Ebselen Improves Ischemia-Reperfusion Injury After Rat Lung Transplantation

The heterocyclic organic compound ebselen (2-phenyl-1,2-benizsoselenazol-3(2H)-one) is a glutathione peroxidase mimick with protective properties against oxidative injury. Ebselen also has anti-inflammatory activity, including attenuation of tumor necrosis factor release and increase of interleukin-10, as shown invivo, in inflammatory and ischemia-reperfusion injuries, including those of the lung. This study was designed to assess its effect on severe ischemia-reperfusion injury in a model of left-sided rat lung isotransplantation. Orthotopic single left-sided lung allotransplantation (Wistar to Wistar) was performed in female rats after a total ischemic time of 18h. In nine recipients given 500mg/kg oral ebselen 1h before transplantation, graft PaO2/FiO2 was improved 24h after transplantation, as evidenced with a mean (standard deviation) PaO2 of 139 (61) mmHg vs. eight controls with 65 (33) mmHg (p=0.009). Bronchoalveolar PMN count was reduced to approximately 50% in the ebselen group compared with controls, whereas no difference in the tumor necrosis factor content was found. We conclude that the improvement of lung function in ebselen-treated transplanted rats is mainly the result of the anti-inflammatory activity of the drug during reperfusio

La1−x_{1-x}Mn1−y_{1-y}O3±δ_{3±δ} buffer layers on inclined substrate deposited MgO templates for coated conductors

Most commercial high-temperature superconducting coated conductors based on ion beam assisted MgO deposited templates use LaMnO3 (LMO) films as the terminating buffer layer. In contrast, coated conductors based on inclined substrate deposition (ISD)-MgO technology are still produced with homoepitaxial (homoepi)-MgO as the cap layer. In this work we report on the deposition of LMO buffer layers on ISD-MgO/homoepi-MgO by electron beam physical vapor deposition. The growth parameters of textured LMO films were studied systematically and their properties were optimized regarding the critical current densitiy (Jc) of the subsequently deposited DyBa2Cu3O7-δ (DyBCO) superconducting films. LMO films without outgrowths at the surface were obtained at growth rates of up to 4 Å/s. Despite the formation of non-stoichiometric LMO films containing 59 % La, single-phase films were obtained at substrate temperatures below 775 circleC and at oxygen partial pressures of up to 4×10-4 mbar due to a large homogeneity region towards La. The Jc values of DyBCO films deposited on LMO were found to be independent of the LMO thickness in a range from 50 nm to 450 nm. DyBCO films on LMO reach Jc = 0.83 MA/cm2 at 77 K in zero applied field. This value is up to 30 % higher than those of DyBCO films grown directly on homoepi-MgO. The wide range of LMO growth parameters and higher Jc values of DyBCO on LMO compared to DyBCO on homoepi-MgO make this material attractive for its use in manufacturing coated conductors based on ISD-MgO technology

Pathophysiological Considerations in Periorbital Necrotizing Fasciitis: A Case Report.

BACKGROUND Periorbital necrotizing fasciitis (PNF) is a rare complication of bacterial infection, associated with irreversible inflammatory destruction of soft tissues like subcutaneous tissue and superficial fascia. PNF can cause visual loss, septic shock and death within hours to days. Since the infection progresses rapidly from a local disease to septic shock, prompt identification and decisive interventions are mandatory. AIM Considering pathophysiology, differential diagnosis, and treatment options, we report a case of PNF and its outcome.Methods: A 69 years old male with febrile periorbital swelling had been diagnosed with bilateral PNF, caused by dual infection with Streptococcus pyogenes (S. pyogenes) and Staphylococcus aureus (S. aureus) based on conjunctival swabs. RESULTS The superantigens produced by S. pyogenes have been identified as key to the rapid dissemination of infection and severity of systemic manifestations. CONCLUSIONS A combination of intravenous antibiotics and regular surgical debridements resulted in a beneficial outcome in our patient

Consequences of different diagnostic ‘gold standards' in test accuracy research: Carpal Tunnel Syndrome as an example

Test accuracy studies assume the existence of a well-defined illness definition and clear-cut diagnostic gold standards or reference standards. However, in clinical reality illness definitions may be vague or a mere description of a set of manifestations, mostly clinical signs and symptoms. This can lead to disagreements among experts about the correct classification of an illness and the adequate reference standard. Using data from a diagnostic accuracy study in carpal tunnel syndrome, we explored the impact of different definitions on the estimated test accuracy and found that estimated test performance characteristics varied considerably depending on the chosen reference standard. In situations without a clear-cut illness definition, randomized controlled trials may be preferable to test accuracy studies for the evaluation of a novel test. These studies do not determine the diagnostic accuracy, but the clinical impact of a novel test on patient management and outcom

Evaluation of Central Auditory Discrimination Abilities in Older Adults

The present study focuses on auditory discrimination abilities in older adults aged 65-89 years. We applied the ‘Leipzig Inventory for Patient Psychoacoustic’ (LIPP), a psychoacoustic test battery specifically designed to identify deficits in central auditory processing. These tests quantify the just noticeable differences (JND) for the three basic acoustic parameters (i.e. frequency, intensity, and signal duration). Three different test modes (monaural, dichotic signal/noise [s/n] and interaural) were used, stimulus level was 35dB sensation level. The tests are designed as three-alternative forced-choice procedure with a maximum-likelihood procedure estimating p=0,5 correct response value. These procedures have proven to be highly efficient and provide a reliable outcome. The measurements yielded significant age-dependent deteriorations in the ability to discriminate single acoustic features pointing to progressive impairments in central auditory processing. The degree of deterioration was correlated to the different acoustic features and to the test modes. Most prominent, interaural frequency and signal duration discrimination at low test frequencies was elevated which indicates a deterioration of time- and phase-dependent processing at brain stem and cortical levels. LIPP proves to be an effective tool to identify basic pathophysiological mechanisms and the source of a specific impairment in auditory processing of the elderly

Characteristics of inflammatory response and repair after experimental blast lung injury in rats.

BACKGROUND AND OBJECTIVES Blast-induced lung injury is associated with inflammatory, which are characterised by disruption of the alveolar-capillary barrier, haemorrhage, pulmonary infiltrateration causing oedema formation, pro-inflammatory cytokine and chemokine release, and anti-inflammatory counter-regulation. The objective of the current study was to define sequence of such alterations in with establishing blast-induced lung injury in rats using an advanced blast generator. METHODS Rats underwent a standardized blast wave trauma and were euthanised at defined time points. Non-traumatised animals served as sham controls. Obtained samples from bronchoalveolar lavage fluid (BALF) at each time-point were assessed for histology, leukocyte infiltration and cytokine/chemokine profile. RESULTS After blast lung injury, significant haemorrhage and neutrophil infiltration were observed. Similarly, protein accumulation, lactate dehydrogenase activity (LDH), alveolar eicosanoid release, matrix metalloproteinase (MMP)-2 and -9, pro-Inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL) -6 raised up. While declining in the level of anti-inflammatory cytokine IL-10 occurred. Ultimately, pulmonary oedema developed that increased to its maximum level within the first 1.5 h, then recovered within 24 h. CONCLUSION Using a stablished model, can facilitate the study of inflammatory response to blast lung injury. Following the blast injury, alteration in cytokine/chemokine profile and activity of cells in the alveolar space occurs, which eventuates in alveolar epithelial barrier dysfunction and oedema formation. Most of these parameters exhibit time-dependent return to their basal status that is an indication to resilience of lungs to blast-induced lung injury

Five Fractions versus Seven Fractions SBRT for Intermediate- and High-Risk Prostate Cancer: A Propensity Score Matched Pair Analysis.

PURPOSE To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. METHODS/MATERIAL We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. RESULTS Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). CONCLUSION Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy

Does the 6-minute walk test in hospitalized COPD patients exclusively correlate with lung function parameters or should psychological factors also be taken into account?

Abstract The 6-minute walk test is generally considered a standard test for the evaluation of short-term maximal physical performance. It has not been evaluated whether psychological factors, such as anxiety or depression, affect the performance or the results of the test. The main aim of this study was to investigate whether a correlation exists between psychological factors and the data from the 6-minute walking test. The study cohort consisted of 85 (♀ = 34 and ♂ = 51) 66 ± 10 (mean ± SD) year-old patients with chronic obstructive pulmonary disease (COPD) hospitalized for disease exacerbation. Forced Expiratory Volume in the first second (FEV1) (% predicted) as predictor for lung function, as well as anxiety and depression symptoms assessed using the Hospital Anxiety and Depression Scale (HADS) as psychological predictors were collected. Bivariate correlations and hierarchical linear regression models were used to analyse the correlations. Walking distance was on average 260m ± 107m and ranged from 64m to 480m. HADS was negatively correlated with 6-min walking distance (r = 0.441, p = .0009, r = -.523, p = 00006). Hierarchical linear regression showed that FEV1 alone explained 33%, and together with the psychological variables anxiety and depression explained 42% of the variance of results from the 6-minute walking test. These findings demonstrated that 11% of the data correlated with the psychological variables alone (p = .011). The effect size for lung function (f2 = .717) and psychological variables (f2 = .352) were high, whereas the socio-demographic variables sex, age, educational level and BMI could not explain any additional variance in our cohort. In conclusion, our study indicates that psychological factors such as symptoms of depression and anxiety are associated with lower physical functional performance in the 6-minute walking test. As such, these factors should also be assessed. Future research is needed to show if treatments of anxiety and depression can improve the walking distance in COPD patients