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International Urogynecology Journal Jul 2024The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani...
INTRODUCTION AND HYPOTHESIS
The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM.
METHODS
This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV.
RESULTS
High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm and 18.87 cm respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact.
CONCLUSIONS
Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.
PubMed: 38951166
DOI: 10.1007/s00192-024-05850-z -
The Journal of Clinical Investigation Jun 2024Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for...
Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.
Topics: Humans; Iron-Sulfur Proteins; Male; Female; Neuromuscular Diseases; Child; Cell Nucleus; Cytoplasm; Metallochaperones
PubMed: 38950322
DOI: 10.1172/JCI179559 -
PloS One 2024Mule duck is vitally important to the production of global duck meat. Here, we present two high-quality haplotypes of a female mule duck (haplotype 1 (H1):1.28 Gb,...
Mule duck is vitally important to the production of global duck meat. Here, we present two high-quality haplotypes of a female mule duck (haplotype 1 (H1):1.28 Gb, haplotype 2 (H2): 1.40 Gb). The continuity (H1: contig N50 = 14.90 Mb, H2: contig N50 = 15.70 Mb) and completeness (BUSCO: H1 = 96.9%, H2 = 97.3%) are substantially better than those of other duck genomes. We detected the structural variations (SVs) in H1 and H2. We observed a positive correlation between autosome length and the number of SVs. Z chromosome was some deficient in deletions and insertions, but W chromosome was some excessive. A total of 1,451 genes were haplotype specific expression (HSEs). Among them, 737 specifically expressed in H1, and 714 specifically expressed in H2. We found that H1 and H2 HSEs tended to be involved in similar biological processes, such as myometrial relaxation and contraction pathways, muscle structure development and phosphorylation. Our haplotype-resolved genome assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in mule duck.
Topics: Animals; Ducks; Haplotypes; Genome; Female; High-Throughput Nucleotide Sequencing
PubMed: 38950038
DOI: 10.1371/journal.pone.0305914 -
Journal of Visualized Experiments : JoVE Jun 2024Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop...
Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.
Topics: Animals; Sepsis; Mice; Disease Models, Animal; Male; Mice, Inbred C57BL; Muscular Diseases; Muscular Atrophy; Muscle, Skeletal; Hindlimb Suspension
PubMed: 38949310
DOI: 10.3791/66685 -
Neurourology and Urodynamics Jul 2024Studies show a significant association between the first vaginal delivery and injuries of the levator ani muscle (LAM), which can cause pelvic floor disorders (PFDs). (Review)
Review
BACKGROUND
Studies show a significant association between the first vaginal delivery and injuries of the levator ani muscle (LAM), which can cause pelvic floor disorders (PFDs).
OBJECTIVES
This study aims to identify the prevalence of short and long-term LAM injuries after vaginal delivery in primiparous women and its influence on PFDs.
METHOD
A systematic review was conducted according to the PRISMA methodology. The databases used were Pubmed, Cochrane, and PEDro. The quality assessment of the evidence was carried out using the Critical Appraisal Skills Programme (CASP). Both the selection of studies and their evaluation were done by two researchers and a third reviewer in cases of disagreement.
RESULTS
From the search, 57 articles were gathered, and 19 were included to match the eligibility criteria. The prevalence of avulsion of the LAM was found in association with vaginal delivery between 13% and 28% ≤ 1 year after delivery and between 16% and 29% > 1 year after delivery. Ballooning was detected between 20% and 37% ≤ 1 year, and 33% of women > 1 year after delivery, appearing to be more common when compared to avulsion. Pelvic organ prolapse (POP) was considered the most common disorder associated with injuries of the LAM, and there seems to be some connection with sexual dysfunction.
CONCLUSION
Avulsion of the LAM and ballooning of the hiatal area have a high prevalence in primiparous women after vaginal delivery and have a strong direct relation to the development of POP.
PubMed: 38948963
DOI: 10.1002/nau.25529 -
BioRxiv : the Preprint Server For... Jun 2024Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of...
VERICIGUAT RESCUES CYCLIC GUANOSINE MONOPHOSPHATE PRODUCTION IN HUMAN AORTIC VASCULAR SMOOTH MUSCLE CELLS AND AUGMENTS VASORELAXATION IN AORTIC RINGS EXPOSED TO HIGH GLUCOSE.
BACKGROUND
Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger, cyclic guanosine monophosphate (cGMP) leading to increased protein kinase G (PKG) activity and vascular smooth muscle relaxation. NO bioavailability is impaired in inflammatory settings, such as high glucose (HG). We examined whether the direct sGC sensitizer/stimulator vericiguat, augments cGMP production in human vascular smooth muscle cells (HVSMC) exposed to high glucose and explored its effect on vasorelaxation.
METHODS
Aortic HVSMCs were exposed to HG for 24h. In the treatment group, cells also received 1uM vericiguat for 24h. After incubation, cGMP and PKG activity were measured. Additionally, thoracic murine aortas were exposed to HG or to normal glucose (NG) control. The rings were then placed in an organ chamber bath and dose response curves to increasing doses of acetylcholine (Ach) and sodium nitroprusside were constructed for three groups: control (normal glucose), HG alone, and HG + vericiguat.
RESULTS
HVSMCs exposed to HG produced significantly less cGMP than those exposed to NG. cGMP production in the presence of HG was rescued when treated with 1uM vericiguat. Additionally, PKG activity was impaired in the presence of HG and enzyme activity was restored with vericiguat. In isolated mouse aortic rings, ACh mediated relaxation was impaired following treatment with HG, but was improved when a HG group was treated with vericiguat.
CONCLUSIONS
The sGC sensitizer/stimulator vericiguat restored cGMP production and PKG activity in the setting of HG. Vericiguat enhanced ACh-mediated vasorelaxation in the setting of HG. The findings suggest clinical studies are warranted to investigate the potential of sGC sensitization/stimulation as a therapeutic intervention to improve vascular endothelial-dependent function that is impaired in pro-inflammatory settings that are associated with the development of atherosclerotic disease.
PubMed: 38948704
DOI: 10.1101/2024.06.21.600154 -
World Journal of Hepatology Jun 2024Sarcopenia and metabolic dysfunction associated steatotic liver disease (MASLD) are closely intertwined. Sarcopenia, traditionally a disease of the older adult and...
Sarcopenia and metabolic dysfunction associated steatotic liver disease (MASLD) are closely intertwined. Sarcopenia, traditionally a disease of the older adult and chronic disease population, has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD. They share similar risk factors of insulin resistance and physical inactivity. Given similar pathophysiology along the liver-muscle axis, sarcopenia has been studied as a risk factor for MASLD, and vice versa. Current research suggests a bidirectional relationship. Given the chronicity of MASLD as a chronic inflammatory liver disease, it can break down muscle mass and lead to sarcopenia, while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver. However, for the longest time, a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes. A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study. However, no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet. Future studies are needed to reach a consensus and reduce diagnostic variation. With similar pathophysiology and shared risk factors between the two diseases, future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.
PubMed: 38948439
DOI: 10.4254/wjh.v16.i6.871 -
PeerJ 2024Abnormal gait is prevalent among the elderly population, leading to reduced physical activity, increased risk of falls, and the potential development of dementia and...
BACKGROUND
Abnormal gait is prevalent among the elderly population, leading to reduced physical activity, increased risk of falls, and the potential development of dementia and disabilities, thus degrading the quality of life in later years. Numerous studies have highlighted the crucial roles of lower limb muscle strength asymmetry and static postural control in gait, and the reciprocal influence of lower limb muscle strength asymmetry on static postural control. However, research exploring the interrelationship between lower limb muscle strength asymmetry, static postural control, and gait performance has been limited.
METHODS
A total of 55 elderly participants aged 60 to 75 years were recruited. Isokinetic muscle strength testing was used to assess bilateral knee extension strength, and asymmetry values were calculated. Participants with asymmetry greater than 15% were categorized as the Asymmetry Group (AG), while those with asymmetry less than 15% were classified in the Symmetry Group (SG). Gait parameters were measured using a plantar pressure gait analysis system to evaluate gait performance, and static postural control was assessed through comfortable and narrow stance tests.
RESULTS
First, participants in the AG demonstrated inferior gait performance, characterized by slower gait speed, longer stance time and percentage of stance time in gait, and smaller swing time and percentage of swing time in gait. Spatial-temporal gait parameters of the weaker limb tended to be abnormal. Second, static postural control indices were higher in AG compared to SG in all aspects except for the area of ellipse during the comfortable stance with eyes open test. Third, abnormal gait parameters were associated with static postural control.
CONCLUSION
Firstly, elderly individuals with lower limb muscle strength asymmetry are prone to abnormal gait, with the weaker limb exhibiting poorer gait performance. Secondly, lower limb muscle strength asymmetry contributes to diminished static postural control in the elderly. Thirdly, the mechanism underlying abnormal gait in the elderly due to lower limb muscle strength asymmetry may be linked to a decline in static postural control.
Topics: Humans; Aged; Muscle Strength; Male; Female; Postural Balance; Lower Extremity; Gait; Middle Aged
PubMed: 38948226
DOI: 10.7717/peerj.17626 -
Regenerative Therapy Jun 2024Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury...
BACKGROUND
Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established.
HYPOTHESIS
The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair.
STUDY DESIGN
A controlled laboratory study.
METHODS
: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. : An SMI model was established with Sprague-Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-β1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment.
RESULTS
: The fibroblast migration ability was suppressed by SE added at a concentration of 10⁴ μg/mL in the culture medium. : In the 1-week model, the SE group exhibited significantly lower TGFβ -1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength.
CONCLUSION
Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair.
CLINICAL RELEVANCE
The findings of this study may contribute to the development of an early intervention method for SMIs.
PubMed: 38948131
DOI: 10.1016/j.reth.2024.05.012 -
Cureus May 2024Degenerative changes of the lumbar intervertebral disc are the most significant causes of enduring lower back pain. The possibility of the diagnosis is limited in people... (Review)
Review
Degenerative changes of the lumbar intervertebral disc are the most significant causes of enduring lower back pain. The possibility of the diagnosis is limited in people with this low back pain. Therefore, it is essential to identify the relevant back pain subgroups. The paraspinal muscles, that is, the muscles that attach to the spine, are necessary for the proper functioning of the spine and the body; insufficiency can result in back pain. Lower back pain disorders are strongly associated with altered function or structure of these paraspinal muscles, especially fibrosis and fatty infiltration. Modic changes are the bone marrow changes of the end plate in the vertebral body seen on MRI. These are strongly related to degeneration of the disc and are common in individuals with back pain symptoms. Articles were selected from Google Scholar using the terms 'Modic changes,' 'end plate changes,' 'paraspinal muscles,' and 'lower back pain. ' This article compiled different studies aiming to enhance the comprehension of biochemical processes resulting in the development of lumbar pain. Search using the keywords 'Modic changes,'' end plate changes lower back pain,' 'paraspinal muscles lower back pain,' and 'Modic changes lower back pain' on Google Scholar yielded 33000, 41000, 49400, and 17,800 results, and 958, 118, 890 and 560 results on Pubmed respectively.
PubMed: 38947594
DOI: 10.7759/cureus.61319