Novel litchi-like Au-Ag nanospheres driven dual-readout lateral flow immunoassay for sensitive detection of pyrimethanil.

Pyrimethanil (PYR) is a fungicide that is harmful to consumers when present in foods at concentrations greater than maximum permitted residue levels. High-performance immunoprobes and dual-readout strategy may be useful for constructing sensitive lateral flow immunoassay (LFIA). Herein, the prepared litchi-like Au-Ag bimetallic nanospheres (LBNPs) exhibited high mass extinction coefficients and fluorescence quenching constants. Benefiting from LBNPs and dual-readout mode, the limits of detection of LBNPs-CM-LFIA and LBNPs-FQ-LFIA for PYR were 0.957 and 0.713 ng mL-1, which were 2.54- and 3.41-fold lower than that of gold nanoparticles-based LFIA, respectively. The limits of quantitation of LBNPs-CM-LFIA and LBNPs-FQ-LFIA were 3.740 and 1.672 ng mL-1, respectively. LBNPs-LFIA was applied to detect PYR in cucumber and grape samples with satisfactory recovery (90%-111%). LBNPs-LFIA showed good agreement with LC-MS/MS for the detection of PYR in the samples. Accordingly, this sensitive and accurate dual-readout LFIA based on LBNPs can be effectively applied for food safety.

High-Performance Fluorescent Microspheres Based on Fluorescence Resonance Energy Transfer Mode for Lateral Flow Immunoassays.

The label with a large Stokes shift and strong fluorescence properties could improve the sensitivity of the lateral flow immunoassay (LFIA). Herein, two aggregation-induced emission (AIE) luminogens with spectral overlap were encapsulated in polymers by using the microemulsion method as a label, and the construction of a fluorescence resonance energy transfer mode was further verified via theoretical calculation and spectral analysis. Satisfactorily, the doped AIE polymer microspheres (DAIEPMs) exhibited a large Stokes shift of 285 nm and a 10.8-fold fluorescence enhancement compared to those of the AIEPMs loaded with acceptors. Benefiting from the excellent optical performance, DAIEPMs were applied to the LFIA for sensitive detection of chlorothalonil, which is an organochlorine pesticide. The limit of detection of the proposed DAIEPMs-LFIA was 1.2 pg/mL, which was 4.8-fold and 11.6-fold lower than those of quantum dot bead LFIA and gold nanoparticle LFIA, respectively. This work provides a new strategy to improve the optical properties of fluorescent materials and construct a sensitive and reliable detection platform.

Effectiveness and acceptability of non-pharmacological interventions in people with mild cognitive impairment: Overview of systematic reviews and network meta-analysis.

BACKGROUND: To explore effectiveness and acceptability of non-pharmacological interventions in mild cognitive impairment (MCI). METHODS: Overview of systematic reviews and network meta-analysis were conducted. Systematic reviews (SRs) were searched via seven databases from June 2015 to June 2020. Randomized controlled trials (RCTs) were retrieved. The Methodological quality was assessed by AMSTAR 2 and RoB 2. Outcomes were effectiveness and acceptability measured by standardized mean differences (SMDs) and odd ratios (ORs) with 95% confidence interval (CI). Pairwise meta-analysis was first conducted, followed by network meta-analysis. RESULTS: A total of 22 SRs and 42 RCTs with 4401 participants were included. The methodological quality of included SRs and RCTs were moderate. There were four interventions, with three types of physical activity (aerobic, muscle-strengthening, and mind-body), three types of cognitive (rehearsal-based, compensatory, and mixed), multicomponent (physical and cognitive component), and nutrition intervention. No significant inconsistency was identified. Regarding intervention effectiveness, muscle-strengthening (SMDs 0.87, 95% CI 0.31-1.43; rank 1), mind-body (0.76, 0.38-1.14; rank 2) and aerobic (0.34, 0.13-0.50; rank 3) were significantly better than the control group and there was no significant difference among these types of intervention . Cognitive intervention of rehearsal-based (1.33, 0.30-2.35; rank 1) and mixed (0.55, 0.00-1.11; rank 2) were significantly better than the control group and there was no significant difference among these types of intervention. Multicomponent intervention (0.32, 0.02-0.62) were significantly better than the control group but not better than the single component group. Regarding acceptability, there was no significant difference among types of intervention. CONCLUSION: Physical activity, cognitive, and multicomponent intervention could be provided regardless of their types and acceptability due to their effectiveness on improved cognitive function for people with MCI.

Dose-response relationship in non-pharmacological interventions for individuals with mild cognitive impairment: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Non-pharmacological interventions (NPIs) are important in cognitive decline prevention in individuals with mild cognitive impairment (MCI). However, the dose-response relationship remains unclear. DESIGN: Systematic review and meta-analysis of randomised controlled trials. METHODS: Seven databases were searched until April 2020. RCTs of NPIs in individuals with MCI were eligible for inclusion. Hedge's g was used to calculate the effect size. A random-effect meta-analysis was used to explore the impact of NPIs on cognition. Subgroup analysis was used to investigate the moderates. The dose was measured by prescription (frequency, intensity, type, time and volume) and intervention characteristics (period, energy expenditure, delivery mode and setting) in NPIs. RESULTS: Forty-two studies with 4401 participants were included. In the NPIs, cognitive intervention (g = 0.167), physical exercise (g = 0.536) and multicomponent intervention (g = 0.386) had significant effect on cognition in individuals with MCI. Dose-response results showed cognition could be significantly improved in 1-2 times/week (p < .05), 60-120 min/session (p < .05), ≥12 weeks (p < .05), supervised (p < .05), clinical setting (p < .05) in cognitive intervention. In physical exercise, cognition could be improved in ≥3 times/week (p < .05), vigorous-intensity (p < .05), muscle-strengthening activity (p < .05), 30-60 min/session (p < .05), 6-12 weeks (p < .05), unsupervised (p < .05), community setting (p < .05). In the multicomponent intervention, cognition could be improved in 1-2 times/week (p < .05), 30-60 min/session (p < .05), 8-16 weeks (p < .05), clinical (p < .05). In nutrition intervention, cognition could be better improved DHA (p < .05), >1000 mg/day (p < .05). CONCLUSIONS: The effectiveness of cognitive intervention is significantly influenced by frequency, time, period, delivery mode and setting. The effectiveness of physical exercise is significantly influenced by frequency, intensity, type, time, period, delivery mode and setting. The effectiveness of multicomponent intervention is significantly influenced by frequency, time, period and setting. The effectiveness of nutrition intervention is significantly influenced by dose and type. RELEVANCE TO CLINICAL PRACTICE: The research summarised the evidence to guide the best prescription of NPIs and helped clinicians design more effective interventions in individuals with MCI.

A Risk Prediction Model Based on Machine Learning for Cognitive Impairment Among Chinese Community-Dwelling Elderly People With Normal Cognition: Development and Validation Study.

BACKGROUND: Identifying cognitive impairment early enough could support timely intervention that may hinder or delay the trajectory of cognitive impairment, thus increasing the chances for successful cognitive aging. OBJECTIVE: We aimed to build a prediction model based on machine learning for cognitive impairment among Chinese community-dwelling elderly people with normal cognition. METHODS: A prospective cohort of 6718 older people from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) register, followed between 2008 and 2011, was used to develop and validate the prediction model. Participants were included if they were aged 60 years or above, were community-dwelling elderly people, and had a cognitive Mini-Mental State Examination (MMSE) score ≥18. They were excluded if they were diagnosed with a severe disease (eg, cancer and dementia) or were living in institutions. Cognitive impairment was identified using the Chinese version of the MMSE. Several machine learning algorithms (random forest, XGBoost, naïve Bayes, and logistic regression) were used to assess the 3-year risk of developing cognitive impairment. Optimal cutoffs and adjusted parameters were explored in validation data, and the model was further evaluated in test data. A nomogram was established to vividly present the prediction model. RESULTS: The mean age of the participants was 80.4 years (SD 10.3 years), and 50.85% (3416/6718) were female. During a 3-year follow-up, 991 (14.8%) participants were identified with cognitive impairment. Among 45 features, the following four features were finally selected to develop the model: age, instrumental activities of daily living, marital status, and baseline cognitive function. The concordance index of the model constructed by logistic regression was 0.814 (95% CI 0.781-0.846). Older people with normal cognitive functioning having a nomogram score of less than 170 were considered to have a low 3-year risk of cognitive impairment, and those with a score of 170 or greater were considered to have a high 3-year risk of cognitive impairment. CONCLUSIONS: This simple and feasible cognitive impairment prediction model could identify community-dwelling elderly people at the greatest 3-year risk for cognitive impairment, which could help community nurses in the early identification of dementia.

Sleep, inflammation and cognitive function in middle-aged and older adults: A population-based study.

BACKGROUND: Sleep plays a key role in preserving cognitive function. However, the optimal strategies of sleep for cognition and the underlying mechanism are not well-established. METHODS: A cross-sectional study was performed using the China Health and Retirement Longitudinal Study (CHARLS), 2011-2012 survey. Self-reported nighttime sleep and afternoon napping data were collected. Fasting blood collected was analyzed for the high-sensitivity C-reactive protein (CRP) and white blood cell. RESULTS: Both nighttime sleep and afternoon napping were significantly associated with cognition after adjusting for confounders (p < 0.05). Precisely, participants with nighttime sleep of 6.1-7h had the highest cognition scores (p < 0.05). Participants with less than 30 min afternoon napping had the highest cognition scores (p < 0.05). The synergistic effect of nighttime sleep and afternoon napping was not significant (p > 0.05). Nighttime sleep and afternoon napping were significantly related to the white blood cell, but not the high-sensitivity CRP. The white blood cell mediated the association between sleep and cognition (p < 0.05). CONCLUSION: Nighttime sleep of six to seven hours and afternoon napping of less than 30 minutes are associated with optimal cognitive function in middle-aged and older people, respectively. Sleep influences cognition partly via the inflammatory profile.

Effects of computerised cognitive training on cognitive impairment: a meta-analysis.

INTRODUCTION: Computerised cognitive training (CCT) has been shown to enhance cognitive function in elderly individuals with cognitive deterioration, but evidence is controversial. Additionally, whether specific CCT is most effective and which stages of cognitive impairment benefit most is unclear. METHODS: We systematically searched nine medical and technological databases to collect randomized controlled trials related to CCT primarily conducted in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). RESULTS: We identified 12 studies in patients with SCD and MCI. Pooled analysis showed that CCT could significantly improve cognitive function (g = 0.518, p = 0.000), especially related to memory. In terms of different types of cognitive training, specific CCT was more efficacious than non-specific CCT (g = 0.381, p = 0.007) or placebo (g = 0.734, p = 0.000) but not traditional CT (p = 0.628). In terms of stages of cognitive deterioration, the effect of CCT on SCD (g = 0.926, p = 0.002) was almost double that of its effect on MCI (g = 0.502, p = 0.000). CONCLUSION: CCT was most effective in cognitive rehabilitation, particularly in the subdomain of memory. Early intervention in SCD is better.

Neuropsychiatric symptoms as prognostic makers for the elderly with mild cognitive impairment: a meta-analysis.

BACKGROUND: Although several neuropsychiatric symptoms (NPSs) have been demonstrated to have value in the prediction of the progression of mild cognitive impairment (MCI) to dementia, these symptoms are less studied for the prediction of the transition from normal cognition (NC) to MCI. METHODS: Prospective cohort studies were included if they reported on at least one NPS at baseline and had MCI as the outcome. RESULTS: We obtained 13 cohort studies with a total population of 33,066. Depression was the most common neuropsychiatric symptom and could significantly predict transition to MCI (RR = 1.49, 95% CI: 1.13-1.86). However, depression was more capable of predicting amnestic MCI (RR=1.43, 95% CI: 1.04-1.83) than non-aMCI (RR= 0.96, 95% CI 95% CI: 0.60-1.33). Subgroup analysis suggested that the association between depression and MCI changed with depression severity, depression criteria, apolipoprotein-E-adjusted status, age, the percentage of females, and follow-up times, but some data were too sparse for a reliable estimate. Regarding other NPSs, there were insufficient data to assess their effect on the development of MCI. However, apathy, anxiety, sleep disturbances, irritability, and agitation might be risk factors for the prediction of NC-MCI transition with strong predictive value. CONCLUSIONS: Depression was associated with an approximately 1.5-fold sincreased risk of the progression to MCI in the population with normal cognition. Other NPSs with underlying predictive value deserve more attention.

Clinical Efficacy and Safety of High-Dose Dexamethasone Plus Low-Dose Rituximab as First-Line Therapy in Newly Diagnosed Primary Immune Thrombocytopenia.

Standard-dose prednisone as first-line therapy for primary immune thrombocytopenia (ITP) can not obtain high long-term responses. Results from high-dose dexamethasone course administered in adult newly diagnosed ITP were promising. The role of standard-dose rituximab in first-line treatment of newly diagnosed ITP were also investigated. We retrospectively analyzed the efficacy and safety of high-dose dexamethasone plus low-dose (100 mg/w) rituximab for treatment of adults newly diagnosed ITP. A total of eighteen patients received dexamethasone 40 mg/day for 4 consecutive days (days + 1 to + 4), rituximab 100 mg once weekly for a total of 4 weeks (days + 7, + 14, + 21 and + 28). Non-responders accepted the repeated dexamethasone treatment every 2 weeks for a total of up to 3 treatment cycles. The overall response was 100% at 28th day. Median follow-up was 17 months (1-33 months). Six patients (33.3%) relapsed. Sustained complete response or response after 6 months and 12 months of follow-up were reached in 83.3% (15/18) and 61.5% (8/13) of patients respectively. The 12-month and 15-month cumulative relapse-free survival were 69.3% and 60.7%. Incidence of adverse effects was 11.1% (2/18). High-dose dexamethasone plus low-dose rituximab therapy had high efficacy and well tolerability as first-line treatment option in newly diagnosed ITP.

Multi-angles of smoking and mild cognitive impairment: is the association mediated by sleep duration?

Although the association between cigarette smoking and risk of mild cognitive impairment (MCI) is controversial, most recent studies have shown that this influence is negative. However, it is unknown how multiple factors of smoking affect MCI, and the mechanisms of different smoking factors are not yet clarified. This study will examine the impact of various angles of smoking on MCI and the potential mediating effects of sleep duration on smoking MCI association in the elderly. In the case group, 109 elderly people who met the inclusion criteria were selected, and 123 were selected in the control group. Participant characteristics include sleep duration and a detailed lifetime history of smoking. After adjusting the relevant covariates, higher odds of MCI occurrence were found in ex-smokers/current smokers; moderate/heavy smokers; smokers for 30-44, 45-59 and more than 60 years; smokers with cumulative smoking duration of 30-44 or more than 60 years and smokers with cumulative dose smoking intensity of 200-399 or 400-599 cigarettes monthly. Elderly subjects who had quit smoking for 21 years or longer were found to have lower odds of MCI occurrence. The indirect effects of smoking on MCI via sleep duration were statistically significant, as the ratio of indirect effect to total effect ranged from 0.14 to 0.29. Smoking affects cognitive function through multi-angles of smoking and influences the cognitive function partly via the duration of sleep.