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Spinocerebellar ataxia (SCA) is a rare neurological illness inherited dominantly that causes severe impairment and premature mortality. While each rare disease may affect individuals infrequently, collectively they pose a significant healthcare challenge. It is mainly carried out due to the expansion of RNA triplet (CAG) repeats, although missense or point mutations can also be induced. Unfortunately, there is no cure; only symptomatic treatments are available. To date, SCA has about 48 subtypes, the most common of these being SCA 1, 2, 3, 6, 7, 12, and 17 having CAG repeats. Using molecular docking and molecular dynamics (MD) simulation, this study seeks to investigate effective natural herbal neuroprotective compounds against CAG repeats, which are therapeutically significant in treating SCA. Initially, virtual screening followed by molecular docking was used to estimate the binding affinity of neuroprotective natural compounds toward CAG repeats. The compound with the highest binding affinity, somniferine, was then chosen for MD simulation. The structural stability, interaction mechanism, and conformational dynamics of CAG repeats and somniferine were investigated via MD simulation. The MD study revealed that during the simulation period, the interaction between CAG repeats and somniferine stabilizes and results in fewer conformational variations. This in silico study suggests that Somniferine can be used as a therapeutic medication against RNA CAG repeats in SCA.
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Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Humanos , Descubrimiento de Drogas/métodos , ARN/química , ARN/metabolismo , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/tratamiento farmacológico , Ataxias Espinocerebelosas/metabolismo , Expansión de Repetición de Trinucleótido , Repeticiones de Trinucleótidos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/químicaRESUMEN
Extracellular vesicles (EVs) are released by all cells, can cross the blood-brain barrier, and have been shown to play an important role in cellular communication, substance shuttling, and immune modulation. In recent years EVs have shifted into focus in multiple sclerosis (MS) research as potential plasma biomarkers and therapeutic vehicles. Yet little is known about the disease-associated changes in EVs in the central nervous system (CNS). To address this gap, we characterized the physical and proteomic changes of mouse spinal cord-derived EVs before and at 16 and 25 days after the induction of experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory model of MS. Using various bioinformatic tools, we found changes in inflammatory, glial, and synaptic proteins and pathways, as well as a shift in the predicted contribution of immune and glial cell types over time. These results show that EVs provide snapshots of crucial disease processes such as CNS-compartmentalized inflammation, re/de-myelination, and synaptic pathology, and might also mediate these processes. Additionally, inflammatory plasma EV biomarkers previously identified in people with MS were also altered in EAE spinal cord EVs, suggesting commonalities of EV-related pathological processes during EAE and MS and overlap of EV proteomic changes between CNS and circulating EVs.
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Encefalomielitis Autoinmune Experimental , Vesículas Extracelulares , Ratones Endogámicos C57BL , Médula Espinal , Vesículas Extracelulares/metabolismo , Animales , Médula Espinal/metabolismo , Médula Espinal/patología , Ratones , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Femenino , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , ProteómicaRESUMEN
BACKGROUND: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused. OBJECTIVE: The aim was to identify genetic risk factors for PD in a South Asian population. METHODS: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early-onset PD) were recruited from 10 specialty movement disorder centers across India over a 2-year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case-only and case-control genetic analyses for PD diagnosis and AoO. RESULTS: A genome-wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease. CONCLUSIONS: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , MutaciónRESUMEN
INTRODUCTION: Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID. METHOD: In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG). RESULTS: The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models. CONCLUSION: The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.
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Discinesias , Enfermedad de Parkinson , Humanos , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/uso terapéutico , Discinesias/tratamiento farmacológico , Predisposición Genética a la Enfermedad , Genotipo , Levodopa/efectos adversos , Levodopa/genética , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido SimpleRESUMEN
The biosynthesis of AgNPs using a methanolic extract of Naringi crenulata is described in this study. UV-visible spectroscopy, X-ray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), particle size analyzer (PSA), scanning electron microscope (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) were used to characterize the synthesized AgNPs. The UV-visible spectrum revealed a sharp peak at 420 nm, which represents silver's strong Plasmon resonance. FTIR and XRD confirmed the functional groups (N-H stretch, alkanes, O-H stretch, carboxylic acid, N-H bend, C-X fluoride, and C-N stretch) and face-centered cubic crystalline structure of synthesized AgNPs. SEM and TEM analyses revealed that the synthesized nanoparticles had a spherical morphology with an average diameter of 32.75 nm. The synthesized AgNPs have antibacterial activity against multidrug-resistant bacteria pathogens such as Vibrio cholerae, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Klebsiella pneumoniae. AgNPs can be synthesized using a methanolic extract of Naringi crenulate, and the resulting particle may have wide range of biological applications.
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Nanopartículas del Metal , Plata , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Espectroscopía Infrarroja por Transformada de Fourier , Escherichia coli , Difracción de Rayos XRESUMEN
The ability of cobalt nanoparticles (CoNPs) to absorb electromagnetic waves led to their use as potential biomedical agents in recent years. The properties of magnetic fluid containing cobalt nanoparticles are extraordinary. Hence, this research was designed to evaluate the Co(NO3)2 reducing the potential of orange peel aqueous extract and assessed their antimicrobial and antioxidant activities. The aqueous extract derived from orange peel had the potential to fabricate the CoNPs from 1 M Co(NO3)2 and the synthesized CoNPs were successfully characterized by standard nanoparticles characterization techniques such as UV-vis spectrophotometer, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), and Dynamic light scattering (DLS) analyses. The FTIR analysis revealed that the synthesized CoNPs were capped with active functional groups. It was characterized by predominant peaks corresponding to carbonyl (CO), amide (CO = ), and C-O of alcohols or phenols. The size and shape of CoNPs were found as 14.2-22.7 nm and octahedral, respectively, under SEM analysis. Furthermore, at increased concentration, the CoNPs demonstrated remarkable antimicrobial activity against common bacterial (Escherichia coli, Staphylococcus aureus,Bacillus subtilis, and Klebsiella pneumoniae) and fungal (Aspergillus niger) pathogens. Furthermore, these CoNPs also showed considerable in-vitro antioxidant activities against various free articles such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Hydrogen Peroxide (H2O2). These results suggest that OP aqueous extract synthesized CoNPs possess considerable biomedical applications.
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Antiinfecciosos , Citrus sinensis , Nanopartículas del Metal , Antioxidantes/farmacología , Plata/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Cobalto , Peróxido de Hidrógeno , Extractos Vegetales/farmacología , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coliRESUMEN
The nanoparticles based drug delivery and treatment related research has been increased significantly in the recent years. Hence, the antibacterial, antifungal, and antioxidant activity potential of pre synthesized and characterized Titanium dioxide nanoparticles (TiO2 NPs) were investigated in this study through respective standard protocols. Interestingly, the obtained results revealed that TiO2 NPs have concentration dependent antibacterial activity against bacterial pathogens such as E. coli, P.mirabilis, V. cholerae, P. aeruginosa, S. typhimurium, and S. aureus at 100 µg mL-1 concentration. Furthermore, these TiO2 NPs showed remarkable antifungal activity against aspergillosis causing fungal pathogens such as A. niger, A. fumigatus, A. nidulans, and A. flavus at 100 µg mL-1 concentration. α-glucosidase. This TiO2 NPs also effectively inhibit the α-amylase (17%) and α-Glucosidase (37%) enzyme activity at 100 µg mL-1 dosage. The DPPH assay revealed that TiO2 NPs effectively scavenge DPPH free radicals by up to 89% at 100 µg mL-1 concentration, which was comparable to butylated hydroxytoluene (96%). These results suggest that the plant-based TiO2 NPs have remarkable in-vitro antibacterial, antifungal, and antioxidant activity. These may be considered for additional in-vitro and in-vivo experiments to assess their potential biomedical applications.
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Coleus , Nanopartículas del Metal , Nanopartículas , Antifúngicos/farmacología , Antifúngicos/química , Antioxidantes/farmacología , Staphylococcus aureus , Escherichia coli , Hipoglucemiantes , alfa-Glucosidasas , Titanio/química , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas/química , Pseudomonas aeruginosa , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/químicaRESUMEN
OBJECTIVE: Central post-stroke pain (CPSP) refers to neuropathic pain in areas of the body corresponding to stroke lesions. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is safe and effective against neuropathic pain. In this randomized double-blind placebo-controlled study, we studied the effect of duloxetine in CPSP patients. METHODS: Consecutive patients satisfying the inclusion criteria were enrolled in the study and were randomized in a simple 1:1 randomization to duloxetine and placebo groups. Baseline demographic, clinical and imaging data were obtained. Prespecified primary outcome was comparison of change in pain intensity from baseline to 4 weeks, as assessed on Numeric Rating Scale (NRS) in both groups. Prespecified secondary outcomes were comparison of change in average pain severity from baseline to 4 weeks as measured on Short-form McGill Pain Questionnaire-2 (SFMPQ-2) score and Pain Disability Index (PDI) score and comparison of Patient Global Impression of Change (PGIC) score at the end of 4 weeks of treatment in both groups. Duloxetine at doses of 30 mg and similarly appearing placebo tablets were given and the dose was doubled if there was no response at the end of 2 weeks. Response to treatment was defined as ≥2 points reduction of NRS pain score. RESULTS: In total, 82 patients were enrolled in the study, 41 in each group. There was a significant difference in reduction in NRS score between duloxetine and placebo group from baseline (6.51 ± 1.03 vs 6.37 ± 1.41) to 4 weeks (3.02 ± 1.70 vs 4.40 ± 1.77, P = .02 for difference in reduction between groups). SFMPQ-2 score (P = .032) and Pain Disability Index score (P = .005) also differ significantly from baseline to 4 weeks between the two groups. PGIC score at the end of 4 weeks was significantly different between the two groups (5.15 ± 1.54 vs 3.89 ± 1.51; P < .001). Responder rate (defined as % of patients with ≥ 2 points reduction on NRS pain score from baseline to end of 4 weeks), on post hoc analysis was found to be significantly higher in duloxetine group (80.5%) than placebo group (43.9%) (P = .042). CONCLUSIONS: Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain.
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Neuralgia , Accidente Cerebrovascular , Humanos , Clorhidrato de Duloxetina/uso terapéutico , Neuralgia/complicaciones , Resultado del Tratamiento , Dimensión del Dolor , Accidente Cerebrovascular/complicaciones , Método Doble CiegoRESUMEN
OBJECTIVE: Neurological disorders are the most common cause of morbidity and mortality in riverside cities. Earlier studies reported the presence of heavy metals in the riverside of Gangetic belt. Our study objective was to determine the prevalence of neurological diseases in Ganga riverside and further divided into sections as just across riverside within 25 kms and non-riverside as 25 kms away from the Ganga river. METHODS: This was a prospective observational study conducted in a tertiary care hospital of selected Gangetic belt. RESULTS: A total of 2016 patients were recorded in this period. Mean age of the participants was 47.89 years, majority were males 59.2%. Most of the patients n = 1154 were from within 25 kms of Ganga riverside and n = 862 patients were from non-riverside (25 kms away from Ganga river). Common neurological diseases were ischemic stroke 22.7%, haemorrhagic stroke 20.7%, seizures 13.7%, septic encephalopathy 9.4%, neuropathy 8.9%, Parkinson's disease 4.3%, myopathy 4.1%, myelitis 2.8%, headache 2.4%, amyotrophic lateral sclerosis 1.9% and functional disorder 1.9%. CONCLUSION: Present study showed that neurological diseases were more common in Ganga riverside and stroke including ischemic and hemorrhagic are most common neurological diseases noted in our study.
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Metales Pesados , Enfermedades del Sistema Nervioso Periférico , Accidente Cerebrovascular , Masculino , Humanos , Persona de Mediana Edad , Femenino , Convulsiones , HospitalesRESUMEN
BACKGROUND: The aim of the study was to investigate the clinical profile, disease burden, quality of life, and treatment patterns of various headache subtypes. METHOD: In this prospective observational study, 815 patients presenting with chief complaints of headache between January 2020 to September 2021 were registered. After a detailed history, clinical examination, and subtyping, they were assessed at baseline with well-validated scales for severity (Visual Analogue Scale-VAS), disability burden (Migraine Disability Assessment- MIDAS), Humanistic burden (Headache Impact Test-HIT-6), and quality of life (World health organization-quality of life-WHO-QoL-8) scores. After initiating adequate management, parameters were reassessed at 3 and 6 months. RESULTS: 549 (67.7%) patients had migraine (395-episodic migraine, 144-chronic migraine), 266 (32.2%) patients had tension-type headache (TTH). Loss of sleep, prolonged working hours, and stress were common triggers. Disease burden, severity, and poor life quality was quite high in migraine patients (76.5% with moderate to severe disability, 61.7% with severe headache at onset, and 72% with poor life quality). All parameters had statistically significant improvement with preventive medication and lifestyle changes. CONCLUSION: In our study, we found migraine was the most common primary headache followed by TTH. Migraine patients had more severity, disease burdens, and inferior quality of life at onset compared to other headaches. With early and proper diagnosis as well as preventive treatment (including lifestyle modifications), all parameters could be reversed positively in a brief time. This is the first study on headache burden and its effect on the quality of life in the north Indian population.
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PURPOSE OF REVIEW: Researchers suggests that patients with COVID-19 develop neuropathic pain within weeks or months following infection and that patients with neuropathic pain and COVID-19 sometimes present with deterioration of neurologic complications and pain exacerbation. The objective of this systematic review is to discuss the case-reports having neuropathic pain during and after COVID-19 infection. RECENT FINDINGS: Case reports that has described about patients getting neuropathy or neuropathic pain around the disease either immediately or late post COVID were included. The data was extracted and qualitatively synthesised. Literature was searched and 939 articles were found. 12 articles were screened as per the eligibility criteria and finally, 6 case reports on neuropathic pain in Covid-19 were selected from the database and manual search and finalised for analysis. 2 cases of herpes zoster and post herpetic neuralgia, 2 cases of intense burning pain, 1 case of trigeminal neuralgia and 1 of brachial plexopathy included for the review. Covid 19 viral neurogenic invasion is something very newly discovered topic of discussion in the field of research. With the passage of time, more cases will emerge and more data will be available for research. The review is registered in Prospero with no. CRD42021257060.
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COVID-19 , Neuralgia Posherpética , Neuralgia , Neuralgia del Trigémino , COVID-19/complicaciones , Humanos , Neuralgia/etiología , Neuralgia Posherpética/complicaciones , Neuralgia del Trigémino/complicacionesRESUMEN
BACKGROUND AND OBJECTIVES: BPPV (benign paroxysmal positional vertigo) is a syndrome marked by brief bouts of vertigo accompanied by rapid changes in head position. Recent ongoing therapeutic approaches used are vestibular rehabilitation exercises and physical maneuvers like the Epley maneuver, Semont maneuver. Gans repositioning maneuver (GRM) is a new hybrid maneuver, consisting of safe and comfortable series of postures that can be conveniently applied on patients with any spinal pathology or even in elderly. METHODS: Randomized controlled/clinical trials of the Gans maneuver were identified. The proportion of patients who improved as a result of each intervention was assessed, as well as the conversion of a 'positive' Dix-Hallpike test to a 'negative' Dix-Hallpike test. RESULTS: Improvement was seen in almost all patients with the Gans maneuver and the Epley Maneuver in three trials with the pooled estimate for random effect model is 1.12 [0.87; 1.43: 100%]. There were no significant side effects from the treatment. DISCUSSION: This study shows that the Gans maneuver is a safe and effective treatment for patients suffering from posterior canal BPPV. TRIAL REGISTRATION: The review is registered in Prospero with no. CRD42021234100.
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Vértigo Posicional Paroxístico Benigno , Posicionamiento del Paciente , Anciano , Vértigo Posicional Paroxístico Benigno/rehabilitación , Humanos , Examen Físico , Postura , Resultado del TratamientoRESUMEN
BACKGROUND: There are very few studies based on the updated dystonia classification. However, a comparison of the idiopathic and non-idiopathic dystonias based on the newer classification has not been done previously. OBJECTIVES: To study and compare the clinicoetiological profile of patients with idiopathic and non-idiopathic dystonia attending a movement disorder clinic of a tertiary care teaching institution. METHODS: All the consecutive dystonia patients from October 2017 to September 2019 fulfilling the inclusion criteria were subjected to a detailed clinical evaluation. Investigations were performed as per requirement. Patients were classified according to the consensus update on phenomenology and classification of dystonia. RESULTS: A total of 183 patients with dystonia were included, with 61.7% (113) males and 38.3% (70) females. The idiopathic group revealed a significantly earlier age of onset with cases slightly outnumbering (n = 96/183, 52.5%) the non-idiopathic group (n = 87/183, 47.5%). Focal dystonias were the commonest type in both the idiopathic (n = 58/96, 60.4%) and non-idiopathic groups (n = 30/87, 34.5%), while generalized dystonia accounted for 26.4% (n = 23/87) of the non-idiopathic cases and only 3.1% (n = 3/96) of the idiopathic cases. The majority of idiopathic cases were isolated dystonia (n = 93/96, 96.9%), while all hemidystonias were non-idiopathic. CONCLUSION: Focal dystonias were the commonest in both idiopathic and non-idiopathic groups, while generalized dystonia was significantly commoner in the non-idiopathic group. Acquired causes like drugs, perinatal insult were the commonest etiology in the non-idiopathic group. Hemidystonia was found exclusively in the non-idiopathic acquired group.
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Distonía , Trastornos Distónicos , Pruebas Diagnósticas de Rutina , Distonía/diagnóstico , Distonía/epidemiología , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/epidemiología , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Coronaviruses mainly affect the respiratory system; however, there are reports of SARS-CoV and MERS-CoV causing neurological manifestations. We aimed at discussing the various neurological manifestations of SARS-CoV-2 infection and to estimate the prevalence of each of them. METHODS: We searched the following electronic databases; PubMed, MEDLINE, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, Cochrane Library, WHO database, and ClinicalTrials.gov . Relevant MeSH terms for COVID-19 and neurological manifestations were used. Randomized controlled trials, non-randomized controlled trials, case-control studies, cohort studies, cross-sectional studies, case series, and case reports were included in the study. To estimate the overall proportion of each neurological manifestations, the study employed meta-analysis of proportions using a random-effects model. RESULTS: Pooled prevalence of each neurological manifestations are, smell disturbances (35.8%; 95% CI 21.4-50.2), taste disturbances (38.5%; 95%CI 24.0-53.0), myalgia (19.3%; 95% CI 15.1-23.6), headache (14.7%; 95% CI 10.4-18.9), dizziness (6.1%; 95% CI 3.1-9.2), and syncope (1.8%; 95% CI 0.9-4.6). Pooled prevalence of acute cerebrovascular disease was (2.3%; 95%CI 1.0-3.6), of which majority were ischaemic stroke (2.1%; 95% CI 0.9-3.3), followed by haemorrhagic stroke (0.4%; 95% CI 0.2-0.6), and cerebral venous thrombosis (0.3%; 95% CI 0.1-0.6). CONCLUSIONS: Neurological symptoms are common in SARS-CoV-2 infection, and from the large number of cases reported from all over the world daily, the prevalence of neurological features might increase again. Identifying some neurological manifestations like smell and taste disturbances can be used to screen patients with COVID-19 so that early identification and isolation is possible.
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Enfermedades del Sistema Nervioso Central/epidemiología , Enfermedades del Sistema Nervioso Central/virología , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Betacoronavirus , COVID-19 , Humanos , Pandemias , Prevalencia , SARS-CoV-2RESUMEN
BACKGROUND & OBJECTIVES: Parkinson's disease (PD) is a motor disorder that affects movement. More than 24 loci and 28 associated genes have been identified to be associated with this disease. The present study accounts for the contribution of two candidates, leucine-rich repeat kinase 2 ( LRRK2) and parkin RBR E3 ubiquitin protein ligase ( PRKN) in the PD patients, and their characterization in silico and in vitro. METHODS: A total of 145 sporadic PD cases and 120 ethnically matched healthy controls were enrolled with their informed consent. Mutation screening was performed by direct DNA sequencing of the targeted exons of LRRK2 and all exons flanking introns of PRKN. The effect of the pathogenic PRKN variants on a drug (MG-132) induced loss of mitochondrial membrane potential (â³ΨM) was measured by a fluorescent dye tetramethylrhodamine methyl ester (TMRM). RESULTS: Twelve and 20 genetic variants were identified in LRRK2 and PRKN, respectively. Interestingly, five out of seven exonic LRRK2 variants were synonymous. Further assessment in controls confirmed the rarity of two such p.Y1527 and p.V1615. Among the pathogenic missense variations (as predicted in silico) in PRKN, two were selected (p.R42H and p.A82E) for their functional study in vitro, which revealed the reduced fluorescence intensity of TMRM as compared to wild type, in case of p.R42H but not the other. INTERPRETATION & CONCLUSIONS: About 6.2 per cent of the cases (9/145) in the studied patient cohort were found to carry pathogenic (as predicted in silico) missense variations in PRKN in heterozygous condition but not in case of LRRK2 which was rare. The presence of two rare synonymous variants of LRRK2 (p.Y1527 and p.V1615) may support the phenomenon of codon bias. Functional characterization of selected PRKN variations revealed p.R42H to cause disruption of mitochondrial membrane potential (â³ΨM) rendering cells more susceptible to cellular stress.
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Enfermedad de Parkinson , Humanos , Leucina , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Mutación , Enfermedad de Parkinson/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Background & objectives: The National AIDS Control Organisation (NACO) and the ICMR-National Institute of Medical Statistics, the nodal agency for conducting HIV estimations in India, have been generating HIV estimates regularly since 2003. The objective of this study was to describe India's biennial HIV estimation 2017 process, data inputs, tool, methodology and epidemiological assumptions used to generate the HIV estimates and trends of key indicators for 2010-2017 at national and State/Union Territory levels. Methods: Demographic Projection (DemProj) and AIDS Impact Modules (AIM) of Spectrum 5.63 software recommended by the United Nations Programme on HIV and AIDS Global Reference Group on HIV Estimates, Modelling and Projections, were used for generating HIV estimations on key indicators. HIV sentinel surveillance, epidemiological and programme data were entered into Estimation Projection Package (EPP), and curve fitting was done using EPP classic model. Finally, calibration was done using the State HIV prevalence of two rounds of National Family Health Survey (NFHS) -3 and -4 and Integrated Biological and Behavioural Surveillance (IBBS), 2014-2015. Results: The national adult prevalence of HIV was estimated to be 0.22 per cent in 2017. Mizoram, Manipur and Nagaland had the highest prevalence over one per cent. An estimated 2.1 million people were living with HIV in 2017, with Maharashtra estimated to have the highest number. Of the 88 thousand annual new HIV infections estimated nationally in 2017, Telangana accounted for the largest share. HIV incidence was found to be higher among key population groups, especially people who inject drugs. The annual AIDS-related deaths were estimated to be 69 thousand nationally. For all indicators, geographic variation in levels and trends between States existed. Interpretation & conclusions: With a slow decline in annual new HIV infections by only 27 per cent from 2010 to 2017 against the national target of 75 per cent by 2020, the national target to end AIDS by 2030 may be missed; although at the sub-national level some States have made better progress to reduce new HIV infection. It calls for reinforcement of HIV prevention, diagnosis and treatment efforts by geographical regions and population groups.
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Infecciones por VIH , Trabajadores Sexuales , Adulto , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Incidencia , India/epidemiología , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Embarazo , PrevalenciaRESUMEN
Intracerebral pneumocephalus is commonly associated with head and facial trauma, ear infection, tumors and surgical interventions. Osteomas are relatively common, benign tumors that occur mainly in the paranasal sinuses, the frontal sinus in particular. Pneumocephalus has been commonly reported with frontal osteoma but isolated presentation as frontotemporal dementia is uncommon. Patient was admitted with complaints of change of behavior and forgetfulness for the last one year. He had progressively become more apathetic and presented with behavioral abnormalities. General physical examinations were within normal limits including the motor and sensory system although neuropsychiatry assessments were below the average level, with features of dementia. Further, MRI brain revealed pneumocephalus in bilateral frontal lobe. CT cisternography revealed a well defined lobulated densely sclerotic lesion of approximate size 20 × 17 × 27mm transverse and cranio-caudal axis respectively arising from right ethmoid sinus. Clinically, the association of pneumocephalus and isolated presentation as frontotemporal dementia has not been described to the best of our knowledge. A single case has been described with ethmoid osteoma. Radiological features were suggestive of osteoid osteoma. The uniqueness of the case is the development of dementia with frontotemporal involvement and resemblance with Frontotemporal Dementia. This is the only case with dementia and pneumocephalus (secondary to osteoid osteoma) to best of our knowledge.
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Neoplasias Óseas/complicaciones , Neoplasias Óseas/diagnóstico por imagen , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/etiología , Osteoma/complicaciones , Osteoma/diagnóstico por imagen , Neoplasias Óseas/patología , Senos Etmoidales/diagnóstico por imagen , Senos Etmoidales/patología , Demencia Frontotemporal/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteoma/patología , Neumocéfalo/complicaciones , Neumocéfalo/diagnóstico por imagen , Neumocéfalo/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Female sex workers (FSWs) have been identified as an important target group for human immunodeficiency virus (HIV)/sexually transmitted infections prevention. OBJECTIVES: This study aimed to describe sociodemographic and sex work characteristics and to identify the risk factors for HIV infection with special focus on the variations between home-based (HB) and non-HB (NHB) FSWs in three high-prevalent North-Eastern states of India: Manipur, Mizoram, and Nagaland. METHODS: Data from the National Integrated Bio-Behavioural Surveillance (IBBS) conducted in India during 2014-2015 were utilized in the study. IBBS is a quantitative survey conducted among identified high risk sub within India. Logistic regression analyses were performed using SAS 9.3.2 to determine the distribution and associations of sociodemographics and risk behaviors with HIV seropositivity of HB and NHB FSWs. RESULTS: HIV prevalence was found higher among NHB FSWs compared to HB FSW (7.3% vs. 4.6%). The proportions of FSW among HB (66.7%) were in sex work for longer duration are significantly higher than for NHB (60.2%) while risk of HIV infection due to injecting drug use was higher in NHB FSW (11.7% vs. 8.7%). Reference to FSW who were currently married, those who were widowed/divorced/separated had 2.73-fold risk of HIV. FSW who did not have any other income source were associated with 1.73 times more risk of HIV infection. Injecting drugs user among FSW respondents had four times higher likelihood to be HIV positive. CONCLUSION: A substantial proportion of NHB FSWs is mobile in nature. Targeted interventions are required urgently to minimize HIV risk among those FSWs especially the widowed/divorced/separated, sex work is only income source and who used injecting drugs for nonmedical purpose.
Asunto(s)
Infecciones por VIH/epidemiología , Trabajadores Sexuales/estadística & datos numéricos , Adolescente , Adulto , Femenino , Humanos , India/epidemiología , Modelos Logísticos , Prevalencia , Asunción de Riesgos , Factores Socioeconómicos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto JovenRESUMEN
Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission, which presents with fluctuating and variable weakness in ocular, bulbar, limb, and respiratory muscles resulting from an antibody-mediated, T-cell-dependent immunologic attack on the postsynaptic membrane of the neuromuscular junction. Although treatment of MG and myasthenic crisis is based on few specific principles, it is highly individualized. We report a successfully treated case of refractory myasthenic crisis who was on a ventilator for 7 months (210 days), perhaps the longest from India, and required multiple cycles of plasma exchange, intravenous immunoglobulin infusion, and one cycle of rituximab. It exemplifies the role of highly individualized therapy and interdisciplinary cooperation in management of refractory myasthenic crisis. HOW TO CITE THIS ARTICLE: Singh RK, Joshi D, Rath S. Successfully Treated Hepatitis B Positive Refractory Myasthenic Crisis with Rituximab. Indian J Crit Care Med 2020;24(1):71-72.