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1.
Ann Neurol ; 95(3): 530-543, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37997483

RESUMEN

OBJECTIVE: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years. RESULTS: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17). INTERPRETATION: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543.


Asunto(s)
Disfunción Cognitiva , Demencia , Enfermedades Neurodegenerativas , Trastornos Parkinsonianos , Trastorno de la Conducta del Sueño REM , Humanos , Trastorno de la Conducta del Sueño REM/diagnóstico , Disfunción Cognitiva/diagnóstico
2.
Artículo en Inglés | MEDLINE | ID: mdl-39288960

RESUMEN

BACKGROUND: Research on the possible influence of lateralised basal ganglia dysfunction on speech in Parkinson's disease is scarce. This study aimed to compare speech in de-novo, drug-naive patients with Parkinson's disease (PD) with asymmetric nigral dopaminergic dysfunction, predominantly in either the right or left hemisphere. METHODS: Acoustic analyses of reading passages were performed. Asymmetry of nigral dysfunction was defined using dopamine transporter-single-photon emission CT (DAT-SPECT). RESULTS: From a total of 135 de novo patients with PD assessed, 47 patients had a lower right and 36 lower left DAT availability in putamen based on DAT-SPECT. Patients with PD with lower left DAT availability had higher dysarthria severity via composite dysarthria index compared with patients with lower right DAT availability (p=0.01). CONCLUSION: Our data support the crucial role of DAT availability in the left putamen in speech. This finding might provide important clues for managing speech following deep brain stimulation.

3.
Mov Disord ; 39(10): 1752-1762, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39001636

RESUMEN

BACKGROUND: Speech dysfunction represents one of the initial motor manifestations to develop in Parkinson's disease (PD) and is measurable through smartphone. OBJECTIVE: The aim was to develop a fully automated and noise-resistant smartphone-based system that can unobtrusively screen for prodromal parkinsonian speech disorder in subjects with isolated rapid eye movement sleep behavior disorder (iRBD) in a real-world scenario. METHODS: This cross-sectional study assessed regular, everyday voice call data from individuals with iRBD compared to early PD patients and healthy controls via a developed smartphone application. The participants also performed an active, regular reading of a short passage on their smartphone. Smartphone data were continuously collected for up to 3 months after the standard in-person assessments at the clinic. RESULTS: A total of 3525 calls that led to 5990 minutes of preprocessed speech were extracted from 72 participants, comprising 21 iRBD patients, 26 PD patients, and 25 controls. With a high area under the curve of 0.85 between iRBD patients and controls, the combination of passive and active smartphone data provided a comparable or even more sensitive evaluation than laboratory examination using a high-quality microphone. The most sensitive features to induce prodromal neurodegeneration in iRBD included imprecise vowel articulation during phone calls (P = 0.03) and monopitch in reading (P = 0.05). Eighteen minutes of speech corresponding to approximately nine calls was sufficient to obtain the best sensitivity for the screening. CONCLUSION: We consider the developed tool widely applicable to deep longitudinal digital phenotyping data with future applications in neuroprotective trials, deep brain stimulation optimization, neuropsychiatry, speech therapy, population screening, and beyond. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Teléfono Inteligente , Humanos , Trastorno de la Conducta del Sueño REM/fisiopatología , Trastorno de la Conducta del Sueño REM/diagnóstico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Transversales , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Biomarcadores , Voz/fisiología , Trastornos Parkinsonianos/fisiopatología , Síntomas Prodrómicos , Trastornos del Habla/etiología
4.
Phys Chem Chem Phys ; 26(39): 25514-25523, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39327870

RESUMEN

In this study, we investigate the effect of mixed surface terminations (F, O, OH) on the properties of M2C MXenes (M = Sc, Ti, V). We explore how different compositions and patterns of terminal groups affect the stability and electronic properties of these 2D materials. The bond dissociation energies and cohesion energies show a clear preference for F-terminations in Sc2C, while Ti- and V-based MXenes prefer O-terminations. Our study is the first to demonstrate that terminal groups on opposite sides of the MXene have little to no influence on each other's electronic structure, allowing for independent chemical environments on each side. In a first of its kind investigation semiconducting forms of studied MXenes (Sc2CF2, Sc2C(OH)2 and Ti2CO2) showed very high sensitivity to conduction-inducing terminations (O, O, and F, respectively) with even minuscule amounts (≈1%) causing the materials to become conductive. This high sensitivity of the band gap to surface terminations may offer an explanation for the challenges in synthesizing semiconducting forms of MXenes.

5.
Int J Mol Sci ; 25(4)2024 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-38396856

RESUMEN

The aim of this study was to conduct QuantiFERON Monitor (QFM) testing in patients with multiple sclerosis (MS), which is used to monitor the state of the immune system through the non-specific stimulation of leukocytes followed by determining the level of interferon-gamma (IFN-γ) released from activated cells. Additionally, we tested the level of selected cytokines (IFN-α, IFN-γ, IL-1α, IL-1ß, IL-1ra, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IL-15, IL-33, VEGF) from stimulated blood samples to further understand the immune response. This study builds upon a previously published study, utilizing activated serum samples that were initially used for IFN-γ determination. However, our current focus shifts from IFN-γ to exploring other cytokines that could provide further insights into the immune response. A screening was conducted using Luminex technology, which yielded promising results. These results were then further elaborated upon using ELISA to provide a more detailed understanding of the cytokine profiles involved. This study, conducted from August 2019 to June 2023, included 280 participants: 98 RRMS patients treated with fingolimod (fMS), 96 untreated patients with progressive MS (pMS), and 86 healthy controls (HC). Our results include Violin plots showing elevated IL-1α in pMS and fMS. Statistical analysis indicated significant differences in the interleukin levels between groups, with IL-1ra and age as key predictors in differentiating HC from pMS and IL-1ra, IL-1α, age, and EDSS in distinguishing pMS from fMS. These findings suggest cytokines' potential as biomarkers in MS progression and treatment response.


Asunto(s)
Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico , Proteína Antagonista del Receptor de Interleucina 1 , Citocinas , Interferón gamma , Sistema Inmunológico
6.
Eur Neurol ; 86(5): 334-340, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37473734

RESUMEN

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease that secondarily leads to axonal loss and associated brain atrophy. Disease-modifying drugs (DMDs) have previously been studied for their ability to affect specific immunity. This study investigates the effect of interferon beta-1a (INF) and glatiramer acetate (GA) administration on changes in innate immunity cell populations. METHODS: Sixty Caucasian female patients with relapsing-remitting MS undergo blood sample testing for 15 blood parameters at baseline, 1 month, 3 months, and 6 months after treatment by GA or IFN (started as their first-line DMD). RESULTS: A statistically significant difference in the change after 6 months was found in the parameter monocytes (relative count) in the group of patients treated with IFN. The median increase was 27.8%. Changes in many of the other 15 parameters studied were 10-20%. CONCLUSION: Innate immunity has long been neglected in MS immunopathology. The findings suggest that IFN treatment may modulate the immune response in MS by affecting monocyte function and may provide insight into the mechanisms of action of IFN in MS.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Femenino , Humanos , Acetato de Glatiramer/uso terapéutico , Interferón beta-1a/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Interferón beta/uso terapéutico , Péptidos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/patología , Inmunidad Innata
7.
J Environ Manage ; 331: 117151, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36638720

RESUMEN

Implementation of green roofs requires a large amount of primary material, especially for constructing the growing media layer. In addition, irrigation of green roofs with potable water is uneconomical and unsustainable. The novel hybrid green roof system proposed in this paper is in line with the principles of circular economy as it incorporates recycled materials into green roof growing media and greywater for irrigation. Two experimental beds were built to evaluate the concept of treating greywater in a constructed wetland prior to using it to irrigate a dual-layer extensive green roof. The growing media in both two extensive green roof beds contained ca. 37.5% by volume of recycled crushed building rubble containing a large proportion of brick. One of the two beds additionally contained 9.5% by volume of sewage sludge-based biochar. The concept of the hybrid roof and novel growing media was evaluated based on laboratory analysis of the growing media and on onsite measurements of hydraulic and thermal performance. The growing media amended with recycled materials developed in this study had hydrophysical properties comparable to commercially available growing media without recycled materials. Observations made during one vegetation season from June to October and a ten day-intensive water quality monitoring campaign during September 2020 showed that the constructed wetland significantly reduced total nitrogen and orthophosphate concentrations in pre-treated greywater. Due to the irrigation method employed, in which water flowed predominantly through drainage mats below the growing media, nutrient-leaching by the irrigation water was avoided. Concentrations of nutrients in the effluent were observed to increase only in response to precipitation. The temperature peak of the bottom green roof layer was shifted by almost 9 h from the peak in air temperature, and temperature fluctuations were significantly reduced. Vegetation on the bed amended with biochar demonstrated more vigorous growth due to available nutrients in the biochar which increased the rate of temperature-reducing evapotranspiration. More water evapotranspirated more water, which provided more water retention capacity confirmed by a lower runoff coefficient. Simple storage routing hydraulic modeling of hybrid green roof runoff using a nonlinear reservoir was performed.


Asunto(s)
Lluvia , Humedales , Calidad del Agua , Carbón Orgánico , Aguas del Alcantarillado , Conservación de los Recursos Naturales/métodos
8.
Ann Neurol ; 90(1): 62-75, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33856074

RESUMEN

OBJECTIVE: This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD). METHODS: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5-3.4 years), 149 with PD (mean duration of disease across language groups 1.7-2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12-month follow-up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria. RESULTS: No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12-month follow-up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups. INTERPRETATION: Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62-75.


Asunto(s)
Enfermedad de Parkinson/diagnóstico , Trastorno de la Conducta del Sueño REM/diagnóstico , Habla/fisiología , Anciano , Anciano de 80 o más Años , Biomarcadores , Progresión de la Enfermedad , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Síntomas Prodrómicos , Trastorno de la Conducta del Sueño REM/fisiopatología
9.
Mov Disord ; 37(3): 619-623, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34837250

RESUMEN

BACKGROUND: Impairments of olfactory and speech function are likely early prodromal symptoms of α-synucleinopathy. OBJECTIVE: The aim of this study is to assess whether dysprosody is present in isolated rapid eye movement sleep behavior disorder (iRBD) with hyposmia/anosmia and a normal nigrostriatal system. METHODS: Pitch variability during speech was investigated in 17 iRBD subjects with normal olfactory function (iRBD-NOF), 30 iRBD subjects with abnormal olfactory function (iRBD-AOF), and 50 healthy controls. iRBD subjects were evaluated using the University of Pennsylvania Smell Identification Test and [123I]-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT). All iRBD subjects completed the 24-month follow-up with DAT-SPECT, speech, and olfactory testing. RESULTS: At baseline, only iRBD-AOF showed monopitch when compared to iRBD-NOF (P = 0.04) and controls (P = 0.03), with no difference between iRBD-NOF and controls (P = 1). At follow-up, dysprosody progressed only in iRBD-AOF with abnormal DAT-SPECT (P = 0.03). CONCLUSION: Prosody is impaired in hyposmic but not in normosmic iRBD subjects before the nigrostriatal dopaminergic transmission is affected (Braak stage 2). © 2021 International Parkinson and Movement Disorder Society.


Asunto(s)
Trastornos del Olfato , Trastorno de la Conducta del Sueño REM , Sinucleinopatías , Dopamina/metabolismo , Humanos , Trastornos del Olfato/diagnóstico por imagen , Trastornos del Olfato/etiología , Tomografía Computarizada de Emisión de Fotón Único/métodos
10.
Mov Disord ; 37(9): 1872-1882, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35799404

RESUMEN

BACKGROUND: Patients with synucleinopathies frequently display language abnormalities. However, whether patients with isolated rapid eye movement sleep behavior disorder (iRBD) have prodromal language impairment remains unknown. OBJECTIVE: We examined whether the linguistic abnormalities in iRBD can serve as potential biomarkers for conversion to synucleinopathy, including the possible effect of mild cognitive impairment (MCI), speaking task, and automation of analysis procedure. METHODS: We enrolled 139 Czech native participants, including 40 iRBD without MCI and 14 iRBD with MCI, compared with 40 PD without MCI, 15 PD with MCI, and 30 healthy control subjects. Spontaneous discourse and story-tale narrative were transcribed and linguistically annotated. A quantitative analysis was performed computing three linguistic features. Human annotations were compared with fully automated annotations. RESULTS: Compared with control subjects, patients with iRBD showed poorer content density, reflecting the reduction of content words and modifiers. Both PD and iRBD subgroups with MCI manifested less occurrence of unique words and a higher number of n-grams repetitions, indicating poorer lexical richness. The spontaneous discourse task demonstrated language impairment in iRBD without MCI with an area under the curve of 0.72, while the story-tale narrative task better reflected the presence of MCI, discriminating both PD and iRBD subgroups with MCI from control subjects with an area under the curve of up to 0.81. A strong correlation between manually and automatically computed results was achieved. CONCLUSIONS: Linguistic features might provide a reliable automated method for detecting cognitive decline caused by prodromal neurodegeneration in subjects with iRBD, providing critical outcomes for future therapeutic trials. © 2022 International Parkinson and Movement Disorder Society.


Asunto(s)
Disfunción Cognitiva , Trastornos del Desarrollo del Lenguaje , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Sinucleinopatías , Disfunción Cognitiva/diagnóstico , Humanos , Lingüística , Enfermedad de Parkinson/complicaciones , Trastorno de la Conducta del Sueño REM/diagnóstico
11.
Eur J Neurol ; 29(1): 81-90, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34498329

RESUMEN

BACKGROUND: The mechanisms underlying speech abnormalities in Parkinson's disease (PD) remain poorly understood, with most of the available evidence based on male patients. This study aimed to estimate the occurrence and characteristics of speech disorder in early, drug-naive PD patients with relation to gender and dopamine transporter imaging. METHODS: Speech samples from 60 male and 40 female de novo PD patients as well as 60 male and 40 female age-matched healthy controls were analyzed. Quantitative acoustic vocal assessment of 10 distinct speech dimensions related to phonation, articulation, prosody, and speech timing was performed. All patients were evaluated using [123]I-2b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single-photon emission computed tomography and Montreal Cognitive Assessment. RESULTS: The prevalence of speech abnormalities in the de novo PD cohort was 56% for male and 65% for female patients, mainly manifested with monopitch, monoloudness, and articulatory decay. Automated speech analysis enabled discrimination between PD and controls with an area under the curve of 0.86 in men and 0.93 in women. No gender-specific speech dysfunction in de novo PD was found. Regardless of disease status, females generally showed better performance in voice quality, consonant articulation, and pauses production than males, who were better only in loudness variability. The extent of monopitch was correlated to nigro-putaminal dopaminergic loss in men (r = 0.39, p = 0.003) and the severity of imprecise consonants was related to cognitive deficits in women (r = -0.44, p = 0.005). CONCLUSIONS: Speech abnormalities represent a frequent and early marker of motor abnormalities in PD. Despite some gender differences, our findings demonstrate that speech difficulties are associated with nigro-putaminal dopaminergic deficits.


Asunto(s)
Enfermedad de Parkinson , Habla , Dopamina , Femenino , Humanos , Masculino , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Trastornos del Habla/diagnóstico por imagen , Trastornos del Habla/etiología , Tomografía Computarizada de Emisión de Fotón Único
12.
Phys Chem Chem Phys ; 23(12): 7247-7260, 2021 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-33876085

RESUMEN

Stacking mismatches in hexagonal boron nitride (h-BN) nanostructures affect their photonic, mechanical, and thermal properties. To access information about the stacked configuration of layered ensembles, highly sophisticated techniques like X-ray photoemission spectroscopy or electron microscopy are necessary. Here, instead, by taking advantage of the geometrical and chemical nature of h-BN, we show how simple structural models, based on shortened interplanar distances, can produce effective charge densities. Accounting these in the non-analytical part of the lattice dynamical description makes it possible to access information about the composition of differently stacked variants in experimental samples characterized by infrared spectroscopy. The results are obtained by density functional theory and confirmed by various functionals and pseudopotential approximations. Even though the method is shown using h-BN, the conclusions are more general and show how effective dielectric models can be considered as valuable theoretical pathways for the vibrational structure of any layered material.

13.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-34445613

RESUMEN

At present, Alzheimer's disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-ß (Aß) peptide in the cerebral spinal fluid of Alzheimer's patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.


Asunto(s)
Trastornos del Conocimiento/tratamiento farmacológico , Agonistas Muscarínicos/farmacología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neurofarmacología , Preparaciones Farmacéuticas/administración & dosificación , Quinuclidinas/farmacología , Tiofenos/farmacología , Animales , Humanos
14.
Molecules ; 26(14)2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34299414

RESUMEN

Two 15-membered octaazamacrocyclic nickel(II) complexes are investigated by theoretical methods to shed light on their affinity forwards binding and reducing CO2. In the first complex 1[NiIIL]0, the octaazamacrocyclic ligand is grossly unsaturated (π-conjugated), while in the second 1[NiIILH]2+ one, the macrocycle is saturated with hydrogens. One and two-electron reductions are described using Mulliken population analysis, quantum theory of atoms in molecules, localized orbitals, and domain averaged fermi holes, including the characterization of the Ni-CCO2 bond and the oxidation state of the central Ni atom. It was found that in the [NiLH] complex, the central atom is reduced to Ni0 and/or NiI and is thus able to bind CO2 via a single σ bond. In addition, the two-electron reduced 3[NiL]2- species also shows an affinity forwards CO2.

15.
Neurol Sci ; 39(12): 2115-2121, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30178269

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system that is often disabling and for which there is currently no cure, though disease-modifying treatment is now available. The aim of this study is to describe the current values of the direct costs of multiple sclerosis (MS) in the Czech Republic. METHODS: Attention is focused on direct medical costs. The costs were monitored in the Czech Republic among 5673 patients in the period between 2011 and 2015. These costs included complex, special and targeted visits at the neurologist, blood collection and the costs of hospitalisation. The results refer to the diagnoses according to the International Statistical Classification of Diseases and Related Health Problems. The attention is focused on MS G35 (NS; brain stem; spinal cord; disseminated; generalised). RESULTS: The average total direct costs per patient per year are 4838.1 €. Not every patient has to be hospitalised during the year, and not every patient has prescribed medication. According to the above data, 12% of patients are hospitalised and 55% of patients are prescribed medication. The minimum average cost per patient without medication and hospitalisation is 54.1 €. CONCLUSION: Cost evaluation across countries is difficult due to the different evidence. If only selected direct costs considered in this study are compared, the absolute economics burden increases over time. The only statistically significant difference in the average price and the time spent is between 2012 and 2013, where the correlation value is 0.597.


Asunto(s)
Costo de Enfermedad , Esclerosis Múltiple/economía , Esclerosis Múltiple/terapia , Costos y Análisis de Costo , República Checa/epidemiología , Femenino , Hospitalización/economía , Humanos , Masculino , Esclerosis Múltiple/epidemiología , Estudios Retrospectivos
16.
J Neural Transm (Vienna) ; 124(4): 463-470, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27933492

RESUMEN

It is currently unknown whether speech and limb motor effectors in Parkinson's disease (PD) are controlled by similar underlying brain processes. Based on computerized objective analysis, the aim of this study was to evaluate potential correlation between speech and mechanical tests of upper limb motor function. Speech and upper limb motor tests were performed in 22 PD patients and 22 healthy controls. Quantitative acoustic analyses of eight key speech dimensions of hypokinetic dysarthria, including quality of voice, sequential motion rates, consonant articulation, vowel articulation, average loudness, loudness variability, pitch variability, and number of pauses, were performed. Upper limb movements were assessed using the motor part of the Unified Parkinson's Disease Rating Scale, contactless three-dimensional motion capture system, blinded expert evaluation, and the Purdue Pegboard Test. Significant relationships were observed between the quality of voice assessed by jitter and amplitude decrement of finger tapping (r = 0.61, p = 0.003), consonant articulation evaluated using voice onset time and expert rating of finger tapping (r = 0.60, p = 0.003), and number of pauses and Purdue Pegboard Test score (r = 0.60, p = 0.004). The current study supports the hypothesis that speech impairment in PD shares, at least partially, similar pathophysiological processes with limb motor dysfunction. Vocal fold vibration irregularities appeared to be influenced by mechanisms similar to amplitude decrement during repetitive limb movements. Consonant articulation deficits were associated with decreased manual dexterity and movement speed, likely reflecting fine motor control involvement in PD.


Asunto(s)
Actividad Motora , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatología , Trastornos del Habla/etiología , Trastornos del Habla/fisiopatología , Extremidad Superior/fisiopatología , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Enfermedad de Parkinson/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Medición de la Producción del Habla
17.
Bioconjug Chem ; 27(10): 2558-2574, 2016 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-27602782

RESUMEN

Cationic colloidal gold nanorods (GNRs) have a great potential as a theranostic tool for diverse medical applications. GNRs' properties such as cellular internalization and stability are determined by physicochemical characteristics of their surface coating. GNRs modified by (16-mercaptohexadecyl)trimethylammonium bromide (MTAB), MTABGNRs, show excellent cellular uptake. Despite their promise for biomedicine, however, relatively little is known about the cellular pathways that facilitate the uptake of GNRs, their subcellular fate and intracellular persistence. Here we studied the mechanism of cellular internalization and long-term fate of GNRs coated with MTAB, for which the synthesis was optimized to give higher yield, in various human cell types including normal diploid versus cancerous, and dividing versus nondividing (senescent) cells. The process of MTABGNRs internalization into their final destination in lysosomes proceeds in two steps: (1) fast passive adhesion to cell membrane mediated by sulfated proteoglycans occurring within minutes and (2) slower active transmembrane and intracellular transport of individual nanorods via clathrin-mediated endocytosis and of aggregated nanorods via macropinocytosis. The expression of sulfated proteoglycans was the major factor determining the extent of uptake by the respective cell types. Upon uptake into proliferating cells, MTABGNRs were diluted equally and relatively rapidly into daughter cells; however, in nondividing/senescent cells the loss of MTABGNRs was gradual and very modest, attributable mainly to exocytosis. Exocytosed MTABGNRs can again be internalized. These findings broaden our knowledge about cellular uptake of gold nanorods, a crucial prerequisite for future successful engineering of nanoparticles for biomedical applications such as photothermal cancer therapy or elimination of senescent cells as part of the emerging rejuvenation approach.


Asunto(s)
Exocitosis , Oro/química , Oro/farmacocinética , Nanotubos/química , Polilisina/química , Polilisina/farmacocinética , Compuestos de Amonio Cuaternario/química , Compuestos de Sulfhidrilo/química , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Técnicas de Química Sintética , Medios de Cultivo , Estabilidad de Medicamentos , Endocitosis/efectos de los fármacos , Endocitosis/fisiología , Exocitosis/efectos de los fármacos , Exocitosis/fisiología , Citometría de Flujo , Humanos , Lisosomas/efectos de los fármacos , Microscopía Confocal , Microscopía Electrónica de Rastreo , Nanotubos/análisis , Proteoglicanos/química , Proteoglicanos/metabolismo , Compuestos de Amonio Cuaternario/síntesis química
19.
RSC Adv ; 14(22): 15220-15231, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38737968

RESUMEN

The microstructure and physical properties of reflective and black aluminum were compared for layers of different thicknesses deposited by magnetron sputtering on fused silica substrates. Reflective Al layers followed the Volmer-Weber growth mechanism classically observed for polycrystalline metal films. On the contrary, the extra nitrogen gas used to deposit the black aluminum layers modified the growth mechanism and changed the film morphologies. Nitrogen cumulated in the grain boundaries, favoring the pinning effect and stopping crystallite growth. High defect concentration, especially vacancies, led to strong columnar growth. Properties reported for black aluminum tend to be promising for sensors and emissivity applications.

20.
Chirality ; 25(11): 810-3, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23966346

RESUMEN

Racemic mixtures of six Tröger's base derivatives were separated by chiral nonaqueous capillary electrophoresis. The separation protocol was optimized first for suitable solvents. Then the applicability of various salts dissolved in organic solvents and their mixtures was evaluated. As chiral selectors ß-cyclodextrin and heptakis(2,6-di-O-methyl)-ß-cyclodextrin at various concentrations were used. The best enantioselectivity for the studied analytes was obtained utilizing formamide as organic nonaqueous solvent containing a mixture of sodium citrate and tris(hydroxymethyl)aminomethane acetate as electrolytes, and ß-cyclodextrin as chiral additive. The experimental results demonstrated the feasibility of nonaqueous capillary electrophoresis for enantioseparation of Tröger's base derivatives. This technique represents a suitable alternative to more commonly used capillary electrophoresis in aqueous environment.

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