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A novel homozygous RSPH4A variant in a family with primary ciliary dyskinesia and literature review.Frontiers in Genetics 2024Primary ciliary dyskinesia (PCD) is a rare heterogeneous disease caused by abnormalities in motile cilia. In this case report, we first analyzed the clinical and...
Primary ciliary dyskinesia (PCD) is a rare heterogeneous disease caused by abnormalities in motile cilia. In this case report, we first analyzed the clinical and genetic data of a proband who was suspected of having PCD on the basis of her clinical and radiological findings. Whole-exome sequencing was performed, and a variant in the gene was identified in the proband. Sanger sequencing was used for validation of variants in the proband, her sister, her daughter and her parents. Finally, the phenotypic features of the patient were analyzed, and the current literature was reviewed to better understand the gene variants in PCD related to hearing loss and the clinical manifestations of the variant in PCD. The chief clinical symptoms of this proband included gradual mixed hearing loss, otitis media, anosmia, sinusitis, recurrent cough and infertility. Her DNA sequencing revealed a novel homozygous T to C transition at position 1321 within exon 3 of according to genetic testing results. This variant had never been reported before. The homozygous variant resulted in an amino acid substitution of tryptophan by arginine at position 441 (p.Trp441Arg). The same variant was also found in the proband's sister, and a heterozygous pathogenic variant was identified among immediate family members, including the proband's daughter and parents. A literature review showed that 16 pathogenic variants in have been reported. Hearing loss had only been observed in patients with the RSPH4A (c.921+3_6delAAGT) splice site mutation, and the specific type of hearing loss was not described.
PubMed: 38818043
DOI: 10.3389/fgene.2024.1364476 -
Haloperidol-induced painless legs and moving toe syndrome in a schizophrenia patient: a case report.Future Science OA 2024Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's...
Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's PoLMT is unknown. We present a case of PoLMT in 45-year-old woman with a history of haloperidol intake for 10 months. Haloperidol was discontinued, and aripiprazole (15 mg) was initiated. After this switch, a reduction in movement was observed in the third and fourth toes; however, the second toe showed no discernible change.
PubMed: 38817384
DOI: 10.2144/fsoa-2023-0207 -
Scientific Reports May 2024Intracerebral hemorrhage (ICH) is a common cerebral vascular disease with high incidence, disability, and mortality. Ferroptosis is a regulated type of iron-dependent,...
Intracerebral hemorrhage (ICH) is a common cerebral vascular disease with high incidence, disability, and mortality. Ferroptosis is a regulated type of iron-dependent, non-apoptotic programmed cell death. There is increasing evidence that ferroptosis may lead to neuronal damage mediated by hemorrhagic stroke mediated neuronal damage. Salvianolic acid A (SAA) is a natural bioactive polyphenol compound extracted from salvia miltiorrhiza, which has anti-inflammatory, antioxidant, and antifibrosis activities. SAA is reported to be an iron chelator that inhibits lipid peroxidation and provides neuroprotective effects. However, whether SAA improves neuronal ferroptosis mediated by hemorrhagic stroke remains unclear. The study aims to evaluate the therapeutic effect of SAA on Ferroptosis mediated by Intracerebral hemorrhage and explore its potential mechanisms. We constructed in vivo and in vitro models of intracerebral hemorrhage in rats. Multiple methods were used to analyze the inhibitory effect of SAA on ferroptosis in both in vivo and in vitro models of intracerebral hemorrhage in rats. Then, network pharmacology is used to identify potential targets and mechanisms for SAA treatment of ICH. The SAA target ICH network combines SAA and ICH targets with protein-protein interactions (PPIs). Find the specific mechanism of SAA acting on ferroptosis through molecular docking and functional enrichment analysis. In rats, SAA (10 mg/kg in vivo and 50 μM in vitro, p < 0.05) alleviated dyskinesia and brain injury in the ICH model by inhibiting ferroptosis (p < 0.05). The molecular docking results and functional enrichment analyses suggested that AKT (V-akt murine thymoma viral oncogene homolog) could mediate the effect of SAA. NRF2 (Nuclear factor erythroid 2-related factor 2) was a potential target of SAA. Our further experiments showed that salvianolic acid A enhanced the Akt /GSK-3β/Nrf2 signaling pathway activation in vivo and in vitro. At the same time, SAA significantly expanded the expression of GPX4, XCT proteins, and the nuclear expression of Nrf2, while the AKT inhibitor SH-6 and the Nrf2 inhibitor ML385 could reduce them to some extent. Therefore, SAA effectively ameliorated ICH-mediated neuronal ferroptosis. Meanwhile, one of the critical mechanisms of SAA inhibiting ferroptosis was activating the Akt/GSK-3β/Nrf2 signaling pathway.
Topics: Animals; Ferroptosis; Cerebral Hemorrhage; Caffeic Acids; Rats; Lactates; Male; Neuroprotective Agents; Rats, Sprague-Dawley; NF-E2-Related Factor 2; Molecular Docking Simulation; Disease Models, Animal; Signal Transduction; Proto-Oncogene Proteins c-akt
PubMed: 38816543
DOI: 10.1038/s41598-024-63277-4 -
EBioMedicine Jun 2024Neurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to...
BACKGROUND
Neurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to investigate how longitudinal trajectories of plasma NfL relate to HD disease stage.
METHODS
108 participants [78 individuals with the HD mutation, and 30 healthy controls (HC)] were included in this study. Individuals with the HD mutation were categorised separately by both HD-Integrated Staging System (HD-ISS) (Study 1) and PIN score-Approximated Staging System (PASS) (Study 2) criteria. Plasma NfL trajectories were examined using Mixed Linear Modeling (MLM); associations with symptom presentation were assessed using Spearman's rho correlations.
FINDINGS
The MLM coefficients for disease stage (HD-ISS β = 32.73, p < 0.0001; PASS β = 33.00, p < 0.0001) and disease stage∗time (HD-ISS β = 7.85, p = 0.004; PASS β = 6.58, p = 0.0047) suggest these are significant contributors to plasma NfL levels. In addition, the plasma NfL rate of change varied significantly across time (HD-ISS β = 3.14, p = 0.04; PASS β = 2.94, p = 0.050). The annualised rate of change was 8.32% for HC; 10.55%, 12.75% and 15.62% for HD-ISS Stage ≤1, Stage 2, and Stage 3, respectively; and 12.13%, 10.46%, 10.33%, 17.52%, for PASS Stage 0, Stage 1, Stage 2, and Stage 3, respectively. Plasma NfL levels correlated with the Symbol Digit Modalities Test (SDMT) in HD-ISS Stage ≤1, and both SDMT and Total Motor Score in Stage 3 (ps < 0.01).
INTERPRETATION
Our findings suggest that plasma NfL levels increase linearly across earlier disease stages, correlating with the cognitive SDMT measure. Thereafter, an increase or surge in plasma NfL levels, paired with correlations with both cognitive and motor measures, suggest a late acceleration in clinical and pathological progression.
FUNDING
NIH (NS111655); the UCSD HDSA CoE; the UCSD ADRC (NIH-NIA P30 AG062429).
Topics: Humans; Huntington Disease; Male; Neurofilament Proteins; Female; Middle Aged; Biomarkers; Longitudinal Studies; Adult; Disease Progression; Aged; Severity of Illness Index
PubMed: 38815362
DOI: 10.1016/j.ebiom.2024.105173 -
The Tohoku Journal of Experimental... May 2024
PubMed: 38811211
DOI: 10.1620/tjem.2024.J035 -
Neurobiology of Disease Aug 2024A number of post-mortem studies conducted in transplanted Huntington's disease (HD) patients from various trials have reported the presence of pathological and misfolded...
A number of post-mortem studies conducted in transplanted Huntington's disease (HD) patients from various trials have reported the presence of pathological and misfolded proteins, in particular mutant huntingtin (mHtt) and phosphorylated tau neuropil threads, in the healthy grafted tissue. Here, we extended these observations with histological analysis of post-mortem tissue from three additional HD patients who had received similar striatal allografts from the fetal tissue transplantation trial conducted in Los Angeles in 1998. Immunohistochemical staining was performed using anti-mHtt antibodies, EM48 and MW7, as well as anti-hyperphosphorylated tau antibodies, AT8 and CP13. Immunofluorescence was used to assess the colocalization of EM48 mHtt aggregates with the neuronal marker MAP2 and/or the extracellular matrix protein phosphacan in both the host and grafts. We confirmed the presence of mHtt aggregates within grafts of all three cases as well as tau neuropil threads in the grafts of two of the three transplanted HD patients. Phosphorylated tau was also variably expressed in the host cerebral cortex of all three subjects. While mHtt inclusions were present within neurons (immunofluorescence co-localization of MAP2 and EM48) as well as within the extracellular matrix of the host (immunofluorescence co-localization of phosphacan and EM48), their localization was limited to the extracellular matrix in the grafted tissue. This study corroborates previous findings that both mHtt and tau pathology can be found in the host and grafts of HD patients years post-grafting.
Topics: Humans; Huntington Disease; tau Proteins; Huntingtin Protein; Male; Middle Aged; Female; Neurons; Adult; Fetal Tissue Transplantation; Aged; Brain Tissue Transplantation
PubMed: 38810948
DOI: 10.1016/j.nbd.2024.106542 -
Rhode Island Medical Journal (2013) Jun 2024
Topics: Humans; Tremor; Toes; Publishing
PubMed: 38810016
DOI: No ID Found -
Rhode Island Medical Journal (2013) Jun 2024The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies and related disorders, generally thromboses, miscarriages, livedo...
The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies and related disorders, generally thromboses, miscarriages, livedo reticularis or heart valve abnormalities. It is thought to have a prevalence of about 40-50 cases per 100,000 in the general population.1 Several neurological disorders have been associated with APS, most commonly stroke, but non-stroke complications, thought due to auto- immune problems, have been noted, with chorea being the most common. Isolated toe tremor, that is, without any other neurological signs or symptoms, has not been reported. We describe a case of recurrent isolated uni- lateral toe tremor in an otherwise healthy woman with long-standing APS.
Topics: Humans; Antiphospholipid Syndrome; Female; Tremor; Toes; Middle Aged
PubMed: 38810009
DOI: No ID Found -
Annals of Transplantation May 2024BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for pediatric liver surgery. MATERIAL AND METHODS Sixty children who underwent liver surgery in our hospital were prospectively selected and randomly allocated into group A (placebo+remifentanil+sevoflurane) or group B (Dex+remifentanil+sevoflurane). Mean arterial pressure (MAP) and heart rate (HR) at different time points, agitation score during awakening, behavioral status, pain level, and the incidence of postoperative adverse effects were compared in both groups. RESULTS Children in group B had lower HR and MAP levels immediately after tracheal extubation and 5 min after tracheal extubation than those in group A. The Aono's scores, PAED agitation scores, and CHIPP scores at 15 min and 30 min of admission to the PACU were lower in group B than in group A. The incidence of agitation during postoperative anesthesia awakening was lower in group B in contrast to group A. There was no significant difference in postoperative adverse reactions between group A and group B. CONCLUSIONS In pediatric liver surgery, the use of Dex+remifentanil+sevoflurane anesthesia can reduce the incidence of EA during the awakening period, stabilize hemodynamic levels, and relieve postoperative pain, and has fewer postoperative adverse effects, which warrants clinical application.
Topics: Humans; Dexmedetomidine; Remifentanil; Sevoflurane; Female; Male; Anesthetics, Inhalation; Child, Preschool; Emergence Delirium; Prospective Studies; Hypnotics and Sedatives; Infant; Child; Psychomotor Agitation; Liver; Anesthesia Recovery Period; Piperidines; Double-Blind Method; Drug Therapy, Combination; Methyl Ethers; Analgesics, Opioid
PubMed: 38803088
DOI: 10.12659/AOT.943281 -
BMC Neurology May 2024Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether...
BACKGROUND
Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations.
METHODS
Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed.
RESULTS
Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD.
CONCLUSION
Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.
Topics: Humans; Torticollis; White Matter; Female; Male; Diffusion Tensor Imaging; Middle Aged; Adult; Nerve Net; Aged
PubMed: 38802755
DOI: 10.1186/s12883-024-03682-4