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Computer Methods in Biomechanics and... Dec 2023The muscle spindle is an essential proprioceptor, significantly involved in sensing limb position and movement. Although biological spindle models exist for years, the...
The muscle spindle is an essential proprioceptor, significantly involved in sensing limb position and movement. Although biological spindle models exist for years, the gold-standard for motor control in biomechanics are still sensors built of homogenized spindle output models due to their simpler combination with neuro-musculoskeletal models. Aiming to improve biomechanical simulations, this work establishes a more physiological model of the muscle spindle, aligned to the advantage of easy integration into large-scale musculoskeletal models. We implemented four variations of a spindle model in Matlab/Simulink®: the Mileusnic et al. (2006) model, Mileusnic model without mass, our enhanced Hill-type model, and our enhanced Hill-type model with parallel damping element (PDE). Different stretches in the intrafusal fibers were simulated in all model variations following the spindle afferent recorded in previous experiments in feline soleus muscle. Additionally, the enhanced Hill-type models had their parameters extensively optimized to match the experimental conditions, and the resulting model was validated against data from rats' triceps surae muscle. As result, the Mileusnic models present a better overall performance generating the afferent firings compared to the common data evaluated. However, the enhanced Hill-type model with PDE exhibits a more stable performance than the original Mileusnic model, at the same time that presents a well-tuned Hill-type model as muscle spindle fibers, and also accounts for real sarcomere force-length and force-velocity aspects. Finally, our activation dynamics is similar to the one applied to Hill-type model for extrafusal fibers, making our proposed model more easily integrated in multi-body simulations.
PubMed: 38126259
DOI: 10.1080/10255842.2023.2293652 -
Movement Disorders : Official Journal... Nov 2023There is a growing body of evidence suggesting that botulinum toxin can alter proprioceptive feedback and modulate the muscle-spindle output for the treatment of...
BACKGROUND
There is a growing body of evidence suggesting that botulinum toxin can alter proprioceptive feedback and modulate the muscle-spindle output for the treatment of dystonia. However, the mechanism for this modulation remains unclear.
METHODS
We conducted a study involving 17 patients with cervical dystonia (CD), seven of whom had prominent CD and 10 with generalized dystonia (GD) along with CD. We investigated the effects of neck vibration, a form of proprioceptive modulation, on spontaneous single-neuron responses and local field potentials (LFPs) recorded from the globus pallidum externus (GPe) and internus (GPi).
RESULTS
Our findings demonstrated that neck vibration notably increased the regularity of neck-sensitive GPi neurons in focal CD patients. Additionally, in patients with GD and CD, the vibration enhanced the firing regularity of non-neck-sensitive neurons. These effects on single-unit activity were also mirrored in ensemble responses measured through LFPs. Notably, the LFP modulation was particularly pronounced in areas populated with burst neurons compared to pause or tonic cells.
CONCLUSION
The results from our study emphasize the significance of burst neurons in the pathogenesis of dystonia and in the efficacy of proprioceptive modulation for its treatment. Moreover, we observed that the effects of vibration on focal CD were prominent in the α band LFP, indicating modulation of pallido-cerebellar connectivity. Moreover, the pallidal effects of vibration in GD with CD involved modulation of cerebro-pallidal θ band connectivity. Our analysis provides insight into how vibration-induced changes in pallidal activity are integrated into the downstream motor circuit. © 2023 International Parkinson and Movement Disorder Society.
Topics: Humans; Torticollis; Globus Pallidus; Deep Brain Stimulation; Dystonic Disorders; Neck
PubMed: 37702261
DOI: 10.1002/mds.29603 -
Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma.Open Life Sciences 2023The aim of this study was to investigate the clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma. Histopathology,...
The aim of this study was to investigate the clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma. Histopathology, immunohistochemistry, and human epidermal growth factor receptor 2 (HER2) gene testing were conducted for seven cases of gastric pleomorphic giant cell carcinoma. In histomorphological terms, all seven cases involved pleomorphic giant cell carcinoma, accounting for more than 10% of the entire tumor, with pleomorphic spindle cells and giant cells mixed with various histomorphological structures of adenocarcinoma with high, intermediate, and low differentiation. There was large heterogeneity in the HER2 protein expression and HER2 gene amplification in the gastric pleomorphic giant cell carcinoma, and both levels of HER2 were focal in three cases, accounting for 42.9% (3/7). The mismatch repair gene proteins MLH1, MSH2, PMS2, and MSH6 were positive. Routine immunohistochemical markers, i.e., pan-cytokeratin, epithelial membrane antigen, villin, caudal-type homeobox 2, E-cadherin, and p53, were positive in the gastric pleomorphic giant cell carcinoma, while vimentin, calponin, smooth muscle actin, nestin, S-100, cluster of differentiation (CD) 99, desmin, and CD34 were focally expressed in both the spindle and the giant cells, with Ki-67-positive cells accounting for 70-80%. Gastric pleomorphic giant cell carcinoma presents multiple histomorphological features and is easily confused with various tumors. Clarifying the histopathological features of this type of tumor is important for differential diagnosis and precise treatment.
PubMed: 37724114
DOI: 10.1515/biol-2022-0683 -
Experimental Physiology Jan 2024The goals of this review are to improve understanding of the aetiology of chronic muscle pain and identify new targets for treatments. Muscle pain is usually associated... (Review)
Review
The goals of this review are to improve understanding of the aetiology of chronic muscle pain and identify new targets for treatments. Muscle pain is usually associated with trigger points in syndromes such as fibromyalgia and myofascial syndrome, and with small spots associated with spontaneous electrical activity that seems to emanate from fibers inside muscle spindles in EMG studies. These observations, added to the reports that large-diameter primary afferents, such as those innervating muscle spindles, become hyperexcitable and develop spontaneous ectopic firing in conditions leading to neuropathic pain, suggest that changes in excitability of these afferents might make an important contribution to the development of pathological pain. Here, we review evidence that the muscle spindle afferents (MSAs) of the jaw-closing muscles become hyperexcitable in a model of chronic orofacial myalgia. In these afferents, as in other large-diameter primary afferents in dorsal root ganglia, firing emerges from fast membrane potential oscillations that are supported by a persistent sodium current (I ) mediated by Na channels containing the α-subunit Na 1.6. The current flowing through Na 1.6 channels increases when the extracellular Ca concentration decreases, and studies have shown that I -driven firing is increased by S100β, an astrocytic protein that chelates Ca when released in the extracellular space. We review evidence of how astrocytes, which are known to be activated in pain conditions, might, through their regulation of extracellular Ca , contribute to the generation of ectopic firing in MSAs. To explain how ectopic firing in MSAs might cause pain, we review evidence supporting the hypothesis that cross-talk between proprioceptive and nociceptive pathways might occur in the periphery, within the spindle capsule.
Topics: Humans; Muscle Spindles; Myalgia; Chronic Pain; Membrane Potentials; Neuralgia; Neurons, Afferent
PubMed: 38103003
DOI: 10.1113/EP090769 -
Cureus Nov 2023Superficial angiomyxomas of the skin are rare benign cutaneous tumors of soft tissue composed of myxoid matrix and thin-walled blood vessels. They can be sporadic or...
Superficial angiomyxomas of the skin are rare benign cutaneous tumors of soft tissue composed of myxoid matrix and thin-walled blood vessels. They can be sporadic or develop in conjunction with the Carney complex. These tumors have a predilection for the trunk, lower limbs, head, neck, and genitalia. Herein, we report a case of superficial angiomyxoma of the axilla in a 42-year-old man. The pedunculated polypoidal mass showed a maximum diameter of 4.5 cm and intra- and extra-lesional vascularity on Doppler, and the histopathology report was suggestive of myxoid matrix with scattered bland stellate and spindle cells and long thin-walled branching blood vessels and inflammatory infiltrate consisting of mainly neutrophils. Smooth muscle actin (SMA), S100, and desmin were found to be negative on immunohistochemistry, but CD34 was discovered to be positive. It was possible to make the diagnosis of superficial angiomyxoma using these histological and immunohistochemical characteristics. Wide local excision, being the preferred treatment, was performed, and the patient was followed up for six months with no signs of recurrence.
PubMed: 38073913
DOI: 10.7759/cureus.48472 -
Journal of Anatomy Aug 2023The structural and functional differences of individual hamstrings have not been sufficiently evaluated. This study aimed to clarify the morphological architecture of...
Unique morphological architecture of the hamstring muscles and its functional relevance revealed by analysis of isolated muscle specimens and quantification of structural parameters.
The structural and functional differences of individual hamstrings have not been sufficiently evaluated. This study aimed to clarify the morphological architecture of the hamstrings including the superficial tendons in detail using isolated muscle specimens, together with quantification of structural parameters of the muscle. Sixteen lower limbs of human cadavers were used in this study. The semimembranosus (SM), semitendinosus (ST), biceps femoris long head (BFlh), and biceps femoris short head (BFsh) were dissected from cadavers to prepare isolated muscle specimens. Structural parameters, including muscle volume, muscle length, fiber length, sarcomere length, pennation angle, and physiological cross-sectional area (PCSA) were measured. In addition, the proximal and distal attachment areas of the muscle fibers were measured, and the proximal/distal area ratio was calculated. The SM, ST, and BFlh were spindle-shaped with the superficial origin and insertion tendons on the muscle surface, and the BFsh was quadrate with direct attachment to the skeleton and BFlh tendon. The muscle architecture was pennate in the four muscles. The four hamstrings possessed either of two types of structural parameters, one with shorter fiber length and larger PCSA, as in the SM and BFlh, and the other with longer fiber length and smaller PCSA, as in the ST and BFsh. Sarcomere length was unique in each of the four hamstrings, and thus the fiber length was suitably normalized using the average sarcomere length for each, instead of uniform length of 2.7 μm. The proximal/distal area ratio was even in the SM, large in the ST, and small in the BFsh and BFlh. This study clarified that the superficial origin and insertion tendons are critical determinants of the unique internal structure and structural parameters representing the functional properties of the hamstring muscles.
Topics: Humans; Hamstring Muscles; Tendons; Muscle Fibers, Skeletal; Lower Extremity; Cadaver; Muscle, Skeletal
PubMed: 36914559
DOI: 10.1111/joa.13860 -
The European Journal of Neuroscience Jul 2023Male and female rats differ in muscle fibre composition, related motor unit contractile properties, and muscle spindle density but not number. On the other hand, their...
Male and female rats differ in muscle fibre composition, related motor unit contractile properties, and muscle spindle density but not number. On the other hand, their motoneurons' intrinsic properties, excitability and firing properties are similar. The aim of this study was to investigate whether apparent sex differences in body mass and muscle force influence the proprioceptive input from muscle spindles to motoneurons. Medial gastrocnemius motoneurons were investigated intracellularly in deeply anaesthetised male and female rats. Monosynaptic Ia excitatory postsynaptic potentials (EPSPs) were evoked using electrical stimulation of primary afferents from homonymous muscle. Data were analysed using a mixed linear model. The central latencies of EPSPs were 0.38-0.80 ms, with no differences in means between males and females. The maximum EPSP amplitude varied between 2.03 and 8.09 mV in males and 1.24 and 6.79 mV in females. The mean maximum EPSP amplitude was 26% higher in males than in females. The mean EPSP rise time, half-decay time and total duration did not differ between the sexes. EPSP amplitudes correlated with the resting membrane potential, input resistance and EPSP rise time in both sexes. The observed sex differences in the Ia proprioceptive input may be related either to mechanical loading differences in males and females associated with their different body mass or hormonal differences influencing the levels of neuromodulation in spinal circuits. The results highlight the importance of taking sex into consideration in the studies on the influence of afferent inputs on MN excitability.
Topics: Female; Male; Animals; Rats; Spinal Cord; Evoked Potentials; Motor Neurons; Muscle Contraction; Muscle, Skeletal; Synapses
PubMed: 37278127
DOI: 10.1111/ejn.16053 -
Turk Patoloji Dergisi 2024Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In...
OBJECTIVE
Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In this study, we evaluated a cohort of ordinary leiomyosarcomas (LMS) for the presence of EBV and described the clinicopathological features deviating from routinely diagnosed cases of EBV-SMT.
MATERIAL AND METHOD
The sections of tissue microarrays including 93 classical LMS occurring in various locations were hybridized with EBER and stained for LMP1 antibody using the Leica Bond Autostainer. EBV real-time PCR assay was performed in 2 EBER-positive cases.
RESULTS
Among the 93 LMS cases, 2 non-uterine cases (2.2%) were positive for EBER and negative for LMP1, and were referred to as `EBV-positive LMS`. Both were females in their 6th decade without immunosuppression. EBV real-time PCR assay revealed the presence of EBV in one of the cases. Tumors were located in the pancreas and chest wall. Morphologically, tumors were rather myxoid, multinodular, and composed of long fascicles of spindle cells with intermediate- to high-grade features. High mitotic activity and focal necrosis were present, whereas no accompanying lymphocytes were detected. One of the patients developed metastatic disease after 3 years.
CONCLUSION
EBV-positive LMS occurring in immunocompetent patients has features distinct from classical EBV-SMT seen in immunosuppressed patients.
Topics: Female; Humans; Male; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Leiomyosarcoma; Smooth Muscle Tumor; Immunocompromised Host
PubMed: 36951222
DOI: 10.5146/tjpath.2023.01600 -
Indian Journal of Pathology &... Nov 2023Angioleiomyoma is a benign neoplasm that arises from vascular smooth muscle cells. Angioleiomyoma of the endometrium is very uncommon. The differential diagnoses of this...
Angioleiomyoma is a benign neoplasm that arises from vascular smooth muscle cells. Angioleiomyoma of the endometrium is very uncommon. The differential diagnoses of this entity are myopericytoma, angiomyofibroblastoma, endometrial stromal tumor, and perivascular epithelioid cell tumor. 31-year-old and 45-year-old patients presented with heavy menstrual bleeding, lower abdomen pain, and dysmenorrhea. Perspeculum and radiological investigations showed an endometrial polyp. They underwent diagnostic hysteroscopy, polypectomy, and endometrial biopsy. Polypectomy specimens of both cases revealed polypoidal lesions lined by the endometrium. The core of the polyp was arranged in long intersecting bundles of spindle cells and interconnecting anastomotic patterns with many intervening thick-walled blood vessels. These spindle cells have oval and cigar-shaped nuclei, fine chromatin, and a moderate amount of eosinophilic cytoplasm, resembling smooth muscle cells. These smooth muscle cells of the vessel wall were merging with the adjacent walls of the blood vessel. There was no nuclear atypia or necrosis. The mitotic rate was 0-1/10 HPF. Focal areas of hyalinization and adipocytic components were noted in one case. The endometrial glands did not show intraepithelial or invasive neoplasia. On immunohistochemistry (IHC), these spindle cells were diffuse and strongly immunopositive for SMA and Desmin. CD34 highlighted the endothelial lining of the prominent thick-walled blood vessels. By correlating with histomorphology and IHC positivity, a diagnosis of angioleiomyomatous polyp of endometrium was rendered. We report two uncommon cases of angioleiomyoma of the endometrium and discuss the differential diagnosis and literature review.
PubMed: 38394403
DOI: 10.4103/ijpm.ijpm_108_23 -
Journal of Cutaneous Pathology Aug 2023Extragastrointestinal stromal tumors (EGISTs) carry the same morphological, immunohistochemical and molecular features as gastrointestinal stromal tumors (GISTs) and...
Extragastrointestinal stromal tumors (EGISTs) carry the same morphological, immunohistochemical and molecular features as gastrointestinal stromal tumors (GISTs) and involve extragastrointestinal tract soft tissue. The majority of reported EGIST cases arise from intraabdominal, retroperitoneal, or pelvic soft tissue. A significant subset of such tumors originates from the gastrointestinal muscle layer, grows in an exophytic manner, then loses attachment to the gastrointestinal tract. Consequently, true EGISTs are exceedingly rare. Herein, we are reporting a case of a vulvar EGIST. A 77-year-old woman presented with a painless subcutaneous nodule on the right perineum. An excisional biopsy showed a fairly circumscribed bland spindle cell lesion in the dermis. The tumor cells were positive for CD117 and ANO1/DOG-1 and negative for smooth muscle myosin, smooth muscle actin, STAT6, low- and high-molecular-weight cytokeratins, SOX10, MART-1, CD10, S-100 protein, and estrogen and progesterone receptors. A diagnosis of EGIST was made and complete excision was recommended. Superficial/subcutaneous EGISTs are extremely rare, and it is important for dermatopathologists to be aware of this entity as it can be misdiagnosed as more common spindle cell neoplasms, both benign and malignant, including but not limited to smooth muscle neoplasms (leiomyoma/leiomyosarcoma), spindle cell melanoma, and sarcomatoid squamous cell carcinoma.
Topics: Humans; Gastrointestinal Stromal Tumors; Leiomyosarcoma; Immunohistochemistry; Proto-Oncogene Proteins c-kit
PubMed: 37127848
DOI: 10.1111/cup.14432