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1.
Wound Repair Regen ; 29(4): 650-666, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34077595

RESUMEN

Fibrotic diseases are still a serious concern for public health, due to their high prevalence, complex etiology and lack of successful treatments. Fibrosis consists of excessive accumulation of extracellular matrix components. As a result, the structure and function of tissues are impaired, thus potentially leading to organ failure and death in several chronic diseases. Myofibroblasts represent the principal cellular mediators of fibrosis, due to their extracellular matrix producing activity, and originate from different types of precursor cells, such as mesenchymal cells, epithelial cells and fibroblasts. Profibrotic activation of myofibroblasts can be triggered by a variety of mechanisms, including the transforming growth factor-ß signalling pathway, which is a major factor driving fibrosis. Interestingly, preclinical and clinical studies showed that fibrotic degeneration can stop and even reverse by using specific antifibrotic treatments. Increasing scientific evidence is being accumulated about the role of sirtuins in modulating the molecular pathways responsible for the onset and development of fibrotic diseases. Sirtuins are NAD+ -dependent protein deacetylases that play a crucial role in several molecular pathways within the cells, many of which at the crossroad between health and disease. In this context, we will report the current knowledge supporting the role of sirtuins in the balance between healthy and diseased myofibroblast activity. In particular, we will address the signalling pathways and the molecular targets that trigger the differentiation and profibrotic activation of myofibroblasts and can be modulated by sirtuins.


Asunto(s)
Miofibroblastos , Sirtuinas , Diferenciación Celular , Fibroblastos , Fibrosis , Humanos , Miofibroblastos/patología , Factor de Crecimiento Transformador beta1 , Cicatrización de Heridas
2.
Pflugers Arch ; 472(10): 1481-1494, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32748018

RESUMEN

In myotonia, reduced Cl- conductance of the mutated ClC-1 channels causes hindered muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. Repetitive contraction temporarily decreases myotonia, a phenomena called "warm up." The underlying mechanism for the reduction of hyperexcitability in warm-up is currently unknown. Since potassium displacement is known to reduce excitability in, for example, muscle fatigue, we characterized the role of potassium in native myotonia congenita (MC) muscle. Muscle specimens of ADR mice (an animal model for low gCl- conductance myotonia) were exposed to increasing K+ concentrations. To characterize functional effects of potassium ion current, the muscle of ADR mice was exposed to agonists and antagonists of the big conductance Ca2+-activated K+ channel (BK) and the voltage-gated Kv7 channel. Effects were monitored by functional force and membrane potential measurements. By increasing [K+]0 to 5 mM, the warm-up phenomena started earlier and at [K+]0 7 mM only weak myotonia was detected. The increase of [K+]0 caused a sustained membrane depolarization accompanied with a reduction of myotonic bursts in ADR mice. Retigabine, a Kv7.2-Kv7.5 activator, dose-dependently reduced relaxation deficit of ADR myotonic muscle contraction and promoted the warm-up phenomena. In vitro results of this study suggest that increasing potassium conductivity via activation of voltage-gated potassium channels enhanced the warm-up phenomena, thereby offering a potential therapeutic treatment option for myotonia congenita.


Asunto(s)
Canales de Cloruro/genética , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Miotonía Congénita/metabolismo , Potasio/metabolismo , Animales , Cloruros/metabolismo , Canales de Potasio KCNQ/metabolismo , Canales de Potasio de Gran Conductancia Activados por el Calcio/agonistas , Canales de Potasio de Gran Conductancia Activados por el Calcio/antagonistas & inhibidores , Masculino , Potenciales de la Membrana , Ratones , Contracción Muscular , Mutación , Miotonía Congénita/genética , Miotonía Congénita/fisiopatología , Bloqueadores de los Canales de Potasio/farmacología
3.
Pflugers Arch ; 472(10): 1533, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32885305

RESUMEN

The original article contains an error during online publication. Table 2 was included during production round and now deleted. The Original article has been corrected.

4.
J Physiol ; 597(1): 225-235, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30284249

RESUMEN

KEY POINTS: During myotonia congenita, reduced chloride (Cl- ) conductance results in impaired muscle relaxation and increased muscle stiffness after forceful voluntary contraction. Repetitive contraction of myotonic muscle decreases or even abolishes myotonic muscle stiffness, a phenomenon called 'warm up'. Pharmacological inhibition of low Cl- channels by anthracene-9-carboxylic acid in muscle from mice and ADR ('arrested development of righting response') muscle from mice showed a relaxation deficit under physiological conditions compared to wild-type muscle. At increased osmolarity up to 400 mosmol L-1 , the relaxation deficit of myotonic muscle almost reached that of control muscle. These effects were mediated by the cation and anion cotransporter, NKCC1, and anti-myotonic effects of hypertonicity were at least partly antagonized by the application of bumetanide. ABSTRACT: Low chloride-conductance myotonia is caused by mutations in the skeletal muscle chloride (Cl- ) channel gene type 1 (CLCN1). Reduced Cl- conductance of the mutated channels results in impaired muscle relaxation and increased muscle stiffness after forceful voluntary contraction. Exercise decreases muscle stiffness, a phenomena called 'warm up'. To gain further insight into the patho-mechanism of impaired muscle stiffness and the warm-up phenomenon, we characterized the effects of increased osmolarity on myotonic function. Functional force and membrane potential measurements were performed on muscle specimens of ADR ('arrested development of righting response') mice (an animal model for low gCl- conductance myotonia) and pharmacologically-induced myotonia. Specimens were exposed to solutions of increasing osmolarity at the same time as force and membrane potentials were monitored. In the second set of experiments, ADR muscle and pharmacologically-induced myotonic muscle were exposed to an antagonist of NKCC1. Upon osmotic stress, ADR muscle was depolarized to a lesser extent than control wild-type muscle. High osmolarity diminished myotonia and facilitated the warm-up phenomenon as depicted by a faster muscle relaxation time (T90/10 ). Osmotic stress primarily resulted in the activation of the NKCC1. The inhibition of NKCC1 with bumetanide prevented the depolarization and reversed the anti-myotonic effect of high osmolarity. Increased osmolarity decreased signs of myotonia and facilitated the warm-up phenomenon in different in vitro models of myotonia. Activation of NKCC1 activity promotes warm-up and reduces the number of contractions required to achieve normal relaxation kinetics.


Asunto(s)
Miotonía Congénita/fisiopatología , Concentración Osmolar , Animales , Bumetanida/farmacología , Modelos Animales de Enfermedad , Femenino , Masculino , Potenciales de la Membrana/efectos de los fármacos , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Miembro 2 de la Familia de Transportadores de Soluto 12/fisiología
5.
Anesthesiology ; 131(5): 983-991, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31206373

RESUMEN

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal disorder triggered by certain anesthetics. Mutations in the ryanodine receptor 1 (RYR1) gene account for about half of MH cases. Discordance between the low incidence of MH and a high prevalence of mutations has been attributed to incomplete penetrance, which has not been quantified yet. The authors aimed to examine penetrance of MH-diagnostic RYR1 mutations and the likelihood of mutation carriers to develop MH, and to identify factors affecting severity of MH clinical expression. METHODS: In this multicenter case-control study, data from 125 MH pedigrees between 1994 and 2017 were collected from four European registries and one Canadian registry. Probands (survivors of MH reaction) and their relatives with at least one exposure to anesthetic triggers, carrying one diagnostic RYR1 mutation, were included. Penetrance (percentage of probands among all genotype-positive) and the probability of a mutation carrier to develop MH were obtained. MH onset time and Clinical Grading Scale score were used to assess MH reaction severity. RESULTS: The overall penetrance of nine RYR1 diagnostic mutations was 40.6% (93 of 229), without statistical differences among mutations. Likelihood to develop MH on exposure to triggers was 0.25 among all RYR1 mutation carriers, and 0.76 in probands (95% CI of the difference 0.41 to 0.59). Penetrance in males was significantly higher than in females (50% [62 of 124] vs. 29.7% [30 of 101]; P = 0.002). Males had increased odds of developing MH (odds ratio, 2.37; 95% CI, 1.36 to 4.12) despite similar levels of exposure to trigger anesthetics. Proband's median age was 12 yr (interquartile range 6 to 32.5). CONCLUSIONS: Nine MH-diagnostic RYR1 mutations have sex-dependent incomplete penetrance, whereas MH clinical expression is influenced by patient's age and the type of anesthetic. Our quantitative evaluation of MH penetrance reinforces the notion that a previous uneventful anesthetic does not preclude the possibility of developing MH.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/genética , Mutación/genética , Penetrancia , Canal Liberador de Calcio Receptor de Rianodina/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Adulto Joven
6.
Clin Anat ; 32(7): 891-895, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31012158

RESUMEN

The ubiquitous network of fascial tissues in the human body is usually regarded as a passive contributor to musculoskeletal dynamics. This review aims to highlight the current understanding of fascial stiffness regulation. Notably the ability for active cellular contraction which may augment the stiffness of fascial tissues and thereby contribute to musculoskeletal dynamics. A related narrative literature search via PubMed and Google Scholar reveals a multitude of studies indicating that the intrafascial presence of myofibroblasts may enable these tissues to alter their stiffness. This contractile tissue behavior occurs not only in several pathological fibrotic contractures but has also been documented in normal fasciae. When viewed at time frames of seconds and minutes the force of such tissue contractions is not sufficient for exerting a significant effect on mechanical joint stability. However, when viewed in a time-window of several minutes and longer, such cellular contractions can impact motoneuronal coordination. In addition, over a time frame of days to months, this cellular activity can induce long-term and severe tissue contractures. These findings tend to question the common clear distinction between active tissues and passive tissues in musculoskeletal dynamics. Clin. Anat. 32:891-895, 2019. © 2019 Wiley Periodicals, Inc.


Asunto(s)
Fascia/fisiología , Miofibroblastos/fisiología , Animales , Fenómenos Biomecánicos , Fascia/anatomía & histología , Humanos , Contracción Muscular/fisiología , Músculo Esquelético/fisiología
7.
Br J Sports Med ; 52(23): 1497, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30072398

RESUMEN

The fascial system builds a three-dimensional continuum of soft, collagen-containing, loose and dense fibrous connective tissue that permeates the body and enables all body systems to operate in an integrated manner. Injuries to the fascial system cause a significant loss of performance in recreational exercise as well as high-performance sports, and could have a potential role in the development and perpetuation of musculoskeletal disorders, including lower back pain. Fascial tissues deserve more detailed attention in the field of sports medicine. A better understanding of their adaptation dynamics to mechanical loading as well as to biochemical conditions promises valuable improvements in terms of injury prevention, athletic performance and sports-related rehabilitation. This consensus statement reflects the state of knowledge regarding the role of fascial tissues in the discipline of sports medicine. It aims to (1) provide an overview of the contemporary state of knowledge regarding the fascial system from the microlevel (molecular and cellular responses) to the macrolevel (mechanical properties), (2) summarise the responses of the fascial system to altered loading (physical exercise), to injury and other physiological challenges including ageing, (3) outline the methods available to study the fascial system, and (4) highlight the contemporary view of interventions that target fascial tissue in sport and exercise medicine. Advancing this field will require a coordinated effort of researchers and clinicians combining mechanobiology, exercise physiology and improved assessment technologies.


Asunto(s)
Adaptación Fisiológica , Traumatismos en Atletas/diagnóstico , Fascia/lesiones , Fascia/fisiología , Enfermedades Musculoesqueléticas/diagnóstico , Envejecimiento , Traumatismos en Atletas/prevención & control , Rendimiento Atlético , Investigación Biomédica , Consenso , Ejercicio Físico/fisiología , Humanos , Enfermedades Musculoesqueléticas/prevención & control , Deportes/fisiología , Medicina Deportiva
8.
Eur J Anaesthesiol ; 35(7): 534-538, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29432380

RESUMEN

BACKGROUND: Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S): The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN: A prospective observational study. SETTING: Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS: During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES: Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS: Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96 ±â€Š0.20 ppm in postanaesthesia unit one, 0.82 ±â€Š0.07 ppm in postanaesthesia unit two. Median concentration was 0.12 (0.34) ppm in postanaesthesia unit one and 0.11 (0.28) ppm in postanaesthesia unit two. CONCLUSION: Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded.


Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Contaminación del Aire Interior/análisis , Anestésicos por Inhalación/análisis , Exposición Profesional/estadística & datos numéricos , Sala de Recuperación/estadística & datos numéricos , Contaminantes Ocupacionales del Aire/efectos adversos , Contaminación del Aire Interior/estadística & datos numéricos , Anestésicos por Inhalación/efectos adversos , Alemania , Humanos , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Estudios Prospectivos , Sevoflurano/efectos adversos , Sevoflurano/análisis , Análisis Espectral/instrumentación , Análisis Espectral/métodos
11.
Sci Rep ; 13(1): 815, 2023 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-36646734

RESUMEN

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools' (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75-0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable.


Asunto(s)
Músculo Esquelético , Columna Vertebral , Fascia , Fantasmas de Imagen , Reproducibilidad de los Resultados , Piel , Ultrasonografía
12.
Acta Myol ; 31(3): 184-95, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23620650

RESUMEN

Muscular dystrophies such as Duchenne muscular dystrophy (DMD) are usually approached as dysfunctions of the affected skeletal myofibres and their force transmission. Comparatively little attention has been given to the increase in connective tissue (fibrosis) which accompanies these muscular changes. Interestingly, an increase in endomysial tissue is apparent long before any muscular degeneration can be observed. Fibrosis is the result of a reactive or reparative process involving mechanical, humoral and cellular factors. Originating from vulnerable myofibres, muscle cell necrosis and inflammatory processes are present in DMD. Muscular recovery is limited due to the limited number and capacity of satellite cells. Hence, a proactive and multimodal approach is necessary in order to activate protective mechanisms and to hinder catabolic and tissue degrading pathways. Several avenues are discussed in terms of potential antifibrotic therapy approaches. These include pharmaceutical, nutritional, exercise-based and other mechanostimulatory modalities (such as massage or yoga-like stretching) with the intention of exerting an anti-inflammatory and antifibrotic effect on the affected muscular tissues. A preventive intervention at an early age is crucial, based on the early and seemingly non-reversible nature of the fibrotic tissue changes. Since consistent assessment is essential, different measurement technologies are discussed.


Asunto(s)
Músculo Esquelético/patología , Distrofia Muscular de Duchenne/patología , Animales , Tejido Conectivo/patología , Ejercicio Físico , Matriz Extracelular/patología , Fibrosis , Calor/uso terapéutico , Humanos , Miofibroblastos/patología
13.
GMS Health Innov Technol ; 16: Doc03, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35910412

RESUMEN

This paper presents a concept for detection of venous air emboli inside the superior vena cava using a central venous catheter with integrated Doppler ultrasound transducer installed on the tip. Several Doppler probes each with a single insonation frequencies of 2 MHz, 4 MHz or 8 MHz are characterized and compared for usefulness in this scenario. During in vitro experiments using an artificial blood circulatory with blood mimicking fluid bubbles with defined volumes were injected and recorded as gaseous embolic events. The in vitro results of measured embolus-blood-ratio values (EBR) in respect to the air bubbles volumes and its echogenicity showed a good correlation with the simulation model of spherical cross section scattering of such air bubbles. It is shown that the probe design still needs some improvements using a 4 MHz insonation frequency to get a useable detection sensitivity in such scenario within vena cava superior. The results suggest that it is possible to estimate the air bubble volume corresponding to the EBR using such a catheter probe.

14.
J Clin Med ; 11(23)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36498690

RESUMEN

Background: Instrument-assisted manual therapy (IAMT) is indicated to improve flexibility, reduce pain, and induce hyperaemia locally and along myofascial chains. The underlying effects are largely unclear. This randomised, placebo-controlled pilot study aimed to gain first insights into these effects, primarily on the structural level, through ultrasonography. Methods: 67 healthy female soccer players aged 20.9 (±3.9) years were examined after right lumbar intervention (IAMT: intervention group (IG), heat application: comparison group (CG), pressure-less placebo: placebo group (PG)). Ultrasonography (absolute movement and shear motion), flexibility tests (passive straight leg raise test (PSLR), lumbar and thoracic double inclinometry), and superficial skin temperature were recorded before (t0), immediately (t1) and 45 min after the intervention (t2). Results: IAMT decreased the absolute mobility of the superficial lamina and its shear motion to the superficial fascia compared with the PG (t1; p < 0.05). PSLR improved in the IG compared with the CG (t2) and PG (t1, t2; p < 0.05). The temperature increased in the IG and CG compared with the PG (t1, t2) and in the CG compared with the IG (t1; p < 0.05). Conclusion: IAMT of the lumbar back briefly reduces absolute mobility of the superficial lamina and its shear motion to the superficial fascia, improves flexibility, and increases the temperature.

15.
Anesthesiology ; 115(2): 398-407, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21753726

RESUMEN

BACKGROUND: Both central sensitization after peripheral tissue injury and the development of opioid tolerance involve activation of N-methyl-D-aspartate (NMDA) receptors. At subanesthetic doses the NMDA receptor antagonist xenon suppresses pain-evoked sensitization of pain-processing areas in the central nervous system. Although numerous studies describe the effect of NMDA receptor antagonists on postoperative pain, clinical studies elucidating their intraoperative analgesic potency when applied in a low dosage are still largely missing. METHODS: To analyze the analgesic effect of low-dose xenon using new application methods, the authors tested nasally applied xenon as an add-on treatment for analgesia in 40 patients undergoing abdominal hysterectomy. Within a randomized double-blind placebo-controlled study design, intraoperative and postoperative requirement of opioids as well as postoperative subjective experiences of pain were measured as primary outcome variables. RESULTS: Intranasal application of xenon significantly reduced intraoperative opioid requirement (mean difference [MD] -2.0 µg/min; 95% CI [CI95]-0.53 to -3.51, Bonferroni correction adjusted P value [pcorr]= 0.028) without relevant side effects and significantly reduced postoperative pain (MD -1.34 points on an 11-point rating scale; CI95 -0.60 to -2.09, pcorr = 0.002). However, postoperative morphine consumption (MD -8.8 µg/min; CI95 1.2 to -18.8, pcorr = 0.24) was not significantly reduced in this study. CONCLUSIONS: Low-dose xenon significantly reduces intraoperative analgesic use and postoperative pain perception. Because NMDA receptor antagonists suppress central sensitization, prevent the development of opioid tolerance, and reduce postoperative pain, the intraoperative usage of NMDA receptor antagonists such as xenon is suggested to improve effectiveness of pain management within a concept of multimodal analgesia.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Xenón/administración & dosificación , Administración Intranasal , Adulto , Analgésicos Opioides/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Receptores de N-Metil-D-Aspartato/fisiología , Xenón/uso terapéutico
16.
Sci Rep ; 11(1): 3445, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33564012

RESUMEN

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, hyperkalemia and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release from myotubes via the ryanodine receptor type 1 (RYR1) and the voltage-dependent L-type calcium channel (CACNA1S). As more than 300 variants of unknown significance have been detected to date, we examined whether freely available pathogenicity prediction tools are able to detect relevant MH causing variants. In this diagnostic accuracy study, blood samples from 235 individuals with a history of a clinical malignant hyperthermia or their close relatives were genetically screened for RYR1 variants of all 106 RYR1 exons and additionally for known variants of CACNA1S. In vitro contracture tests were conducted on muscle biopsies obtained from all individuals, independently of whether a pathogenic variant, a variant of unknown significance or no variant was detected. Comparisons were made to three established bioinformatic pathogenicity detection tools to identify the clinical impact of the variants of unknown significance. All detected genetic variants were tested for pathogenicity by three in silico approaches and compared to the in vitro contracture test. Sensitivity and specificity of exon screening of all individuals listed in our MH database was analyzed. Exon screening identified 97 (41%) of the 235 individuals as carriers of pathogenic variants. Variants of unknown significance were detected in 21 individuals. Variants of unknown significance were subdivided into 19 malignant-hyperthermia-susceptible individuals and 2 non-malignant-hyperthermia-susceptible individuals. All pathogenic variants as well as the malignant-hyperthermia-suspectible variants were correctly identified by the bioinformatic prediction tools. Sensitivity of in silico approaches ranged between 0.71 and 0.98 (Polyphen 0.94 [CI 95% 0.75; 0.99]; Sift 0.98 [CI 95% 0.81; 0.99]; MutationTaster 0.92 [CI 95% 0.75; 0.99]). Specificity differed depending on the used tool (Polphen 0.98 [CI 95% 0.32; 0.99]; Sift 0.98 [CI 95% 0.32; 0.99]; MutationTaster 0.00 [CI 95% 0.00; 0.60]). All pathogenic variants and variants of unknown significance were scored as probably damaging in individuals, demonstrating a high sensitivity. Specificity was very low in one of the three tested programs. However, due to potential genotype-phenotype discordance, bioinformatic prediction tools are currently of limited value in diagnosing pathogenicity of MH-susceptible variants.


Asunto(s)
Bases de Datos de Ácidos Nucleicos , Exones , Variación Genética , Hipertermia Maligna/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Adulto , Canales de Calcio Tipo L/genética , Femenino , Humanos , Masculino , Hipertermia Maligna/diagnóstico , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos
17.
J Clin Med ; 10(22)2021 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-34830642

RESUMEN

BACKGROUND: Foam rolling is a type of self-massage using tools such as foam or roller sticks. However, to date, there is no consensus on contraindications and cautions of foam rolling. A methodological approach to narrow that research gap is to obtain reliable opinions of expert groups. The aim of the study was to develop experts' consensus on contraindications and cautions of foam rolling by means of a Delphi process. METHODS: An international three-round Delphi study was conducted. Academic experts, defined as having (co-) authored at least one PubMed-listed paper on foam rolling, were invited to participate. Rounds 1 and 2 involved generation and rating of a list of possible contraindications and cautions of foam rolling. In round 3, participants indicated their agreement on contraindications and cautions for a final set of conditions. Consensus was evaluated using a priori defined criteria. Consensus on contraindications and cautions was considered as reached if more than 70% of participating experts labeled the respective item as contraindication and contraindication or caution, respectively, in round 3. RESULTS: In the final Delphi process round, responses were received from 37 participants. Panel participants were predominantly sports scientists (n = 21), physiotherapists (n = 6), and medical professionals (n = 5). Consensus on contraindications was reached for open wounds (73% agreement) and bone fractures (84%). Consensus on cautions was achieved for local tissue inflammation (97%), deep vein thrombosis (97%), osteomyelitis (94%), and myositis ossificans (92%). The highest impact/severity of an adverse event caused by contraindication/cautions was estimated for bone fractures, deep vein thrombosis, and osteomyelitis. DISCUSSION: The mechanical forces applied through foam rolling can be considered as potential threats leading to adverse events in the context of the identified contraindications and cautions. Further evaluations by medical professionals as well as the collection of clinical data are needed to assess the risks of foam rolling and to generate guidance for different applications and professional backgrounds.

18.
Artículo en Inglés | MEDLINE | ID: mdl-32322406

RESUMEN

BACKGROUND: Myofascial (self-)treatments, such as foam rollers to therapeutic instruments in manual therapy, are utilized increasingly in prevention and therapy in healthy people, athletes, and patients suffering from chronic back pain. However, there is limited knowledge about the effectiveness of treatment and the underlying mechanisms of myofascial therapies, especially for instrument-assisted manual therapy (IAMT). Therefore, this pilot study will investigate the feasibility and impact of IAMT for the lumbar area compared with heat application and placebo treatment as a basis for calculating the sample size for further full studies. The primary outcomes will be a critical analysis of the feasibility of the measurement protocol in terms of time economy and expressiveness and of the short- and long-term effects on shear motion of the single tissue layers of the lower back obtained through ultrasound imaging. Secondary outcomes will include thickness and compressibility of the lumbar structures and flexibility of the dorsal structures, indentometry, and superficial skin temperature. METHODS: A minimum of 60 healthy, competitive 15-35-year-old female soccer players will be recruited and randomised into three groups. Short-term effects of IAMT on thoracolumbar structures will be compared with heat application and pressure-less placebo treatment. Long-term effects in the IAMT group will be tested after nine further interventions over a 5-week period (2×/week) and compared with the placebo group, which will not receive further treatments but will serve as a control. Intermediate and final testing of both groups will occur in weeks three and five. DISCUSSION: This pilot study will assess the feasibility and the impact of IAMT for the lower back particularly by examining the structural and functional properties of myofascial tissue using diagnostic ultrasound. These outcomes could evaluate the feasibility of the measurements used, shall build a basis for sample size calculation of further full studies, and might generate a greater understanding of myofascial therapies, especially IAMT, for the lower back and its benefits. If this approach proves to be practicable, next steps will be further full studies with soccer players, other sports, and patients with low back pain. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00012252) 20.06.2018; retrospectively registered.

19.
J Bodyw Mov Ther ; 24(4): 1-6, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33218495

RESUMEN

BACKGROUND: Manual palpation is a core skill in physical examination. Assessing elastic properties such as tissue stiffness has the potential for being an important diagnostics tool in the detection of cancer and other diseases. OBJECTIVE: The study describes the newly developed Stiffness Comparison Test (SCT). The aim of our study was to test the SCT as a tool to detect interindividual differences in palpation skill related to gender, age and occupational experience. METHODS: We used eight pairs of polyuterhane gel pads with the stiffness difference decreasing from the first to the last pair. Test subjects were asked to palpate each pair and determine stiffness differences. PARTICIPANTS: We recruited 25 osteopaths, 48 other manual therapists and 50 participants from other non-manual professions. RESULTS: As hypothesized there was no significant difference in SCT performance between the sexes (t(121) = 0.288, p = .774). To investigate if an age-related decline would have an effect on palpation skill, we carried out a linear regression. As hypothesized, the model did not predict any significant associations (F(1, 121) = 2.733, b = -0.149, p = .101, R2 = 0.022). To compare the effect of occupational groups on SCT performance a one-way ANOVA was conducted. There were no statistically significant differences between group means (F(2, 120) = 0.598, p = .552). CONCLUSIONS: The SCT can be used as simple and affordable tool for assessment, teaching and training in all disciplines of manual medicine. Further refinements of the tool are suggested to advance its discrimination power.


Asunto(s)
Individualidad , Palpación , Humanos , Ocupaciones , Examen Físico , Proyectos Piloto
20.
Front Physiol ; 11: 592, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32670080

RESUMEN

Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.

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