Fragrances as a trigger of immune responses in different environments.

Fragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e.g., nickel and fragrance). It has been shown that fragrance allergy leads to Th2/Th22 production of IL-4, IL-5 and IL-13, controlling the development of IgE and mediating hypersensitivity reactions in the lung, such as asthma. Cytokines released during immune response modulate the expression of cytochrome P450 (CYPs) proteins, which can result in alterations of the pharmacological effects of substances in inflammatory diseases. The mechanisms linking environment and immunity are still not completely understood but it is known that aryl hydrocarbon receptor (AhR) is a sensor with conserved ligand-activated transcription factor, highly expressed in cells that controls complex transcriptional programs which are ligand and cell type specific, with CYPs as targeted genes. This review focuses on these important aspects of immune responses of the skin and respiratory tract cells, describing some in vitro models applied to evaluate the mechanisms involved in fragrance-induced allergy.

Thrombospondins Differentially Regulate Proteins Involved in Arterial Remodeling.

Thrombospondins (TSPs) are matricellular glycoproteins expressed in response to vascular injury. TSP-1 and TSP-2 are promotors of arterial remodeling while TSP-5 is believed to be protective. The current study assessed the differential effect of TSPs on protein expression in vascular smooth muscle cells (VSMCs). We hypothesized that TSP-1, TSP-2 and TSP-5 would regulate VSMC proteins involved in arterial remodeling. Human VSMCs were exposed to TSP-1, -2, -5 or serum free media (24 hours). Cell lysates were used to assess the targets TSP-1, TSP-2, TSP-5 and CD44), while the culture media was used to detect TGF-ß1, PDGF-BB, ANGPTL-4 and IL-8. Statistical analysis was performed by t-test and p< 0.05 was considered significant. All TSPs increased their own expression and TSP-5 increased TSP-2. TSP-1 and TSP-2 increased production of ANGPTL-4 and PDGF-BB, while TSP-5 only increased ANGPTL-4. TSP-1 increased exclusively TGF-ß1 and CD44 production. TSP-2 increased TSP-1 expression. All TSPs decreased IL-8. The findings suggest that TSP-1 and TSP-2 may promote vascular remodeling, in part, by increasing ANGPTL-4, PDGF-BB and their own expression. TSP-5 did not upregulate the inflammatory mediators TSP-1, PDGF-BB or TGF-ß1, but upregulated its own expression, which could be a protective mechanism against the response to vascular injury.

Dental care in modern art (1914-2014).

Background Representations of 'dentists in action' in modern art have never been systematically researched. This paper surveys and analyses these portrayals for the first time.Methods Relevant paintings, prints, sculptures, and installations were identified by means of keyword searches in search engines, OPACs and picture libraries as well as handsearch.Results Between 1914 and 2014 more than 75 works of art with dental treatment as a motif appeared across the globe. Virtually every modern style from post-impressionism to 'crossover art' are represented, including world famous artists such as Dubuffet or Dalí. Syringes, Doriot's transmissions and contra-angle handpieces are worked into an iconographic code. In contrast, elements of an increasing hygiene consciousness (gloves, face masks and protective glasses) are integrated only fragmentarily. The dentist-patient relationship is predominantly portrayed professionally and realistically and the stereotype of the male dentist dominates.Discussion For almost a century it has been argued that dentists in action had largely disappeared from artistic production after 1900. The results presented here force a revision of this idea and encourage the further discovery of pictorial sources. Only in this way can the fascinating theme of 'dentistry in art' become an attractive part of dental humanities.

Chaos and Regularity in the Doubly Magic Nucleus

High-resolution experiments have recently lead to a complete identification (energy, spin, and parity) of 151 nuclear levels up to an excitation energy of E_{x}=6.20 MeV in ^{208}Pb [Heusler et al., Phys. Rev. C 93, 054321 (2016)PRVCAN2469-998510.1103/PhysRevC.93.054321]. We present a thorough study of the fluctuation properties in the energy spectra of the unprecedented set of nuclear bound states. In a first approach, we group states with the same spin and parity into 14 subspectra, analyze standard statistical measures for short- and long-range correlations, i.e., the nearest-neighbor spacing distribution, the number variance Σ^{2}, the Dyson-Mehta Δ_{3} statistics, and the novel distribution of the ratios of consecutive spacings of adjacent energy levels in each energy sequence, and then compute their ensemble average. Their comparison with a random matrix ensemble which interpolates between Poisson statistics expected for regular systems and the Gaussian orthogonal ensemble (GOE) predicted for chaotic systems shows that the data are well described by the GOE. In a second approach, following an idea of Rosenzweig and Porter [Phys. Rev. 120, 1698 (1960)PHRVAO0031-899X10.1103/PhysRev.120.1698], we consider the complete spectrum composed of the independent subspectra. We analyze their fluctuation properties using the method of Bayesian inference involving a quantitative measure, called the chaoticity parameter f, which also interpolates between Poisson (f=0) and GOE statistics (f=1). It turns out to be f≈0.9. This is so far the closest agreement with a GOE observed in the spectra of bound states in a nucleus. The same analysis is also performed with spectra computed on the basis of shell model calculations with different interactions (surface-delta interaction, Kuo-Brown, Michigan-three-Yukawa). While the simple surface-delta interaction exhibits features typical for nuclear many-body systems with regular dynamics, the other, more realistic interactions yield chaoticity parameters f close to the experimental values.

The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma.

Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profiling and verification in vivo in HCC xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. Furthermore, myoferlin was required for HCC cell invasion, proliferation and anchorage-independent cell growth. We provide evidence that myoferlin is a crucial gene target of MKL1/2 mediating its effect on oncogene-induced senescence by modulating the activation state of the EGFR and downstream MAPK and p16-/Rb pathways. Depletion of myoferlin in tumour cells from SRF-VP16-derived murine HCCs induced a senescence phenotype. These findings identify MKL1/2 and myoferlin as novel therapeutic targets to treat human HCC by a senescence-inducing strategy.

[The rotationally stable screw-anchor with trochanteric stabilizing plate (RoSA/TSP) : First results in unstable trochanteric femur fractures]. / Der Rotationsstabile Schraubanker mit winkelstabiler Stützplatte (RoSA/TAP) : Erste klinische Evaluation bei instabilen trochantären Frakturen.

BACKGROUND: In unstable trochanteric fractures, the extramedullary rotationally stable screw-anchor (RoSA) combines the benefits of the load and rotational stability of the blade with the advantages of the screw (pull-out resistance, compression capability) in a single load carrier, and was designed to prevent femoral neck shortening by using an additional locked trochanteric stabilizing plate (TSP). OBJECTIVES: The aim of the current prospective cohort study was the clinical evaluation of the RoSA/TSP system regarding the mechanical re-operation rate and the amount of postoperative femoral neck shortening. METHODS: From September 2011 to January 2014 80 patients with unstable trochanteric fractures underwent internal extramedullary fixation with the RoSA/TSP (Königsee Implantate GmbH, Allendorf, Germany). Due to fracture stability and after induction of compression, additional long locked antitelescoping screws (AT, n = 1-4) were placed reaching the femoral head. Radiological (femoral neck shortening) and clinical re-examination of patients (n = 61) was performed 6-10 weeks and 6-10 months later. RESULTS: In the 61 re-examined patients (76 %) femoral neck shortening was very low with 2 mm 6-10 months after operation. Re-operations occurred in 8 % (n = 6) and in 4 % (n = 3) as prophylactic surgical intervention. Whereas one-third (4 %) of re-operations occurred due to iatrogenic surgical problems from the first operation two-thirds of patients (8 %) had a re-operation due to delay of bone union (3× nonunion, 3 planned removals of AT-screws to improve healing). The in-hospital mortality was 3 % (n = 2). CONCLUSIONS: The fixation of unstable trochanteric femur fractures using the RoSA/TSP in a first clinical setting led to a great primary stability, with significant advantages with regard to limited femoral neck shortening. However, the rigidity of the construct with its consequences regarding bone healing can be challenging for the surgeon. Nevertheless, in some cases of revision it could be beneficial for stability.

[Preclinical and clinical management after mass disaster : Experiences from the train collision in Bad Aibling on 9 February 2016]. / Präklinisches und klinisches Management nach Massenunfall : Erfahrungen aus dem Zugunglück Bad Aibling am 9.2.2016.

Mass casualty incidents (MCI) in this day and age represent a special challenge, which initially require on-site coordination and logistics and then a professional distribution of victims (triage) to surrounding hospitals. Technical, logistical and even specialist errors can impair this flow of events. It therefore seems advisable to make a detailed analysis of every MCI. In this article the railway incident from 9 February 2016 is analyzed taking the preclinical and clinical cirumstances into consideration and conclusions for future management are drawn. As a special entity it could be determined that fixed table units in passenger trains represent a particularly dangerous hazard and in many instances in this analysis led to characteristic abdominal and thoracic injuries.

Enzyme-linked immunosorbent assays in seroprevalence studies of Q fever: the need for cut-off adaptation and the consequences for prevalence data.

Large outbreaks of Q fever have recently increased the awareness of this disease as a public health issue. Knowledge of the general impact of Q fever relies mainly on seroprevalence studies and it is fundamental that seroprevalence is assessed accurately. Therefore we evaluated the few enzyme-linked immunosorbent assays (ELISAs) commercially available for this purpose. An outbreak in 2005 in Jena, a city of 100,000 inhabitants, gave us the opportunity for the evaluation. However, we found disappointingly low sensitivities for two (42% and 51%) of three commercial ELISAs for detecting past infection. Nevertheless, all assays had good classification potential but cut-off adaptation is needed. Based on the unequal worldwide distribution of the differently performing tests in studies, Q fever seroprevalence is likely to be underestimated in studies from Europe whereas the data from North America and Australia are likely to be more reliable.

The vertebrate homolog of sulfide-quinone reductase is expressed in mitochondria of neuronal tissues.

Hydrogen sulfide (H2S) can be consumed by both invertebrates and vertebrates as an inorganic substrate. The pathway metabolizing H2S probably involves three mitochondrial enzymes, one of which is sulfide-quinone oxidoreductase (SQR), known as sulfide-quinone reductase-like protein (SQRDL) in vertebrates. Evidence from fission yeast suggests that SQR might have a role in regulating sulfide levels in the cell. Regulation might be essential for H2S to act as a gaseous transmitter (gasotransmitter). The brain is an organ with high activity of gasotransmitters, like nitric oxide (NO) and H2S, which are known to affect synaptic transmission. In this study, we provide evidence that SQRDL is expressed in the mammalian brain. Real-time polymerase chain reaction (PCR) showed an increase in the number of Sqrdl transcripts in the brain with increasing age. Cellular fractionation and subsequent analysis by Western blotting indicated that the protein is located in mitochondria, which is the site of sulfide consumption in the cell. With an immunohistochemical approach, we demonstrated that the SQRDL protein is expressed in neurons, oligodendrocytes, and endothelial cells. Taken together, our data suggest that brain tissue harbors the machinery required for local regulation of sulfide levels.

[Modfied technique for intramedullary femur nail removal]. / Modifizierte Technik zur Entfernung von Oberschenkelnägeln.

BACKGROUND: The indication of implant removal of intramedullary nails is a subject of much discussion. The main concern is the increased morbidity of the preparation of the proximal nail end which can cause postoperative discomfort. The aim of the present study was to develop a soft-tissue protecting extraction technique and to evaluate it in comparison to the standard procedure. MATERIAL AND METHODS: With the modified technique the proximal end of the nail is preparated by a guidewire and the standard reamer used for implantation. This allows a soft-tissue protection with reduced morbidity, especially in patients with ossification. The outcome was assessed 4-20 weeks postoperatively and the operation times compared with those of 10 patients operated with the conventional technique. RESULTS: From 5/09 to 12/10 we treated 9 patients with the mentioned technique. The operation time was reduced from a mean of 74.8 minutes to 32.0 minutes. Eight of nine patients had reduced or no discomfort postoperatively. Eight of nine patients stated that they had a benefit from the operation. CONCLUSION: The modified operation technique is capable of reducing operation time and morbidity in the implant removal of intramedullary nails.

Acoustic radiation contrast in MR images for breast cancer diagnostics--initial phantom study.

Acoustic radiation contrast in magnetic resonance images is an approach to visualize the changes in ultrasonic loss and viscoelastic changes of the sample with the resolution of a magnetic resonance imaging (MRI) system. By irradiating ultrasound (US) into a tissue-mimicking sample, a displacement along the US beam path caused by the acoustic radiation force is obtained. This displacement varies with the US intensity, the duration of irradiation, the US attenuation and the viscoelastic properties of the sample. US pulses of 2.5 MHz with a duration of 20 ms and an intensity of <17 W/cm(2) are used. An MRI sequence was programmed to produce images in which the magnitude of the displacement is visualized by gray value changes. In addition, a finite element simulation of the measurements was performed to demonstrate the feasibility of the method. Through examination of the measurements and the simulations, information about viscoelastic changes was achieved. In this work, measurements on different breast phantoms are presented.

Nuclear acoustic resonance in fluids using piezoelectric nanoparticles.

The influence of acoustic radiation in the form of ultrasound (US) on the nuclear magnetic resonance (NMR) signal of liquids in the presence of piezo- and ferroelectric nanoparticles was investigated. The NMR resonances of 1H and 23Na were influenced by US with a frequency of omega(US)=18.26 MHz. For hydrogen, US with a frequency omega(US)=omega(0) was used where omega(0) is the Larmor frequency of 18.26 MHz. For sodium, US with a frequency omega(US)=2omega(0,Na) was used with omega(0,Na)=9.13 MHz. A detailed description of nanoparticle properties and sample preparation is given. The influence of US on the spin-lattice relaxation time T(1) was determined with an inversion recovery sequence for different concentrations of PZT. An elongation of T(1) of (1)H by 1.7% at a PZT concentration of 0.05% and an elongation of T(1) of (23)Na by 3% at a PZT concentration of 0.04% was observed. The elongation scales with the concentration of the PZT. An possible explanation of the effect of elongation is discussed.

Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model.

The impact of nanoparticles (NPs) in medicine and biology has increased rapidly in recent years. Gold NPs have advantageous properties such as chemical stability, high electron density and affinity to biomolecules, making them very promising candidates as drug carriers and diagnostic tools. However, diverse studies on the toxicity of gold NPs have reported contradictory results. To address this issue, a triple cell co-culture model simulating the alveolar lung epithelium was used and exposed at the air-liquid interface. The cell cultures were exposed to characterized aerosols with 15 nm gold particles (61 ng Au/cm2 and 561 ng Au/cm2 deposition) and incubated for 4 h and 24 h. Experiments were repeated six times. The mRNA induction of pro-inflammatory (TNFalpha, IL-8, iNOS) and oxidative stress markers (HO-1, SOD2) was measured, as well as protein induction of pro- and anti-inflammatory cytokines (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, TNFalpha, INFgamma). A pre-stimulation with lipopolysaccharide (LPS) was performed to further study the effects of particles under inflammatory conditions. Particle deposition and particle uptake by cells were analyzed by transmission electron microscopy and design-based stereology. A homogeneous deposition was revealed, and particles were found to enter all cell types. No mRNA induction due to particles was observed for all markers. The cell culture system was sensitive to LPS but gold particles did not cause any synergistic or suppressive effects. With this experimental setup, reflecting the physiological conditions more precisely, no adverse effects from gold NPs were observed. However, chronic studies under in vivo conditions are needed to entirely exclude adverse effects.

Long-term responses of canine lungs to acidic particles.

Sixteen beagle dogs were housed in four large chambers under minimum restraint. They were exposed for 16 months to clean air and individual baseline data of markers were obtained. For 13 months, eight dogs were further exposed to clean air and eight dogs for 6 h/d to 1-microm MMAD (mass median aerodynamic diameter) acidic sulfate particles carrying 25 micromol H(+) m(-3) into their lungs. To establish functional responses (lung function, cell and tissue integrity, redox balance, and non-specific respiratory defense capacity), each exposed animal served as its own control. To establish structural responses, the eight non-exposed animals served as controls. Acidic particles were produced by nebulization of aqueous sodium hydrogen sulfate at pH 1.5. Only subtle exposure-related changes of lung function and structure were detected. A significant increase in respiratory burst function of alveolar macrophages points to a marginal inflammatory response. This can be explained by the significant production of prostaglandin E(2), activating cyclooxygenase-dependent mechanisms in epithelia and thus inhibiting lung inflammation. The non-specific defense capacity was slightly affected, giving increased tracheal mucus velocity and reduced in vivo dissolution of moderately soluble test particles. Hypertrophy and hyperplasia of bronchial epithelia were not observed, but there was an increase in volume density of bronchial glands and a shift from neutral to acidic staining of epithelial secretory cells in distal airways. The acidic exposure had thus no pathophysiological consequences. It is therefore unlikely that long-term inhalation of acidic particles is associated with a health risk.

Direct visualization of damage cascades in lithium niobate crystals caused by high-energy ions.

Congruently melting undoped lithium niobate crystals are irradiated with 20 MeV (3)He ions which penetrate the entire crystal volume. Radiation damage effects are directly visualized by transmission electron microscopy (TEM) where damage zones with diameters of 4 nm give rise to circular Fresnel fringe contrasts. These regions of modified material, appearing circular in cross-section, are interpreted as damage cascades inflicted by fast Nb and O atoms displaced in knock-on collisions with primary (3)He ions. This two-step displacement process results in local density changes manifested by the contrast behaviour of Fresnel fringes observed in TEM images.

Atomic displacement and disorder in LiNbO(3) single crystal caused by high-energy (3)He ion irradiation: an x-ray absorption spectroscopy study.

Nb K-edge x-ray absorption fine structure spectra from a single lithium niobate (LN) crystal irradiated with high-energy (3)He ions of 41 MeV and from unexposed crystal as the reference material are compared. The differences in the x-ray absorption near edge structure (XANES) spectra are interpreted by simulating Nb K-edge XANES spectra with the FEFF8.2 code. It is found that displacements of Nb and Li atoms, as well as Li and O vacancies, are likely to cause structural disorder leading to change in the refractive index of LN and to diminished birefringence. This finding is in agreement with previous results obtained from SRIM-2003 simulations and transmission electron microscopy measurements.

[Are there therapeutic approaches of non-alcoholic fatty liver disease and its complications?]. / Gibt es Therapieansätze für die nicht-alkoholische Fettleber und ihre Komplikationen?

As little as 10 years ago, there was scepticism as to weather non-alcoholic fatty liver disease is a clinical condition. With the increasing prevalence of obesity, diabetes mellitus and the metabolic syndrome in the general population, non-alcoholic fatty liver disease has become a household diagnosis in clinical practice of several medical specialities. Meanwhile, it is the primary cause for elevated liver enzymes of unknown cause in clinical practice. Treatment is focused on the improvement of insulin resistance and of antioxidative mechanisms, mainly by life-style modifications including weight loss and exercise. Drug therapy cannot be recommended at this time, because studies showing positive effects on morbidity and mortality are still lacking. In addition, issues concerning long term safety and side effects of drugs still have to be resolved.