Abnormal Muscle Research Articles

Transvenous phrenic nerve stimulation reduces diaphragm injury during controlled mechanical ventilation in a preclinical model of ARDS.

Patients with acute respiratory distress syndrome (ARDS) require periods of deep sedation and mechanical ventilation, leading to diaphragm dysfunction. Our study seeks to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) and mechanical ventilation changes the degree of diaphragm injury and cytokines concentration in a preclinical ARDS model. Moderate ARDS was induced in pigs using oleic acid, followed by ventilation for 12 h post-injury with volume-control at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH2O, respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV + TTDN50%, n = 6) or every breath (MV + TTDN100%, n = 6). One group received ventilation only (MV, n = 6). Full-thickness diaphragm and quadricep muscle biopsies were taken at study end. Samples were fixed and stained with hematoxylin and eosin and a point-counting technique was applied to calculate abnormal muscle area fraction. Cytokine concentrations were measured in homogenized tissue using porcine-specific enzyme-linked immunosorbent assay (ELISA) and compared with serum samples. Percentage of abnormal diaphragm tissue was different between MV [8.1% (6.0-8.8)] versus MV + TTDN50% [3.4% (2.1-4.8)], P = 0.010 and MV versus MV + TTDN100% [3.1% (2.5-4.0)], P = 0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups (P < 0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant (P = 0.025). TTDN, delivered in synchrony with mechanical ventilation, mitigated diaphragm injury, as evidenced by less abnormal tissue in the diaphragm samples, in pigs with oleic acid-induced ARDS and is an exciting tool for lung and diaphragm-protective ventilation.NEW & NOTEWORTHY This study adds to our understanding of applying transvenous diaphragm neurostimulation synchronously with mechanical ventilation by examining its effects on diaphragm muscle injury and cytokine concentration patterns in pigs with acute respiratory distress syndrome (ARDS). We observed that using this therapy for 12 h post lung injury mitigated ventilator-induced diaphragm injury and changed the pattern of cytokine concentration measured in diaphragm tissue. These findings suggest that transvenous diaphragm neurostimulation is an exciting tool for lung and diaphragm protective ventilation.

Case report: Two cases of Cleft rhinoplasty

The correction of cleft lip nose deformity remains a great challenge for any cleft surgeon. The nose is a prominent part of the face, and any cleft lip repair directs the beholders’ eyes from the deformed lip to the deformed nose, Controversies exist on the timing of rhinoplasty in cleft lip patients and is categorized as primary rhinoplasty performed at the time of cleft lip repair, intermediate rhinoplasty at the age of 5–11 years and definitive rhinoplasty. This article presents two cases of unilateral nasal cleft in two adults treated by secondary rhinoplasty using an open technique. The primary deformity is an imbalance between abnormal muscle insertion and maxillary skeletal hypoplasia. The general characteristics of this deformity are a very short columella, downward rotation of the tip and diminished nasal projection, and treatment of this depressed and hypoplastic bony scaffolding is the secret to successful secondary rhinoplasty. Proponents of delayed nasal repair suggest that altering the cartilages in early nasal repair at the time of lip repair would complicate future corrective nasal surgeries if the primary repair would prove unsatisfactory. However, we know that repositioning the wing cartilage at the same time as closing the lip respects nasal growth by using a rigorous technique and control of scars The aim of cleft lip rhinoplasty is both aesthetic and functional: to obtain a normal nose with nasal breathing.

Relationship between epicardial adipose tissue and ventricular fibrillation in Brugada syndrome by cardiac computed tomography analysis

Abstract Background Fibrofatty changes in the myocardium of the right ventricular (RV) to right ventricular outflow tract (RVOT) in patients with Brugada syndrome (BrS) may contribute to ventricular conduction delay and ultimately in the development of ventricular fibrillation (VF). In patients with atrial fibrillation (AF), inflammatory infiltration of epicardial adipose tissue (EAT) into the atrial muscle, along with reduced quantity and quality of EAT, has been demonstrated to be associated with the development of AF. We hypothesized that EAT in the RVOT from the RV in patients with BrS may lead to organic abnormalities in the ventricular muscle, resulting in VF. Purpose The purpose of this study was to evaluate the quantity and quality of EAT in patients with BrS using cardiac computed tomography (CT) and to determine the relationship with the occurrence of VF. Methods We retrospectively evaluated 61 of 82 patients with BrS regularly followed in our outpatient clinic from January 2000 to December 2023, who underwent cardiac CT scans. Patients were divided into two groups: those with VF events during follow-up (VF event group) and those without events (VF non-event group). Patient background, various parameters, volume of epicardial adipose tissue (EAT), and CT values from cardiac CT scans were compared between the two groups. EAT volume and CT values were measured for the entire heart and four specific regions: right ventricle (RV-EAT), right ventricular outflow tract (RVOT) to pulmonary artery bifurcation (RVOT-EAT), left ventricle (LV-EAT), and the left coronary artery main trunk circumference (LV summit-EAT) were measured for four specific sites. Results Median age at first diagnosis of BrS was 43 years, 98% were male patients, 41 patients (71%) had symptomatic BrS, and 18 patients (31%) had a family history. During a median follow-up of 72 months (30-136 months), 22 patients (38%) had VF events, including 2 arrhythmic sudden deaths. The median time from diagnosis to the first VF event was 14.3 months (4.3-24.5 months). The VF event group had more overall EAT volume (98.3 cm3 [range: 77.4 to 120.3 cm3] vs. 70.1 cm3 [range: 53.8 to 98.0 cm3], P=0.02) and significantly more RV-EAT volume (18.4 cm3 [range: 11.5 to 28.0 cm3] vs. 11.0 cm3 [range: 7.9 to 18.3 cm3], P=0.008). The CT value of RV-EAT was significantly lower in the VF event group (-83.1±6.1 vs -78.0±6.2, P=0.003), although the RV-EAT/LV-EAT density ratio was not different between the two groups (1.01±0.05 vs 0.99±0.07, P=0.14). On the other hand, the density ratio of RVOT-EAT/LV-EAT was significantly lower in the VF event group (0.95±0.08 vs. 1.00±0.08, P=0.03). Conclusions EAT analysis via CT in patients with BrS revealed that those experiencing VF events during follow-up tended to exhibit greater RV-EAT volume, lower CT values of RV-EAT, and higher CT values of RVOT-EAT density. These findings suggest EAT involvement in VF occurrence in patients with BrS.

Disorders in cytokine synthesis in women with uterine fibroids

In the structure of gynecological diseases, uterine fibroids occupy an “honorable” second place after inflammatory processes of the genital organs, and its share reaches 40%. Uterine fibroids are a benign monoclonal tumor that develops from one abnormal smooth muscle cell of the myometrium, which, as a result of mutation, has the ability to grow unregulated. Common symptoms of the disease include pelvic discomfort or pain, excessive uterine bleeding, secondary anemia, infertility, and bowel and bladder dysfunction. Uterine fibroids can negatively affect the general condition of a woman, causing hormonal, vegetative-vascular and psycho-emotional disorders. Moreover, about 80% of patients with uterine fibroids undergo radical surgical treatment. The mechanisms of development and growth of this benign tumor have not been fully established and remain controversial. The role of immune disorders in the pathogenesis of fibroids is currently being discussed. It has been proven that the growth of fibroids is accompanied by a weakening of immune defense against the background of an increase in the level of proinflammatory cytokines, which are regulators of the processes of proliferation and apoptosis, mediators of the action of sex steroids. The aim of the study was to study the level of some pro-inflammatory cytokines (IL-1β, IL-2, TGF-β2 and MCP-1) in the blood serum of women of reproductive age with uterine fibroids, depending on the size and nature of tumor growth. A comparative analysis of the results of examination of 123 women with uterine fibroids, who made up 2 groups: 1st group of 65 women with simple uterine fibroids and 2nd group of 58 women with rapidly growing uterine fibroids, is presented. The examination included a comprehensive clinical and laboratory study. The level of cytokines (IL-1β, IL- 2, TGF-β2, MCP-1) in the blood serum was assessed by ELISA. It was found that in patients of reproductive age with uterine fibroids, there is an increase in the levels of IL-1β, TGF-β2 and MCP-1. In women with rapidly growing uterine fibroids, these changes are more pronounced. The concentration of IL-2 is reduced in all women with uterine fibroids, regardless of the size and nature of tumor growth. It has been established that an increase in the size of myomatous nodes is accompanied by an increase in immune imbalance: there is an increase in the levels of pro-inflammatory cytokines (IL-1β, TGF-β2, MCP-1) against the background of a reduced content of the lymphokine IL-2, which we regard as possible links in the pathogenesis of uterine fibroids. A pronounced deficiency of IL-2 in the blood serum against the background of a sharp increase in the concentration of TGF-β2 and MCP-1 in the blood of women with uterine fibroids can be considered as a negative criterion for predicting disease progression and used as an additional prognostic marker of tumor growth

Body composition derangements in lung cancer patients treated with first-line pembrolizumab: A multicentre observational study.

While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC. A retrospective review of consecutive patients with treatment-naïve NSCLC and PD-L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre-treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre-established cut-offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival and overall survival (PFS and OS), compared through the log-rank test and the Cox proportional hazards model. Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69years (range 36-85), with a median follow-up of 12months (range 1-131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m2. Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co-morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46-12.6, P<0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22-2.83, P=0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P<0.0001 and 30.7% vs. 73.2%, P<0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co-morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60-4.66, P<0.0001; sarcopenia: aHR 2.24, 95% CI 1.37-3.67, P=0.001; IMAT depot: aHR 2.26, 95% 1.40-3.63, P=0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96-6.01, P<0.0001; sarcopenia: aHR 4.68, 95% CI 2.44-8.99, P<0.0001; IMAT depot: aHR 3.18, 95% 1.72-5.88, P<0.0001). Skeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers.

Ultrasound as a Complementary Tool to Electrodiagnostics in the Evaluation of Compressive Neuropathy of the Common Fibular Nerve

Background: Compressive neuropathy of the common fibular nerve (CFN) is increasingly recognized as an etiology for foot drop and falls. Electrodiagnostic (EDX) studies are widely used to evaluate this condition, but such tests are invasive and costly. As with carpal and cubital tunnel syndromes, there may be patients with characteristic symptoms of CFN compressive neuropathy but normal EDX studies in which ultrasound may aid in decision-making. Purpose: We sought to examine the association between ultrasound and nerve conduction studies (NCS) and electromyography (EMG) in the diagnosis of compressive neuropathy of the CFN. Methods: We performed a retrospective review identifying 104 patients who underwent CFN decompression from January 1, 2015, to June 30, 2023. Patients were included if they had both ultrasound and NCS/EMG prior to CFN decompression for compressive neuropathy and if they were older than 18 years at time of surgery. Patients were excluded if they had entrapment secondary to trauma, iatrogenic injury, or if they had had superficial fibular decompression alone without CFN decompression. After applying exclusion criteria, 17 patients remained in the cohort. Results: Mean ultrasound cross-sectional area and side-to-side (STS) ratios were significantly higher in those with abnormal compound muscle action potential (CMAP) amplitudes versus those with normal CMAP amplitudes. The probability of having an abnormal CMAP amplitude when STS ratio was abnormal was 18 times greater compared with those with normal STS ratio. With each unit increase in STS ratio, CMAP amplitude was reduced by 2.79 mV. Conclusions: This retrospective review found that ultrasound may provide complementary diagnostic information to EMG/NCS for compressive neuropathy of the CFN. Further study is needed to examine the relationship between ultrasound findings for CFN compressive neuropathy and results of surgical decompression.

Skeletal Muscle Energetics in Heart Failure Assessed Using 31P Magnetic Resonance Spectroscopy—A Systematic Review and Meta-Analysis

Introduction: Skeletal muscle (SkM) abnormalities are well-recognised in heart failure (HF). We aimed to systematically review studies of SkM energetics in patients with HF at rest and post-exercise using 31phosphorus magnetic resonance spectroscopy (31P MRS). Methods: A systematic search of cross-sectional studies used predefined search terms related to HF, SkM energetics, and 31P MRS (PROSPERO ID: CRD42023434698). Inclusion criteria for studies are as follows: 1. HF participants versus controls; and 2. SkM energetics assessed using 31P MRS reporting BOTH (i) PCr recovery time and (ii) PCr ratios (PCr/Pi and/or PCr/ATP). The primary outcome was SkM PCr recovery time following exercise, comparing patients with diagnosed HF and healthy controls and reported as standardised mean difference (SMD). Results: Of 465 identified studies, 6 met the inclusion criteria and were conducted from 1987 to 2021, comprising 162 participants (N = 86 HF, N = 76 healthy controls). HF patients (mean age 55.1 ± 4.16 years, 49 (56.9%) male) were reasonably matched to healthy controls (mean age 50 ± 8.9 years, 54 (71%) males). Two studies did not report patients’ ejection fractions (EF); the mean EF among patients from the remaining six studies was 24.8%. No studies specifically included participants with HFpEF and none characterised sarcopenia. HF patients exhibited impaired SkM energetics compared to healthy controls, which were characterised by a significantly increased PCr recovery time (SMD: −1.35, CI: −2.11, −0.59). Conclusions: PCr recovery is significantly impaired in patients with HFrEF. Females were under-represented, no HFpEF studies were identified, and no studies linking abnormal SkM energetics directly to sarcopenia were identified.

Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish.

Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, N-terminal acetylation, is catalyzed by NAA80 in humans. N-terminal acetylation of actin is crucial for maintaining normal cytoskeletal dynamics and cell motility in human cell lines. However, the physiological impact of actin N-terminal acetylation remains to be fully understood. We developed a zebrafish naa80 knockout model and demonstrated that Naa80 acetylates both muscle and non-muscle actins in vivo. Assays with purified Naa80 revealed a preference for acetylating actin N-termini. Zebrafish lacking actin N-terminal acetylation exhibited normal development, morphology, and behavior. In contrast, humans with pathogenic actin variants can present with hypotonia and hearing impairment. Whereas zebrafish lacking naa80 showed no obvious muscle defects or abnormalities, we observed abnormal inner ear development, small otoliths, and impaired response to sound. In conclusion, we have established that zebrafish Naa80 N-terminally acetylates actins in vitro and in vivo, and that actin N-terminal acetylation is essential for normal hearing.

The Role of Cystic Fibrosis Transmembrane Conductance Regulator in Skeletal Muscle Contractile Function

Purpose: Genetic mutations in cystic fibrosis (CF) result in CF transmembrane conductance regulator (CFTR) dysfunction. CFTR is expressed in human skeletal muscle; its effect on skeletal muscle abnormalities is unknown. The study objective is to investigate the role of CFTR in skeletal muscle contractile function. Methods: We conducted a prospective, cross-sectional study comparing 34 adults with minimal and 18 with residual function CFTR mutations, recruited from Toronto Adult CF Centre, St. Michael's Hospital, Unity Health Toronto. Quadriceps, biceps brachii, and handgrip strength was measured with dynamometers; leg muscle power with the stair climb power test. Quadriceps muscle contractility was determined by quadriceps muscle strength normalized to quadriceps muscle size, measured with ultrasound images. Multivariable regression was used for analysis. Results: People with residual function CFTR mutations had higher quadriceps muscle torque normalized to quadriceps layer thickness and to rectus femoris cross-sectional area by 27.5 Nm/cm [95% CI (2.2, 52.8) Nm/cm, P = .034] and 5.6 Nm/cm2 [95% CI (0.3, 10.9) Nm/cm2, P = .041], respectively, compared with those with minimal function CFTR mutations. There were no differences in quadriceps muscle torque (P = .58), leg muscle power (P = .47), biceps brachii muscle force (P = .14), or handgrip force (P = .12) between the 2 mutation groups. Conclusions: CFTR protein may play a role in muscle contractility, implying a limited capacity to exert muscle force per unit of muscle size in people with CF. This suggests that building a greater muscle mass through resistance exercises focusing on muscle hypertrophy in exercise prescription may improve muscle strength in people with CF.

9291 Hypothyroidism impairs skeletal muscle regeneration after injury

Abstract Disclosure: P. Aguiari: None. V. Villani: None. K.Y. Liu: None. G.A. Brent: None. L. Perin: None. A. Milanesi: None. Thyroid hormone (TH) signaling plays an essential role in muscle development and function, in the maintenance of muscle mass, and in regeneration after injury. Disruption of TH signaling results in an abnormal skeletal muscle phenotype, impaired regeneration, and sarcopenia with aging, reflecting the myopathic changes described in hypothyroid patients. Muscle stem cells (MuSCs) are the mediators of post-natal skeletal muscle plasticity. Normally quiescent, in response to injury they enter the cell cycle (myoblasts) and proliferate. Myoblasts then exit the cell cycle and differentiate into myocytes that will fuse with existing myofibers to restore tissue architecture and function. Via TH receptor alpha, TH regulates all the stages of the regeneration program and regulates the expression of multiple myogenic genes. Despite all this evidence, to date there are no studies investigating MuSCs behavior in response to injury during hypothyroidism. We characterized injury-induced regeneration of the tibialis anterior muscle (TAM) in euthyroid and hypothyroid mice, fed a low iodine + 0.15% propylthiouracil diet. To investigate the cell cycle dynamics of MuSCs, we generated Pax7-Fucci mice carrying the fluorescent ubiquitination-based cell-cycle indicator (Fucci) system under the Pax7 promoter. Muscle injury was induced via cardiotoxin injection in the TAM of 3-month-old Pax7-Fucci mice. Hypothyroid mice present signs of impaired regeneration compared to euthyroid mice. From histological analysis, at different time points, we observed smaller fiber diameters, myofibers with central nuclei, and a significantly reduced number of fast glycolytic type IIb fibers, the prevalent muscle fiber type in the TA muscle. ScRNAseq analysis shows that at a late phase of regeneration (14 days after injury) hypothyroid MuSCs and myoblasts are still in the activation state and overexpress genes related to DNA replication and cell proliferation, while genes related to myogenic differentiation and cell cycle exit are downregulated. Differentiated myocytes in the hypothyroid fibers present an immature phenotype and are characterized by overexpression of embryonic/temporary and slow myosin genes and downregulation of mature fast myosins. Cell cycle analysis of the Fucci signal through Flow Cytometry confirmed a higher number of activated hypothyroid MuSCs at 4, 7, and 28 days after injury. These cells accumulate in the S phase and are unable to exit the cell cycle and differentiate towards myocytes. These data demonstrate that hypothyroidism impairs muscle tissue regeneration halting MuSCs progression through the cell cycle, myoblast cell cycle exit, and fiber maturation. Investigating muscle stem cell behavior and response to injury during hypothyroidism is crucial to understanding the mechanism behind thyroid hormone-induced myopathies and identifying possible therapeutical targets. Presentation: 6/2/2024

8670 Hypothyroidism impairs skeletal muscle regeneration after injury

Abstract Disclosure: P. Aguiari: None. V. Villani: None. K.Y. Liu: None. G.A. Brent: None. L. Perin: None. A. Milanesi: None. Thyroid hormone (TH) signaling plays an essential role in muscle development and function, in the maintenance of muscle mass, and in regeneration after injury. Disruption of TH signaling results in an abnormal skeletal muscle phenotype, impaired regeneration, and sarcopenia with aging, reflecting the myopathic changes described in hypothyroid patients. Muscle stem cells (MuSCs) are the mediators of post-natal skeletal muscle plasticity. Normally quiescent, in response to injury they enter the cell cycle (myoblasts) and proliferate. Myoblasts then exit the cell cycle and differentiate into myocytes that will fuse with existing myofibers to restore tissue architecture and function. Via TH receptor alpha, TH regulates all the stages of the regeneration program and regulates the expression of multiple myogenic genes. Despite all this evidence, to date there are no studies investigating MuSCs behavior in response to injury during hypothyroidism. We characterized injury-induced regeneration of the tibialis anterior muscle (TAM) in euthyroid and hypothyroid mice, fed a low iodine + 0.15% propylthiouracil diet. To investigate the cell cycle dynamics of MuSCs, we generated Pax7-Fucci mice carrying the fluorescent ubiquitination-based cell-cycle indicator (Fucci) system under the Pax7 promoter. Muscle injury was induced via cardiotoxin injection in the TAM of 3-month-old Pax7-Fucci mice. Hypothyroid mice present signs of impaired regeneration compared to euthyroid mice. From histological analysis, at different time points, we observed smaller fiber diameters, myofibers with central nuclei, and a significantly reduced number of fast glycolytic type IIb fibers, the prevalent muscle fiber type in the TA muscle. ScRNAseq analysis shows that at a late phase of regeneration (14 days after injury) hypothyroid MuSCs and myoblasts are still in the activation state and overexpress genes related to DNA replication and cell proliferation, while genes related to myogenic differentiation and cell cycle exit are downregulated. Differentiated myocytes in the hypothyroid fibers present an immature phenotype and are characterized by overexpression of embryonic/temporary and slow myosin genes and downregulation of mature fast myosins. Cell cycle analysis of the Fucci signal through Flow Cytometry confirmed a higher number of activated hypothyroid MuSCs at 4, 7, and 28 days after injury. These cells accumulate in the S phase and are unable to exit the cell cycle and differentiate towards myocytes. These data demonstrate that hypothyroidism impairs muscle tissue regeneration halting MuSCs progression through the cell cycle, myoblast cell cycle exit, and fiber maturation. Investigating muscle stem cell behavior and response to injury during hypothyroidism is crucial to understanding the mechanism behind thyroid hormone-induced myopathies and identifying possible therapeutical targets. Presentation: 6/2/2024

Sustained relief with spinal cord stimulator despite anterior lead migration: a case report.

Lead migration is a common complication of spinal cord stimulation, although anterior migration is rare. While early studies suggested that anterior stimulation may produce analgesic effects, it is thought to be poorly tolerated due to abnormal paresthesia and muscle contractions due to its proximity to the corticospinal tract. This case report presents a unique case of sustained pain relief despite anterior lead migration, which suggests that anterior column stimulation may hold clinical significance for pain management. Further studies are needed to explore its analgesic mechanisms and potential therapeutic application. Strategies to prevent lead migration, particularly in the early postoperative period, are also crucial for optimizing outcomes.

The T-Type Calcium Channel CACNA1H is Required for Smooth Muscle Cytoskeletal Organization During Tracheal Tubulogenesis.

Abnormalities of tracheal smooth muscle (SM) formation are associated with several clinical disorders including tracheal stenosis and tracheomalacia. However, the cellular and molecular mechanisms underlying tracheal SM formation remain poorly understood. Here, it is shown that the T-type calcium channel CACNA1H is a novel regulator of tracheal SM formation and contraction. Cacna1h in an ethylnitrosourea forward genetic screen for regulators of respiratory disease using the mouse as a model is identified. Cacna1h mutants exhibit tracheal stenosis, disorganized SM and compromised tracheal contraction. CACNA1H is essential to maintain actin polymerization, which is required for tracheal SM organization and tube formation. This process appears to be partially mediated through activation of the actin regulator RhoA, as pharmacological increase of RhoA activity ameliorates the Cacna1h-mutant trachea phenotypes. Analysis of human tracheal tissues indicates that a decrease in CACNA1H protein levels is associated with congenital tracheostenosis. These results provide insight into the role for the T-type calcium channel in cytoskeletal organization and SM formation during tracheal tube formation and suggest novel targets for congenital tracheostenosis intervention.

Clinical analysis of abnormal muscle response monitoring for hemifacial spasm during microvascular decompression: a retrospective study.

Microvascular decompression (MVD) is a widely recognized therapeutic approach for the treatment of hemifacial spasm (HFS). Abnormal muscle response (AMR) is a distinctive electromyographic finding exclusively in patients with HFS. The purpose of our investigation was to determine the correlation between changes in intraoperative AMR and surgical efficacy, as well as the incidence of postoperative complications in patients with HFS after undergoing MVD. In this retrospective study, we evaluated 145 patients with HFSs treated with MVD, which was maintained for 1year postoperatively. The subjects were divided into two groups based on the persistence or disappearance of AMR. Continuous monitoring of AMR during surgery provided data on persistence. All patients were followed up 1day, 30days, and 1year after MVD. A range of potential predictive factors, such as patient demographics, symptom duration, and morphology and latency of AMR, were analyzed using binary logistic regression to assess their relationship with postoperative non-cure and delayed cure rates. The 1day postoperative cure rate was 77.9%, with a 1year postoperative cure rate of 94.59% and 1day postoperative relief rate of 87.6%. A marked distinction was noted between preoperative and 1year postoperative Cohen grades (P < 0.05). Moreover, 1day after surgery, the outcome demonstrated significant variability, as shown by the binary logistic regression model (χ2 = 62.913, P < 0.05). The results suggested that factors such as age, symptom duration, disappearance of AMR, and preoperative carbamazepine treatment markedly influence outcomes 1day after surgery. The binary logistic regression model for delayed cure at 1year showed significant variability (χ2 = 54.883, P < 0.05). Furthermore, analysis using generalized estimating equations revealed that the duration of postoperative follow-up significantly impacted Cohen grades, as did the disappearance of AMR, with the grade of AMR disappearance being only 10% of that of non-AMR disappearance (P < 0.05). Our findings suggest that MVD is an effective intervention for HFS. Our findings also indicate that factors such as patient age, duration of symptoms, disappearance of AMR, and preoperative carbamazepine therapy are significant predictors of 1day postoperative cure rate. Major predictors for delayed cure at 1year include age, symptom duration, AMR disappearance, preoperative carbamazepine and botulinum neurotoxin administration, single morphology AMR, and offending vertebral artery.

Quantitative MRI in children with Crohn's disease - where do we stand?

Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract, particularly the ileum and colon. This disease is characterized by recurrent bouts of intestinal inflammation with subsequent bowel wall damage, including scarring (i.e., fibrosis) and abnormal smooth muscle proliferation. MR enterography, an MRI examination tailored to assess the small bowel, is a first-line diagnostic tool for diagnosing CD in children, characterization and monitoring of disease severity and extent, and assessment of disease-related complications. To date, such MRI evaluations have been mostly qualitative, which can adversely impact diagnostic performance and inter-radiologist agreement. Quantitative MRI methods have been shown to aid in the evaluation of a variety of medical conditions and have been increasingly investigated in children and adults with CD. In CD, such objective techniques have been used to assist with diagnosis, assess treatment response, and characterize bowel wall histologic abnormalities. In the current work, we will review quantitative MRI methods for detecting and measuring intestinal active inflammation (MRI-based scoring systems, T1 relaxation mapping, diffusion-weighted imaging, intra-voxel incoherent motion, mesenteric phase contrast), bowel wall damage (magnetization transfer), and motility (quantitative cine imaging) in small bowel CD, with an emphasis on the pediatric population.

Modified Dautrey's Procedure for Recurrent Temporomandibular Joint Dislocation.

This study introduced and analyzed the clinical effects of a modified Dautrey's procedure, involving down-fracture of the zygomatic arch and articular tubercle augmentation, for the treatment of recurrent TMJ dislocation. Recurrent TMJ dislocation patients were treated using the modified Dautrey's procedure. The recurrence of joint dislocation, maximal mouth opening (MMO), and pain were evaluated postoperatively. A total of 7 patients were treated using the modified procedure, with no instances of facial nerve injury. No recurrences occurred during the follow-up period of 0.5 to 5 years. The average MMO was 35.4mm and 35.7mm before the operation and during follow-up, respectively. The modified Dautrey's procedure was effective and particularly suitable for elderly patients with abnormal muscle control, resulting in low recurrence.

Stress triggers irritable bowel syndrome with diarrhea through a spermidine-mediated decline in type I interferon.

Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.

Microwave cavity antenna for automatic detection of chicken breast muscles affected by wooden breast defect

Over the past years, artificial selection for meat-type (broiler) chickens has resulted in improved production efficiency, but also in an increased incidence of skeletal muscle abnormalities. In particular, wooden breast (WB) abnormality causes abrupt changes in meat quality and enormous economic losses. Thus, the poultry processing industry requires a reliable method to detect the abnormality in production lines in a non-destructive and contactless way. The present research aimed to evaluate the effect of WB on dielectric properties to develop a potential online technique to distinguish unaffected from affected breasts. Sixty-five pectoralis major muscles were picked 3 h post-mortem from the same flock (42-day-old broilers, 2.8 kg average live weight) and classified by visual inspection according to their phenotype as normal (N, not showing not any signs of the WB condition; n = 33) or WB (exhibiting extensive hardened areas and stiffness perceived by manual palpation throughout the entire fillet; n = 32). WB muscles exhibited remarkably higher values of dielectric constant and loss factor in a wide range of the explored frequencies (200 MHz–14 GHz), suggesting higher water mobility and a higher solvate capacity; this makes the electromagnetic technique for classification promising. Based on the above evidence, a rapid microwave electric technique in the range 1.5 GHz–3 GHz was developed for the online detection of WB. Indeed, combining the use of a cavity antenna (vector network analyzer instrumental chain with partial least square – discriminant analysis), this technique correctly classified 100% of the validation test set.

Multi-Regional Pelvic Floor Muscle Function Diagnosis System Based on Inflatable Stretchable Electrode Array.

Effective prevention and treatment of pelvic floor dysfunction (PFD) necessitates the identification of lesions within the complex pelvic floor muscle (PFM) groups associated with various symptoms. Here, we developed a multi-region pelvic floor muscle functional diagnosis system (MPDS) based on an inflatable stretchable electrode array, which aids in accurately locating areas related to PFD. Clinical diagnostic experiments were conducted on 56 patients with postpartum stress urinary incontinence (PSUI) and 73 postpartum asymptomatic controls. MPDS collects pelvic floor electromyography from all participants. By assessing EMG parameters such as activation time differences (ATD) and using Jensen-Shannon (JS) divergence to verify, with the aim of locating target muscle groups with functional abnormalities. Clinical test results showed that by observing the AT sequence of the PSUI group and the control group, muscle groups with functional abnormalities in the Pubococcygeus muscle (PC) and Puborectalis muscle (PR) regions could be preliminarily diagnosed. In the assessment of regional muscle contribution values based on JS divergence, it was verified that the contribution values of rapid contraction in the PC and PR regions of the PSUI group were relatively lower compared to those of the control group, which correlated with urinary control dysfunction. These experiments demonstrate that the MPDS helps in accurately locating target muscle groups with functional abnormalities, showcasing its potential in precise assessment of complex muscle groups such as PFM, which may improve diagnostic precision and reliability.

Can we differentiate patients with dysferlinopathies and inflammatory myopathies by ultrasound? A discriminant analysis study.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that are characterized by inflammation and muscle weakness. Dysferlinopathies are autosomal recessive limb-girdle muscular dystrophies caused by mutations in DYSF, which share a similar clinical presentation and histopathological inflammatory changes. To determine the sonographic differences between dysferlinopathies and IIM and whether these differences allow their classification. This observational, cross-sectional, and analytical study evaluated 20 muscles from 11 patients with dysferlinopathies and 11 patients with IIM. The patients were matched for age, sex, and disease duration. Clinical and laboratory variables were analyzed. Semi-quantitative scales were used to weigh the gray scale and power Doppler muscle abnormalities. Descriptive statistics were computed and discriminant analysis was performed to determine the ultrasound variables that best predicted the final diagnosis. Forty muscles were evaluated. Atrophy and higher Heckmatt scale scores were observed in patients with dysferlinopathies. A set of three muscles (biceps/brachialis, quadriceps, and gastrocnemius) had a diagnostic accuracy of 100% (sensitivity, 100%; specificity, 100%; canonical coefficient, 0.733 p < 0.001). A set of two formulas was used to classify both diseases correctly. In the present study, scanning of three muscle groups showed high diagnostic accuracy in differentiating dysferlinopathies from MII. Ultrasound can be used as an initial test in patients with suspected muscle disease or as an additional tool to support diagnosis in controversial cases.