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Journal of Muscle Research and Cell... Jun 2024Cholesterol is one of the major components of plasma membrane, where its distribution is nonhomogeneous and it participates in lipid raft formation. In skeletal muscle...
Cholesterol is one of the major components of plasma membrane, where its distribution is nonhomogeneous and it participates in lipid raft formation. In skeletal muscle cholesterol and lipid rafts seem to be important for excitation-contraction coupling and for neuromuscular transmission, involving cholesterol-rich synaptic vesicles. In the present study, nerve and muscle stimulation-evoked contractions were recorded to assess the role of cholesterol in contractile function of mouse diaphragm. Exposure to cholesterol oxidase (0.2 U/ml) and cholesterol-depleting agent methyl-β-cyclodextrin (1 mM) did not affect markedly contractile responses to both direct and indirect stimulation at low and high frequency. However, methyl-β-cyclodextrin at high concentration (10 mM) strongly decreased the force of both single and tetanus contractions induced by phrenic nerve stimulation. This decline in contractile function was more profoundly expressed when methyl-β-cyclodextrin application was combined with phrenic nerve activation. At the same time, 10 mM methyl-β-cyclodextrin had no effect on contractions upon direct muscle stimulation at low and high frequency. Thus, strong cholesterol depletion suppresses contractile function mainly due to disturbance of the neuromuscular communication, whereas muscle fiber contractility remains resistant to decline.
PubMed: 38904733
DOI: 10.1007/s10974-024-09675-7 -
BMC Pulmonary Medicine Jun 2024The diaphragm thickening fraction (DTF) may be a valuable tool for estimating respiratory effort in non-invasive ventilation. The primary aim of this physiological study...
INTRODUCTION
The diaphragm thickening fraction (DTF) may be a valuable tool for estimating respiratory effort in non-invasive ventilation. The primary aim of this physiological study is the investigation of the correlation of DTF with oesophageal pressure swings (ΔP). A secondary aim is to assess the discriminatory capacity of the index tests for different exercise loads.
METHODS
Healthy volunteers underwent spontaneous breathing and non-invasive ventilation with a sequence of different respirator settings. The first sequence was carried out at rest. The same sequence was repeated twice, with additional ergometry of 25 and 50 Watts, respectively. DTF and ΔP were measured during each ventilation configuration.
RESULTS
23 individuals agreed to participate. DTF was moderately correlated with ΔP (repeated measures correlation ρ = 0.410, p < 0.001). Both ΔP and DTF increased consistently with exercise loading in every ventilation configuration, however ΔP showed greater discriminatory capacity.
CONCLUSION
DTF was moderately correlated with ΔP and could discriminate reasonably between exercise loads in a small cohort of non-invasively ventilated healthy subjects. While it may not accurately reflect the absolute respiratory effort, DTF might help titrating individual non-invasive respiratory support. Further investigations are needed to test this hypothesis.
TRIAL REGISTRATION
This study was not prospectively registered.
Topics: Humans; Diaphragm; Male; Noninvasive Ventilation; Female; Adult; Healthy Volunteers; Esophagus; Pressure; Young Adult; Middle Aged; Exercise; Work of Breathing
PubMed: 38902702
DOI: 10.1186/s12890-024-03096-5 -
The Journal of International Medical... Jun 2024This study was performed to explore the predictive value of the diaphragmatic thickness fraction (DTF) combined with the integrated pulmonary index (IPI) for the...
OBJECTIVE
This study was performed to explore the predictive value of the diaphragmatic thickness fraction (DTF) combined with the integrated pulmonary index (IPI) for the extubation outcome in patients with severe acute pancreatitis (SAP).
METHODS
This prospective study involved 93 patients diagnosed with SAP and treated with mechanical ventilation in our hospital from October 2020 to September 2023. The patients were divided into a successful extubation group (61 patients) and an extubation failure group (32 patients) based on the extubation outcomes. The predictive value of the DTF, IPI, and their combination for extubation failure was analyzed.
RESULTS
The DTF and IPI were independent risk factors for extubation failure in patients with SAP undergoing mechanical ventilation. In addition, the combination of the DTF and IPI showed predictive value for extubation failure in these patients.
CONCLUSION
The DTF and IPI hold predictive value for extubation failure in patients with SAP undergoing mechanical ventilation, and their combined use may improve the predictive efficiency.
Topics: Humans; Male; Female; Middle Aged; Airway Extubation; Prospective Studies; Respiration, Artificial; Diaphragm; Adult; Pancreatitis; Predictive Value of Tests; Lung; Ventilator Weaning; Aged; Prognosis; Risk Factors; Severity of Illness Index
PubMed: 38902206
DOI: 10.1177/03000605241258172 -
Physiological Reports Jun 2024This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O [10 min] and 30% O [15 min]) affects exercise performance in mice. Three...
This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O [10 min] and 30% O [15 min]) affects exercise performance in mice. Three hours after the acute exposure, there was an observed increase in mRNA levels of phosphofructokinase (Bayes factor [BF] ≥ 10), mitochondrial transcription factor-A (BF ≥10), PPAR-α (BF ≥3), and PPAR-γ (BF ≥3) in the red gastrocnemius muscle (Gr). Four weeks of exercise training under intermittent (INT), but not continuous (HYP), hyperoxia significantly (BF ≥30) increased maximal exercise capacity compared to normoxic exercise-trained (ET) group. INT group exhibited significantly higher activity levels of 3-hydroxyacyl-CoA-dehydrogenase (HAD) in Gr (BF = 7.9) compared to ET group. Pyruvate dehydrogenase complex activity levels were significantly higher in INT group compared to ET group in white gastrocnemius, diaphragm, and left ventricle (BF ≥3). NT-PGC1α protein levels in Gr (BF = 7.7) and HAD activity levels in Gr (BF = 6.9) and soleus muscles (BF = 3.3) showed a significant positive correlation with maximal work values. These findings suggest that exercise training under intermittent hyperoxia is a beneficial strategy for enhancing endurance performance by improving fatty acid and pyruvic acid utilization.
Topics: Animals; Male; Muscle, Skeletal; Mice; Physical Conditioning, Animal; Physical Endurance; Mice, Inbred C57BL; Hyperoxia; PPAR alpha; PPAR gamma; Phosphofructokinases; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Transcription Factors; DNA-Binding Proteins; Mitochondrial Proteins
PubMed: 38898524
DOI: 10.14814/phy2.16117 -
Contraception Jun 2024Misperceptions about intrauterine devices (IUDs) may dissuade potential users and public beliefs are not well understood. We sought to describe public knowledge of...
OBJECTIVES
Misperceptions about intrauterine devices (IUDs) may dissuade potential users and public beliefs are not well understood. We sought to describe public knowledge of mechanism of action, failure rate, and IUD health risks. Secondary objectives included identifying inaccurate information and sources of information about IUDs.
STUDY DESIGN
We conducted a convenience-based survey of participants living in the United States 18 years and older using Amazon Mechanical Turk and ResearchMatch. We collected information on demographics, reproductive history, and IUD knowledge. We asked about IUD mechanism of action, failure rate, potential health risks, and information sources. We used multivariable logistic regression to test the association between gender and perceived lower (vs. higher) risks of IUDs.
RESULTS
We included 1,597 individuals with 726 (45.5%) self-reported men and 871 (54.5%) self-reported women. For both hormonal and non-hormonal IUDs, participants most often selected implantation prevention as the primary mechanism of action. In our sample, 55.5% of individuals believed the failure rate was greater than five percent. Weight gain, uterine perforation, and expulsion were cited as health risks likely to occur ≥ five percent of the time by 42.1%, 34.3%, and 38.4% of participants, respectively. Participants identified healthcare providers as their primary source of contraceptive information. Our multivariable logistic regression analysis revealed women had higher odds of perceiving IUDs as higher risk risk (aOR = 1.35, 95% CI 1.09 - 1.68) compared to men.
CONCLUSIONS
Individuals underestimated IUD effectiveness while overestimating perceived health risks. Our results highlight areas to target education about IUDs to support informed contraceptive decision-making.
IMPLICATIONS
Even among a largely educated sample, participants misunderstood IUD mechanism of action, underestimated efficacy, and overestimated failure rates and health risks. Providers should begin clinical counseling by assessing baseline knowledge, since mechanism of action, side effect profiles, and concepts like female anatomy should not be assumed to be known.
PubMed: 38897430
DOI: 10.1016/j.contraception.2024.110519 -
Respirology Case Reports Jun 2024Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a... (Clinical Trial)
Clinical Trial
BACKGROUND
Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a 'trial and error' basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE-3 study will evaluate bendopnoea as a screening test for effusion-related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism.
METHODS
PLEASE-3 is a multi-centre prospective study. Eligible patients are assessed at baseline (pre-drainage) and for patients undergoing drainage, up to 72 h post-procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants.
DISCUSSION
This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes.
TRIAL REGISTRATION
Australia New Zealand Clinical Trial Registry ACTRN12622000465752. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Registered on 24 March 2022. This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not-for-profit organisation. Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ [email protected] : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.
PubMed: 38894893
DOI: 10.1002/rcr2.1410 -
Cureus May 2024Bochdalek hernia is an inherited posterior lateral defect in the diaphragm that allows the abdominal organs to herniate into the thoracic cavity. In addition to being...
Bochdalek hernia is an inherited posterior lateral defect in the diaphragm that allows the abdominal organs to herniate into the thoracic cavity. In addition to being the most prevalent variety of congenital diaphragmatic hernia (CDH), it is also the type that is observed on the left hemithorax the majority of the time. Ectopic kidney is an uncommon condition, and the occurrence of ectopic intrathoracic kidney is even more uncommon, accounting for only a few of all the cases of renal ectopias. The occurrence of intrathoracic kidney associated with Bochdalek hernia is infrequent among adult individuals and is typically an incidental finding. A 52-year-old obese female patient presented to the pulmonology outpatient unit and reported experiencing the symptoms of coughing, wheezing, and difficulty in breathing since three years. A chest radiograph revealed an elevated dome of the diaphragm on the right side. A computed tomography (CT) of the chest revealed a defect in the posterior aspect of the right hemi-diaphragm with herniation of the right kidney and retroperitoneal fat into the right hemi-thorax. CT urography showed normal size and enhancement of the intrathoracic kidney with prompt excretion of contrast into the pelvicalyceal system. With regard to the small size of the hernia and considering the absence of complications on CT urography, a conservative treatment was proposed to the patient. The patient was followed up every year. There was no occurrence of renal complications during the follow-up period. When evaluating patients with 'elevated hemi-diaphragm' or thoracic 'mass', it is essential to check for the presence of intrathoracic kidney to avoid undesirable surgical procedures and image-guided biopsies.
PubMed: 38894760
DOI: 10.7759/cureus.60598 -
Sensors (Basel, Switzerland) May 2024This study presents a comprehensive investigation into the design and optimization of capacitive pressure sensors (CPSs) for their integration into capacitive touch...
This study presents a comprehensive investigation into the design and optimization of capacitive pressure sensors (CPSs) for their integration into capacitive touch buttons in electronic applications. Using the Finite Element Method (FEM), various geometries of dielectric layers were meticulously modeled and analyzed for their capacitive and sensitivity parameters. The flexible elastomer polydimethylsiloxane (PDMS) is used as a diaphragm, and polyvinylidene fluoride (PVDF) is a flexible material that acts as a dielectric medium. The Design of Experiment (DoE) techniques, aided by statistical analysis, were employed to identify the optimal geometric shapes of the CPS model. From the prediction using the DoE approach, it is observed that the cylindrical-shaped dielectric medium has better sensitivity. Using this optimal configuration, the CPS was further examined across a range of dielectric layer thicknesses to determine the capacitance, stored electrical energy, displacement, and stress levels at uniform pressures ranging from 0 to 200 kPa. Employing a 0.1 mm dielectric layer thickness yields heightened sensitivity and capacitance values, which is consistent with theoretical efforts. At a pressure of 200 kPa, the sensor achieves a maximum capacitance of 33.3 pF, with a total stored electric energy of 15.9 × 10 J and 0.468 pF/Pa of sensitivity for 0.1 dielectric thickness. These findings underscore the efficacy of the proposed CPS model for integration into capacitive touch buttons in electronic devices and e-skin applications, thereby offering promising advancements in sensor technology.
PubMed: 38894295
DOI: 10.3390/s24113504 -
Journal of Clinical Medicine May 2024Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients...
Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients present a bulbar onset, while 70% have a spinal outbreak. Respiratory involvement represents one of the worst prognostic factors, and its early identification is fundamental for the early starting of non-invasive ventilation and for the stratification of patients. Due to the lack of biomarkers of early respiratory impairment, we aimed to evaluate the role of chest dynamic MRI in ALS patients. We enrolled 15 ALS patients and 11 healthy controls. We assessed the revised ALS functional rating scale, spirometry, and chest dynamic MRI. Data were analyzed by using the Mann-Whitney U test and Cox regression analysis. We observed a statistically significant difference in both respiratory parameters and pulmonary measurements at MRI between ALS patients and healthy controls. Moreover, we found a close relationship between pulmonary measurements at MRI and respiratory parameters, which was statistically significant after multivariate analysis. A sub-group analysis including ALS patients without respiratory symptoms and with normal spirometry values revealed the superiority of chest dynamic MRI measurements in detecting signs of early respiratory impairment. Our data suggest the usefulness of chest dynamic MRI, a fast and economically affordable examination, in the evaluation of early respiratory impairment in ALS patients.
PubMed: 38892814
DOI: 10.3390/jcm13113103 -
International Journal of Molecular... May 2024The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD...
The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.
Topics: Humans; Nephrosis, Lipoid; Proteomics; Podocytes; Kidney Glomerulus; Male; Female; Adult; Proteome; Laser Capture Microdissection; Middle Aged
PubMed: 38891801
DOI: 10.3390/ijms25115613