Aligner therapy in adolescents: first-year results on the impact of therapy on oral health-related quality of life and oral hygiene.

OBJECTIVES: The aim of this multicenter clinical study was to examine the oral health-related quality of life and oral hygiene in adolescents before and during aligner therapy. MATERIALS AND METHODS: Forty subjects (18 ♀, 22 ♂; mean age: 13.6 years) scheduled for aligner therapy (Invisalign® Teen) were given oral health-related quality of life questionnaires, Oral Health Impact Profile (OHIP-G14) and Psychosocial Impact of Dental Aesthetic Questionnaire (PIDAQ), to complete within their treatment (visit 1: 0 start of therapy; visit 2: 0 + 4 weeks; visit 3: 0 + 10 weeks; visit 4: 0 + 6 months; visit 5: 0 + 1 year). To assess oral hygiene, a questionnaire to take home was used, and plaque level was evaluated with the Quigley-Hein Plaque Index (TMQH) modified by Turesky et al. RESULTS: The OHIP-G14 mean score before aligner therapy was 3.3 ± 3.2, and 4.9 ± 5.4 after 1 year. The PIDAQ showed a positive psychological change in the well-being, as well as a more effective at-home oral hygiene regime. On average, the TMQH remained at a low level (grade 2 of 0-5). The initial insertion of the aligners caused the most significant changes in all parameters (except TMQH). CONCLUSION: Oral health-related quality of life is only slightly affected during the first year of aligner therapy in adolescents. Oral hygiene at home is intensified and there is no increased dental plaque accumulation. CLINICAL RELEVANCE: Dentofacial esthetics is a subset of the so-called Oral H-Related Quality of Life (OHRQoL) which should be considered more during orthodontic therapy.

Perfusate adsorption during ex vivo lung perfusion improves early post-transplant lung function.

OBJECTIVE: Improvement in ex vivo lung perfusion protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction. We hypothesize that perfusate adsorption during ex vivo lung perfusion reconditions the allograft to ischemia-reperfusion injury after lung transplantation. METHODS: Donor pig lungs were preserved for 24 hours at 4°C, followed by 6 hours of ex vivo lung perfusion according to the Toronto protocol. The perfusate was additionally adsorbed through a CytoSorb adsorber (CytoSorbents, Berlin, Germany) in the treatment group, whereas control lungs were perfused according to the standard protocol (n = 5, each). Ex vivo lung perfusion physiology and biochemistry were monitored. Upon completion of ex vivo lung perfusion, a left single lung transplantation was performed. Oxygenation function and lung mechanics were assessed during a 4-hour reperfusion period. The inflammatory response was determined during ex vivo lung perfusion and reperfusion. RESULTS: The cytokine concentrations in the perfusate were markedly lower with the adsorber, resulting in improved ex vivo lung perfusion physiology and biochemistry during the 6-hour perfusion period. Post-transplant dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group. Isolated allograft oxygenation function and dynamic compliance continued to be superior in the adsorber group at the end of reperfusion, accompanied by a markedly decreased local inflammatory response. CONCLUSIONS: Implementation of an additional cytokine adsorber has refined the standard ex vivo lung perfusion protocol. Furthermore, cytokine removal during ex vivo lung perfusion improved immediate post-transplant graft function together with a less intense inflammatory response to reperfusion in pigs. Further studies are warranted to understand the beneficial effects of perfusate adsorption during ex vivo lung perfusion in the clinical setting.

Computed Tomography-based evaluation of porcine cardiac dimensions to assist in pre-study planning and optimized model selection for pre-clinical research.

The pig (Sus Scrofa Domestica) is an accepted model for preclinical evaluation of prosthetic heart valves and trans-catheter implantation techniques. Understanding porcine cardiac dimensions through three-dimensional computed tomography (CT), increases preclinical study success, leading to higher cost efficiency and to the observance of the obligation to the 3 R principles. Cardiac CT images of twenty-four Swiss large white pigs were segmented; aortic root, mitral valve, pulmonary trunk, tricuspid valve, as well as the aorto-mitral angle and left atrial height were analyzed. Correlation coefficient (r) was calculated in relation to body weight. In Swiss large white pigs, valvular dimensions, length of the pulmonary artery and ascending aorta as well as left atrial height correlate with body weight. Coronary ostia heights and aorto-mitral angle size can be neglected in animal size selection; no changes were found for either of the two parameters with increasing body weight.

Establishing a pre-clinical growing animal model to test a tissue engineered valved pulmonary conduit.

BACKGROUND: Many valvular pathologies of the heart may be only sufficiently treated by replacement of the valve if a reconstruction is not feasible. However, structural deterioration, thrombosis with thromboembolic events and infective endocarditis are commonly encountered complications over time and often demand a re-operation. In congenital heart disease the lack of small diameter valves with the potential to grow poses additional challenges and limits treatment options to homo- or xenograft implants. METHODS: In this study, a chronic sheep model (24 months follow-up), a self-constructed valved conduit was created out of a tissue engineered (TE) patch (CorMatrix® Cardiovascular, Inc, USA) and implanted in orthotopic right ventricular (RV)-pulmonary artery (PA) position. Thereafter, the sheep were regularly monitored by clinical, laboratory and echocardiographic examinations to evaluate cardiac function and the implanted RV-PA-conduit. DISCUSSION: Here, we summarize the study protocol and our experiences during the perioperative phase and the follow up period and explain how we constructed a valved conduit out of a commercially available TE patch. TRIAL REGISTRATION: License number: ZH 284/14.

Differential Leaflet Remodeling of Bone Marrow Cell Pre-Seeded Versus Nonseeded Bioresorbable Transcatheter Pulmonary Valve Replacements.

This study showed that bone marrow mononuclear cell pre-seeding had detrimental effects on functionality and in situ remodeling of bioresorbable bisurea-modified polycarbonate (PC-BU)-based tissue-engineered heart valves (TEHVs) used as transcatheter pulmonary valve replacement in sheep. We also showed heterogeneous valve and leaflet remodeling, which affects PC-BU TEHV safety, challenging their potential for clinical translation. We suggest that bone marrow mononuclear cell pre-seeding should not be used in combination with PC-BU TEHVs. A better understanding of cell-scaffold interaction and in situ remodeling processes is needed to improve transcatheter valve design and polymer absorption rates for a safe and clinically relevant translation of this approach.

Human cell-derived tissue-engineered heart valve with integrated Valsalva sinuses: towards native-like transcatheter pulmonary valve replacements.

Transcatheter valve replacement indication is currently being extended to younger and lower-risk patients. However, transcatheter prostheses are still based on glutaraldehyde-fixed xenogeneic materials. Hence, they are prone to calcification and long-term structural degeneration, which are particularly accelerated in younger patients. Tissue-engineered heart valves based on decellularized in vitro grown tissue-engineered matrices (TEM) have been suggested as a valid alternative to currently used bioprostheses, showing good performance and remodeling capacity as transcatheter pulmonary valve replacement (TPVR) in sheep. Here, we first describe the in vitro development of human cell-derived TEM (hTEM) and their application as tissue-engineered sinus valves (hTESVs), endowed with Valsalva sinuses for TPVR. The hTEM and hTESVs were systematically characterized in vitro by histology, immunofluorescence, and biochemical analyses, before they were evaluated in a pulse duplicator system under physiological pulmonary pressure conditions. Thereafter, transapical delivery of hTESVs was tested for feasibility and safety in a translational sheep model, achieving good valve performance and early cellular infiltration. This study demonstrates the principal feasibility of clinically relevant hTEM to manufacture hTESVs for TPVR.

Left ventricular blood flow patterns at rest and under dobutamine stress in healthy pigs.

Intracardiac blood flow patterns are affected by the morphology of cardiac structures and are set up to support the heart's pump function. Exercise affects contractility and chamber size as well as pre- and afterload. The aim of this study was to test the feasibility of four-dimensional phase contrast cardiovascular MRI under pharmacological stress and to study left ventricular blood flow under stress. 4D flow data were successfully acquired and analysed in 12 animals. During dobutamine infusion, heart rate and ejection fraction increased (82 ± 5 bpm versus 124 ± 3 bpm/46 ± 9% versus 65 ± 7%; both p < 0.05). A decrease in left ventricular end-diastolic volume (72 ± 14 mL versus 55 ± 8 mL; p < 0.05) and end-systolic volume (40 ± 15 mL versus 19 ± 6 mL; p < 0.05) but no change in stroke volume were observed. Trans-mitral diastolic inflow velocity increased under dobutamine and the trajectory of inflowing blood was directed towards the anterior septum with increased inflow angle (26 ± 5°) when compared with controls (15 ± 2°). In 5/6 animals undergoing stress diastolic vortices developed later, and in 3/6 animals vortices collapsed earlier with significantly smaller cross-sectional area during diastole. The vorticity index was not affected. Under the stress condition direct flow (% ejection within the next heart beat) increased from 43 ± 6% to 53 ± 8%. 4D MRI blood flow acquisition and analysis are feasible in pig hearts under dobutamine-induced stress. Flow patterns characterized by high blood velocity and antero-septally oriented diastolic inflow as well as decreased ventricular volumes are unfavourable conditions for diastolic vortex development under pharmacological stress, and cardiac output is increased by a rise in heart rate and directly ejected left ventricular blood volume.

Quantitative myocardial first-pass cardiovascular magnetic resonance perfusion imaging using hyperpolarized [1-13C] pyruvate.

BACKGROUND: The feasibility of absolute myocardial blood flow quantification and suitability of hyperpolarized [1-13C] pyruvate as contrast agent for first-pass cardiovascular magnetic resonance (CMR) perfusion measurements are investigated with simulations and demonstrated in vivo in a swine model. METHODS: A versatile simulation framework for hyperpolarized CMR subject to physical, physiological and technical constraints was developed and applied to investigate experimental conditions for accurate perfusion CMR with hyperpolarized [1-13C] pyruvate. Absolute and semi-quantitative perfusion indices were analyzed with respect to experimental parameter variations and different signal-to-noise ratio (SNR) levels. Absolute myocardial blood flow quantification was implemented with an iterative deconvolution approach based on Fermi functions. To demonstrate in vivo feasibility, velocity-selective excitation with an echo-planar imaging readout was used to acquire dynamic myocardial stress perfusion images in four healthy swine. Arterial input functions were extracted from an additional image slice with conventional excitation that was acquired within the same heartbeat. RESULTS: Simulations suggest that obtainable SNR and B0 inhomogeneity in vivo are sufficient for the determination of absolute and semi-quantitative perfusion with ≤25% error. It is shown that for expected metabolic conversion rates, metabolic conversion of pyruvate can be neglected over the short duration of acquisition in first-pass perfusion CMR. In vivo measurements suggest that absolute myocardial blood flow quantification using hyperpolarized [1-13C] pyruvate is feasible with an intra-myocardial variability comparable to semi-quantitative perfusion indices. CONCLUSION: The feasibility of quantitative hyperpolarized first-pass perfusion CMR using [1-13C] pyruvate has been investigated in simulations and demonstrated in swine. Using an approved and metabolically active compound is envisioned to increase the value of hyperpolarized perfusion CMR in patients.

Voluntary intake of paracetamol-enriched drinking water and its influence on the success of embryo transfer in mice.

Embryo transfer (ET) in mice is a key technique in biomedical research, and is carried out mostly via surgery by transferring founder embryos into pseudo-pregnant recipient females. To cover post-operative analgesic requirements in surrogate mothers, oral self-administration of painkillers has several advantages, but its effectiveness has also been criticized as voluntary ingestion of the drug can be uncertain. Additionally, concerns about potential negative side effects of analgesics on embryo viability and development have been raised. In this regard, we investigated the impact of orally administered analgesia by comparing the outcome of ET with and without paracetamol in the drinking water (3.5mg/ml) of surrogate mothers. Water intake increased significantly when paracetamol, as a sweet-tasting formulation (children's syrup), was added to the drinking water. Measurements of paracetamol concentrations in blood serum confirmed reasonable drug uptake. Success rate of ETs and the body weight of newborn offspring were not different whether paracetamol was administered for two days after surgery or not. In conclusion, paracetamol in drinking water was consumed voluntarily in substantial doses, without detectable side-effects, by freshly operated surrogate mothers, and can therefore be recommended as a feasible method for providing analgesic treatment for surgical ET in mice.