Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles ...tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age-matched (45-70 yr) controls (n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effect of diabetes was explored by collapsing the diabetes groups (DB) compared with the controls. Skin collagen cross-linking lysylpyridinoline, hydroxylysylpyridinoline (136%, 80%, P < 0.01) and pentosidine concentrations (55%, P < 0.05) were markedly greater in DB. Furthermore, Achilles tendon material stiffness was higher in DB (54%, P < 0.01). Notably, DB also demonstrated higher forefoot/rearfoot peak-plantar-pressure ratio (33%, P < 0.01). Overall, Achilles tendon material stiffness and skin connective tissue cross-linking were greater in diabetic patients compared with controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g., skin and joint capsule) may influence foot gait. The difference in foot pressure distribution may contribute to the development of foot ulcers in diabetic patients.
The knowledge about the effect of estradiol on tendon connective tissue is limited. Therefore, we studied the influence of estradiol on tendon synthesis, structure, and biomechanical properties in ...postmenopausal women. Nonusers (control, n = 10) or habitual users of oral estradiol replacement therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation fractional synthesis rate (FSR) and microdialysis technique (NH(2)-terminal propeptide of type I collagen synthesis). Tendon area and fibril characteristics were determined by MRI and transmission electron microscopy, whereas tendon biomechanical properties were measured during isometric maximal voluntary contraction by ultrasound recording. Tendon FSR was markedly higher in ERT users (P < 0.001), whereas no group difference was seen in tendon NH(2)-terminal propeptide of type I collagen synthesis (P = 0.32). In ERT users, positive correlations between serum estradiol (s-estradiol) and tendon synthesis were observed, whereas change in tendon synthesis from rest to exercise was negatively correlated to s-estradiol. Tendon area, fibril density, fibril volume fraction, and fibril mean area did not differ between groups. However, the percentage of medium-sized fibrils was higher in ERT users (P < 0.05), whereas the percentage of large fibrils tended to be greater in control (P = 0.10). A lower Young's modulus (GPa/%) was found in ERT users (P < 0.05). In conclusion, estradiol administration was associated with higher tendon FSR and a higher relative number of smaller fibrils. Whereas this indicates stimulated collagen turnover in the resting state, collagen responses to exercise were negatively associated with s-estradiol. These results indicate a pivotal role for estradiol in maintaining homeostasis of female connective tissue.
Background:
Previous studies have shown that eccentric training has a positive effect on Achilles tendinopathy, but few randomized controlled trials have compared it with other loading-based ...treatment regimens.
Purpose:
To evaluate the effectiveness of eccentric training (ECC) and heavy slow resistance training (HSR) among patients with midportion Achilles tendinopathy.
Study Design:
Randomized controlled trial; Level of evidence, 1.
Methods:
A total of 58 patients with chronic (>3 months) midportion Achilles tendinopathy were randomized to ECC or HSR for 12 weeks. Function and symptoms (Victorian Institute of Sports Assessment–Achilles), tendon pain during activity (visual analog scale), tendon swelling, tendon neovascularization, and treatment satisfaction were assessed at 0 and 12 weeks and at the 52-week follow-up. Analyses were performed on an intention-to-treat basis.
Results:
Both groups showed significant (P < .0001) improvements in Victorian Institute of Sports Assessment–Achilles and visual analog scale from 0 to 12 weeks, and these improvements were maintained at the 52-week follow-up. Concomitant with the clinical improvement, there was a significant reduction in tendon thickness and neovascularization. None of these robust clinical and structural improvements differed between the ECC and HSR groups. However, patient satisfaction tended to be greater after 12 weeks with HSR (100%) than with ECC (80%; P = .052) but not after 52 weeks (HSR, 96%; ECC, 76%; P = .10), and the mean training session compliance rate was 78% in the ECC group and 92% in the HSR group, with a significant difference between groups (P < .005).
Conclusion:
The results of this study show that both traditional ECC and HSR yield positive, equally good, lasting clinical results in patients with Achilles tendinopathy and that the latter tends to be associated with greater patient satisfaction after 12 weeks but not after 52 weeks.
Background: Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying ...functional mechanisms remain elusive. Purpose: To investigate fibril morphology and mechanical properties in patellar tendinopathy and the effect of HSR on these properties. Study Design: Cohort study; Level of evidence, 2. Methods: Eight male patients with patellar tendinopathy completed 12 weeks of HSR. Nine healthy subjects served as controls. Assessments were conducted at baseline and at 12 weeks. Patients assessed symptoms/function and maximal tendon pain during activity. Tendon biopsy samples were analyzed for fibril density, volume fraction, and mean fibril area. Tendon mechanical properties were assessed using force and ultrasonography samplings. Results: Patients improved in symptoms/function (P = .02) and maximal tendon pain during activity (P = .008). Stiffness and modulus of control and tendinopathy tendons were similar at baseline. Stiffness remained unaffected in control tendons (3487 ± 392 to 3157 ± 327 N/mm, P = .57) but declined in tendinopathic tendons at 12 weeks (3185 ± 187 to 2701 ± 201 N/mm, P = .04). At baseline, fibril volume fraction was equal, fibril density smaller (P = .03), and mean fibril area tended to be higher in tendinopathy versus controls (P = .07). Fibril morphology remained unchanged in controls but fibril density increased (70% ± 18%, P = .02) and fibril mean area decreased (--26% ± 21%, P = .04) in tendinopathic tendons after HSR. Conclusion: Fibril morphology is abnormal in tendinopathy, but tendon mechanical properties are not. Clinical improvements after HSR were associated with changes in fibril morphology toward normal fibril density and mean fibril area. Heavy slow resistance training improved the clinical outcome of patellar tendinopathy, and these improvements were associated with normalization of fibril morphology, most likely due to a production of new fibrils.
Background
Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying ...functional mechanisms remain elusive.
Purpose
To investigate fibril morphology and mechanical properties in patellar tendinopathy and the effect of HSR on these properties.
Study Design
Cohort study; Level of evidence, 2.
Methods
Eight male patients with patellar tendinopathy completed 12 weeks of HSR. Nine healthy subjects served as controls. Assessments were conducted at baseline and at 12 weeks. Patients assessed symptoms/function and maximal tendon pain during activity. Tendon biopsy samples were analyzed for fibril density, volume fraction, and mean fibril area. Tendon mechanical properties were assessed using force and ultrasonography samplings.
Results
Patients improved in symptoms/function (P = .02) and maximal tendon pain during activity (P = .008). Stiffness and modulus of control and tendinopathy tendons were similar at baseline. Stiffness remained unaffected in control tendons (3487 ± 392 to 3157 ± 327 N/mm, P = .57) but declined in tendinopathic tendons at 12 weeks (3185 ± 187 to 2701 ± 201 N/mm, P = .04). At baseline, fibril volume fraction was equal, fibril density smaller (P = .03), and mean fibril area tended to be higher in tendinopathy versus controls (P = .07). Fibril morphology remained unchanged in controls but fibril density increased (70% ± 18%, P = .02) and fibril mean area decreased (—26% ± 21%, P = .04) in tendinopathic tendons after HSR.
Conclusion
Fibril morphology is abnormal in tendinopathy, but tendon mechanical properties are not. Clinical improvements after HSR were associated with changes in fibril morphology toward normal fibril density and mean fibril area. Heavy slow resistance training improved the clinical outcome of patellar tendinopathy, and these improvements were associated with normalization of fibril morphology, most likely due to a production of new fibrils.
This study investigated the effects of heavy resistance training in elderly males with chronic obstructive pulmonary disease (COPD). 18 Home-dwelling male patients (age range: 65–80 years), with a ...mean forced expiratory volume in the first second (FEV1) of 46±3.4% of predicted value, were recruited. Baseline and post-training assessments included: Cross-sectional area (CSA) of quadriceps assessed by MRI, isometric and isokinetic knee extension strength, isometric trunk strength, leg extension power, normal and maximal gait-speed on a 30m track, stair climbing time, number of chair stands in 30s, lung function (FEV1) and self-reported health. Subjects were randomized to a resistance training group (RE, n=9) or a control group conducting breathing exercises (CON, n=9). RE performed heavy progressive resistance training twice a week for 12 weeks. 6 RE and 7 CON completed the study. In RE the following improved (P<0.05): Quadriceps CSA: 4%, isometric knee extension strength: 14%, isokinetic knee extension strength at 60°/s.: 18%, leg extension power: 19%, maximal gait speed: 14%, stair climbing time: 17%, isometric trunk flexion: 5% and self-reported health. In CON no changes were found.
In conclusion, 12 weeks of heavy resistance training twice a week resulted in significant improvements in muscle size, knee extension strength, leg extension power, functional performance and self-reported health in elderly male COPD patients.
Abstract only
Introduction
It remains unknown why tendons improve mechanical properties with loading. However, tendon cell nuclei (TCN) have been claimed to induce these mechanical adaptations, ...although this has not been previously investigated.
Purpose
To quantify the number of TCN in rat Achilles tendon after 12 wk of running.
Methods
8 adult male Sprague‐Dawley rats ran (RR) on a treadmill with 10° incline, 1 h/day, 5 days/wk (17–20 m/min) for 12 wk (which led to improved tendon mechanical properties) and were compared with 11 control rats (CR). Tissue‐Tek embedded serial sections (10 μm) from the mid region of the Achilles tendon were cut longitudinally on a cryostat. Sections were stained with PicroSirius Red and hematoxylin staining. One investigator counted the number of TCN 2–3 times in three separate parts of the mid longitudinal tendon section with fields of 390 μm ×280 μm in a blinded fashion. Unpaired t‐test was used for the statistical analysis (Mean±SE).
Results
Typical Error % for the three parts was 5.3%: There was no difference between running rats vs. control rats (TCN per image (≈ 10
5
μm): RR, 152±9; CR, 146±8, P=0.642).
Conclusion
This new method provided reproducible determination of tendon cell nuclei density. However, even though the tendon mechanical properties were improved, no difference in tendon cell nuclei density between running rats vs. control rats could be detected. Research support: Danish Association of Rheumatism.
•Deep learning algorithm for early detection of sepsis on multi-center Danish data.•Algorithm performance is superior to baseline machine learning models.•Improved decision analysis that accounts for ...early model performance.•Improves clinical utility by enabling earlier sepsis interventions.
The timeliness of detection of a sepsis incidence in progress is a crucial factor in the outcome for the patient. Machine learning models built from data in electronic health records can be used as an effective tool for improving this timeliness, but so far, the potential for clinical implementations has been largely limited to studies in intensive care units. This study will employ a richer data set that will expand the applicability of these models beyond intensive care units. Furthermore, we will circumvent several important limitations that have been found in the literature: (1) Model evaluations neglect the clinical consequences of a decision to start, or not start, an intervention for sepsis. (2) Models are evaluated shortly before sepsis onset without considering interventions already initiated. (3) Machine learning models are built on a restricted set of clinical parameters, which are not necessarily measured in all departments. (4) Model performance is limited by current knowledge of sepsis, as feature interactions and time dependencies are hard-coded into the model.
In this study, we present a model to overcome these shortcomings using a deep learning approach on a diverse multicenter data set. We used retrospective data from multiple Danish hospitals over a seven-year period. Our sepsis detection system is constructed as a combination of a convolutional neural network and a long short-term memory network. We assess model quality by standard concepts of accuracy as well as clinical usefulness, and we suggest a retrospective assessment of interventions by looking at intravenous antibiotics and blood cultures preceding the prediction time.
Results show performance ranging from AUROC 0.856 (3 h before sepsis onset) to AUROC 0.756 (24 h before sepsis onset). Evaluating the clinical utility of the model, we find that a large proportion of septic patients did not receive antibiotic treatment or blood culture at the time of the sepsis prediction, and the model could, therefore, facilitate such interventions at an earlier point in time.
We present a deep learning system for early detection of sepsis that can learn characteristics of the key factors and interactions from the raw event sequence data itself, without relying on a labor-intensive feature extraction work. Our system outperforms baseline models, such as gradient boosting, which rely on specific data elements and therefore suffer from many missing values in our dataset.
The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events ...following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector-based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested.
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