BACKGROUND: We previously reported that deaerated breath condensate pH (dEBC pH) can identify preschool children with recurrent wheezing at high asthma risk. OBJECTIVE: To assess the ability of preschool dEBC pH to predict asthma risk at school age. METHODS: Children of the baseline cohort were recontacted for follow-up. Asthma diagnosis at school age was evaluated according to Global Initiative for Asthma recommendations in 135 children who at baseline had been classified into the following groups: (asymptomatic) atopic wheezers (n = 30), (asymptomatic) nonatopic wheezers (n = 57), allergic rhinitis only (n = 14), and healthy controls (n = 34). RESULTS: All (100%) former atopic wheezers, 12 (21%) of nonatopic wheezers, 2 (14%) of allergic rhinitis group, and 1 (3%) of healthy controls had developed asthma at follow-up. Among all children with baseline wheezing, baseline dEBC pH predicted asthma at follow-up with an area under the receiver operating characteristic curve (AUC) of 0.72 (sensitivity, 0.67; specificity, 0.76; at pH 7.83). Combining pH and Capacity class (CAP) led to substantial gain in sensitivity (0.96) and negative predictive value (NPV, 0.94). Additional clinical information (Asthma Predictive Index, family atopy, family asthma, and inhaled corticosteroids) further increased the potential to predict asthma (AUC, 0.94) and raised sensitivity (0.98) and NPV (0.97) to nearly perfect values. CONCLUSION: Our findings suggest (1) that dEBC pH combined with CAP class may serve as highly sensitive, noninvasive marker for the early detection of young asymptomatic preschool children with increased asthma risk, and (2) the need for additional biomarkers with high specificity to optimize early risk stratification in this clinically challenging scenario. (C) 2020 American Academy of Allergy, Asthma & Immunology

We recruited 25 patients after complete wrist denervation and 60 healthy adults to investigate conscious and unconscious proprioception of the wrist. Ipsi- and contralateral joint-position sense, force sense, and wrist reflexes were measured. The latter were triggered by a trapdoor, recording electromyographic signals from the extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris muscles. No significant differences were found for joint position sense, force sense, and wrist reflexes between both groups, except for reflex time of the flexor carpi ulnaris after denervation of the left wrist as compared with the left flexor carpi ulnaris in controls or in right operated wrists. At a mean follow-up of 32 months (range 8 to 133), we found no proprioceptive deficit of the conscious proprioceptive qualities of joint position sense, force sense, and the unconscious proprioceptive neuromuscular control of wrist reflex time for most muscles after complete wrist denervation. We conclude from this study that complete wrist denervation does not affect the proprioceptive senses of joint position, force sense, and reflex time of the wrist.

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.

Background Physiotherapy (PT) is important for the prevention, treatment, and rehabilitation of joint bleeds in severe hemophilia and von Willebrand’s disease type 3 (VWD). However, only few studies regarding the effect of PT in bleeding disorders in the pediatric age are available.

As a growing field in dentistry, the practical education during the undergraduate curriculum in implant dentistry should be extended. Not only the theoretical background but also practical skills are crucial to place implants in patients. In order to determine the exact implant position, several positioning aids are available. In the present laboratory study, the accuracy of implant insertion using two different guiding modes in a group of inexperienced participants was assessed. After three-dimensional planning using the data of a cone beam computed tomography of artificial mandibles, surgical templates were manufactured by thermoforming. In region 35, a sleeve for the pilot drill was used, whereas in region 45, a sleeve allowing a full-guided implant insertion was inserted. Subsequently, a total of 104 implants were placed by 52 undergraduates. Radiographical assessment of the three-dimensional accuracy was performed. Furthermore, the time required to insert the implants was recorded. Statistical analysis followed. When comparing the three-dimensional accuracy of the virtually planned to the actual inserted implant, a statistically significantly higher accuracy in three-dimensional angulation was achieved for the full-guided (3.388 ± 1.647°) compared to the pilot-drill guided mode (5.792 ± 3.290°). Furthermore, the time required to insert the implant was shorter for the full-guided template (6.23 ± 1.78 min) vs. for the pilot-drill guided (8.84 ± 2.39 min). Both differences reached a statistical significance (p < 0.001). Within the limit of this laboratory study, the results suggest that inexperienced surgeons benefit from a full-guided implant insertion. However, the clinical effects have to be discussed as the mismatch was varying in the decimillimeter range.

Purpose: The aim of the present study was to evaluate the biomechanical stability of osteosynthesis in mandibular condyle fractures using a newly designed rhombic 3-dimensional (3D) condylar fracture plate and compare it with that using standard two 4-hole miniplates and with that in nonfractured condyles. Materials and Methods: Using 200 porcine mandibles, 3 different monocortical plating techniques were evaluated. The condyles were fractured along a defined line tangentially through the sigmoid notch and perpendicular to the posterior border. After anatomic reduction, osteosynthesis was performed using either standard rhombic 3D condylar fracture plates and standard screws (group A) or locking rhombic 3D condylar fracture plates, which were fixed either with standard screws (group B) or locking screws (group C). For comparison, nonfractured condyles (group D) and condyles fixed with standard two 4-hole miniplates and 8 screws (group E) were included. Using a universal mechanical testing machine (TIRA Test 2720; TIRA GmbH Schalkau, Germany), each group was subjected to linear loading from laterally to medially, medially to laterally, anteriorly to posteriorly, and posteriorly to anteriorly. The maximum axial force and displacement at the maximum force were measured. The mean values were compared for statistical significance using analysis of variance with Bonferroni's correction (statistical significance set at P < .05). Results: The main mode of failure in the plating techniques investigated was the pull out of screws from the proximal fragment. We found no statistically significant differences in the stability of osteosynthesis between the two 4-hole miniplates and the rhombic 3D condylar fracture plate when loading from posteriorly to anteriorly, laterally to medially, and medially to laterally. However, when loading from anteriorly to posteriorly, a statistically significant difference between the standard and locking system and the two 4hole miniplate system was observed, with the latter proving more stable. Conclusions: The results of the present biomechanical study suggest that the rhombic 3D condylar frac- ture plates are suitable for the treatment of condylar neck fractures. Both types of the plate are able to resist physiologic strains comparable to the two 4-hole miniplates. (C) 2019 American Association of Oral and Maxillofacial Surgeons

CASP1 variants result in reduced enzymatic activity of procaspase-1 and impaired IL-1β release. Despite this, affected individuals can develop systemic autoinflammatory disease. These seemingly contradictory observations have only partially been explained by increased NF-κB 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.

Non-infectious uveitis is associated with visual impairment and blindness. Non-biologic treatment for non-infectious uveitis is not based on strong evidence. A retrospective chart review was conducted to investigate treatment response to high-dose intravenous methylprednisolone (IVMP) in children with non-infectious uveitis. Fifty-six patients (93 eyes affected) were included. In 29% uveitis was associated with juvenile idiopathic arthritis. Uveitis predominately affected the anterior segment, was bilateral and recurrent. Complications were common and included visual loss, synechiae, cataract and/or retinal lesions. Patients received up to 5 IVMP at monthly intervals. Visual acuity improved at 3 and 6 months. Anterior chamber cells, synechiae, keratic precipitates, papillary and/or macular edema improved at 3 months. Children treated with >= 3 IVMP (vs 1 IVMP) experienced trends towards fewer relapses, fewer cataracts and less frequently required treatment with biologic agents. High-dose IVMP induce rapid improvement in children with non-infectious uveitis. Prospective randomized trials are required to confirm results.

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.

PURPOSEThe aging of zirconia ceramics (Y-TZP) is associated with tetragonal to monoclinic phase transformation. This change in microstructure may affect the optical properties of the ceramic. This study examines the effect of aging on the translucency of different zirconia materials.MATERIALS AND METHODS120 disc-shaped specimens were fabricated from four zirconia materials: Cercon ht white, BruxZir Solid Zirconia, Zenostar T0, Lava Plus (n = 30 per group). Accelerated aging was performed in a steam autoclave (134°C, 0.2 MPa, 5 hours). CIELab coordinates (L*, a*, b*) and luminous reflectance (Y) were measured with a spectrophotometer before and after aging. Contrast ratio (CR) and translucency parameter (TP) were calculated from the L*, a*, b*, and Y tristimulus values. The general linear model (Bonferroni adjusted) was used to compare both parameters before and after aging, as well as between the different zirconia materials (p ≤ 0.05).RESULTSCR and TP differed significantly before and after aging in all groups tested. Before aging, Zenostar T showed the highest and Lava Plus showed the lowest translucency. After aging, Cercon ht and Zenostar T showed the highest and BruxZir and Lava Plus the lowest translucency.CONCLUSIONSAging reduced the translucency in all specimens tested. Furthermore, translucency differed between the zirconia brands tested. Nevertheless, the differences were below the detectability threshold of the human eye. The aging process can influence the translucency and thus the esthetic outcome of zirconia restorations; however, the changes in translucency were minimal and probably undetectable by the human eye.

Dental preparations require a high degree of precision. The goal of the study was to                                                                                                        examine the surface design from the use of different drives.                                                                                             The study was conducted under standardized, clinically simulated conditions. The test subjects prepared surfaces on CEREC VITABLOCS MARK II using three drives that facilitated and did not facilitate contact grinding. In addition, various diamond rotary instruments were used. The waviness parameter Wt (wave depth) showed significantly smaller values for the drives that enabled contact grinding than for the older turbines that did not. No significant differences were found in the comparison of the results for the GENTLEforce 7000 B turbine and the micromotor with speed-enhanced contra-angle piece. The parameter RSm (groove width) showed the highest values for the older turbines.                                                                                                           As relatively large convergence angles are achieved in the dental preparations with patients, the significant differences in waviness on the surfaces have little clinical importance.

ObjectivesPosterior metal ceramic crowns are still widely used as a standard treatment. The aim of this study was to obtain long-term data on their clinical performance.Material and MethodsTen private practitioners participated in this prospective practice-based study. Patients were provided with two crowns each. Two groups were formed. The single crown group comprised 95 patients with 190 crowns. The retainer crown group comprised 138 patients with fixed dental prostheses and 276 retainer crowns.ResultsFor the primary outcome loss of tooth or crown, 20-year survival rates of 78.8% in the single crown group and 67.8% in the retainer crown group were found. Veneering ceramic defects occurred rather frequently, resulting in respective 20-year technical success rates of 74.2% for single crowns and 62.9% for retainer crowns. However, veneering ceramic defects causing crown losses were very rare events.ConclusionsThe results contribute to our knowledge on long-term outcomes of treatments with metal ceramic crowns and show high survival and success rates over 20years.Clinical relevancePosterior metal ceramic crowns are a highly reliable option in private practice settings.

Introduction: The underlying reason of thrombocytopenia in children should be clarified to initiate effective or to avoid unnecessary treatment. For differential diagnostics the measurement of some relatively new platelet parameters (mean platelet volume - MPV, relative and absolute immature platelet fraction - rIPF and aIPF, plateletcrit - PCT, platelet distribution width - PDW, platelet large cell ratio - P-LCR) may be useful but only limited data are available yet. Aims: We determined reference values for these parameters in healthy children of different age groups and evaluated the parameters in pediatric thrombocytopenic patients. Methods: Reference values were determined in 98 apparently healthy children without any medication (43 girls and 55 boys, mean age: 6.3 years, age range: Results: In infants platelet count (PLT: 330,000±74,000/µl), rIPF (2.5±1.5%) and aIPF (8,300±5,100/µl) were significantly higher compared to toddlers (PLT: 291,000±52,000/µl; rIPF: 1.6±0.9%; aIPF: 4,700±2,900/µl) and schoolchildren (PLT: 276,000±63,000/µl; rIPF: 2.0±1.2%; aIPF: 5,300±2,500/µl). MPV was significantly lower in toddlers (9.9±0.7 fl) than in schoolchildren (10.6±0.8 fl). For the other platelet parameters no age dependency was detected. The rIPF and aIPF correlated with PDW, MPV and P-LCR. All platelet parameters did not show a gender dependency. Patients with acute ITP showed significantly lower platelet counts and higher rIPF values compared to the groups of acute leukemia (PLT: 12,000±12,000/µl vs. 87,000±79,000/µl and rIPF: 23.1±9.5% vs. 7.6±4.5%) and of impaired hematopoiesis (75,000±67,000/µl and 12.6±13.6%). Children with chronic ITP displayed significantly elevated rIPF values in comparison with the acute leukemia group (18.5±12.0% vs. 7.6±4.5%) and a significantly increased MPV compared to leukemia patients (12.6±0.9 fl vs. 9.9±0.9 fl) and children with impaired hematopoiesis (10.4±1.5 fl). For aIPF and the other parameters no significant differences among the groups were detected. Conclusions: Compared to already published pediatric data we detected lower reference values for rIPF and aIPF. In the context of the patient9s individual history and a careful clinical examination, the determination of rIPF might be helpful in the thrombocytopenic child to distinguish acute ITP from acute leukemia and a disorder with impaired hematopoiesis. This hypothesis should be investigated in a prospective setting. The relevance of other platelet parameters remains unclear yet. Disclosures No relevant conflicts of interest to declare.

Objective.The autoinflammatory bone disorder chronic nonbacterial osteomyelitis (CNO) covers a wide clinical spectrum, ranging from mild self-limited presentations to chronically active or recurrent courses, which are then referred to as chronic recurrent multifocal osteomyelitis (CRMO). Little is known about treatment options and longterm outcomes. We investigated treatment responses and outcomes in children with CNO.Methods.A retrospective chart review was conducted in a tertiary referral center, covering 2004–2015. Disease activity was measured at 0, 3, 6, 12, and 24 months after treatment initiation, and at the last recorded visit.Results.Fifty-six patients with CNO were identified; 44 had multifocal CNO. Fifty percent of patients relapsed after a median of 2.4 years, and as few as 40% remained relapse-free after 5 years. Nonsteroidal antiinflammatory drugs were used as first-line treatment in 55 patients, inducing remission after 3 months in all individuals with relapse rates of 50% after 2 years. Further treatment included corticosteroids (n = 23), tumor necrosis factor-α (TNF-α) inhibitors (n = 7), and bisphosphonates (n = 8). While 47% of patients with CNO relapsed within 1 year after corticosteroid therapy, favorable outcomes were achieved with TNF-α inhibitors or bisphosphonates (pamidronate).Conclusion.CNO is a chronic disease with favorable outcomes within the first year, but high relapse rates in longterm followup. Particularly, patients with CRMO with long-lasting, uncontrolled inflammation were at risk for the development of arthritis. Our findings underscore the importance of a timely diagnosis and treatment initiation. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Purpose This study aimed to analyze the intra-tumoral heterogeneity of γH2AX foci in tumor specimens following ex vivo radiation to evaluate the potential of γH2AX foci as predictors for radiosensitivity. Material and methods γH2AX foci were quantified in tumor specimens of 3 hHNSCC tumor models with known differences in radiosensitivity after reoxygenation in culture medium (10 h, 24 h), single dose exposure (0 Gy, 4 Gy), and fixation 24 h post-irradiation. Multiple, equally treated samples of the same tumor were analyzed for foci, normalized and fitted in a linear mixed-effects model. Results The ex vivo reoxygenation time had no significant effect on γH2AX foci counts. A significant intra model heterogeneity could be shown for FaDu (p = 0.033) but not for SKX (p = 0.167) and UT-SCC-5 (p = 0.082) tumors, respectively. All tumor models showed a significant intra-tumoral heterogeneity between specimens of the same tumor (p < 0.01) or among microscopic fields of a particular tumor specimen (p < 0.0001). Conclusion Similar results for ex vivo γH2AX foci between 10 h and 24 h reoxygenation time support the applicability of the assay in a clinical setting. The high intra-tumoral heterogeneity underlines the necessity of multiple analyzable samples per patient and therewith the need for an automated foci analysis.

One consequence of demographic change is the increasing demand for biocompatible materials for use in implants and prostheses. This is accompanied by a growing number of experimental animals because the interactions between new biomaterials and its host tissue have to be investigated. To evaluate novel materials and engineered tissues the use of non-destructive imaging modalities have been identified as a strategic priority. This provides the opportunity for studying interactions repeatedly with individual animals, along with the advantages of reduced biological variability and decreased number of laboratory animals. However, histological techniques are still the golden standard in preclinical biomaterial research. The present article demonstrates a detailed method comparison between histology and magnetic resonance imaging. This includes the presentation of their image qualities as well as the detailed statistical analysis for assessing agreement between quantitative measures. Exemplarily, the bony ingrowth of tissue engineered bone substitutes for treatment of a cleft-like maxillary bone defect has been evaluated. By using a graphical concordance analysis the mean difference between MRI results and histomorphometrical measures has been examined. The analysis revealed a slightly but significant bias in the case of the bone volume [Formula: see text] and a clearly significant deviation for the remaining defect width [Formula: see text] But the study although showed a considerable effect of the analyzed section position to the quantitative result. It could be proven, that the bias of the data sets was less originated due to the imaging modalities, but mainly on the evaluation of different slice positions. The article demonstrated that method comparisons not always need the use of an independent animal study, additionally.

Backround: Nitrogen narcosis impairs cognitive function, a fact relevant during SCUBA-diving. Oxygen-enriched air (nitrox) became popular in recreational diving, while evidence of its advantages over air is limited. Aim: Compare effects of nitrox28 and air on two psychometric tests.Methods: In this prospective, double-blind, open-water study, 108 advanced divers (38 females) were randomized to an air or a nitrox-group for a 60-min dive to 24m salt water. Breathing gas effects on cognitive performance were assessed during the dive using a short- and long-term memory test and a number connection test.Results: Nitrox28 divers made fewer mistakes only on the long-term memory test (p=0.038). Female divers remembered more items than male divers (p<0.001). There were no significant differences in the number connection test between the groups.Conclusion: Likely owing to the comparatively low N-2 reduction and the conservative dive, beneficial nitrox28 effects to diver performance were moderate but could contribute to diving safety.

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.

Objectives Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis (CNO), is an autoinflammatory bone disorder. In the absence of diagnostic criteria or biomarkers, CNO/CRMO remains a diagnosis of exclusion. The aim of this study was to identify biomarkers for diagnosing multifocal disease (CRMO). Study design Sera from 71 pediatric CRMO patients, 11 patients with osteoarticular infections, 62 patients with juvenile idiopathic arthritis (JIA), 7 patients with para-infectious or reactive arthritis, and 43 patients with acute leukemia or lymphoma, as well as 59 healthy individuals were collected. Multiplex analysis of 18 inflammation- and/or bone remodeling-associated serum proteins was performed. Statistical analysis included univariate ANOVA, discriminant analysis, univariate receiver operating characteristic (ROC) analysis, and logistic regression analyses. Results For 14 of 18 blood serum proteins, significant differences were determined between CRMO patients, at least one alternative diagnosis, or healthy controls. Multi-component discriminant analysis delivered five biomarkers (IL-6, CCL11/eotaxin, CCL5/RANTES, collagen Iα, sIL-2R) for the diagnosis of CRMO. ROC analysis allowed further reduction to a core set of 2 biomarkers (CCL11/eotaxin, IL-6) that are sufficient to discern between CRMO, healthy controls, and alternative diagnoses. Conclusion Serum biomarkers CCL11/eotaxin and IL-6 differentiate between patients with CRMO, healthy controls, and alternative diagnoses (leukemia and lymphoma, osteoarticular infections, para-infectious arthritis, and JIA). Easily accessible biomarkers may aid in diagnosing CRMO. Further studies testing biomarkers in larger unrelated cohorts are warranted.

The clinical standard for alveolar cleft osteoplasty is augmentation with autologous bone being available in limited amounts and might be associated with donor site morbidity. The aim of the present study was the creation of tissue-engineered bone grafts and their in vivo evaluation regarding their potential to promote osteogenesis in an alveolar cleft model.