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Epilepsia Jul 2024DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small...
OBJECTIVE
DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1-related epilepsy spectrum, and compare the genotype-phenotype correlations observed in our cohort with the literature.
METHODS
Patients harboring de novo DYNC1H1 pathogenic variants were recruited through international collaborations. Clinical data were retrospectively collected. Latent class analysis was performed to identify subphenotypes. Multivariable binary logistic regression analysis was applied to investigate the association with DYNC1H1 protein domains.
RESULTS
DYNC1H1-related epilepsy presented with infantile epileptic spasms syndrome (IESS) in 17 subjects (50%), and in 25% of these individuals the epileptic phenotype evolved into Lennox-Gastaut syndrome (LGS). In 12 patients (35%), focal onset epilepsy was defined. In two patients, the epileptic phenotype consisted of generalized myoclonic epilepsy, with a progressive phenotype in one individual harboring a frameshift variant. In approximately 60% of our cohort, seizures were drug-resistant. Malformations of cortical development were noticed in 79% of our patients, mostly on the lissencephaly-pachygyria spectrum, particularly with posterior predominance in a half of them. Midline and infratentorial abnormalities were additionally reported in 45% and 27% of subjects. We have identified three main classes of subphenotypes on the DYNC1H1-related epilepsy spectrum.
SIGNIFICANCE
We propose a classification in which pathogenic de novo DYNC1H1 variants feature drug-resistant IESS in half of cases with potential evolution to LGS (Class 1), developmental and epileptic encephalopathy other than IESS and LGS (Class 2), or less severe focal or genetic generalized epilepsy including a progressive phenotype (Class 3). We observed an association between stalk domain variants and Class 1 phenotypes. The variants p.Arg309His and p.Arg1962His were common and associated with Class 1 subphenotype in our cohort. These findings may aid genetic counseling of patients with DYNC1H1-related epilepsy.
PubMed: 38953796
DOI: 10.1111/epi.18054 -
The Journal of Sports Medicine and... Jul 2024Isometric strength testing is widely applied in sports science. However, we hypothesized that traditional testing procedures with a dual focus on both peak force (PF)...
BACKGROUND
Isometric strength testing is widely applied in sports science. However, we hypothesized that traditional testing procedures with a dual focus on both peak force (PF) and rate of force development (RFD) may compromise the true assessment of early RFD measures and lower the associative value towards vertical jump performance.
METHODS
Therefore, PF and RFD were assessed for 47 active participants (24 females, 23 males) with a traditional isometric midthigh pull (IMTP) protocol ("push as hard and fast as possible" over 4 s) and an RFD-specific protocol ("push as fast as possible" over 2 s). IMTP measures were compared to squat (SJ), countermovement (CMJ) and drop-jump (DJ) performance.
RESULTS
The RFD-specific protocol provided higher RFD (P<0.05) for time domains up to 100 ms but lower PF (P<0.001). Independent of protocol, SJ and CMJ performance displayed significant, but low-to-moderate correlations with all RFD measures (r=0.30-0.52) as well as PF (r=0.44), whereas DJ did not show any correlation.
CONCLUSIONS
In conclusion, an RFD-specific protocol appears relevant for the assessment of RFD in the time domain up to 100 ms. However, the observed associations between RFD/PF measures and vertical jump performance remained low-to-moderate independent of the IMTP test protocol.
PubMed: 38953761
DOI: 10.23736/S0022-4707.24.15672-1 -
Journal of Animal Physiology and Animal... Jul 2024Eight geldings weighing 544 ± 16 kg were used to evaluate feeding a postexercise protein meal on plasma amino acids during recovery. Horses were fed sweet feed,...
Eight geldings weighing 544 ± 16 kg were used to evaluate feeding a postexercise protein meal on plasma amino acids during recovery. Horses were fed sweet feed, corn, grass hay and equal amounts of a protein pellet (32% CP) with meals (MP group) or postexercise (EP group). Horses exercised 1-2 h/day, 5 days/week, for 12 weeks. A pre and poststudy 4 days total urine and feces collection was conducted. Urine and fecal samples were analyzed for nitrogen (N) to calculate N balance. Blood samples were drawn immediately after and at 1 and 3 h postexercise at the start and end of the study for plasma amino acid concentrations. Absorbed N and N retention were greater for the MP group compared to the EP group (p = 0.038, 0.033 respectively). An interaction revealed an increase in fecal N (p = 0.01) and decreased N digestibility for the MP group compared to the EP group at the end of the study. Plasma concentrations for 8 out of 14 amino acids were less for the EP group immediately after exercise compared to the MP group (p < 0.02). Plasma concentrations of lysine and arginine were greater for the EP group compared to the MP group at 1 and 3 h after exercise (p < 0.05 and 0.04 respectively). Changes were different for 8 out of the 14 amino acids immediately post exercise, 7 out of 14 amino acids at 1 h postexercise and 10 out of 14 amino acids at 3 h postexercise with positive changes for the EP group and negative changes for the MP group. The EP group had improved supply of plasma amino acids in the recovery period that sustained for 3 h postexercise and are indicative of better amino acid supply supporting muscle development.
PubMed: 38953505
DOI: 10.1111/jpn.14012 -
Journal of Anatomy Jul 2024At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the...
At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.
PubMed: 38953435
DOI: 10.1111/joa.14101 -
Clinical Cardiology Jul 2024Papillary muscle (PM) infarction (PMI) detected by cardiac magnetic resonance imaging (CMR) is associated with poor outcomes. Whether PM parameters provide more value...
BACKGROUND
Papillary muscle (PM) infarction (PMI) detected by cardiac magnetic resonance imaging (CMR) is associated with poor outcomes. Whether PM parameters provide more value for mitral regurgitation (MR) management currently remains unclear. Therefore, we examined the prognostic value of PMI using CMR in patients with MR.
METHODS
Between March 2018 and July 2023, we retrospectively enrolled 397 patients with MR undergoing CMR. CMR was used to detect PMI qualitatively and quantitively. We also collected baseline clinical, echocardiography, and follow-up data.
RESULTS
Of the 397 patients with MR (52.4 ± 13.9 years), 117 (29.5%) were assigned to the PMI group, with 280 (70.5%) in the non-PMI group. PMI was demonstrated more in the posteromedial PM (PM-PM, 98/117) than in the anterolateral PM (AL-PM, 45/117). Compared with patients without PMI, patients with PMI had a decreased AL-PM (41.5 ± 5.4 vs. 45.6 ± 5.3)/PM-PM diastolic length (35.0 ± 5.2 vs. 37.9 ± 4.0), PM-longitudinal strain (LS, 20.4 ± 6.1 vs. 24.9 ± 4.6), AL-PM-LS (19.7 ± 6.8 vs. 24.7 ± 5.6)/PM-PM-LS (21.2 ± 7.9 vs. 25.2 ± 6.0), and increased inter-PM distance (25.7 ± 8.0 vs. 22.7 ± 6.2, all p < 0.001). Multiple logistic regression analyses identified male sex (odds ratio [OR] = 3.65, 95% confidence interval = 1.881-7.081, p < 0.001) diabetes mellitus (OR/95% CI/p = 2.534/1.13-5.68/0.024), AL-PM diastolic length (OR/95% CI/p = 0.841/0.77-0.92/< 0.001), PM-PM diastolic length (OR/95% CI/p = 0.873/0.79-0.964/0.007), inter-PM distance (OR/95% CI/p = 1.087/1.028-1.15/0.003), AL-PM-LS (OR/95% CI/p = 0.892/0.843-0.94/< 0.001), and PM-PM-LS (OR/95% CI/p = 0.95/0.9-0.992/0.021) as independently associated with PMI. Over a 769 ± 367-day follow-up, 100 (25.2%) patients had arrhythmia. Cox regression analyses indicated that PMI (hazard ratio [HR]/95% CI/p = 1.644/1.062-2.547/0.026), AL-PM-LS (HR/95% CI/p = 0.937/0.903-0.973/0.001), and PM-PM-LS (HR/95% CI/p = 0.933/0.902-0.965/< 0.001) remained independently associated with MR.
CONCLUSIONS
The CMR-derived PMI and LS parameters improve the evaluation of PM dysfunction, indicating a high risk for arrhythmia, and provide additive risk stratification for patients with MR.
Topics: Humans; Mitral Valve Insufficiency; Male; Female; Papillary Muscles; Retrospective Studies; Middle Aged; Magnetic Resonance Imaging, Cine; Myocardial Infarction; Prognosis; Follow-Up Studies; Aged
PubMed: 38953314
DOI: 10.1002/clc.24312 -
Frontiers in Cardiovascular Medicine 2024In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged.... (Review)
Review
In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged. However, it has been long recognized that diffuse intimal thickening (DIM), which precedes the formation of early fatty streaks in humans, primarily consists of lipid-loaded smooth muscle cells (SMCs) and their secreted proteoglycans. Recent studies have further supported the notion that SMCs constitute the majority of foam cells in advanced atherosclerotic plaques. Given that SMCs are a major component of the vascular wall, they serve as a significant source of microvesicles and exosomes, which have the potential to regulate the physiology of other vascular cells. Notably, more than half of the foam cells present in atherosclerotic lesions are of SMC origin. In this review, we describe several mechanisms underlying the formation of intimal foam-like cells in atherosclerotic plaques. Based on these mechanisms, we discuss novel therapeutic approaches that have been developed to regulate the generation of intimal foam-like cells. These innovative strategies hold promise for improving the management of atherosclerosis in the near future.
PubMed: 38952543
DOI: 10.3389/fcvm.2024.1381520 -
Renal Failure Dec 2024Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study...
AIMS
Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis.
METHODS
This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing and models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.
RESULTS
studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.
CONCLUSION
CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
Topics: STAT3 Transcription Factor; Receptor, Notch1; Diabetic Nephropathies; Animals; Signal Transduction; Fibrosis; Chlorogenic Acid; Humans; Mice; Male; Kidney; Lipid Metabolism; Molecular Docking Simulation; Mice, Inbred C57BL; Diabetes Mellitus, Experimental; Cell Line
PubMed: 38952291
DOI: 10.1080/0886022X.2024.2371988 -
Journal of Pathology and Translational... Jul 2024The blood vessel lumen is an extremely rare location for a benign peripheral nerve sheath tumor like schwannoma. Less than 10 cases have been previously reported. In...
The blood vessel lumen is an extremely rare location for a benign peripheral nerve sheath tumor like schwannoma. Less than 10 cases have been previously reported. In this report, we present a case of a 68-year-old woman who had a soft tissue nodule at the posterior calf of her left leg during a physical examination. Pathological examination was performed after complete surgical excision. The patient underwent follow-up for 12 months after surgery without evidence of recurrence or any other complication. This is the first case of intravascular schwannoma reported as a cause of vein obstruction. Microscopically, the tumor was composed of Schwann spindle cells that were immunoreactive for S100 protein and SOX10. This tumor was surrounded by a well-defined vascular smooth muscle wall. Prospective series are required to improve the knowledge on the underlying mechanisms of intravascular schwannoma development.
PubMed: 38952255
DOI: 10.4132/jptm.2024.05.15 -
Journal of Cachexia, Sarcopenia and... Jul 2024Sarcopenia is an important indicator of ill health and is linked to increased mortality and a reduced quality of life. Age-associated muscle mass indices provide a...
BACKGROUND
Sarcopenia is an important indicator of ill health and is linked to increased mortality and a reduced quality of life. Age-associated muscle mass indices provide a critical tool to help understand the development of sarcopenia. This study aimed to develop sex- and age-specific percentiles for muscle mass indices in a Chinese population and to compare those indices with those from other ethnicities using the National Health and Nutrition Examination Survey (NHANES) data.
METHODS
Whole-body and regional muscle mass was measured by dual-energy X-ray absorptiometry (DXA) in participants of the China Body Composition Life-course (BCL) study (17 203 healthy Chinese aged 3-60 years, male 48.9%) and NHANES (12 663 healthy Americans aged 8-59 years, male 50.4%). Age- and sex-specific percentile curves were generated for whole-body muscle mass and appendicular skeletal muscle mass using the Generalized Additive Model for Location Scale and Shape statistical method.
RESULTS
Values of upper and lower muscle mass across ages had three periods: an increase from age 3 to a peak at age 25 in males (with the 5th and 95th values of 41.5 and 66.4 kg, respectively) and age 23 in females (with the 5th and 95th values of 28.4 and 45.1 kg, respectively), a plateau through midlife (30s-50s) and then a decline after their early 50s. The age at which muscle mass began to decline was 52 years in men with the 5th and 95th percentile values of 43.5 and 64.6 kg, and 51 years in women with the 5th and 95th percentile values of 31.6 and 46.9 kg. Appendicular skeletal muscle mass decreased earlier than whole body muscle mass, especially leg skeletal muscle mass, which decreased slightly after age 49 years in both sexes. In comparison with their US counterparts in the NHANES, the Chinese participants had lower muscle mass indices (all P < 0.001) and reached a muscle mass peak earlier with a lower muscle mass, with the exception of similar values compared with adult Mexican and White participants. The muscle mass growth rate of Chinese children decreased faster than that of other races after the age of 13.
CONCLUSIONS
We present the sex- and age-specific percentiles for muscle mass and appendicular skeletal muscle mass by DXA in participants aged 3-60 from China and compare them with those of different ethnic groups in NHANES. The rich data characterize the trajectories of key muscle mass indices that may facilitate the clinical appraisal of muscle mass and improve the early diagnosis of sarcopenia in the Chinese population.
PubMed: 38952048
DOI: 10.1002/jcsm.13522 -
Nature Medicine Jul 2024For centuries scientists and technologists have sought artificial leg replacements that fully capture the versatility of their intact biological counterparts. However,...
For centuries scientists and technologists have sought artificial leg replacements that fully capture the versatility of their intact biological counterparts. However, biological gait requires coordinated volitional and reflexive motor control by complex afferent and efferent neural interplay, making its neuroprosthetic emulation challenging after limb amputation. Here we hypothesize that continuous neural control of a bionic limb can restore biomimetic gait after below-knee amputation when residual muscle afferents are augmented. To test this hypothesis, we present a neuroprosthetic interface consisting of surgically connected, agonist-antagonist muscles including muscle-sensing electrodes. In a cohort of seven leg amputees, the interface is shown to augment residual muscle afferents by 18% of biologically intact values. Compared with a matched amputee cohort without the afferent augmentation, the maximum neuroprosthetic walking speed is increased by 41%, enabling equivalent peak speeds to persons without leg amputation. Further, this level of afferent augmentation enables biomimetic adaptation to various walking speeds and real-world environments, including slopes, stairs and obstructed pathways. Our results suggest that even a small augmentation of residual muscle afferents restores biomimetic gait under continuous neuromodulation in individuals with leg amputation.
PubMed: 38951635
DOI: 10.1038/s41591-024-02994-9