Cerebrovascular super-resolution 4D Flow MRI - Sequential combination of resolution enhancement by deep learning and physics-informed image processing to non-invasively quantify intracranial velocity, flow, and relative pressure.

The development of cerebrovascular disease is tightly coupled to regional changes in intracranial flow and relative pressure. Image-based assessment using phase contrast magnetic resonance imaging has particular promise for non-invasive full-field mapping of cerebrovascular hemodynamics. However, estimations are complicated by the narrow and tortuous intracranial vasculature, with accurate image-based quantification directly dependent on sufficient spatial resolution. Further, extended scan times are required for high-resolution acquisitions, and most clinical acquisitions are performed at comparably low resolution (>1 mm) where biases have been observed with regard to the quantification of both flow and relative pressure. The aim of our study was to develop an approach for quantitative intracranial super-resolution 4D Flow MRI, with effective resolution enhancement achieved by a dedicated deep residual network, and with accurate quantification of functional relative pressures achieved by subsequent physics-informed image processing. To achieve this, our two-step approach was trained and validated in a patient-specific in-silico cohort, showing good accuracy in estimating velocity (relative error: 15.0 ± 0.1%, mean absolute error (MAE): 0.07 ± 0.06 m/s, and cosine similarity: 0.99 ± 0.06 at peak velocity) and flow (relative error: 6.6 ± 4.7%, root mean square error (RMSE): 0.56 mL/s at peak flow), and with the coupled physics-informed image analysis allowing for maintained recovery of functional relative pressure throughout the circle of Willis (relative error: 11.0 ± 7.3%, RMSE: 0.3 ± 0.2 mmHg). Furthermore, the quantitative super-resolution approach is applied to an in-vivo volunteer cohort, effectively generating intracranial flow images at <0.5 mm resolution and showing reduced low-resolution bias in relative pressure estimation. Our work thus presents a promising two-step approach to non-invasively quantify cerebrovascular hemodynamics, being applicable to dedicated clinical cohorts in the future.

Combining spore germination and heat inactivation to decontaminate materials contaminated with Bacillus anthracis spores.

AIMS: To add a spore germination step in order to reduce decontamination temperature and time requirements compared to the current hot, humid air decontamination parameters, which are 75-80°C, ≥72 h, 70-90% RH, down to ≤60°C and ≤24 h total decontamination time. METHODS AND RESULTS: Bacillus anthracis spore germination with l-alanine+inosine+calcium dipicolinate (CaDPA) was quantified at 0-40°C, several time points and spore concentrations of 5-9 log10 per ml. Germination efficiency at 0-40°C was >99% at <8 log10 spores per ml. The temperature optimum was 20°C. Germination efficiency was significantly higher but slower at 0°C compared to ≥30°C at ≥8 log10 spores per ml. A single germinant application followed by 60°C, 1-h treatment consistently inactivated >2 log10 (>99%) of spores. However, a repeat application of germinant was needed to achieve the objective of ≥6 log10 spore inactivation out of a 7 log10 challenge (≥99·9999%) for ≤24 h total decontamination time for nylon and aircraft performance coating. CONCLUSIONS: l-alanine+inosine+CaDPA stimulated germination across wide temperature and spore concentration ranges. SIGNIFICANCE AND IMPACT OF THE STUDY: Germination expands the scope of spore decontamination to include materials from any industry sector that can be sprayed with an aqueous germinant solution.

4D modelling for rapid assessment of biventricular function in congenital heart disease.

Although more patients with congenital heart disease (CHD) are now living longer due to better surgical interventions, they require regular imaging to monitor cardiac performance. There is a need for robust clinical tools which can accurately assess cardiac function of both the left and right ventricles in these patients. We have developed methods to rapidly quantify 4D (3D + time) biventricular function from standard cardiac MRI examinations. A finite element model was interactively customized to patient images using guide-point modelling. Computational efficiency and ability to model large deformations was improved by predicting cardiac motion for the left ventricle and epicardium with a polar model. In addition, large deformations through the cycle were more accurately modeled using a Cartesian deformation penalty term. The model was fitted to user-defined guide points and image feature tracking displacements throughout the cardiac cycle. We tested the methods in 60 cases comprising a variety of congenital heart diseases and showed good correlation with the gold standard manual analysis, with acceptable inter-observer error. The algorithm was considerably faster than standard analysis and shows promise as a clinical tool for patients with CHD.

An interactive tool for rapid biventricular analysis of congenital heart disease.

Cardiac malformations are the most common birth defect. Better interventions in early life have improved mortality for children with congenital heart disease, but heart failure is a significant problem in adulthood. These patients require regular imaging and analysis of biventricular (left and right ventricular) function. In this study, we describe a rapid method to analyse left and right ventricular shape and function from cardiac MRI examinations. A 4D (3D+time) finite element model template is interactively customized to the anatomy and motion of the biventricular unit. The method was validated in 17 patients and 10 ex-vivo hearts. Interactive model updates were achieved through preconditioned conjugate gradient optimization on a multithread system, and by precomputing points predicted from a coarse mesh optimization.

Hot, humid air decontamination of a C-130 aircraft contaminated with spores of two acrystalliferous Bacillus thuringiensis strains, surrogates for Bacillus anthracis.

AIM: To develop test methods and evaluate survival of Bacillus thuringiensis kurstaki cry(-) HD-1 and B. thuringiensis Al Hakam spores after exposure to hot, humid air inside of a C-130 aircraft. METHODS AND RESULTS: Bacillus thuringiensis spores were either pre-inoculated on 1 × 2 or 2 × 2 cm substrates or aerosolized inside the cargo hold of a C-130 and allowed to dry. Dirty, complex surfaces (10 × 10 cm) swabbed after spore dispersal showed a deposition of 8-10 log10 m(-2) through the entire cargo hold. After hot, humid air decontamination at 75-80°C, 70-90% relative humidity for 7 days, 87 of 98 test swabs covering 0·98 m(2) , showed complete spore inactivation. There was a total of 1·67 log10 live CFU detected in 11 of the test swabs. Spore inactivation in the 98 test swabs was measured at 7·06 log10 m(-2) . CONCLUSIONS: Laboratory test methods for hot, humid air decontamination were scaled for a large-scale aircraft field test. The C-130 field test demonstrated that hot, humid air can be successfully used to decontaminate an aircraft. SIGNIFICANCE AND IMPACT OF THE STUDY: Transition of a new technology from research and development to acquisition at a Technology Readiness Level 7 is unprecedented.

Test methods and response surface models for hot, humid air decontamination of materials contaminated with dirty spores of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam.

AIMS: To develop test methods and evaluate survival of Bacillus anthracis ∆Sterne or Bacillus thuringiensis Al Hakam on materials contaminated with dirty spore preparations after exposure to hot, humid air using response surface modelling. METHODS AND RESULTS: Spores (>7 log10 ) were mixed with humic acid + spent sporulation medium (organic debris) or kaolin (dirt debris). Spore samples were then dried on five different test materials (wiring insulation, aircraft performance coating, anti-skid, polypropylene, and nylon). Inoculated materials were tested with 19 test combinations of temperature (55, 65, 75°C), relative humidity (70, 80, 90%) and time (1, 2, 3 days). The slowest spore inactivation kinetics was on nylon webbing and/or after addition of organic debris. CONCLUSIONS: Hot, humid air effectively decontaminates materials contaminated with dirty Bacillus spore preparations; debris and material interactions create complex decontamination kinetic patterns; and B. thuringiensis Al Hakam is a realistic surrogate for B. anthracis. SIGNIFICANCE AND IMPACT OF THE STUDY: Response surface models of hot, humid air decontamination were developed which may be used to select decontamination parameters for contamination scenarios including aircraft.

Decontamination of materials contaminated with Francisella philomiragia or MS2 bacteriophage using PES-Solid, a solid source of peracetic acid.

AIM: The aim of the study was to develop test methods and evaluate survival of Francisella philomiragia cells and MS2 bacteriophage after exposure to PES-Solid (a solid source of peracetic acid) formulations with or without surfactants. METHODS AND RESULTS: Francisella philomiragia cells (≥7·6 log10 CFU) or MS2 bacteriophage (≥6·8 log10 PFU) were deposited on seven different test materials and treated with three different PES-Solid formulations, three different preneutralized samples and filter controls at room temperature for 15 min. There were 0-1·3 log10 CFU (<20 cells) of cell survival, or 0-1·7 log10 (<51 PFU) of bacteriophage survival in all 21 test combinations (organism, formulation and substrate) containing reactive PES-Solid. In addition, the microemulsion (Dahlgren Surfactant System) showed ≤2 log10 (100 cells) of viable F. philomiragia cells, indicating the microemulsion achieved <2 log10 CFU on its own. CONCLUSIONS: Three PES-Solid formulations and one microemulsion system (DSS) inactivated F. philomiragia cells and/or MS2 bacteriophage that were deposited on seven different materials. SIGNIFICANCE AND IMPACT OF THE STUDY: A test method was developed to show that reactive PES-Solid formulations and a microemulsion system (DSS) inactivated >6 log10 CFU/PFU F. philomiragia cells and/or MS2 bacteriophage on different materials.

Cardiovascular magnetic resonance: deeper insights through bioengineering.

Heart disease is the main cause of morbidity and mortality worldwide, with coronary artery disease, diabetes, and obesity being major contributing factors. Cardiovascular magnetic resonance (CMR) can provide a wealth of quantitative information on the performance of the heart, without risk to the patient. Quantitative analyses of these data can substantially augment the diagnostic quality of CMR examinations and can lead to more effective characterization of disease and quantification of treatment benefit. This review provides an overview of the current state of the art in CMR with particular regard to the quantification of motion, both microscopic and macroscopic, and the application of bioengineering analysis for the evaluation of cardiac mechanics. We discuss the current clinical practice and the likely advances in the next 5-10 years, as well as the ways in which clinical examinations can be augmented by bioengineering analysis of strain, compliance, and stress.

Decontamination of materials contaminated with Bacillus anthracis and Bacillus thuringiensis Al Hakam spores using PES-Solid, a solid source of peracetic acid.

AIMS: To develop test methods and evaluate survival of Bacillus anthracis Ames, B. anthracis ∆Sterne and B. thuringiensis Al Hakam spores after exposure to PES-Solid (a solid source of peracetic acid), including PES-Solid formulations with bacteriostatic surfactants. METHODS AND RESULTS: Spores (≥ 7 logs) were dried on seven different test materials and treated with three different PES-Solid formulations (or preneutralized controls) at room temperature for 15 min. There was either no spore survival or less than 1 log (<10 spores) of spore survival in 56 of 63 test combinations (strain, formulation and substrate). Less than 2.7 logs (<180 spores) survived in the remaining seven test combinations. The highest spore survival rates were seen on water-dispersible chemical agent resistant coating (CARC-W) and Naval ship topcoat (NTC). Electron microscopy and Coulter analysis showed that all spore structures were intact after spore inactivation with PES-Solid. CONCLUSIONS: Three PES-Solid formulations inactivated Bacillus spores that were dried on seven different materials. SIGNIFICANCE AND IMPACT OF THE STUDY: A test method was developed to show that PES-Solid formulations effectively inactivate Bacillus spores on different materials.

Test method development to evaluate hot, humid air decontamination of materials contaminated with Bacillus anthracis ∆Sterne and B. thuringiensis Al Hakam spores.

AIMS: To develop test methods and evaluate the survival of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores after exposure to hot, humid air. METHODS AND RESULTS: Spores (>7 logs) of both strains were dried on six different test materials. Response surface methodology was employed to identify the limits of spore survival at optimal test combinations of temperature (60, 68, 77°C), relative humidity (60, 75, 90%) and time (1, 4, 7 days). No spores survived the harshest test run (77°C, 90% r.h., 7 days), while > 6·5 logs of spores survived the mildest test run (60°C, 60% r.h., 1 day). Spores of both strains inoculated on nylon webbing and polypropylene had greater survival rates at 68°C, 75% r.h., 4 days than spores on other materials. Electron microscopy showed no obvious physical damage to spores using hot, humid air, which contrasted with pH-adjusted bleach decontamination. CONCLUSIONS: Test methods were developed to show that hot, humid air effectively inactivates B. anthracis ∆Sterne and B. thuringiensis Al Hakam spores with similar kinetics. SIGNIFICANCE AND IMPACT OF THE STUDY: Hot, humid air is a potential alternative to conventional chemical decontamination.

Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers.

AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are secreted from enteroendocrine L cells in response to numerous stimuli, including bile salts. Both have multiple effects that are potentially useful in treating diabetes and obesity. L cell number and hormone content in the intestine are highest in the rectum in humans. We investigated the effects of intrarectal sodium taurocholate on plasma GLP-1, PYY, insulin and glucose concentrations, and on food intake of a subsequent meal. METHODS: Ten obese type 2 diabetic volunteers were each studied on five separate occasions after an overnight fast and oral administration of 100 mg sitagliptin 10 h before the study. They then received an intrarectal infusion of either one of four doses of taurocholate (0.66, 2, 6.66 or 20 mmol, each in 20 ml of vehicle) or vehicle alone (1% carboxymethyl cellulose) single-blind over 1 min. Hormone and glucose measurements were made prior to, and for 1 h following, the infusion. The consumption of a previously selected favourite meal eaten to satiety was measured 75 min after the infusion. RESULTS: Taurocholate dose-dependently increased GLP-1, PYY and insulin, with 20 mmol doses resulting in peak concentrations 7.2-, 4.2- and 2.6-fold higher, respectively, than those achieved with placebo (p < 0.0001 for each). Plasma glucose decreased by up to 3.8 mmol/l (p < 0.001). Energy intake was decreased dose-dependently by up to 47% (p < 0.0001). The ED(50) values for effects on integrated GLP-1, insulin, PYY, food intake and glucose-lowering responses were 8.1, 10.5, 18.5, 24.2 and 25.1 mmol, respectively. CONCLUSIONS/INTERPRETATION: Therapies that increase bile salts (or their mimics) in the distal bowel may be valuable in the treatment of type 2 diabetes and obesity.

Decontamination of a hard surface contaminated with Bacillus anthracisΔSterne and B. anthracis Ames spores using electrochemically generated liquid-phase chlorine dioxide (eClO2).

AIMS: To evaluate the inactivation of Bacillus anthracisΔSterne and Ames spores using electrochemically generated liquid-phase chlorine dioxide (eClO(2)) and compare two sporulation and decontamination methods with regard to cost, safety and technical constraints. METHODS AND RESULTS: Spores were prepared via agar and broth methods and subsequently inoculated and dried onto clean, autoclave-sterilized glass coupons. Bacillus anthracis spore inactivation efficacy was evaluated using the modified three-step method (AOAC 2008.05) and a single-tube extraction method. Spores (7·0 ± 0·5 logs) were inactivated within 1 min at room temperature using freshly prepared eClO(2). Bacillus anthracisΔSterne spores decreased in size after eClO(2) treatment as measured using a Beckman Coulter Multisizer. CONCLUSIONS: eClO(2) saturation of a hard surface was an effective B. anthracis sporicide. Broth sporulation and the single-tube extraction method required less time and fewer steps, yielded a higher percentage of phase-bright spores and showed higher spore recovery efficiency compared with AOAC 2008.05, making it more amenable to biosafety level 3 (BSL3) testing of virulent spores. SIGNIFICANCE AND IMPACT OF THE STUDY: Two test methods demonstrated the sporicidal efficacy of eClO(2). A new single-tube extraction test protocol for decontaminants was introduced.

Histological evaluation of repair of the rotator cuff in a primate model.

The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight 'middle-aged' baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically. Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature. Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing.

Comparative anatomy of the rotator cuff.

While the evolution of the bony skeleton of the shoulder girdle is well described, there is little information regarding the soft tissues, in particular of the rotator cuff. We dissected the shoulders of 23 different species and compared the anatomical features of the tendons of the rotator cuff. The alignment and orientation of the collagen fibres of some of the tendons were also examined histologically. The behaviour of the relevant species was studied, with particular reference to the extent and frequency of forward-reaching and overhead activity of the forelimb. In quadrupedal species, the tendons of supraspinatus, infraspinatus and teres minor were seen to insert into the greater tuberosity of the humerus separately. They therefore did not form a true rotator cuff with blending of the tendons. This was only found in advanced primates and in one unusual species, the tree kangaroo. These findings support the suggestion that the appearance of the rotator cuff in the evolutionary process parallels anatomical adaptation to regular overhead activity and the increased use of the arm away from the sagittal plane.

ER: YAG laser for composite removal after bracket debonding: a qualitative SEM analysis.

OBJECTIVE: To qualitatively compare the effectiveness of the Er:YAG laser with conventional methods for removing the composite remnants and the enamel ablation produced after bracket debonding. MATERIALS AND METHODS: Brackets were bonded on 12 extracted premolars and the composite remnants were removed by 3 different methods: tungsten-carbide bur and 2 Er:YAG laser intervals. Four other premolars were used as a control group. Samples were analyzed with scanning electron microscopy (SEM) and the amount of composite remaining on the teeth and the amount of enamel ablated on each sample were qualitatively ranked by 3 examiners. The results were statistically analyzed by the Tukey test. RESULTS: The Er:YAG laser performed significantly better than the conventional technique for removing the composite remnants, but the amount of enamel ablation produced was significantly higher. CONCLUSIONS: The Er:YAG laser can be used to remove composite remnants after orthodontic bracket debonding, but further studies are required to determine the ideal specifications of this type of laser to reduce the amount of enamel ablation produced under the specifications used in this study.

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.

AIMS/HYPOTHESIS: Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. METHODS: We performed a 12 month randomised placebo-controlled study of the effects of treatment with the Cu(II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n = 15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM(bsa)) was the primary endpoint variable. RESULTS: Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM(bsa) by 5.0 +/- 7.2 g/m(2) (mean +/- SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p = 0.0056 compared with placebo) and by 10.6 +/- 7.6 g/m(2) at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p = 0.0088), whereas LVM(bsa) was unchanged by placebo treatment. In a multiple-regression model that explained ~75% of variation (R (2) = 0.748, p = 0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM(bsa). CONCLUSIONS/INTERPRETATION: Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12609000053224 FUNDING: The Endocore Research Trust; Lottery Health New Zealand; the Maurice and Phyllis Paykel Trust; the Foundation of Research, Science and Technology (New Zealand); the Health Research Council of New Zealand; the Ministry of Education (New Zealand) through the Maurice Wilkins Centre for Molecular Biodiscovery; and the Protemix Corporation.

Passive ventricular mechanics modelling using MRI of structure and function.

Patients suffering from dilated cardiomyopathy or myocardial infarction can develop left ventricular (LV) diastolic impairment. The LV remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions and this remodeling process can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element model was developed to incorporate physiological and mechanical information derived from in vivo magnetic resonance imaging (MRI) tissue tagging, in vivo LV cavity pressure recording and ex vivo diffusion tensor MRI (DTMRI) of a canine heart. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion (the primary eigenvector) in each voxel of a DTMRI directly correlates with the myocardial fibre orientation. This model was customized to the geometry of the canine LV during diastasis by fitting the segmented epicardial and endocardial surface data from tagged MRI using nonlinear finite element fitting techniques. Myofibre orientations, extracted from DTMRI of the same heart, were incorporated into this geometric model using a free form deformation methodology. Pressure recordings, temporally synchronized to the tissue tagging MRI data, were used to simulate the LV deformation during diastole. Simulation of the diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. This integrated physiological model will allow more insight into the regional passive diastolic mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction in pathological conditions.

Synovial pathology in an ovine model of osteoarthritis: effect of intraarticular hyaluronan (Hyalgan).

OBJECTIVES: Published scoring methods for quantifying synovitis focus on acute inflammatory parameters, and are unsuitable as outcome measures in experimental surgical models of osteoarthritis (OA). The aim of the present study was to define a modified histopathological scoring system for ovine synovium more suited to the chronic pathology induced by ovine meniscectomy, and to apply it to detect any therapeutic effects following intraarticular injection of hyaluronan (HA) (Hyalgan). METHODS: OA was induced in 12 sheep by bilateral lateral meniscectomy, before weekly intraarticular injections of HA or saline vehicle from 16-20 weeks post-operatively, prior to sacrifice at 26 weeks. Six matched sheep were used as controls. Synovial sections were qualitatively scored for hyperplasia, inflammatory infiltrate, fibrosis, and hypervascularity; cell number, depth of fibrosis, and vessel number were also quantified using a graticule. RESULTS: OA synovia had significantly elevated scores for inflammatory cell infiltration, subintimal fibrosis, vascularity, and aggregate score relative to controls. HA-treated sheep had significantly lower vascularity score (p=0.015), aggregate score (p=0.007), depth of fibrosis (p=0.003) and vessel number (p=0.048) compared to saline-injected sheep. CONCLUSION: This study confirms the presence of a chronic synovitis in this OA model, characterised by subintimal fibrosis and hypervascularity (but only modest infiltrate and minimal intimal hyperplasia), which is partially ameliorated by intraarticular hyaluronate therapy.

Prevalence of malocclusions in a young Brazilian population.

Malocclusions are generally treated in adolescents and adults, but they are established at an early age. The purpose of this study was to determine the prevalence of malocclusions in a young Brazilian population. The sample included 926 children, 8 to 12 years old, attending 5 public schools in the state of Goias, Brazil The type of occlusion was visually determined during the oral exam and statistical analysis, Chi-square test, was performed to correlate the prevalence of malocclusion with gender and with age. 819 patients out of the 926 patients had some type of malocclusion. From those, 513 patients had a class I malocclusion, 201 patients were classified as class II malocclusion, and 105 patients were class III malocclusion. Vertically, 62 patients showed a deep bite and 61 patients had an open bite. Transversely, 40 patients presented a bilateral posterior crossbite, 54 patients had a posterior crossbite on the left side, and 39 patients had a posterior crossbite on the right side. No significant correlation between gender and malocclusions was found and the number of patients with malocclusions between boys and girls were similar. Considering the three spatial planes, there is a high prevalence of malocclusions among the young Brazilian population. Therefore, the dental community must improve health policies and treat malocclusions earlier.

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain.

OBJECTIVE: To evaluate histologic, immunohistochemical, and molecular changes in tendon induced by altered strain in a large-animal model. METHODS: A full-thickness partial-width laceration of the infraspinatus tendon was created in 5 sheep, while 5 sham-operated sheep were used as controls. Sheep were killed after 4 weeks, and 4 differentially stressed tendon regions (tensile or near bone attachment from overstressed or stress-deprived halves) were evaluated for histopathology, proteoglycan (PG) accumulation, and characterization of glycosaminoglycans and aggrecan catabolites. Gene expression of matrix components, enzymes, and inhibitors was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: Histopathologic changes were detected in both overstressed and stress-deprived tensile tendon, but only in stress-deprived tendon near bone. In overstressed and stress-deprived tensile tendon, levels of keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate were increased. In overstressed tensile tendon, levels of ADAMTS-generated aggrecan catabolites were increased. There was increased matrix metalloproteinase 13 (MMP-13) and decreased fibromodulin and decorin expression in all regions. Increased MMP-1, MMP-9, MMP-14, and ADAMTS-1 expression, and decreased type II collagen expression were restricted to stress-deprived tendon. In stress-deprived bone-attachment regions, messenger RNA (mRNA) for aggrecan was decreased, and ADAMTS was increased. In overstressed tensile tendon, aggrecan mRNA was increased, and ADAMTS was decreased. CONCLUSION: The distinct molecular changes in adjacent tissue implicate altered strain rather than humoral factors in controlling abnormal tenocyte metabolism, and highlight the importance of regional sampling. Tendon abnormalities induced by increased strain are accompanied by increased aggrecan, decreased ADAMTS, and low PG expression, which may negatively impact the structural integrity of the tissue and predispose to rupture.