BACKGROUND: According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years. METHODS: We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI. RESULTS: pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient's study partner language domain could predict progression to dementia in A+T+MCI within 2 years. CONCLUSIONS In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.
Alzheimer Disease ; Amyloid beta-Peptides ; Biomarkers ; Cognitive Dysfunction ; Disease Progression ; Humans ; Peptide Fragments ; Positron-Emission Tomography

Objective:Both exposure to heavy metals and alcohol intake have been related to the risk of type 2 diabetes (T2D).In this study,we aimed to assess the potential interactions between metal exposure and alcohol intake on the risk of T2D and prediabetes in a cohort of Chinese male workers.Methods:We conducted a cross-sectional analysis of 26,008 Chinese male workers in an occupational cohort study from 2011 to 2013.We assessed metal exposure and alcohol consumption at baseline in these workers who were aged ≥20 years.Based on occupations which were categorized according to measured urine metal levels,multiple logistic regression analyses were used to evaluate the independent and joint effects of metal and alcohol exposure on the risk of T2D and prediabetes.Results:Risks of T2D (Ptrend =0.001) and prediabetes (Ptrend =0.001) were significantly elevated with increasing number of standard drinks per week,years of drinking,and lifetime alcohol consumption.An adjusted odds ratio (OR) of 6.1 (95％ confidence interval [CI]:4.8-7.8) was observed for the smelting/refining workers (highest metal exposure levels) who had the highest lifetime alcohol consumption (＞873 kg) (Pinteraction =0.018),whereas no statistically significant joint effect was found for prediabetes (Pinteraction =0.515).Conclusions:Both exposures to metal and heavy alcohol intake were associated with the risk of diabetes in this large cohort of male workers.There was a strong interaction between these two exposures in affecting diabetes risk that needs to be confirmed in future studies.

Objective:Both exposure to heavy metals and alcohol intake have been related to the risk of type 2 diabetes (T2D).In this study,we aimed to assess the potential interactions between metal exposure and alcohol intake on the risk of T2D and prediabetes in a cohort of Chinese male workers.Methods:We conducted a cross-sectional analysis of 26,008 Chinese male workers in an occupational cohort study from 2011 to 2013.We assessed metal exposure and alcohol consumption at baseline in these workers who were aged ≥20 years.Based on occupations which were categorized according to measured urine metal levels,multiple logistic regression analyses were used to evaluate the independent and joint effects of metal and alcohol exposure on the risk of T2D and prediabetes.Results:Risks of T2D (Ptrend =0.001) and prediabetes (Ptrend =0.001) were significantly elevated with increasing number of standard drinks per week,years of drinking,and lifetime alcohol consumption.An adjusted odds ratio (OR) of 6.1 (95％ confidence interval [CI]:4.8-7.8) was observed for the smelting/refining workers (highest metal exposure levels) who had the highest lifetime alcohol consumption (＞873 kg) (Pinteraction =0.018),whereas no statistically significant joint effect was found for prediabetes (Pinteraction =0.515).Conclusions:Both exposures to metal and heavy alcohol intake were associated with the risk of diabetes in this large cohort of male workers.There was a strong interaction between these two exposures in affecting diabetes risk that needs to be confirmed in future studies.

This study was purposed to evaluate a method to discriminate the action loci of anticancer agents in G(2) and M phases of cell cycle. The meta-amsacrine (m-AMSA) and vinblastine (VBL), already known as G(2) and M phase arrest agent respectively, were used to induce the arrest of MOLT-4 cells at G(2) and M phases, the change of DNA content was detected by flow cytometry, the morphology of arrested cells was observed by confocal microscopy so as to find the arrest efficacy difference of 2 anticancer agents. As a result, the flow cytometric detection showed that the arrested MOLT-4 cells displayed the raise of peaks in G(2) and M phases, but flow cytometric detection alone can not discriminate the difference between them. The observation with confocal microscopy showed that the MOLT-4 cells arrested by m-AMSA displayed the morphologic features in G(2) phase, while the MOLT-4 cells arrested by VBL displayed the morphologic features in M phase. This observation with confocal microscopy is helpful to discriminate the difference between them. In conclusion, the combination of flow cytometry with confocal microscopy is one of the effective methods to discriminate the kind of G(2) or M phase arresting agent of anticancer drugs.
Antineoplastic Agents ; pharmacology ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Flow Cytometry ; G2 Phase ; drug effects ; Humans ; Microscopy, Confocal ; Tumor Cells, Cultured