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Background: Only few studies deal with the workload of physical therapists and the health consequences, although this occupational group is quite important for the health care system in many industrialized countries (e.g. ca. 136 000 people are currently employed as physical therapists in Germany). Therefore, the current state of knowledge of work-related diseases and disorders of physical therapists is insufficient. The aim of the "Physical Therapist Cohort" (PTC) study is to analyze the association between work-related exposures and diseases among physical therapists in Germany. This article describes the protocol of the baseline assessment of the PTC study.
Methods/Design: A cross-sectional study will be conducted as baseline assessment and will include a representative random sample of approximately 300 physical therapists employed in Germany (exposure group), and a population-based comparison group (n = 300). The comparison group will comprise a sample of working aged (18–65 years) inhabitants of a German city. Variables of interest will be assessed using a questionnaire manual including questions regarding musculoskeletal, dermal, and infectious diseases and disorders as well as psychosocial exposures, diseases and disorders. In addition to subjective measures, a clinical examination will be used to objectify the questionnaire-based results (n = 50).
Discussion: The study, which includes extensive data collection, provides a unique opportunity to study the prospective association of work-related exposures and associated complaints of physical therapists. Baseline results will give first clues with regard to whether and how prevalent main exposures of physiotherapeutic work and typical work areas of physical therapists are associated with the development of work-related diseases. Thereby, this baseline assessment provides the basis for further investigations to examine causal relationships in accordance with a longitudinal design.
Nanoparticles (particles sized between 1 and 100 nanometers) are more and more used in all fields of science and medicine for their physicochemical properties. As gold has traditionally been considered as chemically inert and biocompatible, in particular, gold nanoparticles have been established as valuable tools in several areas of biomedical research. But in contrast to the multitude of studies that addressed the clinical use of gold nanoparticles, only little is known about potential toxicological effects such as induction of inflammatory immune responses, possible apoptotic cell death or developmental growth inhibition in embryos. Therefore the present study performed a systematic review of toxicological data, especially experimentally acquired data concerning in-vivo-toxicity, published in the PubMed. It can be stated that the data in this area of research is still largely limited. Especially, knowledge about size-, charge- and surface-chemistry dependent in-vivo-toxicity is needed to predict the hazard potential of auric nanoparticles (AuNPs) for humans.
T-cell receptor (TCR) polyclonal mature T cells are surprisingly resistant to oncogenic transformation after retroviral insertion of T-cell oncogenes. In a mouse model, it has been shown that mature T-cell lymphoma/leukemia (MTCLL) is not induced upon transplantation of mature, TCR polyclonal wild-type (WT) T cells, transduced with gammaretroviral vectors encoding potent T-cell oncogenes, into RAG1-deficient recipients. However, further studies demonstrated that quasi-monoclonal T cells treated with the same protocol readily induced MTCLL in the recipient mice. It has been hypothesized that in the TCR polyclonal situation, outgrowth of preleukemic cells and subsequent conversion to overt malignancy is suppressed through regulation of clonal abundances on a per-clone basis due to interactions between TCRs and self-peptide-MHC-complexes (spMHCs), while these mechanisms fail in the quasi-monoclonal situation. To quantitatively study this hypothesis, we applied a mathematical modeling approach. In particular, we developed a novel ordinary differential equation model of T-cell homeostasis, in which T-cell fate depends on spMHC-TCR-interaction-triggered stimulatory signals from antigen-presenting cells (APCs). Based on our mathematical modeling approach, we identified parameter configurations of our model, which consistently explain the observed phenomena. Our results suggest that the preleukemic cells are less competent than healthy competitor cells in acquiring survival stimuli from APCs, but that proliferation of these preleukemic cells is less dependent on survival stimuli from APCs. These predictions now call for experimental validation.
The neurophysiological changes associated with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10(-2) for controls and (2.70 ± 0.49)·10(-2) for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.
Ataxin-2 (ATXN2) is implicated mainly in mRNA processing. Some ATXN2 associates with receptor tyrosine kinases (RTK), inhibiting their endocytic internalization through interaction of proline-rich domains (PRD) in ATXN2 with SH3 motifs in Src. Gain of function of ATXN2 leads to neuronal atrophy in the diseases spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). Conversely, ATXN2 knockout (KO) mice show hypertrophy and insulin resistance. To elucidate the influence of ATXN2 on trophic regulation, we surveyed interactions of ATXN2 with SH3 motifs from numerous proteins and observed a novel interaction with Grb2. Direct binding in glutathione S-transferase (GST) pull-down assays and coimmunoprecipitation of the endogenous proteins indicated a physiologically relevant association. In SCA2 patient fibroblasts, Grb2 more than Src protein levels were diminished, with an upregulation of both transcripts suggesting enhanced protein turnover. In KO mouse embryonal fibroblasts (MEF), the protein levels of Grb2 and Src were decreased. ATXN2 absence by itself was insufficient to significantly change Grb2-dependent signaling for endogenous Ras levels, Ras-GTP levels, and kinetics as well as MEK1 phosphorylation, suggesting that other factors compensate for proliferation control. In KO tissue with postmitotic neurons, a significant decrease of Src protein levels is prominent rather than Grb2. ATXN2 mutations modulate the levels of several components of the RTK endocytosis complex and may thus contribute to alter cell proliferation as well as translation and growth.
Background: High-producer TGFβ1 genotypes are associated with severe lung disease in cystic fibrosis (CF), but studies combining IL-8, TNFα-, and TGFβ1(+genotype) levels and their impact on CF lung disease are scarce.
Aim: Assessing the relationship between TGFβ1, IL-8, and TNF-α and lung disease in CF in an exacerbation-free interval.
Methods: Twenty four patients delta F508 homozygous (median age 20.5 y, Shwachman score 75, FEV1(%) 83) and 8 controls (median age 27.5 y) were examined. TGFβ1 was assessed in serum and induced sputum (IS) by ELISA, for IL-8 and TNF-α by chemiluminescence in IS and whole blood. Genotyping was performed for TGFβ1 C−509T and T+869C utilizing RFLP.
Results: TGFβ1 in IS (CF/controls median 76.5/59.1 pg/mL, P < 0.074) was higher in CF. There was a negative correlation between TGFβ1 in serum and lung function (LF) (FEV1 (r = −0.488, P = 0.025), MEF 25 (r = −0.425, P = 0.055), and VC (r = −0.572, P = 0.007)). Genotypes had no impact on TGFβ1 in IS, serum, and LF. In IS TGFβ1 correlated with IL-8 (r = 0.593, P < 0.007) and TNF-α (r = 0.536, P < 0.018) in patients colonized by bacteria with flagellin.
Conclusion: TGFβ1 in serum not in IS correlates with LF. In patients colonized by bacteria with flagellin, TGFβ1 correlates with IL-8 and TNF-α in IS.
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient’s risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.
Background: The pro-inflammatory status of the elderly triggers most of the age-related diseases such as cancer and atherosclerosis. Atherosclerosis, the leading cause world wide of morbidity and death, is an inflammatory disease influenced by life-style and genetic host factors. Stimuli such as oxLDL or microbial ligands have been proposed to trigger inflammation leading to atherosclerosis. It has recently been shown that oxLDL activates immune cells via the Toll-like receptor (TLR) 4/6 complex. Several common single nucleotide polymorphisms (SNPs) of the TLR system have been associated with atherosclerosis. To investigate the role of TLR-6 we analyzed the association of the TLR-6 SNP Pro249Ser with atherogenesis.
Results: Genotyping of two independent groups with CAD, as well as of healthy controls revealed a significant association of the homozygous genotype with a reduced risk for atherosclerosis (odds ratio: 0.69, 95% CI 0.51-0.95, P = 0.02). In addition, we found a trend towards an association with the risk of restenosis after transluminal coronary angioplasty (odds ratio: 0.53, 95% CI 0.24-1.16, P = 0.12). In addition, first evidence is presented that the frequency of this protective genotype increases in a healthy population with age. Taken together, our results define a role for TLR-6 and its genetic variations in modulating the inflammatory response leading to atherosclerosis.
Conclusions: These results may lead to a better risk stratification, and potentially to an improved prophylactic treatment of high-risk populations. Furthermore, the protective effect of this polymorphism may lead to an increase of this genotype in the healthy elderly and may therefore be a novel genetic marker for the well-being during aging.
The leukemia-associated fusion protein RUNX1/ETO is generated by the chromosomal translocation t(8;21) which appears in about 12% of all de novo acute myeloid leukemias (AMLs). Essential for the oncogenic potential of RUNX1/ETO is the oligomerization of the chimeric fusion protein through the nervy homology region 2 (NHR2) within ETO. In previous studies, we have shown that the intracellular expression of peptides containing the NHR2 domain inhibits RUNX1/ETO oligomerization, thereby preventing cell proliferation and inducing differentiation of RUNX1/ETO transformed cells. Here, we show that introduction of a recombinant TAT-NHR2 fusion polypeptide into the RUNX1/ETO growth-dependent myeloid cell line Kasumi-1 results in decreased cell proliferation and increased numbers of apoptotic cells. This effect was highly specific and mediated by binding the TAT-NHR2 peptide to ETO sequences, as TAT-polypeptides containing the oligomerization domain of BCR did not affect cell proliferation or apoptosis in Kasumi-1 cells. Thus, the selective interference with NHR2-mediated oligomerization by peptides represents a challenging but promising strategy for the inhibition of the leukemogenic potential of RUNX1/ETO in t(8;21)-positive leukemia.
Purpose: Scientific evidence is limited regarding the long-term (>10 years) outcomes of large enough numbers of implants (>500) to allow for reliable comparison of subgroups. The purpose of this study was to analyze the outcomes of dental implants placed in an active University Clinic setting and followed for up to 20 years.
Materials and Methods: Data documenting the implant placement, prosthetic reconstruction, and annual follow-up of patients treated at Frankfurt University were extracted from a Structured Query Language database and patients’ written records and evaluated statistically.
Results: Between April of 1991 and May of 2011, 12,737 ANKYLOS® (DENTSPLY Implants Manufacturing GmbH, Mannheim, Germany) implants were placed in 4,206 patients for a variety of clinical indications. The Kaplan–Meier cumulative survival rate (CSR) was 93.3% after 204 months. Most of the failures (198/1.6%) occurred during the first year after implant placement and before prosthesis delivery. A significantly higher (p < .001) number of implants placed in the mandible and in hard quality bone failed than those placed in the maxilla or in weak and normal quality bone. Female patients had significantly higher CSRs (93.7% 204 months) than male patients (92.8% 204 months/p = .029). The implants showed low rates of peri-implant bone loss after 204 months (horizontal: 21 mm: 85.7%, vertical: 21 mm: 85.2%).
Conclusion: ANKYLOS dental implants followed for up to 20 years have high CSRs and low rates of peri-implant bone loss.