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1.
Rheumatol Int ; 44(10): 1909-1921, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39192022

RESUMO

Myositis is associated with reduced quality of life, which is accompanied by significant impairments in muscle endurance and strength, altogether representing cardinal traits in patients with myositis. This randomised controlled trial aimed to investigate the effect of high-intensity resistance training on quality of life in patients with myositis. Thirty-two patients with established, stable myositis were randomised to 16 weeks of high-intensity resistance training (intervention group) or 16 weeks of usual care (control group). Primary outcome was quality of life assessed as the change in the physical component summary score (PCS) of the Short Form-36 health questionnaire from baseline to post-intervention. Secondary outcomes included functional capacity measures, such as functional index 3, and International Myositis Assessment and Clinical Studies Group (IMACS) disease activity and damage core set measures, including manual muscle testing 8 (MMT8). The primary outcome PCS showed an improvement in favour of high-intensity resistance training with a between-group difference of 5.33 (95% CI 0.61; 10.05) (p = 0.03). Additionally, functional index 3 showed a between-group difference indicating greater gains with high-intensity resistance training 11.49 (95% CI 3.37; 19.60) (p = 0.04), along with a between-group improvement in MMT8 1.30 (95% CI 0.09; 2.51) (p = 0.04). High-intensity resistance training for 16 weeks effectively improved quality of life in patients with myositis. Clinical measures of muscle endurance and muscle strength were also found to improve with high-intensity resistance training, while patients stayed in disease remission. Consequently, progressively adjusted high-intensity resistance training is feasible and causes no aggravation of the disease, while benefitting patients with myositis.Clinical trial registration: Clinicaltrials.gov ID: NCT04486261- https://clinicaltrials.gov/study/NCT04486261 .


Assuntos
Força Muscular , Miosite , Resistência Física , Qualidade de Vida , Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Masculino , Feminino , Miosite/reabilitação , Miosite/fisiopatologia , Miosite/terapia , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Idoso , Músculo Esquelético/fisiopatologia
2.
Rheumatol Int ; 44(6): 1077-1087, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581449

RESUMO

Sporadic inclusion body myositis (sIBM) is a subgroup of idiopathic inflammatory myopathies characterised by progressive muscle weakness and skeletal muscle inflammation. Quantitative data on the myofibre morphology in sIBM remains scarce. Further, no previous study has examined fibre type association of satellite cells (SC), myonuclei number, macrophages, capillaries, and myonuclear domain (MD) in sIBM patients. Muscle biopsies from sIBM patients (n = 18) obtained previously (NCT02317094) were included in the analysis for fibre type-specific myofibre cross-sectional area (mCSA), SCs, myonuclei and macrophages, myonuclear domain, and capillarisation. mCSA (p < 0.001), peripheral myonuclei (p < 0.001) and MD (p = 0.005) were higher in association with type 1 (slow-twitch) than type 2 (fast-twitch) fibres. Conversely, quiescent SCs (p < 0.001), centrally placed myonuclei (p = 0.03), M1 macrophages (p < 0.002), M2 macrophages (p = 0.013) and capillaries (p < 0.001) were higher at type 2 fibres compared to type 1 fibres. In contrast, proliferating (Pax7+/Ki67+) SCs (p = 0.68) were similarly associated with each fibre type. Type 2 myofibres of late-phase sIBM patients showed marked signs of muscle atrophy (i.e. reduced mCSA) accompanied by higher numbers of associated quiescent SCs, centrally placed myonuclei, macrophages and capillaries compared to type 1 fibres. In contrast, type 1 fibres were suffering from pathological enlargement with larger MDs as well as fewer nuclei and capillaries per area when compared with type 2 fibres. More research is needed to examine to which extent different therapeutic interventions including targeted exercise might alleviate these fibre type-specific characteristics and countermeasure their consequences in impaired functional performance.


Assuntos
Miosite de Corpos de Inclusão , Regeneração , Humanos , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Macrófagos/patologia , Inflamação/patologia , Biomarcadores/análise , Músculo Esquelético/patologia , Células Satélites de Músculo Esquelético/patologia , Biópsia , Fibras Musculares de Contração Lenta/patologia , Fibras Musculares de Contração Rápida/patologia
3.
Nature ; 547(7662): 191-195, 2017 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-28703182

RESUMO

Quantum mechanics dictates that a continuous measurement of the position of an object imposes a random quantum back-action (QBA) perturbation on its momentum. This randomness translates with time into position uncertainty, thus leading to the well known uncertainty on the measurement of motion. As a consequence of this randomness, and in accordance with the Heisenberg uncertainty principle, the QBA puts a limitation-the so-called standard quantum limit-on the precision of sensing of position, velocity and acceleration. Here we show that QBA on a macroscopic mechanical oscillator can be evaded if the measurement of motion is conducted in the reference frame of an atomic spin oscillator. The collective quantum measurement on this hybrid system of two distant and disparate oscillators is performed with light. The mechanical oscillator is a vibrational 'drum' mode of a millimetre-sized dielectric membrane, and the spin oscillator is an atomic ensemble in a magnetic field. The spin oriented along the field corresponds to an energetically inverted spin population and realizes a negative-effective-mass oscillator, while the opposite orientation corresponds to an oscillator with positive effective mass. The QBA is suppressed by -1.8 decibels in the negative-mass setting and enhanced by 2.4 decibels in the positive-mass case. This hybrid quantum system paves the way to entanglement generation and distant quantum communication between mechanical and spin systems and to sensing of force, motion and gravity beyond the standard quantum limit.

4.
J Environ Manage ; 325(Pt A): 116267, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36419278

RESUMO

Prolonged waterlogging in agricultural fields has severe consequences for the crop development and growth, and could potentially lead to higher N losses. In this study, a 3.93 ha agricultural field in Denmark was separated into two parts of well-drained (WD) and poorly-drained (PD) based on the installation depth of the tile drains. The field was continuously monitored for drainage, soil water dynamics, nitrogen leaching through the drains, and grain dry matter and nitrogen yields in a 4-year period (2017-2020). Furthermore, denitrification potential of the top 1 m of the soil at both parts of the field was measured through the denitrifying enzyme activity assay, and a 1D Daisy model was utilized to capture the differences between water and nitrogen balances at WD and PD. Results indicated that on average over the 4 years, annual harvested nitrogen in the crops at PD was 14% lower compared to WD, with a significant reduction of 33% in 2017-2018, that coincided with the longest period of waterlogging at PD. Moreover, greater losses of nitrogen through leaching from drainage and other pathways were measured at the PD (109 kg N ha-1 ya-1) compared to the WD (95 kg N ha-1 ya-1). Based on the simulations, losses through preferential flow pathways to the drains dominated at PD and most of the denitrification is expected to occur within the topsoil. Future studies could significantly benefit from monitoring the redox dynamics in the top 30 cm of the PD soils, and increasing the depth of tiles drains by redrainage could reduce the N losses of poorly drained agricultural soils.


Assuntos
Areia , Solo , Nitrogênio , Agricultura , Água
5.
Scand J Med Sci Sports ; 32(2): 359-371, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34637559

RESUMO

Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory muscle disease associated with skeletal muscle inflammation and a parallel progressive decline in muscle strength and physical function. Eventually, most sIBM patients require use of wheelchair after about 10 years of diagnosis and assistance to perform activities of daily living. This study presents data from a randomized controlled intervention trial (NCT02317094) that examined the effect of 12 weeks low-load blood-flow restricted (BFR) resistance training on maximal muscle strength, power, rate of force development (RFD), thigh lean mass (TLM), and voluntary muscle activation (VA) in sIBM patients. A time-by-group interaction in knee extensor strength was observed in the stronger leg (p ≤ 0.033) but not the weaker leg. Within-group changes were observed with BFR training (BFR) manifested by increased knee extensor strength in the strongest leg (+13.7%, p = 0.049), whereas non-exercising patients (CON) showed reduced knee extensor strength (-7.7%, p = 0.018). Maximal leg extensor power obtained for the stronger leg remained unchanged following BFR training (+9.5%, p = 0.37) while decreasing in CON (-11.1%, p = 0.05). No changes in TLM were observed. VA declined post-training (p = 0.037) in both BFR (-6.3% points) and CON (-7.5% points). The present data indicate that BFR resistance training can attenuate the rate of decline in mechanical muscle function typically experienced by sIBM patients. The preservation of muscle mass and mechanical muscle function with BFR resistance training may be considered of high clinical importance in sIBM patients to countermeasure the disease-related decline in physical function.


Assuntos
Miosite de Corpos de Inclusão , Treinamento Resistido , Atividades Cotidianas , Humanos , Força Muscular , Músculo Esquelético , Fluxo Sanguíneo Regional , Coxa da Perna
6.
J Med Internet Res ; 24(10): e36671, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36251349

RESUMO

BACKGROUND: Listening programs enable hearing aid (HA) users to change device settings for specific listening situations and thereby personalize their listening experience. However, investigations into real-world use of such listening programs to support clinical decisions and evaluate the success of HA treatment are lacking. OBJECTIVE: We aimed to investigate the provision of listening programs among a large group of in-market HA users and the context in which the programs are typically used. METHODS: First, we analyzed how many and which programs were provided to 32,336 in-market HA users. Second, we explored 332,271 program selections from 1312 selected users to investigate the sound environments in which specific programs were used and whether such environments reflect the listening intent conveyed by the name of the used program. Our analysis was based on real-world longitudinal data logged by smartphone-connected HAs. RESULTS: In our sample, 57.71% (18,663/32,336) of the HA users had programs for specific listening situations, which is a higher proportion than previously reported, most likely because of the inclusion criteria. On the basis of association rule mining, we identified a primary additional listening program, Speech in Noise, which is frequent among users and often provided when other additional programs are also provided. We also identified 2 secondary additional programs (Comfort and Music), which are frequent among users who get ≥3 programs and usually provided in combination with Speech in Noise. In addition, 2 programs (TV and Remote Mic) were related to the use of external accessories and not found to be associated with other programs. On average, users selected Speech in Noise, Comfort, and Music in louder, noisier, and less-modulated (all P<.01) environments compared with the environment in which they selected the default program, General. The difference from the sound environment in which they selected General was significantly larger in the minutes following program selection than in the minutes preceding it. CONCLUSIONS: This study provides a deeper insight into the provision of listening programs on a large scale and demonstrates that additional listening programs are used as intended and according to the sound environment conveyed by the program name.


Assuntos
Auxiliares de Audição , Música , Percepção da Fala , Humanos , Ruído , Smartphone
7.
Sensors (Basel) ; 22(16)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36015695

RESUMO

Eddy currents induced in electrically conductive objects can be used to locate metallic objects as well as to assess the properties of materials non-destructively without physical contact. This technique is useful for material identification, such as measuring conductivity and for discriminating whether a sample is magnetic or non-magnetic. In this study, we carried out experiments and numerical simulations for the evaluation of conductive objects. We investigated the frequency dependence of the secondary magnetic field generated by induced eddy currents when a conductive object is placed in a primary oscillating magnetic field. According to electromagnetic theory, conductive objects have different responses at different frequencies. Using a table-top setup consisting of a fluxgate magnetometer and a primary coil generating a magnetic field with frequency up to 1 kHz, we were able to detect aluminium and steel cylinders using the principle of electromagnetic induction. The experimental results were compared to numerical simulations, with good overall agreement. This technique enables the identification and characterisation of objects using their electrical conductivity and magnetic permeability.

8.
Proteomics ; 19(14): e1900028, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31168896

RESUMO

Adaptation to the environment during development influences the life-long survival of an animal. While brain-wide proteomic changes are expected to underlie such experience-driven physiological and behavioral flexibility, a comprehensive overview of the nature and extent of the proteomic regulation following an environmental challenge during development is currently lacking. In this study, the brain proteome of larval zebrafish is identified and it is determined how it is altered by an exposure to a natural and physical environmental challenge, namely prolonged exposure to strong water currents. A comprehensive larval zebrafish brain proteome is presented here. Furthermore, 57 proteins that are regulated by the exposure to an environmental challenge are identified, which cover multiple functions including neuronal plasticity, the stress response, axonal growth and guidance, spatial learning, and energy metabolism. These represent candidate proteins that may play crucial roles for the adaption to an environmental challenge during development.


Assuntos
Encéfalo/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Animais , Larva , Peixe-Zebra
9.
RNA Biol ; 14(1): 20-28, 2017 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-27801616

RESUMO

The neuronal transcriptome changes dynamically to adapt to stimuli from the extracellular and intracellular environment. In this study, we adapted for the first time a click chemistry technique to label the newly synthesized RNA in cultured hippocampal neurons and intact larval zebrafish brain. Ethynyl uridine (EU) was incorporated into neuronal RNA in a time- and concentration-dependent manner. Newly synthesized RNA granules observed throughout the dendrites were colocalized with mRNA and rRNA markers. In zebrafish larvae, the application of EU to the swim water resulted in uptake and labeling throughout the brain. Using a GABA receptor antagonist, PTZ (pentylenetetrazol), to elevate neuronal activity, we demonstrate that newly transcribed RNA signal increased in specific regions involved in neurogenesis.


Assuntos
Química Click , Imagem Molecular/métodos , Neurônios/metabolismo , RNA/genética , RNA/metabolismo , Animais , Encéfalo/metabolismo , Genes de RNAr , Proteínas de Ligação a Poli(A)/metabolismo , Células Piramidais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peixe-Zebra
10.
Nucleic Acids Res ; 43(Database issue): D940-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25106869

RESUMO

There is rising evidence of an inverse association between chronic diseases and diets characterized by rich fruit and vegetable consumption. Dietary components may act directly or indirectly on the human genome and modulate multiple processes involved in disease risk and disease progression. However, there is currently no exhaustive resource on the health benefits associated to specific dietary interventions, or a resource covering the broad molecular content of food. Here we present the first release of NutriChem, available at http://cbs.dtu.dk/services/NutriChem-1.0, a database generated by text mining of 21 million MEDLINE abstracts for information that links plant-based foods with their small molecule components and human disease phenotypes. NutriChem contains text-mined data for 18478 pairs of 1772 plant-based foods and 7898 phytochemicals, and 6242 pairs of 1066 plant-based foods and 751 diseases. In addition, it includes predicted associations for 548 phytochemicals and 252 diseases. To the best of our knowledge this database is the only resource linking the chemical space of plant-based foods with human disease phenotypes and provides a foundation for understanding mechanistically the consequences of eating behaviors on health.


Assuntos
Bases de Dados Factuais , Dieta , Plantas Comestíveis , Doença , Humanos , Internet , Fenótipo , Compostos Fitoquímicos , Medicina Preventiva
11.
PLoS Comput Biol ; 11(2): e1004048, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25668218

RESUMO

Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.


Assuntos
Biologia Computacional/métodos , Interações Alimento-Droga , Modelos Moleculares , Compostos Fitoquímicos , Animais , Bases de Dados Factuais , Dieta , Doença , Perfilação da Expressão Gênica , Humanos , Camundongos
12.
PLoS Comput Biol ; 10(1): e1003432, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24453957

RESUMO

Awareness that disease susceptibility is not only dependent on genetic make up, but can be affected by lifestyle decisions, has brought more attention to the role of diet. However, food is often treated as a black box, or the focus is limited to few, well-studied compounds, such as polyphenols, lipids and nutrients. In this work, we applied text mining and Naïve Bayes classification to assemble the knowledge space of food-phytochemical and food-disease associations, where we distinguish between disease prevention/amelioration and disease progression. We subsequently searched for frequently occurring phytochemical-disease pairs and we identified 20,654 phytochemicals from 16,102 plants associated to 1,592 human disease phenotypes. We selected colon cancer as a case study and analyzed our results in three directions; i) one stop legacy knowledge-shop for the effect of food on disease, ii) discovery of novel bioactive compounds with drug-like properties, and iii) discovery of novel health benefits from foods. This works represents a systematized approach to the association of food with health effect, and provides the phytochemical layer of information for nutritional systems biology research.


Assuntos
Mineração de Dados/métodos , Suscetibilidade a Doenças , Informática Médica/métodos , Algoritmos , Teorema de Bayes , Neoplasias do Colo/terapia , Progressão da Doença , Alimentos , Humanos , Estilo de Vida , Lipídeos/química , Ciências da Nutrição , Fenótipo , Compostos Fitoquímicos/uso terapêutico , Plantas/química , Software , Biologia de Sistemas
13.
BMC Genomics ; 15: 380, 2014 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-24886433

RESUMO

BACKGROUND: Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets -fruits, vegetables and herbs- are known as a source of molecules with pharmacological properties for treatment of several malignancies. Unquestionably, for developing specific intervention strategies to reduce cancer risk there is a need for a more extensive and holistic examination of the dietary components for exploring the mechanisms of action and understanding the nutrient-nutrient interactions. Here, we used colon cancer as a proof-of-concept for understanding key regulatory sites of diet on the disease pathway. RESULTS: We started from a unique vantage point by having a database of 158 plants positively associated to colon cancer reduction and their molecular composition (~3,500 unique compounds). We generated a comprehensive picture of the interaction profile of these edible and non-edible plants with a predefined candidate colon cancer target space consisting of ~1,900 proteins. This knowledge allowed us to study systematically the key components in colon cancer that are targeted synergistically by phytochemicals and identify statistically significant and highly correlated protein networks that could be perturbed by dietary habits. CONCLUSION: We propose here a framework for interrogating the critical targets in colon cancer processes and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. Our methodology for better delineating prevention of colon cancer by nutritional interventions relies heavily on the availability of information about the small molecule constituents of our diet and it can be expanded to any other disease class that previous evidence has linked to lifestyle.


Assuntos
Neoplasias do Colo/prevenção & controle , Dieta , Neoplasias do Colo/metabolismo , Humanos , Compostos Fitoquímicos/administração & dosagem
14.
J Nanosci Nanotechnol ; 14(2): 1859-71, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24749461

RESUMO

The condensation of water is a phenomenon occurring in multiple situations in everyday life, e.g., when fog is formed or when dew forms on the grass or on windows. This means that this phenomenon plays an important role within the different fields of science including meteorology, building physics, and chemistry. In this review we address condensation models and simulations with the main focus on heterogeneous condensation of water. The condensation process is, at first, described from a thermodynamic viewpoint where the nucleation step is described by the classical nucleation theory. Further, we address the shortcomings of the thermodynamic theory in describing the nucleation and emphasize the importance of nanoscale effects. This leads to the description of condensation from a molecular viewpoint. Also presented is how the nucleation can be simulated by use of molecular models, and how the condensation process is simulated on the macroscale using computational fluid dynamics. Finally, examples of hybrid models combining molecular and macroscale models for the simulation of condensation on a surface are presented.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos , Modelos Moleculares , Propriedades de Superfície , Água/química , Simulação por Computador
15.
Int J Rheum Dis ; 27(3): e15132, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38509721

RESUMO

OBJECTIVE: To investigate the potential associations between functional capacity, muscle strength, body composition, and disease-related measures and quality of life in patients with myositis. METHODS: Baseline measures of functional capacity (functional index 3 (FI3), 2-minute walk test (2MWT), timed up and go (TUG) and 30-s sit-to-stand (30-STS)), muscle strength (incl. leg and handgrip strength), maximal leg extensor power, body composition (appendicular lean mass, fat percentage/mass) and disease-related measures (disease activity & damage core sets) were examined for their associations with quality of life (physical- and mental component summary scores, Short Form 36 questionnaire (SF-36)) by means of Spearman's correlation analysis. RESULTS: A total of 32 patients with myositis were included. Positive correlations between SF-36 physical component summary score (PCS) and FI3, 30-STS, TUG, 2MWT, leg extensor power, leg strength, bench press strength, and handgrip strength were observed. In contrast, fat percentage and fat mass correlated negatively with PCS. In disease-related measures, Extramuscular global assessment, health assessment questionnaire, physician global damage, and patient global damage scores were negatively associated with SF-36 PCS. No correlations to the mental component summary score of SF-36 were observed. CONCLUSION: All measures of functional capacity were positively related to the SF-36 physical component summary score, indicating higher functional capacity positively affects quality of life in patients with myositis. Health assessment questionnaire and patient global damage scores demonstrated the strongest correlations with SF-36 physical component summary scores, further supporting these patient-reported outcomes as viable monitoring tools in patients with myositis.


Assuntos
Miosite , Qualidade de Vida , Humanos , Força da Mão , Força Muscular/fisiologia , Composição Corporal
16.
BMJ Open ; 14(9): e085667, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313282

RESUMO

INTRODUCTION: Patients with lumbar spinal stenosis may have poor balance, decreased physical function and problems maintaining physical activity levels due to radiculopathy. Decompressive surgery is often indicated if conservative management fails to achieve a satisfactory clinical outcome. While surgical management has proven effective at treating radiculopathy, and patients report increased physical function postoperatively, objective measures of postural control and physical activity remain sparse. This study aims to investigate the effects of decompressive surgery on postural control and activity levels of elderly patients with lumbar spinal stenosis using objective measurements. METHODS AND ANALYSIS: This is a 24-month, multicentre, prospective cohort study. Patients ≥65 years of age with MRI-verified symptomatic lumbar central canal stenosis will be recruited from two separate inclusion centres, and all participants will undergo decompressive surgery. Preoperative data are collected up to 3 months before surgery, with follow-up data collected at 3, 6, 12 and 24 months postoperatively. Postural control measurements are performed using the Wii Balance Board, mini Balance Evaluation Systems Test and Tandem test, and data concerning physical activity levels are collected using ActiGraph wGT3X-BT accelerometers. Patient-reported outcomes regarding quality-of-life and physical function are collected from the EuroQol-5D, 36-Item Short Form Health Survey and Zurich Claudication Questionnaire. Primary outcomes are the change in the sway area of centre of pressure and total activity counts per day from baseline to follow-up at 24 months. A sample size of 80 participants has been calculated. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethics Committee of Region Zealand (ID EMN-2022-08110) and the Danish Data Protection Agency (ID REG-100-2022). Written informed consent will be required from all participants before enrolment. All results from the study, whether positive, negative or inconclusive, will be published in international peer-reviewed journals and presented at national and international scientific meetings. Study findings will be further disseminated through national patient associations. TRIAL REGISTRATION NUMBERS: NCT06075862 and NCT06057428.

17.
J Thromb Haemost ; 21(6): 1493-1502, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37037699

RESUMO

BACKGROUND: Mim8 is a novel antifactor IXa/antifactor X bispecific antibody in clinical development for prophylactic treatment of hemophilia A with and without inhibitors. Patients treated with Mim8 may need supplementary bleed treatment under certain conditions such as surgery or major trauma. OBJECTIVES: This study aimed to better understand the response of Mim8 in thrombin generation assays (TGAs) alone or in combination with other hemostatic proteins. METHODS: We used TGAs with different activators (tissue factor (TF) and activated factor XI) to better understand the similarities and differences between the mode of action of Mim8 and factor VIII (FVIII). Following this, we investigated the effects of mixing Mim8 with the main bleed treatment options for persons with hemophilia A with or without inhibitors: FVIII, activated factor VII (FVIIa), and activated prothrombin complex concentrates (aPCC). RESULTS: The results indicated that for patients without inhibitors, Mim8 does not interfere with FVIII's mode of action. For patients with inhibitors, Mim8 mixed with aPCC results in a strong synergistic effect causing thrombin generation far exceeding the normal levels. Contrary to this, mixing Mim8 with FVIIa results in a more controlled additive effect, visible only when using TF as a trigger, which does not exceed the normal level of thrombin generation. CONCLUSION: These findings support the use of approved clinical doses of FVIIa for bleed treatment of patients with FVIII inhibitors treated with Mim8. Additionally, the findings suggest that concomitant use of FVIII and Mim8 is safe for managing breakthrough bleeds.


Assuntos
Hemofilia A , Hemostáticos , Humanos , Fator VIII , Trombina/metabolismo , Fator VIIa/metabolismo , Hemostáticos/uso terapêutico , Hemorragia/tratamento farmacológico , Fator IX/uso terapêutico , Tromboplastina/uso terapêutico , Proteínas Recombinantes/uso terapêutico
18.
Ann Epidemiol ; 87: 100-106, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37903678

RESUMO

PURPOSE: Self-reported information on medical conditions and medicine use is widely used in epidemiological research. We investigated the validity of self-reported medical conditions and medicine use from Danish participants in the Survey of Health, Ageing and Retirement in Europe. METHODS: Self-reported health data were linked at individual level with the National Patient Registry and the Danish National Prescription Registry (n = 5572). Agreement was assessed by kappa value and presented as sensitivity, specificity, predictive values, and odds ratios. RESULTS: The agreement of self-reported medical conditions varied by type (κ = 0.23-0.67), lowest for cholesterol-related diseases, highest for diabetes. Self-reported medicine use varied by medication type (κ = 0.33-0.90) lowest for painkillers, highest for diabetes. Women had lower odds for self-reporting medicine use correctly but higher odds for self-reported diseases. Higher age was associated with lower agreement, while higher education with higher agreement. CONCLUSIONS: Although Danish data from the Survey of Health, Ageing and Retirement in Europe on medical conditions and medicine vary, the data are valid for epidemiological use for most medicine data, and for diseases associated with hospitalizations or influencing everyday life. Caution is warranted for self-reported data from 70+ year olds and people with lower educational level.


Assuntos
Envelhecimento , Diabetes Mellitus , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Autorrelato , Inquéritos e Questionários , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Dinamarca/epidemiologia
19.
Int J Biometeorol ; 56(1): 129-36, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21312044

RESUMO

The aim of the current study was to apply multivariate mixed-effects modeling to analyze experimental data on the relation between air quality and the performance of office work. The method estimates in one step the effect of the exposure on a multi-dimensional response variable, and yields important information on the correlation between the different dimensions of the response variable, which in this study was composed of both subjective perceptions and a two-dimensional performance task outcome. Such correlation is typically not included in the output from univariate analysis methods. Data originated from three different series of experiments investigating the effects of air quality on performance. The example analyses resulted in a significant and positive correlation between two performance tasks, indicating that the two tasks to some extent measured the same dimension of mental performance. The analysis seems superior to conventional univariate statistics and the information provided may be important for the design of performance experiments in general and for the conclusions that can be based on such studies.


Assuntos
Poluição do Ar em Ambientes Fechados , Modelos Lineares , Análise e Desempenho de Tarefas , Ambiente Controlado , Feminino , Pisos e Cobertura de Pisos , Humanos , Análise Multivariada , Ventilação , Local de Trabalho
20.
Neuromuscul Disord ; 32(6): 493-502, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35595645

RESUMO

Sporadic inclusion body myositis (sIBM) is characterised by skeletal muscle inflammation, progressive muscle loss and weakness, which is largely refractory to immunosuppressive treatment. Low-load blood-flow restricted (BFR) training has been shown to evoke gains in myofibre cross sectional area (mCSA) in healthy adults. This could partially be due to the activation and integration of muscle satellite cells (SC) resulting in myonuclei addition. Consequently, this study investigated the effect of 12-weeks lower limb low-load BFR resistance training in sIBM patients on SC and myonuclei content, myofibre size and capillarization. Muscle biopsies from sIBM patients randomised to 12-weeks of low-load BFR resistance training (n = 11) or non-exercising controls (CON) (n = 9) were analysed for SC and myonuclei content, myofibre size and capillarization using three-colour immunofluorescence microscopy and computerised quantification procedures. No between-group differences (time-by-group interactions) or within-groups changes were observed for resident SCs (Pax7+/Six1+), proliferating SCs (Pax7+/ Ki67+), myonuclei (Six1+), type 1 mCSA or capillary number (CD31+). However, a time-by-group interaction for type 2 mCSA was observed (p = 0.04). Satellite cell content, myonuclei number, mCSA and capillary density remained unaffected following 12-weeks low-load BFR resistance training, indicating limited myogenic capacity and satellite cell plasticity in long-term sIBM patients.


Assuntos
Miosite de Corpos de Inclusão , Treinamento Resistido/métodos , Células Satélites de Músculo Esquelético , Adulto , Proliferação de Células , Exercício Físico/fisiologia , Proteínas de Homeodomínio/metabolismo , Humanos , Hipertrofia/patologia , Microscopia de Fluorescência , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/metabolismo , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/terapia , Células Satélites de Músculo Esquelético/fisiologia
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