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For the normal development of pregnancy, a balance between immune tolerance and defense is crucial. However, the mechanisms mediating such a balance are not fully understood. CD83 is a transmembrane protein whose expression has been linked to anti-inflammatory functions of T and B cells. The soluble form of CD83, released by cleavage of the membrane-bound protein, has strong anti-inflammatory properties and was successfully tested in different mouse models. It is assumed that this molecule contributes to the establishment of immune tolerance. Therefore, we postulated that the expression of CD83 is crucial for immune tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound form of CD83 was upregulated in T and B cells during allogeneic murine pregnancies. An upregulation was also evident in the main splenic B cell subtypes: marginal zone, follicular zone, and transitional B cells. We also showed that there was an augmentation in the number of CD83+ cells toward the end of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in terms of CD83 expression and sCD83 release. Progesterone induced a dosis-dependent upregulation of CD83 on T cells. Our data suggest that the regulation of CD83 expression represents a novel pathway of fetal tolerance and protection against inflammatory threats during pregnancy.
A New Kind of Permutation Entropy Used to Classify Sleep Stages from Invisible EEG Microstructure
(2017)
Less invasive caries management techniques for treating cavitated carious primary teeth, which involve the concept of caries control by managing the activity of the biofilm, are becoming common. This study aimed to compare the clinical efficacy (minor/major failures) and survival rates (successful cases without any failures) of 3 carious lesion treatment approaches, the Hall Technique (HT), non-restorative caries treatment (NRCT), and conventional restorations (CR), for the management of occlusoproximal caries lesions (ICDAS 3-5) in primary molars. Results at 2.5 years are presented. A total of 169 children (3- to 8-year-olds) were enrolled in this secondary care-based, 3-arm parallel-group, randomised controlled trial. Participants were allocated to: HT (n = 52; sealing caries with stainless-steel crowns without caries removal), NRCT (n = 52; opening up the cavity and applying fluoride varnish), CR (n = 65; control arm, complete caries removal and compomer restoration). Statistical analyses were: non-parametric Kruskal-Wallis analysis of variance, Mann-Whitney U test and Kaplan-Meier survival analyses. One hundred and forty-two participants (84%; HT = 40/52; NRCT = 44/52; CR = 58/65) had follow-up data of 1-33 months (mean = 26). Overall, 25 (HT = 2, NRCT = 9, CR = 14) of 142 participants (17.6%) presented with at least 1 minor failure (reversible pulpitis, caries progression, or secondary caries; p = 0.013, CI = 0.012-0.018; Mann-Whitney U test). Ten (HT = 1, NRCT = 4, CR = 5) of 142 participants (7.04%) experienced at least 1 major failure (irreversible pulpitis, abscess, unrestorable tooth; p = 0.043, CI = 0.034-0.045). Independent comparisons between 2 samples found that NRCT-CR had no statistically significant difference in failures (p > 0.05), but for CR-HT (p = 0.037, CI = 0.030-0.040) and for NRCT-HT (p = 0.011, CI = 0.010-0.016; Kruskal-Wallis test) significant differences were observed. Cumulative survival rates were HT = 92.5%, NRCT = 70.5%, and CR = 67.2% (p = 0.012). NRCT and CR outcomes were comparable. HT performed better than NRCT and CR for all outcomes. This study was funded by the Paediatric Dentistry Department, Greifswald University, Germany (Trial registration No. NCT01797458).
Background: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. Methods: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Results: Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. Conclusion: We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding.
: Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring
most commonly in adolescents and young adults. Major improvements in disease-free survival have
been achieved by implementing a combination therapy consisting of radical surgical resection of the
tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel
targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active
research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles.
Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown
to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.”
The current article summarizes the potential of CAP in the treatment of human OS and reviews the
underlying molecular mode of action.
Wound antisepsis has undergone a renaissance due to the introduction of highly effective wound-compatible antimicrobial agents and the spread of multidrug-resistant organisms (MDROs). However, a strict indication must be set for the application of these agents. An infected or critically colonized wound must be treated antiseptically. In addition, systemic antibiotic therapy is required in case the infection spreads. If applied preventively, the Wounds-at-Risk Score allows an assessment of the risk for infection and thus appropriateness of the indication. The content of this updated consensus recommendation still largely consists of discussing properties of octenidine dihydrochloride (OCT), polihexanide, and iodophores. The evaluations of hypochlorite, taurolidine, and silver ions have been updated. For critically colonized and infected chronic wounds as well as for burns, polihexanide is classified as the active agent of choice. The combination 0.1% OCT/phenoxyethanol (PE) solution is suitable for acute, contaminated, and traumatic wounds, including MRSA-colonized wounds due to its deep action. For chronic wounds, preparations with 0.05% OCT are preferable. For bite, stab/puncture, and gunshot wounds, polyvinylpyrrolidone (PVP)-iodine is the first choice, while polihexanide and hypochlorite are superior to PVP-iodine for the treatment of contaminated acute and chronic wounds. For the decolonization of wounds colonized or infected with MDROs, the combination of OCT/PE is preferred. For peritoneal rinsing or rinsing of other cavities with a lack of drainage potential as well as the risk of central nervous system exposure, hypochlorite is the superior active agent. Silver-sulfadiazine is classified as dispensable, while dyes, organic mercury compounds, and hydrogen peroxide alone are classified as obsolete. As promising prospects, acetic acid, the combination of negative pressure wound therapy with the instillation of antiseptics (NPWTi), and cold atmospheric plasma are also subjects of this assessment.
Abstract
Der Beitrag richtet sich an Studenten, die sich im Schwerpunkt oder aus Interesse mit dem Kartellrecht beschäftigen. Er will den Einstieg in die Materie erleichtern und auch dem Wiederholenden noch einmal die wichtigsten Denkbrücken zur Lösung eines kartellrechtlichen Falles nach dem GWB aufzeigen. Dabei orientiert er sich nach den möglichen Einstiegsmöglichkeiten in eine Klausur und erläutert Schritt für Schritt die wesentlichen Tatbestandsmerkmale und Probleme.
Background: ‘Quality in medicine' is a term used in a broad sense. In this work the definition and dimensions of quality in medicine and the implementation of a measurement and reporting system in Germany are discussed. Existing applications are described and possible future effects are pointed out. Methods: The ongoing process of implementing a quality reporting system into the German healthcare system is studied by publicly available legal texts, published reactions of stakeholders and publications of G-BA and IQTIG. Definitions of quality, dimensions of quality and quality measurement in medicine are studied by using textbooks as well as the world wide web and PubMed search. Results: Donabedian‘s ‘dimensions of quality' are fundamental in dealing with quality in medicine. Existing measurement and reporting systems have immanent strengths and weaknesses, as the definition of quality is affected by one‘s point of view. The legislator will have to decide which ‘dimension of quality' is mandatory and how to measure it. Conclusion: Quality has become a control instrument with unforeseeable consequences. A clear definition of the used quality concept is as essential as the use of feasible measurement and reporting systems. The use of routine data could be an interesting option.
Background: The plasminogen activator system plays a key role in ovarian cancer (OC) tumor progression. The plasminogen activator inhibitor type 1 (PAI-1) and the recently identified PAI-1 RNA binding protein 1 (PAI-RBP1) are primary regulators of plasminogen activation and thus are putative biomarkers for OC progression. Methods: One hundred fifty six OC patients were analyzed to identify the presence of PAI-1 and PAI-RBP1 and subsequently correlated to clinicopathological parameters. Primary cells obtained from OC patient samples were applied in fluorescence microscopy analysis for examination of PAI-1 and PAI-RBP1 distribution. Results: PAI-1 and PAI-RBP1 have been found to be predictive markers for OC patients' outcome. PAI-1 levels significantly correlated with volume of ascites, FIGO staging, and lymph node status. PAI-RBP1 expression significantly correlated with age at first diagnosis, histological tumor type, presence of distant metastasis (pM), and recurrence. PAI-1 showed a trend toward association and PAI-RBP1 was significantly associated with progression-free survival. Notably, PAI-1 protein in recurrent OC tissues was exclusively localized in the nucleus. Conclusion: This study has shown that a combination of PAI-1 and PAI-RBP1 may represent novel prognostic factor for OC. Prospective trials are needed.