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1.
Environ Res ; 203: 111834, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34358501

RESUMO

Age-specific discrepancy of mortality burden attributed to temperature, measured as years of life lost (YLL), has been rarely investigated. We investigated age-specific temperature-YLL rates (per 100,000) relationships and quantified YLL per death caused by non-optimal temperature in China. We collected daily meteorological data, population data and daily death counts from 364 locations in China during 2006-2017. YLL was divided into three age groups (0-64 years, 65-74 years, and ≥75 years). A distributed lag non-linear model was first employed to estimate the associations of temperature with age-specific YLL rates in each location. Then we pooled the associations using a multivariate meta-analysis. Finally, we calculated age-specific average YLL per death caused by temperature by cause of death and region. We observed greater effects of cold and hot temperature on YLL rates for the elderly compared with the young population by region or cause of death. However, YLL per death due to non-optimal temperature for different regions or causes of death decreased with age, with 2.0 (95 % CI:1.5, 2.5), 1.2 (1.1, 1.4) and 1.0 years (0.9, 1.2) life loss per death for populations aged 0-64 years, 65-74 years and over 75 years, respectively. Most life loss per death results from moderate temperature, especially moderate cold for all age groups. The effect of non-optimal temperature on YLL rates is smaller for younger populations than older ones, while the temperature-related life loss per death was more prominent for younger populations.

2.
Environ Pollut ; 292(Pt B): 118392, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678392

RESUMO

The short-term effects of ambient temperature on mortality have been widely investigated. However, the epidemiological evidence on the long-term effects of temperature on mortality is rare. In present study, we conducted a nationwide quasi-experimental design, which based on a variant of difference-in-differences (DID) approach, to examine the association between long-term exposure to ambient temperature and mortality risk in China, and to analyze the effect modification of population characteristics and socioeconomic status. Data on mortality were collected from 364 communities across China during 2006-2017, and environmental data were obtained for the same period. We estimated a 2.93 % (95 % CI: 2.68 %, 3.18 %) increase in mortality risk per 1 °C decreases in annual temperature, the greater effects were observed on respiratory diseases (5.16 %, 95 % CI: 4.53 %, 5.79 %) than cardiovascular diseases (3.43 %, 95 % CI: 3.06 %, 3.80 %), and on younger people (4.21 %, 95 % CI: 3.73 %, 4.68 %) than the elderly (2.36 %, 95 % CI: 2.06 %, 2.65 %). In seasonal analysis, per 1 °C decreases in average temperature was associated with 1.55 % (95 % CI: 1.23 %, 1.87 %), -0.53 % (95 % CI: -0.89 %, -0.16 %), 2.88 % (95 % CI: 2.45 %, 3.31 %) and 4.21 % (95 % CI: 3.98 %, 4.43 %) mortality change in spring, summer, autumn and winter, respectively. The effects of long-term temperature on total mortality were more pronounced among the communities with low urbanization, low education attainment, and low GDP per capita. In total, the decrease of average temperature in summer decreased mortality risk, while increased mortality risk in other seasons, and the associations were modified by demographic characteristics and socioeconomic status. Our findings suggest that populations with disadvantaged characteristics and socioeconomic status are vulnerable to long-term exposure of temperature, and targeted policies should be formulated to strengthen the response to the health threats of temperature exposure.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China/epidemiologia , Exposição Ambiental/análise , Humanos , Mortalidade , Estações do Ano , Temperatura
3.
Opt Express ; 29(23): 38728-38736, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808919

RESUMO

We described a wavelength locked and spectral narrowed high-power diode laser with a Faraday anomalous dispersion optical filter (FADOF). By an external cavity with a 85Rb FADOF, the central wavelength of the diode laser was precisely locked to the Rb resonance D2 line. The bandwidth was narrowed from the free-running 4 nm to 0.002 nm (1.2 GHz, FWHM). At 4.9 A maximal driven current, the laser produced a continuous wave (CW) output of 18 W with an external cavity efficiency of 80%, either the current or the temperature had no impact on the central wavelength of the diode laser. The Rb cell works well without any damage under a long-time running. This ultra-stable and extreme-narrowed high power diode laser would find many applications in alkali lasers pumping, metastable rare gas laser pumping, spin-exchange optical pumping, and quantum optics.

4.
Eur J Neurosci ; 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34779047

RESUMO

Brain iron affects working memory (WM) but the impact of iron content in deep grey matter nuclei on WM networks is unknown. We aimed to test whether deep grey matter nuclei iron concentration can affect resting-state functional connectivity (rsFC) within brain networks modifying WM performance. An N-back WM paradigm was applied in a hundred healthy younger adults. The participants then underwent a resting-state functional magnetic resonance imaging (fMRI) for brain network analysis and quantitative susceptibility mapping (QSM) imaging for assessment of deep grey matter nuclei iron concentration. Higher substantia nigra (SN) iron concentration was associated with lower rsFC between SN and brain regions of the temporal/frontal lobe but with better WM performance after controlling for age, gender and education. A follow-up mediation analysis also indicated that functional connectivity may mediate the link between SN iron and WM performance. Our results suggest that high SN iron concentration may affect communication between the SN and temporal/frontal lobe and is associated with strengthened WM performance in younger adults.

5.
Opt Lett ; 46(22): 5778-5781, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780460

RESUMO

A novel fiber laser called an oscillating-amplifying integrated fiber laser was studied experimentally, in which the oscillating section and amplifying section share the pump between them. Based on this configuration, a 5-kW fiber laser system with optical-optical efficiency of 80.9% and M2 factor of 1.5 was achieved. The startup and shutdown sequence of the laser was studied in detail. When pumps of the laser were deliberately turned on in an inverted order, such as switching on/off the amplifying section before/after the oscillating section, which is normally disastrous in a classic fiber amplifier, the laser system turned out to operate stably at full power level. Thus, it is verified that there is no priority between the amplifier and the seed in this laser system. It combines the advantages of conventional fiber oscillators and fiber amplifiers, including high efficiency, high reliability, good anti-backreflection, and simple control logic.

6.
Nanomedicine ; : 102491, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34781040

RESUMO

We previously reported that co-delivery of dihydroartemisinin and high mobility group box 1 (HMGB1) siRNAs, using cell penetrating peptide (TAT)-modified cationic liposomes (TAT-CLs-DHA/siRNA), resulted in promising activity for the treatment of inflammatory disease through TLR4 signaling pathway. In the current study, we further investigated the therapeutic effects of TAT-CLs-DHA/siRNA on lupus-prone MRL/lpr mice and explored its effects on B cell responses. In vitro, we found that TAT-CLs-DHA/siRNA suppressed the proliferation and activation of B cells through the TLR4 signaling pathway. Following parenteral administration every 4days, TAT-CLs-DHA/siRNA significantly reduced proteinuria, glomerulonephritis, serum anti-dsDNA antibody and secretion of interleukin (IL)-6, IL-10, IL-17 and IL-21. Moreover, Western blotting showed that TAT-CLs-DHA/siRNA modulated the B-cell intrinsic pathway by downregulating expression of HMGB1, TLR4, MyD88 and NF-κB. This co-delivery system thus represents a promising treatment option for lupus nephritis, and also highlights a novel target of lupus treatment through B cell TLR4 signal pathway.

7.
Front Oncol ; 11: 752158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745982

RESUMO

Background: Brain invasion in meningioma has independent associations with increased risks of tumor progression, lesion recurrence, and poor prognosis. Therefore, this study aimed to construct a model for predicting brain invasion in WHO grade II meningioma by using preoperative MRI. Methods: One hundred seventy-three patients with brain invasion and 111 patients without brain invasion were included. Three mainstream features, namely, traditional semantic features and radiomics features from tumor and tumor-to-brain interface regions, were acquired. Predictive models correspondingly constructed on each feature set or joint feature set were constructed. Results: Traditional semantic findings, e.g., peritumoral edema and other four features, had comparable performance in predicting brain invasion with each radiomics feature set. By taking advantage of semantic features and radiomics features from tumoral and tumor-to-brain interface regions, an integrated nomogram that quantifies the risk factor of each selected feature was constructed and had the best performance in predicting brain invasion (area under the curve values were 0.905 in the training set and 0.895 in the test set). Conclusions: This study provided a clinically available and promising approach to predict brain invasion in WHO grade II meningiomas by using preoperative MRI.

8.
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.

9.
Innovation (N Y) ; 2(4): 100171, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34778857

RESUMO

Although studies have investigated the associations between PM2.5 and mortality risk, evidence from rural areas is scarce. We aimed to compare the PM2.5-mortality associations between urban cities and rural areas in China. Daily mortality and air pollution data were collected from 215 locations during 2014-2017 in China. A two-stage approach was employed to estimate the location-specific and combined cumulative associations between short-term exposure to PM2.5 (lag 0-3 days) and mortality risks. The excess risks (ER) of all-cause, respiratory disease (RESP), cardiovascular disease (CVD), and cerebrovascular disease (CED) mortality for each 10 µg/m3 increment in PM2.5 across all locations were 0.54% (95% confidence interval [CI]: 0.38%, 0.70%), 0.51% (0.10%, 0.93%), 0.74% (0.50%, 0.97%), and 0.52% (0.20%, 0.83%), respectively. Slightly stronger associations for CVD (0.80% versus 0.60%) and CED (0.61% versus 0.26%) mortality were observed in urban cities than in rural areas, and slightly greater associations for RESP mortality (0.51% versus 0.43%) were found in rural areas than in urban cities. A mean of 2.11% (attributable fraction [AF], 95% CI: 1.48%, 2.76%) of all-cause mortality was attributable to PM2.5 exposure in China, with a larger AF in urban cities (2.89% [2.12%, 3.67%]) than in rural areas (0.61% [-0.60%, 1.84%]). Disparities in PM2.5-mortality associations between urban cities and rural areas were also found in some subgroups classified by sex and age. This study provided robust evidence on the associations of PM2.5 with mortality risks in China and demonstrated urban-rural disparities of PM2.5-mortality associations for various causes of death.

10.
Opt Express ; 29(17): 26366-26374, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615073

RESUMO

The transverse mode instability (TMI) has been one of the main limitations for the power scaling of single mode fiber lasers. In this work, we report a 6 kW single mode monolithic fiber laser enabled by effective mitigation of the TMI. The fiber laser employs a custom-made wavelength-stabilized 981 nm pump source, which remarkably enhanced the TMI threshold compared with the wavelength of 976 nm. With appropriately distributing bidirectional pump power, the monolithic fiber laser is scaled to 6 kW with single mode beam quality (M2<1.3). The stability is verified in a continuous operation for over 2 hours with power fluctuation below 1%.

11.
Nat Hum Behav ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711977

RESUMO

Urbanicity is a growing environmental challenge for mental health. Here, we investigate correlations of urbanicity with brain structure and function, neuropsychology and mental illness symptoms in young people from China and Europe (total n = 3,867). We developed a remote-sensing satellite measure (UrbanSat) to quantify population density at any point on Earth. UrbanSat estimates of urbanicity were correlated with brain volume, cortical surface area and brain network connectivity in the medial prefrontal cortex and cerebellum. UrbanSat was also associated with perspective-taking and depression symptoms, and this was mediated by neural variables. Urbanicity effects were greatest when urban exposure occurred in childhood for the cerebellum, and from childhood to adolescence for the prefrontal cortex. As UrbanSat can be generalized to different geographies, it may enable assessments of correlations of urbanicity with mental illness and resilience globally.

12.
Innovation (N Y) ; 2(1): 100072, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34557729

RESUMO

Although numerous studies have investigated premature deaths attributable to temperature, effects of temperature on years of life lost (YLL) remain unclear. We estimated the relationship between temperatures and YLL, and quantified the YLL per death caused by temperature in China. We collected daily meteorological and mortality data, and calculated the daily YLL values for 364 locations (2013-2017 in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces, and 2006-2011 in other locations) in China. A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates (YLL/100,000 population), and a multivariate meta-analysis model was used to pool location-specific associations. Then, YLL per death caused by temperatures was calculated. The temperature and YLL rates consistently showed U-shaped associations. A mean of 1.02 (95% confidence interval: 0.67, 1.37) YLL per death was attributable to temperature. Cold temperature caused 0.98 YLL per death with most from moderate cold (0.84). The mean YLL per death was higher in those with cardiovascular diseases (1.14), males (1.15), younger age categories (1.31 in people aged 65-74 years), and in central China (1.34) than in those with respiratory diseases (0.47), females (0.87), older people (0.85 in people ≥75 years old), and northern China (0.64) or southern China (1.19). The mortality burden was modified by annual temperature and temperature variability, relative humidity, latitude, longitude, altitude, education attainment, and central heating use. Temperatures caused substantial YLL per death in China, which was modified by demographic and regional characteristics.

13.
Front Aging Neurosci ; 13: 723948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566625

RESUMO

The cholinergic system is critical in Parkinson's disease (PD) pathology, which accounts for various clinical symptoms in PD patients. The substantia innominata (SI) provides the main source of cortical cholinergic innervation. Previous studies revealed cholinergic-related dysfunction in PD pathology at early stage. Since PD is a progressive disorder, alterations of cholinergic system function along with the PD progression have yet to be elucidated. Seventy-nine PD patients, including thirty-five early-stage PD patients (PD-E) and forty-four middle-to-late stage PD patients (PD-M), and sixty-four healthy controls (HC) underwent brain magnetic resonance imaging and clinical assessments. We employed seed-based resting-state functional connectivity analysis to explore the cholinergic-related functional alterations. Correlation analysis was used to investigate the relationship between altered functional connectivity and the severity of motor symptoms in PD patients. Results showed that both PD-E and PD-M groups exhibited decreased functional connectivity between left SI and left frontal inferior opercularis areas and increased functional connectivity between left SI and left cingulum middle area as well as right primary motor and sensory areas when comparing with HC. At advanced stages of PD, functional connectivity in the right primary motor and sensory areas was further increased. These altered functional connectivity were also significantly correlated with the Unified Parkinson's Disease Rating Scale motor scores. In conclusion, this study illustrated that altered cholinergic function plays an important role in the motor disruptions in PD patients both in early stage as well as during the progression of the disease.

14.
Front Pharmacol ; 12: 720886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566645

RESUMO

Shiyiwei Shenqi Tablet (SSTs) has been widely used for treatment of different types of cancer including breast cancer. SST has drawn more and more interest due to the low rate of side effects. The aim of this study was to investigate the metabolites in serums of breast cancer patients who received base-line chemotherapy only or combination treatment with SST. An untargeted metabolomics method was developed to investigate the alteration of metabolism in patients' serums using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry. The patients were separated based on the metabolomics data, and further analyses showed that SST treatment can affect the metabolism of glucose, fatty acid, bile acid and amino acid. In particular, SST treatment significantly reduced some short peptides which are potential tumor neoantigens. This study may provide novel insights into the mechanism underlying interaction between SST and base-line chemotherapy in terms of affecting metabolic pathways and thereby changing metabolic products, which might shed new light for clinical medication.

15.
J Phys Chem B ; 125(36): 10108-10118, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34473508

RESUMO

Accurate prediction of RNA structure and folding stability has a far-reaching impact on our understanding of RNA functions. Here we develop Vfold2D-MC, a new physics-based model, to predict RNA structure and folding thermodynamics from the sequence. The model employs virtual bond-based coarse-graining of RNA backbone conformation and generates RNA conformations through Monte Carlo sampling of the bond angles and torsional angles of the virtual bonds. Using a coarse-grained statistical potential derived from the known structures, we assign each conformation with a statistical weight. The weighted average over the conformational ensemble gives the entropy and free energy parameters for the hairpin, bulge, and internal loops, and multiway junctions. From the thermodynamic parameters, we predict RNA structures, melting curves, and structural changes from the sequence. Theory-experiment comparisons indicate that Vfold2D-MC not only gives improved structure predictions but also enables the interpretation of thermodynamic results for different RNA structures, including multibranched junctions. This new model sets a promising framework to treat more complicated RNA structures, such as pseudoknotted and intramolecular kissing loops, for which experimental thermodynamic parameters are often unavailable.


Assuntos
Dobramento de RNA , RNA , Conformação de Ácido Nucleico , Física , Termodinâmica
16.
BMC Public Health ; 21(1): 1534, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380442

RESUMO

BACKGROUND: There existed evidence that type 2 diabetes mellitus (T2DM) prevalence and control rate have seasonal variation. Our study aimed to examine the ambient temperature and fasting plasma glucose (FPG) association and estimate temperature-adjusted T2DM prevalence and control rate. METHODS: Four cross-sectional health surveys with 26,350 respondents were conducted in Guangdong Province from 2007 to 2015. Multistage cluster sampling was used to recruit study participants. The data of demographic characteristics, lifestyle factors, diet and use of hypoglycemic medicine, height, weight, FPG and meteorological information were collected. And an inverse distance-weighted method was employed to estimate daily temperature exposures at the individual' s residential district/county. Base on World Health Organization 2006 criteria, participants were divided into normal fasting glucose (NFG) participants (n = 23,877), known T2DM patients (n = 916) and newly detected T2DM patients (n = 1557). Generalized additive mixed model was employed to evaluate the nonlinear associations between temperature and FPG among different T2DM subgroups. The T2DM prevalence and control rate were estimated based on temperature-FPG association. RESULTS: The curves of temperature and FPG were downward parabola for total, NFG and known T2DM groups, while it was "U"-shaped for newly detected T2DM patients. When temperature decreased from 30 °C to 4 °C, the FPG significantly increased 0.24 (95%CI: 0.15, 0.33) mmol/L, 0.10 (95%CI: 0.06, 0.14) mmol/L and 1.34 (95%CI: 0.56, 2.12) mmol/L in total, NFG and known T2DM groups, respectively. Compared to 19 °C, newly detected T2DM patients' FPGs were increased 0.73 (95%CI: 0.13, 1.30) mmol/L at 4 °C and 0.53 (0.00, 1.07) mmol/L at 30 °C. The model-estimated temperature-adjusted T2DM prevalence had a down and up trend, with 9.7% at 5 °C, 8.9% at 20 °C and 9.4% at 30 °C, respectively. At 5, 10, 15, 20, 25 and 30 °C, the model-estimated temperature-adjusted T2DM control rates were 33.2, 35.4, 38.2, 43.6, 49.1 and 55.2%. CONCLUSION: Temperature was negatively associated with FPG for NFG and known T2DM subgroups, while their association was U-shape for newly detected T2DM patients. Hence, the temperature-adjusted T2DM prevalence show a dip/peak pattern and T2DM control rate display a rising trend when temperature increase. Our findings suggest temperature should be considered in T2DM clinic management and epidemiological survey.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Humanos , Prevalência , Temperatura
17.
Materials (Basel) ; 14(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443195

RESUMO

Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs.

18.
Brain Struct Funct ; 226(8): 2665-2673, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34373950

RESUMO

Increasing evidence suggests that genetic factors play a key role in the development of Parkinson's disease (PD). The variant rs11240572 in the PARK16 gene locus is strongly associated with PD. However, its effect on the pathogenesis of PD is yet to be clarified. The objective of the study was to explore the effect of the PARK16 rs11240572 variant on brain structure in PD patients. A total of 51 PD patients were enrolled in the study and genotyped for the rs11240572 variant. Clinical assessments and MRI scans were conducted across all participants. Voxel-based morphometry (VBM) was used to investigate gray matter volume (GMV) of the whole brain between these two groups. Correlation analysis was performed to identify the relationships between GMV and clinical features. There were 17 rs11240572-A variant carriers and 34 non-carriers, with no significant demographic differences between these two groups. Compared with non-carriers, rs11240572-A carriers showed increased GMV in the left caudate nucleus and putamen, but decreased GMV in the left superior temporal gyrus and supramarginal gyrus. In non-carriers, left basal ganglia GMV was positively correlated with UPDRS III (r = 0.365, p = 0.034) and bradykinesia (r = 0.352, p = 0.042), but negatively correlated with MMSE (r = - 0.344, p = 0.047), while in carriers negative correlation between basal ganglia GMV and MMSE was also observed (r = - 0.666, p = 0.004). Moreover, the GMV of left temporoparietal cortex was positively associated with cognitive function in both groups (carriers, r = 0.692, p = 0.002; non-carriers, r = 0.879, p < 0.001). When reducing the sample size of non-carriers to the level of the carrier sample, similar correlations were observed in both groups. Our study showed that the PARK16 rs11240572 variant affects the brain structure of patients with PD, especially in the basal ganglia and temporoparietal cortex. This indicated that this variant might play an important role in the pathogenesis of PD.

19.
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.

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