Electrode Polarization Effects in Broadband Dielectric Spectroscopy

In the present work, we provide broadband dielectric spectra showing strong electrode polarization effects for various materials, belonging to very different material classes. This includes both ionic and electronic conductors as, e.g., salt solutions, ionic liquids, human blood, and colossal-dielectric-constant materials. These data are intended to provide a broad data base enabling a critical test of the validity of phenomenological and microscopic models for electrode polarization. In the present work, the results are analyzed using a simple phenomenological equivalent-circuit description, involving a distributed parallel RC circuit element for the modeling of the weakly conducting regions close to the electrodes. Excellent fits of the experimental data are achieved in this way, demonstrating the universal applicability of this approach. In the investigated ionically conducting materials, we find the universal appearance of a second dispersion region due to electrode polarization, which is only revealed if measuring down to sufficiently low frequencies. This indicates the presence of a second charge-transport process in ionic conductors with blocking electrodes.Comment: 9 pages, 6 figures, experimental data are provided in electronic form (see "Data Conservancy"

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978

Fall risk in an active elderly population – can it be assessed?

BACKGROUND: Falls amongst elderly people are often associated with fractures. Training of balance and physical performance can reduce fall risk; however, it remains a challenge to identify individuals at increased risk of falling to whom this training should be offered. It is believed that fall risk can be assessed by testing balance performance. In this study a test battery of physiological parameters related to balance and falls was designed to address fall risk in a community dwelling elderly population. RESULTS: Ninety-four elderly males and females between 70 and 80 years of age were included in a one year follow-up study. A fall incidence of 15% was reported. The test battery scores were not different between the fallers and non-fallers. Test scores were, however, related to self-reported health. In spite of inclusion of dynamic tests, the test battery had low fall prediction rates, with a sensitivity and specificity of 50% and 43% respectively. CONCLUSION: Individuals with poor balance were identified but falls were not predicted by this test battery. Physiological balance characteristics can apparently not be used in isolation as adequate indicators of fall risk in this population of community dwelling elderly. Falling is a complex phenomenon of multifactorial origin. The crucial factor in relation to fall risk is the redundancy of balance capacity against the balance demands of the individuals levels of fall-risky lifestyle and behavior. This calls for an approach to fall risk assessment in which the physiological performance is evaluated in relation to the activity profile of the individual

The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3(+) Regulatory T Cells

Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of T-reg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic Treg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling Treg cell development. However, MAZR-deficient T-reg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral Treg cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a Treg cell-intrinsic transcriptional network that modulates Treg cell development.</p

Does clinical examination aid in the diagnosis of urinary tract infections in women? A systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Clinicians should be aware of the diagnostic values of various symptoms, signs and antecedents. This information is particularly important in primary care settings, where sophisticated diagnostic approaches are not always feasible. The aim of the study is to determine the probability that various symptoms, signs, antecedents and tests predict urinary tract infection (UTI) in women.</p> <p>Methods</p> <p>We conducted a systematic search of the MEDLINE and EMBASE databases to identify articles published in all languages through until December 2008. We particularly focused on studies that examined the diagnostic accuracy of at least one symptom, sign or patient antecedent related to the urinary tract. We included studies where urine culture, a gold standard, was preformed by primary care providers on female subjects aged at least 14 years. A meta-analysis of the likelihood ratio was performed to assess variables related to the urinary tract symptoms.</p> <p>Results</p> <p>Of the 1, 212 articles identified, 11 met the selection criteria. Dysuria, urgency, nocturia, sexual activity and urgency with dysuria were weak predictors of urinary tract infection, whereas increases in vaginal discharge and suprapubic pain were weak predictors of the absence of infection. Nitrites or leukocytes in the dipstick test are the only findings that clearly favored a diagnosis of UTI.</p> <p>Conclusions</p> <p>Clinical findings do not aid in the diagnosis of UTI among women who present with urinary symptoms. Vaginal discharge is a weak indicator of the absence of infection. The urine dipstick test was the most reliable tool for detecting UTI.</p

Decellularized pig pulmonary heart valves-Depletion of nucleic acids measured by proviral PERV pol

BACKGROUND: Decellularized human pulmonary heart valve (dhHV) scaffolds have been shown to be the gold standard especially for younger, adolescent patients. However, human heart valves are limited in availability. Xenogeneic decellularized pig heart valves (dpHV) may serve as alternative. METHODS: The efficacy of DNA reduction processes upon decellularization of heart valves from German Landrace pigs was analyzed by measurements of remaining nucleic acids including proviral porcine endogenous retrovirus (PERV) sequences. Porcine pulmonary heart valves (pPHV) were decellularized by three different protocols and further treated with DNaseI or Benzonase, at varying incubation times. DNA isolated from valve associated muscle (m), valve cusp (c), and pulmonary artery (pa) was monitored by PCR and qRT-PCR using GAPDH and the PERV polymerase (pol) for read-out. RESULTS: Decellularization of pPHV led to a significant reduction of DNA (&gt;99%) which could be further significantly increased for (m) and (pa) by nuclease treatment, reducing proviral PERV pol from approximately 5 × 107 to 5 × 103 copies/mg in nuclease treated tissues. CONCLUSIONS: Both nucleases demonstrated comparable activities. But DNaseI revealed to be less consistent for PERV, especially at muscular tissue. Noteworthy, remaining proviral sequences are still detectable by PCR; however, due to the absence of the cellular replication machinery the production of infectious particles is not expected. Decellularization and nuclease treatment of pPHV is an efficient procedure to reduce the DNA content including PERV, thus represents a valuable option to increase virus safety independently from the source animal background

Characterization of porcine endogenous retrovirus particles released by the CRISPR/Cas9 inactivated cell line PK15 clone 15

The infection of human transplant recipients by porcine endogenous retrovirus (PERV) is a safety issue for xenotransplantation (XTx). CRISPR/Cas9 technology has enabled the generation of pigs free of functional PERVs, and the susceptibility of these animals to reinfection by PERVs remains unclear. To assess virological safety, we characterized a cell line in which PERVs have been inactivated by CRISPR/Cas9 (PK15 clone 15) for its susceptibility to infectious PERV. First, basal expression of PERV pol, the porcine PERV-A receptor (POPAR), and reverse transcriptase (RT) activity of PERV were determined. PK15 clone 15 cells were inoculated with PERV and monitored post infection for virus expression and RT activity. Particles were visualized by electron microscopy. Our data show that PK15 clone 15 cells still produce viral proteins that assemble to produce impaired viral particles. These virions have an irregular morphology that diverges from that of mature wild type. The particles are no longer infectious when tested in a downstream infection assay using supernatants of PK15 clone 15 cells to infect susceptible swine testis-IOWA (ST-IOWA) cells. The expression of POPAR was quantified to exclude the possibility that lack of susceptibility to reinfection, for PERV-A, is caused by absence of viral host receptor(s). PK15 and PK15 clone 15 cells do, in fact, express POPAR equally. PERV RT inactivation mediated by CRISPR/Cas9 does not compromise virus assembly but affects virion structure and proviral integration. The constitutive virion production seems to maintain cellular resistance to superinfection and possibly indicates a protective side effect of this specific CRISPR/Cas9 mediated RT inactivation

Development of recommendations for university level assessment at the Ulm Medical Faculty

Objective: The aim of this project was to develop, within a limited time frame, recommendations based on the "Guidelines for internal assessment in the medical curriculum" of the GMA assessment committee and the Baden-Württemberg competence center for assessment in medical education. This paper describes the adaptation of generally formulated GMA guidelines to specific faculty requirements. Methods: The development of "recommendations for university assessment at the Ulm medical faculty" was performed in several steps. All departments as well as student representatives were involved in this stepwise process of guideline adjustment , , therefore securing a broad participation in this change management process , . Finally, the recommendations were approved by the official faculty board.The entire process took eight months. All participants received compensation for their time from official teaching funds. Results: After passing the faculty board, the assessment recommendations based on the GMA quality standards were published as an examination standard for students and examiners. Among faculty members, there was consensus to improve assessment quality according to the recommendations and to participate actively in the process of guideline implementation. Several assessment-improving projects have commenced as a result of this commitment. Conclusions: We showed that it is possible to develop assessment recommendations based on GMA quality standards within a few months if those who are responsible for the implementation are promptly involved in the development process and if it is possible to integrate the recommendations into existing structures.Zielsetzung: Ziel des vorgestellten Projekts war es, auf der Basis der "Leitlinien zu Fakultäts-internen Leistungsnachweisen während des Medizinstudiums" der Gesellschaft für Medizinische Ausbildung (GMA) und des Kompetenzzentrums Prüfungen Baden-Württemberg innerhalb eines abgesteckten Zeitrahmens für die Medizinische Fakultät der Universität Ulm Empfehlungen für fakultätsinterne Prüfungen zu erarbeiten. Anhand des Ulmer Beispiels wird dargestellt, wie allgemein formulierte Leitlinien auf spezifische Anforderungen einer Fakultät übertragen werden können. Methodik: Die Erstellung von "Empfehlungen zu universitären Prüfungen in der Medizinischen Fakultät Ulm" erfolgte in 3 Arbeitsphasen. Zunächst erfolgte ein Abgleich der bereits gängigen Ulmer Prüfungspraxis mit den Leitlinien und die Identifikation fehlender Anteile. Dann wurde, um die für Veränderungsprozesse wichtige breite Partizipation sicher zu stellen , , in einem modifizierten Delphi-Verfahren , die schrittweise Anpassung der Leitlinien an die Ulmer Anforderungen vorgenommen. Im letzten Schritt erfolgte schließlich die Verabschiedung der Empfehlungen durch die Fakultätsgremien.Der gesamte Prozess nahm acht Monate in Anspruch und wurde von einer aus Studiengebühren finanzierten wissenschaftlichen Mitarbeiterin des Studiendekanats begleitet.Ergebnisse: Mit Verabschiedung im Fakultätsrat liegen der Medizinischen Fakultät Ulm jetzt Empfehlungen zu Prüfungen nach den Qualitätsstandards der GMA vor, die künftig Prüfern und Studierenden als Orientierung dienen werden. Innerhalb der Fakultät besteht Konsens, die Qualität der Prüfungen gemäß diesen Empfehlungen zu verbessern und aktiv an einer Umsetzung der Vorgaben mitzuwirken. Aktuell sind dazu bereits zahlreiche Projekte angestoßen worden. Schlussfolgerung: Die Erstellung von Empfehlungen zu Prüfungen nach den Qualitätsstandards der GMA kann innerhalb eines relativ kurzen Zeitraumes erfolgen, sofern die für die Durchführung Verantwortlichen in die Entwicklungsprozesse einbezogen werden und eine Passung in bestehende Strukturen gelingt