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Cardiovascular Diabetology Nov 2023Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network of microvessels... (Review)
Review
Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network of microvessels beyond well-known and documented target organs, i.e., the retina, kidney, and peripheral nerves. Indeed, an intact microvascular bed is crucial for preserving each organ's specific functions and achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related microvascular dysfunction leads to widespread multiorgan consequences in still-overlooked non-traditional target organs such as the brain, the lung, the bone tissue, the skin, the arterial wall, the heart, or the musculoskeletal system. All these organs are vulnerable to the physiopathological mechanisms that cause microvascular damage in diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, and endothelial dysfunction) and collectively contribute to abnormalities in the microvessels' structure and function, compromising blood flow and tissue perfusion. However, the microcirculatory networks differ between organs due to variations in haemodynamic, vascular architecture, and affected cells, resulting in a spectrum of clinical presentations. The aim of this review is to focus on the multifaceted nature of microvascular impairment in diabetes through available evidence of specific consequences in often overlooked organs. A better understanding of diabetes microangiopathy in non-target organs provides a broader perspective on the systemic nature of the disease, underscoring the importance of recognising the comprehensive range of complications beyond the classic target sites.
Topics: Humans; Microcirculation; Diabetes Mellitus; Diabetic Angiopathies; Hyperglycemia; Retina; Kidney; Microvessels; Peripheral Nerves
PubMed: 37968679
DOI: 10.1186/s12933-023-02056-3 -
Cureus Jul 2023Fibrodysplasia ossificans progressiva (FOP), also known as Stoneman syndrome, is a rare genetic disorder characterized by abnormal bone development caused by activating... (Review)
Review
Fibrodysplasia ossificans progressiva (FOP), also known as Stoneman syndrome, is a rare genetic disorder characterized by abnormal bone development caused by activating mutations of the gene. FOP affects both the developmental and postnatal stages, resulting in musculoskeletal abnormalities and heterotopic ossification. Current treatment options for FOP are limited, emphasizing the need for innovative therapeutic approaches. Challenges in the development of management criteria for FOP include difficulties in recruitment due to the rarity of FOP, disease variability, the absence of reliable biomarkers, and ethical considerations regarding placebo-controlled trials. This narrative review provides an overview of the disease and explores emerging strategies for FOP treatment. Gene therapy, particularly the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system, holds promise in treating FOP by specifically targeting the gene mutation. Another gene therapy approach being investigated is RNA interference, which aims to silence the mutant gene. Small molecule inhibitors targeting glycogen synthase kinase-3β and modulation of the bone morphogenetic protein signaling pathway are also being explored as potential therapies for FOP. Stem cell-based approaches, such as mesenchymal stem cells and induced pluripotent stem cells, show potential in tissue regeneration and inhibiting abnormal bone formation in FOP. Immunotherapy and nanoparticle delivery systems provide alternative avenues for FOP treatment.
PubMed: 37521595
DOI: 10.7759/cureus.42614 -
Einstein (Sao Paulo, Brazil) 2023Miranda et al. reported a correlation between the significance of injuries to osseous, chondral, tendon, and ligamentous tissues in participants with low-grade versus...
UNLABELLED
Miranda et al. reported a correlation between the significance of injuries to osseous, chondral, tendon, and ligamentous tissues in participants with low-grade versus high-grade acute ankle sprains. They demonstrated that participants with high-grade ankle sprains presented with shorter calcaneonavicular distances and increased rates of structural abnormalities compared to those with low-grade sprains. Special attention should be paid to acute ankle sprains in emergency settings to avoid failure in detecting severe injuries that could lead to chronic pain, impairment, or instability. Participants presenting acute ankle sprains (<15 days) were divided into low-grade versus high-grade sprain,according to the presence of a complete tear in at least one component of lateral ligament complex. High-grade ankle sprains group presented increased rates of medial malleolus bone bruise, deltoid ligament tears,extensor retinaculum lesions, and articular effusion. The calcaneonavicular distance was statistically shorter in patients with high-grade sprains (median, 3.0mm) when compared to those with low-grade sprains (median, 4.0mm) Objective: To correlate the significance of osseous, chondral, tendon, and ligamentous injuries with anatomical variations in low-grade versus high-grade acute ankle sprains.
METHODS
We retrospectively identified the magnetic resonance imaging findings of acute ankle sprains (<15 days). Participants with a history of previous sprains, arthritis, tumors, infections, or inflammatory conditions were excluded. Images were independently evaluated by two musculoskeletal radiologists and assessed for osseous, chondral, tendon, and ligamentous injuries and anatomical variations. Participants were divided into low-grade versus high-grade sprain groups, according to the presence of a complete tear in at least one component of the lateral ligament complex.
RESULTS
The final study group comprised 100 magnetic resonance images (mean age, 36 years), the majority of males (54%), the right ankle (52%), and a mean sprain duration of 5 days. Participants with high-grade sprains presented with increased rates of medial malleolus edema (p<0.001), moderate and large articular effusions (p=0.041), and shorter calcaneonavicular distance (p=0.008). Complete tears of the anterior talofibular ligament and calcaneofibular ligaments were observed in 100% and 51.2% of the participants in the High-Grade Group, respectively. The deltoid ligament complex was partially torn in this group (55.8% versus 8.8%, p<0.001). Extensor tendon retinaculum lesions occurred significantly more frequently in this group (41.9%) compared to the overall study population (23%) (p<0.001).
CONCLUSION
Participants with high-grade ankle sprains presented with shorter calcaneonavicular distances and increased rates of medial malleolus edema, deltoid complex partial tears, extensor retinaculum lesions, and articular effusion.
Topics: Male; Humans; Adult; Retrospective Studies; Sprains and Strains; Ankle Joint; Magnetic Resonance Imaging; Ankle Injuries; Rupture; Edema
PubMed: 37820199
DOI: 10.31744/einstein_journal/2023AO0162 -
International Journal of Molecular... Aug 2023The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of... (Review)
Review
The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader-Willi (PWS) and Schaaf-Yang syndrome (SYS). PWS is caused by paternal deletion, maternal uniparental disomy, or imprinting defects that lead to loss of expression of a maternally imprinted region of chromosome 15 encompassing non-coding RNAs and five protein-coding genes; SYS patients have a mutation in one of them, . Throughout life, PWS and SYS patients suffer from musculoskeletal deficiencies, intellectual disabilities, and hormonal abnormalities, which lead to compulsive behaviors like hyperphagia and temper outbursts. Management of PWS and SYS is mostly symptomatic and cures for these debilitating disorders do not exist, highlighting a clear, unmet medical need. Research over several decades into the molecular and cellular roles of PWS genes has uncovered that several impinge on the neuroendocrine system. In this review, we will discuss the expression and molecular functions of PWS genes, connecting them with hormonal imbalances in patients and animal models. Besides the observed hormonal imbalances, we will describe the recent findings about how the loss of individual genes, particularly , affects the molecular mechanisms of hormone secretion. These results suggest that evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function.
Topics: Animals; Syndrome; Anxiety; Hypothalamus; Mammals; Neurosecretory Systems
PubMed: 37685915
DOI: 10.3390/ijms241713109 -
Heliyon Aug 2023This study examined the prevalence of musculoskeletal disorders (MSDs) and their associated factors among 1st to 4th-year students at Walailak University who attended...
OBJECTIVE
This study examined the prevalence of musculoskeletal disorders (MSDs) and their associated factors among 1st to 4th-year students at Walailak University who attended virtual classrooms for 1 week, 1 month, and 3 months.
METHOD
A cross-sectional study was conducted among 382 students aged 18-23 years with no history of musculoskeletal disease or psychiatric disorder who had at least three months of virtual classroom learning. Statistical analysis was performed using chi-squared and Fisher's exact tests.
RESULTS
Most musculoskeletal abnormalities occurred in the shoulders, head and neck, and lower back at 1 week, 1 month, and 3 months, respectively. At one week and one month in virtual classrooms, the occurrence of MSDs among the students was correlated with psychosocial factors (p < 0.05), and at three months, MSDs were associated with personal factors such as body mass index and psychosocial factors (p < 0.05).
CONCLUSION
Stress management for students should be implemented in virtual classrooms to prevent MSDs.
PubMed: 37520958
DOI: 10.1016/j.heliyon.2023.e18461 -
Frontiers in Pain Research (Lausanne,... 2023Widespread pain and hyperalgesia are characteristics of chronic musculoskeletal pain conditions, including fibromyalgia syndrome (FM). Despite mixed evidence, there is... (Review)
Review
Widespread pain and hyperalgesia are characteristics of chronic musculoskeletal pain conditions, including fibromyalgia syndrome (FM). Despite mixed evidence, there is increasing consensus that these characteristics depend on abnormal pain augmentation and dysfunctional pain inhibition. Our recent investigations of pain modulation with individually adjusted nociceptive stimuli have confirmed the mechanical and thermal hyperalgesia of FM patients but failed to detect abnormalities of pain summation or descending pain inhibition. Furthermore, our functional magnetic resonance imaging evaluations of spinal and brainstem pain processing during application of sensitivity-adjusted heat stimuli demonstrated similar temporal patterns of spinal cord activation in FM and HC participants. However, detailed modeling of brainstem activation showed that BOLD activity during "pain summation" was increased in FM subjects, suggesting differences in brain stem modulation of nociceptive stimuli compared to HC. Whereas these differences in brain stem activation are likely related to the hypersensitivity of FM patients, the overall central pain modulation of FM showed no significant abnormalities. These findings suggest that FM patients are hyperalgesic but modulate nociceptive input as effectively as HC.
PubMed: 38116188
DOI: 10.3389/fpain.2023.1284103 -
Journal of Nanobiotechnology Feb 2024Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among the elderly population. In this study, macrophage-derived exosomes were isolated...
Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among the elderly population. In this study, macrophage-derived exosomes were isolated and identified. Exosomes were subjected to microRNA (miRNA) sequencing and bioinformatic analysis, and differentially expressed miRNAs were verified. miR-26b-5p target genes were confirmed through target-site mutation combined with a dual-luciferase reporter assay. The effects of miR-26b-5p on macrophage polarization and chondrocyte hypertrophy were assessed in vitro. miR-26b-5p agomir was applied to mice with OA induced by anterior cruciate ligament transection (ACLT). The therapeutic effects of miR-26b-5p were evaluated via pain behavior experiments and histological observations. In vitro, miR-26b-5p repolarized M1 macrophages to an anti-inflammatory M2 type by targeting the TLR3 signaling pathway. miR-26b-5p could target COL10A1, further inhibiting chondrocyte hypertrophy induced by M1 macrophage-conditioned medium (M1-CM). In vivo, miR-26b-5p agomir ameliorated gait abnormalities and mechanical allodynia in OA mice. miR-26b-5p treatment attenuated synovitis and cartilage degeneration, thereby delaying OA progression. In conclusion, M2 macrophage-derived exosomal miR-26b-5p could protect articular cartilage and ameliorate gait abnormalities in OA mice by targeting TLR3 and COL10A1. miR-26b-5p further affected macrophage polarization and chondrocyte hypertrophy. Thus, this exosomal miR-26b-5p-based strategy might be a potential method for OA treatment.
Topics: Aged; Animals; Humans; Mice; Chondrocytes; Hypertrophy; Macrophages; MicroRNAs; Osteoarthritis; Toll-Like Receptor 3; Collagen Type X; Exosomes
PubMed: 38374072
DOI: 10.1186/s12951-024-02336-4 -
British Medical Bulletin Sep 2023Joint hypermobility (JHM) is a common physical trait. It may occur alone or in combination with musculoskeletal (MSK) pain, outside or within more complex phenotypes....
BACKGROUND
Joint hypermobility (JHM) is a common physical trait. It may occur alone or in combination with musculoskeletal (MSK) pain, outside or within more complex phenotypes. Hypermobility spectrum disorders (HSD) are diagnosed in individuals with JHM and related MSK pain, when an alternative diagnosis cannot be identified. Conversely, the Ehlers-Danlos syndrome (EDS) encompasses a group of rare hereditary connective tissue disorders featuring JHM along with other pleiotropic manifestations. The 2017 EDS Classification identifies 13 different subtypes. Hypermobile EDS (HEDS) is the only EDS variant still lacking a confirmatory test.
SOURCES OF DATA
Literature was reviewed searching for the most relevant papers related to key arguments. Particular attention was focused on papers published after the 2017 Classification.
AREAS OF AGREEMENT
Definition, epidemiology, assessment tools and patterns of JHM are presented. The morbid nature of the 2017 EDS Classification and of the 'spectrum' is also illustrated.
AREAS OF CONTROVERSY
We discuss current limitations and disagreements concerning the 'spectrum', HSD and HEDS.
GROWING POINTS
In the clinical context, elucidation of the pathophysiology of pain related to JHM should develop in parallel with the analysis of pleiotropic manifestations of syndromes with JHM.
AREAS TIMELY FOR DEVELOPING RESEARCH
Future challenges concerning classification, nosology, diagnosis and management of JHM, EDS and related disorders are discussed.
Topics: Humans; Syndrome; Joint Instability; Ehlers-Danlos Syndrome; Pain; Phenotype
PubMed: 37350130
DOI: 10.1093/bmb/ldad013 -
Journal of Indian Association of... 2023Diphallia (penile duplication) is a rare congenital malformation with an incidence of about 1 per 5-6 million newborns. The severity of diphallia varies from a small...
Diphallia (penile duplication) is a rare congenital malformation with an incidence of about 1 per 5-6 million newborns. The severity of diphallia varies from a small accessory penile-like tissue to complete true penile duplication with other deformities, usually involving the urogenital, gastrointestinal, and musculoskeletal systems. Pseudodiphallia, as a rare kind of diphallia, is characterized by a small accessory penile-like tissue without a normal penile anatomy structure. A 5.5-year-old male child was brought to the pediatric surgery outpatient department by the parents with complaint of difficulty in retracting the prepucial foreskin and the presence of some growth near the glans. There were no other complaints in specific. Clinical examination revealed foreskin retractable with difficulty and small conical lump smaller than the original glans approximately size ~1 cm diameter at the base attached horizontally at the left side of the original glans at the coronal sulcus and visible incomplete clefting in between the 2 glans visible from the aerial view. After approval from anesthetist, the patient was operated under general anesthesia by excision of pseudodiphallia. Urethral catheterization and circumcision of the penis after taking informed parental consent. Postoperatively, the period was uneventful. The patient responded well to the symptomatic treatment and was orally allowed on the same day evening. Urinary catheter was removed on 5 postoperative day. The patient was discharged on oral symptomatic medication and was advice for follow-up.
PubMed: 38173637
DOI: 10.4103/jiaps.jiaps_30_23