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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.
CONCLUSIONS
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 -
Tomography (Ann Arbor, Mich.) Jun 2024The aim of the present study was to determine the gender respiratory differences of bilateral diaphragm thickness, respiratory pressures, and pulmonary function in...
The aim of the present study was to determine the gender respiratory differences of bilateral diaphragm thickness, respiratory pressures, and pulmonary function in patients with low back pain (LBP). A sample of 90 participants with nonspecific LBP was recruited and matched paired by sex (45 women and 45 men). Respiratory outcomes included bilateral diaphragm thickness by ultrasonography, respiratory muscle strength by maximum inspiratory (MIP) and expiratory (MEP) pressures, and pulmonary function by forced expiratory volume during 1 s (FEV), forced vital capacity (FVC) and FEV/FVC spirometry parameters. The comparison of respiratory outcomes presented significant differences ( < 0.001), with a large effect size ( = 1.26-1.58) showing means differences (95% CI) for MIP of -32.26 (-42.99, -21.53) cm HO, MEP of -50.66 (-64.08, -37.25) cm HO, FEV of -0.92 (-1.18, -0.65) L, and FVC of -1.00 (-1.32, -0.69) L, with lower values for females versus males. Gender-based respiratory differences were presented for maximum respiratory pressures and pulmonary function in patients with nonspecific LBP. Women presented greater inspiratory and expiratory muscle weakness as well as worse lung function, although these differences were not linked to diaphragm thickness during normal breathing.
Topics: Humans; Male; Female; Diaphragm; Low Back Pain; Ultrasonography; Adult; Middle Aged; Sex Factors; Respiratory Function Tests; Lung; Spirometry; Muscle Strength; Vital Capacity; Forced Expiratory Volume
PubMed: 38921944
DOI: 10.3390/tomography10060067 -
Geriatrics (Basel, Switzerland) May 2024Diaphragm muscle dysfunction is increasingly recognized as a fundamental marker of several age-related diseases and conditions including chronic obstructive pulmonary... (Review)
Review
Diaphragm muscle dysfunction is increasingly recognized as a fundamental marker of several age-related diseases and conditions including chronic obstructive pulmonary disease, heart failure and critical illness with respiratory failure. In older individuals with physical frailty and sarcopenia, the loss of muscle mass and function may also involve the diaphragm, contributing to respiratory dysfunction. Ultrasound has recently emerged as a feasible and reliable strategy to visualize diaphragm structure and function. In particular, it can help to predict the timing of extubation in patients undergoing mechanical ventilation in intensive care units (ICUs). Ultrasonographic evaluation of diaphragmatic function is relatively cheap, safe and quick and can provide useful information for real-time monitoring of respiratory function. In this review, we aim to present the current state of scientific evidence on the usefulness of ultrasound in the assessment of diaphragm dysfunction in different clinical settings, with a particular focus on older patients. We highlight the importance of the qualitative information gathered by ultrasound to assess the integrity, excursion, thickness and thickening of the diaphragm. The implementation of bedside diaphragm ultrasound could be useful for improving the quality and appropriateness of care, especially in older subjects with sarcopenia who experience acute respiratory failure, not only in the ICU setting.
PubMed: 38920426
DOI: 10.3390/geriatrics9030070 -
Journal of Anaesthesiology, Clinical... 2024The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in...
The efficacy of ultrasound-guided upper thoracic erector spinae plane block for postoperative analgesia in proximal shoulder surgery and its effect on phrenic nerve function: A prospective exploratory study.
BACKGROUND AND AIMS
The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same.
MATERIAL AND METHODS
Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h.
RESULTS
A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 μg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14).
CONCLUSION
The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread.
PubMed: 38919449
DOI: 10.4103/joacp.joacp_434_22 -
Cureus May 2024Industrial accidents involving compressed air can lead to significant colonic injuries, ranging from minor tears to complete perforations. This study investigates a case...
Industrial accidents involving compressed air can lead to significant colonic injuries, ranging from minor tears to complete perforations. This study investigates a case of colonic barotrauma in a 40-year-old male oil refinery worker who suffered symptoms of lower abdominal discomfort, distension, and tenderness following the application of compressed air to his anus. Diagnostic tests, including blood count, abdominal X-ray, and ultrasonography, indicated fecal impaction, dilated bowel loops, and free gas under the diaphragm. An exploratory laparotomy revealed a 4 cm x 2 cm hole in the colon at the hepatic flexure. There were also small breaks in the mucosa at the junction of the recto-sigmoid. We surgically repaired the perforation with primary closure, metrogyl lavage, and the placement of an intra-abdominal pelvic drain. Two weeks later, the patient recovered without any complications and was discharged. This case report highlights the severe risks of non-medical compressed air exposure, as well as the critical need for immediate surgical intervention and preventive safety measures in industrial settings.
PubMed: 38919243
DOI: 10.7759/cureus.61096