43 research outputs found

    CASP1 variants influence subcellular caspase-1 localization, pyroptosome formation, pro-inflammatory cell death and macrophage deformability

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    CASP1 variants result in reduced enzymatic activity of procaspase-1 and impaired IL-1ÎČ release. Despite this, affected individuals can develop systemic autoinflammatory disease. These seemingly contradictory observations have only partially been explained by increased NF-ÎșB activation through prolonged interaction of variant procaspase-1 with RIP2. To identify further disease underlying pathomechanisms, we established an in vitro model using shRNA-directed knock-down of procaspase-1 followed by viral transduction of human monocytes (THP-1) with plasmids encoding for wild-type procaspase-1, disease-associated CASP1 variants (p.L265S, p.R240Q) or a missense mutation in the active center of procaspase-1 (p.C285A). THP1-derived macrophages carrying CASP1 variants exhibited mutation-specific molecular alterations. We here provide in vitro evidence for abnormal pyroptosome formation (p.C285A, p.240Q, p.L265S), impaired nuclear (pro)caspase-1 localization (p.L265S), reduced pro-inflammatory cell death (p.C285A) and changes in macrophage deformability that may contribute to disease pathophysiology of patients with CASP1 variants. This offers previously unknown molecular pathomechanisms in patients with systemic autoinflammatory disease

    Additional file 1: of Acute and preventive management of anaphylaxis in German primary school and kindergarten children

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    Excerpt of the questionnaire for teachers/child-care providers about anaphylactic reactions in children (questions not shown concerned demographic background). (DOCX 21 kb

    Additional file 2: of Acute and preventive management of anaphylaxis in German primary school and kindergarten children

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    List of items that were included in questionnaire for parents about anaphylactic reactions in children. (DOCX 26 kb

    The Use of Orientation Templates and Free-Hand Implant Insertion in Artificial Mandibles - An Experimental Laboratory Examination in Fifth-Year Dental Students

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    Implant dentistry is a growing field in the education of undergraduate dental students. The present laboratory study evaluates factors which may potentially influence the accuracy of free-hand implant insertion and the use of an orientation template. After three-dimensional planning using coDiagnostiXTM, orientation templates, including sleeves for the pilot-drill in regions 41 and 45, were manufactured by thermoforming. Sixty-one fifth year dental students inserted one implant using the orientation template and another implant free-hand in an artificial mandible. Information regarding age, sex, handedness, education, and the time required for implant insertion were recorded. Subsequently, the mandibles were scanned using cone-beam-computed tomography and the accuracy of the implant position was assessed, while statistical analysis followed. The free-hand implant insertion resulted in a distal deviation of −1.34 ± 5.15° and a mesial mismatch of 0.06 ± 0.79 mm at the artificial bone level compared to the sleeves. When using the orientation templates, the deviation decreased to −0.67 ± 3.48° and a distal mismatch of −0.22 ± 0.62 mm was achieved. The difference was statistically significant for the mismatch (p < 0.049). Regarding the limitations of our study, it could be said that the accuracy level achieved by dental undergraduates using implant placement with orientation templates is comparable to that in other studies

    Clinical Test of Masticatory Efficacy in Patients with Maxillary/Mandibular Defects Due to Tumors

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    Background: The goal of the study was to evaluate the masticatory efficacy in patients who had been provided with resection prostheses after tumor removal in the maxillary/ mandibular region. These patients complained of impairment of masticatory function. Patients and Methods: 3 groups of patients were compared under clinical-experimental conditions. A uniform chewing material was masticated by the participants under standardized conditions. A sieving procedure was used to evaluate the masticatory efficacy. Analysis of the particle sizes and particle masses obtained was performed with the aid of computers. Results: The results showed that the masticatory efficacy of the patients with resection prostheses was the lowest of the 3 groups compared. The number of existing supporting zones and the location of the defect were found to be important influencing factors. Recording of the dietary habits of all patients was performed using a standardized dietary questionnaire. These data were analyzed using the corresponding software of the German Nutrition Society. With regard to the patients with resection prostheses, it was revealed that they often switched to food that did not require mastication. Conclusions: A nutritional guideline for patients with resection prostheses was developed, which is available for downloading free of charge on the Internet.Hintergrund: Ziel der Untersuchung war die PrĂŒfung der KaueffektivitĂ€t bei Patienten, die mit Resektionsprothesen nach Tumorentfernung im Kieferbereich versorgt worden waren. Diese Patienten klagten ĂŒber eine EinschrĂ€nkung der mastikatorischen Funktion. Patienten und Methoden: Unter klinisch xperimentellen Bedingungen erfolgte der Vergleich von 3 Patientengruppen. Unter standardisierten Bedingungen zerkleinerten die Patienten einheitliches Kaugut. Zur Bewertung der KaueffektivitĂ€t wurde ein Siebverfahren eingesetzt. Die Auswertung der ermittelten PartikelgrĂ¶ĂŸen und Partikelmassen erfolgte computergestĂŒtzt. Ergebnisse: Die Ergebnisse zeigten, dass im Vergleich der 3 Gruppen die KaueffektivitĂ€t der Patienten mit Resektionsprothesen am geringsten war. Die Zahl der vorhandenen StĂŒtzzonen des Restgebisses und die Defektlokalisation wurden als bedeutsame Einflussfaktoren ermittelt. Die Erfassung der ErnĂ€hrungsgewohnheiten aller Patienten erfolgte mittels eines standardisierten ErnĂ€hrungsfragebogens. Diese Daten wurden mit der zugehörigen Software der Deutschen Gesellschaft fĂŒr ErnĂ€hrung ausgewertet. Bei den Patienten mit Resektionsprothesen zeigte sich, dass diese auf Nahrungsmittel ausweichen, die kein Kauen erfordern. Schlussfolgerungen: Es wurde eine ErnĂ€hrungsrichtlinie fĂŒr Patienten mit Resektionsprothesen abgeleitet, die zum kostenfreien Herunterladen im Internet zur VerfĂŒgung steht.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugĂ€nglich

    Development of a Diagnostic Clinical Score for Hemodynamically Significant Patent Ductus Arteriosus

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    There is no consensus about the hemodynamic significance and, therefore, the need to treat a persistent ductus arteriosus in preterm newborns. Since the diagnosis of a hemodynamically significant persistent ductus arteriosus (hsPDA) is made by a summary of non-uniform echo-criteria in combination with the clinical deterioration of the preterm neonate, standardized clinical and ultrasound scoring systems are needed. The objective of this study was the development of a clinical score for the detection and follow-up of hsPDA. In this observational cohort study of 154 preterm neonates (mean gestational age 28.1 weeks), clinical signs for the development of hsPDA were recorded in a standardized score and compared to echocardiography. Analyzing the significance of single score parameters compared to the diagnosis by echocardiography, we developed a short clinical score (calculated sensitivity 84% and specificity 80%). In conclusion, this clinical diagnostic PDA score is non-invasive and quickly to implement. The continuous assessment of defined clinical parameters allows for a more precise diagnosis of hemodynamic significance of PDA and, therefore, should help to detect preterm neonates needing PDA-treatment. The score, therefore, allows a more targeted use of echocardiography in these very fragile preterm neonates

    Beneficial effect of enriched air nitrox on bubble formation during scuba diving. An open-water study.

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    Bubble formation during scuba diving might induce decompression sickness. This prospective randomised and double-blind study included 108 advanced recreational divers (38 females). Fifty-four pairs of divers, 1 breathing air and the other breathing nitrox28 undertook a standardised dive (24 ± 1 msw; 62 ± 5min) in the Red Sea. Venous gas bubbles were counted (Doppler) 30-<45 min (early) and 45-60 min (late) post-dive at jugular, subclavian and femoral sites. Only 7% (air) vs. 11% (air28Ÿ) (n.s.) were bubble-free after a dive. Independent of sampling time and breathing gas, there were more bubbles in the jugular than in the femoral vein. More bubbles were counted in the air-group than in the air28-group (pooled vein: early: 1845 vs. 948; P = 0.047, late: 1817 vs. 953; P = 0.088). The number of bubbles was sex-dependent. Lastly, 29% of female air divers but only 14% of male divers were bubble-free (P = 0.058). Air28Ÿ helps to reduce venous gas emboli in recreational divers. The bubble number depended on the breathing gas, sampling site and sex. Thus, both exact reporting the dive and in particular standardising sampling characteristics seem mandatory to compare results from different studies to further investigate the hitherto incoherent relation between inert gas bubbles and DCS.info:eu-repo/semantics/publishe

    Evaluation of Selected Speech Parameters after Prosthesis Supply in Patients with Maxillary or Mandibular Defects

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    Background: Ablative surgery of oropharyngeal tumors frequently leads to defects in the speech organs, resulting in impairment of speech up to the point of unintelligibility. The aim of the present study was the assessment of selected parameters of speech with and without resection prostheses. Patients and Methods: The speech sounds of 22 patients suffering from maxillary and mandibular defects were recorded using a digital audio tape (DAT) recorder with and without resection prostheses. Evaluation of the resonance and the production of the sounds /s/, /sch/, and /ch/ was performed by 2 experienced speech therapists. Additionally, the patients completed a non-standardized questionnaire containing a linguistic self-assessment. Results: After prosthesis supply, the number of patients with rhinophonia aperta decreased from 7 to 2 while the number of patients with intelligible speech increased from 2 to 20. Correct production of the sounds /s/, /sch/, and /ch/ increased from 2 to 13 patients. A significant improvement of the evaluated parameters could be observed only in patients with maxillary defects. The linguistic self-assessment showed a higher satisfaction in patients with maxillary defects. Conclusion: In patients with maxillary defects due to ablative tumor surgery, an increase in speech performance and intelligibility is possible by supplying resection prostheses

    3D Printing of Bone Grafts for Cleft Alveolar Osteoplasty – In vivo Evaluation in a Preclinical Model

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    One of the most common hereditary craniofacial anomalies in humans are cleft lip and cleft alveolar bone with or without cleft palate. Current clinical practice, the augmentation of the persisting alveolar bone defect by using autologous bone grafts, has considerable disadvantages motivating to an intensive search for alternatives. We developed a novel therapy concept based on 3D printing of biodegradable calcium phosphate-based materials and integration of osteogenic cells allowing fabrication of patient-specific, tissue-engineered bone grafts. Objective of the present study was the in vivo evaluation of implants in a rat alveolar cleft model. Scaffolds were designed according to the defect's geometry with two different pore designs (60° and 30° rotated layer orientation) and produced by extrusion-based 3D plotting of a pasty calcium phosphate cement. The scaffolds filled into the artificial bone defect in the palate of adult Lewis rats, showing a good support. Half of the scaffolds were colonized with rat mesenchymal stromal cells (rMSC) prior to implantation. After 6 and 12 weeks, remaining defect width and bone formation were quantified histologically and by microCT. The results revealed excellent osteoconductive properties of the scaffolds, a significant influence of the pore geometry (60° > 30°), but no enhanced defect healing by pre-colonization with rMSC
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