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Molecular Neurobiology Jun 2024MicroRNA (miRNA) are usually 18-25 nucleotides long non-coding RNA targeting post-transcriptional regulation of genes involved in various biological processes. The... (Review)
Review
MicroRNA (miRNA) are usually 18-25 nucleotides long non-coding RNA targeting post-transcriptional regulation of genes involved in various biological processes. The function of miRNA is essential for maintaining a homeostatic cellular condition, regulating autophagy, cellular motility, and inflammation. Dysregulation of miRNA is responsible for multiple disorders, including neurodegeneration, which has emerged as a severe problem in recent times and has verified itself as a life-threatening condition that can be understood by the continuous destruction of neurons affecting various cognitive and motor functions. Parkinson's disease (PD) is the second most common, permanently debilitating neurodegenerative disorder after Alzheimer's, mainly characterized by uncontrolled tremor, stiffness, bradykinesia or akinesia (slowness in movement), and post-traumatic stress disorder. PD is mainly caused by the demolition of the primary dopamine neurotransmitter secretory cells and dopaminergic or dopamine secretory neurons in the substantia nigra pars compacta of the midbrain, which are majorly responsible for motor functions. In this study, a systematic evaluation of research articles from year 2017 to 2022 was performed on multiple search engines, and lists of miRNA being dysregulated in PD in different body components were generated. This study highlighted miR-7, miR-124, miR-29 family, and miR-425, showing altered expression levels during PD's progression, further regulating the expression of multiple genes responsible for PD.
PubMed: 38823001
DOI: 10.1007/s12035-024-04261-x -
The Journal of Pharmacy Technology :... Oct 2023Acute encephalopathy is a common symptom encountered in critically ill patients and may be associated with Wernicke's encephalopathy (WE) or serotonin syndrome (SS). We...
Acute encephalopathy is a common symptom encountered in critically ill patients and may be associated with Wernicke's encephalopathy (WE) or serotonin syndrome (SS). We describe a patient who presented with clinical manifestations of both WE and SS and who responded to treatment for both pathologies. A 56-year-old male presented after being found unresponsive and in a questionable tonic-clonic state. Past medical history was significant for depression managed with fluoxetine 20 mg by mouth daily and alcohol use disorder. A physical exam revealed severe clonus in the bilateral lower extremities; diffuse hyperreflexia along with akinesia on the left upper extremity; ophthalmoplegia; and persistent tachycardia despite pharmacologic interventions. It was learned that the patient had been taking his fluoxetine 3 times per day rather than daily as prescribed. Oral cyproheptadine was administered at a 12 mg initial dose followed by 4 mg every 6 hours. A thiamine regimen of 500 mg intravenous (IV) every 8 hours in addition to folic acid 1 mg IV every 24 hours was initiated to treat WE. Physical symptoms of both WE and SS resolved within 48 hours, and the patient was ultimately discharged to home in stable condition. The clinical diagnosis of both WE and SS in this case is supported by the Caine and Hunter criteria, respectively, as well as the resolution of symptoms with accepted treatment modalities for each. It is important for clinicians to be cognizant of potential overlapping pathologies when patients present with nonspecific symptoms, especially acute encephalopathy, in the intensive care unit.
PubMed: 37745730
DOI: 10.1177/87551225231195536 -
Movement Disorders : Official Journal... Jun 2024Isolated Rapid Eye Movement (REM) sleep Behavior Disorder (iRBD) requires quantitative tools to detect incipient Parkinson's disease (PD).
BACKGROUND
Isolated Rapid Eye Movement (REM) sleep Behavior Disorder (iRBD) requires quantitative tools to detect incipient Parkinson's disease (PD).
METHODS
A motor battery was designed and compared with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) in people with iRBD and controls. This included two keyboard-based tests (BRadykinesia Akinesia INcoordination tap test and Distal Finger Tapping) and two dual tasking tests (walking and finger tapping).
RESULTS
We included 33 iRBD patients and 29 controls. The iRBD group performed both keyboard-based tapping tests more slowly (P < 0.001, P = 0.020) and less rhythmically (P < 0.001, P = 0.006) than controls. Unlike controls, the iRBD group increased their walking duration (P < 0.001) and had a smaller amplitude (P = 0.001) and slower (P = 0.007) finger tapping with dual task. The combination of the most salient motor markers showed 90.3% sensitivity for 89.3% specificity (area under the ROC curve [AUC], 0.94), which was higher than the MDS-UPDRS-III (minus action tremor) (69.7% sensitivity, 72.4% specificity; AUC, 0.81) for detecting motor dysfunction.
CONCLUSION
Speed, rhythm, and dual task motor deterioration might be accurate indicators of incipient PD in iRBD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; REM Sleep Behavior Disorder; Male; Female; Aged; Middle Aged; Parkinson Disease; Psychomotor Performance; Walking; Severity of Illness Index
PubMed: 38470080
DOI: 10.1002/mds.29779 -
Experimental Brain Research Feb 2024Depression is a common non-motor symptom in Parkinson's disease (PD) that includes anhedonia and impacts quality of life but is not effectively treated with conventional...
Depression is a common non-motor symptom in Parkinson's disease (PD) that includes anhedonia and impacts quality of life but is not effectively treated with conventional antidepressants clinically. Vagus nerve stimulation improves treatment-resistant depression in the general population, but research about its antidepressant efficacy in PD is limited. Here, we administered peripheral non-invasive focused ultrasound to hemiparkinsonian ('PD') and non-parkinsonian (sham) rats to mimic vagus nerve stimulation and assessed its antidepressant-like efficacy. Following 6-hydroxydopamine (6-OHDA) lesion, akinesia-like immobility was assessed in the limb-use asymmetry test, and despair- and anhedonic-like behaviors were evaluated in the forced swim test and sucrose preference test, respectively. After, tyrosine hydroxylase immuno-staining was employed to visualize and quantify dopaminergic degeneration in the substantia nigra pars compacta, ventral tegmental area, and striatum. We found that PD rats exhibited akinesia-like immobility and > 90% reduction in tyrosine hydroxylase immuno-staining ipsilateral to the lesioned side. PD rats also demonstrated anhedonic-like behavior in the sucrose preference test compared to sham rats. No 6-OHDA lesion effect on immobility in the forced swim test limited conclusions about the efficacy of ultrasound on despair-like behavior. However, ultrasound improved anhedonic-like behavior in PD rats and this efficacy was sustained through the end of the 1-week recovery period. The greatest number of animals demonstrating increased sucrose preference was in the PD group receiving ultrasound. Our findings here are the first to posit that peripheral non-invasive focused ultrasound to the celiac plexus may improve anhedonia in PD with further investigation needed to reveal its potential for clinical applicability.
Topics: Humans; Rats; Animals; Anhedonia; Rats, Wistar; Tyrosine 3-Monooxygenase; Quality of Life; Parkinson Disease; Oxidopamine; Antidepressive Agents; Sucrose; Disease Models, Animal
PubMed: 38059986
DOI: 10.1007/s00221-023-06750-2 -
Clinical Nuclear Medicine Jun 2024Progressive supranuclear palsy (PSP) is the most prevalent form of degenerative atypical parkinsonism. Clinical manifestations of PSP commonly encompass deficits in...
Progressive supranuclear palsy (PSP) is the most prevalent form of degenerative atypical parkinsonism. Clinical manifestations of PSP commonly encompass deficits in vertical gaze, postural stability, akinesia, and cognitive impairment. The characteristic metabolic pattern observed in PSP through FDG PET displays hypometabolism in the midbrain, striatum, thalamus, and frontal lobe. However, visual interpretation of midbrain hypometabolism poses challenges. In this report, we aim to elucidate a novel observation termed the "loss of Mickey Mouse ears' sign," which signifies midbrain hypometabolism as detected through visual assessment of FDG PET images.
Topics: Supranuclear Palsy, Progressive; Humans; Positron-Emission Tomography; Fluorodeoxyglucose F18; Male; Aged
PubMed: 38598736
DOI: 10.1097/RLU.0000000000005229 -
European Journal of Obstetrics,... Jan 2024To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM).
OBJECTIVE
To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM).
STUDY DESIGN
This was a retrospective study of nine cases with NM diagnosed by prenatal or postnatal clinical features and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, exome sequencing (ES) results, and pregnancy outcomes.
RESULTS
All of the nine cases were detected to have NM-causing variants, involving NEB gene in 2 cases, ACTA1 in 3 cases, KLHL40 in 3 cases, and TPM2 in 1 case. Almost all (8/9) had normal first-trimester ultrasound scans except one who had an increased nuchal translucency. Seven (7/9) cases had second-trimester abnormal ultrasounds with fetal akinesia and/or extremity anomalies. Two (2/9) had only third-trimester abnormal ultrasounds with fetal akinesia and polyhydramnios, with one combined with fetal growth restriction. Four pregnancies with a positive prenatal ES were terminated, while five having not receiving prenatal ES continued to term. Only one infant survived 1 year old, and four passed away within 12 months.
CONCLUSION
Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies.
Topics: Pregnancy; Female; Humans; Infant; Myopathies, Nemaline; Retrospective Studies; Polyhydramnios; Ultrasonography, Prenatal; Pregnancy Outcome; Muscle Proteins
PubMed: 38071834
DOI: 10.1016/j.ejogrb.2023.12.005 -
Prenatal Diagnosis Dec 2023Fetal arthrogryposis is a well-recognised ultrasonographic phenotype, caused by both genetic, maternal and extrinsic factors. When present with fetal growth restriction,...
Fetal arthrogryposis is a well-recognised ultrasonographic phenotype, caused by both genetic, maternal and extrinsic factors. When present with fetal growth restriction, pulmonary hypoplasia and multiple joint contractures, it is often referred to as fetal akinesia deformation sequence (FADS). Historically, elucidating genetic causes of arthryogryposis/FADS has been challenging; there are now more than 150 genes known to cause arthrogryposis through myopathic, neuromuscular and metabolic pathways affecting fetal movement. FADS is associated with over 400 medical conditions making prenatal diagnosis challenging. Here we present a case of FADS diagnosed at 19 weeks gestation with progression to severe fetal hydrops and stillbirth at 26-weeks gestation. Initial investigations including combined first trimester screening, TORCH (infection) screen and chromosomal microarray were normal. Trio whole exome sequencing (WES) detected compound heterozygous likely pathogenic CACNA1S gene variants associated with autosomal dominant (AD) and autosomal recessive (AR) congenital myopathy and FADS. To our knowledge, this is the first prenatal diagnosis of this condition.
Topics: Pregnancy; Female; Humans; Arthrogryposis; Stillbirth; Prenatal Diagnosis; Edema; Calcium Channels, L-Type
PubMed: 38111203
DOI: 10.1002/pd.6471 -
Scientific Reports Jan 2024Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by...
Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by impaired neuromuscular transmission. Most CMS originate from defects in the muscle nicotinic acetylcholine receptor, but the underlying molecular pathogenesis is only poorly understood. Here we show that RNAi-mediated silencing of FADS-related proteins rapsyn and NUP88 in foetal fibroblasts alters organisation of the actin cytoskeleton. We show that fibroblasts from two independent FADS individuals have enhanced and shorter actin stress fibre bundles, alongside with an increased number and size of focal adhesions, with an otherwise normal overall connectivity and integrity of the actin-myosin cytoskeleton network. By proximity ligation assays and bimolecular fluorescence complementation, we show that rapsyn and NUP88 localise nearby adhesion plaques and that they interact with the focal adhesion protein paxillin. Based on these findings we propose that a respective deficiency in rapsyn and NUP88 in FADS alters the regulation of actin dynamics at focal adhesions, and thereby may also plausibly dictate myofibril contraction in skeletal muscle of FADS individuals.
Topics: Humans; Actins; Arthrogryposis; Receptors, Nicotinic; Myasthenic Syndromes, Congenital
PubMed: 38242956
DOI: 10.1038/s41598-023-50615-1 -
Revista de La Facultad de Ciencias... Mar 2024to describe a patient with myocardial ischemia with multiple causes.
OBJECTIVE
to describe a patient with myocardial ischemia with multiple causes.
CLINICAL CASE
This clinical case describes a 58-year-old man with a history of hypertension, dyslipidemia, COPD and previous myocardial infarction (AMI). He went to the emergency room with chest pain and dyspnea. Findings included bibasal crackles, electrocardiogram with old anterior fibrosis, elevated NT-ProBNP, and echocardiogram with septoapical akinesia. During hospitalization, he experienced tachyarrhythmia and hemodynamic deterioration, undergoing electrical cardioversion (CVE). Non-ST segment elevation acute coronary syndrome (NSTEACS) complicated with ventricular arrhythmia and acute pulmonary edema was diagnosed. Coronary angiography revealed coronary ectasias without obstructive lesions, but with mild stenosis in three vessels. The patient was successfully treated with non-invasive ventilation, diuretics, vasodilators and anticoagulation. The discharge was granted with the plan to further studies to optimize and guide treatment and finally the diagnosis of Myocardial Infarction with Non-Obstructive Arteries (MINOCA) and the presence of coronary ectasias was addressed.
CONCLUSION
it is important to highlight the non-ischemic causes in MINOCA and the association between coronary ectasia and cardiovascular events, which is why we emphasize the need for more studies to better understand the relationship between these phenomena.
Topics: Humans; Dilatation, Pathologic; MINOCA; Retrospective Studies
PubMed: 38537091
DOI: 10.31053/1853.0605.v81.n1.43231 -
HGG Advances Apr 2024Biallelic loss-of-function variants in the MUSK gene result in two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder...
Biallelic loss-of-function variants in the MUSK gene result in two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder that has a range of severity from severe neonatal-onset weakness to mild adult-onset weakness, and (2) fetal akinesia deformation sequence (OMIM: 208150), a form of pregnancy loss characterized by severe muscle weakness in the fetus. The MUSK gene codes for muscle-specific kinase (MuSK), a receptor tyrosine kinase involved in the development of the neuromuscular junction. Here, we report a case of neonatal-onset MUSK-related CMS in a patient harboring compound heterozygous deletions in the MUSK gene, including (1) a deletion of exons 2-3 leading to an in-frame MuSK protein lacking the immunoglobulin 1 (Ig1) domain and (2) a deletion of exons 7-11 leading to an out-of-frame, truncated MuSK protein. Individual domains of the MuSK protein have been elucidated structurally; however, a complete MuSK structure generated by machine learning algorithms has clear inaccuracies. We modify a predicted AlphaFold structure and integrate previously reported domain-specific structural data to suggest a MuSK protein that dimerizes in two locations (Ig1 and the transmembrane domain). We analyze known pathogenic variants in MUSK to discover domain-specific genotype-phenotype correlations; variants that lead to a loss of protein expression, disruption of the Ig1 domain, or Dok-7 binding are associated with the most severe phenotypes. A conceptual model is provided to explain the severe phenotypes seen in Ig1 variants and the poor response of our patient to pyridostigmine.
PubMed: 38566418
DOI: 10.1016/j.xhgg.2024.100288