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2.
Lab Chip ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656325

RESUMO

A microfluidic pump is presented that generates its pumping action via the EWOD (electrowetting-on-dielectric) effect. The flow is generated by the periodic movement of liquid-vapor interfaces in a large number (≈106) of microcavities resulting in a volume change of approx. 0.5 pl per cavity per pump stroke. The total flow resulting from all microcavities adds up to a few hundred nanolitres per cycle. Passive, topologically optimized, non-mechanical Tesla valves are used to rectify the flow. As a result, the micropump operates without any moving components. The dimensioning, fabrication, and characterization process of the micropump are described. Device fabrication is done using conventional manufacturing processes from microsystems technology, enabling cost-effective mass production on wafer-level without additional assembly steps like piezo chip-level bonding, etc. This allows for direct integration into wafer-based microfluidic or lab-on-a-chip applications. Furthermore, first measurement results obtained with prototypes of the micropump are presented. The voltage- and frequency-dependent pump performance is determined. The measurements show that a continuous flow rate larger than 0.2 ml min-1 can be achieved at a maximum pump pressure larger than 12 mbar.

3.
J Physiol ; 602(7): 1371-1384, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38482557

RESUMO

Previous in vitro and in situ studies have reported a shift in optimal muscle fibre length for force generation (L0) towards longer length at decreasing activation levels (also referred to as length-dependent activation), yet the relevance for in vivo human muscle contractions with a variable activation pattern remains largely unclear. By a combination of dynamometry, ultrasound and electromyography (EMG), we experimentally obtained muscle force-fascicle length curves of the human soleus at 100%, 60% and 30% EMGmax levels from 15 participants aiming to investigate activation-dependent shifts in L0 in vivo. The results showed a significant increase in L0 of 6.5 ± 6.0% from 100% to 60% EMGmax and of 9.1 ± 7.2% from 100% to 30% EMGmax (both P < 0.001), respectively, providing evidence of a moderate in vivo activation dependence of the soleus force-length relationship. Based on the experimental results, an approximation model of an activation-dependent force-length relationship was defined for each individual separately and for the collective data of all participants, both with sufficiently high accuracy (R2 of 0.899 ± 0.056 and R2 = 0.858). This individual approximation approach and the general approximation model outcome are freely accessible and may be used to integrate activation-dependent shifts in L0 in experimental and musculoskeletal modelling studies to improve muscle force predictions. KEY POINTS: The phenomenon of the activation-dependent shift in optimal muscle fibre length for force generation (length-dependent activation) is poorly understood for human muscle in vivo dynamic contractions. We experimentally observed a moderate shift in optimal fascicle length towards longer length at decreasing electromyographic activity levels for the human soleus muscle in vivo. Based on the experimental results, we developed a freely accessible approximation model that allows the consideration of activation-dependent shifts in optimal length in future experimental and musculoskeletal modelling studies to improve muscle force predictions.


Assuntos
Músculo Esquelético , Tendões , Humanos , Tendões/fisiologia , Fenômenos Biomecânicos , Músculo Esquelético/fisiologia , Contração Muscular/fisiologia , Eletromiografia
4.
Sci Rep ; 14(1): 6875, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519507

RESUMO

Human tendons adapt to mechanical loading, yet there is little information on the effect of the temporal coordination of loading and recovery or the dose-response relationship. For this reason, we assigned adult men to either a control or intervention group. In the intervention group, the two legs were randomly assigned to one of five high-intensity Achilles tendon (AT) loading protocols (i.e., 90% maximum voluntary contraction and approximately 4.5 to 6.5% tendon strain) that were systematically modified in terms of loading frequency (i.e., sessions per week) and overall loading volume (i.e., total time under loading). Before, at mid-term (8 weeks) and after completion of the 16 weeks intervention, AT mechanical properties were determined using a combination of inverse dynamics and ultrasonography. The cross-sectional area (CSA) and length of the free AT were measured using magnetic resonance imaging pre- and post-intervention. The data analysis with a linear mixed model showed significant increases in muscle strength, rest length-normalized AT stiffness, and CSA of the free AT in the intervention group (p < 0.05), yet with no marked differences between protocols. No systematic effects were found considering the temporal coordination of loading and overall loading volume. In all protocols, the major changes in normalized AT stiffness occurred within the first 8 weeks and were mostly due to material rather than morphological changes. Our findings suggest that-in the range of 2.5-5 sessions per week and 180-300 s total high strain loading-the temporal coordination of loading and recovery and overall loading volume is rather secondary for tendon adaptation.


Assuntos
Tendão do Calcâneo , Adulto , Humanos , Masculino , Tendão do Calcâneo/fisiologia , Fenômenos Biomecânicos , Contração Isométrica/fisiologia , Imageamento por Ressonância Magnética , Força Muscular , Ultrassonografia
5.
J Exp Biol ; 227(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506185

RESUMO

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed steps and the recovery steps. Sixty-three healthy older adults (71.2±5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (P<0.05). These modifications were observed for up to four recovery steps and were more pronounced (P<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may improve the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.


Assuntos
Marcha , Caminhada , Eletromiografia , Caminhada/fisiologia , Locomoção , Músculo Esquelético/fisiologia , Fenômenos Biomecânicos
6.
Scand J Med Sci Sports ; 34(1): e14555, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268075

RESUMO

An imbalanced adaptation of muscle strength and tendon stiffness in response to training may increase tendon strain (i.e., the mechanical demand on the tendon) and consequently tendon injury risk. This study investigated if personalized tendon loading inducing tendon strain within the effective range for adaptation (4.5%-6.5%) can reduce musculotendinous imbalances in male adolescent handball athletes (15-16 years). At four measurement time points during a competitive season, we assessed knee extensor muscle strength and patellar tendon mechanical properties using dynamometry and ultrasonography and estimated the tendon's structural integrity with a peak spatial frequency (PSF) analysis of proximal tendon ultrasound scans. A control group (n = 13) followed their usual training routine, an intervention group (n = 13) integrated tendon exercises into their training (3x/week for ~31 weeks) with a personalized intensity corresponding to an average of ~6.2% tendon strain. We found a significant time by group interaction (p < 0.005) for knee extensor muscle strength and normalized patellar tendon stiffness with significant increases over time only in the intervention group (p < 0.001). There were no group differences or time-dependent changes in patellar tendon strain during maximum voluntary contractions or PSF. At the individual level, the intervention group demonstrated lower fluctuations of maximum patellar tendon strain during the season (p = 0.005) and a descriptively lower frequency of athletes with high-level tendon strain (≥9%). The findings suggest that the personalized tendon loading program reduced muscle-tendon imbalances in male adolescent athletes, which may provide new opportunities for tendon injury prevention.


Assuntos
Ligamento Patelar , Traumatismos dos Tendões , Adolescente , Masculino , Humanos , Tendões , Músculo Esquelético/diagnóstico por imagem , Ligamento Patelar/diagnóstico por imagem , Atletas
7.
J Exp Biol ; 226(22)2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37901934

RESUMO

The soleus is the main muscle for propulsion during human running but its operating behavior across the spectrum of physiological running speeds is currently unknown. This study experimentally investigated the soleus muscle activation patterns and contractile conditions for force generation, power production and efficient work production (i.e. force-length potential, force-velocity potential, power-velocity potential and enthalpy efficiency) at seven running speeds (3.0 m s-1 to individual maximum). During submaximal running (3.0-6.0 m s-1), the soleus fascicles shortened close to optimal length and at a velocity close to the efficiency maximum, two contractile conditions for economical work production. At higher running speeds (7.0 m s-1 to maximum), the soleus muscle fascicles still operated near optimum length, yet the fascicle shortening velocity increased and shifted towards the optimum for mechanical power production with a simultaneous increase in muscle activation, providing evidence for three cumulative mechanisms to enhance mechanical power production. Using the experimentally determined force-length-velocity potentials and muscle activation as inputs in a Hill-type muscle model, a reduction in maximum soleus muscle force at speeds ≥7.0 m s-1 and a continuous increase in maximum mechanical power with speed were predicted. The reduction in soleus maximum force was associated with a reduced force-velocity potential. The increase in maximum power was explained by an enhancement of muscle activation and contractile conditions until 7.0 m s-1, but mainly by increased muscle activation at high to maximal running speed.


Assuntos
Músculo Esquelético , Corrida , Humanos , Fenômenos Biomecânicos/fisiologia , Músculo Esquelético/fisiologia , Corrida/fisiologia , Contração Muscular/fisiologia
8.
Scand J Med Sci Sports ; 33(12): 2561-2572, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37697699

RESUMO

Imbalances between muscle strength and tendon stiffness may cause high-level tendon strain during maximum effort muscle contractions and lead to tendon structural impairments and an increased risk for tendinopathy in adolescent athletes. However, it remains unclear whether the development of musculotendinous imbalances is influenced by sex. At four measurement time points during a competitive season, we measured quadriceps femoris muscle strength and patellar tendon mechanical properties in 15 female (14.3 ± 0.7 years) and 13 male (16.0 ± 0.6 years) elite handball players of similar maturity using dynamometry and ultrasonography. To estimate the tendon's structural integrity, the peak spatial frequency (PSF) of proximal tendon ultrasound scans was determined. Females demonstrated significantly lower muscle strength (p < 0.001) and patellar tendon stiffness (p < 0.001) than males with no significant changes over time (p > 0.05). Tendon strain during isometric maximum voluntary contractions and PSF neither differed between sexes nor changed significantly over time (p > 0.05). We found lower fluctuations in muscle strength (p < 0.001) in females during the season but no differences in the fluctuations of tendon strain, stiffness, and PSF (p > 0.05). Descriptively, there was a similar frequency (~40%) of athletes with high-level tendon strain (>9%) in both sexes. These findings suggest that the lower strength capacity of female athletes is paralleled by lower tendon stiffness. Thereby, muscle-tendon imbalances occur to a similar extent in both sexes leading to increased strain levels during the season, which indicates the need for specific tendon training.


Assuntos
Ligamento Patelar , Esportes , Tendinopatia , Humanos , Masculino , Adolescente , Feminino , Tendões/diagnóstico por imagem , Tendões/fisiologia , Ligamento Patelar/diagnóstico por imagem , Músculo Quadríceps/fisiologia , Atletas
9.
Sports Med Open ; 9(1): 83, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37673828

RESUMO

BACKGROUND: High tendon strain leads to sub-rupture fatigue damage and net-catabolic signaling upon repetitive loading. While high levels of tendon strain occur in adolescent athletes at risk for tendinopathy, a direct association has not yet been established. Therefore, in this prospective longitudinal study, we examined the hypothesis that adolescent athletes who develop patellar tendon pain have shown increased levels of strain in advance. METHODS: In 44 adolescent athletes (12-17 years old), patellar tendon mechanical properties were measured using ultrasonography and inverse dynamics at four time points during a season. Fourteen athletes developed clinically relevant tendon pain (SYM; i.e., reduction of the VISA-P score of at least 13 points), while 23 remained asymptomatic (ASYM; VISA-P score of > 87 points). Seven cases did not fall into one of these categories and were excluded. Tendon mechanical properties of SYM in the session before the development of symptoms were compared to a randomly selected session in ASYM. RESULTS: Tendon strain was significantly higher in SYM compared to ASYM (p = 0.03). The risk ratio for developing symptoms was 2.3-fold higher in athletes with tendon strain ≥9% (p = 0.026). While there was no clear evidence for systematic differences of the force applied to the tendon or tendon stiffness between SYM and ASYM (p > 0.05), subgroup analysis indicated that tendon force increased prior to the development of symptoms only in SYM (p = 0.034). DISCUSSIO: The study provides novel longitudinal evidence that high tendon strain could be an important risk factor for patellar tendinopathy in adolescent athletes. We suggest that inadequate adaptation of tendon stiffness to increases in muscle strength may occur if adolescent athletes are subject to mechanical loading which does not  provide effective tendon stimulation.

10.
R Soc Open Sci ; 10(8): 230007, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37650058

RESUMO

The objective of the study was to explore how biarticular mechanisms of the gastrocnemii muscles may provide an important energy source for power and work at the ankle joint with increasing running speed. Achilles tendon force was quantified as a proxy of the triceps surae muscle force and the contribution of the monoarticular soleus and the biarticular gastrocnemii to the mechanical power and work performed at the ankle joint was investigated in three running speeds (transition 2.0 m s-1, slow 2.5 m s-1, fast 3.5 m s-1). Although the contribution of the soleus was higher, biarticular mechanisms of the gastrocnemii accounted for a relevant part of the performed mechanical power and work at the ankle joint. There was an ankle-to-knee joint energy transfer in the first part of the stance phase and a knee-to-ankle joint energy transfer during push-off via the gastrocnemii muscles, which made up 16% of the total positive ankle joint work. The rate of knee-to-ankle joint energy transfer increased with speed, indicating a speed-related participation of biarticular mechanisms in running. This energy transfer via the gastrocnemii seems to occur with negligible energy absorption/production from the quadriceps vasti contractile elements and is rather an energy exchange between elastic structures.

11.
BMC Pulm Med ; 23(1): 227, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365532

RESUMO

BACKGROUND: Recent studies have shown that thoracic ultrasound (TUS) is not inferior to chest radiography (CR) in detecting pneumothorax (PTX). It is unclear if adopting TUS can reduce the number of CR in the daily clinical routine. This retrospective study investigates the utilization of post-interventional CR and TUS for PTX detection after the introduction of TUS as the method of choice in an interventional pulmonology unit. METHODS: All interventions with CR or TUS for ruling out PTX performed in the Pneumology Department of the University Hospital Halle (Germany) 2014 to 2020 were included. The documented TUS and CR performed before (period A) and after the introduction of TUS as the method of choice (period B), as well as the number of diagnosed and missed PTX were recorded. RESULTS: The study included 754 interventions (110 in period A and 644 in period B). The proportion of CR decreased from 98.2% (n = 108) to 25.8% (n = 166) (p < 0.001). During period B, a total of 29 (4.5%) PTX were diagnosed. Of these, 28 (96.6%) were detected on initial imaging (14 by CR, 14 by TUS ). One PTX (0.2%) was initially missed by TUS, none by CR. Confirmatory investigations were ordered more frequently after TUS (21 of 478, 4.4%) than after CR (3 of 166, 1.8%). CONCLUSION: The use of TUS in interventional pulmonology can effectively reduce the number of CR and thus save resources. However, CR may still be favored in specific circumstances or if pre-existing conditions limit sonographic findings.


Assuntos
Pneumotórax , Pneumologia , Humanos , Pneumotórax/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia , Alemanha , Radiografia Torácica
12.
Biology (Basel) ; 12(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37372156

RESUMO

Increasing walking speed is accompanied by an increase of the mechanical power and work performed at the ankle joint despite the decrease of the intrinsic muscle force potential of the soleus (Sol) and gastrocnemius medialis (GM) muscles. In the present study, we measured Achilles tendon (AT) elongation and, based on an experimentally determined AT force-elongation relationship, quantified AT force at four walking speeds (slow 0.7 m.s-1, preferred 1.4 m.s-1, transition 2.0 m.s-1, and maximum 2.6 ± 0.3 m.s-1). Further, we investigated the mechanical power and work of the AT force at the ankle joint and, separately, the mechanical power and work of the monoarticular Sol at the ankle joint and the biarticular gastrocnemii at the ankle and knee joints. We found a 21% decrease in maximum AT force at the two higher speeds compared to the preferred; however, the net work of the AT force at the ankle joint (ATF work) increased as a function of walking speed. An earlier plantar flexion accompanied by an increased electromyographic activity of the Sol and GM muscles and a knee-to-ankle joint energy transfer via the biarticular gastrocnemii increased the net ATF mechanical work by 1.7 and 2.4-fold in the transition and maximum walking speed, respectively. Our findings provide first-time evidence for a different mechanistic participation of the monoarticular Sol muscle (i.e., increased contractile net work carried out) and the biarticular gastrocnemii (i.e., increased contribution of biarticular mechanisms) to the speed-related increase of net ATF work.

13.
J Am Soc Mass Spectrom ; 34(4): 720-727, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36891615

RESUMO

Mass spectrometry imaging (MSI) is a surface analysis technique that produces chemical images and is commonly used for biological and biomedical research. Multimodal imaging combines multiple imaging modes in order to get a more comprehensive view of a sample. Multimodal MSI images are often acquired using multiple MSI instruments, which leads to issues regarding image registration and increases the chance of sample damage or degradation during sample transfer. These problems can be solved by using a single instrument that can image in multiple modes. In order to improve the efficiency of multimodal imaging and investigate complementary modes of MSI, we have modified a prototype Bruker timsTOF fleX by adding secondary ion mass spectrometry (SIMS) and secondary electron (SE) imaging capabilities while preserving the ability to perform matrix-assisted laser desorption/ionization (MALDI). We show multimodal images collected on this instrument that required only trivial registration and were acquired without sample transfer between imaging trials. Furthermore, we characterize the performance of SIMS, SE, and MALDI imaging and compare the performance of the modified instrument to a commercial timsTOF fleX.


Assuntos
Elétrons , Espectrometria de Massa de Íon Secundário , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massa de Íon Secundário/métodos
14.
J Clin Med ; 12(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36769750

RESUMO

BACKGROUND: As inter-limb asymmetries can be associated with higher injury risk, we aimed to investigate their role in Achilles tendinopathy patients. METHODS: In Achilles tendinopathy patients (n = 41), we assessed inter-limb asymmetries of mechanical, material, and morphological musculoskeletal properties and function and how those were affected by 12 weeks of exercise intervention (high-load protocol, n = 13; Alfredson protocol, n = 11). Moreover, we assessed whether asymmetry reductions correlated with improved Patient-Reported Outcomes (VISA-A score). RESULTS: At baseline, tendinopathic tendons demonstrated lower tendon force (p = 0.017), lower tendon stress (p < 0.0001), larger tendon cross-sectional area (CSA) (p < 0.001), and increased intratendinous (p = 0.042) and tendon overall (p = 0.021) vascularization. For the high-load group, PRE-to-POST asymmetry comparisons revealed an asymmetry increase for the counter-movement jump (CMJ) (p = 0.034) and PRE-to-POST VISA-A score improvements correlated with CSA asymmetry reductions (p = 0.024). Within the Alfredson group, PRE-to-POST VISA-A score improvements correlated with CMJ asymmetry reductions (p = 0.044) and tendon stiffness asymmetry increases (p = 0.037). POST-to-POST in-between group comparisons revealed lower asymmetry in the high-load group for tendon elongation (p = 0.021) and tendon strain (p = 0.026). CONCLUSIONS: The tendinopathic limb differs from the asymptomatic limb while therapeutic exercise interventions have little effect on asymmetries. Asymmetry reductions are not necessarily associated with tendon health improvements.

15.
Sports Med Open ; 8(1): 149, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36538166

RESUMO

BACKGROUND: Assuming that the mechanisms inducing adaptation in healthy tendons yield similar responses in tendinopathic tendons, we hypothesized that a high-loading exercise protocol that increases tendon stiffness and cross-sectional area in male healthy Achilles tendons may also induce comparable beneficial adaptations in male tendinopathic Achilles tendons in addition to improving pain and function. OBJECTIVES: We investigated the effectiveness of high-loading exercise in Achilles tendinopathy in terms of inducing mechanical (tendon stiffness, maximum strain), material (Young's modulus), morphological (tendon cross-sectional area (CSA)), maximum voluntary isometric plantar flexor strength (MVC) as well as clinical adaptations (Victorian Institute of Sports Assessment-Achilles (VISA-A) score and pain (numerical rating scale (NRS))) as the primary outcomes. As secondary outcomes, drop (DJ) and counter-movement jump (CMJ) height and intratendinous vascularity were assessed. METHODS: We conducted a controlled clinical trial with a 3-month intervention phase. Eligibility criteria were assessed by researchers and medical doctors. Inclusion criteria were male sex, aged between 20 and 55 years, chronic Achilles tendinopathy confirmed by a medical doctor via ultrasound-assisted assessment, and a severity level of less than 80 points on the VISA-A score. Thirty-nine patients were assigned by sequential allocation to one of three parallel arms: a high-loading intervention (training at ~ 90% of the MVC) (n = 15), eccentric exercise (according to the Alfredson protocol) as the standard therapy (n = 15) and passive therapy (n = 14). Parameters were assessed pre- and-post-intervention. Data analysis was blinded. RESULTS: Primary outcomes: Plantar flexor MVC, tendon stiffness, mean CSA and maximum tendon strain improved only in the high-loading intervention group by 7.2 ± 9.9% (p = 0.045), 20.1 ± 20.5% (p = 0.049), 8.98 ± 5.8% (p < 0.001) and -12.4 ± 10.3% (p = 0.001), respectively. Stiffness decreased in the passive therapy group (-7.7 ± 21.2%; p = 0.042). There was no change in Young's modulus in either group (p > 0.05). The VISA-A score increased in all groups on average by 19.8 ± 15.3 points (p < 0.001), while pain (NRS) dropped by -0.55 ± 0.9 points (p < 0.001). SECONDARY OUTCOMES: CMJ height decreased for all groups (-0.63 ± 4.07 cm; p = 0.005). There was no change in DJ height and vascularity (p > 0.05) in either group. CONCLUSION: Despite an overall clinical improvement, it was exclusively the high-loading intervention that induced significant mechanical and morphological adaptations of the plantar flexor muscle-tendon unit. This might contribute to protecting the tendon from strain-induced injury. Thus, we recommend the high-loading intervention as an effective (alternative) therapeutic protocol in Achilles tendinopathy rehabilitation management in males. CLINICAL TRIALS REGISTRATION NUMBER: NCT02732782.

16.
Front Oncol ; 12: 995744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387105

RESUMO

NUT carcinoma (NC) is a rare and extremely aggressive form of cancer, usually presenting with intrathoracic or neck manifestations in adolescents and young adults. With no established standard therapy regimen and a median overall survival of only 6.5 months, there is a huge need for innovative treatment options. As NC is genetically driven by a single aberrant fusion oncoprotein, it is generally characterized by a low tumor mutational burden, thus making it immunologically cold and insusceptible to conventional immunotherapy. Recently, we have demonstrated that oncolytic viruses (OVs) are able to specifically infect and lyse NC cells, thereby turning an immunologically cold tumor microenvironment into a hot one. Here, we report an intensive multimodal treatment approach employing for the first time an OV (talimogene laherparepvec (T-VEC); IMLYGIC®) together with the immune checkpoint inhibitor pembrolizumab as an add-on to a basic NC therapy (cytostatic chemotherapy, radiation therapy, epigenetic therapy) in a patient suffering from a large thoracic NC tumor which exhibits an aberrant, unique BRD3:NUTM1 fusion. This case demonstrates for the first time the feasibility of this innovative add-on immunovirotherapy regimen with a profound, repetitive and durable replication of T-VEC that is instrumental in achieving tumor stabilization and improvement in the patient´s quality of life. Further, a previously unknown BRD3:NUTM1 fusion gene was discovered that lacks the extraterminal domain of BRD3.

17.
Microsyst Nanoeng ; 8: 97, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36089943

RESUMO

A multistage optimization method is developed yielding Tesla valves that are efficient even at low flow rates, characteristic, e.g., for almost all microfluidic systems, where passive valves have intrinsic advantages over active ones. We report on optimized structures that show a diodicity of up to 1.8 already at flow rates of 20 µl s- 1 corresponding to a Reynolds number of 36. Centerpiece of the design is a topological optimization based on the finite element method. It is set-up to yield easy-to-fabricate valve structures with a small footprint that can be directly used in microfluidic systems. Our numerical two-dimensional optimization takes into account the finite height of the channel approximately by means of a so-called shallow-channel approximation. Based on the three-dimensionally extruded optimized designs, various test structures were fabricated using standard, widely available microsystem manufacturing techniques. The manufacturing process is described in detail since it can be used for the production of similar cost-effective microfluidic systems. For the experimentally fabricated chips, the efficiency of the different valve designs, i.e., the diodicity defined as the ratio of the measured pressure drops in backward and forward flow directions, respectively, is measured and compared to theoretical predictions obtained from full 3D calculations of the Tesla valves. Good agreement is found. In addition to the direct measurement of the diodicities, the flow profiles in the fabricated test structures are determined using a two-dimensional microscopic particle image velocimetry (µPIV) method. Again, a reasonable good agreement of the measured flow profiles with simulated predictions is observed.

19.
J Clin Gastroenterol ; 56(2): e126-e130, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538442

RESUMO

OBJECTIVE: Knowledge about SARS-CoV2 and coronavirus disease 2019 (COVID-19) is growing fast. Massive changes in the health care system imposed by the COVID-19 pandemic clearly impact the overall quality of medical care. In this survey, we aim to explore experiences and concerns of patients with inflammatory bowel disease (IBD) regarding the current pandemic. METHODS: A 40-item web-based questionnaire on disease-related experiences and concerns during the COVID-19 pandemic was made available to patients with IBD from 28 April 2020 to 31 July 2020. RESULTS: An increased risk of SARS-CoV2 infection was a concern for 56.7% of the 1199 patients (aged 41.3±12.8, women 77%, Crohn's disease 58.8%, ulcerative colitis 38.5%); 61.7% feared an increased risk of severe disease course of COVID-19. Effective preventive measures in either outpatient practices or hospitals were observed by 84.7% of the patients. Appointments with an IBD specialist were canceled in 38.7%, frequently on the patients' initiative. Telecommunication visits were considered an acceptable alternative to personal visits by 71.0%. Medication was reduced or paused in 6.9% because of the pandemic. A swab (SARS-CoV2-PCR) was done in 13.2% of the patients; only 3 patients (0.25%) were tested positive. CONCLUSION: The COVID-19 pandemic is a major concern of patients with IBD. However, the cumulative prevalence in our cohort is low. Patients at risk should be identified and counseled individually. When required because of the local COVID-19 situation, telecommunication visits and liberal prescription policies are advisable to reduce in-person contacts, while ensuring continuous therapy and maintaining communication with patients.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Pandemias , RNA Viral , SARS-CoV-2
20.
Sensors (Basel) ; 21(21)2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34770691

RESUMO

The consideration of the Achilles tendon (AT) curvature is crucial for the precise determination of AT length and strain. We previously established an ultrasound-kinematic-based method to quantify the curvature, using a line of reflective foil skin markers covering the AT from origin to insertion. The current study aimed to simplify the method by reducing the number of markers while maintaining high accuracy. Eleven participants walked (1.4 m/s) and ran (2.5, 3.5 m/s) on a treadmill, and the AT curvature was quantified using reflective foil markers aligned with the AT between the origin on the gastrocnemius myotendinous-junction (tracked by ultrasound) and a marker on the calcaneal insertion. Foil markers were then systematically removed, and the introduced error on the assessment of AT length and strain was calculated. We found a significant main effect of marker number on the measurement error of AT length and strain (p<0.001). Using more than 30% of the full marker-set for walking and 50% for running, the R2 of the AT length error saturated, corresponding to average errors of <0.1 mm and <0.15% strain. Therefore, a substantially reduced marker-set, associated with a marginal error, can be recommended for considering the AT curvature in the determination of AT length and strain.


Assuntos
Tendão do Calcâneo , Corrida , Tendão do Calcâneo/diagnóstico por imagem , Fenômenos Biomecânicos , Humanos , Músculo Esquelético , Ultrassonografia , Caminhada
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