Predictors of self-reported health-related quality of life according to the EQ-5D-Y in chronically ill children and adolescents with asthma, diabetes, and juvenile arthritis: longitudinal results.

PURPOSE: Health-related quality of life (HRQoL) is an important patient-reported outcome in clinical and health research. The EQ-5D-Y assesses child and adolescent HRQoL by five items on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as a visual analogue scale (VAS) on the current health state. This study investigates predictors of self-reported HRQoL according to the EQ-5D-Y in chronically ill children and adolescents using longitudinal data. METHODS: Data from the German Kids-CAT study on children and adolescents with asthma, diabetes, and juvenile arthritis gathered over a period of six months were analyzed (n = 310; 7-17 years old; 48% female). Self-, parent-, and pediatrician-reported data were collected from June 2013 to October 2014. Generalized linear mixed models and linear mixed models served to examine effects of socio-demographic as well as disease- and health-specific predictors on the items as well as on the VAS of the EQ-5D-Y. RESULTS: Ceiling effects for the EQ-5D-Y indicated low burden of disease in the analyzed sample. Longitudinal analyses revealed associations between less health complaints and better HRQoL for all investigated HRQoL domains. Further, age- and gender-specific effects, and associations of better disease control, longer duration of the disease and less mental health problems with better HRQoL were found. CONCLUSIONS: Subjective health complaints and mental health problems should be considered in the care of children and adolescents with asthma, diabetes, and juvenile arthritis. Future research should suggest administering the items of the EQ-5D-Y with five instead of three response options, and investigate HRQoL over a longer period.

[Individual Motivational Interventions after Alcohol-Related Event Treated in Hospital - Effective Option for Secondary Prevention in Adolescence?] / Motivierende Kurzinterventionen nach Krankenhausaufenthalt bei Alkoholintoxikation bei Jugendlichen ­ Effektive Option sekundärer Prävention?

Individual Motivational Interventions after alcohol-related event treated in Hospital - Effective Option for Secondary Prevention in Adolescence? In a prospective, randomized, single-blind study 48 adolescents between 13 and 17 years answered a standardized questionnaire about their behavior of alcohol-consumption after an alcohol-related event with hospitalization. They were divided in 2 groups by randomization: Group A (n=28) took part in an individual motivational intervention (HaLT-Präventionsprojekt), Group B (n=20) did not get any intervention. Six and 12 weeks after the hospitalization the same questionnaire was answered again by telephone-based interviews. The interviewer did not know to which group the interview-partner belonged. 58% (n=28) of all adolescents drank less alcohol or in a lower frequency than before the alcohol-related event. 17% (n=8) did not drink any alcohol in that period of 12 weeks. 54% (n=26) explained, that they had no events of drunkenness in that period. 38% (n=18) did not change their behavior in consumption of alcohol. 6% (n=3) drank more or in higher frequency than before. We could not find any significant difference in the behavior of alcohol-consumption of both groups: 58% (A) resp. 65% (B) drank less than the time before the alcohol-related event (χ²=0,6269; p=0,4285). An influence of the individual motivational intervention could not be shown. Further studies should include interventions for parents and peers.

Coordinating Role of RXRα in Downregulating Hepatic Detoxification during Inflammation Revealed by Fuzzy-Logic Modeling.

During various inflammatory processes circulating cytokines including IL-6, IL-1ß, and TNFα elicit a broad and clinically relevant impairment of hepatic detoxification that is based on the simultaneous downregulation of many drug metabolizing enzymes and transporter genes. To address the question whether a common mechanism is involved we treated human primary hepatocytes with IL-6, the major mediator of the acute phase response in liver, and characterized acute phase and detoxification responses in quantitative gene expression and (phospho-)proteomics data sets. Selective inhibitors were used to disentangle the roles of JAK/STAT, MAPK, and PI3K signaling pathways. A prior knowledge-based fuzzy logic model comprising signal transduction and gene regulation was established and trained with perturbation-derived gene expression data from five hepatocyte donors. Our model suggests a greater role of MAPK/PI3K compared to JAK/STAT with the orphan nuclear receptor RXRα playing a central role in mediating transcriptional downregulation. Validation experiments revealed a striking similarity of RXRα gene silencing versus IL-6 induced negative gene regulation (rs = 0.79; P<0.0001). These results concur with RXRα functioning as obligatory heterodimerization partner for several nuclear receptors that regulate drug and lipid metabolism.

Inflammatory regulation of steroid sulfatase: A novel mechanism to control estrogen homeostasis and inflammation in chronic liver disease.

BACKGROUND & AIMS: Chronic inflammatory liver diseases are associated with estrogen excess and feminization in men, which is thought to be due to compromised liver function to break down estrogens. The goal of this study is to determine whether the inflammatory induction of steroid sulfatase (STS), which converts inactive estrogen sulfates to active estrogens, may have contributed to the estrogen excess in chronic liver disease. METHODS: We performed bioinformatic analysis, real-time PCR, immunohistochemistry, and UPLC/MS-MS to analyze hepatic STS expression and serum estrogen levels in patients with chronic liver diseases. The crosstalk between NF-κB pathway and STS-regulated estrogen signaling was investigated by electrophoretic mobility shift assay, chromatin immunoprecipitation, luciferase assay and gene knockdown experiments in human hepatocytes. RESULTS: Hepatic STS was induced in patients with chronic inflammatory liver diseases, which was accompanied by increased circulating estrogen levels. The human STS gene, but not the mouse Sts gene, was induced by inflammatory stimuli in hepatic cells. Mechanistically, STS was established as a novel NF-κB target gene, whose induction facilitated the conversion of inactive estrogen sulfates to active estrogens, and consequently attenuated the inflammatory response. In contrast, genetic or pharmacological inhibition of STS or a direct blockade of estrogen signaling sensitized liver cells to the transcriptional activation of NF-κB and inflammatory response, possibly through the inhibition of IκB kinase activation. CONCLUSIONS: Our results suggest a negative feedback loop in chronic inflammatory liver diseases, in which the inflammatory activation of NF-κB induces STS gene expression. The induced STS facilitates the conversion of inactive estrogen sulfates to active estrogens, which in return attenuates the NF-κB-mediated inflammation.

A systematic comparison of the impact of inflammatory signaling on absorption, distribution, metabolism, and excretion gene expression and activity in primary human hepatocytes and HepaRG cells.

Inflammatory processes are associated with compromised metabolism and elimination of drugs in the liver, largely mediated by proinflammatory cytokines, such as interleukin-6. The Hepa-RG cell line is an established surrogate for primary human hepatocytes (PHH) in drug metabolism and toxicity studies. However, the impact of inflammatory signaling on HepaRG cells has not been well characterized. In this study, the response of primary human hepatocytes and HepaRG cells to interleukin (IL)-6 was comparatively analyzed. For this purpose, broad-spectrum gene expression profiling, including acute-phase response genes and a large panel of drug-metabolizing enzyme and transporter (DMET) genes as well as their modifiers and regulators, was conducted in combination with cytochrome P450 (P450) activity measurements. Exposure of PHH and HepaRG cells to IL-6 resulted in highly similar coordinated reduction of DMET mRNA, including major ATP-binding cassette transporters (ABCs), P450s, glutathione S-transferases (GSTs), uridine diphosphate glucuronosyltransferases (UGTs), and solute carriers (SLCs). Enzyme activities of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 were reduced upon 48-72 hours exposure to IL-6 in PHH and HepaRG. However, although these effects were not significant in PHH due to large interindividual donor variability, the impact on HepaRG was more pronounced and highly significant, thus emphasizing the advantage of HepaRG as a more reproducible model system. Exposure of HepaRG cells to interleukin-1ß and tumor necrosis factor α resulted in similar effects on gene expression and enzyme activities. The present study emphasizes the role of proinflammatory cytokines in the regulation of drug metabolism and supports the use of HepaRG in lieu of PHH to minimize subject variability.

Early root surface colonization by human periodontal ligament fibroblasts following treatment with different biomaterials.

OBJECTIVES: The present in-vitro study examined the effects of different biomaterials on early root surface colonization by human periodontal ligament (PDL) fibroblasts using confocal-laser-scanning-microscopy (CLSM). MATERIALS AND METHODS: Fifteen periodontally-diseased teeth were extracted, treated with scaling/root planing and longitudinally cut to obtain 30 root fragments. Fragments were treated either with 24% EDTA following application of enamel matrix derivative (EMD), 24% EDTA or EMD only, nanocrystalline hydroxyapatite (NHA) paste or oily calcium hydroxide suspension (OCHS) for 1 h each. The analogue untreated root specimens served as controls. Root fragments were incubated with human PDL fibroblasts and cellular proliferation and morphology were evaluated after 1, 3, 5 and 8 days using CLSM-visualization and image recognition software. RESULTS: The rate of cellular proliferation was different among treatment modalities examined (p = 0.019). Except treatment with NHA paste all treatment modalities improved cellular proliferation on root surfaces at all different points of time compared with the control specimens. A significant difference between treatment modalities was observed between EMD and NHA paste (p = 0.008). No synergistic effect could be demonstrated comparing root surface conditioning with 24% EDTA and EMD application compared to 24% EDTA or EMD application only. CONCLUSION: The present results suggest that initial root surface colonization by PDL fibroblasts may be enhanced by root surface conditioning with 24% EDTA and application of EMD, application of 24% EDTA or EMD alone and OCHS. The addition of 24% EDTA for root surface conditioning prior to EMD application provided no synergistic effects in terms of early root surface colonization by PDL fibroblasts.

Evaluation of the clinical safety and performance of a narrow diameter (2.9 mm) bone-level implant: a 1-year prospective single-arm multicenter study.

PURPOSE: Narrow-diameter implants facilitate single-tooth restoration when interdental or inter-implant spaces and bone volume are inadequate for using standard diameter implants. This study reports the short-term data on the clinical safety and performance of a bone-level-tapered two-piece implant with a 2.9 mm diameter in the clinical practice setting. This study was retrospectively registered on March 1st, 2016 (NCT02699866). METHODS: Implants were placed in partially healed extraction sockets of the central and lateral incisors in the mandible and lateral incisors in the maxilla for single-tooth replacement. The primary outcome was to assess implant survival at 12 months after placement. Secondary outcomes included implant success, pink esthetic score, marginal bone-level changes, and safety. RESULTS: Twenty four males and 17 females with a mean age of 44.5 (± 18.3 standard deviation) received the implant. Three out of 41 implants were lost yielding a survival rate of 92.7% (95%-CI: 79.0%; 97.6%) at 1 year. One patient reported an ongoing foreign body sensation, pain, and/or dysesthesia at month 12. The average pink esthetic score at 6 months was 11.2 (95%-CI: 10.5; 11.9). The bone level was stable with a mean bone-level change of-0.3 mm (± 0.42 mm standard deviation) at 1 year after implantation. No serious adverse events or adverse device events were reported. CONCLUSIONS: The use of a 2.9 mm diameter bone-level-tapered implant is a safe and reliable treatment option for narrow tooth gaps at the indicated locations. Overall performance and good survival rates support their use in cases, where wider implants are unsuitable.

Seroprevalence of human polyomavirus 9 and cross-reactivity to African green monkey-derived lymphotropic polyomavirus.

Human polyomavirus 9 (HPyV9) was discovered recently in immunocompromised patients and shown to be genetically closely related to B-lymphotropic polyomavirus (LPyV). No serological data are available for HPyV9, but human antibodies against LPyV have been reported previously. To investigate the seroepidemiology of HPyV9 and the sero-cross-reactivity between HPyV9 and LPyV, a capsomer-based IgG ELISA was established using the major capsid protein VP1 of HPyV9 and LPyV. VP1 of an avian polyomavirus was used as control. For HPyV9, a seroprevalence of 47 % was determined in healthy adults and adolescents (n = 328) and 20 % in a group of children (n =101). In both groups, the seroreactivities for LPyV were less frequent and the ELISA titres of LPyV were lower. Of the HPyV9-reactive sera, 47 % reacted also with LPyV, and the titres for both PyVs correlated. Sera from African green monkeys, the natural hosts of LPyV, reacted also with both HPyV9 and LPyV, but here the HPyV9 titres were lower. This potential sero-cross-reactivity between HPyV9 and LPyV was confirmed by competition assays, and it was hypothesized that the reactivity of human sera against LPyV may generally be due to cross-reactivity between HPyV9 and LPyV. The HPyV9 seroprevalence of liver transplant recipients and patients with neurological dysfunctions did not differ from that of age-matched controls, but a significantly higher seroprevalence was determined in renal and haematopoietic stem-cell transplant recipients, indicating that certain immunocompromised patient groups may be at a higher risk for primary infection with or for reactivation of HPyV9.

Quantification of bacterial indicators and zoonotic pathogens in dairy wastewater ponds.

Zoonotic pathogens in land-applied dairy wastewaters are a potential health risk. The occurrence and abundance of 10 pathogens and 3 fecal indicators were determined by quantitative real-time PCR (qPCR) in samples from 30 dairy wastewaters from southern Idaho. Samples tested positive for Campylobacter jejuni, stx(1)- and eaeA-positive Escherichia coli, Listeria monocytogenes, Mycobacterium avium subsp. paratuberculosis, and Salmonella enterica, with mean recoveries of genomic DNA corresponding to 10(2) to 10(4) cells ml(-1) wastewater. The most predominant organisms were C. jejuni and M. avium, being detected in samples from up to 21 and 29 of 30 wastewater ponds, respectively. The qPCR detection limits for the putative pathogens in the wastewaters ranged from 16 cells ml(-1) for M. avium to 1,689 oocysts ml(-1) for Cryptosporidium. Cryptosporidium and Giardia spp., Yersinia pseudotuberculosis, and pathogenic Leptospira spp. were not detected by qPCR.

Relation between bone quality values from ultrasound transmission velocity and implant stability parameters--an ex vivo study.

AIM: The objective of this study was to determine the relationship between bone qualities measured by ultrasound transmission velocity (UTV) and primary implant stability parameters measured by radiofrequency analysis (RFA) and push-out test (POT) in an ex-vivo model. MATERIALS AND METHODS: Three blocks of fresh porcine bone samples were obtained from different anatomic regions, correlating to cortical, mixed and cancellous bone. Mechanical bone qualities of these samples were measured using UTV (expressed in m/s) prior to implantation. Three similar implants (4.1 × 11 mm, AstraTech OS) were inserted into each of the procured bone blocks. The evaluation of implant-bone interface stability was evaluated by RFA expressed as implant stability quotient (ISQ), and POT measured in Newton (N). RESULTS: For cortical, mixed and cancellous bone samples UTV values showed a mean of 2049.33, 1728.67 and 1427.67 m/s, respectively. For the implants inserted into cortical, mixed and cancellous bone samples the mean RFA (ISQ) values were 94.33, 81.33 and 63.11, whereas the POT values were >2000, 680 and 290 N, respectively. There was a strong correlation between UTV values and implant stability parameters that was shown descriptively by scatter box plots. CONCLUSION: The bone quality measurements obtained by UTV values significantly correlated to primary implant stability values measured by RFA and push-out test. Moreover, UTV was able to significantly differentiate between the different bone types. This suggested that UTV may be considered as a reasonable instrument to measure bone quality preoperatively and would help clinicians predict primary implant stability before implant insertion.

Promotion of osteogenic cell response using quasicovalent immobilized fibronectin on titanium surfaces: introduction of a novel biomimetic layer system.

PURPOSE: Despite the undeniable potential of cell adhesion molecules such as fibronectin to support osteogenic cell responses and consecutive dental implant healing, the most beneficial mode of application onto titanium implant surfaces still requires investigation. Unspecific fibronectin adsorption on titanium dioxide (TiO(2)) surfaces can result in low-loading, high-desorption rates and protein-metal interactions with impaired biologic activity. The aim of the present study was to monitor the osteogenic cell responses (cell adhesion, proliferation, and differentiation) specifically to fibronectin biofunctionalized TiO(2). MATERIALS AND METHODS: An innovative biomimetic streptavidin-biotin layer system allows flexible, but stable, specific binding of biotinylated biomolecules such as fibronectin on TiO(2) surfaces. Transparent glass disks were sputtered with TiO(2). The biomimetic layer system was immobilized by self-assembly and consisted of silane, biotin-derivate, streptavidin, and biotinylated fibronectin (bFN). For the control group, unbiotinylated fibronectin was directly coated onto TiO(2). Early cell adhesion dynamics were quantified using automated processing of light microscopy images within the first 24 hours. Relative mRNA expression of integrin-ß1, cyclin D1, runt-related gene 2, alkaline phosphatase, and osteocalcin was obtained using quantitative real-time polymerase chain reactions 3 and 7 days after incubation. RESULTS: Although untreated TiO(2) preserved a rather immature osteogenic phenotype, both unbiotinylated fibronectin and bFN promoted osteogenic cell adhesion and cell differentiation. In particular, runt-related gene 2 expression was significantly promoted by bFN after 3 days. In contrast, cyclin D1 expression was decreased for unbiotinylated fibronectin and bFN after 7 days. CONCLUSIONS: The introduced biomimetic layer system contributes a coherent immobilization approach of adhesion molecules with promotion of osteogenic cell response in vitro.

Spin electron paramagnetic resonance of albumin for diagnosis of oral squamous cell carcinoma (OSCC).

OBJECTIVES: Albumin has a known capability to modulate free serum concentrations of proteins produced by tumour cells. The technique of spin probe labelling of albumin followed by electron paramagnetic resonance (EPR) spectroscopy may allow identification of these structural and functional changes, which regularly occur as consequence of binding tumour metabolites as ligands. The aim of the present study was a proof of principle evaluation of EPR-analysis of peripheral blood samples as possible predictor for oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: The present study is designed as gender-matched cohort. EPR was tested after retrieval of peripheral blood samples. The study group is represented by 32 patients with OSCC, and the control group consisted of 30 healthy patients. RESULTS: Overall analysis exhibited a diagnostic sensitivity of 72% (23/32 OSCC group) and a specificity of 80% (24/30 control group). Subgroup analysis revealed ten patients with elevated leukocytes (>10,000/µl; n = 9 [OSCC group] and n = 1 [control group]). After exclusion of patients with elevated white blood cell count, sensitivity considerably increased to 87% and specificity to 83%. CONCLUSION: EPR analysis of peripheral blood samples might be appropriate to support the clinician in primary and follow-up diagnosis of potential tumours such as OSCC. Unfortunately, subgroup analysis characterises the method vulnerable to inflammation. CLINICAL RELEVANCE: Nevertheless, our preliminary results are intriguing, as diagnosis of OSCC appears possible by simple peripheral blood examination. Thus, further appraisal of this novel method with inclusion of different tumour entities, systemic conditions and inflammation in a larger study population appears highly valuable.

A New Method for the Calculation of Characteristics of Disc Springs with Trapezoidal Cross-Sections and Rounded Edges.

In the European standards specifying disc spring manufacturing, geometry, shape and characteristic, an edge rounding is prescribed. Common methods for the calculation of disc spring characteristics, even in these standards, are based on a rectangular cross-section. This discrepancy can lead to a considerable divergence of the computed characteristic from the characteristic determined by testing. In literature, this divergence has not yet been examined with regard to rounded edges. In this paper, a new method addressing this problem is introduced. For this purpose, the geometry of idealized disc springs is parameterized. Based on four edge radii and two angles of the inner and outer faces, equations to compute the initial cone angle and the lever arm are introduced. These equations are used to formulate an algorithm to adapt other computation methods to non-rectangular cross-sections and rounded edges. The method is applied to the formulas by Almen-Laszlo, Curti-Orlando, Zheng and those by Kobelev. FE simulations of disc springs with rounded edges and a non-rectangular cross-section were used to verify the new formulas. The results show that the introduced method can be applied to known characteristic computation methods and result in a model expansion taking cross-section variations into account. The adjusted characteristics show more accurate alignment to the FE simulation for the cross-section variations investigated. These findings not only close the geometric gap between the manufacturing guidelines and the computation on an analytical basis, they also define a new parameter space for designs of disc springs and a corresponding force computation method to optimize spring characteristics.

Robust Determination of Fatigue Crack Propagation Thresholds from Crack Growth Data.

The robust determination of the threshold against fatigue crack propagation ΔKth is of paramount importance in fracture mechanics based fatigue assessment procedures. The standards ASTM E647 and ISO 12108 introduce operational definitions of ΔKth based on the crack propagation rate da/dN and suggest linear fits of logarithmic ΔK- da/dN test data to calculate ΔKth. Since these fits typically suffer from a poor representation of the actual curvature of the crack propagation curve, a method for evaluating ΔKth using a nonlinear function is proposed. It is shown that the proposed method reduces the artificial conservativeness induced by the evaluation method as well as the susceptibility to scatter in test data and the influence of test data density.

Adsorption and conformation behavior of biotinylated fibronectin on streptavidin-modified TiO(X) surfaces studied by SPR and AFM.

It is well-known that protein-modified implant surfaces such as TiO(2) show a higher bioconductivity. Fibronectin is a glycoprotein from the extracellular matrix (ECM) with a major role in cell adhesion. It can be applied on titanium oxide surfaces to accelerate implant integration. Not only the surface concentration but also the presentation of the protein plays an important role for the cellular response. We were able to show that TiO(X) surfaces modified with biotinylated fibronectin adsorbed on a streptavidin-silane self-assembly multilayer system are more effective regarding osteoblast adhesion than surfaces modified with nonspecifically bound fibronectin. The adsorption and conformation behavior of biotinylated and nonbiotinylated (native) fibronectin was studied by surface plasmon resonance (SPR) spectroscopy and atomic force microscopy (AFM). Imaging of the protein modification revealed that fibronectin adopts different conformations on nonmodified compared to streptavidin-modified TiO(X) surfaces. This conformational change of biotinylated fibronectin on the streptavidin monolayer delivers a fibronectin structure similar to the conformation inside the ECM and therefore explains the higher cell affinity for these surfaces.

Bisphosphonates: restrictions for vasculogenesis and angiogenesis: inhibition of cell function of endothelial progenitor cells and mature endothelial cells in vitro.

Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is one of the main side effects in patients treated with bisphosphonates for metastasis to the bone or osteoporosis. BP-ONJ usually occurs in patients treated with highly potent nitrogen-containing bisphosphonates. The exact mechanism of action and etiopathology is still unknown. In addition to inhibition of bone remodelling, an anti-angiogenetic effect has become the focus of research. The aim of these study was to investigate the effect of different bisphosphonates on human umbilicord vein endothelial cells (HUVEC) and endothelial progenitor cells (EPC), which play an important role in angiogenesis. Using varying concentrations, the impact of one non-nitrogen-containing bisphosphonate (clodronate) and three nitrogen-containing bisphosphonates (ibandronate, pamidronate and zoledronate) on HUVEC and EPC was analysed. The biologic behaviour of HUVEC after incubation with different bisphosphonates was measured in a Boyden migration assay as well as in a 3D angiogenesis assay. The number of apoptotic cells was measured by Tunnel assay. To underline the importance of neoangiogenesis in the context of BP-ONJ, we measured the EPC number after incubation with different bisphosphonates in vitro. HUVEC and EPC were significantly influenced by bisphosphonates at different concentrations compared with the non-treated control groups. The nitrogen-containing bisphosphonates pamidronate and zoledronate had the greatest impact on the cells, whereas clodronate followed by ibandronate was less distinct on cell function. These results underline the hypothesis that inhibited angiogenesis induced by bisphosphonates might be of relevance in the development and maintenance of BP-ONJ. The increased impact by highly potent bisphosphonates on HUVEC and EPC may explain the high prevalence of BP-ONJ in patients undergoing this treatment.

[Health-related quality of life of children and adolescents with primary nocturnal enuresis who are undergoing therapy]. / Gesundheitsbezogene Lebensqualität von Kindern und Jugendlichen mit primärer Enuresis nocturna unter Therapie.

BACKGROUND: Primary nocturnal enuresis (PNE) affects a relevant proportion of children (10-15% at school entrance). While a significant impact on psychological well-being and self-esteem of children has been reported, the consequences for Health-Related Quality of Life (HRQoL) have been less addressed. The aim of this investigation is the analysis of HRQoL of PNE under therapy with an established questionnaire. METHODS: The KINDL­R questionnaire for HRQoL with 24 items in 6 dimensions was sent to all patients of the enuresis outpatient clinic (ages 7-17 years, minimum 3 months of therapy, no achieved dryness). Actual number of wet nights and eventual comorbidities were extracted from the clinical data. RESULTS: Of 57 questionnaires sent by mail, 47 were returned from patients and parents (82.5%). The patient results did not show a correlation between HRQoL and age, but there was a negative correlation of physical well-being and increasing age (r = -0.259, p < 0.05). A marked negative correlation was seen between bed-wetting frequency and HRQoL (r = -0.372, p < 0.05), especially in the dimensions "self-worthiness" (r = -0.399, p < 0.005) and "chronic-generic" (r = -0.383, p < 0.05). DISCUSSION: During enuresis treatment without achieved dryness, the patients did not show systematic limitation in HRQoL compared to reference populations. This is in contrast to limitations in HRQoL and self-esteem before therapy, but may possibly be explained by the correlation of this dimension with bed-wetting frequency in this study and the reported improvement through treatment in other studies. Both factors support the need and importance of adequate PNE therapy.

Diversity and abundance of zoonotic pathogens and indicators in manures of feedlot cattle in Australia.

The occurrence of 10 pathogens and three fecal indicators was assessed by quantitative PCR in manures of Australian feedlot cattle. Most samples tested positive for one or more pathogens. For the dominant pathogens Campylobacter jejuni, Listeria monocytogenes, Giardia spp., Cryptosporidium spp., and eaeA-positive Escherichia coli, 10² to 107 genome copies g⁻¹ (dry weight) manure were recovered.

Long-term response of osteogenic cells on micron and submicron-scale-structured hydrophilic titanium surfaces: sequence of cell proliferation and cell differentiation.

OBJECTIVE: Modifications of surface topography and surface chemistry are key factors for guiding target cells during dental implant healing. Recent in vitro studies confirmed promotion of early osteogenic cell differentiation on submicron scaled surfaces in particular when hydrophilized. However, no long-term observations on both osteogenic cell proliferation as well as on cell maturation have been reported for respectively modified surfaces. Aim of this study was to monitor osteogenic cell proliferation and expression of specific osteogenic cell differentiation markers on a protein level over an extended period of 3 weeks with respect to surface modifications. MATERIAL AND METHODS: Modified titanium (Ti) disks were obtained from Institute Straumann, representing the following surfaces: smooth pretreatment (PT), sandblasted/acid etched (SLA), and hydrophilized (modSLA). Surface topography was analyzed by scanning electron microscopy, surface elemental composition was assessed by X-Ray Photoelectronic Spectroscopy (XPS). Tissue culture polystyrene (TCPS) served as a control substrate. Human osteogenic cells (HOB-c) were cultivated on the respective substrates. After 24 hrs, 48 hrs, 72 hrs, 7 d, 14 d and 21 d, cell count was assessed as well as osteogenic cell differentiation utilizing cellular Quantitative Immuno-Cytochemistry (QIC) assay for collagen type I (COL), alkaline phosphatase (AP), osteopontin (OPN) and osteocalcin (OC). Data were normalized with respect to internal controls. RESULTS: In contrast to the other modified Ti disks, modSLA stands out due to low surface carbon contamination. TCPS and PT surfaces preserved a rather immature, mitotic active osteogenic phenotype (high proliferation rates, no increase of OC production), SLA and especially modSLA surfaces promoted the maturation of osteogenic precursors into post-mitotic osteoblasts. In detail, modSLA resulted in lowest cell proliferation rates, but exhibited highest expression rates of OC. DISCUSSION: Our results, which confirm previous studies, reveal long-term promotion of osteogenic cell maturation by topography (micron and submicron scale roughness) and surface hydrophilicity.

On the Influence of Ultimate Number of Cycles on Lifetime Prediction for Compression Springs Manufactured from VDSiCr Class Spring Wire.

For the generation of fatigue curves by means of fatigue tests, an ultimate number of cycles must be chosen. This ultimate number of cycles also limits the permissible range of the fatigue curve for the design of components. This introduces extremely high costs for testing components that are to be used in the Very High Cycle Fatigue regime. In this paper, we examine the influence of the ultimate number of cycles of fatigue tests on lifetime prediction for compression springs manufactured from VDSiCr class spring wire. For this purpose, we propose a new kind of experiment, the Artificial Censoring Experiment (ACE). We show that ACEs may be used to permissibly extrapolate the results of fatigue tests on compression springs by ensuring that a batch-specific minimum ultimate number of cycles has been exceeded in testing. If the minimum ultimate number of cycles has not been exceeded, extrapolation is inadmissible. Extrapolated results may be highly non-conservative, especially for models assuming a pronounced fatigue limit.