Orthodontic forces have been reported to significantly increase nicotine-induced periodontal bone loss. At present, however, it is unknown, which further (side) effects can be expected during orthodontic treatment at a nicotine exposure corresponding to that of an average European smoker. 63 male Fischer344 rats were randomized in three consecutive experiments of 21 animals each (A/B/C) to 3 experimental groups (7 rats, 1/2/3): (A) cone-beam-computed tomography (CBCT); (B) histology/serology; (C) reversetranscription quantitative real-time polymerase chain reaction (RT-qPCR)/cotinine serology—(1) control; (2) orthodontic tooth movement (OTM) of the first and second upper left molar (NiTi closed coil spring, 0.25 N); (3) OTM with 1.89 mg·kg? 1 per day s.c. of L(? )-nicotine. After 14 days of OTM, serum cotinine and IL-6 concentration as well as orthodontically induced inflammatory root resorption (OIIRR), osteoclast activity (histology), orthodontic tooth movement velocity (CBCT, within 14 and 28 days of OTM)and relative gene expression of known inflammatory and osteoclast markers were quantified in the dental-periodontal tissue (RT–Qpcr). Animals exposed to nicotine showed significantly heightened serum cotinine and IL-6 levels corresponding to those of regular European smokers. Both the extent of root resorption, osteoclast activity, orthodontic tooth movement and gene expression of inflammatory and osteoclast markers were significantly increased compared to controls with and without OTM under the influence of nicotine. We conclude that apart from increased periodontal bone loss, a progression of dental root resorption and accelerated orthodontic tooth movement are to be anticipated during orthodontic therapy, if nicotine consumption is present. Thus patients should be informed about these risks and the necessity of nicotine abstinence during treatment.

The aim of this study was to investigate the physiological foramen diameter, shape and distance between physiological and anatomical apex of maxillary and mandibular first and second molars. Accurate knowledge of the physiological foramina morphology; thus, inherent mechanical shaping technical hindrances, is decisive when taking the corresponding root canal final preparation decision. The morphological dimensions of a total of 1 727 physiological foramina were investigated by means of micro-computed tomography. Mean narrow and wide (to a high number, oval) diameters of the physiological foramen were 0.24, 0.22 and 0.33 mm and 0.33, 0.31 and 0.42 mm in mesiobuccal (MB), distobuccal (DB) and palatal (P) roots in maxillary first molars; 0.24, 0.22 and 0.33 mm and 0.41, 0.33 and 0.44 in MB, DB, and P roots in maxillary second molars. Mandibular first molars showed mean narrow and wide diameters of 0.24 and 0.30 mm and of 0.39 and 0.46 mm in mesial (M) and distal (D) roots; second mandibular molars showed 0.25 and 0.31 mm and 0.47 mm in M and D roots. The mean distance between the physiological foramina and anatomical apex was 0.82, 0.81 and 1.02 mm and 0.54, 0.43 and 0.63 mm in MB, DB and P roots of the maxillary first and second molars, respectively. A mean distance of 0.95 mm (M) and 1.05 mm (D) in the first and 0.78 mm (M) and 0.81 mm (D) in the second mandibular molars was observed. Based on the results obtained, assumable recommendations for final preparation size of the physiological foramen were calculated. However, when taking into consideration, the resulting standard deviations of marginal errors must be cautiously considered when taking a final decision in clinical endodontic treatment.

Wearable sensor systems which allow for remote or self-monitoring of health-related parameters are regarded as one means to alleviate the consequences of demographic change. This paper aims to summarize current research in wearable sensors as well as in sensor-enhanced health information systems. Wearable sensor technologies are already advanced in terms of their technical capabilities and are frequently used for cardio-vascular monitoring. Epidemiologic predictions suggest that neuropsychiatric diseases will have a growing impact on our health systems and thus should be addressed more intensively. Two current project examples demonstrate the benefit of wearable sensor technologies: long-term, objective measurement under daily-life, unsupervised conditions. Finally, up-to-date approaches for the implementation of sensor-enhanced health information systems are outlined. Wearable sensors are an integral part of future pervasive, ubiquitous and person-centered health care delivery. Future challenges include their integration into sensor-enhanced health information systems and sound evaluation studies involving measures of workload reduction and costs.
Delivery of Health Care ; Health Information Systems ; Medical Informatics ; Monitoring, Ambulatory

Wearable sensor systems which allow for remote or self-monitoring of health-related parameters are regarded as one means to alleviate the consequences of demographic change. This paper aims to summarize current research in wearable sensors as well as in sensor-enhanced health information systems. Wearable sensor technologies are already advanced in terms of their technical capabilities and are frequently used for cardio-vascular monitoring. Epidemiologic predictions suggest that neuropsychiatric diseases will have a growing impact on our health systems and thus should be addressed more intensively. Two current project examples demonstrate the benefit of wearable sensor technologies: long-term, objective measurement under daily-life, unsupervised conditions. Finally, up-to-date approaches for the implementation of sensor-enhanced health information systems are outlined. Wearable sensors are an integral part of future pervasive, ubiquitous and person-centered health care delivery. Future challenges include their integration into sensor-enhanced health information systems and sound evaluation studies involving measures of workload reduction and costs.
Delivery of Health Care ; Health Information Systems ; Medical Informatics ; Monitoring, Ambulatory

Presently, allergy diagnosis and therapy procedures are undergoing a transition phase in which allergen extracts are being step-by-step replaced by molecule-based products. The new developments will allow clinicians to obtain detailed information on sensitization patterns, more accurate interpretation of allergic symptoms, and thus improved patients' management. In this respect, recombinant technology has been applied to develop this new generation of molecule-based allergy products. The use of recombinant allergens allows full validation of identity, quantity, homogeneity, structure, aggregation, solubility, stability, IgE-binding and the biologic potency of the products. In contrast, such parameters are extremely difficult to assay and standardize for extract-based products. In addition to the possibility of bulk production of wild type molecules for diagnostic purposes, recombinant technology opened the possibility of developing safer and more efficacious products for allergy therapy. A number of molecule-based hypoallergenic preparations have already been successfully evaluated in clinical trials, bringing forward the next generation of allergy vaccines. In this contribution, we review the latest developments in allergen characterization, molecule-based allergy diagnosis, and the application of recombinant allergens in therapeutic setups. A comprehensive overview of clinical trials using recombinant allergens as well as synthetic peptides is presented.
Allergens/*immunology ; Humans ; Hypersensitivity/*immunology/*therapy ; Immunotherapy/methods ; Recombinant Proteins/immunology

Presently, allergy diagnosis and therapy procedures are undergoing a transition phase in which allergen extracts are being step-by-step replaced by molecule-based products. The new developments will allow clinicians to obtain detailed information on sensitization patterns, more accurate interpretation of allergic symptoms, and thus improved patients' management. In this respect, recombinant technology has been applied to develop this new generation of molecule-based allergy products. The use of recombinant allergens allows full validation of identity, quantity, homogeneity, structure, aggregation, solubility, stability, IgE-binding and the biologic potency of the products. In contrast, such parameters are extremely difficult to assay and standardize for extract-based products. In addition to the possibility of bulk production of wild type molecules for diagnostic purposes, recombinant technology opened the possibility of developing safer and more efficacious products for allergy therapy. A number of molecule-based hypoallergenic preparations have already been successfully evaluated in clinical trials, bringing forward the next generation of allergy vaccines. In this contribution, we review the latest developments in allergen characterization, molecule-based allergy diagnosis, and the application of recombinant allergens in therapeutic setups. A comprehensive overview of clinical trials using recombinant allergens as well as synthetic peptides is presented.
Allergens/*immunology ; Humans ; Hypersensitivity/*immunology/*therapy ; Immunotherapy/methods ; Recombinant Proteins/immunology

Objective: The present study investigated, whether computer-aided therapy in patients with Parkinson’s disease is equivalent/non-inferior to conventional Lee Silvermann Voice Treatment (LSVT)-BIGtherapy in respect to motor outcome as measured by the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) and quality of life as measured by the Parkinson’s Disease Questionnaire (PDQ-39). Methods: In this controlled, rater-blinded study, 34 patients were included and 24 patients randomized to train seven standard exercises of the BIG-therapy either by a computer (BeBIG-group) or by a certified LSVT-BIG therapist (ThBIG-group) over four weeks. Equivalence was assessed by comparing the confidence interval of the BeBIG-group to the equivalence margin of the ThBIG-group. Results: There were no significant group differences in respect to age, disease duration, L-dopa equivalent daily dose or clinical stage of the disease. Both groups profited significantly from the therapy as demonstrated by an improvement in the MDS-UPDRS-III of 9.17 point in the BeBIG-group and of 8.92 points in the ThBIG-group. There was a non-significant decrease in the PDQ-39 of 9.23 points in the BeBIG-group and 4.23 points in the ThBIG-group. However, equivalence could not be demonstrated as the improvement of the BeBIG-group exceeded the confidence interval of the ThBIG-group. Conclusion: Physical training by a computer as well as by a therapist improves motor symptoms and quality of life in Parkinson’s disease. Both therapies are not equivalent, superiority of the computerized training can however not be concluded, as the study was only designed to test for non-inferiority. Therefore, computerized training can be considered as an add-on-therapy

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Objective: Impaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice. Methods: A non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions. Results: Based on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment. Conclusion AdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice.