Information from well-established dementia risk models can guide targeted intervention to prevent dementia, in addition to the main purpose of quantifying the probability of developing dementia in ...the future.
We conducted a systematic review of published studies on existing dementia risk models. The models were assessed by sensitivity, specificity and area under the curve (AUC) from receiver operating characteristic analysis.
Of 8462 studies reviewed, 61 articles describing dementia risk models were identified, with the majority of the articles modelling late life risk (n=39), followed by those modelling prediction of mild cognitive impairment to Alzheimer's disease (n=15), mid-life risk (n=4) and patients with diabetes (n=3). Age, sex, education, Mini Mental State Examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery, Alzheimer's Disease Assessment Scale-cognitive subscale, body mass index, alcohol intake and genetic variables are the most common predictors included in the models. Most risk models had moderate-to-high predictive ability (AUC>0.70). The highest AUC value (0.932) was produced from a risk model developed for patients with mild cognitive impairment.
The predictive ability of existing dementia risk models is acceptable. Population-specific dementia risk models are necessary for populations and subpopulations with different characteristics.
Membrane technology is one of the most promising technologies for separation and purification that is routinely and commercially employed in aqueous solutions. In comparison, its applications in ...organic solvents are severely underdeveloped mainly due to the poor stability of traditional polymer membranes in organic solvents. The emerging materials such as crosslinked polymers, covalent organic frameworks, metal–organic frameworks, conjugated microporous polymers, carbon molecular sieves, and graphene provide the solutions to address this problem. The membranes constructed with these novel materials show outstanding separation performance in regard to both high selectivity and solvent permeability, greatly pushing forward utilization of membrane technology in organic media. Here, an overview of the most important organic mixtures that need to be separated, the major separation processes adopted nowadays in organic solvents, and the recent progress in new developed membranes is provided.
Leaning lessons from seawater desalination and water purification, great efforts are being devoted to extend membrane separation from aqueous solutions to the organic phase. The different separation processes and new developed materials, which promote the application of membrane separation in organic liquids, are reviewed.
Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and ...meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.
Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.
A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).
Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
Controversies persist regarding the association between blood pressure (BP) and the risks of cognitive impairment and dementia due to inconsistent definitions of BP exposure and varying population ...characteristics. Here, we searched PubMed and performed a meta-analysis of the influence of BP exposure on the risks of cognitive disorders in prospective studies. Dose-response analyses were performed to illustrate the existence of linear/nonlinear relationships. The credibility of each meta-analysis was evaluated according to the risk of bias, inconsistency, and imprecision. Of the 31 628 citations, 209 were included in our systematic review, among which 136 were eligible for the meta-analysis. Overall, stronger associations were found in midlife than late-life. Moderate-quality evidence indicated that midlife hypertension was related to a 1.19- to 1.55-fold excess risk of cognitive disorders. Dose-response analyses of 5 studies indicated that midlife systolic BP >130 mm Hg was associated with an increased risk of cognitive disorders. With regard to BP exposure in late-life, high systolic BP, low diastolic BP, excessive BP variability, and orthostatic hypotension were all associated with an increased dementia risk. Encouragingly, the use of antihypertensive medications exhibited a 21% reduction in dementia risk. The U-shaped dose-response curve indicated that the protective window of diastolic BP level was between 90 and 100 mm Hg for low risk of Alzheimer disease. The relationships between BP variables and cognitive disorders are age- and BP type-dependent. Antihypertensive medications were associated with a reduced risk of dementia. However, the optimal dose, duration, and type for preventing cognitive disorders warrant further investigation.
Cholinesterase inhibitors and memantine have been approved for management of Alzheimer's disease (AD), but there has been no consensus about the choice of various types and doses of drugs at ...different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs.
We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017. The primary outcomes were the mean overall changes in cognitive function and responders who had any adverse events. We conducted a random-effects network meta-analysis.
Forty-one RCTs were included in this study. Compared with placebo, galantamine 32 mg daily (standardized mean difference - 0.51, 95% credible interval - 0.67 to - 0.35), galantamine 24 mg daily (- 0.50, - 0.61 to - 0.40), and donepezil 10 mg daily (- 0.40, - 0.51 to - 0.29) were probably the most effective agents on cognition for mild to moderate AD, and memantine 20 mg combined with donepezil 10 mg (0.76, 0.39 to 1.11) was recommended for moderate to severe patients. Memantine showed the best profile of acceptability. Rivastigmine transdermal 15-cm
patch was the best optional treatment both in function and global changes. None of the medicines was likely to improve neuropsychiatric symptoms through this analysis.
Pharmacological interventions have beneficial effects on cognition, function, and global changes, but not on neuropsychiatric symptoms, through current network meta-analysis. The choice of drugs may mainly depend on the disease severity and clinical symptoms.
The compost-derived humic substances (HS) can function as electron mediators for promoting hematite bioreduction because of its redox capacity. Humification process can affect redox capacities of ...compost-derived HS by changing its intrinsic structure. However, the redox properties of compost-derived HS linking with hematite bioreduction during composting still remain unclear. Herein, we investigated the redox capacities of compost-derived HS, and assessed the responses of the redox capacities to the hematite bioreduction. The result showed that compost-derived HS (i.e., humic acids (HA) and fulvic acids (FA)) were able to accept electrons from Shewanella oneidensis MR-1, and the electron accepting capacity was increased during composting. Furthermore, it could be functioned as electron mediators for promoting the hematite bioreduction, achieving 1.19-2.15 times compared with the control experience. Not only the aromatic structures (quinone) but also the non-quinone structures such as nitrogen- and sulfur-containing functional moieties were served as the redox-active functional groups of compost-derived HS. Our work proved that the aromatic functional groups and the heteroatom structures (especially N) were important to the hematite bioreduction. This study highlights the redox-active properties of compost-derived HS and its impact on the microbial reduction of iron mineral. Redox capacity of compost-derived HS might mitigate the environmental risk of contaminants when the composting production was added into the contaminated soils as low-cost repair materials
The microbial reducing capacities of compost-derived HSs are investigated, and they are employed in the process of hematite bioreduction. Compost-derived HSs can accept electrons from microorganism respiration. The reduced compost-derived HS can donate electrons to dissolved Fe(III) or hematite. The aromatic- and heteroatom-structures are the main redox-active groups. Compost-derived HSs are considered as electron mediators to further promote hematite bioreduction. Display omitted
Introduction
Cognitive impairment is a debilitating manifestation in Parkinson’s disease (PD). We sought to investigate predictors of PD-CI (PD with cognitive impairment).
Methods
We systematically ...searched PubMed and Cochrane Library for prospective cohort studies and pooled estimates via random-effects models. Primary analyses for all types of cognitive impairments and subgroup analyses by separate outcomes were conducted.
Results
A total of 28,009 studies were identified, of which 57 studies with 31 factors were included in the meta-analysis. In the primary analysis, 13 factors were associated with PD-CI, comprising advanced age relative risk (RR) = 1.07, 95% confidence interval (CI) = 1.03–1.12, age at onset (RR = 4.43, 95% CI = 1.87–10.54), postural-instability-gait disorder (RR = 3.76, 95% CI = 1.36–10.40), higher Hoehn and Yahr stage (RR = 1.83, 95% CI = 1.35–2.47), higher UPDRS III score (RR = 1.04, 95% CI = 1.01–1.08), rapid eye movement sleep behavior disorder (RR = 3.72, 95% CI = 1.20–11.54), hallucinations (RR = 3.09, 95% CI = 1.61–5.93), orthostatic hypotension (RR = 2.98, 95% CI = 1.41–6.28), anxiety (RR = 2.59, 95% CI = 1.18–5.68),
APOE
ε2 (RR = 6.47, 95% CI = 1.29–32.53),
APOE
ε4 (RR = 3.04, 95% CI = 1.88–4.91), electroencephalogram theta power > median (RR = 2.93, 95% CI = 1.61–5.33), and alpha power < median (RR = 1.77, 95% CI = 1.07–2.92). In the subgroup analysis,
MAPT
H1/H1 genotype increased the risk of dementia in PD. Sixty-four studies were included in the systematic review, of which 12 factors were additionally correlated with PD-CI using single studies.
Conclusions
Advanced age, genetic variation in
APOE
and
MAPT
, gait disturbance, motor assessments, non-motor symptoms, and electroencephalogram may be promising predictors for PD-CI.
In this work, spinel NiCo2O4 is prepared by a facile sol–gel method with the effect of three different chelating agents including citric acid (CA), oxalic acid (OA) and ethylenediamine tetraacetic ...acid (EDTA) explored upon the fabrication methodology and resulting electrochemical and supercapacitor properties. The electrochemical measurements reveal that NiCo2O4 prepared using OA exhibits ultrahigh specific capacitance of 1254 F g−1 at 2 A g−1 due to the resultant high specific surface area, while NiCo2O4 prepared by EDTA exhibits the best rate capability and cycling stability owing to the subsequent large pore size. The obvious differences can be primarily ascribed to the use of the differing chelating agents which are shown, for the first time, to greatly affect the particle size, pore structure and specific surface area of the fabricated NiCo2O4. Such work is of fundamental importance and demonstrates that the tailoring of these different properties can be readily obtained through the use of differing chelating and is responsible for the observed differing electrochemical properties. Additionally, first-principles calculations were employed to investigate the electronic structure of NiCo2O4, which can help to further understand its excellent electrochemical behaviors. These results above provide a facile, cost-effective and high-performance strategy for supercapacitor electrode applications.
Display omitted
•Spinel NiCo2O4 was prepared by sol–gel method using three chelating agents.•The effect of different chelating agents on the electrochemical properties of the NiCo2O4 was firstly investigated.•The first-principles were used for calculation.•High specific capacitance of 1254 F g−1 at 2 A g−1 was obtained using oxalic acid as chelating agent.
Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic ...purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.
Display omitted
•TAMs with low expression of RARγ exhibit oncogenic functions in CRC•Tumor-derived lactate inhibits macrophage RARγ expression via histone lactylation•RARγ regulates TRAF6-IL-6-STAT3 signaling to connect inflammation and tumorigenesis•Nordihydroguaiaretic acid effectively exhibits antitumor action by targeting RARγ
Li et al. show that tumor-associated macrophages exhibiting low expression of RARγ are linked to an unfavorable prognosis in patients with colorectal cancer (CRC). Lactylation-induced RARγ downregulation in macrophages contributes to CRC tumorigenesis by boosting TRAF6-IL-6-STAT3 signaling. Nordihydroguaiaretic acid targets RARγ to impede tumor growth within the tumor microenvironment.
The associations between obesity and Alzheimer's disease (AD) at different ages have been debated. Recent evidence implied the protective effects of metabolically healthy obesity on AD. We ...hypothesized that obesity and lipids could mitigate the detrimental impacts of AD pathological changes among metabolically healthy individuals in late life. In this study, a total of 604 metabolically healthy participants with normal cognition were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Multiple linear regression models were used to test the associations of body mass index (BMI) or lipids with cerebrospinal fluid (CSF) biomarkers after adjustment for age, gender, education, and Apolipoprotein E‐ɛ4 (APOE‐ɛ4). The results showed the lower CSF levels of total tau protein (t‐tau: p = .0048) and phosphorylated tau protein (p‐tau: p = .0035) in obese participants than in non‐obese participants, even after correcting for covariates. Moreover in late life, higher BMI was associated with decreased CSF t‐tau (β: −0.15, p = .0145) and p‐tau (β: −0.17, p = .0052). As for lipids, higher levels of total cholesterol (TC) and low‐density lipoprotein cholesterol (LDL‐C) were associated with decreased CSF t‐tau (TC: β: −0.16, p = .0115; LDL‐C: β: −0.16, p = .0082) and p‐tau (TC: β: −0.15, p = .0177; LDL‐C: β: −0.14, p = .0225) in obese participants. Furthermore, these associations were only significant in participants with late‐life obesity and APOE‐ɛ4 non‐carriers. Overall, in a cognitively normal population, we found metabolically healthy obesity and lipids in late life might be protective factors for neurodegenerative changes.
In a metabolically healthy population with normal cognition, we found that obese individuals had lower levels of CSF tau‐related biomarkers than non‐obese individuals in late life, and there were protective associations of TC or LDL‐C with CSF tau‐related biomarkers in the late‐life obese population. These findings provided new evidence that healthy obesity and lipids in late life might be protective factors for neurodegeneration, which may help us to clarify the associations of obesity or lipids with some neurodegenerative diseases.
PDF
