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1.
Neurology ; 102(12): e209483, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38833653

RESUMO

BACKGROUND AND OBJECTIVES: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. METHODS: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). RESULTS: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. DISCUSSION: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.


Assuntos
Sistema Glinfático , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Doença de Parkinson/psicologia , Masculino , Feminino , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Estudos Retrospectivos , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética , Cognição/fisiologia , Testes Neuropsicológicos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo
2.
Orthop J Sports Med ; 12(6): 23259671241252421, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840789

RESUMO

Background: The effect of local corticosteroid (CS) injections on rotator cuff muscles remains poorly defined, despite the significance of muscle quality as a crucial prognostic factor for patients with rotator cuff tears (RCTs). Purpose: To compare alterations in gene and protein expression patterns in the rotator cuff muscles of patients with RCTs who received frequent joint CS injections with alterations in those without a history of CS injections. Study Design: Controlled laboratory study. Methods: A total of 24 rotator cuff muscle samples with medium-sized tears from 12 patients with a frequent joint CS injection history (steroid group; 7 men and 5 women who had received ≥5 injections with at least 1 within the previous 3 months; mean age, 63.0 ± 7.2 years) and 12 age- and sex-matched control patients without a history of CS injections (no-steroid group) were acquired. Alterations in the expression of genes and proteins associated with adipogenesis, myogenesis, inflammation, and muscle fibrosis were compared between the groups using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Statistical analysis included comparison of group means using the Mann-Whitney U test, chi-square test, or Fisher exact test and logistic regression for multivariate analysis. Results: In the steroid group, the mRNA expression levels of adipogenic CCAAT/enhancer-binding protein alpha (C/EBPα; P = .008) and muscle atrophy-related genes (atrogin; P = .019) were significantly higher, and those of myogenic differentiation 1 (MyoD; P = .035), inflammatory interleukin 6 (IL-6; P = .035), and high mobility group box 1 (P = .003) were significantly lower compared with the no-steroid group. In addition, MyoD (P = .041) and IL-6 (P = .026) expression were decreased in the steroid versus no-steroid group. Immunohistochemistry revealed increased expression of C/EBPα and atrogin and decreased expression of MyoD and IL-6 in the steroid versus no-steroid group. Conclusion: Patients with RCTs and a history of frequent CS injections exhibited an upregulation of adipogenic and muscle atrophy-related genes and proteins within the rotator cuff muscles and a downregulation in the expression of myogenic and inflammatory genes and proteins in the same muscles. Clinical Relevance: These altered gene and protein expressions by frequent local CS injections may cause poor outcomes in patients with RCTs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38750786

RESUMO

BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (ASES and constant score), and clinical scores (VAS). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (ASES score and constant score), and clinical score (VAS) during the 2-year post-surgery period (all p>0.05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years post-surgery, did not significantly vary between the groups (all p>0.05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity post-surgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.

5.
Front Aging Neurosci ; 16: 1369522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737587

RESUMO

Introduction: Cerebrospinal fluid (CSF) flow is involved in brain waste clearance and may be impaired in neurodegenerative diseases such as Parkinson's disease. This study aims to investigate the relationship between the CSF pulsation and the development of dementia in Parkinson's disease (PD) patients using EPI-based fMRI. Methods: We measured CSF pulsation in the 4th ventricle of 17 healthy controls and 35 PD patients using a novel CSF pulsation index termed "CSFpulse" based on echo-planar imaging (EPI)-based fMRI. The PD patients were classified into a PD with dementia high-risk group (PDD-H, n = 19) and a low risk group (PDD-L, n = 16), depending on their development of dementia within 5 years after initial brain imaging. The size of the 4th ventricle was measured using intensity-based thresholding. Results: We found that CSF pulsation was significantly higher in PD patients than in healthy controls, and that PD patients with high risk of dementia (PDD-H) had the highest CSF pulsation. We also observed an enlargement of the 4th ventricle in PD patients compared to healthy controls. Conclusion: Our results suggest that CSF pulsation may be a potential biomarker for PD progression and cognitive decline, and that EPI-based fMRI can be a useful tool for studying CSF flow and brain function in PD.

6.
Nat Commun ; 15(1): 4524, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806492

RESUMO

Membrane fusion, merging two lipid bilayers, is crucial for fabricating artificial membrane structures. Over the past 40 years, in contrast to precise and controllable membrane fusion in-vivo through specific molecules such as SNAREs, controlling the fusion in-vitro while fabricating artificial membrane structures in physiological ionic solutions without fusion proteins has been a challenge, becoming a significant obstacle to practical applications. We present an approach consisting of an electric field and a few kPa hydraulic pressure as an additional variable to physically control the fusion, enabling tuning of the shape and size of the 3D freestanding lipid bilayers in physiological ionic solutions. Mechanical model analysis reveals that pressure-induced parallel/normal tensions enhance fusion among membranes in the microwell. In-vitro peptide-membrane assay, mimicking vesicular transport via pressure-assisted fusion, and stability of 38 days with in-chip pressure control via pore size-regulated hydrogel highlight the potential for diverse biological applications.


Assuntos
Bicamadas Lipídicas , Fusão de Membrana , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Íons/química , Membranas Artificiais , Hidrogéis/química , Pressão , Peptídeos/química
7.
Artigo em Inglês | MEDLINE | ID: mdl-38698293

RESUMO

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.

8.
Sci Rep ; 14(1): 8781, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627497

RESUMO

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages' role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/fisiologia , Células Endoteliais , Síndrome da Liberação de Citocina , Macrófagos , Organoides
9.
Clin Nucl Med ; 49(6): 521-528, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38584352

RESUMO

PURPOSE OF THE REPORT: Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson's disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD. MATERIALS AND METHODS: In this retrospective analysis, we enrolled 187 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET at initial assessment and serial cognitive assessments during the follow-up period (>5 years). Patients with PD were classified into 2 groups: the PD with dementia (PDD)-high-risk (PDD-H; n = 47) and the PDD-low-risk (PDD-L; n = 140) groups according to dementia conversion within 5 years of PD diagnosis. We explored between-group differences in the regional uptake in the early-phase 18 F-FP-CIT PET images. We additionally performed a linear discriminant analysis to develop a prediction model for early PDD conversion. RESULTS: The PDD-H group exhibited hypoperfusion in Alzheimer's disease (AD)-prone regions (inferomedial temporal and posterior cingulate cortices, and insula) compared with the PDD-L group. A prediction model using regional uptake in the right entorhinal cortex, left amygdala, and left isthmus cingulate cortex could optimally distinguish the PDD-H group from the PDD-L group. CONCLUSIONS: Regional hypoperfusion in the AD-prone regions on early-phase 18 F-FP-CIT PET can be a useful biomarker for predicting early dementia conversion in patients with PD.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Feminino , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Demência/diagnóstico por imagem , Demência/fisiopatologia , Pessoa de Meia-Idade , Circulação Cerebrovascular , Tropanos , Estudos Retrospectivos
10.
J Orthop Surg (Hong Kong) ; 32(1): 10225536241243166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38546214

RESUMO

Background: Over the last few decades, shoulder surgery has undergone rapid advancements, with ongoing exploration and the development of innovative technological approaches. In the coming years, technologies such as robot-assisted surgeries, virtual reality, artificial intelligence, patient-specific instrumentation, and different innovative perioperative and preoperative planning tools will continue to fuel a revolution in the medical field, thereby pushing it toward new frontiers and unprecedented advancements. In relation to this, shoulder surgery will experience significant breakthroughs. Main body: Recent advancements and technological innovations in the field were comprehensively analyzed. We aimed to provide a detailed overview of the current landscape, emphasizing the roles of technologies. Computer-assisted surgery utilizing robotic- or image-guided technologies is widely adopted in various orthopedic specialties. The most advanced components of computer-assisted surgery are navigation and robotic systems, with functions and applications that are continuously expanding. Surgical navigation requires a visual system that presents real-time positional data on surgical instruments or implants in relation to the target bone, displayed on a computer monitor. There are three primary categories of surgical planning that utilize navigation systems. The initial category involves volumetric images, such as ultrasound echogram, computed tomography, and magnetic resonance images. The second type is based on intraoperative fluoroscopic images, and the third type incorporates kinetic information about joints or morphometric data about the target bones acquired intraoperatively. Conclusion: The rapid integration of artificial intelligence and deep learning into the medical domain has a significant and transformative influence. Numerous studies utilizing deep learning-based diagnostics in orthopedics have remarkable achievements and performance.


Assuntos
Robótica , Cirurgia Assistida por Computador , Humanos , Inteligência Artificial , Ombro , Fluoroscopia
11.
Parasit Vectors ; 17(1): 151, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519993

RESUMO

ABSTRACT: BACKGROUND: Clonorchis sinensis infection is one of the risk factors that provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis and even cholangiocarcinoma (CCA). Disrupted or aberrant intercellular communication among liver-constituting cells leads to pathological states that cause various hepatic diseases. This study was designed to investigate the pathological changes caused by C. sinensis excretory-secretory products (ESPs) in non-cancerous human cell lines (cholangiocytes [H69 cell line] and human hepatic stellate cells [LX2 cell line]) and their intercellular crosstalk, as well the pathological changes in infected mouse liver tissues. METHODS: The cells were treated with ESPs, following which transforming growth factor beta 1 (TGF-ß1) and interleukin-6 (IL-6) secretion levels and epithelial-mesenchymal transition (EMT)- and fibrosis-related protein expression were measured. The ESP-mediated cellular motility (migration/invasion) between two cells was assessed using the Transwell and three-dimensional microfluidic assay models. The livers of C. sinensis-infected mice were stained using EMT and fibrotic marker proteins. RESULTS: Treatment of cells with ESPs increased TGF-ß1 and IL-6 secretion and the expression of EMT- and fibrosis-related proteins. The ESP-mediated mutual cell interaction further affected the cytokine secretion and protein expression levels and promoted cellular motility. N-cadherin overexpression and collagen fiber deposition were observed in the livers of C. sinensis-infected mice. CONCLUSIONS: These findings suggest that EMT and biliary fibrosis occur through intercellular communication between cholangiocytes and hepatic stellate cells during C. sinensis infection, promoting malignant transformation and advanced hepatobiliary abnormalities.


Assuntos
Neoplasias dos Ductos Biliares , Clonorquíase , Clonorchis sinensis , Humanos , Animais , Camundongos , Clonorquíase/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Clonorchis sinensis/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Células Estreladas do Fígado/metabolismo , Fibrose , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Transição Epitelial-Mesenquimal
13.
Nat Commun ; 15(1): 1695, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402240

RESUMO

Prominent techniques such as real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and rapid kits are currently being explored to both enhance sensitivity and reduce assay time for diagnostic tests. Existing commercial molecular methods typically take several hours, while immunoassays can range from several hours to tens of minutes. Rapid diagnostics are crucial in Point-of-Care Testing (POCT). We propose an approach that integrates a time-series deep learning architecture and AI-based verification, for the enhanced result analysis of lateral flow assays. This approach is applicable to both infectious diseases and non-infectious biomarkers. In blind tests using clinical samples, our method achieved diagnostic times as short as 2 minutes, exceeding the accuracy of human analysis at 15 minutes. Furthermore, our technique significantly reduces assay time to just 1-2 minutes in the POCT setting. This advancement has the potential to greatly enhance POCT diagnostics, enabling both healthcare professionals and non-experts to make rapid, accurate decisions.


Assuntos
Doenças Transmissíveis , Aprendizado Profundo , Humanos , Testes de Diagnóstico Rápido , Testes Imediatos , Ensaio de Imunoadsorção Enzimática , Sensibilidade e Especificidade , Sistemas Automatizados de Assistência Junto ao Leito
14.
Aging Dis ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38300638

RESUMO

As a part of the glymphatic system, the choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain. We investigated the association between CP volume (CPV), amyloid-ß (Aß) burden, and cognition in patients on the Alzheimer's disease (AD) continuum. We retrospectively reviewed the records of 203 patients on the AD continuum and 82 healthy controls who underwent brain magnetic resonance imaging and 18F-florbetaben positron emission tomography. Automatic segmentation was performed, and the CPV was calculated. Cognitive function was assessed using detailed neuropsychological tests, and patients on the AD continuum were categorized into the non-dementia and dementia groups. The relationships between CPV, Aß burden, and cognitive function were assessed using multivariate linear regression and linear mixed model. CPV was greater in the AD group than in the healthy control group (1.50 vs. 1.30, P < 0.001), but was comparable between the AD non-dementia and dementia groups (1.50 vs. 1.48, P = 0.585). After adjusting for age and sex, a larger CPV was significantly associated with greater global Aß deposition (ß = 0.20, P = 0.002). Larger CPV was also associated with worse general cognitive function assessed using the sum of boxes of the clinical dementia rating scale (ß = 0.85, P = 0.034) and lower composite scores for memory (ß = -0.68, P = 0.002) and frontal/executive function domains (ß = -0.65, P < 0.001). In addition, a larger CPV was associated with a more rapid decline in Mini-Mental State Examination scores in the AD dementia group (ß = -0.58, P = 0.004). The present study demonstrated that CP enlargement was associated with increased Aß deposition and impaired memory and frontal/executive function in patients on the AD continuum.

15.
Biofabrication ; 16(2)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38373340

RESUMO

Versatile and efficient regulation of the mechanical properties of the extracellular matrix is crucial not only for understanding the dynamic changes in biological systems, but also for obtaining precise and effective cellular responses in drug testing. In this study, we developed a well plate-based hydrogel photo-crosslinking system to effectively control the mechanical properties of hydrogels and perform high-throughput assays. We improved cell biocompatibility by using gelatin methacryloyl (GelMA) with a visible light photo-crosslinking method. Multiple cell-laden GelMA hydrogels were simultaneously and uniformly created using multi-arrayed 520 nm light-emitting diodes in a well plate format. The elastic modulus of the hydrogels can be widely adjusted (0.5-30 kPa) using a photo-crosslinking system capable of independently controlling the light intensity or exposure time for multiple samples. We demonstrate the feasibility of our system by observing enhanced bone differentiation of human mesenchymal stem cells (hMSCs) cultured on stiffer hydrogels. Additionally, we observed that the osteogenic fate of hMSCs, affected by the different mechanical properties of the gel, was regulated by parathyroid hormone (PTH). Notably, in response to PTH, hMSCs in a high-stiffness microenvironment upregulate osteogenic differentiation while exhibiting increased proliferation in a low-stiffness microenvironment. Overall, the developed system enables the generation of multiple cell-laden three-dimensional cell culture models with diverse mechanical properties and holds significant potential for expansion into drug testing.


Assuntos
Hidrogéis , Hormônio Paratireóideo , Humanos , Hidrogéis/farmacologia , Osteogênese , Gelatina/farmacologia , Metacrilatos , Engenharia Tecidual/métodos
16.
J Mov Disord ; 17(2): 171-180, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38346940

RESUMO

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is recommended for general cognitive evaluation in Parkinson's disease (PD) patients. However, age- and education-adjusted cutoffs specifically for PD have not been developed or systematically validated across PD cohorts with diverse education levels. METHODS: In this retrospective analysis, we utilized data from 1,293 Korean patients with PD whose cognitive diagnoses were determined through comprehensive neuropsychological assessments. Age- and education-adjusted cutoffs were formulated based on 1,202 patients with PD. To identify the optimal machine learning model, clinical parameters and MoCA domain scores from 416 patients with PD were used. Comparative analyses between machine learning. METHODS: and different cutoff criteria were conducted on an additional 91 consecutive patients with PD. RESULTS: The cutoffs for cognitive impairment decrease with increasing age within the same education level. Similarly, lower education levels within the same age group correspond to lower cutoffs. For individuals aged 60-80 years, cutoffs were set as follows: 25 or 24 years for those with more than 12 years of education, 23 or 22 years for 10-12 years, and 21 or 20 years for 7-9 years. Comparisons between age- and education-adjusted cutoffs and the machine learning method showed comparable accuracies. The cutoff method resulted in a higher sensitivity (0.8627), whereas machine learning yielded higher specificity (0.8250). CONCLUSION: Both the age- and education-adjusted cutoff. METHODS: and machine learning. METHODS: demonstrated high effectiveness in detecting cognitive impairment in PD patients. This study highlights the necessity of tailored cutoffs and suggests the potential of machine learning to improve cognitive assessment in PD patients.

17.
Parkinsonism Relat Disord ; 121: 106024, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38377658

RESUMO

INTRODUCTION: This study aimed to investigate whether regional cerebral perfusion patterns on early-phase 18F-FP-CIT PET scans, which is typically coupled to cerebral metabolism, predict the long-term prognosis of Parkinson's disease (PD). METHODS: We enrolled 397 drug-naïve patients with early-stage PD who underwent dual-phase 18F-FP-CIT PET scans. After quantifying the early-phase 18F-FP-CIT PET images, cluster analysis was performed to delineate the PD subtypes according to the patterns of regional cerebral perfusion. We compared the risk of developing levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia between the PD subtypes. RESULTS: Cluster analysis classified patients into three subtypes: cluster 1 (relatively preserved cortical uptake; n = 175), cluster 2 (decreased uptake in the frontal, parietal, and temporal regions; n = 151), and cluster 3 (decreased uptake in more extensive regions, additionally involving the lateral occipital regions; n = 71). Cluster 1 was characterized by a younger age-of-onset, less severe motor deficits, less severely decreased 18F-FP-CIT binding in the caudate, and better cognitive performance. Cluster 3 was characterized by an older age-of-onset, more severe motor deficits, and poorer cognitive performance. Cluster 2 was intermediate between clusters 1 and 3. Cox regression analyses demonstrated that clusters 2 and 3 had a higher risk for dementia conversion than cluster 1, whereas the risk for developing LID, wearing-off, and FOG did not differ among the clusters. CONCLUSION: The patterns of regional cerebral perfusion can provide information on long-term prognosis with regards to cognitive, but not motor aspects of patients with early-stage PD.


Assuntos
Demência , Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Tropanos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos
18.
Arthroscopy ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38311267

RESUMO

PURPOSE: To determine the effects of topical tranexamic acid (TXA) administration on tendon adhesions, shoulder range of motion (ROM), and tendon healing in an acute rotator cuff repair rat model. METHODS: A total of 20 Sprague Dawley rats were used. Tendon adhesion, ROM, and biomechanical and histological analysis of tendon-bone healing was conducted at 3 and 6 weeks after surgery. The rats underwent rotator cuff repair surgery on both shoulders and were administered TXA via subacromial injections. The tendon adhesion was evaluated macroscopically and histologically. Biomechanical tendon healing was measured using a universal testing machine, and histological analysis was quantified by H&E, Masson's trichrome, and picrosirius red staining. RESULTS: At 3 weeks after surgery, the adhesion score was significantly lower in the TXA group (2.10 ± 0.32) than in the control group (2.70 ± 0.48) (P = .005), but there was no significant difference between the 2 groups at 6 weeks. Regarding ROM, compared with the control group, the TXA group showed significantly higher external rotation (36.35° ± 4.52° vs 28.42° ± 4.66°, P < .001) and internal rotation (45.35° ± 9.36° vs 38.94° ± 5.23°, P = .013) 3 weeks after surgery. However, at 6 weeks, there were no significant differences in external and internal rotation between the 2 groups. In the biomechanical analysis, no significant differences in gross examination (3 weeks, P = .175, 6 weeks, P = .295), load to failure (3 weeks, P = .117, 6 weeks, P = .295), or ultimate stress (3 weeks, P = .602, 6 weeks, P = .917) were noted between the 2 groups 3 and 6 weeks after surgery. In the histological analysis of tendon healing, no significant differences in the total score (3 weeks, P = .323, 6 weeks, P = .572) were found between the 2 groups 3 and 6 weeks after surgery. CONCLUSIONS: Topical TXA administration showed a beneficial effect in reducing tendon adhesions and improving ROM 3 weeks postoperatively and had no effect at 6 weeks. This suggests that additional intervention with TXA may be useful in achieving long-term improvement in shoulder stiffness. Additionally, TXA may increase tissue ground substance accumulation in the late postoperative period but does not adversely affect tendon-bone interface healing. CLINICAL RELEVANCE: The use of TXA after rotator cuff repair has no effect on tendon-bone interface healing in clinical practice and can improve shoulder stiffness in the early postoperative period. Additional research on the long-term effects is needed.

19.
Alzheimers Res Ther ; 16(1): 24, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297344

RESUMO

BACKGROUND: Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson's disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD. METHODS: This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion. RESULTS: TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (ß = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (ß = - 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014). CONCLUSIONS: This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.


Assuntos
Disfunção Cognitiva , Demência , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Índice de Massa Corporal , Cognição , Testes Neuropsicológicos , Demência/diagnóstico , Obesidade
20.
NPJ Parkinsons Dis ; 10(1): 4, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172188

RESUMO

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

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