Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 248
Filtrar
1.
Brain Imaging Behav ; 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34973120

RESUMO

Tremor in Parkinson's disease (PD) has distinct responsiveness to dopamine, which is supposed not be exclusively related to dopamine deficiency but has a close relationship with cholinergic system. This phenomenon indicates that cholinergic system may be an important regulatory for distinct dopamine responsiveness of parkinsonian tremor. Through investigating the alterations of cholinergic and dopaminergic network during levodopa administration, we aimed at exploring the mechanisms of differed dopamine responsiveness of parkinsonian tremor. Fifty-two PD patients with tremor were enrolled. MRI scanning, UPDRS III and its sub-symptom scores were collected in OFF and ON status (dopaminergic challenge test). Then, patients were divided into two groups (dopamine-resistant tremor and dopamine-responsive tremor) according to the tremor change rate median score. Dopaminergic and cholinergic network were obtained. LASSO regression was conducted to identify functional connectivity with distinct reactivity during levodopa administration between groups. Afterwards, detailed group comparisons, interaction and correlation analyses were performed. The reactivity of cholinergic connectivity showed the highest possibility to distinguish two groups, especially connectivity of right basal forebrain 123 to right parietal operculum cortex (R.BF123-R.PO). After levodopa administration, connectivity of R.BF123-R.PO was decreased for dopamine-responsive tremor while which remained unchanged for dopamine-resistant tremor. The reactivity of R.BF123-R.PO was negatively correlated with tremor change rate. Reduced cholinergic connectivity to parietal operculum may be an underlying mechanism for the responsive tremor in PD and the distinct cholinergic reactivity of parietal operculum to levodopa may be a core pathophysiology for the differed DA responsiveness of tremor in PD.

2.
Clin Transl Radiat Oncol ; 32: 59-68, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34935776

RESUMO

Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC. Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified. Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect. Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.

3.
Front Aging Neurosci ; 13: 755630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867281

RESUMO

Background: Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer's disease (AD) and has a high risk of progression to AD. Cigarette smoking is one of the important modifiable risk factors in AD progression. Cholinergic dysfunction, especially the nucleus basalis of Meynert (NBM), is the converging target connecting smoking and AD. However, how cigarette smoking affects NBM connectivity in MCI remains unclear. Objective: This study aimed to evaluate the interaction effects of condition (non-smoking vs. smoking) and diagnosis [cognitively normal (CN) vs. MCI] based on the resting-state functional connectivity (rsFC) of the NBM. Methods: After propensity score matching, we included 86 non-smoking CN, 44 smoking CN, 62 non-smoking MCI, and 32 smoking MCI. All subjects underwent structural and functional magnetic resonance imaging scans and neuropsychological tests. The seed-based rsFC of the NBM with the whole-brain voxel was calculated. Furthermore, the mixed effect analysis was performed to explore the interaction effects between condition and diagnosis on rsFC of the NBM. Results: The interaction effects of condition × diagnosis on rsFC of the NBM were observed in the bilateral prefrontal cortex (PFC), bilateral supplementary motor area (SMA), and right precuneus/middle occipital gyrus (MOG). Specifically, the smoking CN showed decreased rsFC between left NBM and PFC and increased rsFC between left NBM and SMA compared with non-smoking CN and smoking MCI. The smoking MCI showed reduced rsFC between right NBM and precuneus/MOG compared with non-smoking MCI. Additionally, rsFC between the NBM and SMA showed a significant negative correlation with Wechsler Memory Scale-Logical Memory (WMS-LM) immediate recall in smoking CN (r = -0.321, p = 0.041). Conclusion: Our findings indicate that chronic nicotine exposure through smoking may lead to functional connectivity disruption between the NBM and precuneus in MCI patients. The distinct alteration patterns on NBM connectivity in CN smokers and MCI smokers suggest that cigarette smoking has different influences on normal and impaired cognition.

4.
Hum Brain Mapp ; 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34904766

RESUMO

Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large-scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamics and cognition in PD. Spatiotemporal dynamics of the phase interactions of resting-state blood-oxygen-level-dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical-cortical fiber connectivity impairment, cortical synchronization/metastability, and cognitive performance were then assessed. We found that cortical synchronization and metastability in PD patients were significantly decreased. To examine whether this is an effect of dopamine depletion, we investigated 45 PD patients both ON and OFF dopamine replacement therapy, and found that cortical synchronization and metastability are significantly increased in the ON state. The extent of cortical synchronization and metastability in the OFF state reflected cognitive performance and mediates the difference in cognitive performance between the PD and NC groups. Furthermore, both the thalamic volume and thalamocortical fiber connectivity had positive relationships with cortical synchronization and metastability in the dopaminergic OFF state, and mediate the difference in cortical synchronization between the PD and NC groups. In addition, thalamic volume also reflected cognitive performance, and cortical synchronization/metastability mediated the relationship between thalamic volume and cognitive performance in PD patients. Together, these results highlight that subcortical dysfunction and reduced dopamine levels are responsible for decreased cortical synchronization and metastability, further affecting cognitive performance in PD. This might lead to biomarkers being identified that can predict if a patient is at risk of developing dementia.

5.
J Alzheimers Dis ; 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34958031

RESUMO

BACKGROUND: Cerebral microinfarcts (CMIs) might cause measurable disruption to brain connections and are associated with cognitive decline, but the association between CMIs and motor impairment is still unclear. OBJECTIVE: To assess the CMIs effect on motor function in vivo and explore the potential neuropathological mechanism based on graph-based network method. METHODS: We identified 133 non-demented middle-aged and elderly participants who underwent MRI scanning, cognitive, and motor assessment. The short physical performance battery (SPPB) assessed motor function, including balance, walking speed, and chair stand. We grouped participants into 34 incident CMIs carriers and 99 non-CMIs carriers as controls, depending on diffusion-weighted imaging. Then we assessed the independent CMIs effects on motor function and explored neural mechanisms of CMIs on motor impairment via mapping of degree centrality (DC) and eigenvector centrality (EC). RESULTS: CMIs carriers had worse motor function than non-carriers. Linear regression analyses showed that CMIs independently contributed to motor function. CMIs carriers had decreased EC in the precuneus, while increased DC and EC in the middle temporal gyrus and increased DC in the inferior frontal gyrus compared to controls (p < 0.05, corrected). Correlation analyses showed that EC of precuneus was related to SPPB (r = 0.25) and balance (r = 0.27); however, DC (r = -0.25) and EC (r = -0.25) of middle temporal gyrus was related with SPPB in all participants (p < 0.05, corrected). CONCLUSION: CMIs represent an independent risk factor for motor dysfunction. The relationship between CMIs and motor function may be attributed to suppression of functional hub region and compensatory activation of motor-related regions.

6.
Hum Brain Mapp ; 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967488

RESUMO

Temporal lobe epilepsy (TLE) is a network disorder with a high incidence of memory impairment. Memory processing ability highly depends on the dynamic coordination between distinct modules within the hippocampal network. Here, we investigate the relationship between memory phenotypes and modular alterations of dynamic functional connectivity (FC) in the hippocampal network in TLE patients. Then, 31 healthy controls and 66 TLE patients with hippocampal sclerosis were recruited. The patients were classified into memory-intact (MI, 35 cases) group and memory-deficit (MD, 31 cases) group, each based on individual's Wechsler Memory Scale-Revised score. The sliding-windows approach and graph theory analysis were used to analyze the hippocampal network based on resting state functional magnetic resonance imaging. Temporal properties and modular metrics were calculated. Two discrete and switchable states were revealed: a high modularized state (State I) and a low modularized state (State II), which corresponded to either anterior or posterior hippocampal network dominated pattern. TLE was prone to drive less State I but more State II, and the tendency was more obvious in TLE-MD. Additionally, TLE-MD showed more widespread alterations of modular properties compared with TLE-MI across two states. Furthermore, the dynamic modularity features had unique superiority in discriminating TLE-MD from TLE-MI. These findings demonstrated that state transitions and modular function of dissociable hippocampal networks were altered in TLE and more importantly, they could reflect different memory phenotypes. The trend revealed potential values of dynamic FC in elucidating the mechanism underlying memory impairments in TLE.

7.
Hum Brain Mapp ; 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34970835

RESUMO

Identifying a whole-brain connectome-based predictive model in drug-naïve patients with Parkinson's disease and verifying its predictions on drug-managed patients would be useful in determining the intrinsic functional underpinnings of motor impairment and establishing general brain-behavior associations. In this study, we constructed a predictive model from the resting-state functional data of 47 drug-naïve patients by using a connectome-based approach. This model was subsequently validated in 115 drug-managed patients. The severity of motor impairment was assessed by calculating Unified Parkinson's Disease Rating Scale Part III scores. The predictive performance of model was evaluated using the correlation coefficient (rtrue ) between predicted and observed scores. As a result, a connectome-based model for predicting individual motor impairment in drug-naïve patients was identified with significant performance (rtrue  = .845, p < .001, ppermu  = .002). Two patterns of connection were identified according to correlations between connection strength and the severity of motor impairment. The negative motor-impairment-related network contained more within-network connections in the motor, visual-related, and default mode networks, whereas the positive motor-impairment-related network was constructed mostly with between-network connections coupling the motor-visual, motor-limbic, and motor-basal ganglia networks. Finally, this predictive model constructed around drug-naïve patients was confirmed with significant predictive efficacy on drug-managed patients (r = .209, p = .025), suggesting a generalizability in Parkinson's disease patients under long-term drug influence. In conclusion, this study identified a whole-brain connectome-based model that could predict the severity of motor impairment in Parkinson's patients and furthers our understanding of the functional underpinnings of the disease.

8.
Small ; : e2104401, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825486

RESUMO

2D van der Waals (vdW) semiconductors hold great potentials for more-than-Moore field-effect transistors (FETs), and the efficient utilization of their theoretical performance requires compatible high-k dielectrics to guarantee the high gate coupling efficiency. The deposition of traditional high-k dielectric oxide films on 2D materials usually generates interface concerns, thereby causing the carrier scattering and degeneration of device performance. Here, utilizing a space-confined epitaxy growth approach, the authors successfully obtained air-stable ultrathin indium phosphorus sulfide (In2 P3 S9 ) nanosheets, the thickness of which can be scaled down to monolayer limit (≈0.69 nm) due to its layered structure. 2D In2 P3 S9 exhibits excellent insulating properties, with a high dielectric constant (≈24) and large breakdown voltage (≈8.1 MV cm-1 ) at room temperature. Serving as gate insulator, ultrathin In2 P3 S9 nanosheet can be integrated into MoS2 FETs with high-quality dielectric/semiconductor interface, thus providing a competitive electrical performance of device with subthreshold swings (SS) down to 88 mV dec-1 and a high ON/OFF ratio of 105 . This study proves an important strategy to prepare 2D vdW high-k dielectrics, and greatly facilitates the ongoing research of 2D materials for functional electronics.

9.
CNS Neurosci Ther ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821045

RESUMO

OBJECTIVE: The International Parkinson and Movement Disorder Society (MDS) has published research criteria for prodromal Parkinson's disease (pPD), which includes cognitive impairment as a prodromal marker. However, the clinical features of mild cognitive impairment (MCI) in pPD remain unknown. Our study aimed to evaluate the frequency and clinical features of mild cognitive impairment of pPD in the elderly in China. METHODS: The cross-sectional community-based study recruited 2688 participants aged ≥50 years. Subjects were diagnosed with pPD according to the MDS criteria. Overall, 39 pPD and 22 healthy controls underwent comprehensive clinical and neuropsychological assessment. MCI was also diagnosed by the MDS criteria. Next, we investigated the relationship between clinical factors and cognition. RESULTS: Among the 2,663 dementia-free and Parkinson disease (PD)-free participants, 55 met the criteria for pPD (2.1%) and 23 pPD met the criteria for MCI. Memory, attention/working memory, and executive function were the most frequent impaired domains, and amnestic MCI multidomain phenotype was the most frequent MCI subtype (69.57%) in pPD. Additionally, correlation analysis revealed that the global cognitive performance was negatively related to UPDRS-III score (r = -0.456, p = 0.004). CONCLUSION: MCI, specifically impairment in memory, attention/working memory, and executive domain, is present at the prodromal stage of PD. In addition, cognitive performance is correlated with motor symptoms in pPD. Our results reflect that cognitive profile, combined with motor symptoms, can help clinicians to identify individuals with pPD early, as those would be the optimal candidates for neuroprotective therapy.

10.
Respir Med ; 190: 106681, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34784563

RESUMO

BACKGROUND: Small airway dysfunction (SAD) is an early lesion of chronic respiratory disease that is best detected using impulse oscillometry (IOS). Few studies have investigated risk factors for IOS-defined SAD (IOS-SAD) in a large population. We aimed to explore the clinical features of and risk factors for IOS-SAD in a community-based population. METHODS: We divided subjects into IOS-SAD and non-SAD groups based on a cutoff of >0.07 kPa/L/s in the difference between the resistance at 5 Hz versus the resistance at 20 Hz (R5-R20). All participants underwent spirometry, IOS, and completed a questionnaire; some participants underwent computed tomography (CT). We analyzed the risk factors for SAD based on binary logistic regression. RESULTS: The total cohort comprised 1327 subjects. The prevalence of IOS-SAD was 32.9% (437/1327). Compared with the non-SAD group, the IOS-SAD group was older (64.0 ± 7.8 vs. 59.6 ± 7.8 years, p < 0.001), included less never-smokers (30.2% vs. 35.8%, p < 0.001), had greater airway resistance and worse lung function, indicated by a larger R5-R20 (0.15 ± 0.08 vs. 0.03 ± 0.02 kPa/L/s, p < 0.001) and smaller forced expiratory volume in 1 s to forced vital capacity after bronchodilation (60.2 ± 14.4% vs. 72.6 ± 10.0%, p < 0.001); on CT, the IOS-SAD group had higher prevalences of emphysema and gas trapping. Risk factors for SAD were older age, high BMI, smoking, childhood cough, and asthma. CONCLUSION: Subjects with IOS-SAD had increased airway resistance and visible CT changes. Individuals with smoking exposure, advanced age, high BMI, childhood cough, and asthma were more prone to SAD. CLINICAL TRIAL REGISTRATION: ChiCTR1900024643.

11.
J Immunother Cancer ; 9(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34782428

RESUMO

BACKGROUND: Toripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1. We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC). METHODS: We conducted a single-arm, phase II trial with patients with rNPC who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate at 3 months post radiotherapy. The secondary endpoints included safety profiles, progression-free survival (PFS). RESULTS: Between May 2019 and January 2020, a total of 25 patients with rNPC were enrolled (18 men (72.0%) and 7 women (28.0%); median (IQR) age, 49.0 (43.5-52.5) years). With a median (IQR) follow-up duration of 14.6 months (13.1-16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month PFS was 91.8% (95% CI 91.7% to 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine kinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively. CONCLUSIONS: Toripalimab combined with IMRT was tolerable and showed promising antitumor activity in patients with rNPC. TRIAL REGISTRATION NUMBER: NCT03854838.

12.
Neuroimage Clin ; 32: 102873, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34749290

RESUMO

Degeneration of the locus coeruleus (LC) is recognized as a critical hallmark of Parkinson's disease (PD). Recent studies have reported that noradrenaline produced from the LC has critical effects on brain functional organization. However, it is unknown if LC degeneration in PD contributes to cognitive/motor manifestations through modulating brain functional organization. This study enrolled 94 PD patients and 68 healthy controls, and LC integrity was measured using the contrast-to-noise ratio of the LC (CNRLC) calculated from T1-weighted magnetic resonance imaging. We used graph-theory-based network analysis to characterize brain functional organization. The relationships among LC degeneration, network disruption, and cognitive/motor manifestations in PD were assessed. Whether network disruption was a mediator between LC degeneration and cognitive/motor impairments was assessed further. In addition, an independent PD subgroup (n = 35) having functional magnetic resonance scanning before and after levodopa administration was enrolled to evaluate whether LC degeneration-related network deficiencies were independent of dopamine deficiency. We demonstrated that PD patients have significant LC degeneration compared to healthy controls. CNRLC was positively correlated with Montreal Cognitive Assessment score and the nodal efficiency (NE) of several cognitive-related regions. Lower NE of the superior temporal gyrus was a mediator between LC degeneration and cognitive impairment in PD. However, levodopa treatment could not normalize the reduced NE of the superior temporal gyrus (mediator). In conclusion, we provided evidence for the relationship between LC degeneration and extensive network disruption in PD, and highlight the role of network disorganization in LC degeneration-related cognitive impairment.

13.
J Phys Condens Matter ; 33(49)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34479213

RESUMO

Two-dimensional (2D) materials have attracted broad interests and been extensively exploited for a variety of functional applications. Moreover, one-dimensional (1D) atomic crystals can also be integrated into 2D templates to create mixed-dimensional heterostructures, and the versatility of combinations provides 2D-1D heterostructures plenty of intriguing physical properties, making them promising candidate to construct novel electronic and optoelectronic nanodevices. In this review, we first briefly present an introduction of relevant fabrication methods and structural configurations for 2D-1D heterostructures integration. We then discuss the emerged intriguing physics, including high optical absorption, efficient carrier separation, fast charge transfer and plasmon-exciton interconversion. Their potential applications such as electronic/optoelectronic devices, photonic devices, spintronic devices and gas sensors, are also discussed. Finally, we provide a brief perspective for the future opportunities and challenges in this emerging field.

14.
Sci Rep ; 11(1): 18773, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548502

RESUMO

Extensive loss of natural wetlands caused by changes in land use largely diminishes the food resources essential for the survival of migratory waterbirds. Globally, the decline in waterbird populations in East Asia is the most serious, with 64% of these populations showing a decreasing trend. In this study, we applied DNA metabarcoding to examine the spatiotemporal variations and diversities in the dietary compositions of migratory waterbirds in a natural/artificial wetland complex in Asia. By investigating 110 fecal samples from the endangered black-faced spoonbill (Platalea minor) wintering in the wetland, our results show that P. minor had a broad dietary spectrum. The birds fed on at least 26 species in the classes Actinopterygii and Malacostraca, with Mugiliformes, Cichliformes, and Gobiiformes being the main taxa in their diets. Our results also demonstrated clear patterns of the spatiotemporal variations between the roosting groups and intraspecific variations between the individuals, which potentially reflect some of their feeding habits, and the probable usage of different habitat types in the wetland complex. Using high-throughput sequencing, we were able to elucidate the food resources that are critical to P. minor non-invasively, this method can also be used to provide invaluable information for the conservation of many other waterbird species.

15.
Front Aging Neurosci ; 13: 683783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526888

RESUMO

Background: Before the apparent cognitive decline, subjects on the course of Alzheimer's disease (AD) can have significantly altered spontaneous brain activity, which could be potentially used for early diagnosis. As previous studies investigating local brain activity may suffer from the problem of cortical signal aliasing during volume-based analysis, we aimed to investigate the cortical functional alterations in the AD continuum using a surface-based approach. Methods: Based on biomarker profile "A/T," we included 11 healthy controls (HC, A-T-), 22 preclinical AD (CU, A+T+), 33 prodromal AD (MCI, A+T+), and 20 AD with dementia (d-AD, A+T+) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate the changes of spontaneous brain activity, which was performed in the classic frequency band (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz) band, and slow-5 (0.01-0.027 Hz) band. Results: Under classic frequency band and slow-4 band, analysis of covariance (ANCOVA) showed that there were significant differences of standardized ALFF (zALFF) in the left posterior cingulate cortex (PCC) among the four groups. The post-hoc analyses showed that under the classic frequency band, the AD group had significantly decreased zALFF compared with the other three groups, and the cognitively unimpaired (CU) group had decreased zALFF compared with the healthy control (HC) group. Under the slow-4 band, more group differences were detected (HC > CU/MCI > d-AD). The accuracy of classifying CU, mild cognitive impairment (MCI), and AD from HC by left PCC activity under the slow-4 band were 0.774, 0.744, and 0.920, respectively. Moreover, the zALFF values of the left PCC had significant correlations with cerebrospinal fluid (CSF) biomarkers and neuropsychological tests. Conclusions: Spontaneous brain activity in the left PCC may decrease in preclinical AD when cognitive functions were relatively normal. The combination of a surfaced-based approach and specific frequency band analysis may increase sensitivity for the identification of preclinical AD subjects.

16.
Front Aging Neurosci ; 13: 725246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539385

RESUMO

Background: Late-onset Alzheimer's disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the general "polygenic hazard score" (PHS) be a good choice to identify the individual genetic risk for AD; and (2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology. Methods: We collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum included from the ADNI database. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter (GM) volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established. Results: We found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before GM atrophy, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum. Conclusion: PHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, which might underpin the AD pathogenesis.

17.
Front Aging Neurosci ; 13: 693787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349635

RESUMO

Assessing glymphatic function using in-vivo imaging method is of great value for understanding its contribution to major brain diseases. In the present study, we aim to validate the association between a variety of risk factors and a potential index of glymphatic function-Diffusion Tensor Image Analysis Along the Perivascular Space (ALPS index). We enrolled 142 subjects from communities and performed multi-modality magnetic resonance imaging scans. The ALPS index was calculated from diffusion tensor imaging data, and its associations with demographic factors, vascular factors were investigated using regression analyses. We found that the ALPS index was negatively associated with age (ß = -0.284, p < 0.001). Compared to males, females had significantly higher ALPS index (ß = -0.243, p = 0.001). Hypertensive subjects had significantly lower ALPS index compared to non-hypertensive subjects (ß = -0.189, p = 0.013). Furthermore, venous disruption could decrease ALPS index (ß = -0.215, p = 0.003). In general, our results are in consistent with previous conceptions and results from animal studies about the pathophysiology of glymphatic dysfunction. Future studies utilizing this method should consider introducing the above-mentioned factors as important covariates.

18.
J Parkinsons Dis ; 11(4): 1631-1640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366373

RESUMO

BACKGROUND: The widely divergent responsiveness of Parkinson's disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment. OBJECTIVE: To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo. METHODS: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of the Unified Parkinson's Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness. RESULTS: A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = -0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration. CONCLUSION: LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa.

19.
BMC Cancer ; 21(1): 934, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412621

RESUMO

The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.


Assuntos
Bactérias/imunologia , Microbioma Gastrointestinal , Sistema Imunitário/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Probióticos/uso terapêutico , Animais , Humanos , Neoplasias/imunologia , Neoplasias/microbiologia
20.
Oral Oncol ; 121: 105494, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34425533

RESUMO

BACKGROUND: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. METHODS: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. RESULTS: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. CONCLUSION: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...