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Traditional ergonomic risk assessment tools such as the Rapid Upper Limb Assessment (RULA) are often not sensitive enough to evaluate well-optimized work routines. An implementation of kinematic data captured by inertial sensors is applied to compare two work routines in dentistry. The surgical dental treatment was performed in two different conditions, which were recorded by means of inertial sensors (Xsens MVN Link). For this purpose, 15 (12 males/3 females) oral and maxillofacial surgeons took part in the study. Data were post processed with costume written MATLAB® routines, including a full implementation of RULA (slightly adjusted to dentistry). For an in-depth comparison, five newly introduced levels of complexity of the RULA analysis were applied, i.e., from lowest complexity to highest: (1) RULA score, (2) relative RULA score distribution, (3) RULA steps score, (4) relative RULA steps score occurrence, and (5) relative angle distribution. With increasing complexity, the number of variables times (the number of resolvable units per variable) increased. In our example, only significant differences between the treatment concepts were observed at levels that are more complex: the relative RULA step score occurrence and the relative angle distribution (level 4 + 5). With the presented approach, an objective and detailed ergonomic analysis is possible. The data-driven approach adds significant additional context to the RULA score evaluation. The presented method captures data, evaluates the full task cycle, and allows different levels of analysis. These points are a clear benefit to a standard, manual assessment of one main body position during a working task.
Background: Musculoskeletal disorders (MSD) are common among dental professionals. The most common areas affected are the trunk, neck, shoulders and wrists. Current evidence suggests that the causes of MSD can be found in the physical demands of the profession. Posture and movement during treatment is influenced by the arrangement of the treatment concept (patient chair, equipment and cabinets). It has not been investigated whether the ergonomic risk differs between the treatment concepts.
Methods: To evaluate the prevalence of MSD in dental professionals, 1000 responses will be collected from a nationwide (Germany) online questionnaire (mod. Nordic Questionnaire and mod. Meyer questionnaire). In order to assess the ergonomic risk of the treatment techniques used in the four treatment concepts, 3D movement analyses are carried out with inertial sensors. For this purpose, 20 teams of dentists and dental assistants from four dental fields of specializations (generalists, orthodontists, endodontists and oral surgeons) and a student control group will be recruited. Each team will execute field specific standardized treatments at a dummy head. Measurements are carried out in each of the four treatment concepts. The data will be analyzed using the Rapid Upper Limb Assessment (RULA) which will be modified for the evaluation of objective data.
Conclusions: On the basis of these investigations, a substantial gain of knowledge regarding work-related MSD in the field of dentistry and its potential biomechanical causes is possible. For the first time, objective and differentiated comparisons between the four treatment concepts are possible for different fields of dental specialization. Up to now, statically held positions of the trunk and proximal upper extremities, but also the repetitive movements of the hands have been considered a risk for MSD. Since both are included in the RULA, dental activities can be assessed in a detailed but also global manner with regard to ergonomic risks.
Background; Musculoskeletal disorders (MSD) are a common health problem among dentists. Dental treatment is mainly performed in a sitting position. The aim of the study was to quantify the effect of different ergonomic chairs on the sitting position. In addition, it was tested if the sitting position of experienced workers is different from a non-dental group.
Methods; A total of 59 (28 m/31f) subjects, divided into two dentist groups according to their work experience (students and dentists (9 m/11f) < 10 years, dentists (9 m/10f) ≥ 10 years) and a control group (10 m/10f) were measured. A three-dimensional back scanner captured the bare back of all subjects sitting on six dentist’s chairs of different design. Initially, inter-group comparisons per chair, firstly in the habitual and secondly in the working postures, were carried out. Furthermore, inter-chair comparison was conducted for the habitual as well as for the working postures of all subjects and for each group. Finally, a comparison between the habitual sitting posture and the working posture for each respective chair (intra-chair comparison) was conducted (for all subjects and for each group). In addition, a subjective assessment of each chair was made.
For the statistical analysis, non-parametric tests were conducted and the level of significance was set at 5%.
Results: When comparing the three subject groups, all chairs caused a more pronounced spinal kyphosis in experienced dentists. In both conditions (habitual and working postures), a symmetrical sitting position was assumed on each chair.
The inter-chair comparisons showed no differences regarding the ergonomic design of the chairs. The significances found in the inter-chair comparisons were all within the measurementerror and could, therefore, be classified as clinically irrelevant.
The intra-chair comparison (habitual sitting position vs. working sitting position) illustrated position-related changes in the sagittal, but not in the transverse, plane. These changes were only position-related (forward leaned working posture) and were not influenced by the ergonomic sitting design of the respective chair. There are no differences between the groups in the subjective assessment of each chair.
Conclusions; Regardless of the group or the dental experience, the ergonomic design of the dentist’s chair had only a marginal influence on the upper body posture in both the habitual and working sitting postures. Consequently, the focus of the dentist’s chair, in order to minimize MSD, should concentrate on adopting a symmetrical sitting posture rather than on its ergonomic design.
Hintergrund: Ab Frühjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoV‑2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab März 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitäre Hals-Nasen-Ohren(HNO)-Heilkunde für die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 Universitäts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von März bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4 % (29/39) an, dass es zu einer Verschlechterung ihrer Forschungstätigkeit infolge der Pandemie gekommen sei. Von 61,5 % (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine Einschränkung der Präsenzlehre berichtet und 97,5 % (38/39) führten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4 % der Klinikdirektoren die Weiterbildung der Assistenten nicht gefährdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die Einführung innovativer digitaler Konzepte für die studentische Lehre belegt eindrücklich das große innovative Potenzial und die schnelle Reaktionsfähigkeit der HNO-Universitätskliniken, um auch während der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfüllen.
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3Δex1-6) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
Background: In general, the prevalence of work-related musculoskeletal disorders (WMSD) in dentistry is high, and dental assistants (DA) are even more affected than dentists (D). Furthermore, differentiations between the fields of dental specialization (e.g., general dentistry, endodontology, oral and maxillofacial surgery, or orthodontics) are rare. Therefore, this study aims to investigate the ergonomic risk of the aforementioned four fields of dental specialization for D and DA on the one hand, and to compare the ergonomic risk of D and DA within each individual field of dental specialization. Methods: In total, 60 dentists (33 male/27 female) and 60 dental assistants (11 male/49 female) volunteered in this study. The sample was composed of 15 dentists and 15 dental assistants from each of the dental field, in order to represent the fields of dental specialization. In a laboratory setting, all tasks were recorded using an inertial motion capture system. The kinematic data were applied to an automated version of the Rapid Upper Limb Assessment (RULA). Results: The results revealed significantly reduced ergonomic risks in endodontology and orthodontics compared to oral and maxillofacial surgery and general dentistry in DAs, while orthodontics showed a significantly reduced ergonomic risk compared to general dentistry in Ds. Further differences between the fields of dental specialization were found in the right wrist, right lower arm, and left lower arm in DAs and in the neck, right wrist, right lower arm, and left wrist in Ds. The differences between Ds and DAs within a specialist discipline were rather small. Discussion: Independent of whether one works as a D or DA, the percentage of time spent working in higher risk scores is reduced in endodontologists, and especially in orthodontics, compared to general dentists or oral and maxillofacial surgeons. In order to counteract the development of WMSD, early intervention should be made. Consequently, ergonomic training or strength training is recommended.
Plattenepithelkarzinome des oberen Aerodigestivtraktes (SCCHN) sind Karzinome, die in den westlichen Industrienationen mit dem sechsten Rang in den Tumorstatistiken recht häufig sind. Ihre Inzidenz ist positiv mit einem erhöhten Tabak- und Alkoholkonsum und dem männlichen Geschlecht korreliert. Die Standardtherapie besteht in der Regel in einer operativen Sanierung und einer adjuvanten Radio- beziehungsweise Radio-Chemotherapie. Eine Induktionschemotherapie verspricht fortgeschrittene Primärtumoren und Tumoren vor einer operativen Intervention zu verkleinern. Jedoch besteht hierbei immer noch das Problem der hohen Rezidivfreundlichkeit dieser Tumoren, die wahrscheinlich mit der hohen Anzahl an G0-Phase-Zellen korreliert ist. Die vorliegende Arbeit hat die Frage untersucht, ob es möglich ist mit einer vorgeschalteten Stimulation durch Wachstumsfaktoren die Anzahl der G0-Phase-Zellen signifikant zu reduzieren und dadurch die gesamte Population der Tumorzellen sensibler für eine chemotherapeutische Intervention zu machen. Hierbei wurden besonders die Wachstumsfaktoren EGF und Serotonin als Stimulus verwendet. Die untersuchten Chemotherapeutika waren Mab425 und ZD1839, die die Signaltransduktion über einen EGFR-vermittelten Weg blockieren, sowie Docetaxel und Cisplatin, die als zytotoxische Substanzen wirksam sind. Die Untersuchungen wurden in vitro an drei Zelllinien durchgeführt. Detroit-562 und A431 bezogen wir von ATCC. Die Zelllinie UMSCC-10B wurde uns freundlicherweise von Thomas Carey von der University of Michigan zur Verfügung gestellt. Im Rahmen von Sondierungsversuchen stimulierten die Zellen mit IL-6, Serotonin, EGF und GCSF und fanden mit Hilfe der FACS-Analyse heraus, dass eine Kombination von EGF und Serotonin zur am stärksten ausgeprägten Stimulation der von uns untersuchten Zellen führte. In einem dreiphasigen Versuchsablauf wurden vier verschiedene Probengruppen untersucht. Zum einen eine Kontrollgruppe, die weder stimuliert noch chemotherapiert wurde. Eine Gruppe, die vor einer chemotherapeutischen Intervention mit Serotonin und EGF stimuliert wurde. Eine weitere Gruppe, die ausschließlich mit Serotonin und EGF stimuliert wurde und eine Gruppe, die nur eine Chemotherapie erhielt. Nach der Kultivierung der entsprechenden Proben, wurden die Zellen geerntet und zur Weiterverarbeitung vorbereitet. Es wurde mit Hilfe der Western-Blot-Analyse die Aktivität der Proteine untersucht, die an der über EGFR vermittelten Signaltransduktion beteiligt sind. Dazu wurden Antikörper gegen Proteine der Signaltransduktion eingesetzt, die dann mit Hilfe von zweiten Antikörpern erkannt wurden. Zum anderen wurden immunhistochemische Zellausstriche angefertigt mit einer Antikörperfärbung gegen das Kernprotein Ki-67, die uns zwischen proliferierenden und nichtproliferierenden Zellen unterscheiden ließ. Es erfolgte eine Auswertung der Gesamtzellanzahl bezogen auf die Reduktion der G0-Phase-Zellen. Die statistische Auswertung erfolgte mittels des Mann-Withney-U-Tests und des Wilcoxon- Tests. Hierbei lag das Signifikanzniveau bei 5%. Als Ergebnis kann man festhalten, dass eine signifikante Reduktion der Anzahl an G0-Phase-Zellen bei einer Vorstimulation und anschließender Chemotherapie durch Docetaxel oder Cisplatin zu beobachten war. Eine chemotherapeutische Intervention durch Mab425 und ZD1839 führte zwar zu einer Reduktion der Zellanzahl, aber nicht zu vergleichbar signifikanten Ergebnissen wie bei einer Intervention mit Docetaxel oder Cisplatin. Hieraus lässt sich der Schluss ableiten, dass eine chemotherapeutische Intervention auf Basis einer Blockade der durch EGFR vermittelten Signaltransduktion nicht ausreichend ist, es also einer zytotoxischen Komponente bedarf, um die Gesamtzellzahl signifikant zu reduzieren. Trotzdem nicht bei allen untersuchten Chemotherapeutika eine signifikante Reduktion der G0-Phase-Zellen beobachtet werden konnte, zeigten unsere Untersuchungen zum ersten Mal, dass durch eine Stimulation mit Wachstumsfaktoren vor einer chemotherapeutischen Intervention, die Sensibilität der Tumorzellen bei SCCHN für eine Chemotherapie durch eine Reduktion der G0-Phase-Zellen erhöht wird.
Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. Methods A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. Results Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. Conclusion There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent.
Hepatocellular carcinoma (HCC) is highly resistant to anticancer therapy and novel therapeutic strategies are needed. Chronotherapy may become a promising approach because it may improve the efficacy of antimitotic radiation and chemotherapy by considering timing of treatment. To date little is known about time‐of‐day dependent changes of proliferation and DNA damage in HCC. Using transgenic c‐myc/transforming growth factor (TGFα) mice as HCC animal model, we immunohistochemically demonstrated Ki67 as marker for proliferation and γ‐H2AX as marker for DNA damage in HCC and surrounding healthy liver (HL). Core clock genes (Per1, Per2, Cry1, Cry2, Bmal 1, Rev‐erbα and Clock) were examined by qPCR. Data were obtained from samples collected ex vivo at four different time points and from organotypic slice cultures (OSC). Significant differences were found between HCC and HL. In HCC, the number of Ki67 immunoreactive cells showed two peaks (ex vivo: ZT06 middle of day and ZT18 middle of night; OSC: CT04 and CT16). In ex vivo samples, the number of γ‐H2AX positive cells in HCC peaked at ZT18 (middle of the night), while in OSC their number remained high during subjective day and night. In both HCC and HL, clock gene expression showed a time‐of‐day dependent expression ex vivo but no changes in OSC. The expression of Per2 and Cry1 was significantly lower in HCC than in HL. Our data support the concept of chronotherapy of HCC. OSC may become useful to test novel cancer therapies.
An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease
(2019)
Aims: Pompe disease is caused by pathogenic mutations in the alpha 1,4‐glucosidase (GAA) gene and in patients with late onset Pome disease (LOPD), genotype–phenotype correlations are unpredictable. Skeletal muscle pathology includes glycogen accumulation and altered autophagy of various degrees. A correlation of the muscle morphology with clinical features and the genetic background in GAA may contribute to the understanding of the phenotypic variability.
Methods: Muscle biopsies taken before enzyme replacement therapy were analysed from 53 patients with LOPD. On resin sections, glycogen accumulation, fibrosis, autophagic vacuoles and the degree of muscle damage (morphology‐score) were analysed and the results were compared with clinical findings. Additional autophagy markers microtubule‐associated protein 1A/1B‐light chain 3, p62 and Bcl2‐associated athanogene 3 were analysed on cryosections from 22 LOPD biopsies.
Results: The myopathology showed a high variability with, in most patients, a moderate glycogen accumulation and a low morphology‐score. High morphology‐scores were associated with increased fibrosis and autophagy highlighting the role of autophagy in severe stages of skeletal muscle damage. The morphology‐score did not correlate with the patient's age at biopsy, disease duration, nor with the residual GAA enzyme activity or creatine‐kinase levels. In 37 patients with LOPD, genetic analysis identified the most frequent mutation, c.‐32‐13T>G, in 95%, most commonly in combination with c.525delT (19%). No significant correlation was found between the different GAA genotypes and muscle morphology type.
Conclusions: Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.