Environmental Science and Pollution Research

Correction to: Ecological risk assessment of metals in sediments and selective plants of Uchalli Wetland Complex (UWC)—a Ramsar site The correct image of Figure 4 is shown in this paper. The original article has been corrected. Fig. 4: Scree plot of heavy metals in sediments. The graph shown in upper right corner shows the concentration of principle components variables in a loading plot.

Recent advances on advanced oxidation process for sustainable water management

Environment-health link in a context of urban agricultures: studies of oral exposure to pollutants in order promote the human health

Photocatalytic oxidation of toluene and isopropanol by LaFeO 3 /black-TiO 2 Abstract Large amount of volatile organic compounds (VOCs) are emitted from industrial, mobile, and domestic sources, causing adverse effects on human health and environment. Among VOCs, toluene and isopropanol (IPA) are commonly used as solvent, soldering flux, and spray paint and their emissions need to be reduced. Several VOCs abatement technologies are available to reduce VOC emission and photocatalytic oxidation of VOC is regarded as a viable technique due to its advantage of utilizing solar energy. TiO2 has been investigated for its oxidation capability toward VOCs because of its good photocatalytic activity. However the utilization is limited to UV due to its wider bandgap; furthermore, its fast recombination rate of electron-hole pair reduces the oxidation rate of VOCs. Black-TiO2 and perovskite-type photocatalyst such as LaFeO3 can be applied to enhance photocatalytic activity due to narrower bandgap and longer electron-hole pair lifetime. In this study, black-TiO2 and LaFeO3 are prepared and investigated for their photocatalytic oxidation rates toward toluene and IPA. Results show that toluene removals achieved with black-TiO2 and LaFeO3 are 89% and 98% while IPA removals are 90% and 94%, respectively. Both photocatalysts show better photocatalytic activity than TiO2 and good absorption capability toward visible light. Graphical abstract

Regulating nitrate excess in lettuce-planted greenhouse soil with available carbon addition through irrigation Abstract Nitrate excess is common in greenhouse soils, imposing environmental risks and degrading vegetable quality. In this study, the effectiveness of adding sucrose as available carbon through irrigation to cut nitrate excess in lettuce-planted soil was investigated under impacts of soil texture and irrigation type. In the pot experiment using two loam soils of same origin with different clay to sand ratios (50.2% and 39.8%) and nitrate excess (116.1 and 417.7 mg/kg N), three-time sucrose addition through flood irrigation was more effective in lowering net formation of nitrate-based inorganic N and increasing lettuce yield in the soil with the higher clay to sand ratio, and sucrose addition at 150–450 mg/kg reduced nitrate accumulation and leaching, and nitrate content of lettuce at harvest by 62.5–89.6%, 19.3–36.1%, and 11.4–76.0%, respectively. In the micro-plot field experiment with two-time sucrose addition at 0.6–1.2 g/L through furrow irrigation (42 mm) into two other soils of same origin with different clay to sand ratios (56.9%, 48.4%), nitrate accumulation at 0–30-cm depth at the prone-leaching furrow location at harvest decreased by 30.9–36.0% under the higher clay to sand ratio but increased by about 35% under the lower clay to sand ratio. The nitrate content and yield of ridge-planted lettuce was less affected in either soil. Hence, carbon addition rate, irrigation type, and clay to sand ratio all affected the effect of available carbon addition on nitrate accumulation in vegetable-planted soil, and their joint impacts need better quantification for cutting nitrate excess in soil and improving vegetable quality and even yield.

Effects of vermicomposting on the main chemical properties and bioavailability of Cd/Zn in pure sludge Abstract To study the effects of vermicomposting on the chemical properties and bioavailability of Cd/Zn in sludge, earthworms (Eisenia foetida) at different densities were inoculated into pure sludge, and sludge and earthworms were collected regularly to determine the earthworm biomass, the main chemical indexes, the structure of the functional groups, and the Cd/Zn content in the sludge. The results showed that the growth curve of earthworms in pure sludge could be well fitted by the logistic model. Earthworm activity eventually reduced the total organic carbon (TOC), fulvic acid (FA), and C/N ratio and increased the electrical conductivity (EC), total nitrogen (TN), humic acid (HA), and HA/FA ratio in the sludge. TOC, TN, and pH inhibited the bioavailability of Cd/Zn, while HA and EC promoted the bioavailability of Cd/Zn. Earthworm activity ultimately increased the content of Cd/Zn in the sludge. The bioavailability of Cd/Zn was reduced during the rapid growth period of the earthworms but increased during the stable growth period of the earthworms. A suitable vermicomposting time should be determined to ensure the activation or passivation of Cd/Zn.

Metal content in the liver, kidney, and feathers of Northern gannets, Morus bassanus , sampled on the Spanish coast Abstract The value of birds as bioindicators for monitoring the environmental inorganic elements has been globally recognized. In this context, due to its well-known ecology and population stability, the Northern gannet (Morus bassanus) could be particularly useful. Dead Northern gannets (n = 30) were collected and samples from the liver, kidney, and feathers were taken, dried, mineralized, and finally analyzed via ICP-MS. Metals and metalloids, namely As, Cd, Hg, Pb, and Zn, associated with environmental pollution and toxicity on living organisms, were evaluated. The mean highest concentrations of As, Hg, and Zn were found in the liver (0.916, 7.026, and 89.81 mg/kg dry weight, respectively). For Cd, the kidney showed the highest mean concentration (17.51 mg/kg dry weight), whereas for Pb, this value corresponded to the feathers (0.399 mg/kg dry weight). Significant differences were found between the age classes in terms of contaminant concentrations, with the adults exhibiting higher metal levels. This difference was significantly relevant for Pb and Hg, where the effect of age was observed for all the considered tissues. When considering the effect of gender, no significant differences were observed, in agreement with similar studies performed in other geographical regions. Finally, positive correlations between the concentrations of Hg and Pb in the feathers and in the liver (r = 0.688, p < 0.001 and r = 0.566, p < 0.001, respectively) were observed, as well as between the feather and kidney concentrations (r= 0.685, p < 0.001) indicating the possibility to use feathers, a non-invasive biomonitoring tissue, for better understanding Hg and Pb exposure in seabirds.

Evaluation of the association between urinary cadmium levels below threshold limits and the risk of diabetes mellitus: a dose-response meta-analysis Abstract As cadmium levels are increasing in the environment, the adverse effects of cadmium exposure specifically associated with chronic diseases are receiving increasing attention. Several population–based studies have been conducted on the association between cadmium and diabetes mellitus (DM) but have reported controversial results. Here, we aimed to evaluate the association between cadmium exposure and DM. In this meta-analysis, a random effects model was used because there was evidence of heterogeneity among studies. A dose-response relationship was assessed through a restricted cubic spline model with three knots. The results showed a positive association between cadmium levels in the body and DM (OR = 1.27; 95% CI, 1.07–1.52). The cadmium levels in the body were defined on the basis of combined urinary and blood cadmium. Subgroup analysis further indicated a positive association between urinary cadmium levels and DM (OR = 1.31; 95% CI, 1.02–1.69). The dose-response analysis results showed a positive association between levels of urinary cadmium above 2.43 μg/g creatinine and DM, and the risk of DM increased by 16% for each l μg/g creatinine increase in urinary cadmium levels. The results from our meta-analysis indicate that cadmium levels in the body are positively associated with DM, and urinary cadmium levels above 2.43 μg/g creatinine are associated with an increased risk of DM.

Performance of desulfurization ash for the preparation of grouting fire prevention material Abstract The accumulation of desulfurization ash from coal-fired power plants can lead to serious waste of land resources and environmental safety problems. This work presents an experimental study on the feasibility of recycling original desulfurization ash as the main raw materials, and a new green grouting material was prepared. The results indicate that a desulfurization ash–based grouting fire prevention material which was prepared according to the following ingredient design (a water-to-solid ratio of 1.0:1 and a hydroxyethyl cellulose content of 0.09% desulfurization ash, 12% quicklime, 0.6% Na2SO4, and 0.05% triethanolamine, 80 °C curing). The slurry's viscosity meets requirements, and its suspension, liquidity, and consolidation strength are better than those of clay under the same conditions. In addition, the grouting material's inhibitor ratio is increased with temperature increase, which means it has good flame retardancy. Environmental performance tests concluded that when desulfurization ash as-recycled admixture is used for the preparation of grouting fire prevention material, from the technique point of view, the environmental safety of them is very good.

Adsorption mechanism of Pb 2+ ions by Fe 3 O 4 , SnO 2 , and TiO 2 nanoparticles Abstract Nanosized sorbents for the removal of heavy metal ions are preferred due to high surface area, smaller size, and enhanced reactivity during adsorbate/adsorbent interactions. In the present study, Fe3O4, SnO2, and TiO2nanoparticles were prepared by microemulsion-assisted precipitation method. The particles were characterized by BET surface area, X-rays diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, transmittance electron microscopy (TEM), and X-ray photoelectron (XPS) spectroscopy. The respective particle sizes calculated from TEM were 7 nm (± 2), 10 nm (± 2), and 20 nm (± 3) for Fe3O4, SnO2, and TiO2. The adsorbents were employed for the adsorption of Pb2+ ions from the aqueous solutions. The respective maximum adsorption capacity for Fe3O4, SnO2, and TiO2 nanoparticles was 53.33, 47.21, and 65.65 mg/g at 313 K. Based on the exchange reaction taking place on the surfaces of Fe3O4, SnO2, and TiO2, it is concluded that Pb2+ ions are adsorbed in hydrated form. The X-ray photoelectron spectroscopy (XPS) studies also support the exchange mechanism and confirmed the presence of elements like Fe, Sn, Ti, Pb, and O and their oxidation states. Both Langmuir and Freundlich models in non-linear form were applied, however, based on RL values, the Langmuir model fits well to the sorption data. Moreover, adsorption parameters were also determined by using non-linear form of the Langmuir model along with statistical approaches to remove error. The qm and Kb values confirm better adsorption capacity and binding strength for Pb2+ ions as compared to the values reported in the literature.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Der Hautarzt

Pigmentierte Flecken als mögliche Frühzeichen genetischer Syndrome Zusammenfassung Einzelne kongenitale oder in früher Kindheit auftretende Pigmentflecken sind unbedeutend, in Mehrzahl, bei großer oder einem Muster folgender Ausdehnung sind sie jedoch nicht selten erstes Anzeichen eines zugrunde liegenden genetischen Syndroms. Der vorliegende Beitrag gibt einen Überblick über die klinische Signifikanz multipler Café-au-lait-Flecken, multipler Lentigines und von Pigmentmosaiken und diskutiert die Differenzialdiagnose hiermit assoziierter Syndrome. Deren Frühdiagnose, an der der Dermatologe entscheidenden Anteil haben kann, ist nicht nur für die Erbberatung wichtig, sondern kann auch zur Vermeidung z. T. lebensbedrohlicher Komplikationen beitragen.

Rolle des Dermatologen bei der Syndromerkennung

Panorama Dermatologische Praxis

Adulter Morbus Still Zusammenfassung Der adulte Morbus Still manifestiert sich als seltenes autoinflammatorisches Syndrom typischerweise mit der Symptomtrias hohes Fieber, Still-Exanthem und Gelenkbeteiligung. Die Diagnosestellung erfolgt anhand der Diagnosekriterien nach Yamaguchi und nach umfangreicher Ausschlussdiagnostik anderer rheumatologischer, infektiöser und maligner Erkrankungen. Standardtherapie ist die Behandlung mit systemischen Steroiden. Bei unzureichendem Therapieerfolg kommen Basistherapeutika wie Azathioprin, Methotrexat oder Interleukin-1- und -6-Blocker zum Einsatz.

Haaranomalien bei syndromalen Erkrankungen Zusammenfassung Genetisch bedingte Erkrankungen mit Hyper- oder Hypotrichose sind klinisch und genetisch ausgesprochen heterogen. Dies trifft in besonderem Maße auf ektodermale Dysplasien, aber auch auf hereditäre Syndrome zu, bei denen außer den Haaren weitere Strukturen und Organe betroffen sind. In dieser Übersichtsarbeit besprechen wir verschiedene Krankheitsbilder mit vermehrtem und vermindertem Haarwachstum, wobei der Fokus auf den klinischen Merkmalen und den zugrunde liegenden genetischen Defekten liegt.

Follikuläre Hyperkeratosen bei Zöliakie

Stigmatisierungserleben bei Psoriasis – qualitative Analyse aus Sicht von Betroffenen, Angehörigen und Versorgern Zusammenfassung Hintergrund Zahlreiche Studien zeigen, dass Psoriasis mit starken Einbußen in nahezu allen Dimensionen der gesundheitsbezogenen Lebensqualität einhergeht. Ein wichtiger Aspekt dabei ist das Stigmatisierungserleben der Betroffenen. Fragestellung Ziel dieser Studie war die Erfassung des Stigmatisierungserlebens von Menschen mit Psoriasis und Erfahrungen mit Stigmatisierung aus Sicht von Betroffenen, Angehörigen und medizinischen Versorgern. Material und Methoden Durchgeführt wurden qualitative Erhebungen in Form von Fokusgruppen und Einzelinterviews mit Betroffenen, Angehörigen und medizinischen Versorgern. Die Daten wurden inhaltsanalytisch ausgewertet. Ergebnisse Die Ergebnisse zeigen, dass Stigmatisierung von allen befragten Gruppen wahrgenommen wird. Auch wurde deutlich, dass dabei die Selbststigmatisierung eine besondere Rolle einnimmt: Betroffene, Angehörige und medizinische Versorger beschreiben sie als größte Belastung bzw. Einschränkung der Betroffenen in verschiedenen Lebensbereichen, wie Arbeit, Freizeit und Partnerschaft. Dabei zeigten sich keine wesentlichen Unterschiede im Geschlecht und über verschiedene Altersgruppen hinweg. Schlussfolgerung Mögliche Wissensdefizite Nichtbetroffener und falsche Annahmen der Betroffenen über die Einstellungen Nichtbetroffener können beispielsweise im Rahmen von Begegnungen zwischen Betroffenen und Nichtbetroffenen, aber auch zwischen Betroffenen und medizinischen Versorgern, abgebaut werden und somit das öffentliche wie auch das Selbststigma reduzieren.

Rezepturvorschläge zu Mometasonfuroat-Kombinationen

Zwei neutrophile Dermatosen und ein multiples Myelom Zusammenfassung Das Pyoderma gangraenosum und die subkorneale Pustulose sind neutrophile Erkrankungen. Bei einem Patienten können sehr selten unterschiedliche neutrophile Dermatosen gemeinsam auftreten, auch mit einer zeitlichen Latenz. Darüber hinaus scheint es einen indirekten Zusammenhang zwischen einer Ig(Immunglobulin)A-Gammopathie und einer neutrophilen Dermatose zugeben. Deshalb muss bei Vorliegen einer neutrophilen Dermatose eine Gammopathie immer abgeklärt werden.

Syndrome mit vaskulären Anomalien der Haut Zusammenfassung Hintergrund Bei vielen komplexen genetischen Syndromen stellen unterschiedliche vaskuläre Nävi oft ein wichtiges diagnostisches Merkmal dar. Ziel der Arbeit In der Praxis tätige Dermatologen sollen in die Lage versetzt werden, diese kutanen Zeichen zu erkennen und einzuordnen. Material und Methoden Anhand der Literatur und eigener Beobachtungen beschreibt diese Übersicht 14 verschiedene Syndrome, bei denen unterschiedliche kapilläre Nävi vom Dermatologen als Leitsymptom erkannt werden können. Ergebnisse Die folgenden Kapillarnävi lassen sich in der Syndromdiagnostik unterscheiden: Naevus flammeus des Sturge-Weber-Syndroms (GNAQ); Portweinnävus vom Proteus-Typ (AKT1); Portweinnävus vom Typ „PIK3CA-related overgrowth spectrum" (PROS); medianer Portweinfleck vom PROS-Typ; retikulärer Kapillarnävus als Hinweis auf das Megalenzephalie-Kapillarnävus-Syndrom, das ebenfalls zum PROS gezählt wird; Cutis marmorata teleangiectatica congenita (Van-Lohuizen-Syndrom); Naevus roseus; Naevus vascularis mixtus; rhodoider Nävus (RASA1); Naevus anaemicus als Hinweis auf Neurofibromatose 1; Carter-Mirzaa-Flecken (STAMBP). Schlussfolgerung Eine diagnostische Schwierigkeit besteht darin, dass noch längst nicht alle mit Kapillarnävi assoziierten Syndrome molekular aufgeklärt sind. Aus diesem Grund haftet dieser Übersicht etwas Vorläufiges an. Anderseits besteht für praktisch tätige Dermatologen die faszinierende Möglichkeit, die weiteren molekulargenetischen Fortschritte auf diesem Gebiet dadurch voranzutreiben, dass sie angesichts ungewöhnlicher vaskulärer Anomalien den Spezialisten aus Dermatologie, Pädiatrie und Humangenetik jene Fragen stellen, die für eine molekulare Syndromerkennung wichtig sind.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medizinrecht

Anmerkung zu BSG, Urt. v. 24.10.2018 – B 6 KA 43/17 R (Thüringer LSG)

Anmerkung zu BSG, Urt. v. 24.10.2018 – B 6 KA 44/17 R (LSG Schleswig-Holstein)

Rechtsprechung kurz berichtet

Anmerkung zu BGH, Urt. v. 15.11.2018 – III ZR 69/17 (OLG Dresden)

Inkompatibilitätsregelungen des Transplantationsgesetzes bei der "Hirntod"-Diagnostik

Hinweisgeber im Krankenhaus

Anmerkung zu BGH, Beschl. v. 14.11.2018 – XII ZB 107/18 (LG Landshut)

Konkretisierung einer Patientenverfügung Zusammenfassung 1. Die erforderliche Konkretisierung einer Patientenverfügung kann sich im Einzelfall bei einer weniger detaillierten Benennung bestimmter ärztlicher Maßnahmen durch die Bezugnahme auf ausreichend spezifizierte Krankheiten oder Behandlungssituationen ergeben. Ob in solchen Fällen eine hinreichend konkrete Patientenverfügung vorliegt, ist dann durch Auslegung der in der Verfügung enthaltenen Erklärungen zu ermitteln (im Anschluss an Senatsbeschluss BGHZ 214, 62 = FamRZ 2017, 748). 2. Urkunden über formbedürftige Willenserklärungen sind nach allgemeinen Grundsätzen auszulegen. Außerhalb der Urkunde liegende Umstände dürfen dabei aber nur berücksichtigt werden, wenn der einschlägige rechtsgeschäftliche Wille des Erklärenden in der formgerechten Urkunde einen wenn auch nur unvollkommenen oder andeutungsweisen Ausdruck gefunden hat. 3. Die vom Beschwerdegericht vorgenommene Auslegung einer Patientenverfügung kann vom Rechtsbeschwerdegericht grundsätzlich nur darauf überprüft werden, ob der Auslegungsstoff vollständig berücksichtigt worden ist, ob gesetzliche oder allgemein anerkannte Auslegungsregeln, sonstige Erfahrungssätze oder die Denkgesetze verletzt sind oder ob die Auslegung auf Verfahrensfehlern beruht.

Plausibilitätsprüfung – Mindestzeiten bei Nebeneinanderberechnung von Gesprächsleistungen und Ordinationskomplex Zusammenfassung 1. Der Ordinationskomplex gewinnt (auch) für das Tageszeitprofil eines Vertragsarztes dann Bedeutung, wenn in der Leistungslegende oder in einer Anmerkung zu einer anderen Gebührenordnungsposition des EBM-Ä für den Fall der gleichzeitigen Leistungserbringung eine erhöhte Mindestzeit vorgegeben ist. 2. Ergeben sich in einer wegen auffälligen Tageszeitprofilen durchgeführten Prüfung Anhaltspunkte, die auf eine systematisch unrichtige Abrechnung hindeuten, ist die Kassenärztliche Vereinigung berechtigt, die Prüfung auch dann auf Folgequartale auszudehnen, wenn in diesen Quartalen keine auffälligen Tageszeitprofile vorlagen. 3. Die Angaben eines Vertragsarztes gegenüber der KÄV über eine von ihm erbrachte Leistung sind dann grob fahrlässig unrichtig erfolgt, wenn der Vertragsarzt sich vorwerfbar der naheliegenden Erkenntnis verschlossen hat, dass die Leistung nur unter bestimmten Voraussetzungen abrechenbar ist (Leitsätze des Bearbeiters).

Heranziehung eines ermächtigten Krankenhausarztes zum ärztlichen Bereitschaftsdienst Zusammenfassung Ein ermächtigter Krankenhausarzt kann nicht zum ärztlichen Bereitschaftsdienst herangezogen werden. (Leitsatz des Bearbeiters)

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Orofacial Orthopedics / Fortschritte der Kieferorthopädie

Influence of the three-dimensional printing technique and printing layer thickness on model accuracy Abstract Objective The accuracies of three-dimensional (3D) printed dental models using various digital light processing (DLP) and stereolithography (SLA) printers at different thicknesses were compared. Materials and methods Based on digital dental models (originally digitized using R700; 3Shape, Copenhagen, Denmark), physical dental models were printed using three types of DLP printers: (1) EvoDent (UnionTec, Shanghai, China) with layer thicknesses of 50 μm and 100 μm; (2) EncaDent (Encashape, WuXi, China) with layer thicknesses of 20, 30, 50 and 100 μm; (3) Vida HD (Envisioned, Dearborn, MI, USA) with layer thicknesses of 50 and 100 μm. Models with the SLA printer Form 2 (Formlabs, Somerville, MA, USA) were printed with layer thicknesses of 25, 50 and 100 μm. All 22 printed models were converted to digital dental models using a D2000 model scanner (3 Shape, Copenhagen, Denmark) and compared three-dimensionally to the source files using Geomagic Qualify 12.0 (3D Systems, Rock Hill, SC, USA). Results The printing accuracy of all printers was higher at 50 μm. When the layer thickness was set at 100 μm, the printing speed and printing accuracy of DLP printer were both superior to those of the SLA printer. In all groups, the EvoDent 50 μm group had the highest consistency with the source files (mean absolute deviation of 0.0233 mm in the maxilla and 0.0301 mm in the mandible). While the accuracy of Form 2 100 μm group was the lowest (mean absolute deviation of 0.0511 mm in the maxilla and 0.0570 mm in the mandible). Conclusion For the 3D printers studied, 50 μm was the optimum layer thickness for DLP technology, and the printing accuracy using SLA technology increased with decreasing layer thickness. The DLP technology also had higher printing accuracy at a layer thickness of 100 μm. EvoDent 50 μm had the highest and Form 2 100 μm the lowest printing accuracy.

Gender-dependent impact of aging on facial proportions Abstract Purpose Facial proportions in younger people have been evaluated in several studies. However, the number of older people who need orthognathic surgery is growing steadily. The aim of this study was to evaluate facial morphology in Caucasians accounting for age and gender. Methods Three-dimensional facial scans of 240 healthy volunteers were taken. The subjects were divided into males and females, then into three groups by age (21–35, 36–50 and 51–65 years). Landmarks and artificial planes were placed in the scans. Distances, relations and angles between them and the artificial frontal plane were recorded. Results Nearly all distances between the tragion and the landmarks in the middle of the face increased with the age of the volunteers. Therefore, the soft tissue of the face grows horizontally with increasing age. Also, the length of the upper lip increased with age. The percentage of subnasale-stomion and stomion-menton distances of the total subnasale-stomion-menton measurement changed significantly (men: p = 0.149; women: p < 0.001) during aging in females but not in males. The landmarks in the upper and middle third of the face were closer to the frontal plane in women than in men. Conclusion Using the created frontal plane for evaluating landmarks in the sagittal plane facilitates measuring positions of soft tissue. There are significant changes in distances, angles and relations during aging which can be very important for planning orthognathic surgery.

Mitteilungen der DGKFO

Biomechanical analysis of initial incisor crowding alignment in the periodontally reduced mandible using the finite element method Abstract Aims To reduce remaining plaque niches due to dental malocclusion after periodontal treatment and to avoid reinflammation of periodontitis, severe anterior crowding can be treated orthodontically. The treatment indication is motivated by aesthetic and functional needs. In this study the biomechanical behaviour of crowded lower front teeth in reduced periodontium is analysed. Methods Using the finite element (FE) method, a model of the mandible was constructed with an anterior crowding of 4 mm and a vertical bone loss of 4 mm in the front tooth area. A 0.3 mm (0.012″) round superelastic nickel titanium (NiTi) arch wire was fitted to an ideal positioned teeth set-up and was inserted into the brackets of teeth 34 to 44 in the crowded model. The premolars were used as the anchorage unit. Material parameters were adopted from previous investigations, including bone (homogenous, isotropic, E = 2 GPa), teeth (E = 20 GPa) and healthy periodontal ligament (PDL, bilinear elastic; E1 = 0.05 MPa; E2 = 0.2 MPa; ε12 = 7%). All simulations were compared to simulations with a physiological periodontal model to assess the effect of bone loss at teeth 42 to 32. Additionally, the influence of three arch wire materials (nonsuperelastic NiTi, superelastic NiTi and stainless steel) were analysed in a reduced model, including only brackets in position of the crowded front teeth, wire and ligatures. Wire force levels and stresses were determined to assess the influence of material variation. Results Initial tooth mobility is increased by a factor of 2.5 in case of a moderate periodontal defect. Front teeth with reduced attachment display increased strains in the periodontal ligament up to a factor of 2. Forces in the model with reduced periodontium were decreased by a factor of 2. Comparing different aligning arch wires, stainless steel appears to have the highest force and stress levels. Force levels of this alloy were 7.5 times higher than with the superelastic NiTi wire. Force levels of nonsuperelastic NiTi appeared to be 1.8 times higher than superelastic NiTi. Calculated stresses with stainless steel were 5 times higher than with the nonsuperelastic NiTi and 10 times higher than with superelastic NiTi. Conclusion Periodontally reduced incisors 42 to 32 are associated with an increased load on periodontal tissue and increased level of tooth mobility during fixed orthodontic treatment. This has to be considered by reducing orthodontic force levels and by selecting mechanics that reduce the load to the tissue.

Impact of specific orthodontic parameters on the oral health-related quality of life in children and adolescents Abstract Purpose The aim of the present study was to analyse the impact of specific orthodontic findings on oral health-related quality of life (OHRQoL) when taking into consideration age and psychological factors in children and adolescents. Methods In all, 250 children and adolescents with an indication for orthodontic diagnostics were recruited using a multicentre study design. Using validated and internationally acknowledged questionnaires, we assessed OHRQoL, health-related quality of life (HRQoL), self-esteem and behavioural problems. We also examined a selection of specific orthodontic findings using photos, model casts and cephalometric analyses, and investigated the impact of these parameters on OHRQoL using simple linear regression analyses. Thereafter, we added all the significant specific orthodontic and psychological parameters to a multiple linear regression model using a stepwise forwards selection procedure. Results We were able to identify different specific orthodontic findings that have a significant impact on OHRQoL. These were the type of lip closure, the position of the chin, the Little-index of the upper jaw, the overjet, the overbite and the ANB angle. Moreover, we were able to demonstrate that psychological and some specific orthodontic parameters have a significant impact on OHRQoL. Conclusion Specific orthodontic findings have a significant impact on patients' perceived OHRQoL. Further longitudinal studies are required to investigate whether the treatment and correction of these malocclusions also improve the OHRQoL of children and adolescents.

Dimensional changes of the alveolar ridge contour of the premolar extraction site in adolescents Abstract Purpose Premolar extraction in orthodontic therapy is common in adolescent patients. Knowledge of the tissue reaction in an extraction site is mainly based on studies with animal and adults. Thus, we aim to describe the time-dependent dimensional changes of the alveolar ridge contour of the premolar extraction site in adolescents. Methods Clinical data were obtained from a randomized controlled clinical trial (Universal Trial Number U1111-1132-6655), comparing treatment modalities with orthodontic space closure was initiated after 2–4 weeks (group A) and ≥ 12 weeks after tooth extraction (group B). Dental casts taken before the tooth extraction (T1) and before initiation of the space closure (T2) were digitalized with a 3D scanner and superimposed to analyze the dimensional changes of the alveolar ridge in early and later stage of wound healing. Linear mixed models were used for statistical analysis. Results Plaster models of 25 patients (mean age 15.2 years, 11 male and 14 female) with 66 extraction sites were enrolled. The average atrophic changes from tooth extraction to the early stage of wound healing (group A, n = 41) were in total 27.5% ± 11.8; labially 31.3% ± 15.1 and orally 23.6% ± 13.4. In group B (n = 25) the average atrophic changes were in total 38.6% ± 12.1; labially 46.2% ± 16.7; orally 31.3% ± 18.9. The atrophic changes between the groups in total (p = 0.031) and at the labial side (p = 0.012) were significant. The jaw affiliation was a significant parameter for all examined areas in regard to all cases (labial p = 0.019; oral p = 0.020; total p = 0.001). Atrophic changes between genders were not statistically different. Conclusions Alveolar atrophy increased over time after extraction primarily in the lower jaw at the labial side. The main atrophy occurred in the first healing phase of the extraction socket. Thus, timely coordination is important to preserve sufficient bone levels. The atrophic changes of the alveolar ridge in adolescents parallel those reported for adults.

Relationship between alveolar bone thickness, tooth root morphology, and sagittal skeletal pattern Abstract Purpose The goal of this work was to examine the relationship between sagittal facial pattern and thickness of alveolar bone in conjunction with root morphology of teeth by using cone beam computed tomography (CBCT). Methods The study was carried out on the CBCT scans from 3 group of patients (n = 20 in each group). The first group involved skeletal class 1, the second group involved skeletal class 2, and the third group involved skeletal class 3 patients. In all, 14 permanent teeth and interdental regions in the maxilla and mandible were evaluated. Root length and root width were measured on each tooth. Buccal cortical bone thickness, cancellous bone thickness, and lingual cortical bone thicknesses were measured in each interdental region. Analysis of variance, Kruskall–Wallis H and Mann–Whitney U tests were used for statistical comparisons. Results No significant difference was found between the groups for root length, root width, buccal cortical bone and lingual cortical bone thickness. A significant difference was observed between the groups for cancellous bone thickness as it was thicker in skeletal class 2 group. Cortical bone was thicker in the mandible compared to maxilla on both buccal and lingual sides and it was thicker in the posterior region compared to the anterior region on the buccal side. Conclusions Differences in cancellous bone thickness between different sagittal facial patterns and differences in cortical bone thickness between different alveolar regions should be taken into consideration when planning orthodontic tooth movements and anchorage mechanics.

Expression of lubricin in rat posterior mandibular condylar cartilage following functional mandibular forward repositioning Abstract Purpose The aim of the present study was to investigate the effects of mandibular forward repositioning on expression of lubricin in rat posterior condylar cartilage. Methods In total, fifty 5‑week-old female Sprague Dawley rats were divided randomly into experimental groups and control groups. The animals in the experimental groups were fitted with modified acrylic inclined planes to advance the mandible, whereas rats in the normal control groups were left intact. Rats were sacrificed on days 3, 7, 14, 21, and 30, and temporomandibular joint (TMJ) samples were collected. The expression of lubricin of the posterior mandibular condylar cartilage was evaluated by immunohistochemistry. Results In the control groups, higher expression of lubricin was observed in the proliferative zone of the posterior mandibular condylar cartilage compared with the hypertrophic zone during the experimental period. Compared with the control group, the positive signals for lubricin of the posterior mandibular condylar cartilage in the experimental animals were significantly higher on days 7, 14, and 21; however, no statistical difference was found on day 3 or 30. Conclusions Data analyses suggest that the bite jumping appliance temporarily enhanced lubricin expression, providing a good mechanical environment for the physiologic growth of the condyle and mandible, and contributes to TMJ remodeling by the regulation of condylar chondrocyte proliferation.

Mitteilungen der DGKFO

Influence of enamel sealing with a light-cured filled sealant before bracket bonding on the bond failure rate during fixed orthodontic therapy Abstract Purpose Fluoride-containing adhesives for enamel sealing are commonly used for the prevention of white spot lesions during fixed orthodontic treatment. Thus, we examined whether enamel sealing with L.E.D. ProSeal® (Reliance Orthodontic Products Inc., Itasca, IL, USA) before bracket bonding increases the rate of bond failure during orthodontic treatment. Methods In 20 adolescents (11–16 years, 10 male/10 female) at the start of fixed therapy, self-ligating SmartClip™SL3 metal brackets (3M Unitek, Monovia, CA, USA) were bonded to cleaned and conditioned (40% H3PO4, 30 s) buccal enamel surfaces of all permanent teeth except molars using Transbond™ XT (3M Unitek). In a split-mouth design, either L.E.D. ProSeal® (1st/3rd quadrant) or Clinpro™ XT Varnish (2nd/4th quadrant; 3M Unitek) was applied to enamel surfaces before (ProSeal®) or after (Clinpro™ XT Varnish) bracket bonding (200 teeth each; light curing: 20 s, Ortholux™ Luminous, 3M Unitek). Cumulative bond failure as total number of teeth with bracket detachment since start of therapy was documented every 3 months for a total of 12 months. Results Cumulative bond failure was higher for enamel sealing before bonding from 6 months onward reaching significance at 12 months (34/200) compared to sealing after bonding (24/200): p = 0.038; Cramér's V = 0.488; odds ratio (OR) = 1.5; relative risk (RR) = 1.4. The higher loss rate was limited to the lower arch, but evident within 3 months reaching significance at 9 and 12 months (p = 0.019/0.011, V = 0.636/0.630; OR = 1.7/1.75, RR = 1.5/1.6). In general, cumulative bond failure at 12 months was higher in the lower arch, but this was only significant for teeth sealed before bonding (p = 0.001, V = 0.303, OR = 3.4, RR = 2.8). Conclusions Enamel sealing with L.E.D. ProSeal® should be performed after bracket bonding to prevent increased bond failure and bracket loss in the lower dental arch.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Mycopathologia

Investigation on Microecology of Hair Root Fungi in Androgenetic Alopecia Patients Abstract Background This study focused on the differences in hairy root fungal microecology between androgenetic alopecia patients and healthy individuals. Methods Light microscopy was used to observe the morphology of hairy roots. Morphological observations were also performed in the positive specimens using scanning electron microscopy and transmission electron microscopy. The high-throughput sequencing method was used to detect the fungal microecology of hairy roots at different sites. Moreover, the comparison of fungal loads of Malassezia in different group and scalp area were tested by PCR. Results The fungi in the hair root observed by optical microscopy are mainly Malassezia yeast. The positive rate of Malassezia in the hair loss group (60%) was higher than that in the control group (40%). The detection efficiency of Malassezia examined by scanning electron microscopy was higher than that by light microscopy. Results acquired from high-throughput molecular sequencing of fungi suggested that Ascomycota was the dominant species, whereas in the occipital hair roots of the control group Basidiomycota was the dominant species in the hair loss group. Malassezia followed by Trichosporon were the most abundant fungal genera. The changes in abundance at the top and occipital region of the control group were more significant than those of the genus Fusarium, followed by Epicoccum and Malassezia. The load of Malassezia located on calvaria in the alopecia group was significantly higher than that in the control group. In the alopecia group, the load of Malassezia on the scalp was higher than that on the occipital region. The load of Malassezia globosa and Malassezia restricta in the hair loss group was higher on calvaria and occipital areas. Conclusion Malassezia had a positive correlation with the incidence of androgenic alopecia.

High-Virulence Cat-Transmitted Ocular Sporotrichosis Abstract The article describes an atypical case of cat-transmitted ocular sporotrichosis due Sporothrix brasiliensis in a young patient. This report contributes significantly to knowledge of sporotrichosis as an important neglected tropical disease. In addition, this condition is an important public health problem in ascending incidence.

Candida albicans Elicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer's Patches Abstract The details of how gut-associated lymphoid tissues such as Peyer's patches (PPs) in the small intestine play a role in immune surveillance, microbial differentiation and the mucosal barrier protection in response to fungal organisms such as Candida albicans are still unclear. We particularly focus on PPs as they are the immune sensors and inductive sites of the gut that influence inflammation and tolerance. We have previously demonstrated that CD11c+ phagocytes that include dendritic cells and macrophages are located in the sub-epithelial dome within PPs sample C. albicans. To gain insight on how specific cells within PPs sense and respond to the sampling of fungi, we gavaged naïve mice with C. albicans strains ATCC 18804 and SC5314 as well as Saccharomyces cerevisiae. We measured the differential gene expression of sorted CD45+ B220+ B-cells, CD3+ T-cells and CD11c+ DCs within the first 24 h post-gavage using nanostring nCounter® technology. The results reveal that at 24 h, PP phagocytes were the cell type that displayed differential gene expression. These phagocytes were able to sample C. albicans and discriminate between strains. In particular, strain ATCC 18804 upregulated fungal-specific pro-inflammatory genes pertaining to innate and adaptive immune responses. Interestingly, PP CD11c+ phagocytes also differentially expressed genes in response to C. albicans that were important in the protection of the mucosal barrier. These results highlight that the mucosal barrier not only responds to C. albicans, but also aids in the protection of the host.

Inhibitory Effects of Photodynamic Inactivation on Planktonic Cells and Biofilms of Candida auris Abstract Candida auris is an emerging pathogen that has caused numerous severe infections in recent years, and has therefore become a global concern for public health agencies. Most conventional antifungal agents, especially fluconazole, have shown limited effects on this pathogen. New methods to restrict this pathogen are in urgent demand. Antimicrobial photodynamic therapy (aPDT) has been shown to be a promising technique against multiple pathogenic fungi. This study sought to determine the in vitro effect of aPDT using methylene blue (MB) combined with light-emitting diode (LED) on the viability of planktonic cells and biofilms of five clinical strains of C. auris. MB (8, 16 and 32 μg/ml) was applied as the photosensitizer, and a LED (635 nm, 12 and 24 J/cm2) device was used as light source to activate the photosensitizer. The results showed that there was no growth of tested C. auris strains following aPDT on planktonic cultures. In addition, aPDT exhibited colony-forming unit reduction of up to 7.20 log10 against C. auris biofilms. These data demonstrate that in vitro aPDT with MB and LED offers promising potential for the treatment of C. auris infections.

Diversity of Onygenalean Fungi in Keratin-Rich Habitats of Maharashtra (India) and Description of Three Novel Taxa Abstract Extensive survey was carried out in the state of Maharashtra, India, as part of a 3-year project to explore keratinophilic fungal diversity for conservation and biotechnological potential. A total of 578 soil samples were collected from keratin-rich habitats across 24 districts of Maharashtra State. Hair-baiting technique and micro-dilution drop-trail method were employed for isolation and purification of keratinophilic fungi from soil. A total of 66 species belonging to 17 genera of order Onygenales were recorded in hair baits. Eleven taxa were found to be new to science, most of which were rare as they were recorded in only one sample out of the > 500 samples analyzed. Three novel taxa have been characterized at morphological and molecular level and described here as new to science. These taxa include Currahmyces indicus gen. et sp. nov., Canomyces reticulatus gen. et sp. nov., Ctenomyces indicus sp. nov. All these novel taxa are morphologically and phylogenetically distinct from known taxa of order Onygenales. The study indicates that systematic sampling of a larger area is needed to uncover the hidden (unknown) diversity of keratinophilic fungi which is overlooked in sporadic samplings as evident from previous studies.

Elbow Malformation with Osteoarthritis and Bone Destruction Caused by Chromoblastomycosis

Persistent hematogenous dissemination in pulmonary P. jiroveci infection Abstract Pneumocystis jiroveci pneumonia in non-HIV patients is infrequent and characterized by atypical presentations and increased severity. Although hematogenous dissemination from the lungs can lead to extrapulmonary infections, isolation of oocysts from blood in human subjects has not been documented. We report a case of P. jiroveci pneumonia with persistent isolation of oocysts from blood and positivity of P. jiroveci polymerase chain reaction. The patient presented with bilateral diffuse pulmonary nodules and received prolonged treatment with trimethoprim/sulfamethoxazole.

Mild Paracoccidioidomycosis Misdiagnosed as a Subcutaneous Mycosis

Antifungal Susceptibility Profile of Candida Albicans Isolated from Vulvovaginal Candidiasis in Xinjiang Province of China Abstract We investigated the antifungal susceptibility profiles of 207 independent Candida albicans strains isolated from patients with vulvovaginal candidiasis (VVC) in Xinjiang Province of China. Using CLSI M27-A3 and M27-S4 guidelines, anidulafungin and micafungin were the most active drugs against C. albicans showing an MIC50/MIC90 corresponding to 0.016/0.0313 µg/mL, followed by caspofungin (0.25/0.25 µg/mL), posaconazole (0.125/0.5 µg/mL), ravuconazole (0.063/1 µg/mL), itraconazole (0.125/1 µg/mL), amphotericine B (0.5/1 µg/mL), isavuconazole (0.063/2 µg/mL), 5-flucytosine (1/2 µg/mL), voriconazole (0.125/4 µg/mL), and fluconazole (0.5/4 µg/mL). 96.1% (199)–100.0% (207) isolates were sensitive to the three echinocandins tested, amphotericine B and 5-flucytosine. The in vitro activity of triazoles against all isolates tested was variable; itraconazole and voriconazole had reduced the activity to almost half of the isolates (55.1% (114) and 51.2% (106) susceptible, respectively). Fluconazole was active against 76.3% (158) isolates tested. The new triazoles ravuconazole, isavuconazole and posaconazole showed good in vitro potency against 89.9% (186)–95.2% (197) of isolates with the geometric mean MIC (µg/mL) of 0.10, 0.12 and 0.14 µg/mL, respectively. In conclusion, our study indicates that for effective management of systemic candidiasis in Xinjiang Province of China, it is important to determine the susceptibility profiles of isolated C. albicans from patients with VVC.

Early Interaction of Alternaria infectoria Conidia with Macrophages Abstract Fungi of the genus Alternaria are ubiquitous indoor and outdoor airborne agents, and individuals are daily exposed to their spores. Although its importance in human infections and, particularly in respiratory allergies, there are no studies of how Alternaria spp. spores interact with host cells. Our aim was to study the early interaction of Alternaria infectoria spores with macrophages, the first line of immune defense. RAW 264.7 macrophages were infected with A. infectoria conidia, and the internalization and viability of conidia once inside the macrophages were quantified during the first 6 h of interaction. Live cell imaging was used to study the dynamics of this interaction. TNF-α production was quantified by relative gene expression, and the concentration of other cytokines (IL-1α, IL-1β, IL-6, IL-4, IL-10, IL-17, GM-CSF and INF-γ) and a chemokine, MIP-1α, was quantified by ELISA. Conidia were rapidly internalized by macrophages, with approximately half internalized after 30 min of interaction. During the first 6 h of interaction, macrophages retained the ability to mitotically divide while containing internalized conidia. The classical macrophage-activated morphology was absent in macrophages infected with conidia, and TNF-α and other cytokines and chemokines failed to be produced. Thus, macrophages are able to efficiently phagocyte A. infectoria conidia, but, during the first 6 h, no effective antifungal response is triggered, therefore promoting the residence of these fungal conidia inside the macrophages.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Molecular & Cellular Toxicology

Long non-coding RNA RP11-6O2.4 indicates poor prognosis and suppresses cell cycle progression through the p38-MAPK signaling pathway in gastric cancer Abstract Backgrounds: The role of long non-coding RNAs (lncRNA) in gastric cancer (GC) has been highlighted in studies conducted over the past decade. However, the potential clinical value and the mechanisms of action of RP11–6O2.4 in GC have not been thoroughly elucidated to date. The specific aim of the present study was to assess RP11–6O2.4 and to explore its role in human GC. Methods: Quantitative real-time polymerase chain reaction (qPCR) was performed to analyze the expression levels of RP11-6O2.4 in GC tissues, paired adjacent noncancerous tissues (ANTs) and GC cell lines. In addition, the correlation between RP11–6O2.4 expression and the clinical characteristics and prognosis of patients with GC was statistically analyzed. The effects of RP11-6O2.4 on the GC cell cycle transformation through the p38-MAPK signaling pathway were explored by flow cytometry, qPCR and Western blot analysis after treatment with SB203580, a p38MAPK specific inhibitor, in vitro. Results: The expression levels of RP11-6O2.4 in GC tissues were significantly lower than the paired ANTs (P<0.05). In addition, RP11–6O2.4 expression was significantly lower in cases with older age, longer maximum tumor diameter, higher ASA grade and deeper invasive depth (P<0.05). RP11–6O2.4 expression was significantly higher in cases with well/middle differentiation than poor/no differentiation; higher in cases without lymph node metastasis than in lymph node metastasis; and higher in cases in stage I/II than in stage III/IV. An in vitro assay showed that RP11–6O2.4 induced G0/G1 phase cell cycle arrest, likely by regulating the p38-MAPK signaling pathway. Conclusion: The above mentioned data suggested that RP11–6O2.4 was a tumor-suppressor gene in GC. RP11-6O2.4 might play an important role in the cell cycle transformation by regulating the p38-MAPK signaling pathway, thereby representing a specific biomarker and a potential molecular target for the treatment of GC.

Comparison of three human liver cell lines for in vitro drug-induced liver injury assessment: Huh7, HepaRG, and stem cell-derived hepatocytes Abstract Backgrounds: Drug-induced liver injury (DILI) is a major causal factor for failure in clinical trials and withdrawal of drugs from pharmaceutical markets. Therefore, a human cell-based in vitro system has been established to overcome the limitations of preclinical trials. However, previous studies focused on the drug metabolism in each cell line or described to be superior in one single cell line for assessing DILI. In this study, we used Huh7, HepaRG, and Hepatosight-S cells to evaluate the liver toxicity and dysfunction driven by DILI-inducing drugs. Methods: Cytotoxicity of 17 DILI-inducing drugs was assessed by LDH release assay and the drug-induced liver dysfunction was confirmed by albumin secretion. Furthermore, we analyzed the expression levels of phase I and phase II enzymes and nuclear receptors in each cell lines. Results: DILI-inducing drugs were differently detected in each cell line because each cell line differs on the expression of drug metabolic enzymes which associated with reactivity on DILI inducing drugs. Conclusion: To predict the responses of DILI-inducing drugs in human liver cells, using diverse cell lines having different drug metabolic capabilities is more suitable for predicting DILI.

Covalent conjugates of granulin-epithelial precursor-siRNA with arginine-rich peptide for improved stability and intracellular delivery in hepatoma cells Abstract Backgrounds: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, little is known about the molecular mechanisms of HCC development, progression, or effective therapeutic approaches. Recently, granulin-epithelin precursor (GEP) has been suggested as a novel factor that can control HCC cell proliferation. Thus, we aimed to develop new cell-permeable and stable genetic agents that can control GEP expression in HepG2 cells. Methods: Small interfering RNA-GEP (GEP siRNA) was used for the development of therapeutic agents for HCC treatment. GEP siRNA was first modified by adding polyethylene glycol (PEG) at the terminus. Arginine-rich peptide (ARP) was chemically conjugated with PEGylated GEP siRNA. Chemical conjugates of GEP siRNA-PEG-ARP were evaluated for cytotoxicity and bioavailability, including stability against DNase I enzymatic activity and GSH. The conjugate was further evaluated for intracellular distribution and cell proliferation effects. Results: The optimal conjugation ratio of GEP siRNA to ARP was a 1:10 molar ratio, and stability was confirmed using DNase I and glutathione stability assays. Conjugates showed increased intracellular uptake and distribution in HepG2 cells. Interestingly, HepG2 cells treated with conjugates showed significantly decreased cell proliferation. Conclusion: These results provide insights into the importance of chemical modification of unstable genetic therapeutics for HCC treatment. Conjugation of PEGylated GEP siRNA with ARP may be a potential HCC therapeutic agent.

Interactive effects between components in binary mixtures of zinc sulfate and iron oxide nanoparticles on Daphnia magna Abstract Backgrounds: The concern in the toxicological impact of nanomaterials on aquatic organisms has grown, due to the high adsorption capacity for (in) organic compounds in the aquatic environment. In order to evaluate the toxicity of mixtures composed with metal ion and metal oxide nanoparticles and the interaction between components in binary mixtures, we tested the mixture toxicity of iron oxide nanoparticles (i.e., PVP-Fe3O4 NPs) and zinc sulfate (ZnSCU) on Daphnia magna. Methods: The toxicity of binary mixtures with different concentration-combinations were identified by the effective concentration values (ECxmix) based on the concentration-response curves. Concentration addition index (CAI) and effect addition index (EAI) were applied for examining the interaction between components in binary mixtures. Results: The findings from this study implied the ZnSO4 had a high toxic effect on D. magna more than PVP-Fe3O4 NPs and the synergistic toxicity in binary mixtures were depended on the toxic effects of ZnSO4 and their exposure concentration rather than those of PVP-Fe3O4 NPs. Interestingly, the antagonistic effects between ZnSO4 and PVP-Fe3O4 NPs in binary mixtures showed in the high concentration-combinations suggesting that antagonism in toxicity may be due to the high adsorption capacity of PVP-Fe3O4 NPs for organic compounds. Conclusion: In this study, synergistic- and antagonistic effects in binary mixtures with various concentrationcombinations will provide important information for elucidating the toxicity mechanism of mixtures composed inorganic compounds and metal oxide nanoparticles (MONPs). However, in order to conduct the risk assessment of environmental nanoparticle, further studies regarding the mixture toxicity of nanomaterials with environmentally relevant concentrations and the interaction between components will be required.

Novel GRN mutations in Koreans with Alzheimer's disease Abstract Backgrounds Alzheimer's disease (AD) and fronto-temporal dementia (FTD) are the two most common neurodegenerative diseases leading to early onset dementia (<65 years). Mutations in the amyloid precursor protein, presenilin, and presenilin 2 genes are involved in some cases of familial early-onset AD (EOAD), while the microtubule-associated protein tau (MAPT) and pro-granulin (GRN) mutations have been mainly identifed in FTD patients. Clinically, FTD was often misdiag-nosed and confused with AD or psychiatric disorders, which could be a challenge in disease diagnosis. Methods: We performed mutation analysis of GRN in 89 Korean patients with clinically diagnosed EOAD. In silico predictions were also performed for the variants to estimate their role in different disorders. Results: No pathological mutations in MAPT was identified, but we identified two novel genetic variations in the GRN gene: p.Leu585Phe (c.1767G>T) and c.IVS8+23_+26delTGGG, which occurred independently in two EOAD patients (frequenct of 2/89, 2.2%). Using a combination of clinical and association studies, in silico prediction, and 3-D modeling software, we suggest that both mutations are probably pathogenic and involved in FTD. Conclusion: Our data suggest that it would be important to re-examine EOAD patients who had been diagnosed when the FTD spectrum was not well described and the causative FTD genes had not yet been identifed. In addition, we propose initially analyzing genes associated with the frst form of suspected dementia and, if the results are negative, studying genes implicated in the other form of dementia.

Roles of integrins in regulating metastatic potentials of cancer cell derived exosomes Abstract Purpose of review: Exosomes are nano-sized extracellular vesicles ranging from 30–150 nm in diameter. Exosomes interact with nearby or distantly localized recipient cells by involving ligand/receptor binding at the surface of recipient cells or fusion with plasma membrane of recipient cells. A number of recent literatures support the role of integrins in mediating metastatic process of cancer cell derived exosomes. While exosomes need to dock on the surface of recipient cells to transmit signals or transfer their contents, the process of docking and uptake of exosomes by recipient cells is poorly understood. This review discusses the recent reports that suggest the potential roles of exosomal integrins in mediating docking and uptake of exosomes, and how these processes are related to metastatic potentials of cancer cell derived exosomes. Recent findings: Exosomal integrins (α6β4, α6β1, αvβ5, αvβ3, αvβ6) and exosomal integrin ligands (vinculin, fibronectin) have been recently reported to play roles in cancer metastasis. As exosomes are involved in cell-to-cell communication, integrins and their ligands in cancer cell derived exosomes can contribute to progression by selecting target tissues and triggering integrin mediated signaling cascades to form new metastatic niche. Recent studies also suggest that exosomal integrins and their ligands can be targeted for developing exosome based diagnostics and therapies.

Mild NO preconditioning protects H9c2 cells against NO-induced apoptosis through activation of PI3K/Akt and PKA-dependent pathways Abstract Backgrounds: Nitric oxide (NO) plays a key role in cardioprotection. Its role against cardioprotection is dependent on the level of NO. Although it is well known that NO preconditioning has cardioprotective effects, but its mechanism remains unsatisfactory. Methods: To induce NO preconditioning, H9c2 cells were treated with low NO concentration and subsequently induced apoptosis by high NO. The signalling and anti-apoptotic effects of NO preconditioning were monitored by Western blotting, facs analysis. Results: Sodium nitroprusside (SNP)-induced cytotoxicity was inhibited by low SNP (0.3 mM) preconditioning. Furthermore, low SNP phosphorylated Akt/FoxO1 in the presence of high SNP (1.5 mM), while phosphorylated Akt/FoxO1 and viability were reversed by PI3K inhibitor. Also, low NO-induced CREB phosphorylation with high NO was inhibited by PKA inhibitor, indicating that NO preconditioning protects NO-induced cytotoxicity in PKA dependently. Apoptotic inhibition with NO preconditioning was accompanied with increased Bcl-2, decreased Bax, and caspase3 activation, which was all reversed by LY294002. Conclusion: Our results indicate that low NO preconditioning prevent subsequent high NO-induced apoptosis via Akt/PKA/CREB activation in H9c2 cells.

LncRNA MALAT1 protects human umbilical vein endothelial cells against ox-LDL triggered cell death through regulation of MGP Abstract Backgrounds: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is an lncRNA that has been suggested as a key regulator in the onset of atherosclerosis (AS). This study described the role of MAL-AT1 in oxidized low density lipoprotein (ox-LDL)-induced endothelial cells death. Methods: Human umbilical vein endothelial cells (HU-VECs) were subjected to ox-LDL, before which the expression of MALAT1 was overexpressed by transfection. CCK-8 assay, flow cytometer detection, and western blot were carried out to evaluate cell viability, apoptosis and autophagy. qRT-PCR and western blot analyses were performed to investigate the regulatory relationship between MALAT1, Matrix Gla protein (MGP) and mTOR signaling to decode the underlying mechanism. Results: Up-regulation of MALAT1 attenuated ox-LDL-induced HUVECs lose, as evidenced by the promoted cell viability, and the decreased apoptosis rate. This finding was coupled with the down-regulated p53, Bax, active-caspase-3, Beclin-1 and LC3-II, as well as the up-regulated Bcl-2 and p62. Meanwhile, MALAT1 up-regulation promoted the phosphorylation of p70S6K and mTOR, and the expression of MGP. MGP up-regulation exhibited MALAT1-like propoties in preventing ox-LDL-induced cell death and mTOR deactivation. Of contrast, MGP silence affected HUVECs survival and mTOR signaling resulted in contrary impacts. Conclusion: The present work described that MALAT1 up-regulation prevented ox-LDL-mediated apoptosis and autophagy in HUVECs. The protective effects of MALAT1 might be partially via up-regulating MGP, which led to the activation of mTOR signaling.

Transcriptomics and proteomics analysis of Aβ (1-42)-induced neurotoxicity Abstract Backgrounds: β-Amyloid (Aβ) is a principal constituent of senile plaques in Alzheimer's disease (AD) and induces neuronal cell death. The molecular mechanism of how Aβ evokes neuronal cell death remains complicated, which were investigated in the present study. Methods: Using the human neuroblastoma cell line SHSY5Y, we investigated the neurotoxic effects of human β-Amyloid 1–42 (Aβ1–42) aggregates on gene expression profile and protein expression profile by using the Agilent GeneChip Human 1A (V2) Oligo MicroArray, Quantitative Real-time PCR, PF-2D and Western blot analysis. Results: Our results show that Aβ1–42 specifically influences gene and protein expression such as EGR1, eIF5A, PDE8A, ERp57 and ERp5 in pathways associated with apoptotic process, protein translation, cAMP catabolic process and response to endoplasmic reticulum stress. Conclusion: Although Genes with significant changes in transcriptomic analysis matched very few of the proteins identified in proteomics analysis, our findings will strengthen our knowledge concerning the molecular mechanisms underlying AD.

Prevention and relaxation effects of Liriope platyphylla on bronchial asthma in vitro model by suppressing the activities of MAPK/NF-κB pathway Abstract Backgrounds: Bronchial asthma (BA) is a common type of asthma, defined as a chronic inflammation, hyperplasia, and hypercontraction of the airway. In this study, we investigated whether Liriope platyphylla extract (LPP) can help prevent inflammation, suppress hyperplasia, and support relaxation via regulation of MAPK/NF-κB activity. Methods: To investigate the inflammation prevention effects, A549 cells, a human airway epithelial cell line, were pretreated with various concentration of LPP and then treated with EGF recombinant (10 ng/mL). Anti-hyperplasia and muscle relaxation experiments were performed with asthma condition human bronchial smooth muscle (hBSM) cells. The effects of LPP on MAPK/NF-κB activity and MAPK/NF-κB-related signaling, such as COX-2 and iNOS expression, was analyzed through western blot analysis. The mRNA expression levels of Th-2-cell-related cytokines, including IL-6 and TNF-α, and contraction-related factors, such as PLCβ, IP3R, and MLCK, were determined by real-time PCR. Results: LPP pretreatment significantly reduced MAPK/NF-κB activity in EGF-induced asthma condition A549 cells. Therefore, there was significant suppression of both COX-2 and iNOS expression. In addition, the mRNA expression of IL-6 and TNF-α was dose depen-dently reduced. Although there was no statistical significance, factors related to contraction showed a tendency to decrease. Conclusion: Based on our results, we believe that LPP shows good potential for application as a therapeutic agent for asthma through inflammation prevention and bronchial smooth muscle relaxation.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
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6948891480

alsfakia@gmail.com