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Journal of Orthopaedic Surgery and... Jun 2024To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT).
OBJECTIVES
To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT).
MATERIAL AND METHODS
The T1- and T2-weighted imaging, Q-dixon, and T1-mapping MRI data of 38 children with CMT were retrospectively analyzed. The region of interest (ROI) was manually drawn at the level of the largest cross-sectional area of the SCM on the affected side. MaZda software was used to obtain the texture features of the T2WI sequences of the ROI in healthy and affected SCM. A radiomics diagnostic model based on muscle texture features was constructed using logistic regression analysis. Fatty infiltration grade was calculated by hematoxylin and eosin staining, and fibrosis ratio by Masson staining. Correlation between the MRI parameters and pathological indicators was analyzed.
RESULTS
There was positive correlation between fatty infiltration grade and mean value, standard deviation, and maximum value of the Q-dixon sequence of the affected SCM (correlation coefficients, 0.65, 0.59, and 0.58, respectively, P < 0.05).Three muscle texture features-S(2,2)SumAverg, S(3,3)SumVarnc, and T2WI extreme difference-were selected to construct the diagnostic model. The model showed significant diagnostic value for CMT (P < 0.05). The area under the curve of the multivariate conditional logistic regression model was 0.828 (95% confidence interval 0.735-0.922); the sensitivity was 0.684 and the specificity 0.868.
CONCLUSION
The radiomics diagnostic model constructed using T2WI muscle texture features and MRI signal values appears to have good diagnostic efficiency. Q-dixon sequence can reflect the fatty infiltration grade of CMT.
Topics: Humans; Torticollis; Magnetic Resonance Imaging; Male; Female; Retrospective Studies; Child, Preschool; Child; Infant; Severity of Illness Index; Neck Muscles; Adolescent
PubMed: 38902712
DOI: 10.1186/s13018-024-04827-4 -
General Hospital Psychiatry Jun 2024Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting...
PURPOSE
Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine.
METHODS
Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale.
RESULTS
The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles.
CONCLUSIONS
The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.
PubMed: 38901166
DOI: 10.1016/j.genhosppsych.2024.06.005 -
Journal of Clinical PsychopharmacologyDeutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use...
Deutetrabenazine Provides Long-Term Benefit for Tardive Dyskinesia Regardless of Underlying Condition and Dopamine Receptor Antagonist Use: A Post Hoc Analysis of the 3-Year, Open-Label Extension Study.
BACKGROUND
Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.
METHODS
Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794). In RIM-TD, deutetrabenazine was titrated based on dyskinesia control and tolerability. In this post hoc analysis of RIM-TD, total motor Abnormal Involuntary Movement Scale (AIMS) score and adverse events (AEs) were analyzed by underlying condition and DRA use at parent study baseline.
RESULTS
Of 343 patients enrolled in RIM-TD, 336 were included in the analysis by underlying condition, and 337 were included in the analysis by DRA use. One hundred eighty-nine of 205 (92%) patients with psychotic disorders (schizophrenia/schizoaffective disorder) and 65 of 131 (50%) with mood and other disorders (depression/bipolar disorder/other) were receiving a DRA. Mean (SE) deutetrabenazine doses at week 145 were 40.4 (1.13), 38.5 (1.21), 39.9 (1.00), and 38.5 (1.48) mg/d for patients with psychotic disorders, those with mood and other disorders, and those receiving DRAs or not, respectively. Mean (SD) changes in total motor AIMS score from this study baseline to week 145 were -6.3 (4.53), -7.1 (4.92), -6.1 (4.42), and -7.5 (5.19). Exposure-adjusted incidence rates (number of AEs/patient-years) of AEs were similar across groups: any (1.02, 1.71, 1.08, 1.97), serious (0.10, 0.12, 0.10, 0.12), and leading to discontinuation (0.07, 0.05, 0.06, 0.05).
CONCLUSIONS
Long-term deutetrabenazine provided clinically meaningful improvements in TD-related movements, with a favorable benefit-risk profile, regardless of underlying condition or DRA use.
Topics: Humans; Tardive Dyskinesia; Male; Female; Tetrabenazine; Middle Aged; Adult; Dopamine Antagonists; Psychotic Disorders; Aged; Antipsychotic Agents; Schizophrenia; Treatment Outcome
PubMed: 38901008
DOI: 10.1097/JCP.0000000000001885 -
Cell Biology and Toxicology Jun 2024Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through...
Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.
Topics: Animals; Peptides; Endosomes; Autophagy; Cell Nucleus; Drosophila Proteins; Active Transport, Cell Nucleus; Drosophila melanogaster; Machado-Joseph Disease; Enterocytes; Disease Models, Animal; Ataxin-3; Drosophila
PubMed: 38900277
DOI: 10.1007/s10565-024-09891-4 -
Epigenetics Dec 2024Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade...
Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.
Topics: Humans; Machado-Joseph Disease; DNA Methylation; Male; Female; Adult; Middle Aged; Mutation; Heterozygote; Case-Control Studies; Ataxin-3; 5-Methylcytosine; Aged; Epigenesis, Genetic
PubMed: 38900099
DOI: 10.1080/15592294.2024.2368995 -
ACS Pharmacology & Translational Science Jun 2024The 5-hydroxytryptamine-3 receptor (5-HTR), a subtype of serotonin receptor, is a ligand-gated ion channel crucial in mediating fast synaptic transmission in the central... (Review)
Review
The 5-hydroxytryptamine-3 receptor (5-HTR), a subtype of serotonin receptor, is a ligand-gated ion channel crucial in mediating fast synaptic transmission in the central and peripheral nervous systems. This receptor significantly influences various neurological activities, encompassing neurotransmission, mood regulation, and cognitive processing; hence, it may serve as an innovative target for neurological disorders. Multiple studies have revealed promising results regarding the beneficial effects of these phytoconstituents and extracts on conditions such as nausea, vomiting, neuropathic pain depression, anxiety, Alzheimer's disease, cognition, epilepsy, sleep, and dyskinesia via modulation of 5-HTR in the pathophysiology of neurological disorder. The review delves into a detailed exploration of , , and studies and clinical studies that discussed phytoconstituents acting on 5-HTR and attenuates difficulties in neurological diseases. The diverse mechanisms by which plant-derived phytoconstituents influence 5-HTR activity offer exciting avenues for developing innovative therapeutic interventions. Besides producing an agonistic or antagonistic effect, some phytoconstituents exert modulatory effects on 5-HTR activity through multifaceted mechanisms. These include γ-aminobutyric acid and cholinergic neuronal pathways, interactions with neurokinin (NK)-1, NK2, serotonergic, and γ-aminobutyric acid(GABA)ergic systems, dopaminergic influences, and mediation of calcium ions release and inflammatory cascades. Notably, the phytoconstituent's capacity to reduce oxidative stress has also emerged as a significant factor contributing to their modulatory role. Despite the promising implications, there is currently a dearth of exploration needed to understand the effect of phytochemicals on the 5-HTR. Comprehensive preclinical and clinical research is of the utmost importance to broaden our knowledge of the potential therapeutic benefits associated with these substances.
PubMed: 38898946
DOI: 10.1021/acsptsci.4c00084 -
World Journal of Clinical Cases Jun 2024Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,...
BACKGROUND
Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases, otolaryngological diseases, central nervous system abnormalities, reproductive system abnormalities, and cardiac function abnormalities. General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease.
CASE SUMMARY
A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture. Three years prior, he had been diagnosed with PCD. At that time, he had experienced several episodes of pneumonia, sinusitis, and chronic middle ear infections, for which he underwent surgical interventions. At the current admission, he presented with cough and sputum but no other respiratory symptoms. A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe. For the surgical procedure and postoperative pain management, combined spinal-epidural anesthesia was employed. The patient's postoperative pain score was measured by the numerical rating scale (NRS). On the day of surgery, his NRS was 5 points. By the second postoperative day, the NRS score had decreased to 2-3 points. The epidural catheter was removed on the fourth day following the operation. The patient was subsequently discharged no respiratory complications.
CONCLUSION
We performed combined spinal-epidural anesthesia in a patient with PCD. The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.
PubMed: 38898834
DOI: 10.12998/wjcc.v12.i17.3183 -
Annals of Plastic Surgery Jun 2024Dermatochalasis with lateral hooding and medial orbital fat loss are common signs of aging in the upper eyelid. Removing the excess skin in this area through infrabrow...
PURPOSE
Dermatochalasis with lateral hooding and medial orbital fat loss are common signs of aging in the upper eyelid. Removing the excess skin in this area through infrabrow skin excision can effectively lift the loose skin of the upper eyelid and minimizes visible scarring. Additionally, we have identified three compartments of orbital fat prolapse based on orbital anatomy. Transferring volume from the lateral compartment to the intermediate region can flatten the lateral upper eyelid and create medial fullness, which ultimately rejuvenates the upper eyelid. This study presents an operative method for correcting age-related changes in the upper eyelid using this technique.
METHODS
A total of 34 eyelids from 17 patients underwent a surgical procedure involving infrabrow skin excision, along with repositioning and lifting of lateral orbital fat. The inclusion criteria consisted of patients with moderate to severe upper eyelid dermatochalasis, coupled with middle fat loss and lateral hooding. To correct lateral hooding and restore midfacial fullness, lateral orbital fat was repositioned to an intermediate position, and the orbicularis oculi muscle was fold-sutured to the corrugator supercilii muscle.
RESULTS
The mean age of the patients was 55.59 ± 3.20 years, with a range of 48 to 61 years. The mean follow-up period was 9.94 ± 1.35 months, ranging from 8 to 12 months. Patients were evaluated at 1-month, 3-month, and 6-month intervals. The Strasser system was used to evaluate the surgical outcomes at 3 months. All patients achieved good surgical outcomes, expressed through satisfactory cosmetic improvements, and improved visual field. The procedure effectively corrected lateral hooding and loss of middle orbital fat through infrabrow skin excision. No complications, such as wound dehiscence, lagophthalmos, noticeable scarring, ocular dyskinesia, or sensory changes, were observed.
CONCLUSIONS
The combination of infrabrow skin excision, repositioning of lateral orbital fat, and lifting of the orbicularis oculi muscle effectively addresses moderate to severe dermatochalasis, lateral hooding, medial fat loss, and improves elasticity of the anterior wall of the upper lid in our patients. This procedure can produce satisfactory and long-lasting aesthetic results with an inconspicuous scar beneath the brow.
PubMed: 38896863
DOI: 10.1097/SAP.0000000000004006 -
Frontiers in Veterinary Science 2024A 4-year-old male neutered Boston Terrier was presented with status epilepticus. He was diagnosed with idiopathic epilepsy and hospitalized with supportive care. During...
A 4-year-old male neutered Boston Terrier was presented with status epilepticus. He was diagnosed with idiopathic epilepsy and hospitalized with supportive care. During hospitalization, the patient developed both supraventricular and ventricular arrhythmias as well as focal left ventricular dyskinesis. Cardiac troponin I was significantly increased, which was supportive of myocardial damage. Neurogenic stunned myocardium was suspected, and the patient was treated and responded to esmolol. Follow-up echocardiography demonstrated the resolution of the ventricular dyskinesia. This report describes the clinical presentation, diagnostic findings, treatment, management, and outcome of the first reported case of naturally occurring neurogenic stunned myocardium in a dog. Electrocardiogram monitoring, cardiac troponin I, and echocardiography should be considered in patients presenting with seizure activity, especially when exhibiting cluster seizures or in status epilepticus.
PubMed: 38895716
DOI: 10.3389/fvets.2024.1376107 -
Sensors (Basel, Switzerland) Jun 2024The interpretability of gait analysis studies in people with rare diseases, such as those with primary hereditary cerebellar ataxia (pwCA), is frequently limited by the...
The interpretability of gait analysis studies in people with rare diseases, such as those with primary hereditary cerebellar ataxia (pwCA), is frequently limited by the small sample sizes and unbalanced datasets. The purpose of this study was to assess the effectiveness of data balancing and generative artificial intelligence (AI) algorithms in generating synthetic data reflecting the actual gait abnormalities of pwCA. Gait data of 30 pwCA (age: 51.6 ± 12.2 years; 13 females, 17 males) and 100 healthy subjects (age: 57.1 ± 10.4; 60 females, 40 males) were collected at the lumbar level with an inertial measurement unit. Subsampling, oversampling, synthetic minority oversampling, generative adversarial networks, and conditional tabular generative adversarial networks (ctGAN) were applied to generate datasets to be input to a random forest classifier. Consistency and explainability metrics were also calculated to assess the coherence of the generated dataset with known gait abnormalities of pwCA. ctGAN significantly improved the classification performance compared with the original dataset and traditional data augmentation methods. ctGAN are effective methods for balancing tabular datasets from populations with rare diseases, owing to their ability to improve diagnostic models with consistent explainability.
Topics: Humans; Female; Male; Middle Aged; Gait; Cerebellar Ataxia; Rare Diseases; Artificial Intelligence; Algorithms; Adult; Gait Analysis; Aged
PubMed: 38894404
DOI: 10.3390/s24113613