54 research outputs found

    Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTRΔF508/ΔF508 Pigs

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    Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion.Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CF(ΔF508/ΔF508) with CFTR(-/-) piglets and found significantly greater forskolin-stimulated secretion rates in the ΔF508 vs. the null piglets (1.4±0.8, n = 4 vs. 0.2±0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ∼4 times greater in adult than in neonatal nasal glands.These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ΔF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections

    Natural Variation in Partial Resistance to Pseudomonas syringae Is Controlled by Two Major QTLs in Arabidopsis thaliana

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    BACKGROUND: Low-level, partial resistance is pre-eminent in natural populations, however, the mechanisms underlying this form of resistance are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used the model pathosystem Pseudomonas syringae pv. tomato DC3000 (Pst) - Arabidopsis thaliana to study the genetic basis of this form of resistance. Phenotypic analysis of a set of Arabidopsis accessions, based on evaluation of in planta pathogen growth revealed extensive quantitative variation for partial resistance to Pst. It allowed choosing a recombinant inbred line (RIL) population derived from a cross between the accessions Bayreuth and Shahdara for quantitative genetic analysis. Experiments performed under two different environmental conditions led to the detection of two major and two minor quantitative trait loci (QTLs) governing partial resistance to Pst and called PRP-Ps1 to PRP-Ps4. The two major QTLs, PRP-Ps1 and PRP-Ps2, were confirmed in near isogenic lines (NILs), following the heterogeneous inbred families (HIFs) strategy. Analysis of marker gene expression using these HIFs indicated a negative correlation between the induced amount of transcripts of SA-dependent genes PR1, ICS and PR5, and the in planta bacterial growth in the HIF segregating at PRP-Ps2 locus, suggesting an implication of PRP-Ps2 in the activation of SA dependent responses. CONCLUSIONS/SIGNIFICANCE: These results show that variation in partial resistance to Pst in Arabidopsis is governed by relatively few loci, and the validation of two major loci opens the way for their fine mapping and their cloning, which will improve our understanding of the molecular mechanisms underlying partial resistance

    Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

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    BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom

    Bookbinding for Puerto Rico: Culture, Food, Folklore

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    Eight advanced printmaking students will exhibit their artist books and conduct a hands on bookbinding workshop at Southern Graphics Council International in Puerto Rico, demonstrating the book structures they created. Under the mentorship of Professor Nicole Hand, the students will work in pairs and design four different book structures that they will exhibit and demonstrate, while participants learn how to create their own. The design and content of each book will be based on the groups research on culture, food, and folklore in Puerto Rico. This project is part of the community outreach and humanitarian efforts the Southern Graphics Council International has adapted for this conference due to the loss the community has experienced after several natural disasters

    Effects of electrically induced muscle contraction on flexion reflex in human spinal cord injury

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    Study aims to examine changes in the magnitude of the flexion reflex following functional electrical stimulation (FES) of the rectus femoris (RF) muscle. The incidence of the early component of the flexion reflex (120 ms) was observed in all subjects during control conditions and following sensorimotor conditioning. FES applied to the RF muscle (above and below MT) in the main induced a significant early and long lasting depression of the long latency flexion reflex. The depression of the flexion reflex was a result of multisensory actions on flexion reflex pathways resulting from the direct and indirect (mechanical) consequences of electrically induced muscle contraction on cutaneous and muscle afferents. Our findings emphasize the importance of sensory feedback mechanisms in modulating flexion reflex excitability, and highlight the need for rehabilitation professionals to consider the central actions of FES-induced afferent feedback when incorporating FES into a rehabilitation program

    Massive hemoptysis due to primary mucoepidermoid carcinoma of the lung in a 12-year-old

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    A 12-year-old African male patient presented with a history of progressive weight loss of several months duration and a complaint of persistent hemoptysis. Radiological examination (chest X-ray and computerized tomographic scan) confirmed the presence of a mass in the lower lobe of the right lung. Following hospitalization, the hemoptysis intensified and the patient was anesthetized for endobronchial examination and biopsy in order to establish the nature and extent of the pulmonary mass. Shortly after intubation, severe rapid intraparenchymal hemorrhage of the right lung occurred which led to sudden cardiac arrest. The patient was successfully resuscitated and was then admitted to the intensive care unit whilst still intubated. The endobronchosopic examination and biopsy procedure were abandoned and the right lung mass remained undiagnosed. A brain CT-scan performed shortly thereafter confirmed that hypoxic damage was present. The patient showed no improvement and finally succumbed one month later.http://link.springer.com/journal/120242017-09-30hb2017Forensic MedicineOral Pathology and Oral Biolog
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