A protocol for physiological mechanical testing of cortical bone using digital volume correlation

As we age, an imbalance and uncoupling in the remodeling process deteriorates the intracortical network and subsequently weakens our bones. Impaired mechanical strength, structural degradation, and deficient material composition point to a loss of bone quality that leads to osteoporosis. As bone quality and strength decrease, patients become at high risk for osteoporotic fractures during a fall or other atypical loading conditions. Among these fractures, femoral neck fractures (or cervical hip fractures) lead to high mortality rates and societal costs. Dual-energy x-ray absorptiometry (DEXA) is the current gold standard for measuring apparent bone mineral density for diagnosing osteoporosis, but it continues to be an imperfect predictor of osteoporotic fracture risk. Thus, high resolution imaging techniques paired with mechanical testing and simulations are needed to better understand how the cortical pore network distributes load and which microstructural properties are the best indicators of fracture risk. Additionally, exercise is known to improve overall bone health, but targeted exercise interventions in the femoral neck have been less successful. The overall objectives of this thesis were twofold. First, we aimed to quantify the physiological level of strain in the proximal femur during regular activity and characterize the resulting mechanical environment. Second, we aimed to perform a digital volume correlation (DVC) error analysis on cortical bone and perform mechanical testing to develop a protocol for loading bone and measuring local strains using DVC. To investigate the normal level of strain in the femoral neck, we used 3D subject-specific finite element (FE) models to compare principal strains and their orientations for three loading configurations: [1] hip joint force, gluteus medius, gluteus maximus, gluteus minimus, vasti, iliopsoas, and several other smaller hip spanning muscles, [2] hip joint, gluteus medius, gluteus minimus, and the iliopsoas, and [3] hip joint force only. The principal strains and their orientations were compared in four quadrants of 8 regions during walking. Our findings indicate that including muscle forces result in more physiologically accurate FE models, and they support the hypothesis that FE models used to calculate femoral neck strains during walking should not neglect the contribution of muscle forces. These results help establish a baseline for the normal level of strain in the femoral neck which will help create new exercise interventions that cause bone adaptation and subsequent strengthening of the femoral neck. For the DVC analysis, a pair of consecutive micro-CT scans was acquired of specimens from the superior neck, inferior neck and middle diaphysis with no motion between the scans. The effect of three DVC input parameters on strain error was assessed via a Design of Experiments (DOE). Although the femoral neck specimens had large in-plane strain errors, the ezz component was 1,330 microstrain, which indicates that uniaxial compression/tension testing of these specimens via DVC is feasible. Loaded DVC of femoral neck specimen may help elucidate the relationship between intracortical pore morphology and local strain, which may one day lead to new insights into (re)modelling mechanisms and femoral neck fragility

Injury prevention strategies at the FIFA 2014 World Cup: perceptions and practices of the physicians from the 32 participating national teams

Purpose The available scientific research regarding injury prevention practices in international football is sparse. The purpose of this study was to quantify current practice with regard to (1) injury prevention of top-level footballers competing in an international tournament, and (2) determine the main challenges and issues faced by practitioners in these national teams. Methods A survey was administered to physicians of the 32 competing national teams at the FIFA 2014 World Cup. The survey included 4 sections regarding perceptions and practices concerning non-contact injuries: (1) risk factors, (2) screening tests and monitoring tools, (3) preventative strategies and (4) reflection on their experience at the World Cup. Results Following responses from all teams (100%), the present study revealed the most important intrinsic (previous injury, accumulated fatigue, agonist:antagonist muscle imbalance) and extrinsic (reduced recovery time, training load prior to and during World Cup, congested fixtures) risk factors during the FIFA 2014 World Cup. The 5 most commonly used tests for risk factors were: flexibility, fitness, joint mobility, balance and strength; monitoring tools commonly used were: medical screen, minutes/matches played, subjective and objective wellness, heart rate and biochemical markers. The 5 most important preventative exercises were: flexibility, core, combined contractions, balance and eccentric. Conclusions The present study showed that many of the National football (soccer) teams’ injury prevention perceptions and practices follow a coherent approach. There remains, however, a lack of consistent research findings to support some of these perceptions and practices

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Background and Hypothesis: The acquired von Willebrand syndrome (AvWS), which predisposes to bleeding events, is often related to valvular heart diseases. We investigated possible implications of AvWS and factor VIII levels in patients with moderate to severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). Methods and Results: 123 patients with moderate to severe MR were prospectively enrolled. Complete measurements of von Willebrand Factor activity (vWFAct), von Willebrand Factor antigen (vWFAg), and factor VIII expression before and 4 weeks after TMVR were available in 85 patients. At baseline, seven patients had a history of gastrointestinal bleeding, two patients suffered bleeding events during their hospital stay, and one patient had a bleeding 4 weeks after TMVR. Even though vWFAct, vWFAct/vWFAg ratio and vWFAg values did not change after TMVR, we observed a significantly lower vWFAct/vWFAg ratio in patients with primary MR as compared to patients with secondary MR both at baseline (p = 0.022) and 4 weeks following the TMVR procedure (p = 0.003). Additionally, patients with a mean mitral valve gradient ≥4 mmHg after TMVR had significantly lower vWFAct/vWFAg ratios as compared to patients with a mean mitral valve gradient <4 mmHg (p = 0.001). Conclusions: MR of primary etiology was associated with lower vWFAct/vWFAg ratio, hinting toward HMWM loss due to shear stress caused by eccentric regurgitation jets. In addition, morphological changes leading to postprocedural transmitral gradients ≥4 mmHg were related to lower vWFAct/vWFAg ratio 4 weeks after the procedure. Alterations of the vWFAct/vWFAg ratio in turn did not translate into a greater risk for bleeding events

Fostering Program Comprehension in Novice Programmers - Learning Activities and Learning Trajectories

This working group asserts that Program Comprehension (ProgComp) plays a critical part in the process of writing programs. For example, this paper is written from a basic draft that was edited and revised until it clearly presented our idea. Similarly, a program is written incrementally, with each step tested, debugged and extended until the program achieves its goal. Novice programmers should develop program comprehension skills as they learn to code so that they are able both to read and reason about code created by others, and to reflect on their code when writing, debugging or extending it. To foster such competencies our group identified two main goals: (g1) to collect and define learning activities that explicitly address key components of program comprehension and (g2) to define tentative theoretical learning trajectories that will guide teachers as they select and sequence those learning activities in their CS0/CS1/CS2 or K-12 courses. The WG has completed the first goal and laid down a strong foundation towards the second goal as presented in this report. After a thorough literature review, a detailed description of the Block Model is provided, as this model has been used with a dual purpose, to classify and present an extensive list of ProgComp tasks, and to describe a possible learning trajectory for a complex task, covering different cells of the Block Model matrix. The latter is intended to help instructors to decompose complex tasks and identify which aspects of ProgComp are being fostered

Fluorescent mannosides serve as acceptor substrates for glycosyltransferase and sugar-1-phosphate transferase activities in <i>Euglena gracilis</i> membranes

Synthetic hexynyl α-D-mannopyranoside and its α-1,6-linked disaccharide counterpart were fluorescently labelled through CuAAC click chemistry with 3-azido-7-hydroxycoumarin. The resulting triazolyl-coumarin adducts, which were amenable to analysis by TLC, HPLC and mass spectrometry, proved to be acceptor substrates for α-1,6-ManT activities in mycobacterial membranes, as well as α- and β-GalT activities in trypanosomal membranes, benchmarking the potential of the fluorescent acceptor approach against earlier radiochemical assays. Following on to explore the glycobiology of the benign protozoan alga Euglena gracilis, α-1,3- and α-1,2-ManT activities were detected in membrane preparations, along with GlcT, Glc-P-T and GlcNAc-P-T activities. These studies serve to demonstrate the potential of readily accessible fluorescent glycans as substrates for exploring carbohydrate active enzymes

Valgus and varus deformity after wide-local excision, brachytherapy and external beam irradiation in two children with lower extremity synovial cell sarcoma: case report

BACKGROUND: Limb-salvage is a primary objective in the management of extremity soft-tissue sarcoma in adults and children. Wide-local excision combined with radiation therapy is effective in achieving local tumor control with acceptable morbidity and good functional outcomes for most patients. CASE PRESENTATION: Two cases of deformity after wide-local excision, brachytherapy and external beam irradiation for lower-extremity synovial cell sarcoma are presented and discussed to highlight contributing factors, time course of radiation effects and orthopedic management. In an effort to spare normal tissues from the long-term effects of radiation therapy, more focal irradiation techniques have been applied to patients with musculoskeletal tumors including brachytherapy and conformal radiation therapy. As illustrated in this report, the use of these techniques results in the asymmetric irradiation of growth plates and contributes to the development of valgus or varus deformity and leg-length discrepancies. CONCLUSIONS: Despite good functional outcomes, progressive deformity in both patients required epiphysiodesis more than 3 years after initial management. There is a dearth of information related to the effects of radiation therapy on the musculoskeletal system in children. Because limb-sparing approaches are to be highlighted in the next generation of cooperative group protocols for children with musculoskeletal tumors, documentation of the effects of surgery and radiation therapy will lead to improved decision making in the selection of the best treatment approach and in the follow-up of these patients

A Widespread Distribution of Genomic CeMyoD Binding Sites Revealed and Cross Validated by ChIP-Chip and ChIP-Seq Techniques

Identifying transcription factor binding sites genome-wide using chromatin immunoprecipitation (ChIP)-based technology is becoming an increasingly important tool in addressing developmental questions. However, technical problems associated with factor abundance and suitable ChIP reagents are common obstacles to these studies in many biological systems. We have used two completely different, widely applicable methods to determine by ChIP the genome-wide binding sites of the master myogenic regulatory transcription factor HLH-1 (CeMyoD) in C. elegans embryos. The two approaches, ChIP-seq and ChIP-chip, yield strongly overlapping results revealing that HLH-1 preferentially binds to promoter regions of genes enriched for E-box sequences (CANNTG), known binding sites for this well-studied class of transcription factors. HLH-1 binding sites were enriched upstream of genes known to be expressed in muscle, consistent with its role as a direct transcriptional regulator. HLH-1 binding was also detected at numerous sites unassociated with muscle gene expression, as has been previously described for its mouse homolog MyoD. These binding sites may reflect several additional functions for HLH-1, including its interactions with one or more co-factors to activate (or repress) gene expression or a role in chromatin organization distinct from direct transcriptional regulation of target genes. Our results also provide a comparison of ChIP methodologies that can overcome limitations commonly encountered in these types of studies while highlighting the complications of assigning in vivo functions to identified target sites

Motor, cognitive and mobility deficits in 1000 geriatric patients : protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study

© The Author(s). 2020 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.info:eu-repo/semantics/publishedVersio