Search Results (73)

Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by an array of mutations in the dystrophin gene, with the most commonly mutated regions being exons 48–55. One of the several existing approaches to treat DMD is gene therapy, based on alternative splicing and mutant exon skipping. Testing of such therapy requires animal models that carry mutations homologous to those found in human patients. Here, we report the generation of two genetically modified mouse lines, named “insT” and “insG”, with distinct mutations at the same position in exon 51 that lead to a frameshift, presumably causing protein truncation. Hemizygous males of both lines exhibit classical signs of muscular dystrophy in all muscle tissues except for the cardiac tissue. However, pathological changes are more pronounced in one of the lines. Membrane localization of the protein is reduced to the point of absence in one of the lines. Moreover, an increase in full-length isoform mRNA was detected in diaphragms of insG line mice. Although further work is needed to qualify these mutations as sole origins of dissimilarity, both genetically modified mouse lines are suitable models of DMD and can be used to test gene therapy based on alternative splicing. Full article

Aging disrupts multiple homeostatic processes, including autophagy, a cellular process for the recycling and degradation of defective cytoplasmic structures. Acute treatment with the autophagy inhibitor chloroquine blunts the maximal forces generated by the diaphragm muscle, but the mechanisms underlying neuromuscular dysfunction in old age remain poorly understood. We hypothesized that chloroquine treatment increases the presynaptic retention of the styryl dye FM 4-64 following high-frequency nerve stimulation, consistent with the accumulation of unprocessed bulk endosomes. Diaphragm-phrenic nerve preparations from 24-month-old male and female C57BL/6 × 129 J mice were incubated with FM 4-64 (5 µM) and either chloroquine (50 µM) or vehicle during 80 Hz phrenic nerve stimulation. Acute chloroquine treatment significantly decreased FM 4-64 intensity at diaphragm neuromuscular junctions following 80 Hz phrenic nerve stimulation, consistent with disrupted synaptic vesicle recycling. A similar reduction was evident in regions with the greatest FM 4-64 fluorescence intensity, which most likely surround synaptic vesicle release sites. In the absence of nerve stimulation, chloroquine treatment significantly increased FM 4-64 intensity at diaphragm neuromuscular junctions. These findings highlight the importance of autophagy in regulating presynaptic vesicle retrieval (including vesicle recycling and endosomal processing) and support the role of autophagy impairments in age-related neuromuscular dysfunction. Full article

The stress status of a soil pressure cell placed in soil is very different from its stress state in a uniform fluid medium. The use of the calibration coefficient provided by the soil pressure cell manufacturer will produce a large error. In order to improve the measurement accuracy of the interface-type earth pressure cell placed in soil, this paper focuses on a single-membrane resistive earth pressure cell installed on the surface of a structure, analyzing the influence of loading and unloading cycles, the thickness and particle size of the sand filling, and the depth of the earth pressure cell inserted in the structure on the calibration curve and matching error, which were analyzed through calibration tests. The results show that when the sand filling thickness is less than D (D is the diameter of the earth pressure cell), the calibration curve is unstable in relation to the increase in the number of loading and unloading cycles, which will cause the sand calibration coefficient used for stress conversion to not be used normally. When the sand filling thickness in the calibration bucket increases from 0.285D to 5D, the absolute value of the matching error first decreases and then increases, such that the optimal sand filling thickness is 3D. The output of the earth pressure cell increases with the decrease in sand particle size under the same load, and there is a significant difference between the theoretical calculation value and the experimental value of the matching error; aiming at this difference, an empirical formula is derived to reflect the ratio of the diameter of the induction diaphragm of the earth pressure cell to the maximum particle size of the sand filling. When the depth of the earth pressure cell inserted in the structure is “0”, the sensing surface is flush with the structure and the absolute value of the matching error is the smallest. Changes in the horizontal placement of the soil pressure cell in the calibration bucket result in significant differences in both the output and hysteresis of the calibration curve. To improve the measurement accuracy of soil pressure cells in scaled tests for applications such as in the retaining walls of excavation pits, tunnel outer surfaces, pile tops, pile ends, and soil pressure measurements in soil, calibration of the soil pressure cells is required before testing. Due to the considerable difference in the stress states of the soil pressure cell between granular media and uniform fluid media, calibration in soil is essential. During in-soil calibration, factors such as cyclic loading and unloading, soil compression, sand thickness and particle size, and the placement of the soil pressure cell all affect the calibration results. This paper primarily investigates the influence of these factors on the calibration curve and matching error. This study found that, as the sand thickness increases, the matching error decreases initially and then increases. Full article

Wearable sensor devices have found a great deal of application in medicine on account of their small size and high sensitivity, and flexible elastomer materials are essential for their practical use. In this study we undertake CAD-assisted design of a capacitive pressure sensor (CPS) using COMSOL-Multiphysics software (6.0) to investigate its medical capabilities. The CPS was constructed in the shape of a cylinder, where the dielectric layer consists of air sandwiched between a polysilicon base and polydimethylsiloxane (PDMS) membrane. Simulations show that the CPS has a capacitance of 1.28 pF and stores 0.644 pJ of energy under an electric field of 1 kPa. The pressure sensitivity of the CSP diminished with an increase in the forward pressure, indicating that there is a non-linear dependence of pressure on the capacitance. This nonlinearity was most pronounced at lower pressures, where for small changes in pressure, the capacitance changed more significantly in correlation due to minor changes to the diaphragm. Higher pressure, however, prevented differentiation due to the large amount of diaphragm bending and changes in the properties of the materials. Dielectric capacitance grew widely in respect to applied pressure, with a low capacitance growth rate exhibited under high steady-state pressure. As expected, the stored energy was directly proportional to the pressure increase, reflecting the characteristic quadratic dependence of a capacitor on pressure. Temperature differences from 22 to 40 °C were also logged. However, the change in the dielectric constant of air remained minimal and it was noted that a 10 °C rise in temperature caused a much greater capacitance increase of about 53.28% and an energy increase of about 52.38%. Validation of the numerical approach with respect to its analytical results showed high accuracy with a margin of error less than one percent, thus proving the model’s reliability and usefulness in forecasting CPS performance under different conditions. The results of the simulations are encouraging for the further development of the CPS as it may be effectively integrated into the architecture of wearable devices for medical purposes, enhancing patient care and diagnostic processes. Full article

γ-Aminobutyric acid (GABA) has a significant impact on the functioning of not only the central but also the peripheral part of the nervous system. Recently, various elements of the GABAergic signaling system have been discovered in the area of the neuromuscular junction of mammals. At the same time, the functional activity of membrane-bound GABA transporters (GATs) and their role in neuromuscular transmission have not been identified. In the present study, performed on a neuromuscular preparation of the mouse diaphragm, the effect of GABA transporter inhibitors (nipecotic acid and β-alanine) on the force of muscle contraction was assessed. It was found that in the presence of both compounds in the bathing solution, the force of contractions caused by stimulation of the motor nerve dropped by 30–50%. However, when the muscle was stimulated directly, no effect of GABA transporter inhibitors on the contractile force was observed. The depressant effect of β-alanine induced by nerve stimulation was completely abolished by the GABA_B receptor blocker CGP 55845. GABA transporters were detected at the neuromuscular junction using immunohistochemistry. Thus, our results indicate that GABA transporters are localized in the area of the neuromuscular junction, and their activity affects the muscle contraction force. This influence is most likely due to the removal of GABA released during nerve stimulation and activating GABA receptors, which leads to a decrease in the contraction force of the striated muscles. Full article

Objectives: This study aimed to describe the outcomes of a staged procedure combining Descemet membrane endothelial keratoplasty (DMEK) and sutureless scleral fixation (SSF) of a one-piece intraocular lens (IOL) in a case series. Co-performing endothelial keratoplasty (EK) and SSF is associated with intraoperative and postoperative complications such as graft deployment difficulties, air migration, graft detachment, and IOL opacification or tilt, all of which are evaluated in this study. Methods: This is a retrospective observational case series. Clinical data were collected from eight eyes of eight patients who underwent DMEK for endothelial failure and had previously received an SSF with one-piece IOL following complete vitrectomy. During DMEK surgery, an air leak test was conducted to check for air migration into the posterior chamber. If instability was detected, pupilloplasty was performed. Intraoperative and postoperative data, including DMEK graft unfolding time, were collected. Corrected Distance Visual Acuity (CDVA), refraction, endothelial cell density (ECD), central corneal thickness (CCT), intraocular pressure (IOP), and complications were recorded over a 12-month follow-up period. Results: We performed pupilloplasty in four patients (50%). The median CDVA improved from preoperative 0.85 logMAR (range: 0.60 to 1.00) at baseline to 0.18 logMAR (range: 0.10 to 0.70, p = 0.012) at 12 months. The median refraction value changed significantly from −1.00 to −0.50 at 12 months. The median percentage reduction in ECD after 12 months was 33.4% (range 30 to 40). The median baseline CCT was 689 μm (range: 651 to 701) at baseline visit and 541.5 μm (range: 525 to 591, p = 0.008) at 12 months. The median IOP was reduced significantly during follow-up. The median graft unfolding time was 6 min (5 to 9). One patient required rebubbling for partial detachment on postoperative day one. No complications occurred within 12 months. Conclusions: The effective compartmentalization of the anterior and posterior chambers in vitrectomized eyes with an SSF one-piece IOL and pupilloplasty can facilitate critical steps of DMEK surgery in complex eyes. Additionally, the air leak test could prove useful in identifying the need for iris-lens diaphragm reconstruction. Full article

In nephrotic syndrome, the podocyte filtration structures are damaged in a process called foot process effacement. This is mediated by the actin cytoskeleton; however, which actins are involved and how they interact with other filtration components, like the basement membrane, remains poorly understood. Here, we used the well-established Drosophila pericardial nephrocyte—the equivalent of podocytes in flies—knockdown models (RNAi) to study the interplay of the actin cytoskeleton (Act5C, Act57B, Act42A, and Act87E), alpha- and beta-integrin (basement membrane), and the slit diaphragm (Sns and Pyd). Knockdown of an actin gene led to variations of formation of actin stress fibers, the internalization of Sns, and a disrupted slit diaphragm cortical pattern. Notably, deficiency of Act5C, which resulted in complete absence of nephrocytes, could be partially mitigated by overexpressing Act42A or Act87E, suggesting at least partial functional redundancy. Integrin localized near the actin cytoskeleton as well as slit diaphragm components, but when the nephrocyte cytoskeleton or slit diaphragm was disrupted, this switched to colocalization, both at the surface and internalized in aggregates. Altogether, the data show that the interdependence of the slit diaphragm, actin cytoskeleton, and integrins is key to the structure and function of the Drosophila nephrocyte. Full article

Podocyte health is vital for maintaining proper glomerular filtration in the kidney. Interdigitating foot processes from podocytes form slit diaphragms which regulate the filtration of molecules through size and charge selectivity. The abundance of lipid rafts, which are ordered membrane domains rich in cholesterol and sphingolipids, near the slit diaphragm highlights the importance of lipid metabolism in podocyte health. Emerging research shows the importance of sphingolipid metabolism to podocyte health through structural and signaling roles. Dysregulation in sphingolipid metabolism has been shown to cause podocyte injury and drive glomerular disease progression. In this review, we discuss the structure and metabolism of sphingolipids, as well as their role in proper podocyte function and how alterations in sphingolipid metabolism contributes to podocyte injury and drives glomerular disease progression. Full article

Advanced respiratory monitoring encompasses a diverse range of mini- or noninvasive tools used to evaluate various aspects of respiratory function in patients experiencing acute respiratory failure, including those requiring extracorporeal membrane oxygenation (ECMO) support. Among these techniques, key modalities include esophageal pressure measurement (including derived pressures), lung and respiratory muscle ultrasounds, electrical impedance tomography, the monitoring of diaphragm electrical activity, and assessment of flow index. These tools play a critical role in assessing essential parameters such as lung recruitment and overdistention, lung aeration and morphology, ventilation/perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient–ventilator synchrony. In contrast to conventional methods, advanced respiratory monitoring offers a deeper understanding of pathological changes in lung aeration caused by underlying diseases. Moreover, it allows for meticulous tracking of responses to therapeutic interventions, aiding in the development of personalized respiratory support strategies aimed at preserving lung function and respiratory muscle integrity. The integration of advanced respiratory monitoring represents a significant advancement in the clinical management of acute respiratory failure. It serves as a cornerstone in scenarios where treatment strategies rely on tailored approaches, empowering clinicians to make informed decisions about intervention selection and adjustment. By enabling real-time assessment and modification of respiratory support, advanced monitoring not only optimizes care for patients with acute respiratory distress syndrome but also contributes to improved outcomes and enhanced patient safety. Full article

In this paper, we present a novel three-dimensional (3D) coupled configuration of piezoelectric micromachined ultrasound transducers (pMUTs) by combing a curved and an annular diaphragm for transmit performance optimization in biomedical applications. An analytical equivalent circuit model (EQC) is developed with varied excitation methods to incorporate the acoustic–structure coupling of the curved and annular diaphragm-coupled pMUTs (CAC-pMUTs). The model-derived results align well with the reference simulated by the finite element method (FEM). Using this EQC model, we optimize the key design parameters of the CAC-pMUTs in order to improve the output sound pressure, including the width of the annular membrane, the thickness of the passive layer, and the phase difference of the driving voltage. In the anti-phase mode, the designed CAC-pMUTs demonstrate a transmit efficiency 285 times higher than that of single annular pMUTs. This substantial improvement underscores the potential of CAC-pMUTs for large array applications. Full article

This work presents a simple method to extract the piezoelectric coefficient $d_{31}$ based on analytical model fitting. A theoretical circuit model is developed for a piezoelectric circular membrane actuator based on PZT thin film. The circular diaphragm consists of a 12 µm silicon layer, an 800 nm thick PZT layer, and a 200 nm Ti/Pt layer, featuring a single 50% inner top electrode coverage. The proposed model is validated by the finite element method with a 2D axisymmetric model of a PZT piezoelectric membrane. Further, piezoelectric coefficient $d_{31}$ is extracted by fitting the Laser Doppler Vibrometer (LDV) experimental result with the analytical model. Full article

This study presents a new design for a MEMS electrostatic speaker array with out-of-plane piston-like diaphragm displacement using a simplified silicon-on-insulator microfabrication process. The device comprises an array of parallel actuating membranes with small circular mechanically open but acoustically sealed apertures that enable controlled etching of the buried oxide to be released directly from the front side, but retain a high acoustic impedance acting as a flat membrane. This approach simplifies the microfabrication process, requiring only two lithography masks and increasing process tolerances. Preliminary experimental measurements validate the concept and demonstrate the electromechanical and acoustic performance compared with theoretical models. Full article

Background: Congenital diaphragmatic hernia (CDH) repair can be challenging, particularly when a larger defect is present. Barbed sutures prevent the suture from slipping back after approximation of the tissues. Although introduced almost 2 decades ago, barbed sutures have not been widely used for CDH repair. We report our initial experience and pitfalls. Methods: All patients presenting with CDH from 2021 onward underwent repair using barbed sutures. Demographics, operative parameters, complications, and outcomes were prospectively recorded. Results: A total of 13 patients underwent CDH repair during the study interval (median age 6 days, range 3 days to 5.75 years). Median operative time was 89 min (range 46 to 288 min). Five thoracoscopic and eight open procedures were performed. Severe pulmonary hypertension and ECMO (extracorporeal membrane oxygenation) were considered contraindications for thoracoscopic repair. The included patients were compared to a historic controlled group performed without barbed sutures. The barbed suture facilitated easy and quick closure of the defects in most cases and obviated the need for knot tying. One patient in the thoracoscopic group had a patch placed due to high tension after the barbed sutures tore the diaphragm. At a median follow-up time of 15 months (range 2 to 34 months), one patient had died, and one patient with complete diaphragmatic agenesis was home-ventilated. There were no recurrences. Median operative time trended lower (89 min) than in the historic control group repaired without barbed sutures (119 min, p < 0.06) after eliminating outliers with large, complex patch repairs. Conclusions: Barbed sutures simplify congenital diaphragmatic hernia repair regardless of whether a minimal-invasive or open approach is performed. Patch repair is not a contraindication for using barbed sutures. The resulting potential time savings make them particularly useful in patients with cardiac or other severe co-morbidities in which shorter operative times are essential. In cases with high tension, though, the barbs may tear through and produce a “saw” effect on the tissue with subsequent damage. Full article

With the continuous improvement in human awareness of environmental protection, energy savings, and emission reduction, as well as the vigorous development of precision machinery and process technology, energy-saving and efficient diaphragm pumps have become a hot research topic at home and abroad. The diaphragm pump is a membrane-isolated reciprocating transport pump that isolates the transport medium from the piston through the diaphragm and can be used to transport high-viscosity, volatile, and corrosive media, and the symmetrical structure can make it easier for the diaphragm pump to achieve stable operation, reduce vibration and noise, and extend the life of the pump. This paper summarizes the development and research status of diaphragm pumps in recent years, including diaphragm pump structure, working principle, category, cavitation research, wear research, fault diagnosis research, vibration and noise research, fluid–solid-interaction research, and optimum research on one-way valves and diaphragms. It also puts forward some reasonable and novel viewpoints, such as applying the theory of entropy production to explore the motion mechanism of diaphragm pumps, optimizing the performance of diaphragm pumps, using new technologies to study new materials for diaphragm pumps, and designing diaphragm protection devices. This review provides valuable references and suggestions for the future development and research of diaphragm pumps. Full article

For rubber-like materials, there are three popular methods of equibiaxial tension available: inflation tension, equibiaxial planar tension, and radial tension. However, no studies have addressed the accuracy and comparability of these tests. In this work, we model the tension tests for a hyperelastic electroactive polymer (EAP) membrane material using finite element method (FEM) and investigate their experimental accuracy. This study also analyzes the impact of apparatus structure parameters and specimen dimensions on experimental performances. Additionally, a tensile efficiency is proposed to assess non-uniform deformation in equibiaxial planar tension and radial tension tests. The sample points for calculating deformation in inflation tensions should be taken near the top of the inflated balloon to obtain a more accurate characteristic curve; the deformation simulation range will be constrained by the material model and its parameters within a specific limit (λ ≈ 1.9); if the inflation hole size is halved, the required air pressure must be doubled to maintain equivalent stress and strain values, resulting in a reduction in half in inflation height and decreased accuracy. The equibiaxial planar tension test can enhance uniform deformation and reduce stress errors to as low as 2.1% (at λ = 4) with single-corner-point tension. For circular diaphragm specimens in radial tension tests, increasing the number of cuts and using larger punched holes results in more uniform deformation and less stress error, with a minimum value of 3.83% achieved for a specimen with 24 cuts and a 5 mm punched hole. In terms of tensile efficiency, increasing the number of tensile points in the equibiaxial planar tension test can improve it; under radial tension, increasing the number of cuts and decreasing the diameter of the punched hole on the specimen has a hedging effect. The findings of this study are valuable for accurately evaluating various equibiaxial tension methods and analyzing their precision, as well as providing sound guidance for the effective design of testing apparatus and test plans. Full article