Abnormal Muscle Research Articles

P128 Quantitative ultrasonography reveals skeletal muscle abnormalities in female carriers of DMD pathogenic variants

P128 Quantitative ultrasonography reveals skeletal muscle abnormalities in female carriers of DMD pathogenic variants

The Effect of Bitter Orange Aroma Therapy on Reducing Pain Intensity in Labor Multigravids at Clinik Masitah Year 2023

Pain labor can increase emotional stress on the birthing mother, and can cause fatigue and can have an impact on abnormal uterine muscle function during labor leading to birth complications. One of the non-pharmacological therapies to reduce labor pain is bitter orange aromatherapy, which is a non-pharmacological therapy to reduce or relieve pain in mothers who give birth in the first stage. The type of research used in this research is a quasi experiment with a nonequivalent control group design. Sampling used purposive sampling technique as many as 22 people. Data collection used a visual analog scale pain measuring instrument, data analysis used the Wilcoxon test. The results of the study showed that there was a difference in decreasing the intensity of the pain scale in stage 1 before and after administering bitter orange aroma therapy with a p-value (0.003) and an α value (0.05). Labor pain is caused by contractions of the uterine muscles, stretching of the uterine muscles and psychological conditions, in this case fear, anxiety and tension which can trigger the production of prostaglandine hormones, causing stress. Stress conditions can affect the body's ability to withstand pain. One way to treat pain in birthing mothers is by using non-pharmacological methods by administering bitter orange aromatherapy. Bitter orange aroma therapy influence the decline intensity pain in the first stage of multigravida labor active in the clinic still in 2023

Consequences of group III/IV afferent feedback and respiratory muscle work on exercise tolerance in heart failure with reduced ejection fraction.

Exercise intolerance and exertional dyspnoea are the cardinal symptoms of heart failure with reduced ejection fraction (HFrEF). In HFrEF, abnormal autonomic and cardiopulmonary responses arising from locomotor muscle group III/IV afferent feedback is one of the primary mechanisms contributing to exercise intolerance. HFrEF patients also have pulmonary system and respiratory muscle abnormalities that impair exercise tolerance. Thus, the primary impetus for this review was to describe the mechanistic consequences of locomotor muscle group III/IV afferent feedback and respiratory muscle work in HFrEF. To address this, we first discuss the abnormal autonomic and cardiopulmonary responses mediated by locomotor muscle afferent feedback in HFrEF. Next, we outline how respiratory muscle work impairs exercise tolerance in HFrEF through its effects on locomotor muscle O2 delivery. We then discuss the direct and indirect evidence supporting an interaction between locomotor muscle group III/IV afferent feedback and respiratory muscle work during exercise in HFrEF. Last, we outline future research directions related to locomotor and respiratory muscle abnormalities to progress the field forward in understanding the pathophysiology of exercise intolerance in HFrEF. NEW FINDINGS: What is the topic of this review? This review is focused on understanding the role that locomotor muscle group III/IV afferent feedback and respiratory muscle work play in the pathophysiology of exercise intolerance in patients with heart failure. What advances does it highlight? This review proposes that the concomitant effects of locomotor muscle afferent feedback and respiratory muscle work worsen exercise tolerance and exacerbate exertional dyspnoea in patients with heart failure.

An Artificial Intelligence Exercise Coaching Mobile App: Development and Randomized Controlled Trial to Verify Its Effectiveness in Posture Correction.

Insufficient physical activity due to social distancing and suppressed outdoor activities increases vulnerability to diseases like cardiovascular diseases, sarcopenia, and severe COVID-19. While bodyweight exercises, such as squats, effectively boost physical activity, incorrect postures risk abnormal muscle activation joint strain, leading to ineffective sessions or even injuries. Avoiding incorrect postures is challenging for novices without expert guidance. Existing solutions for remote coaching and computer-assisted posture correction often prove costly or inefficient. This study aimed to use deep neural networks to develop a personal workout assistant that offers feedback on squat postures using only mobile devices-smartphones and tablets. Deep learning mimicked experts' visual assessments of proper exercise postures. The effectiveness of the mobile app was evaluated by comparing it with exercise videos, a popular at-home workout choice. Twenty participants were recruited without squat exercise experience and divided into an experimental group (EXP) with 10 individuals aged 21.90 (SD 2.18) years and a mean BMI of 20.75 (SD 2.11) and a control group (CTL) with 10 individuals aged 22.60 (SD 1.95) years and a mean BMI of 18.72 (SD 1.23) using randomized controlled trials. A data set with over 20,000 squat videos annotated by experts was created and a deep learning model was trained using pose estimation and video classification to analyze the workout postures. Subsequently, a mobile workout assistant app, Home Alone Exercise, was developed, and a 2-week interventional study, in which the EXP used the app while the CTL only followed workout videos, showed how the app helps people improve squat exercise. The EXP significantly improved their squat postures evaluated by the app after 2 weeks (Pre: 0.20 vs Mid: 4.20 vs Post: 8.00, P=.001), whereas the CTL (without the app) showed no significant change in squat posture (Pre: 0.70 vs Mid: 1.30 vs Post: 3.80, P=.13). Significant differences were observed in the left (Pre: 75.06 vs Mid: 76.24 vs Post: 63.13, P=.02) and right (Pre: 71.99 vs Mid: 76.68 vs Post: 62.82, P=.03) knee joint angles in the EXP before and after exercise, with no significant effect found for the CTL in the left (Pre: 73.27 vs Mid: 74.05 vs Post: 70.70, P=.68) and right (Pre: 70.82 vs Mid: 74.02 vs Post: 70.23, P=.61) knee joint angles. EXP participants trained with the app experienced faster improvement and learned more nuanced details of the squat exercise. The proposed mobile app, offering cost-effective self-discovery feedback, effectively taught users about squat exercises without expensive in-person trainer sessions. Clinical Research Information Service KCT0008178 (retrospectively registered); https://cris.nih.go.kr/cris/search/detailSearch.do/24006.

Current insights into the role of miRNA-125 in cardiovascular disease: potential biological markers and therapeutic targets

Recently, miRNAs are being used as diagnostic markers for various pathological conditions. This review analyzed the main studies devoted to the role of miRNA-125 in the development of cardiovascular diseases. Members of the miRNA-125 family are involved in cell differentiation, proliferation, and apoptosis by targeting mRNAs associated with these cellular processes. This miRNA can enhance or inhibit pathological processes such as oncogenesis, muscle abnormalities, neurological disorders, and others. Members of the miRNA-125 family also influence the development and function of immune cells and are involved in immunological defense. Research shows that the miRNA-125 family is associated with cardiac development. They also play an important role in pathophysiological conditions of the cardiovascular system. However, the same miRNA-125 family members play different roles in different pathological processes. For example, miRNA-125b overexpression in cardiomyocytes can inhibit their apoptosis and inflammatory response. However, miRNA-125b is also a regulator of cardiac fibrosis; its overexpression in cardiac fibroblasts can enhance their proliferation. Therefore, in pathological conditions, miRNA-125b excess aggravates myocardial fibrosis and remodeling, destroys the original morphological structure of the heart, disrupts neovascularization processes, and aggravates apoptosis of cardiomyocytes in the damaged area. Thus, to avoid adverse reactions, the optimal dose and timing of therapeutic intervention using members of the miRNA-125 family, their inhibitors, and mimetics must be carefully determined. An expanded and accurate understanding of miRNA-125 functions in gene regulatory networks associated with cardiovascular pathology will enable the development of novel and innovative therapeutic strategies.

The Effect of SERCA Activation on Functional Characteristics and Signaling of Rat Soleus Muscle upon 7 Days of Unloading.

Skeletal muscle abnormalities and atrophy during unloading are accompanied by the accumulation of excess calcium in the sarcoplasm. We hypothesized that calcium accumulation may occur, among other mechanisms, due to the inhibition of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity. Consequently, the use of the SERCA activator will reduce the level of calcium in the sarcoplasm and prevent the negative consequences of muscle unloading. Wistar rats were randomly assigned into one of three groups (eight rats per group): control rats with placebo (C), 7 days of unloading/hindlimb suspension with placebo (7HS), and 7 days of unloading treated with SERCA activator CDN1163 (7HSC). After seven days of unloading the soleus muscle, the 7HS group displayed increased fatigue in the ex vivo test, a significant increase in the level of calcium-dependent CaMK II phosphorylation and the level of tropomyosin oxidation, as well as a decrease in the content of mitochondrial DNA and protein, slow-type myosin mRNA, and the percentage of slow-type muscle fibers. All of these changes were prevented in the 7HSC group. Moreover, treatment with CDN1163 blocked a decrease in the phosphorylation of p70S6k, an increase in eEF2 phosphorylation, and an increase in MuRF-1 mRNA expression. Nevertheless, there were no differences in the degree of fast and slow muscle fiber atrophy between the 7HS and 7HSC groups. Conclusion: SERCA activation during 7 days of unloading prevented an increase in soleus fatigue, the decrease of slow-type myosin, mitochondrial markers, and markers of calcium homeostasis but had no effect on muscle atrophy.

Aortic Dissection and a Previously Unreported ACTA2 Missense Variant Mutation in a Young Patient: A Case Report.

Hereditary connective tissue disease is known to cause aortic lesions at an early age. Familial aortic aneurysm/dissection is caused due to an ACTA2 mutation that affects smooth muscle structure. We present a case of a 15-year-old boy with a mild developmental disorder in whom no abnormalities were identified on previous physical examinations. The patient presented with severe left heart failure, extensive dissection from the ascending aorta to the common iliac artery, and myocardial and cerebral infarctions. He underwent an urgent Bentall surgery. Six months later, the patient underwent surgical reconstruction of the abdominal aorta from the aortic arch and returned to normal daily activities. Pathological examination demonstrated the absence of elastic fibers but presence of abundant reticular fibers and mucopolysaccharides from the tunica intima to the media. Genetic testing revealed a heterozygous missense variant of the ACTA2 gene. To the best of our knowledge, this is the first sporadic case of structurally abnormal smooth muscle organization resulting in clinical symptoms with no previously reported pathogenicity.

How differences in anatomy and physiology and other aetiology affect the way we label and describe speech in individuals with cleft lip and palate.

Speech in individuals with cleft lip and/or palate (CLP) is a complex myriad of presenting symptoms. It is uniquely associated with the structural difference of velopharyngeal insufficiency (VPI), together with a wide and heterogeneous range of other aetiologies which often co-occur. The nature of the speech sound disorder (SSD) including VPI may also change over the course of an individual's care pathway. Differences in terminology and approaches to analysis are currently used, resulting in confusion internationally. Additionally, current diagnostic labels and classification systems in SSD do not capture the complexity and full nature of speech characteristics in CLP. This paper aims to explore the different aetiologies of cleft palate/VPI speech and to relate aetiology with speech characteristic(s). In so doing, it attempts to unravel the different terminology used in the field, describing commonalities and differences, and identifying overlaps with the speech summary patterns used in the United Kingdom and elsewhere. The paper also aims to explore the applicability of current diagnostic labels and classification systems in the non-cleft SSD literature and illustrate certain implications for speech intervention in CLP. The different aetiologies were identified from the literature and mapped onto cleft palate/VPI speech characteristics. Different terminology and approaches to analysis are defined and overlaps described. The applicability of current classification systems in SSD is discussed including additional diagnostic labels proposed in the field. Aetiologies of cleft palate/VPI speech identified include developmental (cognitive-linguistic), middle ear disease and fluctuating hearing loss, altered oral structure, abnormal facial growth, VPI-structural (abnormal palate muscle) and VPI-iatrogenic (maxillary advancement surgery). There are four main terminologies used to describe cleft palate/VPI speech: active/passive and compensatory/obligatory, which overlap with the four categories used in the UK speech summary patterns: anterior oral cleft speech characteristics (CSCs), posterior oral CSCs, non-oral CSCs and passive CSCs, although not directly comparable. Current classification systems in non-cleft SSD do not sufficiently capture the full nature and complexity of cleft palate/VPI speech. Our attempt at identifying the heterogeneous range of aetiologies provides clinicians with a better understanding of cleft palate/VPI speech to inform the management pathway and the nature and type of speech intervention required. We hope that the unravelling of the different terminology in relation to the UK speech summary patterns, and those used elsewhere, reduces confusion and provides more clarity for clinicians in the field. Diagnostic labels and classification require international agreement. What is already known on the subject Speech associated with cleft palate/velopharyngeal insufficiency (VPI) is a complex myriad of speech characteristics with a wide and heterogeneous range of aetiologies. Different terminology and speech summary patterns are used to describe the speech characteristics. The traditional classification of cleft palate/VPI speech is Articulation Disorder, although evidence is building for Phonological Disorder and contrastive approaches in cleft speech intervention. What this paper adds to existing knowledge This paper explores the range of aetiologies of cleft palate/VPI speech (e.g., altered oral structure, abnormal facial growth, abnormal palate muscle and iatrogenic aetiologies) and attempts to relate aetiology with speech characteristic(s). An attempt is made at unravelling the different terminology used in relation to a well-known and validated approach to analysis, used in the United Kingdom and elsewhere. Complexities of current diagnostic labels and classifications in Speech Sound Disorder to describe cleft palate/VPI speech are discussed. What are the potential or actual clinical implications of this work? There needs to be a common language for describing and summarising cleft palate/VPI speech. Speech summary patterns based on narrow phonetic transcription and correct identification of aetiology are essential for the accurate classification of the speech disorder and identification of speech intervention approaches. There is an urgent need for research to identify the most appropriate type of contrastive (phonological) approach in cleft lip and/or palate.

Lateral Spread Response: Unveiling the Smoking Gun for Cured Hemifacial Spasm.

Hemifacial spasm (HFS) is a rare disorder characterized by involuntary facial muscle contractions. The primary cause is mechanical compression of the facial nerve by nearby structures. Lateral spread response (LSR) is an abnormal muscle response observed during electromyogram (EMG) testing and is associated with HFS. Intraoperative monitoring of LSR is crucial during surgery to confirm successful decompression. Proper anesthesia and electrode positioning are important for accurate LSR monitoring. Stimulation parameters should be carefully adjusted to avoid artifacts. The disappearance of LSR during surgery is associated with short-term outcomes, but its persistence does not necessarily indicate poor long-term outcomes. LSR monitoring has both positive and negative prognostic value, and its predictive ability varies across studies. Early disappearance of LSR can occur before decompression and may indicate better clinical outcomes. Further research is needed to fully understand the implications of LSR monitoring in HFS surgery.

Oxidative stress mediates the inhibitory effects of Manzamine A on uterine leiomyoma cell proliferation and extracellular matrix deposition via SOAT inhibition

Uterine fibroids, the most common benign tumors of the myometrium in women, are characterized by abnormal extracellular matrix deposition and uterine smooth muscle cell neoplasia, with high recurrence rates. Here, we investigated the potential of the marine natural product manzamine A (Manz A), which has potent anti-cancer effects, as a treatment for uterine fibroids. Manz A inhibited leiomyoma cell proliferation in vitro and in vivo by arresting cell cycle progression and inducing caspase-mediated apoptosis. We performed target prediction analysis and identified sterol o-acyltransferases (SOATs) as potential targets of Manz A. Cholesterol esterification and lipid droplet formation were reduced by Manz A, in line with reduced SOAT expression. As a downstream target of SOAT, Manz A also prevented extracellular matrix deposition by inhibiting the β-catenin/fibronectin/metalloproteinases axis and enhanced autophagy turnover. Excessive free fatty acid accumulation by SOAT inhibition led to reactive oxygen species to impair mitochondrial oxidative phosphorylation and trigger endoplasmic reticulum stress via PERK/eIF2α/CHOP signaling. The inhibitory effect of ManzA on cell proliferation was partially restored by PERK knockdown and eliminated by tauroursodeoxycholic acid, suggesting oxidative stress plays a critical role in the mechanism of action of Manz A. These findings suggest that targeting SOATs by Manz A may be a promising therapeutic approach for uterine fibroids.

AAV-mediated delivery of secreted acid α-glucosidase with enhanced uptake corrects neuromuscular pathology in Pompe mice.

Gene therapy is under advanced clinical development for several lysosomal storage disorders. Pompe disease, a debilitating neuromuscular illness affecting infants, children, and adults with different severity, is caused by a deficiency of lysosomal glycogen-degrading enzyme acid α-glucosidase (GAA). Here, we demonstrated that adeno-associated virus-mediated (AAV-mediated) systemic gene transfer reversed glycogen storage in all key therapeutic targets - skeletal and cardiac muscles, the diaphragm, and the central nervous system - in both young and severely affected old Gaa-knockout mice. Furthermore, the therapy reversed secondary cellular abnormalities in skeletal muscle, such as those in autophagy and mTORC1/AMPK signaling. We used an AAV9 vector encoding a chimeric human GAA protein with enhanced uptake and secretion to facilitate efficient spread of the expressed protein among multiple target tissues. These results lay the groundwork for a future clinical development strategy in Pompe disease.

Analysis of abnormal muscle activities in patients with loss of cervical lordosis: a cross-sectional study

BackgroundThis study aimed to detect the differences in cervical muscle activation patterns in people with versus without cervical lordosis and explore the possible mechanism of cervical pain originating therein.MethodsThis cross-sectional design included 39 participants without and 18 with normal cervical lordosis. Muscular activation was measured for 5 s in both groups using surface electromyography. Subsequently, the root mean square (RMS) of muscle amplitude was obtained at the bilateral splenius capitis, upper and lower parts of the splenius cervicis, upper and lower parts of the semispinalis cervicis, sternocleidomastoid, upper trapezius, and rhomboid muscles in five cervical positions: 0° (resting), 30° of flexion, 30° of extension, 60° of extension, and upon a 1-kg load on the head in a resting posture.ResultsThe RMS values of the upper trapezius muscle at all postures and the rhomboid muscles at 60° of extension were significantly lower in the loss of lordosis than control group. Comparing the RMS ratio of each posture to the resting position, the ratio of the upper trapezius at flexion was significantly higher and that of the rhomboids at 60° of extension and upon loading was significantly lower in the loss of lordosis than control group. Moreover, the pattern changes in the RMS values according to posture showed a similar shape in these two muscles, and lower in the loss of lordosis than the normal group.ConclusionsThe loss of normal cervical alignment may correlate with predisposed conditions such as reduced muscle activation of the trapezius and rhomboid muscle, and may also provoke over-firing of the upper trapezius muscle, possibly increasing neck musculoskeletal pain.Trial registration.Clinicaltrials.gov, registration number: NCT03710785.

Diffusion tensor imaging of horizontal extraocular muscles in patients with concomitant and paralytic esotropia.

To assess metrics of diffusion tensor imagining (DTI) in evaluating microstructural abnormalities of horizontal extraocular muscles (EOM) in esotropia. Six adult concomitant esotropia patients, 5 unilateral abducent paralysis patients and 2 healthy volunteers were enrolled. Conventional magnetic resonance imaging (MRI) and DTI were performed on all subjects using 3T MR scanner. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of medial and lateral rectus muscles were measured and compared between patients group and control group. Medial rectus MD and RD within the adducted eye of concomitant patients was significantly greater than that in unilateral abducent paralysis patients (0.259×10-2 mm2/s vs 0.207×10-2 mm2/s, P=0.014; 0.182×10-2 mm2/s vs 0.152×10-2 mm2/s, P=0.017). Both strabismus patients showed a significantly decreased MD and AD than that obtained in normal controls for lateral rectus muscles (P<0.05). Medial rectus MD of the adducted eye in concomitant strabismus patients was significantly decreased than that in healthy controls (0.259×10-2 mm2/s vs 0.266×10-2 mm2/s, P=0.010). Lateral rectus AD of the adducted eye in concomitant strabismus patients was significantly decreased as compared with that in healthy controls (0.515×10-2 mm2/s vs 0.593×10-2 mm2/s, P=0.013). No statistically significant differences were present between the adducted and fixating eyes in concomitant strabismus patients. DTI represents a feasible technique to assess tissue characteristics of EOM. The effects of eye position changes on DTI parameters are subtle. Decreased MD and RD could be evidence for remodeling of the medial rectus muscle contracture. Lower medial and lateral recuts MD of concomitant esotropia patients indicates a thinner fibrous structure of the EOM. Lower MD and AD should be general character of esotropia.

CFTR dysfunction in smooth muscle drives TGFβ dependent airway hyperreactivity

BackgroundThe primary underlying defect in cystic fibrosis (CF) is disrupted ion transport in epithelia throughout the body. It is unclear if symptoms such as airway hyperreactivity (AHR) and increased airway smooth muscle (ASM) volume in people with CF are due to inherent abnormalities in smooth muscle or are secondary to epithelial dysfunction. Transforming Growth Factor beta 1 (TGFβ) is an established genetic modifier of CF lung disease and a known driver of abnormal ASM function. Prior studies have demonstrated that CF mice develop greater AHR, goblet cell hyperplasia, and ASM hypertrophy after pulmonary TGFβ exposure. However, the mechanism driving these abnormalities in CF lung disease, specifically the contribution of CFTR loss in ASM, was unknown.MethodsIn this study, mice with smooth muscle-specific loss of CFTR function (Cftrfl/fl; SM-Cre mice) were exposed to pulmonary TGFβ. The impact on lung pathology and physiology was investigated through examination of lung mechanics, Western blot analysis, and pulmonary histology.ResultsCftrfl/fl; SM-Cre mice treated with TGFβ demonstrated greater methacholine-induced AHR than control mice. However, Cftrfl/fl; SM-Cre mice did not develop increased inflammation, ASM area, or goblet cell hyperplasia relative to controls following TGFβ exposure.ConclusionsThese results demonstrate a direct smooth muscle contribution to CF airway obstruction mediated by TGFβ. Dysfunction in non-epithelial tissues should be considered in the development of CF therapeutics, including potential genetic therapies.

Spontaneous pulmonary herniation in post-polio syndrome.

Pulmonary hernias are typically a result of trauma, thoracic operations, or congenital defects. Spontaneous lung hernias without a prior overt injury are notably rare. The presence of spontaneous lung hernias has not been reported in post-polio syndrome. Post-polio syndrome is a late sequela of poliomyelitis that usually presents 30-40years after the initial illness with new presentations of progressive muscle weakness, abnormal muscle fatigue, muscle atrophy, and myalgia. This case report describes the presentation and imaging of a post-polio patient with an atraumatic, spontaneous lung hernia. A discussion on pulmonary hernias, diagnostic imaging, and management is also included.

Effects of a Mitochondrial Targeted Ubiquinol (MitoQ) on Vascular Function and Exercise Capacity in Chronic Kidney Disease: A Randomized Controlled Pilot Study.

Mitochondrial derived oxidative stress is implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondrial targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (Mean±SEM: Age, 62±3years; eGFR, 45±3ml/min/1.732) received 4 weeks of 20mg/day MitoQ (MTQ) or placebo (PLB). Outcomes assessed at baseline and follow up included macrovascular function measured by flow mediated dilation; microvascular function assessed by laser Doppler flowmetry combined with intradermal microdialysis; aortic hemodynamics assessed by oscillometery; and exercise capacity by cardiopulmonary exercise testing. Compared to PLB, MTQ improved flow mediated dilation (baseline vs follow up: MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; p=0.04). MTQ improved microvascular function (DCVC: MTQ, 4.50 ± 2.57 vs. PLB -2.22 ± 2.67%; p=0.053). Central aortic systolic and pulse pressures were unchanged, however, MTQ prevented increases in augmentation pressures that were observed in the PLB group (p=0.026). MTQ did not affect exercise capacity. This study demonstrates potential for a mitochondrial targeted ubiquinol to improve vascular function in CKD. The findings hold promise for future investigations of mitochondrial targeted therapies in CKD.

CORR Insights®: Are Abnormal Muscle Biomechanics and Patient-reported Outcomes Associated in Patients With Hip Dysplasia?

CORR Insights®: Are Abnormal Muscle Biomechanics and Patient-reported Outcomes Associated in Patients With Hip Dysplasia?

Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome

ObjectivesPatients with Loeys-Dietz syndrome demonstrate a heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement. This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome and characterizes smooth muscle cell phenotype in Loeys-Dietz syndrome aneurysmal and normal-sized downstream aorta. MethodsPatients with genetically confirmed Loeys-Dietz syndrome (n = 8) underwent prophylactic aortic arch replacement during valve-sparing aortic root replacement. Four-dimensional flow magnetic resonance imaging studies were performed in 4 patients with Loeys-Dietz syndrome (valve-sparing aortic root replacement + arch) and compared with patients with contemporary Marfan syndrome (valve-sparing aortic root replacement only, n = 5) and control patients (without aortopathy, n = 5). Aortic tissues from 4 patients with Loeys-Dietz syndrome and 2 organ donors were processed for anatomically segmented single-cell RNA sequencing and histologic assessment. ResultsPatients with Loeys-Dietz syndrome valve-sparing aortic root replacement + arch had no deaths, major morbidity, or aortic events in a median of 2 years follow-up. Four-dimensional magnetic resonance imaging demonstrated altered flow parameters in patients with postoperative aortopathy relative to controls, but no clear deleterious changes due to arch replacement. Integrated analysis of aortic single-cell RNA sequencing data (>49,000 cells) identified a continuum of abnormal smooth muscle cell phenotypic modulation in Loeys-Dietz syndrome defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These modulated smooth muscle cells populated the Loeys-Dietz syndrome tunica media with gradually reduced density from the overtly aneurysmal root to the nondilated arch. ConclusionsPatients with Loeys-Dietz syndrome demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant valve-sparing aortic root replacement + arch operations. Abnormal smooth muscle cell–mediated aortic remodeling occurs within the normal diameter, clinically at-risk Loeys-Dietz syndrome arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in Loeys-Dietz syndrome.

Comparative Analysis of Muscle Synergy between Patients with Shoulder Impingement Syndrome and Healthy Controls: A Preliminary Study.

Shoulder impingement syndrome can be caused by a muscle imbalance around the shoulder joint. It would be beneficial for therapy to implement rehabilitation exercises based on intermuscular coordination in order to achieve muscle balance. This study presents the muscle synergy characteristics of patients with shoulder impingement syndrome, which can be used to develop rehabilitation exercises. During pick and place task, the muscle synergy obtained from eight shoulder muscles in patients and healthy subjects was compared. The experimental results revealed that patients have low contributed muscle synergy structures for the serratus anterior and infraspinatus.Clinical relevance- This proposes that patients with shoulder impingement syndrome may have abnormal muscle synergy structure which can be used for assessment.

Asynchrony Injures Lung and Diaphragm in Acute Respiratory Distress Syndrome.

Patient-ventilator asynchrony is often observed during mechanical ventilation and is associated with higher mortality. We hypothesized that patient-ventilator asynchrony causes lung and diaphragm injury and dysfunction. Prospective randomized animal study. University research laboratory. Eighteen New Zealand White rabbits. Acute respiratory distress syndrome (ARDS) model was established by depleting surfactants. Each group (assist control, breath stacking, and reverse triggering) was simulated by phrenic nerve stimulation. The effects of each group on lung function, lung injury (wet-to-dry lung weight ratio, total protein, and interleukin-6 in bronchoalveolar lavage), diaphragm function (diaphragm force generation curve), and diaphragm injury (cross-sectional area of diaphragm muscle fibers, histology) were measured. Diaphragm RNA sequencing was performed using breath stacking and assist control (n = 2 each). Inspiratory effort generated by phrenic nerve stimulation was small and similar among groups (esophageal pressure swing ≈ -2.5 cm H2O). Breath stacking resulted in the largest tidal volume (>10 mL/kg) and highest inspiratory transpulmonary pressure, leading to worse oxygenation, worse lung compliance, and lung injury. Reverse triggering did not cause lung injury. No asynchrony events were observed in assist control, whereas eccentric contractions occurred in breath stacking and reverse triggering, but more frequently in breath stacking. Breath stacking and reverse triggering significantly reduced diaphragm force generation. Diaphragmatic histology revealed that the area fraction of abnormal muscle was ×2.5 higher in breath stacking (vs assist control) and ×2.1 higher in reverse triggering (vs assist control). Diaphragm RNA sequencing analysis revealed that genes associated with muscle differentiation and contraction were suppressed, whereas cytokine- and chemokine-mediated proinflammatory responses were activated in breath stacking versus assist control. Breath stacking caused lung and diaphragm injury, whereas reverse triggering caused diaphragm injury. Thus, careful monitoring and management of patient-ventilator asynchrony may be important to minimize lung and diaphragm injury from spontaneous breathing in ARDS.