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1.
Nano Lett ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39075987

RESUMEN

Strain is a powerful tool for tuning the properties of two-dimensional materials. Here, we investigated the effects of large, uniform biaxial compressive strain on the superconducting phase transition of multilayered 2H-NbSe2 flakes. We observed a consistent decrease in the critical temperature of NbSe2 flakes induced by the large thermal compression of a polymeric substrate (>1.2%) at cryogenic temperatures. For thin flakes (∼10 nm thick), a strong modulation of the critical temperature up to 1.5 K is observed, which monotonically decreases with increasing flake thickness. The effects of biaxial compressive strain remain significant even for relatively thick samples up to 80 nm thick, indicating efficient transfer of strain not only from the substrate to the flakes but also across several van der Waals layers. This work demonstrates that compressive strain induced from substrate thermal deformation can effectively tune phase transitions at low temperatures in 2D materials.

2.
One Health ; 18: 100690, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39010960

RESUMEN

Paslahepevirus balayani (formerly known as hepatitis E virus) is an emerging cause of foodborne disease in Europe, transmitted mainly by the consumption of raw or undercooked pork. Since little is known about the presence of the virus in several pork products that are eaten uncooked, our aim was to evaluate the prevalence of Paslahepevirus balayani in groups of commercial pork products intended for human consumption subjected to different processing techniques. A total of 1265 samples of pork products from Spain were divided into four groups and tested for the presence of Paslahepevirus balayani RNA: unprocessed pig and wild boar meat frozen at -20 °C (n = 389), dry-cured pork products (n = 391), dry-cured and salted pork products (n = 219), and boiled products (n = 266) (none of these products contained pork liver). Five samples were positive for Paslahepevirus balayani RNA (overall prevalence: 0.4%; 95% CI: 0.17% - 0.92%). All positive samples were from unprocessed meat stored at -20 °C, with a prevalence in this group of 1.3% (95% CI: 0.42-3.44); two samples came from pigs (1.1%; 95% CI: 0.13-3.81) and three from wild boar (1.5%; 95% CI: 0.31-4.28). None of the pork samples in the other groups was positive. In conclusion, Paslahepevirus balayani was found in unprocessed swine products form Spain, but not in processed products intended to be consumed undercooked, demonstrating that transmission of this zoonotic virus by eating these pork products should be more seriously considered.

3.
Health Equity ; 8(1): 301-306, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011077

RESUMEN

Background: The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians. Methods: A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences. Demographic data, clinical characteristics, neuroimaging data, treatment intervals, follow-up visits, and clinical outcomes were collected. Results: A total of 3009 suspected stroke patients were attended to in the telestroke network from 2019 to 2023, of which 42.74% were women. Women were older (p < 0.001) and less independent upon arrival (p = 0.006) than men. There was no difference in the treatment received or in the treatment time intervals between the groups. Importantly, there was no difference in modified Rankin scale scores at 3 months between sexes. At 3 months post-stroke follow-up, women had fewer imaging tests (p = 0.018) and fewer outpatient visits (p < 0.001) than men. Conclusions: No significant difference between men and women has been found in the acute treatment of stroke in a large telestroke network. However, the same is not true for the follow-up and management of patients after the acute phase. This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.

4.
Vet Sci ; 11(7)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39057970

RESUMEN

Nutrition plays an important role in shaping the gut microbiome composition, although the impact of diet on the urinary microbiome (i.e., urobiome) remains unknown. The aim of this pilot study was to discover how nutritional features affect the diversity and composition of the urobiome in dogs. Dietary histories were obtained for 15 clinically healthy adult dogs, including limited nutrient (protein, fat, crude fiber), commercial diet brand, and dietary diversity profiles. The urine samples were collected via cystocentesis, followed by sequencing of the bacterial 16S rRNA gene. The data were analyzed to determine associations between major nutrients and dietary sources with the urobiome's composition. The protein, fat, and crude fiber contents had no statistically significant effect on the alpha or beta diversity. However, the beta diversity values differed (PERMANOVA; p = 0.017, R2 = 0.10) between dogs fed one commercial diet brand compared to dogs consuming any other brand. The beta diversity values also differed (p = 0.019, R2 = 0.10) between dogs consuming more diverse daily diets compared to those consuming less diverse diets (≥3 or <3 unique food sources, respectively). Overall, the results of this pilot study suggest that diet might impact the urobiome and support further exploration of the relationship between diet and the urobiome's composition in dogs.

5.
J Phys Chem Lett ; 15(24): 6355-6362, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38857301

RESUMEN

Strain engineering represents a pivotal approach to tailoring the optoelectronic properties of two-dimensional (2D) materials. However, typical bending experiments often encounter challenges, such as layer slippage and inefficient transfer of strain from the substrate to the 2D material, hindering the realization of their full potential. In our study, using molybdenum disulfide (MoS2) as a model 2D material, we have demonstrated that layers obtained through gold-assisted exfoliation on flexible polycarbonate substrates can achieve high-efficient strain transfer while also mitigating slippage effects, owing to the strong interfacial interaction established between MoS2 and gold. We employ differential reflectance and Raman spectroscopy for monitoring strain changes. We successfully applied uniaxial strains of up to 3% to trilayer MoS2, resulting in a notable energy shift of 168 meV. These values are comparable only to those obtained in encapsulated samples with organic polymers.

6.
Mov Disord ; 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38881224

RESUMEN

BACKGROUND: Defects in GNAO1, the gene encoding the major neuronal G-protein Gαo, are related to neurodevelopmental disorders, epilepsy, and movement disorders. Nevertheless, there is a poor understanding of how molecular mechanisms explain the different phenotypes. OBJECTIVES: We aimed to analyze the clinical phenotype and the molecular characterization of GNAO1-related disorders. METHODS: Patients were recruited in collaboration with the Spanish GNAO1 Association. For patient phenotyping, direct clinical evaluation, analysis of homemade-videos, and an online questionnaire completed by families were analyzed. We studied Gαo cellular expression, the interactions of the partner proteins, and binding to guanosine triphosphate (GTP) and G-protein-coupled receptors (GPCRs). RESULTS: Eighteen patients with GNAO1 genetic defects had a complex neurodevelopmental disorder, epilepsy, central hypotonia, and movement disorders. Eleven patients showed neurological deterioration, recurrent hyperkinetic crisis with partial recovery, and secondary complications leading to death in three cases. Deep brain stimulation improved hyperkinetic crisis, but had inconsistent benefits in dystonia. The molecular defects caused by pathogenic Gαo were aberrant GTP binding and hydrolysis activities, an inability to interact with cellular binding partners, and reduced coupling to GPCRs. Decreased localization of Gαo in the plasma membrane was correlated with the phenotype of "developmental and epileptic encephalopathy 17." We observed a genotype-phenotype correlation, pathogenic variants in position 203 were related to developmental and epileptic encephalopathy, whereas those in position 209 were related to neurodevelopmental disorder with involuntary movements. Milder phenotypes were associated with other molecular defects such as del.16q12.2q21 and I344del. CONCLUSION: We highlight the complexity of the motor phenotype, which is characterized by fluctuations throughout the day, and hyperkinetic crisis with a distinct post-hyperkinetic crisis state. We confirm a molecular-based genotype-phenotype correlation for specific variants. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

8.
Nanoscale ; 16(18): 8968-8974, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38646962

RESUMEN

One of the primary objectives in contemporary electronics is to develop sensors that are not only scalable and cost-effective but also environmentally sustainable. To achieve this goal, numerous experiments have focused on incorporating nanomaterial-based films, which utilize nanoparticles or van der Waals materials, on paper substrates. In this article, we present a novel fabrication technique for producing dry-abraded van der Waals films on paper, demonstrating outstanding electrical characteristics. We assess the quality and uniformity of these films by conducting a spatial resistivity characterization on a 5 × 5 cm2 dry-abraded WS2 film with an average thickness of 25 µm. Employing transfer length measurements with varying channel length-to-width ratios, we extract critical parameters, including sheet resistance and contact resistance. Notably, our findings reveal a resistivity approximately one order of magnitude lower than previous reports. The film's inherent disorder manifests as an asymmetric distribution of resistance values for specific geometries. We explore how this behavior can be effectively modeled through a random resistance network (RRN), which can reproduce the experimentally observed resistance distribution. Finally, we investigate the response of these devices under applied uniaxial strain and apply the RRN model to gain a deeper understanding of this process.

9.
J Anim Sci Biotechnol ; 15(1): 33, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38431668

RESUMEN

BACKGROUND: Nursery pigs undergo stressors in the post-weaning period that result in production and welfare challenges. These challenges disproportionately impact the offspring of primiparous sows compared to those of multiparous counterparts. Little is known regarding potential interactions between parity and feed additives in the post-weaning period and their effects on nursery pig microbiomes. Therefore, the objective of this study was to investigate the effects of maternal parity on sow and offspring microbiomes and the influence of sow parity on pig fecal microbiome and performance in response to a prebiotic post-weaning. At weaning, piglets were allotted into three treatment groups: a standard nursery diet including pharmacological doses of Zn and Cu (Con), a group fed a commercial prebiotic only (Preb) based on an Aspergillus oryzae fermentation extract, and a group fed the same prebiotic plus Zn and Cu (Preb + ZnCu). RESULTS: Although there were no differences in vaginal microbiome composition between primiparous and multiparous sows, fecal microbiome composition was different (R2 = 0.02, P = 0.03). The fecal microbiomes of primiparous offspring displayed significantly higher bacterial diversity compared to multiparous offspring at d 0 and d 21 postweaning (P < 0.01), with differences in community composition observed at d 21 (R2 = 0.03, P = 0.04). When analyzing the effects of maternal parity within each treatment, only the Preb diet triggered significant microbiome distinctions between primiparous and multiparous offspring (d 21: R2 = 0.13, P = 0.01; d 42: R2 = 0.19, P = 0.001). Compositional differences in pig fecal microbiomes between treatments were observed only at d 21 (R2 = 0.12, P = 0.001). Pigs in the Con group gained significantly more weight throughout the nursery period when compared to those in the Preb + ZnCu group. CONCLUSIONS: Nursery pig gut microbiome composition was influenced by supplementation with an Aspergillus oryzae fermentation extract, with varying effects on performance when combined with pharmacological levels of Zn and Cu or for offspring of different maternal parity groups. These results indicate that the development of nursery pig gut microbiomes is shaped by maternal parity and potential interactions with the effects of dietary feed additives.

10.
ACS Appl Mater Interfaces ; 16(12): 15596-15604, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38500411

RESUMEN

In this study, we show a direct correlation between the applied mechanical strain and an increase in monolayer MoS2 photoresponsivity. This shows that tensile strain can improve the efficiency of monolayer MoS2 photodetectors. The observed high photocurrent and extended response time in our devices are indicative that devices are predominantly governed by photogating mechanisms, which become more prominent with applied tensile strain. Furthermore, we have demonstrated that a nonencapsulated MoS2 monolayer can be used in strain-based devices for many cycles and extensive periods of time, showing endurance under ambient conditions without loss of functionality. Such robustness emphasizes the potential of MoS2 for further functionalization and utilization of different flexible sensors.

12.
Animals (Basel) ; 14(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38540008

RESUMEN

The supplementation of live yeast in pig diets is common in the post-weaning phase due to its prebiotic and probiotic effects, but little is known regarding the potential of feeding live yeast to gestating or lactating sows for transferring such benefits to their offspring through maternal programming. The objective of this study was to investigate the effects of live yeast supplementation in sow diets during late gestation and lactation on their reproductive performance and its impact on offspring performance and gut microbiomes in the post-weaning period. Three dietary treatments were imposed on 92 mixed-parity sows during late gestation and lactation based upon the inclusion level of live yeast in corn/soybean meal-based diets: Control (0% yeast), Low (0.1% yeast), and High (0.5% yeast). Nursery pigs in the Low group displayed the highest feed intake in the post-weaning period and greater total gain and average daily gain in comparison to pigs in the High group. The gut microbiomes of nursery pigs differed in composition according to maternal dietary treatment groups at days 4 and 28 post weaning, highlighting higher abundances of bacterial genera typically associated with fermentation roles in the gut microbiomes of offspring of yeast-fed sows. These results indicate that the supplementation of live yeast in sow diets, depending on the inclusion level, may result in beneficial performance and specific microbiome traits for their offspring in the post-weaning period.

13.
Transl Anim Sci ; 8: txae030, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510065

RESUMEN

The objectives of this study were to determine a practical approach to feeding elevated dietary zinc (Zn) to gestating sows in a commercial setting and to confirm preweaning mortality could be reduced by feeding high Zn to sows during different periods of gestation. The study was conducted at a commercial sow farm in the upper Midwest. Mixed parity sows (n = 267) over three consecutive weekly farrowing groups (sows farrowing within 1 wk) were assigned randomly to one of the three dietary treatments within parity. Treatments consisted of: (1) control sows fed a corn-soybean meal diet containing 206 mg/kg total supplemental Zn supplied by zinc hydroxychloride; (2) breed-to-farrow: as control + 147 mg/kg supplemental Zn as ZnSO4 (353 mg/kg total supplemental Zn) fed from 5 d after breeding to farrowing; and (3) day 110-to-farrow: as control fed from breeding to farrowing + 4,079 mg/kg supplemental Zn as ZnSO4 (4,285 mg/kg total supplemental Zn) starting day 110 of gestation until farrowing. At farrowing, individual piglets were weighed and identified within 12 h of birth. Data were analyzed using PROC GLIMMIX of SAS and the model considered the fixed effect of dietary treatment and random effect of farrowing group. Dietary treatments did not affect number of total pigs born per litter. For breed-to-farrow sows, there was an increase in the percentage of pigs born alive compared to sows fed the control and day 110-to-farrow treatments (P < 0.001). The number of stillborn pigs expressed as a percentage of total litter size at birth decreased for breed-to-farrow sows (P < 0.001) compared with control or day 110-to-farrow sows. Mortality of low birth weight piglets from birth to weaning did not differ among dietary treatments (P = 0.305); however, a trend for decreasing post-natal mortality (P = 0.068) of normal birth weight pigs was observed for pigs born to sows fed elevated Zn 5 d before farrowing. In conclusion, feeding elevated Zn to sows throughout gestation increased the proportion of pigs born alive suggesting that elevated gestational Zn intake makes piglets more robust to endure the stresses of farrowing and decreases intrapartum mortality. Under the conditions of this study, elevated Zn intake of sows did not influence piglet post-natal survival. However, feeding high zinc throughout gestation may decrease piglet mortality during the parturition process.

14.
Front Psychiatry ; 15: 1304300, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38352654

RESUMEN

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the cerebro-cerebellar circuit, particularly in genetic autism related to SHANK3 or SYNGAP1 protein dysfunction function and autism associated with in utero exposure to the anti-seizure medications valproic acid and topiramate, may contribute to the disease presentation. Initially, a discussion contextualizing AMPAr signaling in the cerebro-cerebellar circuitry and microstructural circuit considerations is offered. Subsequently, a detailed review of the literature implicating mutations or deletions of SHANK3 and SYNGAP1 in disrupted AMPAr signaling reveals how bidirectional pathogenic modulation of this key circuit may contribute to autism. Finally, how pharmacological exposure may interact with this pathway, via increased risk of autism diagnosis with valproic acid and topiramate exposure and potential treatment of autism using AMPAr modulator perampanel, is discussed. Through the lens of the review, we will offer speculation on how neuromodulation may be used as a rational adjunct to therapy. Together, the present review seeks to synthesize the disparate considerations of circuit understanding, genetic etiology, and pharmacological modulation to understand the mechanistic interaction of this important and complex disorder.

15.
Behav Brain Res ; 463: 114901, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38341101

RESUMEN

The rotarod test, a sensorimotor assessment that allows for quantitative evaluation of motor coordination in rodents, has extensive application in many research fields. The test results exhibit extreme between-study variability, sometimes making it challenging to conclude the validity of certain disease models and related therapeutic effects. Although the variation in test paradigms may account for this disparity, some features of rotarod apparatus including rod diameter make differences. However, it is unknown whether the width of animal compartment has a role in rotarod performance. Here we comprehensively evaluated the active rotarod performance and adverse incidents in multiple strains of mice on an 11-cm- or a 5-cm-wide compartment apparatus. We found that mouse behaviors on these apparatuses were surprisingly different. It took a markedly longer time to train mice on the narrow- than wide-compartment rotarod. Further, non-transgenic B6129S and tau knockout mice aged 11 months and beyond showed different levels of improvement based on the compartment width. These mice had no overt improvements on accelerating rotarod over 4-5 training sessions on the narrow compartment, contrary to marked progress on the wide counterpart. The incidents of mice passively somersaulting round and fragmented running occurred significantly more on the wide than narrow compartment during accelerating rotarod sessions. Mice fell off rod more frequently on narrow than wide compartments upon attempt to turn around and when moving backward on rod. The pros and cons of narrow versus wide compartments are informative as to how to choose a rotarod apparatus that best fits the animal models used.


Asunto(s)
Modelos Animales , Ratones , Animales , Ratones Noqueados , Prueba de Desempeño de Rotación con Aceleración Constante , Modelos Animales de Enfermedad
17.
Eur J Paediatr Neurol ; 48: 121-128, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38241904

RESUMEN

OBJECTIVE: To analyze the differences in clinical management during the epilepsy transition process from pediatric to adult care and to determine the quality of life and degree of satisfaction of patients and caregivers during the transition. METHODS: This is a longitudinal study including patients with epilepsy transferred from pediatric to adult epilepsy care between 2013 and 2017. Patients had a minimum follow-up of 3 years before the transition visit and at least 3 years consulting in the adults section. Clinical characteristics were retrieved from the medical chart. Quality of life and satisfaction questionnaires were administered by online access to patients and caregivers at the end of the adult follow-up period. RESULTS: 99 patients (50.5 % women, mean transition age 16.5 ± 1 years old) were included. Before the transition visit, 90 % of patients received a transition discussion and 88 % had a formal clinical report. In the pediatric period, patients were visited more frequently, had more EEGs and genetic studies, and were seen by the same neuropediatrician (P<0.05). In the adult period, patients underwent a larger number of prolonged video EEGs and were prescribed polytherapy more often (P<0.05). Quality of life remained steady during the entire transition, but satisfaction with the care received was significantly higher during the pediatric period. CONCLUSIONS: Significant differences were seen in epilepsy care during transition from pediatric to adult management, and this had an impact on the degree of satisfaction reported by patients and caregivers. Our results provide evidence of the potential value of development and early implementation of a protocolled transition program.


Asunto(s)
Epilepsia , Transición a la Atención de Adultos , Adulto , Humanos , Niño , Femenino , Adolescente , Masculino , Estudios Longitudinales , Calidad de Vida , Epilepsia/diagnóstico , Epilepsia/terapia , Encuestas y Cuestionarios
18.
J Autism Dev Disord ; 2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38246963

RESUMEN

The aim of this research was to study the effect of a horseback-riding programme on postural control in a group of autistic children (ASD). Nine children aged 9 to 12 years participated in this study through a multiple baseline across subjects design. The whole programme took place over nine months. Participants followed a previously developed specific horseback-riding programme, consisting of 45-minute sessions held twice a week for at least three months. To evaluate postural control, the average velocity of the centre of pressure displacement was measured by means of a posturographic platform. Results indicated that this intervention with horses had a positive effect on the postural control in children with ASDs.

19.
Neurol Sci ; 45(3): 1007-1016, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37853291

RESUMEN

BACKGROUND: Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. AIM: To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). METHODS: Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. RESULTS: Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18 years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40 years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. CONCLUSIONS: This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.


Asunto(s)
Atención a la Salud , Enfermedades del Sistema Nervioso , Adulto , Adolescente , Humanos , Niño , Encuestas y Cuestionarios , Europa (Continente) , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/terapia , Enfermedades Raras/diagnóstico , Enfermedades Raras/terapia
20.
Brain ; 147(4): 1511-1525, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37988272

RESUMEN

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.


Asunto(s)
Afasia Progresiva Primaria , Apraxias , Afasia Progresiva Primaria no Fluente , Humanos , Afasia de Broca/patología , Disartria , Apraxias/patología , Lenguaje , Habla
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