Canal wall reconstruction and mastoid obliteration with composite multi-fractured osteoperiosteal flap

We used inferior pedicled composite multi-fractured osteoperiosteal flap (CMOF), our original and new surgical approach, to obliterate the mastoid cavity and reconstruct the external auditory canal (EAC) to prevent the open cavity problems. CMOF was used to obliterate the mastoid cavity and reconstruct the EAC in 24 patients (13 women, 11 men; age span 12–51 years) who underwent radical mastoidectomy to treat the chronic otitis media between 1998 and 2004. Small meatoplasty was done in all 24 patients to relive their aesthetical concerns. Temporal bone CT scanning was done to observe the neo-osteogenesis in the mastoidectomy cavity and the CMOF, and the EAC volume was measured postoperatively. All our patients were followed-up for 2 years. The epithelization of the new EAC in our patients was complete at the end of the second month. Cholesteatoma, granulation, and recurrence of osteitis did not occur in any of the patients. We saw the new bone formation filling the mastoid cavity in the postoperative temporal bone CT scanning images. The mean volume of the new EAC on the 24th month was 1.83 ± 0.56 cm(3). We had an almost natural EAC, which owed its existence to the neo-osteogenesis that grows behind the CMOF, which we use to obliterate the mastoid cavity and to reconstruct the EAC

Maximal respiratory static pressures in patients with different stages of COPD severity

<p>Abstract</p> <p>Background</p> <p>In this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects. We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD. Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values.</p> <p>Subject and methods</p> <p>110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study. Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe.</p> <p>Results</p> <p>Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects. Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV₁(forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height. MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV₁.</p> <p>Conclusion</p> <p>The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD.</p

Is it harder to know or to reason? Analyzing two-tier science assessment items using the Rasch measurement model

Two-tier multiple-choice (TTMC) items are used to assess students’ knowledge of a scientific concept for tier 1 and their reasoning about this concept for tier 2. But are the knowledge and reasoning involved in these tiers really distinguishable? Are the tiers equally challenging for students? The answers to these questions influence how we use and interpret TTMC instruments. We apply the Rasch measurement model on TTMC items to see if the items are distinguishable according to different traits (represented by the tier), or according to different content sub-topics within the instrument, or to both content and tier. Two TTMC data sets are analyzed: data from Singapore and Korea on the Light Propagation Diagnostic Instrument (LPDI), data from the United States on the Classroom Test of Scientific Reasoning (CTSR). Findings for LPDI show that tier-2 reasoning items are more difficult than tier-1 knowledge items, across content sub-topics. Findings for CTSR do not show a consistent pattern by tier or by content sub-topic. We conclude that TTMC items cannot be assumed to have a consistent pattern of difficulty by tier—and that assessment developers and users need to consider how the tiers operate when administering TTMC items and interpreting results. Researchers must check the tiers’ difficulties empirically during validation and use. Though findings from data in Asian contexts were more consistent, further study is needed to rule out differences between the LPDI and CTSR instruments

Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion

Background: TH17 cells are proposed to play a role in the pathology of asthma, including steroid-resistant (SR) disease. We previously identified a steroid-enhancing function of vitamin D in patients with SR asthma in restoring the impaired response to steroids for production of the anti-inflammatory cytokine IL-10. / Objective: We sought to investigate the production of the TH17-associated cytokines IL-17A and IL-22 in culture in patients with moderate-to-severe asthma defined on the basis of their clinical response to steroids and the susceptibility of this response to inhibition by steroids and the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25[OH]2D3). / Methods: PBMCs were stimulated in culture with or without dexamethasone and 1,25(OH)2D3. A cytometric bead array, ELISA, and intracellular cytokine staining were used to assess cytokine production. The role of CD39 in inhibition of the TH17 response was studied by using quantitative real-time PCR, flow cytometry, and addition of the antagonist POM-1 to culture. / Results: Asthmatic patients synthesized much higher levels of IL-17A and IL-22 than nonasthmatic control subjects, with patients with SR asthma expressing the highest levels of IL-17A. Glucocorticoids did not inhibit IL-17A cytokine expression in patients and enhanced production in cultures from control subjects. Treatment with 1,25(OH)2D3 with or without dexamethasone significantly reduced both IL-17A and IL-22 levels. An antagonist of the ectonucleotidase CD39 reversed 1,25(OH)2D3-mediated inhibition of the IL-17A response. / Conclusion: Patients with severe asthma exhibit increased levels of TH17 cytokines, which are not inhibited by steroids. 1,25(OH)2D3 inhibits TH17 cytokine production in all patients studied, irrespective of their clinical responsiveness to steroids, identifying novel steroid-enhancing properties of vitamin D in asthmatic patients

A Dual Inhibitory Mechanism Sufficient to Maintain Cell-Cycle-Restricted CENP-A Assembly

Chromatin featuring the H3 variant CENP-A at the centromere is critical for its mitotic function and epigenetic maintenance. Assembly of centromeric chromatin is restricted to G1 phase through inhibitory action of Cdk1/2 kinases in other phases of the cell cycle. Here, we identify the two key targets sufficient to maintain cell-cycle control of CENP-A assembly. We uncovered a single phosphorylation site in the licensing factor M18BP1 and a cyclin A binding site in the CENP-A chaperone, HJURP, that mediated specific inhibitory phosphorylation. Simultaneous expression of mutant proteins lacking these residues results in complete uncoupling from the cell cycle. Consequently, CENP-A assembly is fully recapitulated under high Cdk activities, indistinguishable from G1 assembly. We find that Cdk-mediated inhibition is exerted by sequestering active factors away from the centromere. Finally, we show that displacement of M18BP1 from the centromere is critical for the assembly mechanism of CENP-A

Cosmic rays and molecular clouds

This paper deals with the cosmic-ray penetration into molecular clouds and with the related gamma--ray emission. High energy cosmic rays interact with the dense gas and produce neutral pions which in turn decay into two gamma rays. This makes molecular clouds potential sources of gamma rays, especially if they are located in the vicinity of a powerful accelerator that injects cosmic rays in the interstellar medium. The amplitude and duration in time of the cosmic--ray overdensity around a given source depend on how quickly cosmic rays diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray observations of molecular clouds can be used both to locate the sources of cosmic rays and to constrain the properties of cosmic-ray diffusion in the Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics 2012, 27 pages, 10 figure

Biomarker Changes Associated with Tuberculin Skin Test (TST) Conversion: A Two-Year Longitudinal Follow-Up Study in Exposed Household Contacts

Background:A high prevalence (50-80%) of Tuberculin Skin Test Positivity (TST+ \u3eor=10 mm indurations) has been reported in TB endemic countries. This pool forms a huge reservoir for new incident TB cases. However, immune biomarkers associated with TST conversion are largely unknown. The objective of this study was to identify immune biomarkers associated with TST conversion after acute Mycobacterium tuberculosis (MTB) Methodology/Principal Findings:A 24 month longitudinal study was carried out in a recently MTB exposed cohort of household contacts (HC = 93, 75% TST+). Control group consisted of unexposed community controls (EC = 59, 46%TST+). Cytokine secretion was assessed in whole blood cultures in response to either mycobacterial culture filtrate (CF) antigens or mitogens (PHA or LPS) using Elisa methodology. Compared to the EC group, the HC group at recruitment (Kruskal-Wallis Test) showed significantly suppressed IFN gamma (p = 0.0001), raised IL-10 (p = 0.0005) and raised TNF alpha (p = 0.001) in response to CF irrespective of their TST status. Seventeen TST-HC, showed TST conversion when retested at 6 months. Post TST conversion (paired t tests) significant increases were observed for CF induced IFN gamma (p = 0.038), IL-10 (p = 0.001) and IL-6 (p = 0.006). Cytokine responses were also compared in the exposed HC group with either recent infection [(TST converters (N = 17)] or previous infection [TST+ HC (N = 54)] at 0, 6, 12 and 24 months using ANOVA on repeated measures. Significant differences between the exposed HC groups were noted only at 6 months. CF induced IFN gamma was higher in previously infected HC group (p = 0.038) while IL-10 was higher in recently infected HC group (p = 0.041). Mitogen induced cytokine secretion showed similar differences for different group.Conclusions/Significance:Our results suggest that TST conversion is associated with early increases in IFN gamma and IL-10 responses and precedes latency by several months post exposure

The impact of electronic records on patient safety : a qualitative study

BACKGROUND: Our aim was to explore NHS staff perceptions and experiences of the impact on patient safety of introducing a maternity system. METHODS: Qualitative semi-structured interviews were conducted with 19 members of NHS staff who represented a variety of staff groups (doctors, midwives, health care assistants), staff grades (consultant and midwife grades) and wards within a maternity unit. Participants represented a single maternity unit at a NHS teaching hospital in the North of England. Interviews were conducted during the first 12 months of the system being implemented and were analysed thematically. RESULTS: Participants perceived there to be an elevated risk to patient safety during the system's implementation. The perceived risks were attributed to a range of social and technical factors. For example, poor system design and human error which resulted in an increased potential for missing information and inputting error. CONCLUSIONS: The first 12 months of introducing the maternity system was perceived to and in some cases had already caused actual risk to patient safety. Trusts throughout the NHS are facing increasing pressure to become paperless and should be aware of the potential adverse impacts on patient safety that can occur when introducing electronic systems. Given the potential for increased risk identified, recommendations for further research and for NHS trusts introducing electronic systems are proposed

Surprisingly High Specificity of the PPD Skin Test for M. tuberculosis Infection from Recent Exposure in The Gambia

BACKGROUND: Options for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia. METHODOLOGY/PRINCIPAL FINDINGS: Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6–35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p<0.0001). With increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive contacts who were PPD skin test positive increased (p<0.0001), and the proportion of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased (p<0.0001); the converse did not occur. CONCLUSIONS/SIGNIFICANCE: The PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited