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Physiology International Jun 2024Whole-body vibration (WBV) is used to enhance physical performance in sports and rehabilitation. The present study analyzed the effects of remobilization with WBV on the...
BACKGROUND
Whole-body vibration (WBV) is used to enhance physical performance in sports and rehabilitation. The present study analyzed the effects of remobilization with WBV on the soleus muscle of Wistar rats.
METHODS
Twenty-eight animals were separated into four experimental groups (n = 7): CON (control); IM (immobilized); FR (immobilization and free remobilization); and WBV (immobilization and remobilization with WBV). The immobilization of the pelvic limb was carried out according to the standard protocol using a plaster cast for 15 days. For remobilization with WBV, a Frequency of 60 Hz was applied for 10 min, five days a week, for two weeks. After the remobilization period, the animals were euthanized, and the right soleus muscle was dissected followed by processing for histomorphometric analysis and immunolocalization of Aquaporin 1 (AQP1).
RESULTS
We observed a reduced larger diameter in IM compared to CON, with restored values in WBV. For the estimation of connective tissue, a significant increase was observed in the immobilized groups, while a reduction was noted in the remobilized groups. AQP1 expression decreased significantly in IM and increased in WBV.
CONCLUSION
Immobilization caused morphofunctional damage to the soleus muscle, and remobilization with WBV is efficient and offers advantages over free remobilization.
PubMed: 38935438
DOI: 10.1556/2060.2024.00404 -
Medical Molecular Morphology Jun 2024The thymus is where T cells, among the most important immune cells involved in biological defense and homeostasis, are produced and developed. The thymus plays an... (Review)
Review
The thymus is where T cells, among the most important immune cells involved in biological defense and homeostasis, are produced and developed. The thymus plays an important role in the defense against infection and cancer as well as the prevention of autoimmune diseases. However, the thymus gland atrophies with age, which might have pathological functions, and in some circumstances, there is a congenital defect in the thymus. These can be the cause of many diseases related to the dysregulation of T cell functions. Thus, the enhancement and/or normalization of thymic function may lead to protection against and treatment of a wide variety of diseases. Therefore, thymus transplantation is considered a strong candidate for permanent treatment. The status and issues related to thymus transplantation for possible immunotherapy are discussed although it is still at an early stage of development.
PubMed: 38935299
DOI: 10.1007/s00795-024-00394-z -
Investigative Ophthalmology & Visual... Jun 2024The purpose of this study was to develop and validate prediction model for myopic macular degeneration (MMD) progression in patients with high myopia.
PURPOSE
The purpose of this study was to develop and validate prediction model for myopic macular degeneration (MMD) progression in patients with high myopia.
METHODS
The Zhongshan High Myopia Cohort for model development included 660 patients aged 7 to 70 years with a bilateral sphere of ≤-6.00 diopters (D). Two hundred twelve participants with an axial length (AL) ≥25.5 mm from the Chinese Ocular Imaging Project were used for external validation. Thirty-four clinical variables, including demographics, lifestyle, myopia history, and swept source optical coherence tomography data, were analyzed. Sequential forward selection was used for predictor selection, and binary classification models were created using five machine learning algorithms to forecast the risk of MMD progression over 10 years.
RESULTS
Over a median follow-up of 10.9 years, 133 patients (20.2%) showed MMD progression in the development cohort. Among them, 69 (51.9%) developed newly-onset MMD, 11 (8.3%) developed patchy atrophy from diffuse atrophy, 54 (40.6%) showed an enlargement of lesions, and 9 (6.8%) developed plus signs. Top six predictors for MMD progression included thinner subfoveal choroidal thickness, longer AL, worse best-corrected visual acuity, older age, female gender, and shallower anterior chamber depth. The eXtreme Gradient Boosting algorithm yielded the best discriminative performance (area under the receiver operating characteristic curve [AUROC] = 0.87 ± 0.02) with good calibration in the training cohort. In a less myopic external validation group (median -5.38 D), 48 patients (22.6%) developed MMD progression over 4 years, with the model's AUROC validated at 0.80 ± 0.008.
CONCLUSIONS
Machine learning model effectively predicts MMD progression a decade ahead using clinical and imaging indicators. This tool shows promise for identifying "at-risk" high myopes for timely intervention and vision protection.
Topics: Humans; Male; Female; Middle Aged; Adult; Machine Learning; Tomography, Optical Coherence; Aged; Disease Progression; Algorithms; Adolescent; Child; Young Adult; Macular Degeneration; Myopia, Degenerative; Follow-Up Studies; Risk Factors; Forecasting; Risk Assessment; Visual Acuity
PubMed: 38935031
DOI: 10.1167/iovs.65.6.40 -
Voprosy Kurortologii, Fizioterapii, I... 2024The number of middle-aged and elderly population is increasing every year. At the same time, the course of most chronic diseases worsens with age, which can be explained...
UNLABELLED
The number of middle-aged and elderly population is increasing every year. At the same time, the course of most chronic diseases worsens with age, which can be explained by significant changes in body composition, including redistribution and increase of fat mass and decrease in muscle and skeletal mass. Thus, a decrease in muscle mass becomes intrinsic for the body from the age of 40 and develops on average by 0.5-1.0% per year. The prevalence of patients with sarcopenia is estimated to be between 11 and 50% in different age groups of population: middle, elderly and senile. In addition, the decline in physical activity associated with the urbanization and automation of labor exacerbates the disease at a younger age, which predicts an increase in the number of such patients in the future.
OBJECTIVE
To determine the role of physical rehabilitation in sarcopenia.
MATERIAL AND METHODS
A systematic review including studies found in PubMed, MedLine, Scopus and Web of Science Core Collections databases for 2019-2022 was conducted. The used enrollment criteria were the following: systematic reviews, including cross-over or cohort studies targeting at persons aged from 40 to 90 years of both sexes, with available data on sarcopenia, its severe form or other combinations of physical performance markers called sarcopenia. The mandatory parameter for inclusion in the study was the presence of the effectiveness assessment of physical rehabilitation without limiting its parameters. The systematic review was performed in accordance with the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020.
RESULTS
The best kind of training are 30-60-minute comprehensive methods with predominance of resistance exercises with minimum duration of the course of 3 months and frequency of 3 inconsistent in-person trainings per week under the supervision of a specialist for patients with sarcopenia in order to increase muscle strength and mass, as well as performance. The intensity should consist of the following parameters: start with fewer sets but more repetitions (12-15) with less intensity (55% of maximum) and move to more sets with less repetition (4-6) and greater intensity (>80% of maximum).
CONCLUSION
This article describes the parameters of exercises that are most effective in terms of muscle strength and mass increase and safe for patients. The compilation and further study of this complex in practice are needed.
Topics: Sarcopenia; Humans; Female; Male; Aged; Middle Aged; Adult; Aged, 80 and over
PubMed: 38934959
DOI: 10.17116/kurort202410103156 -
Neural Regeneration Research Jun 2024Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor (AR) gene, which encodes a...
Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology.
Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor (AR) gene, which encodes a ligand-dependent transcription factor. The mutant AR protein, characterized by polyglutamine expansion, is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in SBMA patients. These aggregates alter protein-protein interactions and compromise transcriptional activity. In this study, we reported that in both cultured N2a cells and mouse brain, mutant AR with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-derived neurotrophic factor (MANF). Overexpression of MANF ameliorated the neurotoxicity of mutant AR through the inhibition of mutant AR aggregation. Conversely, knocking down endogenous MANF in the mouse brain exacerbated neuronal damage and mutant AR aggregation. Our findings suggest that inhibition of MANF expression by mutant AR is a potential mechanism underlying neurodegeneration in SBMA.
PubMed: 38934406
DOI: 10.4103/NRR.NRR-D-23-01666 -
Neural Regeneration Research Jun 2024Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target...
Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury-specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research (in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc (AXER-204), fasudil, phosphatase and tensin homolog protein (PTEN) antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide, (-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.
PubMed: 38934397
DOI: 10.4103/NRR.NRR-D-24-00176 -
Neural Regeneration Research Jun 2024Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of...
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
PubMed: 38934395
DOI: 10.4103/NRR.NRR-D-24-00067 -
Neuro-degenerative Diseases Jun 2024Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and...
INTRODUCTION
Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients.
METHODS
Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot.
RESULTS
GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1390-1556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles.
CONCLUSION
The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases.
PubMed: 38934198
DOI: 10.1159/000540006 -
Frontiers in Neurology 2024Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome with heterogeneous symptoms, which makes it a challenge for early diagnosis. The mutation...
Case report: Misdiagnosed orolingual dyskinesia as a consequence of seizures in a chorea-acanthocytosis patient with a novel variation from a family with consanguineous marriage.
Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome with heterogeneous symptoms, which makes it a challenge for early diagnosis. The mutation of is considered intimately related to the pathogenesis of ChAc. To date, diverse mutation patterns of , consisting of missense, nonsense, and frameshift mutations, have been reported. In this study, we first report a clinical case that was misdiagnosed as epilepsy due to recurrent seizures accompanied by tongue bite for 9 months, which was not rectified until seizures were controlled and involuntary orolingual movements with awareness became prominent and were confirmed to be orolingual dyskinesia. The patient was eventually diagnosed as ChAc based on whole-exome sequencing revealing novel homozygous c.2061dup (frameshift mutation) and c.6796A > T dual mutations in . The patient from a family with consanguineous marriage manifested epileptic seizures at onset, including both generalized tonic-clonic seizures and absence but normal long-term electroencephalography, and gradually developed orofacial dyskinesia, including involuntary tongue protrusion, tongue biting and ulcers, involuntary open jaws, occasionally frequent eye blinks, and head swings. The first test of the peripheral blood smear was negative, and repeated checks confirmed an elevated percentage of acanthocytes by 15-21.3%. Structural brain MRI indicated a mildly swollen left hippocampus and parahippocampal gyrus and a progressively decreased volume of the bilateral hippocampus 1 year later, along with atrophy of the head of the caudate nucleus but no progression in 1 year. We deeply analyzed the reasons for long-term misdiagnosis in an effort to achieve a more comprehensive understanding of ChAc, thus facilitating early diagnosis and treatment in future clinical practice.
PubMed: 38933328
DOI: 10.3389/fneur.2024.1352467 -
Acta Endocrinologica (Bucharest,... 2023Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is...
BACKGROUND
Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is counteracted by increased collagen production, deposition and scarring. However, only recently a specific subpopulation of modified fibroblasts with contractile properties, namely "myofibroblasts" (MFBs) have been linked to HT.
AIM
Our ultrastructural study aims to delineate the presence and contribution of MFBs to the fibrotic milieu of HT.
MATERIAL AND METHODS
Tissue biopsies were obtained from 5 HT-diagnosed patients and specimens were examined using a Transmission Electron Microscope (TEM).
RESULTS
Histopathological examination indicated extensive microvilli atrophy and atypical vacuolations of the thyroid follicular cells in the HT samples. In addition to interstitial extravasated lymphocytes, capillaries were encircled by MFBs (mean distance from lumen 1.248± 0.43µm) with the characteristic electron-dense α-smooth muscle actin (α-SMA), confirmable in higher magnifications. Myofibroblastic projections were found to have significantly higher representation near the capillary lumen compared to the impaired endothelial lining (P < 0.01).
CONCLUSION
Our TEM findings suggest that the intrusion of endothelia by myofibroblastic projections can be a significant factor towards the malfunction of follicular cells in HT patients and offer a paradigmal understanding of the ultrastructural interactions that may underlie the HT pathology.
PubMed: 38933253
DOI: 10.4183/aeb.2023.415