Search

With current advances in medicine, many surgical methods have emerged for the reconstruction of soft and hard tissue defects of the head and neck. Current literature provides only a limited amount of evidence in studies addressing differences in quality of life for specific therapeutic measures in microvascular reconstruction. The validated University of Washington quality of life questionnaire version 4 (UW-QoL v4), a distress thermometer, and two questions addressing donor-site morbidity were sent to 134 patients at a tertiary care centre. All participants had undergone a type of microvascular reconstructive surgery of the head and neck. They were distributed into three groups according to the defect and type of treatment: defects reconstructed by soft-tissue microvascular tissue transfer, defects involving the hard tissue and treated by alloplastic reconstruction, and hard tissue defects receiving microvascular osseous reconstruction. A total of 82 patients completed the questionnaire in full and returned it. Patients from all the groups showed improved distress thermometer values postoperatively. Those who underwent osseous microvascular reconstruction had better functional items than those who had alloplastic reconstruction plates. Donor-site morbidity was rated low in all groups. Microvascular osseous reconstructive surgery might help to improve functional outcomes in patients with osseous defects more than alloplastic reconstruction.

Glioblastoma (GBM) is the most common primary malignant brain cancer in adults. A hallmark of GBM is aggressive invasion of tumor cells into the surrounding normal brain. Both the current standard of care and targeted therapies have largely failed to specifically address this issue. Therefore, identifying key regulators of GBM cell migration and invasion is important. The leukemia-associated Rho guanine nucleotide exchange factor (LARG) has previously been implicated in cell invasion in other tumor types; however, its role in GBM pathobiology remains undefined. Herein, we report that the expression levels of LARG and ras homolog family members C (RhoC), and A (RhoA) increase with glial tumor grade and are highest in GBM. LARG and RhoC protein expression is more prominent in invading cells, whereas RhoA expression is largely restricted to cells in the tumor core. Knockdown of LARG by siRNA inhibits GBM cell migration in vitro and invasion ex vivo in organotypic brain slices. Moreover, siRNA-mediated silencing of RhoC suppresses GBM cell migration in vitro and invasion ex vivo, whereas depletion of RhoA enhances GBM cell migration and invasion, supporting a role for LARG and RhoC in GBM cell migration and invasion. Depletion of LARG increases the sensitivity of GBM cells to temozolomide treatment. Collectively, these results suggest that LARG and RhoC may represent unappreciated targets to inhibit glioma invasion.

Natural product (NP)-based antibiotics have been exploited for more than eighty years and continue saving uncountable lives every year. However, antimicrobial RD is inadequate to counteract antimicrobial resistance. The majority of marketed antibiotics are inspired by NP classes that were discovered more than 50 years ago. With the advent of advanced genomic approaches, cultivation methods, and modern analytical techniques, NP discovery holds promise that there are way more powerful antibiotic scaffolds to be discovered. However, the currently lean antibiotic RD pipeline shows a clear trend away from NP-based programs and innovative compounds are also rare in early stages. Within this review, we give an overview of the current NP antibiotic development pipeline, elaborate constraints the field is facing, and suggest measures to streamline NP-based antibiotic discovery. It is unlikely that NPs have lost significance, but reinforcement of discovery will require more targeted efforts and support to revitalize this established source.

Zusammenfassung Hintergrund Venose Thromboembolien (VTE) manifestieren sich hauptsachlich in der tiefen Venenthrombose (TVT) oder der Lungenembolie (LE) und stellen weltweit die dritthaufigste kardiovaskulare Erkrankung dar. Belastbare Daten zur VTE-Inzidenz fur Deutschland liegen derzeit jedoch nicht vor. Ziel der Arbeit Schatzung und Vergleich der Inzidenz der VTE auf Basis unterschiedlicher Routinedaten des deutschen Gesundheitswesens. Methoden Zur Schatzung und zum Vergleich der Inzidenz der VTE, TVT und LE wurden zwei Datensatze, die sowohl Informationen aus dem ambulanten als auch aus dem stationaren Bereich enthalten, herangezogen: der Datentransparenzverordnungs-Datensatz (DaTraV), der Daten aller gesetzlich Versicherten enthalt, und der Datensatz des Health Risk Institutes (HRI), der Daten von ca. 70 einzelnen Krankenkassen enthalt. Zusatzlich wurde eine arztbasierte Datenbank (IMS Disease Analyzer), die Informationen aus dem ambulanten Bereich enthalt, als Datenquelle genutzt. Ergebnisse Alters- und geschlechtsspezifische Verlaufe der VTE-Krankheitslast waren zwischen allen genutzten Datenbanken vergleichbar. Im Hinblick auf die Hohe der Krankheitslast ergaben sich zwischen den Datenbanken jedoch deutliche Unterschiede. Die Analyse der DaTraV-Daten ergab eine VTE-Inzidenz von 0,14%. Ergebnisse basierend auf Daten der HRI-Daten waren vergleichbar (0,17–0,20%). Die VTE-Inzidenz auf Basis des IMS Disease Analyzers war hingegen vergleichsweise hoch (0,32%). Diskussion Ergebnisse zur VTE-Inzidenz, die auf den DaTraV-Daten und HRI-Daten basieren, lassen sich gut in den internationalen Forschungskontext einordnen, wohingegen die Analyse des IMS Disease Analyzers aufgrund der Mehrfachzahlung erkrankter Personen vermutlich zu einer Uberschatzung der VTE-Inzidenz fuhrte. Unterschiedliche Routinedaten des Gesundheitswesens konnen teilweise zu sehr heterogenen Ergebnissen fuhren. Die Wahl der adaquaten Datenquelle bei Routinedatenanalysen sollte daher in Abhangigkeit von der vorliegenden Fragestellung und der Qualitat der Datensatze erfolgen.

This in vitro study evaluated the effects of different abutment axial heights on the retentiveness of adhesively and self-adhesively luted zirconia copings. Ankylos implants were embedded in resin blocks. Two groups of titanium abutments (“long”, height: 6.79 mm, taper: 4.8°; “short”, height: 4.31 mm, taper: 4.8°; Compartis-ISUS, DeguDent) were used for the luting of CAD/CAM-fabricated zirconia copings (Compartis, DeguDent) with an adhesive (Multilink Automix; Ivoclar Vivadent) and a self-adhesive (RelyX Unicem; 3M ESPE) composite. After water storage and 5000 thermocycles (5 °C/55 °C), retention forces were evaluated using a universal testing machine (Zwick). Significant differences were determined via two-way ANOVA and t-tests with Bonferroni-Holm correction. Significant interactions between abutment geometry and luting agents were observed. RelyX Unicem showed the highest levels of retentiveness, irrespective of the varying abutment geometries (mean values long/short: 487.7 N/447.9 N). When Multilink Automix was used, removal forces were significantly lower (311.7 N/101.1 N) and negatively affected by the use of the shorter abutments. Customized long abutments supported better retention forces than customized short abutments for both luting agents.

Parasitoids may change host behavior in order to improve their survival during the pupal stage. This has been observed in some ichneumonid wasps (Polysphincta genus group), which are able to induce modifications in the movements of host spiders during web construction. These changes usually result in web patterns distinct from those of normal webs of spiders. In this study, we describe the behavioral change in the orb-weaver spider Metazygia laticeps (Araneidae), parasitized by a new species of parasitoid wasp, Polysphincta sinearanea sp. n. (Ichneumonidae), which has a high prevalence in M. laticeps populations. This parasitoid induces behavioral changes in M. laticeps that result in the complete suppression of the normal orb-web structure. The absence of the orb probably reduces accumulation of debris and interception of insects by the webs (factors that could result in the rupture of threads that hold the shelter of the web) during the period from cocoon construction to the emergence of the adult wasp. Also, the suppression of the normal orb-web structure implies that resources that would have been invested in the web will be available to the larva wasp.

Despite improvements in the management of patients in critical care, about 3% patients who have an operation with curative intent for oral squamous cell carcinoma (SCC) do not survive their stay in hospital. Our aim was to assess the risk factors for postoperative death that were independent of the stage of the cancer, or the age and sex of the patients. We screened 4760 consecutive inpatients at a maxillofacial tertiary care centre from 2011 to 2016, and 34 of them had died within the first three months after operation. We matched them with a further 34 patients with the same TNM stage, age, and sex. General personal and clinical data and preoperative laboratory values were screened, and we applied a Charlson Comorbidity Score (for anaesthetic risk) for each group. Patients' mean (SD) age was 66 (12) years old. There was no significant difference in sex (p=1), age (p=0.718), or TNM classification. Those who died after operation had significantly more renal (p=0.027) and gastrointestinal (p=0.006) diseases, but cardiac diseases (p=0.468) and diabetes mellitus (p=1) were not significant risk factors in themselves. Patients who died postoperatively had significantly worse risk scores (p=0.001) overall. The most common causes of death were septic shock (n=10) and acute cardiac (n=9) or respiratory failure (n=7). Our findings suggested that general diseases were not intrinsically a contraindication for operation with curative intent. The Charlson Comorbidity Score helped to detect potentially fatal courses and could be useful in the preoperative assessment of patients whose general health is not good.

Multi-spheres and Superquadrics are popular approaches for addressing particle shape effect in the Discrete Element Method (DEM). This study focuses on the mechanical characteristics of cubical particles, modeled by the two methods (using EDEM and LIGGGHTS), through conducting a series of numerical case studies at both single particle and bulk levels. In the first part of the study, several testing scenarios, which clarify the impact, interlocking, sliding and tilting characteristics of the particle, are discussed and the respective simulations are carried out. The results emphasize the importance of surface bumpiness and edge sharpness in the single-particle behaviour and are used for informing the bulk response. Further, role of the two shape descriptors on bulk response is evaluated in angle of repose, Jenike shear and silo flow simulations. The results of these tests are assessed both at the micro, directly through DEM outputs, and at the meso- and macro-scales, using a coarse graining technique. It is seen that the properties of edge and surface in superquadric and multi-sphere particles considerably influence the heap profile in the angle of repose test. However, in a Jenike direct shear, the shape complexity only significantly affects the shear strength, porosity and mode of motion when the packing is dense. Additionally, in silo discharge, the effect of shape features is even less on the flow pattern and mass flow rate but is found to have a significant influence on the stress distribution.

Demand for healthcare services is unprecedented. Society is struggling to afford the cost. Pricing of biopharmaceutical products is under scrutiny, especially by payers and Health Technology Assessment agencies. As we discuss here, rapidly advancing technologies, such as Real-World Data (RWD), are being utilized to increase understanding of disease. RWD, when captured and analyzed, produces the Real-World Evidence (RWE) that underpins the economic case for innovative medicines. Furthermore, RWD can inform the understanding of disease, help identify new therapeutic intervention points, and improve the efficiency of research and development (R&D), especially clinical trials. Pursuing precompetitive collaborations to define shared requirements for the use of RWD would equip service-providers with the specifications needed to implement cloud-based solutions for RWD acquisition, management and analysis. Only this approach would deliver cost-effective solutions to an industry-wide problem.

Numerous in vivo, in vitro and clinical studies report on beneficial effects of strontium with respect to increased bone growth. Based on this knowledge the aim of this study was to evaluate early and late osseointegration stages of functionalized titanium implants showing sustained release of strontium (Sr) and further investigate its potential systemic effect. Strontium functionalized (Ti-Sr-O) and Grade 4 (Control) titanium implants were inserted in the femoral condyle of New Zealand White rabbits. The Ti-Sr-O coating was characterized using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectrometry (EDX) for structure, coating thickness and chemical composition. Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) was used to evaluate released strontium in vitro while Atomic Absorption Spectrometry (AAS) was utilized to monitor serum levels of strontium and calcium. Additionally, histological and tomographic analysis of bone-to-implant contact (BIC%) and bone formation (BF%) was performed, following implantation periods of two or twelve weeks, respectively. Median values for BIC% for Ti-Sr-O revealed significant differences within the two-and twelve-week observation periods, while exceeding BF% was discovered especially after twelve weeks when performing the histological evaluation. The results from the micro-computed tomography (mu-CT) showed no significant differences, when comparing the experimental groups. AAS measurements did not indicate a systemic effect by the local strontium release. Within the limitations of the study, it was shown that a Ti-Sr-O coating with sustained release characteristics of strontium, accelerates bone apposition and represents a potential potent surface modification for endosseous medical implant devices.Statement of SignificanceThis study presents first data with respect to early and late in vivo response on a strontium functionalized titanium surface comprising a nanotopography manufactured by a magnetron sputtering process. We investigated different osseointegration stages of screw-shaped implants with dental implant geometries in a rabbit femur model observing beneficial effects of the functionalized surface on bone-to-implant contact and bone formation caused by tailored release of the bone anabolic strontium. Histomorphometrical data revealed that a functionalized titanium surface with controlled liberation of strontium accelerates osseointegration while spectrometry measurements did not indicate a potential systemic effect of this osteoinductive agent and could thus have impact on modifications of medical implant devices. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND.

Polysphinctine wasps are exclusive parasitoids of spiders and their host utilisation strategies are highly taxonomically specific. In this study, the host utilisation of two Australasian parasitoid wasps of the genus Eriostethus was studied for the first time. Our study revealed considerable differences in host-parasitoid interactions between Eriostethus minimus associated with 3D tangle web-building spiders from the family Theridiidae (new family record for Eriostethus) and E. perkinsi associated with 2D orb-web weaving spiders from the family Araneidae. A pupa of the former species was located in a spider retreat in the centre of an unmodified 3D tangle web and the pupal cocoon had a sparsely woven and partially transparent wall. In contrast, a cocoon of the latter species was suspended at the centre of a modified irregular sparse 3D cocoon web and the pupal cocoon had a strong, densely woven cocoon wall. This difference in host utilisation is not in agreement with the synonymisation of Millironia with Eriostethus.

Cytoskeletal motor proteins are essential to the function of a wide range of intracellular mechano-systems. The biophysical characterization of their movement along their filamentous tracks is therefore of large importance. Toward this end, single-molecule, in vitro stepping-motility assays are commonly used to determine motor velocity and run length. However, comparing results from such experiments has proved difficult due to influences from variations in the experimental conditions and the data analysis methods. Here, we investigate the movement of fluorescently labeled, processive, dimeric motor proteins and propose a unified algorithm to correct the measurements for finite filament length as well as photobleaching. Particular emphasis is put on estimating the statistical errors associated with the proposed evaluation method, as knowledge of these values is crucial when comparing measurements from different experiments. Testing our approach with simulated and experimental data from GFP-labeled kinesin-1 motors stepping along immobilized microtubules, we show 1) that velocity distributions should be fitted by a t location-scale probability density function rather than by a normal distribution; 2) that the impossibility to measure events shorter than the image acquisition time needs to be taken into account; 3) that the interaction time and run length of the motors can be estimated independent of the filament length distribution; and 4) that the dimeric nature of the motors needs to be considered when correcting for photobleaching. Moreover, our analysis reveals that controlling the temperature during the experiments with a precision below 1 K is of importance. We believe our method will not only improve the evaluation of experimental data, but also allow for better statistical comparisons between different populations of motor proteins (e.g., with distinct mutations or linked to different cargos) and filaments (e.g., in distinct nucleotide states or with different posttranslational modifications). Therefore, we include a detailed workflow for image processing and analysis (including MATLAB code), serving as a tutorial for the estimation of motility parameters in stepping-motility assays.

Based on e(+)e(-) annihilation data samples collected with the BESIII detector at the BEPCII collider at 13 center-of-mass energies from 4.008 to 4.600 GeV, measurements of the Born cross section o ...

We study the decays of J / ψ and ψ ( 3686 ) to the final states Σ ( 1385 ) 0 Σ ¯ ( 1385 ) 0 and Ξ 0 Ξ ¯ 0 based on a single baryon tag method using data samples of ( 1310.6 ± 7.0 ) × 10 6 J / ψ and ( 447.9 ± 2.9 ) × 10 6 ψ ( 3686 ) events collected with the BESIII detector at the BEPCII collider. The decays to Σ ( 1385 ) 0 Σ ¯ ( 1385 ) 0 are observed for the first time. The measured branching fractions of J / ψ and ψ ( 3686 ) to Ξ 0 Ξ ¯ 0 are in good agreement with, and much more precise than, the previously published results. The angular parameters for these decays are also measured for the first time. The measured angular decay parameter for J / ψ → Σ ( 1385 ) 0 Σ ¯ ( 1385 ) 0 , α = − 0.64 ± 0.03 ± 0.10 , is found to be negative, different to the other decay processes in this measurement. In addition, the “12% rule” and isospin symmetry in the decays of J / ψ and ψ ( 3686 ) to Ξ Ξ ¯ and Σ ( 1385 ) Σ ¯ ( 1385 ) are tested.

Background Radiation therapy (RT) of the head and neck region is often accompanied by serious side effects. Research in this area is needed to improve treatment outcomes and ameliorate therapy tolerance. Laboratory rodents are barely matching today's clinical standards in RT research. Yet domestic swine (Sus scrofa domestica) have previously proved suitable for various advanced tests in clinical research and training. We therefore investigated whether S. scrofa domestica is also appropriate for irradiation of the mandible. Study Design A common scheme for irradiation treatment of S. scrofa domestica mandibles in a split-mouth design was acquired by applying computed tomography (CT) scanning under sedation. Basing on close anatomic resemblance, a standard treatment plan comprising 2 opposed irradiation fields could be accomplished. Results RT was carried out in a clinical environment with 2 × 9 Gy. The resulting operating procedure facilitated complication-free sedation, transport, positioning, CT scanning, and effective irradiation. Conclusion Based on common standards applied for RT in humans, domestic pigs can be employed to progress RT clinical research. Due to their human-like anatomy, physiology, size, and weight, the swine model is expedient for advancing experimental RT of the head and neck area.

Biochar (BC) is increasingly used as soil amendment; however, its stability and alteration in the soil environment are still unclear. Here, we investigated BC decomposition and changes of BC characteristics during a long-term incubation experiment. 13C-depleted BCs were incubated for two years in an acidic Planosol and a calcareous Chernozem, respectively. BC decomposition inferred from the C isotope signature of the incubated materials was marginal. Yet, small angle X-ray scattering showed that the surface roughness of the BCs increased over time. Mid-infrared spectra indicated changes in the BCs' molecular characteristics upon aging. There was an overall increase of infrared bands assigned to H- and O-containing functional groups, especially carboxylic groups. Contact angle measurements revealed that the hydrophobic surfaces of freshly produced BCs became more hydrophilic during soil incubation. Our results suggest that BC aging is strongly influenced by soil traits. In the more acidic Planosol, these aging processes were accelerated.