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Muscle & Nerve Jun 2024Point-of-care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with...
INTRODUCTION/AIMS
Point-of-care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with neuromuscular diaphragmatic dysfunction, paradoxical thinning of the diaphragm during inspiration is observed on ultrasound; however, its frequency, electrodiagnostic associations, and prognostic significance remain uncertain.
METHODS
Medical records of patients presenting to two electrodiagnostic laboratories (Mayo Clinic, Rochester, Minnesota and University of Alberta, Edmonton, Alberta) from January 1, 2022 to December 31, 2022, for evaluation of suspected neuromuscular respiratory failure, were reviewed.
RESULTS
214 patients were referred and 19 patients excluded due to incomplete information. Of 195 patients (384 hemidiaphragms), 104 had phrenic neuropathy, 12 had myopathy, and 79 had no evidence of neuromuscular disease affecting the diaphragm. Paradoxical thinning occurred in 31 (27%) patients with neuromuscular diaphragmatic dysfunction and was unilateral in 30, the majority (83%) having normal contralateral ultrasound. Phrenic nerve conduction studies and diaphragm electromyography results did not distinguish patients with paradoxical thinning versus without. Most patients (71%) with paradoxical thinning required non-invasive ventilation (NIV), including 16 with unilateral paradoxical thinning. Paradoxical thinning and BMI ≥30 kg/m were risk factors for requiring NIV in multivariable logistic regression analysis, with odds ratios of 2.887 (95% CI:1.166, 7.151) and 2.561 (95% CI: 1.186, 5.532), respectively.
DISCUSSION
Paradoxical thinning of the diaphragm occurs in patients with prominent neuromuscular diaphragmatic dysfunction, most commonly from phrenic neuropathy, and is a significant risk factor for requiring NIV. Unilateral paradoxical thinning is sufficient for needing NIV. BMI ≥30 kg/m additionally increases risk of requiring NIV in patients with neuromuscular diaphragmatic dysfunction.
PubMed: 38935447
DOI: 10.1002/mus.28194 -
Materials (Basel, Switzerland) Jun 2024A combined stamping-bulging forming process was proposed to achieve high-precision forming of large-diameter, ultra-thin-walled, superalloy welded S-type corrugated...
A combined stamping-bulging forming process was proposed to achieve high-precision forming of large-diameter, ultra-thin-walled, superalloy welded S-type corrugated diaphragms. The underlying principle is to enhance the diaphragm's forming accuracy by increasing the plastic deformation region and reducing springback. Using the ABAQUS version 6.14 finite element analysis software, finite element models were constructed for the stamping, hydraulic bulging, and combined stamping-bulging forming processes of the welded S-type metal corrugated diaphragms. A comparative analysis was conducted on the forming processes of the welded S-type metal corrugated diaphragms under the three forming methods, focusing on equivalent stress, distribution of wall thickness, and forming accuracy. This analysis determined the optimal forming process and the corresponding process parameters for superalloy welded S-type metal corrugated diaphragms. The results show that under a constant drawing force, as the bulging pressure increases, the plastic deformation of the straight sections of the diaphragm becomes more pronounced, resulting in improved shape accuracy. The combined stamping-bulging forming process guarantees the highest degree of shape accuracy for the diaphragm. The optimal process parameters were identified as a 30 t force and a 5 MPa pressure, with a maximum shape error of 0.02 mm. Concerning a plate thickness of 0.3 mm, the maximum deviation rate was found to be 6.7%, which represents a 30% improvement over traditional stamping processes. The maximum wall thinning rate was found to be 3.3%, a 1% reduction compared to traditional stamping processes, confirming the process's feasibility.
PubMed: 38930198
DOI: 10.3390/ma17122829 -
Antioxidants (Basel, Switzerland) May 2024Duchenne muscular dystrophy (DMD) is one of the most frequent and severe childhood muscle diseases. Its pathophysiology is multifaceted and still incompletely...
Duchenne muscular dystrophy (DMD) is one of the most frequent and severe childhood muscle diseases. Its pathophysiology is multifaceted and still incompletely understood, but we and others have previously shown that oxidative stress plays an important role. In particular, we have demonstrated that inhibition of mitochondrial monoamine oxidases could improve some functional and biohumoral markers of the pathology. In the present study we report the use of dystrophic mice to evaluate the efficacy of a dual monoamine oxidase B (MAO-B)/semicarbazide-sensitive amine oxidase (SSAO) inhibitor, PXS-5131, in reducing inflammation and fibrosis and improving muscle function. We found that a one-month treatment starting at three months of age was able to decrease reactive oxygen species (ROS) production, fibrosis, and inflammatory infiltrate in the tibialis anterior (TA) and diaphragm muscles. Importantly, we also observed a marked improvement in the capacity of the gastrocnemius muscle to maintain its force when challenged with eccentric contractions. Upon performing a bulk RNA-seq analysis, PXS-5131 treatment affected the expression of genes involved in inflammatory processes and tissue remodeling. We also studied the effect of prolonged treatment in older dystrophic mice, and found that a three-month administration of PXS-5131 was able to greatly reduce the progression of fibrosis not only in the diaphragm but also in the heart. Taken together, these results suggest that PXS-5131 is an effective inhibitor of fibrosis and inflammation in dystrophic muscles, a finding that could open a new therapeutic avenue for DMD patients.
PubMed: 38929061
DOI: 10.3390/antiox13060622 -
Foods (Basel, Switzerland) Jun 2024This study aims to improve press equipment for safflower oil production by using a mechanism that optimizes pressure distribution within screw turns. A detailed analysis...
This study aims to improve press equipment for safflower oil production by using a mechanism that optimizes pressure distribution within screw turns. A detailed analysis of the main components of the produced safflower oil was performed, encompassing both quantitative and qualitative assessments. Through the exploration of dependencies governing the safflower oil pressing process on the screw press, the optimal parameters were determined. As a result of the research, the optimal diaphragm gap between the gape cylinder and the pressing screw was determined, with the optimal oil yield percentage achieved at ω = 6.2 rad/s and δ = 5 mm. The study also compared the performance of the existing Dream Modern ODM-01 screw press and its upgraded version by analyzing the extracted oil. The results reveal changes in the quantitative and qualitative composition of the main oil components following the operation of the existing and the modernized screw presses. For instance, the amount of unsaturated fatty acids, such as oleic acid (7.7 ± 0.566%), linoleic acid (85.3 ± 1.185%), and linolenic acid (1.2 ± 0.223%), increased. There was an increase in the presence of inorganic substances in safflower oil: iron (0.023 ± 0.031 mg/kg), phosphorus (0.086 ± 0.059 mg/kg), silicium (0.136 ± 0.075 mg/kg), and others. The findings of this study hold significant commercial value and offer promising prospects for global market implementation.
PubMed: 38928850
DOI: 10.3390/foods13121909 -
International Journal of Molecular... Jun 2024Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed...
Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed myocardial titin expression and titin hypophosphorylation leading to titin filament stiffening. Beside these well-studied alterations at the cardiomyocyte level, exercise intolerance is another hallmark of HFpEF caused by molecular alterations in skeletal muscle (SKM). Currently, there is a lack of data regarding titin modulation in the SKM of HFpEF. Therefore, the aim of the present study was to analyze molecular alterations in limb SKM (tibialis anterior (TA)) and in the diaphragm (Dia), as a more central SKM, with a focus on titin, titin phosphorylation, and contraction-regulating proteins. This study was performed with muscle tissue, obtained from 32-week old female ZSF-1 rats, an established a HFpEF rat model. Our results showed a hyperphosphorylation of titin in limb SKM, based on enhanced phosphorylation at the PEVK region, which is known to lead to titin filament stiffening. This hyperphosphorylation could be reversed by high-intensity interval training (HIIT). Additionally, a negative correlation occurring between the phosphorylation state of titin and the muscle force in the limb SKM was evident. For the Dia, no alterations in the phosphorylation state of titin could be detected. Supported by data of previous studies, this suggests an exercise effect of the Dia in HFpEF. Regarding the expression of contraction regulating proteins, significant differences between Dia and limb SKM could be detected, supporting muscle atrophy and dysfunction in limb SKM, but not in the Dia. Altogether, these data suggest a correlation between titin stiffening and the appearance of exercise intolerance in HFpEF, as well as a differential regulation between different SKM groups.
Topics: Animals; Heart Failure; Rats; Diaphragm; Connectin; Phosphorylation; Disease Models, Animal; Female; Muscle, Skeletal; Stroke Volume; Muscle Contraction; Physical Conditioning, Animal; Muscle Proteins
PubMed: 38928324
DOI: 10.3390/ijms25126618 -
International Journal of Molecular... Jun 2024Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced...
Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-β1, oxidative loads, Masson's trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis ( < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed ( < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity ( < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.
Topics: Animals; Bleomycin; Diaphragm; Mice; Fibrosis; Disease Models, Animal; Mice, Inbred C57BL; Acute Lung Injury; Male; Respiration, Artificial; Class Ib Phosphatidylinositol 3-Kinase; Transforming Growth Factor beta1; Apoptosis; Quinoxalines; Thiazolidinediones
PubMed: 38928077
DOI: 10.3390/ijms25126370 -
Cancers Jun 2024Worldwide, lung cancer remains the predominant cause of cancer cases and deaths and poses significant health challenges, with surgical resection being a key treatment....
Worldwide, lung cancer remains the predominant cause of cancer cases and deaths and poses significant health challenges, with surgical resection being a key treatment. Post-surgery, patients often experience functional impairments. This study aimed to develop a comprehensive ICF version for assessing the functional profile and disability in lung cancer patients post-thoracic surgery undergoing pulmonary rehabilitation using the ICF and WHODAS 2.0 tool. We analyzed the correlation between the ICF Core Set and WHODAS 2.0 data to understand the impact on daily functioning. This study included 50 patients (23 F, 27 M) from the Clinic of Thoracic Surgery and Respiratory Rehabilitation in Lodz. Essential ICF codes were determined using the Delphi method, and assessments were conducted on the third day post-operation. Statistical analyses included various tests with α = 0.05. The results showed no impairments in voice functions (b310), respiration rates (b4400), and diaphragm functions (b4451), but there were significant issues with chest pain (b28011), respiratory muscle functions (b445), exercise tolerance (b455), and muscle endurance (b740). In Activities and Participation and Environmental Factors, most codes were not problematic, except for employment (d845, d850) and atmospheric pressure (e2252). Significant correlations were found between mobility limitations (d410, d460) and self-care (d510, d540) with the WHODAS 2.0 results. The comprehensive ICF Core Set effectively described the functional profile of post-surgery patients, confirming its utility and highlighting the impact of disability on daily functioning.
PubMed: 38927985
DOI: 10.3390/cancers16122281 -
Molecular Metabolism Jun 2024A high proportion of women with advanced epithelial ovarian cancer (EOC) experience weakness and cachexia. This relationship is associated with increased morbidity and...
OBJECTIVES
A high proportion of women with advanced epithelial ovarian cancer (EOC) experience weakness and cachexia. This relationship is associated with increased morbidity and mortality. EOC is the most lethal gynecological cancer, yet no preclinical cachexia model has demonstrated the combined hallmark features of metastasis, ascites development, muscle loss and weakness in adult immunocompetent mice.
METHODS
Here, we evaluated a new model of ovarian cancer-induced cachexia with the advantages of inducing cancer in adult immunocompetent C57BL/6J mice through orthotopic injections of EOC cells in the ovarian bursa. We characterized the development of metastasis, ascites, muscle atrophy, muscle weakness, markers of inflammation, and mitochondrial stress in the tibialis anterior (TA) and diaphragm ∼45, ∼75 and ∼90 days after EOC injection.
RESULTS
Primary ovarian tumour sizes were progressively larger at each time point while severe metastasis, ascites development, and reductions in body, fat and muscle weights occurred by 90 Days. There were no changes in certain inflammatory (TNFα), atrogene (MURF1 and Atrogin) or GDF15 markers within both muscles whereas IL-6 was increased at 45 and 90 Day groups in the diaphragm. TA weakness in 45 Day preceded atrophy and metastasis that were observed later (75 and 90 Day, respectively). The diaphragm demonstrated both weakness and atrophy in 45 Day. In both muscles, this pre-severe-metastatic muscle weakness corresponded with considerable reprogramming of gene pathways related to mitochondrial bioenergetics as well as reduced functional measures of mitochondrial pyruvate oxidation and creatine-dependent ADP/ATP cycling as well as increased reactive oxygen species emission (hydrogen peroxide). Remarkably, muscle force per unit mass at 90 days was partially restored in the TA despite the presence of atrophy and severe metastasis. In contrast, the diaphragm demonstrated progressive weakness. At this advanced stage, mitochondrial pyruvate oxidation in both muscles exceeded control mice suggesting an apparent metabolic super-compensation corresponding with restored indices of creatine-dependent adenylate cycling.
CONCLUSION
This mouse model demonstrates the concurrent development of cachexia and metastasis that occurs in women with EOC. The model provides physiologically relevant advantages of inducing tumour development within the ovarian bursa in immunocompetent adult mice. Moreover, the model reveals that muscle weakness in both TA and diaphragm precedes severe metastasis while weakness also precedes atrophy in the TA. An underlying mitochondrial bioenergetic stress corresponded with this early weakness. Collectively, these discoveries can direct new research towards the development of therapies that target pre-atrophy and pre-severe-metastatic weakness during EOC in addition to therapies targeting cachexia.
PubMed: 38925248
DOI: 10.1016/j.molmet.2024.101976 -
Computers in Biology and Medicine Jun 2024The CAS3D image processing method intuitively applies a combination of Fourier space and real space 3D analysis algorithms to volumetric images of single skeletal muscle...
The CAS3D image processing method intuitively applies a combination of Fourier space and real space 3D analysis algorithms to volumetric images of single skeletal muscle fiber Myosin II Second Harmonic Generation (SHG) XYZ image data. Our developed tool automatically quantifies the myofibrillar orientation in muscle samples by determining the cosine angle sum of intensity gradients in 3D (CAS3D) while determining the mean sarcomere length (SL) and sample orientation. The expected CAS3D values could be reproduced from ideal artificial data sets. Applied random noise in artificial images lowers the detected CAS3D value, and for noise levels below 20%, the correlation can be approximated by a linear function with a slope of -0.006 CAS3D/noise%. The deviations in SL and orientation detection were determined on ideal and noisy artificial data sets and were statistically indistinguishable from 0 (null hypothesis t-test P > 0.1). The software was applied to a previously published data set of single skeletal muscle fiber volumetric SHG image data from a rat intensive care unit (ICU) model of ventilator-induced diaphragm dysfunction (VIDD) with treatment regimens involving the small anti-inflammatory molecules BGP-15, vamorolone, or prednisolone. Our method reliably reproduced the results of the previous work and improved the standard deviation of the cosine angle sum detection in all sample groups from a mean of 0.03 to 0.008. This improvement is achieved by applying analysis algorithms to the whole volumetric images in 3D in contrast to the previously common method of slice-wise XY analysis.
PubMed: 38925088
DOI: 10.1016/j.compbiomed.2024.108618 -
Journal of Occupational and... Jun 2024Ideally, measuring exposures to volatile organic compounds should allow for modifying sampling duration without loss in sensitivity. Traditional sorbent-based sampling...
Ideally, measuring exposures to volatile organic compounds should allow for modifying sampling duration without loss in sensitivity. Traditional sorbent-based sampling can vary sampling duration, but sensitivity may be affected when capturing shorter tasks. Diaphragm and capillary flow controllers allow for a range of flow rates and sampling durations for air sampling with evacuated canisters. The goal of this study was to evaluate the extent to which commercialized capillary flow controllers satisfy the bias (±10%) and accuracy (±25%) criteria for air sampling methods as established by the National Institute for Occupational Safety and Health (NIOSH) using the framework of ASTM D6246 to compare their performance with diaphragm flow controllers in a long-term field study. Phase 1 consisted of a series of laboratory tests to evaluate capillary flow controller flow rates with respect to variations in temperature (-15-24 °C). The results demonstrated a slight increase in flow rate with lower temperatures. In Phase 2, the capillary flow controller was evaluated utilizing a matrix of parameters, including time-weighted average concentration, peak concentration (50-100× base concentration), air velocity across the sampler inlet (0.41-0.5 m/s), relative humidity (20-80%), and temperature (10-32 °C). Comparison of challenge concentrations with reference concentrations revealed the aggregate bias and overall accuracy for four tested compounds to be within the range of criteria for both NIOSH and ASTM standards. Additionally, capillary flow controllers displayed lower variability in flow rate and measured concentration (RSD: 2.4% and 4.3%, respectively) when compared with diaphragm flow controllers (RSD: 6.9% and 7.2%, respectively) for 24-hr laboratory tests. Phase 3 involved further testing of flow rate variability for both diaphragm and capillary flow controllers in a field study. The capillary flow controller displayed a lower level of variability (RSD: 5.2%) than the diaphragm flow controller (RSD: 8.0%) with respect to flow rate, while allowing for longer durations of sampling.
PubMed: 38924715
DOI: 10.1080/15459624.2024.2345150