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1.
Nano Lett ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311749

RESUMEN

This study represents a highly sensitive and selective approach to protein screening using surface-enhanced Raman scattering (SERS) facilitated by octahedral Au nanotrenches (OANTs). OANTs are a novel class of nanoparticles characterized by narrow, trench-like excavations indented into the eight facets of a Au octahedron. This unique configuration maximizes electromagnetic near-field focusing as the gap distance decreases to ∼1 nm. Owing to geometrical characteristics of the OANTs, near-field focusing can be maximized through the confinement and reflectance of light trapped within the trenches. We used Ni ions and molecular linkers to confer selective binding affinity for His-tagged proteins on the surfaces of the OANTs for SERS-based protein screening. Remarkably, SERS-based protein screening with the surface-modified OANTs yielded outstanding screening capabilities: 100% sensitivity and 100% selectivity in distinguishing His-tagged human serum albumin (HSA) from native HSA. This highlights the significantly enhanced protein screening capabilities achieved through the synergistic combination of SERS and the OANTs.

2.
Opt Lett ; 49(16): 4630-4633, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146121

RESUMEN

A full-field swept-source optical coherence tomography (FF-SS-OCT) for in vivo murine retinal imaging is demonstrated. The on-axis FF-SS-OCT system was built in a Mach-Zehnder interferometer configuration employing a tunable laser source with an adjustable sweep rate and sweep range in conjunction with a fast 2D-CMOS camera. A large field retinal (coherent) illumination was accomplished using an imaging interface comprised of a short-focal length imaging lens and a contact lens. The magnification between the camera and retina (spatial sampling) was appropriately chosen to record the microscopic structural features of the retina in the image. A pupil stop was employed in the detection path to reject unwanted backscattering from the mouse eye and other sources and limit aberrations distorting the retinal images. In vivo mouse retinal imaging was performed at a sweep rate of 150 Hz to acquire volumes unaffected by the system vibrations, which predominated at lower frequencies. Operating the FF-SS-OCT at this speed yielded an effective axial scan rate of 20 million A-scans/s and a field of view of 820 × 410 µm (24.12° × 12.06°). High-quality retinal B-scans and enface images of the retina were obtained with the SS-FF-OCT, revealing all major retinal layers and vascular plexuses.


Asunto(s)
Retina , Tomografía de Coherencia Óptica , Tomografía de Coherencia Óptica/métodos , Animales , Ratones , Retina/diagnóstico por imagen
3.
Front Plant Sci ; 15: 1411837, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39157516

RESUMEN

Ralstonia pseudosolanacearum, a notorious phytopathogen, is responsible for causing bacterial wilt, leading to significant economic losses globally in many crops within the Solanaceae family. Despite various cultural and chemical control strategies, managing bacterial wilt remains a substantial challenge. This study demonstrates, for the first time, the effective use of plant-induced bacterial gene silencing against R. pseudosolanacearum, facilitated by Tobacco rattle virus-mediated gene silencing, to control bacterial wilt symptoms in Nicotiana benthamiana. The methodology described in this study could be utilized to identify novel phytobacterial virulence factors through both forward and reverse genetic approaches. To validate plant-induced gene silencing, small RNA fractions extracted from plant exudates were employed to silence bacterial gene expression, as indicated by the reduction in the expression of GFP and virulence genes in R. pseudosolanacearum. Furthermore, treatment of human and plant pathogenic Gram-negative and Gram-positive bacteria with plant-generated small RNAs resulted in the silencing of target genes within 48 hours. Taken together, the results suggest that this technology could be applied under field conditions, offering precise, gene-based control of target bacterial pathogens while preserving the indigenous microbiota.

4.
Adv Sci (Weinh) ; : e2400398, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958553

RESUMEN

The androgen receptor (AR) is an attractive target for treating prostate cancer, considering its role in the development and progression of localized and metastatic prostate cancer. The high global mortality burden of prostate cancer, despite medical treatments such as androgen deprivation or AR antagonist therapy, highlights the need to explore alternative strategies. One strategy involves the use of heterobifunctional degraders, also known as proteolysis-targeting chimeras, which are novel small-molecule therapeutics that inhibit amplified or mutated targets. Here, the study reports a novel cereblon-based AR degrader, UBX-390, and demonstrates its superior activity over established AR degraders, such as ARV-110 or ARCC-4, in prostate cancer cells under short- and long-term treatment conditions. UBX-390 suppresses chromatin binding and gene expression of AR and demonstrates substantial efficacy in the degradation of AR mutants in patients with treatment-resistant prostate cancer. UBX-390 is presented as an optimized AR degrader with remarkable potential for treating castration-resistant prostate cancer.

5.
NPJ Biofilms Microbiomes ; 10(1): 50, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902263

RESUMEN

During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as 'maskne' (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either 'pathogen helper (PH)' or 'pathogen inhibitor (PIn)' strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen.


Asunto(s)
COVID-19 , Máscaras , Microbiota , Piel , Animales , Ratones , Humanos , COVID-19/microbiología , COVID-19/virología , Piel/microbiología , Acné Vulgar/microbiología , SARS-CoV-2 , Femenino , Metagenómica/métodos , Modelos Animales de Enfermedad , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Interacciones Microbianas , Dermatitis por Contacto/etiología
6.
Artículo en Inglés | MEDLINE | ID: mdl-38865224

RESUMEN

With the growing complexity and volume of data, visualizations have become more intricate, often requiring advanced techniques to convey insights. These complex charts are prevalent in everyday life, and individuals who lack knowledge in data visualization may find them challenging to understand. This paper investigates using Large Language Models (LLMs) to help users with low data literacy understand complex visualizations. While previous studies focus on text interactions with users, we noticed that visual cues are also critical for interpreting charts. We introduce an LLM application that supports both text and visual interaction for guiding chart interpretation. Our study with 26 participants revealed that the in-situ support effectively assisted users in interpreting charts and enhanced learning by addressing specific chart-related questions and encouraging further exploration. Visual communication allowed participants to convey their interests straightforwardly, eliminating the need for textual descriptions. However, the LLM assistance led users to engage less with the system, resulting in fewer insights from the visualizations. This suggests that users, particularly those with lower data literacy and motivation, may have over-relied on the LLM agent. We discuss opportunities for deploying LLMs to enhance visualization literacy while emphasizing the need for a balanced approach.

7.
Am J Pathol ; 194(8): 1571-1580, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38762116

RESUMEN

Duchenne muscular dystrophy (DMD), caused by loss-of-function mutations in the dystrophin gene, results in progressive muscle weakness and early fatality. Impaired autophagy is one of the cellular hallmarks of DMD, contributing to the disease progression. Molecular mechanisms underlying the inhibition of autophagy in DMD are not well understood. In the current study, the DMD mouse model mdx was used for the investigation of signaling pathways leading to suppression of autophagy. Mammalian target of rapamycin complex 1 (mTORC1) was hyperactive in the DMD muscles, accompanying muscle weakness and autophagy impairment. Surprisingly, Akt, a well-known upstream regulator of mTORC1, was not responsible for mTORC1 activation or the dystrophic muscle phenotypes. Instead, leucyl-tRNA synthetase (LeuRS) was overexpressed in mdx muscles compared with the wild type. LeuRS activates mTORC1 in a noncanonical mechanism that involves interaction with RagD, an activator of mTORC1. Disrupting LeuRS interaction with RagD by the small-molecule inhibitor BC-LI-0186 reduced mTORC1 activity, restored autophagy, and ameliorated myofiber damage in the mdx muscles. Furthermore, inhibition of LeuRS by BC-LI-0186 improved dystrophic muscle strength in an autophagy-dependent manner. Taken together, our findings uncovered a noncanonical function of the housekeeping protein LeuRS as a potential therapeutic target in the treatment of DMD.


Asunto(s)
Autofagia , Modelos Animales de Enfermedad , Leucina-ARNt Ligasa , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones Endogámicos mdx , Debilidad Muscular , Distrofia Muscular de Duchenne , Animales , Masculino , Ratones , Leucina-ARNt Ligasa/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones Endogámicos C57BL , Debilidad Muscular/metabolismo , Debilidad Muscular/patología , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/patología , Distrofia Muscular de Duchenne/metabolismo , Transducción de Señal
8.
Food Res Int ; 187: 114378, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763650

RESUMEN

Although chocolates are often chosen for sensory pleasure, they are also selected to enhance mood and relieve emotional stress, or potentially chosen for its perceived health benefits if stress adversely affects physical well-being. This study aimed to investigate whether emotional stress influenced the motivations behind chocolate selection, subsequent liking, and emotional response. Participants were divided into a control group (n = 76) and a group with induced acute stress (n = 74). Stimuli were presented as dark chocolate packaging, each evoking sensory appeal, health, and emotional stress relief. Participants chose one stimulus from three options that they were most inclined to consume and evaluated the overall liking and emotional attributes of the stimuli. They also rated the overall liking and emotional attributes of three types of chocolates, each identical but paired with distinct stimuli. Their food attitudes were also assessed. Stress did not change the choice of stimuli, indicating that stress did not influence the motivation for chocolate selection. Instead, the choice of stimuli aligned with participants' food attitudes; those favoring sensory appeal and emotional stress relief prioritized pleasure in their usual food choices. Stress tended to increase liking and chocolate-associated positive emotions with sensory appeal, as opposed to others, to immediately alleviate negative emotions. The most robust motivation to consume chocolates was sensory pleasure, irrespective of stress, because of a preestablished association between sensory pleasure and mood enhancement.


Asunto(s)
Chocolate , Conducta de Elección , Emociones , Preferencias Alimentarias , Motivación , Estrés Psicológico , Humanos , Femenino , Masculino , Preferencias Alimentarias/psicología , Adulto Joven , Adulto , Estrés Psicológico/psicología , Placer , Adolescente
9.
Front Cell Infect Microbiol ; 14: 1287557, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577619

RESUMEN

Despite extensive knowledge of antibiotic-targeted bacterial cell death, deeper understanding of antibiotic tolerance mechanisms is necessary to combat multi-drug resistance in the global healthcare settings. Regulatory RNAs in bacteria control important cellular processes such as cell division, cellular respiration, metabolism, and virulence. Here, we investigated how exposing Escherichia coli to the moderately effective first-generation antibiotic cephalothin alters transcriptional and post-transcriptional dynamics. Bacteria switched from active aerobic respiration to anaerobic adaptation via an FnrS and Tp2 small RNA-mediated post-transcriptional regulatory circuit. From the early hours of antibiotic exposure, FnrS was involved in regulating reactive oxygen species levels, and delayed oxygen consumption in bacteria. We demonstrated that bacteria strive to maintain cellular homeostasis via sRNA-mediated sudden respiratory changes upon sublethal antibiotic exposure.


Asunto(s)
Antibacterianos , ARN , Antibacterianos/farmacología , Anaerobiosis , Respiración de la Célula , Bacterias , Respiración , Regulación Bacteriana de la Expresión Génica
10.
Nano Lett ; 24(14): 4233-4240, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38557069

RESUMEN

This study represents the synthesis of a novel class of nanoparticles denoted as annular Au nanotrenches (AANTs). AANTs are engineered to possess embedded, narrow circular nanogaps with dimensions of approximately 1 nm, facilitating near-field focusing for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via a surface-enhanced Raman scattering (SERS)-based immunoassay. Notably, AANTs exhibited an exceedingly low limit of detection (LOD) of 1 fg/mL for SARS-CoV-2 spike glycoproteins, surpassing the commercially available enzyme-linked immunosorbent assay (ELISA) by 6 orders of magnitude (1 ng/mL from ELISA). To assess the real-world applicability, a study was conducted on 50 clinical samples using an SERS-based immunoassay with AANTs. The results revealed a sensitivity of 96% and a selectivity of 100%, demonstrating the significantly enhanced sensing capabilities of the proposed approach in comparison to ELISA and commercial lateral flow assay kits.


Asunto(s)
COVID-19 , Nanopartículas del Metal , Humanos , SARS-CoV-2 , Oro , COVID-19/diagnóstico , Inmunoensayo/métodos , Espectrometría Raman/métodos
11.
J Chem Phys ; 160(12)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38516976

RESUMEN

This study investigated the segmental dynamics of polymers near polymer-polymer interfaces by probing the rotation of polymer-tethered fluorescent molecules using imaging rotational fluorescence correlation microscopy. Multilayered films were utilized to provide spatial selectivity relative to different polymer-polymer interfaces. In the experimental setup, for the overlayer polymer, polystyrene (PS) was employed and a 15 nm-thick probe-containing layer was placed ≈25 nm apart from different underlayer polymers with glass transition temperatures (Tg) either lower or higher than that of PS. The underlayer of poly-n-butyl methacrylate had 72 K lower Tg than that of PS, whereas polymethyl methacrylate and polysulfone had 22 and 81 K higher Tg, respectively, than that of PS. Two key dynamic features of the glass transition, the non-Arrhenius temperature dependence and stretched relaxation, were examined to study the influence of soft and hard confinements on the segmental dynamics of the overlayer polymer near the polymer-polymer interfaces. Although complications exist in the probing location owing to the diffusion of the polymer-tethered probe during the annealing protocol to consolidate the multilayers, the results suggest that either the segmental dynamics of the polymer near the polymer-polymer interface do not change owing to the soft and hard confinements or the interfacial perturbation is very short ranged.

12.
Nano Lett ; 24(13): 3930-3936, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38513221

RESUMEN

Detecting weakly adsorbing molecules via label-free surface-enhanced Raman scattering (SERS) has presented a significant challenge. To address this issue, we propose a novel approach for creating tricomponent SERS substrates using dual-rim nanorings (DRNs) made of Au, Ag, and CuO, each possessing distinct functionalities. Our method involves depositing different metals on Pt nanoring skeletons to obtain each nanoring with varying surface compositions while maintaining a similar size and shape. Next, the mixture of these nanorings is transferred into a monolayer assembly with homogeneous intermixing on a solid substrate. The surface of the CuO DRNs has dangling bonds (Cu2+) that facilitate the strong adsorption of carboxylates through the formation of chelating bonds, while the combination of Au and Ag DRNs significantly enhances the SERS signal intensity through a strong coupling effect. Notably, the tricomponent assemblies enable the successful SERS-based analysis of biomolecules such as amino acids, proteins, nucleobases, and nucleotides.


Asunto(s)
Oro , Nanopartículas del Metal , Oro/química , Espectrometría Raman/métodos , Plata/química , Adsorción , Nanopartículas del Metal/química
13.
Biomed Opt Express ; 15(3): 1815-1830, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38495707

RESUMEN

High-speed, phase contrast retinal and blood flow imaging using an adaptive optics partially confocal multi-line ophthalmosocope (AO-pcMLO) is described. It allows for simultaneous confocal and phase contrast imaging with various directional multi-line illumination by using a single 2D camera and a digital micromirror device (DMD). Both vertical and horizontal line illumination directions were tested, for photoreceptor and vascular imaging. The phase contrast imaging provided improved visualization of retinal structures such as cone inner segments, vessel walls and red blood cells with images being acquired at frame rates up to 500 Hz. Blood flow velocities of small vessels (<40 µm in diameter) were measured using kymographs for capillaries and cross-correlation between subsequent images for arterioles or venules. Cardiac-related pulsatile patterns were observed with normal resting heart-beat rate, and instantaneous blood flow velocities from 0.7 to 20 mm/s were measured.

14.
ACS Nano ; 18(10): 7402-7410, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38411049

RESUMEN

In this research, we designed a stepwise synthetic method for Au@Pt hexapods where six elongated Au pods are arranged in a pairwise perpendicular fashion, sharing a common point (the central origin in a Cartesian-coordinate-like hexapod shape), featured with tip-selectively decorated Pt square nanoplates. Au@Pt hexapods were successfully synthesized by applying three distinctive chemical reactions in a stepwise manner. The Pt adatoms formed discontinuous thin nanoplates that selectively covered six concave facets of a Au truncated octahedron and served as etching masks in the succeeding etching process, which prevented underlying Au atoms from being oxidized. The subsequent isotropic etching proceeded radially, starting from the bare Au surface, carving the central nanocrystal in a concave manner. By controlling the etching conditions, Au@Pt hexapods were successfully fabricated, wherein the core Au domain is connected to six protruding arms, which hold Pt nanoplates at the ends. Due to their morphology, Au@Pt hexapods feature distinctive optical properties in the near-infrared region, as a proof of concept, allowing for surface-enhanced Raman spectroscopy (SERS)-based monitoring of in situ CO electrooxidation. We further extended our synthetic library by tailoring the size of the Pt nanoplates and neck widths of Au branches, demonstrating the validity of selective blocking and etching-based colloidal synthesis.

15.
Front Cell Neurosci ; 18: 1334244, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38419656

RESUMEN

Introduction: Enhancer of zeste homolog 2 (Ezh2) is responsible for trimethylation of histone 3 at lysine 27 (H3K27me3), resulting in repression of gene expression. Here, we explore the role of Ezh2 in forebrain GABAergic interneuron development. Methods: We removed Ezh2 in the MGE by generating Nkx2-1Cre;Ezh2 conditional knockout mice. We then characterized changes in MGE-derived interneuron fate and electrophysiological properties in juvenile mice, as well as alterations in gene expression, chromatin accessibility and histone modifications in the MGE. Results: Loss of Ezh2 increases somatostatin-expressing (SST+) and decreases parvalbumin-expressing (PV+) interneurons in the forebrain. We observe fewer MGE-derived interneurons in the first postnatal week, indicating reduced interneuron production. Intrinsic electrophysiological properties in SST+ and PV+ interneurons are normal, but PV+ interneurons display increased axonal complexity in Ezh2 mutant mice. Single nuclei multiome analysis revealed differential gene expression patterns in the embryonic MGE that are predictive of these cell fate changes. Lastly, CUT&Tag analysis revealed that some genomic loci are particularly resistant or susceptible to shifts in H3K27me3 levels in the absence of Ezh2, indicating differential selectivity to epigenetic perturbation. Discussion: Thus, loss of Ezh2 in the MGE alters interneuron fate, morphology, and gene expression and regulation. These findings have important implications for both normal development and potentially in disease etiologies.

16.
Mol Plant Microbe Interact ; 37(4): 380-395, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38114195

RESUMEN

Bemisia tabaci (whitefly) is a polyphagous agroeconomic pest species complex. Two members of this species complex, Mediterranean (MED) and Middle-East-Asia Minor 1 (MEAM1), have a worldwide distribution and have been shown to manipulate plant defenses through effectors. In this study, we used three different strategies to identify three MEAM1 proteins that can act as effectors. Effector B1 was identified using a bioinformatics-driven effector-mining strategy, whereas effectors S1 and P1 were identified in the saliva of whiteflies collected from artificial diet and in phloem exudate of tomato on which nymphs were feeding, respectively. These three effectors were B. tabaci specific and able to increase whitefly fecundity when transiently expressed in tobacco plants (Nicotiana tabacum). Moreover, they reduced growth of Pseudomonas syringae pv. tabaci in Nicotiana benthamiana. All three effectors changed gene expression in planta, and B1 and S1 also changed phytohormone levels. Gene ontology and KEGG pathway enrichment analysis pinpointed plant-pathogen interaction and photosynthesis as the main enriched pathways for all three effectors. Our data thus show the discovery and validation of three new B. tabaci MEAM1 effectors that increase whitefly fecundity and modulate plant immunity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Hemípteros , Nicotiana , Animales , Nicotiana/genética , Nicotiana/microbiología , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/microbiología , Solanum lycopersicum/parasitología , Pseudomonas syringae/fisiología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/metabolismo , Fertilidad/genética
17.
J Am Chem Soc ; 145(50): 27397-27406, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38078409

RESUMEN

Here, we report the synthesis of three-dimensional plasmonic nanolenses for strong near-field focusing. The nanolens exhibits a distinctive structural arrangement composed of nanoporous sponge-like networks within their interior. We denote these novel nanoparticles as "Au octahedral nanosponges" (Au Oh NSs). Employing a carefully planned multistep synthetic approach with Au octahedra serving as sacrificial templates, we successfully synthesized Au Oh NSs in solution. The porous domains resembling sponges contributed to enhanced scattering and absorption of incident light within metal ligaments. This optical energy was subsequently transferred to the nanospheres at the vertex, where near-field focusing was maximized. We named this observed enhancement a "lightning-sphere effect". Using single particle-by-particle surface-enhanced Raman scattering (SERS), we optimized the morphological dimensions of the spheres and porous domains to achieve the most effective near-field focusing. In the context of bulk SERS measurements targeting weakly adsorbing analytes (2-chloroethyl phenyl sulfide) in the gas phase, we achieved a low detection limit of 10 ppb. For nonadsorbing species (dimethyl methyl phosphonate), utilization of hybrid SERS substrates consisting of Au Oh NSs and metal-organic frameworks as gas-adsorbing intermediate layers was highly effective for successful SERS detection.

18.
PLoS One ; 18(11): e0293942, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37930972

RESUMEN

Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are included as a core clinical feature in Dementia with Lewy Bodies (DLB). A newly developed Noise Pareidolia Test (NPT) was proposed as a possible surrogate marker for VH in DLB patients as increased pareidolic responses correlated with informant-corroborated accounts of VH. This association could, however, be mediated by visuoperceptual impairment. To understand the drivers of performance on the NPT, we contrasted performances in patient groups that varied both in terms of visuoperceptual ability and rates of VH. N = 43 patients were studied of whom n = 13 had DLB or PD with Dementia (PDD); n = 13 had PD; n = 12 had typical, memory-onset Alzheimer's Disease (tAD); and n = 5 had Posterior Cortical Atrophy (PCA) due to Alzheimer's disease. All patient groups reported pareidolias. Within the Lewy body disorders (PD, DLB, PDD), there was no significant difference in pareidolic response rates between hallucinating and non-hallucinating patients. Visuoperceptual deficits and pareidolic responses were most frequent in the PCA group-none of whom reported VH. Regression analyses in the entire patient cohort indicated that pareidolias were strongly predicted by visuoperceptual impairment but not by the presence of VH. These findings suggest that pareidolias reflect the underlying visuoperceptual impairment of Lewy body disorders, rather than being a direct marker for VH.


Asunto(s)
Enfermedad de Alzheimer , Ilusiones , Enfermedad por Cuerpos de Lewy , Enfermedad de Parkinson , Humanos , Alucinaciones , Ilusiones/fisiología
19.
J Alzheimers Dis ; 95(3): 1253-1262, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37661879

RESUMEN

BACKGROUND: Objective measurement of regional cortical atrophy in individual patients would be a highly desirable adjunct for diagnosis of degenerative dementias. OBJECTIVE: We hypothesized that increasing the resolution of magnetic resonance scans would improve the sensitivity of cortical atrophy detection for individual patients. METHODS: 46 participants including 8 semantic-variant primary progressive aphasia (svPPA), seven posterior cortical atrophy (PCA), and 31 cognitively unimpaired participants underwent clinical assessment and 3.0T brain scans. SvPPA and PCA were chosen because there is overwhelming prior knowledge of the expected atrophy pattern. Two sets of T1-weighted images with 0.8 mm3 (HighRes) and conventional 1.0 mm3 (ConvRes) resolution were acquired. The cortical ribbon was segmented using FreeSurfer software to obtain surface-based thickness maps. Inter-sequence performance was assessed in terms of cortical thickness and sub-cortical volume reproducibility, signal-to-noise and contrast-to-noise ratios. For clinical cases, diagnostic effect size (Cohen's d) and lesion distribution (z-score and t-value maps) were compared between HighRes and ConvRes scans. RESULTS: The HighRes scans produced higher image quality scores at 90 seconds extra scan time. The effect size of cortical thickness differences between patients and cognitively unimpaired participants was 15-20% larger for HighRes scans. HighRes scans showed more robust patterns of atrophy in expected regions in each and every individual patient. CONCLUSIONS: HighRes T1-weighted scans showed superior precision for identifying the severity of cortical atrophy in individual patients, offering a proof-of-concept for clinical translation. Studying svPPA and PCA, two syndromes with well-defined focal atrophy patterns, offers a method to clinically validate and contrast automated algorithms.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Humanos , Encéfalo/patología , Enfermedad de Alzheimer/patología , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos , Atrofia/patología
20.
Diagnostics (Basel) ; 13(18)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37761369

RESUMEN

Pelvic floor muscles (PFMs) play a crucial role in maintaining pelvic organ support and continence. However, pelvic floor dysfunction (PFD), often resulting from insufficient PFM control, poses a substantial global health challenge for women. This study aims to explore the relationship between levator ani muscle elasticity when assessed through transperineal shear-wave elastography (SWE) and bladder base displacement, quantified using transabdominal ultrasonography (TAUS), as a means to comprehensively evaluate PFM function. A total of 42 nulliparous women participated in this study. Participants received instructions on proper PFM contractions using Kegel exercises. Levator ani muscle elasticity was assessed both at rest and during contractions using transperineal SWE, while bladder base displacement was simultaneously measured through TAUS. Repeated measures demonstrated strong intraclass correlation coefficients of 0.906 at rest and 0.687 during contractions for levator ani muscle elasticity. The mean elasticity values were 24.7 ± 4.5 kPa at rest and 62.1 ± 10.4 kPa during contractions. Additionally, the mean bladder base displacement was 7.2 ± 2.5 mm, and the normalized bladder base displacement via body mass index was 0.3 ± 0.1 mm. Significantly, a moderate correlation was identified between the PFM function, represented by the difference in levator ani elasticity during contractions and resting, and bladder base displacement (r = 0.486, p = 0.001). These findings underscore the potential utility of transperineal SWE as a reliable and noninvasive method to assess levator ani muscle elasticity and, consequently, PFM function. In conclusion, this study sheds light on the interplay between PFM elasticity and bladder base displacement, offering insights into PFM function assessments. The observed correlation suggests the clinical relevance of SWE in providing valuable information for treatment planning in PFD. These findings contribute to a deeper understanding of PFM dynamics, ultimately aiding in the effective management of PFD among women.

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