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1.
Alzheimers Dement ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713803

RESUMO

INTRODUCTION: The impact of early-life tobacco exposure on dementia has remained unknown. METHODS: Using the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all-cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted. RESULTS: The time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk. DISCUSSION: Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks. HIGHLIGHTS: Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method - the accelerated failure model - to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups.

2.
J Neurol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656621

RESUMO

BACKGROUND: Alzheimer's disease (AD) is on the rise in our aging society, making it crucial to identify additional risk factors to mitigate its increasing incidence. This systematic review and meta-analysis aimed to provide updated evidence regarding the association between sleep and AD. METHODS: We conducted a comprehensive search of MEDLINE, EMBASE, and Web of Science databases from inception to July 2023 to identify longitudinal studies. Adjusted relative risks were pooled for each sleep characteristic, and a dose-response analysis was performed specifically for sleep duration. RESULTS: A total of 15,278 records were initially retrieved, and after screening, 35 records were ultimately included in the final analysis. The results showed that insomnia (RR, 1.43; 95%CI, 1.17-1.74), sleep-disordered breathing (RR, 1.22; 95%CI, 1.07-1.39), as well as other sleep problems, including sleep fragmentation and sleep-related movement disorders, were associated with a higher risk of developing AD, while daytime napping or excessive daytime sleepiness (RR, 1.18; 95%CI, 1.00-1.40) only exhibited a trend toward a higher risk of AD development. Furthermore, our analysis revealed a significant association between self-reported sleep problems (RR, 1.34; 95%CI, 1.26-1.42) and the incidence of AD, whereas this association was not observed with sleep problems detected by objective measurements (RR, 1.14; 95%CI, 0.99-1.31). Moreover, both quite short sleep duration (< 4 h) and long duration (> 8 h) were identified as potential risk factors for AD. CONCLUSIONS: Our study found the association between various types of sleep problems and an increased risk of AD development. However, these findings should be further validated through additional objective device-based assessments. Additional investigation is required to establish a definitive causal connection between sleep problems and AD.

3.
Transl Psychiatry ; 14(1): 184, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600070

RESUMO

The prevalence of Alzheimer's disease (AD) is increasing as the population ages, and patients with AD have a poor prognosis. However, knowledge on factors for predicting the survival of AD remains sparse. Here, we aimed to systematically explore predictors of AD survival. We searched the PubMed, Embase and Cochrane databases for relevant literature from inception to December 2022. Cohort and case-control studies were selected, and multivariable adjusted relative risks (RRs) were pooled by random-effects models. A total of 40,784 reports were identified, among which 64 studies involving 297,279 AD patients were included in the meta-analysis after filtering based on predetermined criteria. Four aspects, including demographic features (n = 7), clinical features or comorbidities (n = 13), rating scales (n = 3) and biomarkers (n = 3), were explored and 26 probable prognostic factors were finally investigated for AD survival. We observed that AD patients who had hyperlipidaemia (RR: 0.69) were at a lower risk of death. In contrast, male sex (RR: 1.53), movement disorders (including extrapyramidal signs) (RR: 1.60) and cancer (RR: 2.07) were detrimental to AD patient survival. However, our results did not support the involvement of education, hypertension, APOE genotype, Aß42 and t-tau in AD survival. Our study comprehensively summarized risk factors affecting survival in patients with AD, provided a better understanding on the role of different factors in the survival of AD from four dimensions, and paved the way for further research.


Assuntos
Doença de Alzheimer , Humanos , Masculino , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Biomarcadores , Estudos de Casos e Controles , Genótipo , Fatores de Risco , Proteínas tau/genética
4.
NPJ Parkinsons Dis ; 10(1): 48, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429295

RESUMO

Parkinson's disease (PD) is a heterogeneous movement disorder with different motor subtypes including tremor dominant (TD), indeterminate and postural instability, and gait disturbance (PIGD) motor subtypes. Plasma glial fibrillary acidic protein (GFAP) was elevated in PD patients and may be regarded as a biomarker for motor and cognitive progression. Here we explore if there was an association between plasma GFAP and different motor subtypes and whether baseline plasma GFAP level can predict motor subtype conversion. Patients with PD classified as TD, PIGD or indeterminate subtypes underwent neurological evaluation at baseline and 2 years follow-up. Plasma GFAP in PD patients and controls were measured using an ultrasensitive single molecule array. The study enrolled 184 PD patients and 95 control subjects. Plasma GFAP levels were significantly higher in the PIGD group compared to the TD group at 2-year follow-up. Finally, 45% of TD patients at baseline had a subtype shift and 85% of PIGD patients at baseline remained as PIGD subtypes at 2 years follow-up. Baseline plasma GFAP levels were significantly higher in TD patients converted to PIGD than non-converters in the baseline TD group. Higher baseline plasma GFAP levels were significantly associated with the TD motor subtype conversion (OR = 1.283, P = 0.033) and lower baseline plasma GFAP levels in PIGD patients were likely to shift to TD and indeterminate subtype (OR = 0.551, P = 0.021) after adjusting for confounders. Plasma GFAP may serve as a clinical utility biomarker in differentiating motor subtypes and predicting baseline motor subtypes conversion in PD patients.

5.
J Neurol ; 271(5): 2672-2683, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372747

RESUMO

BACKGROUND: Epigenetics contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to characterize the DNA methylation profiles associated with clinical heterogeneity in disease progression and survival among patients. METHODS: We included a cohort of 41 patients with sporadic ALS, with a median follow-up of 86.9 months, and 27 rigorously matched healthy controls. Blood-based genome-wide DNA methylation analysis was conducted. RESULTS: A total of 948 progression rate-associated differentially methylated positions, 298 progression rate-associated differentially methylated regions (R-DMRs), 590 survival time-associated DMPs, and 197 survival time-associated DMRs (S-DMRs) were identified, using complementary grouping strategies. Enrichment analysis of differentially methylated genes highlighted the involvement of synapses and axons in ALS progression and survival. Clinical analysis revealed a positive correlation between the average methylation levels of the R-DMR in PRDM8 and disease progression rate (r = 0.479, p = 0.002). Conversely, there was an inverse correlation between the average methylation levels of the R-DMR in ANKRD33 and disease progression rate (r = - 0.476, p = 0.002). In addition, patients with higher methylation levels within the S-DMR of ZNF696 experienced longer survival (p = 0.016), while those with elevated methylation levels in the S-DMR of RAI1 had shorter survival (p = 0.006). CONCLUSION: DNA methylation holds promise as a potential biomarker for tracking disease progression and predicting survival outcome and also offers targets for precision medicine.


Assuntos
Esclerose Lateral Amiotrófica , Metilação de DNA , Progressão da Doença , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Epigênese Genética , Estudo de Associação Genômica Ampla , Seguimentos
6.
Brain Behav Immun ; 117: 447-455, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38336023

RESUMO

BACKGROUND: Multiple evidence has suggested the complex interplay between Parkinson's disease (PD) and systemic inflammation marked by C-reactive protein (CRP) and interleukin 6 (IL-6). Nevertheless, the findings across studies have shown inconsistency, and the direction of the effect remains controversial. Here, we aimed to explore the link between CRP and IL-6 and the risk of PD. METHODS: Based on data from the UK Biobank, we investigated the association between baseline CRP and IL-6 and the risk of incident PD with Cox proportional hazards regression analysis. We further performed extensive genetic analyses including genetic correlation, polygenic risk score (PRS), and pleiotropic enrichment based on summary statistics from previous genome-wide association studies. RESULTS: A higher level of CRP at baseline was associated with a lower risk of PD (HR = 0.85, 95 % CI: 0.79-0.90, P = 4.23E-07). The results remained consistent in the subgroup analyses stratified by sex, age and body mass index. From the genetic perspective, a significant negative genetic correlation was identified between CRP and PD risk (correlation: -0.14, P = 6.31E-05). Higher PRS of CRP was associated with a lower risk of PD (P = 0.015, beta = -0.04, SE = 0.017). Moreover, we observed significant pleiotropic enrichment for PD conditional on CRP, and identified 13 risk loci for PD, some of which are implicated in immune functionality and have been linked to PD, including CTSB, HNF4A, PPM1G, ACMSD, and NCOR1. In contrast, no significant association was identified between IL-6 and PD. CONCLUSIONS: Systemic inflammation at baseline measured by CRP level is associated with decreased future risk of PD. These discoveries contribute to a deeper comprehension of the role of inflammation in the risk of PD, and hold implications for the design of therapeutic interventions in clinical trials.


Assuntos
Estudo de Associação Genômica Ampla , Doença de Parkinson , Humanos , Interleucina-6/genética , Doença de Parkinson/genética , Estudos Prospectivos , Inflamação/genética , Proteína C-Reativa , Estratificação de Risco Genético , Proteína Fosfatase 2C
7.
Neurobiol Aging ; 134: 40-42, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984314

RESUMO

Mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene has been identified as a causative gene for autosomal dominant Parkinson's disease (PD), with the p.Y314S variant potentially associated with polyneuropathy in PD patients. The objectives of our study were to screen for UQCRC1 variants in Chinese patients with early-onset PD (EOPD) and explore the role of UQCRC1 in EOPD. We investigated the rare variants in 913 EOPD patients in our cohort using whole-exome sequencing, assessing their link to PD at both allele and gene levels. A total of 7 rare variants (minor allele frequency < 0.1%) of UQCRC1 were identified. However, no excessive burden of rare UQCRC1 variants was suggested in the EOPD patients. Further analysis with larger sample size and diverse regions is needed to determine the role of UQCRC1 in PD.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons , Doença de Parkinson , Humanos , Idade de Início , China , Sequenciamento do Exoma , Doença de Parkinson/genética , Complexo III da Cadeia de Transporte de Elétrons/genética
8.
Mol Neurobiol ; 61(4): 2265-2269, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37870677

RESUMO

DnaJ heat shock protein family member C7 gene (DNAJC7) has been identified as a genetic risk factor for amyotrophic lateral sclerosis (ALS). In our study, we aimed to screen for rare variants in DNAJC7 in a large cohort of Chinese ALS patients, and investigate the genotype-phenotype correlation of DNAJC7 in ALS. Four (0.19%) variants of DNAJC7 with minor allele frequency (MAF) < 0.1% among 2124 patients were identified, including 1 protein-truncating variant and 3 missense variants, all of which were predicted to be damaging. The patients carrying variants of DNAJC7 in our cohort tented to have a limb onset and a relatively slow disease progression. However, burden analysis did not show an enrichment of rare damaging variants in ALS patients compared to controls. Further analysis involving diverse regions and larger sample size is necessary to elucidate the role of DNAJC7 in the pathogenicity of ALS.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/genética , Estudos de Associação Genética , Mutação de Sentido Incorreto , Frequência do Gene , China , Proteínas de Choque Térmico/genética , Chaperonas Moleculares
9.
Neuroepidemiology ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38035555

RESUMO

Objectives Oral health problem is prevalent in the elderly population which is also at high risk of Parkinson's disease (PD). However, the association between self-reported oral health and PD is still unclear. We aimed to explore the association between baseline self-reported oral health (mouth ulcers, painful gums, bleeding gums, loosen teeth, toothache, dentures) and future incidence of PD. Methods Participants were enrolled in the UK biobank from 2006 to 2010 and those without PD at baseline were included in the current study. We used Cox regression analysis to explore the question and adjusted for age, sex, body mass index, smoking, drinking, ethnicity, education, socioeconomic status, and average total household income before tax. Results We included 421180 participants with a mean age of 56.26 years old and 46.5% of them were male. And 2339 participants were diagnosed with PD in the follow-up. Mouth ulcers, loosen teeth, dentures, toothache, and bleeding gums were not related to the risk of PD. Painful gums were related to a higher risk of PD (HR: 1.39, 95%CI: 1.12-1.72, P = 0.003), and similar results were reached after adjusting for gene risk (HR: 1.39, 95%CI: 1.12-1.73, P = 0.003), or source of diagnosis (HR: 1.39, 95%CI: 1.12-1.72, P = 0.002), and time of diagnosis (HR: 1.29, 95%CI: 1.03-1.63, P = 0.02). Conclusions Our study has demonstrated a substantial correlation between painful gums and elevated susceptibility to PD, underscoring the potential advantages of implementing oral health interventions for decreasing the risk of PD.

10.
Ann Neurol ; 94(5): 933-941, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37528491

RESUMO

OBJECTIVE: Age at onset (AAO) is an essential clinical feature associated with disease progression and mortality in amyotrophic lateral sclerosis (ALS). Identification of genetic variants and environmental risk factors influencing AAO of ALS could help better understand the disease's biological mechanism and provide clinical guidance. However, most genetic studies focused on the risk of ALS, while the genetic background of AAO is less explored. This study aimed to identify genetic and environmental determinants for AAO of ALS. METHODS: We performed a genome-wide association analysis using a Cox proportional hazards model on AAO of ALS in 10,068 patients. We further conducted colocalization analysis and in-vitro functional exploration for the target variants, as well as Mendelian randomization analysis to identify risk factors influencing AAO of ALS. RESULTS: The total heritability of AAO of ALS was ~0.16 (standard error [SE] = 0.03). One novel locus rs2046243 (CTIF) was significantly associated with earlier AAO by ~1.29 years (p = 1.68E-08, beta = 0.10, SE = 0.02). Functional exploration suggested this variant was associated with increased expression of CTIF in multiple tissues including the brain. Colocalization analysis detected a colocalization signal at the locus between AAO of ALS and expression of CTIF. Causal inference indicated higher education level was associated with later AAO. INTERPRETATION: These findings improve the current knowledge of the genetic and environmental etiology of AAO of ALS, and provide a novel target CTIF for further research on ALS pathogenesis and potential therapeutic options to delay the disease onset. ANN NEUROL 2023;94:933-941.


Assuntos
Esclerose Lateral Amiotrófica , Estudo de Associação Genômica Ampla , Humanos , Idade de Início , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
11.
J Neurol ; 270(9): 4444-4450, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37278914

RESUMO

BACKGROUND: The pathogenesis of PD has not been fully elucidated, but recent studies have shown that the adaptive immune system may play a role in the pathology of PD. However, there is a lack of longitudinal studies exploring the relationship between peripheral adaptive immune indicators and the rate of disease progression in PD. METHODS: We included early PD patients with disease duration < 3 years and assessed the severity of clinical symptoms and peripheral adaptive immune system indicators (CD3+, CD4+, CD8+ T lymphocyte subsets, CD4+:CD8+ ratio, IgG, IgM, IgA, C3, C4) at baseline. Clinical symptoms were followed up every year. We used the Unified Parkinson's Disease Rating Scale (UPDRS) to assess the disease severity and the Montreal Cognitive Assessment (MoCA) to assess global cognitive function. RESULT: A total of 152 PD patients were eventually included. The linear mixed model showed no significant association between baseline peripheral blood adaptive immune indicators and baseline MoCA scores or UPDRS part III scores. A higher baseline CD3+ lymphocyte percentage was associated with a slower rate of decline in MoCA scores. Baseline immune indicators were not associated with the rate of change of the UPDRS part III scores. CONCLUSION: The subset of peripheral T lymphocytes was related to the rate of cognitive decline in early PD patients, suggesting that the peripheral adaptive immune system may be involved in the process of cognitive decline in early PD.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Doença de Parkinson , Humanos , Disfunção Cognitiva/complicações , Progressão da Doença , Transtornos Cognitivos/etiologia , Biomarcadores
13.
Mov Disord ; 38(6): 1099-1104, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37046398

RESUMO

BACKGROUND: Recently, homozygous variants in PTPA were identified as the disease cause for two pedigrees with early-onset parkinsonism and intellectual disability. Although the initial link between PTPA and parkinsonism has been established, further replication was still necessary. OBJECTIVES: To evaluate the genetic role of PTPA in Parkinson's disease (PD). METHODS: We analyzed rare variants of PTPA in cohorts of Asian and European ancestries (Ncase = 2743, Ncontrol = 8177) with whole-exome sequencing, and further explored the functional effect of the target variant. RESULTS: One patient with early-onset PD from a consanguineous family carried the homozygous variant p.Met329Val, while her parents and elder sister with heterozygous p.Met329Val were healthy. This patient developed minor cognitive decline within 1 year, with a Montreal Cognitive Assessment (MoCA) score dropping from 28 to 25. Functional exploration with overexpression studies suggested that this variant was associated with decreased protein phosphatase 2A (PTPA) protein level by affecting protein stability, but not mRNA expression. CONCLUSIONS: These results have broadened the mutation spectrum of PTPA, and paved the way for further research into the role of PTPA in PD. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Transtornos Parkinsonianos , Idoso , Feminino , Humanos , Disfunção Cognitiva/complicações , Heterozigoto , Mutação/genética , Doença de Parkinson/complicações , Transtornos Parkinsonianos/complicações
14.
J Neurol ; 270(5): 2438-2450, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36670248

RESUMO

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with rapid progression and high mortality. Physical activity (PA) has been identified as a major risk factor for ALS. However, the results across studies are still controversial. We aimed to explore the association between different types of PA and ALS. METHODS: The PubMed, EMBASE, Cochrane and Web of Science databases were systematically searched for case-control and cohort studies which explored the relationship between PA and ALS from inception to October 2022. The data were analyzed to generate a pooled effect and 95% confidence interval (CI). RESULTS: A total of 16,686 articles were included in the systematic search. After filtering, 28 studies from online database and 6 studies from references of relevant articles remained in the analysis. Individuals with a history of vigorous physical activity (OR 1.26, 95% CI 1.06-1.49), occupational-related activity (OR 1.14, 95% CI 1.04-1.25), leisure time activity (OR 1.08, 95% CI 1.04-1.12), unclassified PA (OR 1.05 95% CI 1.02-1.09) and professional athletes (SMR 5.23, 95% CI 2.67-10.25; SIR 2.54, 95% CI 1.37-4.69) were in higher risk of developing ALS. In contrast, sport-related activity (OR 0.97, 95% CI 0.76-1.26) was not associated with ALS. CONCLUSIONS: Vigorous physical activity, occupational-related activity, leisure time activity, unclassified PA and professional athletes were associated with a higher risk of ALS, while sport-related activity showed no association with ALS. Our findings clarified the relation between different types of PA and ALS and provided some practicable advice for the lifestyle of high-risk populations.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/etiologia , Fatores de Risco , Exercício Físico , Estudos de Coortes , Estilo de Vida
15.
J Neurol ; 270(3): 1361-1370, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36472687

RESUMO

BACKGROUND: Changes in the cognitive function of patients with restless legs syndrome is a growing area of research. Although several studies have been performed to investigate the association between restless legs syndrome (RLS) and cognitive function, the outcomes are still controversial. The meta-analysis aimed to elucidate the relationship between RLS and cognition, including global cognition and various cognitive domains including memory, attention, executive function, and spatial cognition. METHODS: We searched the MEDLINE, EMBASE, and Web of Science databases from inception to November 2022 to screen eligible records. The means and standard deviations of cognitive test scores were obtained to calculate the standard mean difference and 95% confidence intervals. RESULTS: A total of 1437 records were collected from the initial search and 16 records involving 4635 individuals were ultimately included in the systematic review and meta-analysis. Our data suggest negative associations between RLS and global cognition (SMD, - 0.42; 95% CI - 0.72 to - 0.11; I2 = 76.6%) and attention (SMD, - 0.43; 95% CI - 0.73 to - 0.12; I2 = 85.3%). No significant differences in memory (SMD, - 0.01; 95% CI - 0.31 to 0.28; I2 = 68.0%), executive function (SMD, - 0.10; 95% CI, - 0.30 to 0.11; I2 = 52.1%), or spatial cognition (SMD, - 0.17; 95% CI - 0.38 to 0.03; I2 = 58.5%) were observed between the RLS and control groups. Moreover, the strength of the results was modified by age but not by sex or region. CONCLUSIONS: Our findings suggest that RLS is negatively correlated with cognitive function, particularly global cognition and attention. However, the causal relationship, considering more confounders, is worthy of further exploration.


Assuntos
Síndrome das Pernas Inquietas , Humanos , Adulto , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/epidemiologia , Cognição , Função Executiva , Atenção
16.
Front Neurosci ; 15: 745227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557073

RESUMO

Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep.

17.
Nano Lett ; 21(11): 4643-4653, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34038136

RESUMO

DNA quantification is important for biomedical research, but the routinely used techniques rely on nucleic acid amplification which have inherent issues like cross-contamination risk and quantification bias. Here, we report a CRISPR-Cas12a-based molecular diagnostic technique for amplification-free and absolute quantification of DNA at the single-molecule level. To achieve this, we first screened out the optimal reaction parameters for high-efficient Cas12a assay, yielding over 50-fold improvement in sensitivity compared with the reported Cas12a assays. We further leveraged the microdroplet-enabled confinement effect to perform an ultralocalized droplet Cas12a assay, obtaining excellent specificity and single-molecule sensitivity. Moreover, we demonstrated its versatility and quantification capability by direct counting of diverse virus's DNAs (African swine fever virus, Epstein-Barr virus, and Hepatitis B virus) from clinical serum samples with a wide range of viral titers. Given the flexible programmability of crRNA, we envision this amplification-free technique as a versatile and quantitative platform for molecular diagnosis.


Assuntos
Vírus da Febre Suína Africana , Infecções por Vírus Epstein-Barr , Vírus da Febre Suína Africana/genética , Animais , Sistemas CRISPR-Cas , DNA/genética , Herpesvirus Humano 4 , Suínos
18.
Front Pharmacol ; 12: 728908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35153734

RESUMO

Background: Although multiple randomized controlled trials (RCTs) and systematic review and meta-analysis were performed to investigate the efficiency and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids in the treatment of acute renal colic, the therapeutic regimen of renal colic is still controversial. Therefore, the aim of this study was to derive a more concise comparison of the effectiveness and safety between NSAIDs and opioids in the treatment for patients with acute renal colic by a systematic review and meta-analysis. Design: We searched PubMed, Embase, and Cochrane Central Register of controlled trials for seeking eligible studies. The pooled mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) was calculated using the random effects model. The primary outcome was assessed according to the Grading of Recommendations Assessment, Development and Evaluation. Results: A total of 18 studies involving 3,121 participants were included in the systematic review and meta-analysis. No significant difference between the NSAID and opioid groups was observed, with changes in the visual analog scale (VAS) at 0-30 min (MD = 0.79, 95% CI: -0.51, 2.10). NSAIDs in the form of intravenous administration (IV) had no better effect on the changes in the VAS at 0-30 min, when compared to opioids (MD = 1.25, 95% Cl: -4.81, 7.3). The NSAIDs group in the form of IV had no better outcome compared to the opioids group, as well as the VAS at 30 min (MD = -1.18, 95% Cl: -3.82, 1.45; MD = -2.3, 95% Cl: -5.02, 0.42, respectively). Moreover, similar results of this outcome were also seen with the VAS at 45 min (MD = -1.36, 95% Cl: -5.24, 2.52). Besides, there was a statistical difference in the incidence of later rescue (RR = 0.76, 95% CI: 0.66, 0.89), drug-related adverse events (RR = 0.44, 95% CI: 0.27, 0.71), and vomiting (RR = 0.68, 95% CI: 0.49, 0.96). Conclusion: There is no significant difference between the NSAIDs and opioids in the treatment of renal colic in many outcomes (e.g., the VAS over different periods using different injection methods at 30 and 60 min), which has been focused on in this study. However, the patients who were treated using NSAIDs by clinicians can benefit from fewer side effects.

19.
J Infect ; 81(2): e1-e5, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32360881

RESUMO

OBJECTIVES: A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. METHODS: We collected 626 surface swabs within the Zhongnan Medical Center in Wuhan in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major PPE. The SARS-CoV-2 RNAs were detected by reverse transcription-PCR. RESULTS: The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects were self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were the most contaminated PPE. CONCLUSION: Our findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention among HCWs during the outbreak of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Infecção Hospitalar/transmissão , Surtos de Doenças/estatística & dados numéricos , Monitoramento Ambiental , Hospitais , Transmissão de Doença Infecciosa do Paciente para o Profissional , Pneumonia Viral/transmissão , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Surtos de Doenças/prevenção & controle , Desinfecção , Contaminação de Equipamentos/prevenção & controle , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Unidades de Terapia Intensiva , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2
20.
Appl Opt ; 57(13): 3606, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726538

RESUMO

This publisher's note amends the funding section in Appl. Opt.56, 9006 (2017)APOPAI0003-693510.1364/AO.56.009006.

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