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International audience; Recent knowledge about biological joint morphogenesis opens new perspectives in mechanics to automate joint contact surface design. The present work evaluates the feasibility of a generative design method inspired by the joint morphogenesis process to develop contact surfaces. A finite element model of joint morphogenesis reported in literature was implemented. This morphogenesis process was adapted and implemented for mechanical applications. The results show that the bioinspired joint shaping process adds matter in the zones next to the contact zone decreasing the contact pressure (up to 57%). The results demonstrate the feasibility of implementing biological growing rules in generative design. Biologically inspired design, Geometry, Stress .

To analyze the structure of antibiotic prescriptions by dentists in Germany during a time-period of four years in relation to medical antibiotic prescriptions.We collected nationwide data from all statutory health insurances on dental prescriptions of systemic antibiotics from 2012 to 2015. The annual reports of the "Research Institute for Local Health Care Systems" (WIdO, Berlin) provided the basis for this longitudinal data base analysis. The types of antibiotics, the number of prescriptions and the prescribed 'defined daily doses' (DDD) were analyzed. The results were compared to antibiotic prescriptions of German physicians.An average of 8.8% per year of all antibiotic prescriptions is issued by dentists. The mostly prescribed antibiotic is amoxicillin. The share of amoxicillin on all dental prescriptions increased from 35.6% in 2012 to 45.8% in 2015 (p 0.01). About three-quarters of all dentally prescribed DDD can be attributed to amoxicillin and clindamycin. On the part of the physicians the proportion of clindamycin is 18 fold lower than in the dental field.Dental and medical antibiotic prescriptions in Germany show statistically significant differences regarding the shares of the prescribed antibiotics. In an international comparison the high proportion of Clindamycin in Germany is noticeable.

Using a 445-nm semiconductor laser for tissue incision, an effective cut is expected due to the special absorption properties of blue laser light in soft tissues. The aim of the present study was the histological evaluation of tissue samples after incision with a 445-nm diode laser. Forty soft tissue specimens were obtained from pork oral mucosa and mounted on a motorized linear translation stage. The handpiece of a high-frequency surgery device, a 970-nm semiconductor laser, and a 445-nm semiconductor laser were connected to the slide, allowing a constant linear movement (2 mm/s) and the same distance of the working tip to the soft tissue’s surface. Four incisions were made each: (I) 970-nm laser with conditioned fiber tip, contact mode at 3-W cw; (II–III): 445-nm laser with non-conditioned fiber tip, contact mode at 2-W cw, and non-contact mode (1 mm) at 2 W; and (IV): high-frequency surgery device with straight working tip, 90° angulation, contact mode at 50 W. Histological analysis was performed after H&E staining of the embedded specimens at 35-fold magnification. The comparison of the incision depths showed a significant difference depending on the laser wavelength and the selected laser parameters. The highest incision depth was achieved with the 445-nm laser contact mode (median depth 0.61 mm, min 0.26, max 1.17, interquartile range 0.58) (p

Mehr als 50 Prozent der Patienten in der Zahnarztpraxis sind heutzutage multimorbid und nehmen deshalb mehr als ein Medikament ein (Halling 2013). Hieraus konnen sich wichtige arzneimittelbezogene Probleme (ABP) oder unerwunschte Arzneimittelwirkungen (UAW) wie Nebenwirkungen und Interaktionen mit zahnarztlich rezeptierten Medikamenten wie Analgetika, Antibiotika und Lokalanasthetika ergeben. Dieser Beitrag soll helfen, Nebenwirkungen und Interaktionen im Rahmen einer Polypharmazie zu erkennen, um die Medikation optimal an die Bedurfnisse und die Versorgungssituation des Patienten anzupassen.

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer&rsquo, s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction, p &lt, 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization.

Monocarboxylate transporters (MCT) 1, 2 and 4 play an important role in tumor metabolism. The amount of lactate transported by MCT's highly correlates with overall survival. Furthermore, glycolysis and hypoxia are possible causes for radiation resistance.An oral squamous cell carcinoma cell line (CAL27, ATCC) was analyzed in an in vitro cell assay. After incubation with two different inhibitors for MCT1 (AR-C122982/SR-13800 and AR-C155858/SR-13801, Tocris) or for MCT4 (simvastatin, Sigma-Aldrich and 2-cyano-3-(4-hydroxyphenyl)-2-propenoic acid (CHC), Tocris), cells were irradiated with six gray with a Gammacell 2000 (Nuklear Data). For analysis, cell counting assay, wound healing assay, MTT assay and clonogenic assay were applied.Cell counting assay showed significant lower results for simvastatin, CHC and for the highest concentrations of AR-C122982 and AR-C155858 (p0.03). Additionally, cell counts decreased significantly with irradiation after 72 hours (p0.05) only for AR-C122982, CHC and simvastatin. The clonogenic assay confirmed these results with substantially reduced growth when incubated with CHC, simvastatin and AR-C155858 (p0.002). Furthermore, MCT1 and 4 inhibition led to highly reduced migration (p0.05). There again, comparing the wound healing assay of irradiated to non-irradiated tests showed contrary results (controls: p0.001; AR-C155858: p0.05; AR-C122982: p0.32; CHC: p0.1; simvastatin p0.1). The MTT assay presented significant effects with MCT1 and 4 inhibition (simvastatin/AR-C122982/CHC: p0.007). Irradiated cells showed significantly lower expression after only 48 h compared to non-irradiated cells (simvastatin/AR-C122982/CHC: p0.02).Inhibition of MCT, especially MCT4 may represent a possible tool to overcome radiation resistance in tumor cell lines.MCT Inhibitors may be used as a possible therapeutic approach to sensitize OSCC to radiation.

Melanoma-associated antigens A had been detected repeatedly in oral squamous cell carcinoma, but not in healthy mucosa. Additionally, patients with MAGE-A expressing cancers are regarded to have a worse survival prognosis, so that MAGE-A are supposed to be part of carcinogenesis. Which role these antigens fulfill within OSCC is still, up today, largely unknown. This study examines the hypothesis that MAGE-A is being produced in OSCC but not in mucosa tissue and if MAGE-A has any correlation to clinical patient’s parameters like tumor size, lymph node metastasis, distant metastasis, overall survival, and recurrence. For this purpose, 50 tumor samples and 39 mucosa samples were analyzed by means of PCR and immunohistochemical staining with the antibody 6C1. Forty of 41 stained tumor samples showed a positive antibody reaction with a maximum staining rate of 53%. Sixteen mucosa samples showed a mild positive reaction. The PCR revealed a linear expression pattern of MAGE-A in which the genes are proportionally expressed in OSCC. We did not find any relationship between MAGE-A and tumor size, overall survival, or recurrence. There was also no connection between MAGE-A and tumor parameters Hif-1 and LDH. Their expression was detected tendentially in tumors with higher staging, advanced lymph node metastasis, and rising age of the patients. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis (p = 0.007 and p = 0.004). Patients got distant metastasis and influence of MAGE-A on metastatic behavior could not be verified. The genes MAGE-A3 and -A4 are consequently qualified as tumor markers in the field of diagnosis and follow-up of OSCC. Two genes have great potential as target proteins in immunotherapy. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis.

Purpose To analyze the prescribing patterns of analgesics by dentists in Germany during an investigation period of five years in comparison to analgesic prescriptions by physicians and in relation to international prescribing data. Materials and methods We analyzed nationwide data of all prescriptions of analgesics and antiphlogistics (except strong opioids) on the basis of the annual reports of the German statutory health insurances from 2012 to 2016. The types of analgesics, the number of prescriptions and the prescribed 'defined daily doses' (DDD) itemized by dentists and physicians were analyzed. The results were compared with each other and assigned to international dental prescribing data. Results During the investigation period the number of dental prescriptions of analgesics decreased by 3.4%, on the part of the physicians the increase amounted to 10.4%. Ibuprofen is the first line analgesic in Germany, its share in the dental analgesic prescription volume increased from 61.9% in 2012 to 88.1% in 2016. In the international comparison it could be demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) play the most important role in nearly all countries. Conclusions Continual training activities and international monitoring of dental analgesic prescription patterns are necessary to develop guidelines for the rational and appropriate use of analgesics in dentistry.

Background/aim Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. Materials and methods In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. Results LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. Conclusion Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ), numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates, nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Further, the cell architecture and expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP-related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Background Photodynamic therapies (PDT) have become increasingly popular in the adjuvant treatment of different tumour entities. Chemotherapeutic agents, such as cisplatin may be used in combination with low-level laser therapy (LLLT) as laser photochemotherapy. The aim of this study was to investigate the effect of LLLT on cell bioviability of normal and malignant bone cells under chemotherapeutic conditions with either cisplatin or zolendronic acid in vitro. Methods Primary human osteoblasts (HOB) and an osteosarcoma cell line (Saos-2) were treated with different concentrations of zolendronic acid or cisplatin and irradiated twice with a diode laser (wavelength 670 nm, 120 s, energy outputs of 100mW/cm2, continuous wave mode). Cell viability was tested by XTT-assay and via histomorphological analysis. Results LLLT alone increased bioviability for both cell lines. LLLT lowered HOB viability at the three highest concentrations of cisplatin and zolendronic acid. For Saos-2, LLLT reduced cell viability at every concentration of cisplatin. In cases of incubation with zolendronic acid, similar to osteoblasts, LLLT lowered cell viability at the highest concentration only. Conclusions Based on the conditions of this study, laser photochemotherapy may be able to raise the cytotoxicity of cisplatin and zolendronic acid in benign and malignant bone cells. This could be of interest in the development of new therapeutic treatment modalities against neoplastic bone diseases like osteosarcoma.

Tagging systems allow users to interactively annotate a pool of shared resources using descriptive strings called tags . Tags are used to guide users to interesting resources and help them build communities that share their expertise and resources. As tagging systems are gaining in popularity, they become more susceptible to tag spam : misleading tags that are generated in order to increase the visibility of some resources or simply to confuse users. Our goal is to understand this problem better. In particular, we are interested in answers to questions such as: How many malicious users can a tagging system tolerate before results significantly degrade? What types of tagging systems are more vulnerable to malicious attacks? What would be the effort and the impact of employing a trusted moderator to find bad postings? Can a system automatically protect itself from spam, for instance, by exploiting user tag patterns? In a quest for answers to these questions, we introduce a framework for modeling tagging systems and user tagging behavior. We also describe a method for ranking documents matching a tag based on taggers' reliability. Using our framework, we study the behavior of existing approaches under malicious attacks and the impact of a moderator and our ranking method.

Low-level laser therapy (LLLT) is used in parodontitis treatment in combination with an antimicrobial photosensitizer. The purpose of this study was to investigate the combination of LLLT with cisplatin and zoledronic acid as potential photosensitizer in-vitro.Primary human fibroblasts (PHF) and head and neck squamous cell carcinoma cells (HNSCC, exactly UM-SCC-3) were treated with different concentrations of zoledronatic acid and cisplatin and irradiated twice with a diode laser (wavelength 670 nm, 2 min). Cell viability was tested by XTT assay and histomorphological analysis with HE staining.LLLT increased bioviability for both cell lines (p0.001). LLLT lowered PHF viability at the highest concentrations of cisplatin (p = 0.027 and p = 0.005) and zoledronic acid (p0.001). For HNSCCs, LLLT reduced cell viability at every concentration of cisplatin (all p0.05). In cases of incubation with zoledronic acid, similar to fibroblasts, laser therapy lowered cell viability at the highest concentration only (p0.001).Within the limits of this study, it can be concluded that LLLT enhances the effect of cisplatin and zoledronic acid in the discussed cells in order to develop new therapeutic options for cysts in the cranio-maxillofacial region and other appropriate indications.

Dobutamine is recommended for the treatment of sepsis-related circulatory failure in international guidelines. Furthermore, dobutamine has been demonstrated to improve liver function and hepatic perfusion after experimental hemorrhagic shock. Yet, it is unknown whether dobutamine may also induce hepatoprotective effects in sepsis. This study was designed to investigate the effect of dobutamine on survival, hepatic function, and microcirculation after polymicrobial sepsis in rat. Under general anesthesia, male Sprague-Dawley rats (n = 25/group) underwent pretreatment with dobutamine (10 μg/kg per minute) in the presence or absence of β1-receptor antagonist esmolol (500 μg/kg per minute), esmolol alone, or vehicle for 6 h, before induction of sepsis (cecal ligation and incision [CLI]). Sham-operated animals were treated likewise but underwent no CLI. Five hours after CLI, either liver function was assessed by plasma disappearance rate of indocyanine green (n = 5/group), or intravital microscopy was performed (n = 5/group) for evaluation of hepatic perfusion index and hepatic integrity (as propidium iodide-stained cells per field). Alternatively, survival time after induction of CLI was monitored under general anesthesia (n = 15/group). Compared with controls, dobutamine pretreatment significantly improved plasma disappearance rate of indocyanine green (13.8% ± 4.1% vs. 20.6% ± 4.6%; P = 0.029), hepatic perfusion index (275.0 ± 126.1 vs. 703.5 ± 177.4 pL/s per mm; P < 0.001), hepatocellular injury (22.2 ± 6.7 vs. 6.4 ± 3.1 cells per field; P < 0.001), and survival time (326 ± 20 vs. 603 ± 41 min; P < 0.001). Coadministration of esmolol abolished the protective effect of dobutamine completely. Our results indicate that pretreatment with dobutamine may improve survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat via β1-adrenoceptor activation. Dobutamine could therefore play a relevant role for hepatoprotection under septic conditions.

We present "Turkalytics," a novel analytics tool for human computation systems. Turkalytics processes and reports logging events from workers in real-time and has been shown to scale to over one hundred thousand logging events per day. We present a state model for worker interaction that covers the Mechanical Turk (the SCRAP model) and a data model that demonstrates the diversity of data collected by Turkalytics. We show that Turkalytics is effective at data collection, in spite of it being unobtrusive. Lastly, we describe worker locations, browser environments, activity information, and other examples of data collected by our tool.

A fundamental premise of tagging systems is that regular users can organize large collections for browsing and other tasks using uncontrolled vocabularies. Until now, that premise has remained relatively unexamined. Using library data, we test the tagging approach to organizing a collection. We find that tagging systems have three major large scale organizational features: consistency, quality, and completeness. In addition to testing these features, we present results suggesting that users produce tags similar to the topics designed by experts, that paid tagging can effectively supplement tags in a tagging system, and that information integration may be possible across tagging systems.

Automatically clustering web pages into semantic groups promises improved search and browsing on the web. In this paper, we demonstrate how user-generated tags from large-scale social bookmarking websites such as del.icio.us can be used as a complementary data source to page text and anchor text for improving automatic clustering of web pages. This paper explores the use of tags in 1) K-means clustering in an extended vector space model that includes tags as well as page text and 2) a novel generative clustering algorithm based on latent Dirichlet allocation that jointly models text and tags. We evaluate the models by comparing their output to an established web directory. We find that the naive inclusion of tagging data improves cluster quality versus page text alone, but a more principled inclusion can substantially improve the quality of all models with a statistically significant absolute F-score increase of 4%. The generative model outperforms K-means with another 8% F-score increase.

Melatonin may attenuate organ damage via direct antioxidative properties, and was recently demonstrated to reduce cardiac and hepatic injury through receptor-dependent effects. However, the relevance of an isolated activation of melatonin receptors for organ protection, excluding direct antioxidant effects, has not been established yet. This study was designed to investigate whether therapy with melatonin receptor agonist and hypnotic substance ramelteon may improve liver function, hepatic perfusion, and hepatic integrity after hemorrhagic shock in rat.Prospective, randomized, controlled study.University research laboratory.Male Sprague-Dawley rats (n = 10 per group).Animals underwent hemorrhagic shock (mean arterial pressure 35 +/- 5 mm Hg for 90 mins) and were resuscitated with shed blood and Ringer's lactate (2 hrs). At the end of shock, animals were treated with ramelteon (1.0 mg/kg intravenously), melatonin receptor antagonist luzindole plus ramelteon (each 1.0 mg/kg intravenously), or vehicle.In vitro, ramelteon displayed no relevant antioxidant capacity in an 2,2'-Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assay, compared with melatonin. In vivo, liver function was assessed by plasma disappearance rate of indocyanine green, and intravital microscopy was performed for evaluation of hepatic perfusion index, nicotinamide adenine dinucleotide phosphate autofluorescence, and hepatic integrity. Compared with vehicle controls, ramelteon therapy significantly improved plasma disappearance rate of indocyanine green (7.89 +/- 2.12% vs. 13.67 +/- 2.51%; p = 0.006), hepatic perfusion index (352.04 +/- 111.78 pl/sec/mm vs. 848.81 +/- 181.38 pl/sec/mm; p = 0.002), nicotinamide adenine dinucleotide phosphate autofluorescence and hepatocellular injury. Coadministration of luzindole abolished the protective effect of ramelteon with respect to liver function and nicotinamide adenine dinucleotide phosphate autofluorescence.Ramelteon therapy improves liver function, hepatic perfusion, and hepatocellular integrity after hemorrhagic shock in rat. This demonstrates that an isolated activation of melatonin receptors may be sufficient for organ protection, independent from direct antioxidant effects. The hypnotic ramelteon could thus play an interesting role in future sedation concepts for critical care patients.

In this paper, we look at the "social tag prediction" problem. Given a set of objects, and a set of tags applied to those objects by users, can we predict whether a given tag could/should be applied to a particular object? We investigated this question using one of the largest crawls of the social bookmarking system del.icio.us gathered to date. For URLs in del.icio.us, we predicted tags based on page text, anchor text, surrounding hosts, and other tags applied to the URL. We found an entropy-based metric which captures the generality of a particular tag and informs an analysis of how well that tag can be predicted. We also found that tag-based association rules can produce very high-precision predictions as well as giving deeper understanding into the relationships between tags. Our results have implications for both the study of tagging systems as potential information retrieval tools, and for the design of such systems.

Social bookmarking is a recent phenomenon which has the potential to give us a great deal of data about pages on the web. One major question is whether that data can be used to augment systems like web search. To answer this question, over the past year we have gathered what we believe to be the largest dataset from a social bookmarking site yet analyzed by academic researchers. Our dataset represents about forty million bookmarks from the social bookmarking site del.icio.us. We contribute a characterization of posts to del.icio. us: how many bookmarks exist (about 115 million), how fast is it growing, and how active are the URLs being posted about (quite active). We also contribute a characterization of tags used by bookmarkers. We found that certain tags tend to gravitate towards certain domains, and vice versa. We also found that tags occur in over 50 percent of the pages that they annotate, and in only 20 percent of cases do they not occur in the page text, backlink page text, or forward link page text of the pages they annotate. We conclude that social bookmarking can provide search data not currently provided by other sources, though it may currently lack the size and distribution of tags necessary to make a significant impact

Tagging systems allow users to interactively annotate a pool of shared resources using descriptive tags. As tagging systems are gaining in popularity, they become more susceptible to tag spam: misleading tags that are generated in order to increase the visibility of some resources or simply to confuse users. We introduce a framework for modeling tagging systems and user tagging behavior. We also describe a method for ranking documents matching a tag based on taggers' reliability. Using our framework, we study the behavior of existing approaches under malicious attacks and the impact of a moderator and our ranking method.

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