environmental change and societal transformations on the Georgia coast during the Late Archaic period

Influence of probenecid on the pharmacokinetics and pharmacodynamics of sorafenib

Prior studies have demonstrated an organic anion transporter 6 (OAT6)-mediated accumulation of sorafenib in keratinocytes. The OAT6 inhibitor probenecid decreases sorafenib uptake in skin and might, therefore, decrease sorafenib-induced cutaneous adverse events. Here, the influence of probenecid on sorafenib pharmacokinetics and toxicity was investigated. Pharmacokinetic sampling was performed in 16 patients on steady-state sorafenib treatment at days 1 and 15 of the study. Patients received sorafenib (200–800 mg daily) in combination with probenecid (500 mg two times daily (b.i.d.)) on days 2–15. This study was designed to determine bioequivalence with geometric mean Area under the curve from zero to twelve hours (AUC0–12 h) as primary endpoint. During concomitant probenecid, s

Identification of miRNA from Porphyra yezoensis by High-Throughput Sequencing and Bioinformatics Analysis

BACKGROUND: miRNAs are a class of non-coding, small RNAs that are approximately 22 nucleotides long and play important roles in the translational level regulation of gene expression by either directly binding or cleaving target mRNAs. The red alga, Porphyra yezoensis is one of the most important marine economic crops worldwide. To date, only a few miRNAs have been identified in green unicellar alga and there is no report about Porphyra miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: To identify miRNAs in Porphyra yezoensis, a small RNA library was constructed. Solexa technology was used to perform high throughput sequencing of the library and subsequent bioinformatics analysis to identify novel miRNAs. Specifically, 180,557,942 reads produced 13,324 unique miRNAs representing 224 conserved miRNA families that have been identified in other plants species. In addition, seven novel putative miRNAs were predicted from a limited number of ESTs. The potential targets of these putative miRNAs were also predicted based on sequence homology search. CONCLUSIONS/SIGNIFICANCE: This study provides a first large scale cloning and characterization of Porphyra miRNAs and their potential targets. These miRNAs belong to 224 conserved miRNA families and 7 miRNAs are novel in Porphyra. These miRNAs add to the growing database of new miRNA and lay the foundation for further understanding of miRNA function in the regulation of Porphyra yezoensis development

Anastral spindle assembly and γ-tubulin in Drosophila oocytes

<p>Abstract</p> <p>Background</p> <p>Anastral spindles assemble by a mechanism that involves microtubule nucleation and growth from chromatin. It is still uncertain whether γ-tubulin, a microtubule nucleator essential for mitotic spindle assembly and maintenance, plays a role. Not only is the requirement for γ-tubulin to form anastral <it>Drosophila </it>oocyte meiosis I spindles controversial, but its presence in oocyte meiosis I spindles has not been demonstrated and is uncertain.</p> <p>Results</p> <p>We show, for the first time, using a bright GFP fusion protein and live imaging, that the <it>Drosophila </it>maternally-expressed γTub37C is present at low levels in oocyte meiosis I spindles. Despite this, we find that formation of bipolar meiosis I spindles does not require functional γTub37C, extending previous findings by others. Fluorescence photobleaching assays show rapid recovery of γTub37C in the meiosis I spindle, similar to the cytoplasm, indicating weak binding by γTub37C to spindles, and fits of a new, potentially more accurate model for fluorescence recovery yield kinetic parameters consistent with transient, diffusional binding.</p> <p>Conclusions</p> <p>The FRAP results, together with its mutant effects late in meiosis I, indicate that γTub37C may perform a role subsequent to metaphase I, rather than nucleating microtubules for meiosis I spindle formation. Weak binding to the meiosis I spindle could stabilize pre-existing microtubules or position γ-tubulin for function during meiosis II spindle assembly, which follows rapidly upon oocyte activation and completion of the meiosis I division.</p