Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 392
Filtrar
1.
Aging (Albany NY) ; 13(undefined)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620734

RESUMO

High-fat diet (HFD) has been associated with neuroinflammation and apoptosis in distinct brain regions. To explore the effect of short-term (7, 14 and 21 days) high-fat overfeeding on apoptosis, inflammatory signaling proteins, APP changes and glial cell activities in cerebral cortex and cerebellum. Mice were fed with HFD for different lengths (up to 21 days) and after each time body weights of mice was tested, then the apoptotic proteins, IL-1ß, APP, BACE1and MAPKs, Akt and NF-κB signaling activity were evaluated by western blots. Results demonstrate that short period of high-fat overnutrition significantly promotes apoptosis, APP expression at day 21 of cerebral cortex and at day 7 of cerebellum compared to chow diet. In addition, increased GFAP+astrocytes, Iba-1+microglia and IL-1ß 30 were observed in cerebral cortex after 21 days HFD, but no changes for 7 days overfeeding of cerebellum. Serendipitously, ERK1/2 pathway was activated both in cerebral cortex and cerebellum for different time course of HFD. Furthermore, increased phospho-p38 MAPK level was observed in cerebellum only. In consistent with in vivo results, SH-SY5Y cells treatment with cholesterol (50 µM, 100 µM) for 48 h culture in vitro demonstrated that pro-apoptotic proteins were enhanced as well. In brief, short-term HFD consumption increases sensitivity to apoptosis, APP and IL-1ß production as well as gliosis in cerebral cortex and cerebellum, which may be related to enhancement of ERK1/2 and p38 MAPK activation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34509379

RESUMO

BACKGROUND: Drug-drug interactions (DDIs) cause many preventable hospitalizations and admissions. Efforts have been made to raise DDI awareness and reduce DDI occurrence; for example, Medicare Part D Star Ratings, a health plan quality assessment program, included a DDI measure. Previous research reported racial and ethnic disparities in health services utilization and that racial and ethnic minorities, compared with non-Hispanic whites (whites), may be less likely to be targeted for a similar measure, a Star Ratings adherence measure for diabetes medications. OBJECTIVE: This study aimed to investigate whether any racial and ethnic disparities are associated with the DDI measure in Part D Star Ratings among Medicare populations with diabetes, hypertension, and hyperlipidemia. METHODS: This cross-sectional study analyzed a 2017 Medicare Part D data sample, including 3,960,813 beneficiaries. Because the inclusion in the denominator of the Star Ratings DDI measure was determined by the use of a list of target medications, the likelihood of using a listed target medication was compared between racial and ethnic minorities and whites. Individuals with diabetes, hypertension, and hyperlipidemia were included in the analysis owing to the high prevalence of these conditions. Patient- and community-level characteristics were adjusted by logistic regression. RESULTS: Of the entire study sample, 26.2% used a target medication. Compared with whites, most racial and ethnic minorities were less likely to use a target medication. For example, among individuals with diabetes, blacks, Hispanics, Asians/Pacific Islanders, and others had, respectively, 14% (odds ratio 0.86 [95% CI 0.84-0.88]), 5% (0.95 [0.93-0.98]), 12% (0.88 [0.84-0.92]), and 10% (0.90 [0.87-0.93]) lower odds compared with whites. Findings were similar among hypertension and hyperlipidemia cohorts, except that Hispanics had similar odds of use as whites. CONCLUSION: Most racial and ethnic minorities may have lower likelihood of being targeted for the DDI measure compared with whites. Future studies should examine whether these disparities affect health outcomes and devise new DDI measures for racial and ethnic minorities.

3.
CNS Neurosci Ther ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551193

RESUMO

AIM: The role of vascular dementia (VaD)-associated genes in Alzheimer's disease (AD) remains elusive despite similar clinical and pathological features. We aimed to explore the relationship between these genes and AD in the Chinese population. METHODS: Eight VaD-associated genes were screened by a targeted sequencing panel in a sample of 3604 individuals comprising 1192 AD patients and 2412 cognitively normal controls. Variants were categorized into common variants and rare variants according to minor allele frequency (MAF). Common variant (MAF ≥ 0.01)-based association analysis was conducted by PLINK 1.9. Rare variant (MAF < 0.01) association study and gene-based aggregation testing of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test), respectively. Age at onset (AAO) and Mini-Mental State Examination (MMSE) association studies were performed with PLINK 1.9. Analyses were adjusted for age, gender, and APOE ε4 status. RESULTS: Four common COL4A1 variants, including rs874203, rs874204, rs16975492, and rs1373744, exhibited suggestive associations with AD. Five rare variants, NOTCH3 rs201436750, COL4A1 rs747972545, COL4A1 rs201481886, CST3 rs765692764, and CST3 rs140837441, showed nominal association with AD risk. Gene-based aggregation testing revealed that HTRA1 was nominally associated with AD. In the AAO and MMSE association studies, variants in GSN, ITM2B, and COL4A1 reached suggestive significance. CONCLUSION: Common variants in COL4A1 and rare variants in HTRA1, NOTCH3, COL4A1, and CST3 may be implicated in AD pathogenesis. Besides, GSN, ITM2B, and COL4A1 are probably involved in the development of AD endophenotypes.

4.
Adv Mater ; : e2104623, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34590356

RESUMO

Protonated 3d transition-metal oxides often display low electronic conduction, which hampers their application in electric, magnetic, thermoelectric, and catalytic fields. Electronic conduction can be enhanced by co-inserting oxygen acceptors simultaneously. However, the currently used redox approaches hinder protons and oxygen ions co-insertion due to the selective switching issues. Here, a thermal hydration strategy for systematically exploring the synthesis of conductive protonated oxides from 3d transition-metal oxides is introduced. This strategy is illustrated by synthesizing a novel layered-oxide SrCoO3 H from the brownmillerite SrCoO2.5 . Compared to the insulating SrCoO2.5 , SrCoO3 H exhibits an unprecedented high electronic conductivity above room temperature, water uptake at 250 °C, and a thermoelectric power factor of up to 1.2 mW K-2 m-1 at 300 K. These findings open up opportunities for creating high-conductive protonated layered oxides by protons and oxygen ions co-doping.

5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(8): 793-799, 2021 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34565721

RESUMO

OBJECTIVES: Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2. Thus, the aim of this study is to evaluate the effect of CAG repeats on the AAO of patients with SCA2 in China. METHODS: A total of 119 patients with SCA2 were enrolled and were divided into 2 groups according to their major phenotype: 17 patients from 9 families with Parkinson's syndrome were grouped as the Parkinson's disease-SCA2 (PD-SAC2); 91 patients from 66 SCA2 families and 11 sporadic SCA2 patients were grouped as the ataxia-SCA2 (A-SCA2). Blood samples were obtained from the subjects, and the CAG repeat length in ATXN2 and other (CAG)n-containing genes was screened using fluorescent PCR. The Spearman's rank correlation between the CAG repeat length in (CAG)n-containing genes and AAO was analyzed. Regression analysis was performed to investigate whether the CAG repeat length could explain the variant of AAO. A t-test was used to compare the difference of CAG repeat length in (CAG)n-containing genes between the PD-SAC2 and A-SCA2 groups. RESULTS: The CAG repeat length in the longer allele of ATXN2 was negatively correlated with AAO of SCA2 (R=-0.251, P<0.05), and the CAG repeat length could explain 41.7% of the variation of AAO. AAO negatively correlated with the CAG repeat length in the shorter allele of ATXN7 (R=-0.251, P=0.006) or in the longer allele of TBP gene (R=-0.197, P=0.034). A tendency of delay in the AAO was also observed in patients with SCA2 carrying the CAG repeat within the ATXN3, CACNA1A, ATXN7, TBP, and RAI1. In addition, we found that the CAG repeat length in ATXN7 and ATXN2 between the A-SCA2 and the PD-SCA2 groups was significantly different (both P<0.05). CONCLUSIONS: The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. The CAG repeat length in ATXN3, CACNA1A, ATXN7, TBP, and RAI1 genes might be a potential factor associated with the AAO of SCA2. The CAG repeat in ATXN7 might be a potential factor affecting the Parkinson's syndrome in SCA2.


Assuntos
Proteínas do Tecido Nervoso , Ataxias Espinocerebelares , Idade de Início , Alelos , China/epidemiologia , Humanos , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética
6.
PLoS Negl Trop Dis ; 15(8): e0009696, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398890

RESUMO

Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of the host. Schistosome eggs induce M2 macrophages-rich granulomas and these M2 macrophages play critical roles in the maintenance of granuloma and subsequent fibrosis. Reactive oxygen species (ROS), which are highly produced by stimulated macrophages during infection and necessary for the differentiation of M2 macrophages, are massively distributed around deposited eggs in the liver. However, whether ROS are induced by schistosome eggs to subsequently promote M2 macrophage differentiation, and the possible underlying mechanisms as well, remain to be clarified during S. japonicum infection. Herein, we observed that extensive expression of ROS in the liver of S. japonicum-infected mice. Injection of ROS inhibitor in infected mice resulted in reduced hepatic granulomatous responses and fibrosis. Further investigations revealed that inhibition of ROS production in S. japonicum-infected mice reduces the differentiation of M2, accompanied by increased M1 macrophage differentiation. Finally, we proved that S. japonicum egg antigens (SEA) induce a high level of ROS production via both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and mitochondria in macrophages. Our study may help to better understand the mechanism of schistosomiasis japonica-induced hepatic pathology and contribute to the development of potential therapeutic strategies by interfering with ROS production.

7.
NPJ Genom Med ; 6(1): 69, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389718

RESUMO

Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enrolled, including 1592 with Alzheimer's disease (AD), 110 with frontotemporal dementia (FTD), and 93 with dementia with Lewy bodies (DLB). Genes targeted sequencing analysis were performed. According to the American College of Medical Genetics (ACMG) guidelines, 39 pathogenic/likely pathogenic (P/LP) variants were identified in 47 unrelated patients in 14 different genes, including PSEN1, PSEN2, APP, MAPT, GRN, CHCHD10, TBK1, VCP, HTRA1, OPTN, SQSTM1, SIGMAR1, and abnormal repeat expansions in C9orf72 and HTT. Overall, 33.3% (13/39) of the variants were novel, the identified P/LP variants were seen in 2.2% (35/1592) and 10.9% (12/110) of AD and FTD cases, respectively. The overall molecular diagnostic rate was 2.6%. Among them, PSEN1 was the most frequently mutated gene (46.8%, 22/47), followed by PSEN2 and APP. Additionally, the age at onset of patients with P/LP variants (51.4 years), ranging from 30 to 83 years, was ~10 years earlier than those without P/LP variants (p < 0.05). This study sheds insight into the genetic spectrum and clinical manifestations of neurodegenerative dementias in South China, further expands the existing repertoire of P/LP variants involved in known dementia-associated genes. It provides a new perspective for basic research on genetic pathogenesis and novel guiding for clinical practice of neurodegenerative dementia.

8.
Medicine (Baltimore) ; 100(31): e26877, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397865

RESUMO

ABSTRACT: High health care and medication expenditures pose a financial burden on Americans seeking care. It is imperative to determine the role of affordability in influencing access to health care and medications.To investigate the association between financial burden and health care access by comparing the effects of absolute and relative financial burdens, measured by total health care/medication expenditure (Expenditure) and health care/medication expenditure as a share of annual family income (Expenditure Share), respectively.Delay in receiving health care services and delay in obtaining prescription medications.A cross-sectional analysis of the 2017 Medical Expenditure Panel Survey using multivariate logistic regressions with Expenditure and Expenditure Share variables standardized to facilitate comparison.While both absolute and relative financial burdens were found to be positively associated with the outcomes, the relative measure had a significantly higher association that was about twice as much as the absolute one. For the outcome of delay in getting health care, the standardized odds ratios (OR) for health care expenditure and health care expenditure as a share of family income were 1.13 (95% confidence interval [CI] = 1.09-1.18) and 1.25 (95% CI = 1.20-1.32), respectively. For the outcome of delay in getting medications, the standardized OR for medication expenditure and medication expenditure as a share of family income were 1.11 (95% CI = 1.08-1.15) and 1.23 (95% CI = 1.18-1.29), respectively.The study illustrated the importance of including income in policy considerations intended to balance value, access, and affordability. Specifically, income should be included in measures assessing the value of medications.


Assuntos
Efeitos Psicossociais da Doença , Custos e Análise de Custo , Gastos em Saúde , Acesso aos Serviços de Saúde , Renda/estatística & dados numéricos , Medicamentos sob Prescrição/economia , Custos de Medicamentos/normas , Custos de Medicamentos/estatística & dados numéricos , Características da Família , Feminino , Estresse Financeiro , Acesso aos Serviços de Saúde/normas , Acesso aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
9.
J Manag Care Spec Pharm ; 27(8): 971-981, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34337985

RESUMO

BACKGROUND: Previous studies have documented factors influencing medication nonadherence among the Medicare population, but few studies have examined medication nonadherence among the Medicare low-income subsidy (LIS) population. Furthermore, little is known about the factors associated with nonadherence among this population, especially those with prevalent chronic conditions such as type 2 diabetes, hypertension, or heart failure. OBJECTIVE: To examine factors associated with the likelihood of medication nonadherence among Medicare LIS recipients with type 2 diabetes, hypertension, or heart failure. METHODS: This was a retrospective analysis of 2012-2013 Medicare Parts A, B, and D claims (most recent available for this research) linked to the Area Health Resources Files. Beneficiaries aged 65 years or older with continuous Medicare coverage and receiving any LIS were included. Individuals were categorized into full LIS or partial LIS groups. Nonadherence was determined by the proportion of days covered less than 80% for specified oral type 2 diabetes, hypertension, and heart failure medications, as defined by the Pharmacy Quality Alliance. A multivariate logistic regression was used to determine and compare individual-level and community-level characteristics associated with nonadherence among the entire study sample, the full LIS group, and the partial LIS group. RESULTS: The study sample included 505,771 Medicare beneficiaries, with 448,509 (88.7%) receiving full LIS and 57,262 (11.3%) receiving partial LIS. The proportion of individuals nonadherent was higher among the full LIS population (33.2%) than that of the partial LIS population (30.8%). Among the entire population, younger age was associated with nonadherence (OR = 0.98; 95% CI = 0.98-0.99). Men were more likely to be nonadherent than women (OR = 1.12; 95% CI = 1.11-1.14). Compared with non-Hispanic Whites, racial/ethnic minorities had higher nonadherence. Compared with beneficiaries who were non-Hispanic White, the ORs for those who were Black, Hispanic, Asian, and other were 1.41 (95% CI = 1.38-1.43), 1.58 (95% CI = 1.55-1.61), 1.08 (95% CI = 1.05-1.11), and 1.63 (95% CI = 1.56-1.70), respectively. There were higher nonadherence rates among patients living in communities with lower socioeconomic characteristics, such as a metropolitan statistical area (MSA vs non-MSA; OR = 1.05, 95% CI = 1.04-1.07). A higher risk adjustment summary score, indicating worse health status, was associated with an increased likelihood of medication nonadherence (OR = 1.21; 95% CI = 1.20-1.22). These patterns were similar among the full and partial LIS groups. CONCLUSIONS: Individual- and community-level characteristics were associated with the likelihood of medication nonadherence among Medicare LIS recipients with type 2 diabetes, hypertension, or heart failure. These characteristics included younger age, male sex, racial/ethnic minorities, living in lower socioeconomic communities, and a higher risk adjustment summary score. This study provided insight into medication nonadherence within the Medicare LIS population and identified the need to consider these factors when developing future policies to improve medication adherence. DISCLOSURES: This study was funded by the Pharmaceutical Research & Manufacturers of America (PhRMA), which was involved in the preparation and revision of the manuscript. Dougherty is employed by PhRMA. Todor was a PQA-CVS Health Foundation Scholar who was funded to work on this study. Hines is employed by Pharmacy Quality Alliance. Wang reports grants from AbbVie, Curo, Bristol Myers Squibb, and Pfizer, during the time of this study, and fees from the PhRMA Foundation for work on its Heath Outcomes Research Advisor Committee. The other authors have nothing to disclose. This study was presented as a poster at the online 2020 PQA Annual Meeting, May 7, 2020.

10.
Eur J Neurol ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255403

RESUMO

BACKGROUND AND PURPOSE: The purpose was to provide an overview of genotype and phenotype distribution in a cohort of patients with Charcot-Marie-Tooth disease (CMT) and related disorders from central south China. METHODS: In all, 435 patients were enrolled and detailed clinical data were collected. Multiplex ligation-dependent probe amplification for PMP22 duplication/deletion and CMT multi-gene panel sequencing were performed. Whole exome sequencing was further applied in the remaining patients who failed to achieve molecular diagnosis. RESULTS: Among the 435 patients, 216 had CMT1, 14 had hereditary neuropathy with pressure palsies (HNPP), 178 had CMT2, 24 had distal hereditary motor neuropathy (dHMN) and three had hereditary sensory and autonomic neuropathy (HSAN). The overall molecular diagnosis rate was 70%: 75.7% in CMT1, 100% in HNPP, 64.6% in CMT2, 41.7% in dHMN and 33.3% in HSAN. The most common four genotypes accounted for 68.9% of molecular diagnosed patients. Relatively frequent causes were missense changes in PMP22 (4.6%) and SH3TC2 (2.3%) in CMT1; and GDAP1 (5.1%), IGHMBP2 (4.5%) and MORC2 (3.9%) in CMT2. Twenty of 160 detected pathogenic variants and the associated phenotypes have not been previously reported. Broad phenotype spectra were observed in six genes, amongst which the pathogenic variants in BAG3 and SPTLC1 were detected in two sporadic patients presenting with the CMT2 phenotype. CONCLUSIONS: Our results provided a unique genotypic and phenotypic landscape of patients with CMT and related disorders from central south China, including a relatively high proportion of CMT2 and lower occurrence of PMP22 duplication. The broad phenotype spectra in certain genes have advanced our understanding of CMT.

11.
Neurobiol Aging ; 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34275688

RESUMO

To analyze the mutational spectrum of known ALS causative genes in China ALS patients. We comprehensively analyzed 51 ALS causative genes by combining different sequencing technologies in 753 unrelated ALS patients from Central South China. The mean age at onset (AAO) was 53.7±11.4 years. The AAO was earlier in the autosomal dominant (AD) ALS patients than in the sporadic ALS (sALS) patients. Bulbar onset was more frequent in females than in males. SOD1 was the most frequently mutated gene in the AD-ALS and the sALS patients, followed by the ATXN2 and FUS genes in the AD-ALS patients and the NEK1 and CACNA1H genes in the sALS patients. Patients with RDVs in the SOD1 or FUS genes had an earlier AAO than the mean AAO of all the patients, while the patients with RDVs in the NEK1 gene showed later onset. SOD1 gene was the most commonly mutated gene in ALS patients in China, followed by ATXN2 and NEK1. The phenotype might be determined synergistically by sex and genetic variants.

12.
J Colloid Interface Sci ; 603: 844-855, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34237602

RESUMO

A sandwich-like melamine/phytic acid/silicon nitride hybrid (SW-Si3N4) sheets were prepared by supramolecular wrapping as the hybrid flame retardants for thermoplastic polyurethane (TPU). The introduction of Si3N4 sheets as a template could not only induce the generation of two-dimensional phytic/melamine (PAMA) capping layers, but also produce the synergistic flame-retardant effect on TPU composites. Cone test showed that heat release rate (HRR), smoke production rate (SPR) and total smoke production (TSP) values of TPU were decreased obviously by adding SW-Si3N4. TG-IR test indicated the dramatic inhibition of aromatic compound, hydrocarbons, CO and HCN release. Besides, the thermal conductivity of composites was obviously improved by adding SW-Si3N4. This work may provide better reference for developing multi-functional TPU composites for diverse application.


Assuntos
Retardadores de Chama , Poliuretanos , Temperatura Alta , Condutividade Térmica
13.
Virol J ; 18(1): 126, 2021 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118952

RESUMO

BACKGROUND: Tens of million cases of coronavirus disease-2019 (COVID-19) have occurred globally. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. The aim of the present study is to investigate the laboratory characteristics of the viral load, lymphocyte subset and cytokines in asymptomatic individuals with SARS-CoV-2 infection in comparison with those in symptomatic patients with COVID-19. METHODS: From January 24, 2020, to April 11, 2020, 48 consecutive subjects were enrolled in this study. Viral loads were detected by RT-PCR from throat-swab, sputum and feces samples. Lymphocyte subset levels of CD3 + , CD4 + , and CD8 + T lymphocytes, B cells and NK cells were determined with biological microscope and flow cytometric analysis. Plasma cytokines (IL2, IL4, IL5, IL6, IL8, IL10, TNF-α, IFN-α and IFN-γ) were detected using flow cytometer. Analysis of variance (ANOVA), Chi-square or Fisher's exact test and Pearson's Correlation assay was used for all data. RESULTS: Asymptomatic (AS), mild symptoms (MS) and severe or critical cases (SCS) with COVID-19 were 11 (11/48, 22.9%), 26 (54.2%, 26/48) and 11 cases (11/48, 22.9%), respectively. The mean age of AS group (47.3 years) was lower than SCS group (63.5 years) (P < 0.05). Diabetes mellitus in AS, MS and SCS patients with COVID-19 were 0, 6 and 5 cases, respectively, and there was a significant difference between AS and SCS (P < 0.05). No statistical differences were found in the viral loads of SARS-CoV-2 between AS, MS and SCS groups on admission to hospital and during hospitalization. The concentration of CD 3 + T cells (P < 0.05), CD3 + CD4 + T cells (P < 0.05), CD3 + CD8 + T cells (P < 0.01), and B cells (P < 0.05) in SCS patients was lower than in AS and MS patients, while the level of IL-5 (P < 0.05), IL-6 (P < 0.05), IL-8 (P < 0.01) and IL-10 (P < 0.01), and TNF-α (P < 0.05) was higher. The age was negatively correlated with CD3 + T cells (P < 0.05), CD3 + CD4 + T cells (P < 0.05), and positively correlated with IL-2 (P < 0.001), IL-5 (P < 0.05), IL-6 (P < 0.05) IL-8 (P < 0.05), and IL-10 (P < 0.05). The viral loads were positively correlated with IL-2 (P < 0.001), IL-5 (P < 0.05), IL-6 (P < 0.05) IL-8 (P < 0.05) and IL-10 (P < 0.05), while negatively correlated with CD 3 + T cells (P < 0.05) and CD3 + CD4 + T cells (P < 0.05). CONCLUSIONS: The viral loads are similar between asymptomatic, mild and severe or critical patients with COVID-19. The severity of COVID-19 may be related to underlying diseases such as diabetes mellitus. Lymphocyte subset and plasma cytokine levels may be as the markers to distinguish severely degrees of disease, and asymptomatic patients may be as an important source of infection for the COVID-19.


Assuntos
COVID-19/patologia , Citocinas/sangue , Subpopulações de Linfócitos/patologia , SARS-CoV-2 , Carga Viral , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Estado Terminal , Complicações do Diabetes/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Adulto Jovem
14.
Neurobiol Aging ; 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34172279

RESUMO

Alzheimer's disease (AD) and frontotemporal dementia (FTD) overlap clinically and pathologically. However, the role of FTD-associated genes in patients with AD remained unclear. To explore the relationship between FTD-associated genes and AD risk, we investigated 14 FTD-associated genes via targeted next-generation sequencing panel or whole-genome sequencing in a total of 721 AD patients and 1391 controls. Common variant-based association analysis and gene-based association test of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test) respectively. As a result, 2 common variants, UBQLN1 rs1044175 (p value = 2.76 × 10-4) and MAPT rs2258689 (p value = 5.71 × 10-4), differed significantly between AD patients and controls. Additionally, gene-based analysis aggregating rare variants demonstrated that HNRNPA1 reached statistical significance in the SKAT-O test (p value = 2.24 × 10-3). Protein-protein interaction analysis showed that UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Our study indicated that UBQLN1, MAPT, and HNRNPA1 are implicated in the pathogenesis of AD in the mainland Chinese population.

15.
J Neurol ; 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129120

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder. Mitochondrial dysfunction is involved in the complex pathophysiology of ALS; however, the role of mitochondrial DNA (mtDNA) variants in ALS is poorly understood. We aimed to elucidate the role of mtDNA variants in the pathogenesis of ALS. METHODS: The mitochondrial haplogroups of 585 ALS patients and 371 healthy controls were determined; 38 ALS patients and 42 controls underwent long-range polymerase chain reaction combined with next-generation sequencing technology to analyze whole mitochondrial genome variants. RESULTS: A higher percentage of variants accumulated in ALS patients than in controls. Analysis of coding region variations that were further stratified by mtDNA genes revealed that nonsynonymous variants were more vulnerable in ALS patients than in controls, particularly in the ND4L, ND5, and ATP8 genes. Moreover, pathogenic nonsynonymous variants tended to over-represent in ALS patients. Unsurprisingly, nonsynonymous variants were not related to the phenotype. Haplogroup analysis did not found evidence of association between haplogroups with the risk of ALS, however, patients belonging to haplogroup Y and M7c were prone to develop later onset of ALS. CONCLUSIONS: This is the first study to profile mtDNA variants in ALS patients from mainland China. Our results suggest that an increase in the number of nonsynonymous variants is linked to the pathogenesis of ALS. Moreover, haplogroup Y and M7c may modulate the clinical expression of ALS. Our findings provide independent, albeit limited, evidence for the role of mtDNA in the pathogenesis of ALS.

16.
Neuroimage ; 237: 118133, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33951515

RESUMO

Accurate epileptogenic zone (EZ) or seizure onset zone (SOZ) localization is crucial for epilepsy surgery optimization. Previous animal and human studies on epilepsy have reported that changes in blood oxygen level-dependent (BOLD) signals induced by epileptic events could be used as diagnostic markers for EZ or SOZ localization. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recording is gaining interest as a non-invasive tool for preoperative epilepsy evaluation. However, EEG-fMRI studies have reported inconsistent and ambiguous findings. Therefore, it remains unclear whether BOLD responses can be used for accurate EZ or SOZ localization. In this study, we used simultaneous EEG-fMRI recording in a rat model of 4-aminopyridine-induced acute focal seizures to assess the spatial concordance between individual BOLD responses and the SOZ. This was to determine the optimal use of simultaneous EEG-fMRI recording in the SOZ localization. We observed a high spatial consistency between BOLD responses and the SOZ. Further, dynamic BOLD responses were consistent with the regions where the seizures were propagated. These results suggested that simultaneous EEG-fMRI recording could be used as a noninvasive clinical diagnostic technique for localizing the EZ or SOZ and could be an effective tool for mapping epileptic networks.

17.
Curr Med Res Opin ; 37(9): 1581-1588, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34039232

RESUMO

OBJECTIVE: Older patients with Alzheimer's disease (AD) are challenged with adhering to complex medication regimens. We examined effects of Comprehensive Medication Review (CMR), a required Medicare Part D Medication Therapy Management (MTM) program component, on medication adherence among AD patients. METHODS: This retrospective study analyzed 100% of 2016-2017 Medicare claims covering the entire United States, linked to Area Health Resources Files. Medicare beneficiaries aged ≥65 years were included. Propensity score matching identified comparable intervention and comparison groups with the intervention defined as receiving a CMR in 2017. A difference-in-differences analysis included in multivariate logistic regressions an interaction term between CMR receipt and year 2017. The outcome measured was nonadherence to diabetes, hypertension and hyperlipidemia medications, with nonadherence defined as proportion of days covered <80% for study medications. RESULTS: Unadjusted comparisons indicated the proportion of nonadherence for intervention group members decreased from 2016 to 2017 but increased for the comparison group. In adjusted analyses, reduction in medication nonadherence among the intervention group remained higher: odds ratios for the interaction term were 0.62 (95% confidence interval [CI] = 0.54-0.71), 0.54 (95% CI = 0.50-0.58) and 0.50 (95% CI = 0.47-0.53) respectively for diabetes, hypertension and hyperlipidemia medications. This suggests that the likelihood of nonadherence in the intervention group was respectively reduced by 38%, 46% and 50% more than the comparison group. CONCLUSIONS: CMR was found to reduce nonadherence to diabetes, hypertension and hyperlipidemia medications among older Medicare beneficiaries with AD. This provides evidence that the MTM program is effective for a population with unique medication compliance challenges.

18.
Sci Rep ; 11(1): 9376, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931669

RESUMO

Regulator of G-protein signaling 7 (RGS7) is predominately present in the nervous system and is essential for neuronal signaling involving G-proteins. Prior studies in cultured cells showed that RGS7 is regulated via proteasomal degradation, however no protein is known to facilitate proteasomal degradation of RGS7 and it has not been shown whether this regulation affects G-protein signaling in neurons. Here we used a knockout mouse model with conditional deletion of arginyltransferase (Ate1) in the nervous system and found that in retinal ON bipolar cells, where RGS7 modulates a G-protein to signal light increments, deletion of Ate1 raised the level of RGS7. Electroretinographs revealed that lack of Ate1 leads to increased light-evoked response sensitivities of ON-bipolar cells, as well as their downstream neurons. In cultured mouse embryonic fibroblasts (MEF), RGS7 was rapidly degraded via proteasome pathway and this degradation was abolished in Ate1 knockout MEF. Our results indicate that Ate1 regulates RGS7 protein level by facilitating proteasomal degradation of RGS7 and thus affects G-protein signaling in neurons.

19.
CNS Neurosci Ther ; 27(8): 930-940, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33942994

RESUMO

AIMS: NOTCH3 gene mutations predominantly cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a common etiology of subcortical vascular dementia (SVaD). Besides, there may be a pathogenic link between NOTCH3 variants and Alzheimer's disease (AD). We aimed to study the role of NOTCH3 variants in AD and SVaD patients. METHODS: We recruited 763 patients with dementia (667 AD and 96 SVaD) and 365 healthy controls from the Southern Han Chinese population. Targeted capture sequencing was performed on NOTCH3 coding and adjacent intron regions to detect the pathogenic variants in AD and SVaD. The relationship between common or rare NOTCH3 variants and AD was further analyzed using Plink1.9. RESULTS: Five known pathogenic variants (p.R182C, p.C201S, p.R544C, p.R607C, and p.R1006C) and two novel likely pathogenic variants (p.C201F and p.C1061F) were detected in 16 SVaD patients. Additionally, no pathogenic or likely pathogenic variants were found in AD patients. NOTCH3 was not associated with AD in either single-variant association analysis or gene-based association analysis. CONCLUSION: Our findings broaden the mutational spectrum of NOTCH3 and validate the pathogenic role of NOTCH3 mutations in SVaD, but do not support the notion that NOTCH3 variation influences the risk of AD.

20.
Aging (Albany NY) ; 13(8): 11352-11362, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33833133

RESUMO

BACKGROUND: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population. METHOD: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients. RESULTS: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013). CONCLUSIONS: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Substância Branca/patologia , Idade de Início , Idoso , Alelos , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Homocisteína/metabolismo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...