Previous studies have shown that high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cognitive function across a range of concentrations. However, recent studies have ...suggested that very high HDL-C levels may lead to poorer outcomes. Therefore, we aimed to investigate the relationship between different concentrations of HDL-C and cognitive impairment risk. We collected data from 3632 participants aged over 60 years from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014 to assess the relationship between HDL-C and cognitive function. Cognitive function was evaluated with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, the animal fluency test (AFT), and the digit symbol substitution test (DSST). We used restricted cubic spline models and logistic regression to examine the association between HDL-C and cognitive function. A U-shaped was observed between HDL-C and cognitive outcomes, individuals with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (greater than or equal to 2.50 mmol/L) were associated with increased risk of cognitive impairment (OR = 2.19; 95% CI, 1.12-4.28) compared with those with HDL-C levels in the range of 1.50 to 1.99 mmol/L in older adults after adjustment for confounding factors. Interaction test demonstrated that relationship between very high HDL-C and the risk of cognitive impairment was not changed in different sex and race group (P for interaction > 0.05). Very high HDL-C levels were associated with an increased risk of cognitive impairment. HDL-C may not be a protective factor for maintaining brain health in older adults at very high levels.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The present study aims to use structural equation modelling (SEM) with multiple regression pathways to examine direct and indirect links from diet and metabolic traits to microvascular endothelial ...dysfunction (ED) among middle-aged Chinese males.
The study was conducted in middle-aged Chinese males, who underwent a health check-up between 2018 and 2019. Data on lifestyle behaviour factors (physical activity, diet pattern, sleep quality and diet data underwent factor analysis in advance) and metabolic risk factors referring to metabolic traits were introduced into the SEM to examine inter-relationship among these factors and their association with ED, as evaluated by the reactive hyperaemia index (RHI).
Both exploratory factor analysis and confirmatory factor analysis identified two major dietary patterns: 'prudent pattern' and 'western pattern'. The univariate test suggested that only triglycerides (TGs) and prudent dietary pattern were directly associated with RHI. Furthermore, prudent dietary pattern had an indirect association with RHI via TG (prudent diet→TG: β=-0.15, p<0.05; TG→RHI: β=-0.17, p<0.001). As to confirming the hypothesised association between variables apart, physical activity frequency was correlated to the decrease in TG (β=-0.29, p<0.001), but had no direct correlation to RHI.
The network of direct and indirect associations among diet pattern and cardiometabolic risk factors with RHI measured ED among middle-aged males. The most significant modifiable factors identified were TG and prudent diet pattern, which needs to be targeted as preventive strategies for early microvascular impairment.
The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property. It has been shown that α-mangostin ...(αM)-loaded poly(ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles (NP-αM) specifically increased low density lipoprotein receptor (LDLR) expression in microglia and improved clearance of amyloid beta (Aβ) after multiple administration. However, how do the nanoparticles cross the blood‒brain barrier and access microglia remain unknown. Here, we studied the brain delivery property of PEG-PLA nanoparticles under different conditions, finding that the nanoparticles exhibited higher brain transport efficiency and microglia uptake efficiency after αM loading and multiple administration. To reveal the mechanism, we performed proteomic analysis to characterize the composition of protein corona formed under various conditions, finding that both drug loading and multiple dosing affect the composition of protein corona and subsequently influence the cellular uptake of nanoparticles in b.End3 and BV-2 cells. Complement proteins, immunoglobulins, RAB5A and CD36 were found to be enriched in the corona and associated with the process of nanoparticles uptake. Collectively, we bring a mechanistic understanding about the modulator role of protein corona on targeted drug delivery, and provide theoretical basis for engineering brain or microglia-specific targeted delivery system.
Drug loading and multiple dosing affect the composition of protein corona. Complement proteins, immunoglobulins, RAB5A and CD36 in protein corona influence nanoparticles uptake in brain endothelial cells and microglia. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation of mitochondrial calcium ion (Ca2+) ...homeostasis and the mitochondrial permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to the mitochondrial dysfunction cascade in AD pathogenesis. Herein, a “two‐hit braking” therapeutic strategy to synergistically halt mitochondrial Ca2+ overload and mPTP opening to put the mitochondrial dysfunction cascade on a brake is proposed. To achieve this goal, magnesium ion (Mg2+), a natural Ca2+ antagonist, and siRNA to the central mPTP regulator cyclophilin D (CypD), are co‐encapsulated into the designed nano‐brake; A matrix metalloproteinase 9 (MMP9) activatable cell‐penetrating peptide (MAP) is anchored on the surface of nano‐brake to overcome the blood‐brain barrier (BBB) and realize targeted delivery to the mitochondrial dysfunction cells of the brain. Nano‐brake treatment efficiently halts the mitochondrial dysfunction cascade in the cerebrovascular endothelial cells, neurons, and microglia and powerfully alleviates AD neuropathology and rescues cognitive deficits. These findings collectively demonstrate the potential of advanced design of nanotherapeutics to halt the key upstream signaling pathways of mitochondrial dysfunction to provide a powerful strategy for AD modifying therapy.
Matrix metalloproteinase 9 activatable cell‐penetrating peptide (MAP) on the nano‐brake mediates its efficient entry into the target cells. With siRNA reducing the expression of cyclophilin D and magnesium ion suppressing calcium ion overload, nano‐brake halts the overall mitochondrial dysfunction cascade in the cerebrovascular endothelial cells, neurons, astrocytes and microglia and largely alleviates the neuropathology and cognitive deficits of Alzheimer's disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Each year, over 15,000 preschoolers die from unintentional injuries in China. Many interventions proven to work in other nations have not been implemented nationwide in China. The rapid popularity of ...smartphones offers an opportunity to overcome this limitation and disseminate evidence-based interventions to the large population of China. This study aims to assess the effectiveness of an app-based intervention for caregivers of preschoolers to prevent unintentional injury among young Chinese children.
A single-blinded, 6-month, parallel-group cluster randomized controlled trial with 1:1 allocation ratio will be conducted in Changsha, China. In total, 2626 caregivers of preschoolers ages 3-6 years old who own a smartphone will be recruited from 20 preschools. Clusters will be randomized at the preschool level and allocated to either the control group (routine education plus app-based parenting education excluding unintentional injury prevention) or the intervention group (routine education plus app-based parenting education including unintentional injury prevention). The app-based injury prevention program was developed based on the Theory of Planned Behavior, the Haddon Matrix, the Mobile Learning framework, and a needs assessment. Data collection will be conducted at baseline, 3-month, and 6-month follow-up via app-based survey plus printed questionnaire survey. The primary outcome measure is unintentional injury incidence among preschoolers in the past 3 months. Secondary outcome measures include economic losses due to unintentional injury in the past 3 months, the Incremental Cost-Effectiveness Ratios (ICERs), and parent's attitudes and behaviors concerning supervision to prevent preschooler unintentional injury in the past week. An intention-to-treat approach will be used to evaluate outcome measures. Chi-square tests will examine differences for outcome measures between groups at each time point and generalized estimation equations (GEE) will test the overall effectiveness of the app-based intervention. Missing outcome data will be imputed using the Expectation Maximization algorithm (EM).
This trial will examine evidence concerning the effectiveness of an innovative app-based intervention for caregivers of Chinese preschoolers. If effective, the app-based intervention could offer an effective population-based intervention option to cost-effectively promote unintentional injury prevention in countries and regions where injury control is under-supported.
ChiCTR-IOR-17010438 . Registered 15 January 2017.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Objective
To investigate the incidence of falls in elderly aged 65 years and above among outpatients and inpatients, and to analyze its related factors and identify prevention strategies.
...Methods
A retrospective analysis was conducted on 451 patients aged 65 years and above who received comprehensive geriatric assessment in outpatients and inpatients from the Department of Geriatrics in the Second Xiangya Hospital from March 2021 to March 2022. According to whether there had been at least one fall in the past year, the patients were divided into a fall group and a non‐fall group. Data were collected from the We‐Chat applet of comprehensive geriatric assessment. A
t
test and chi‐square test were performed to compare the difference between the two groups. Logistic regression analysis was then conducted to identify factors associated with falls.
Results
(1) The incidence of falls among the outpatient and inpatient was 28.8%. (2) The rate of light, moderate, and heavy dependence on daily living ability and decreased mobile balance ability were higher in the fall group than those in the non‐fall group. The average calf circumference in the fall group was significantly lower than that in the non‐fall group. (3) The prevalence of diabetes and eye diseases in the fall group was significantly higher than that in the non‐fall group. (4) The percentage of insomnia and suspicious insomnia cases in the fall group was higher than that in the non‐fall group. The mean scores for dysphagia, frailty, and incontinence were higher and the mean malnutrition score was lower in the fall group than in the non‐fall group. (5) Multiple logistic regression analysis showed that frailty, insomnia, and malnutrition were independent influencing factors of fall (OR = 1.955, 1.652, 10.719,
P
= 0.044, 0.041, 0.025, respectively).
Conclusions
The incidence of falls among outpatients and inpatients aged 65 years and above is high. Frailty, insomnia, and malnutrition are the main factors influencing falls in these patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Studies examining the risk factors for dyskinesia in Parkinson's disease (PD) have been inconsistent, and racial differences exist. Since there have been no systematic studies of the characteristics ...of dyskinesia in the Mainland Chinese population, we sought to elucidate the risk factors for dyskinesia.
A total of 1974
patients from Mainland China were systematically investigated by univariable and multivariable analyses. PD patients with and without dyskinesia were stratified into 4 groups according to levodopa equivalent daily dose (LEDD) and analyzed by a Cox proportional hazards model. A longitudinal study of 87 patients with dyskinesia was classified into 3 groups according to the duration from onset of PD to the initiation of levodopa, and comparisons among groups were analyzed by the Mann-Whitney test.
Early age of onset, long disease duration, being female, high LEDD, low UPDRS III scores (ON-state) and high Hoehn-Yahr stage (ON-state) were predictors of dyskinesia. Dyskinesia was levodopa dosage-dependent, and the incidence increased remarkably when LEDD exceeded 300 mg/d (
< 0.05). The emergence of dyskinesia had no association with the initiation time of levodopa, and if the latter was more than 4 years, the duration of time on chronic levodopa free of motor complications was significantly shortened.
We found risk factors for the prediction of dyskinesia. Our data shows that physicians should be cautious if the LEDD exceeds 300 mg/d. The development of dyskinesia was not correlated with the time of levodopa initiation.
Background Neck-shoulder pain is one of the most common discomfort symptoms among nursing staff, mostly caused by a heavy workload, restricted workstation, and prolonged poor posture. Objective To ...investigate the prevalence of neck-shoulder pain among nursing staff in tertiary general hospitals in Hunan Province, and to analyze workload-related risk factors. Methods From October to December 2018, a multi-stage stratified randomized cluster sampling method was adopted to select a total of 1 200 nursing staff who met the inclusion andexclusion criteria in six tertiary general hospitals from five geographic subdivisions of Hunan Province were selected. A self-designed questionnaire was used to collect demographic characteristics, and past 1-month prevalence of neck-shoulder pain, a neck disability index (NDI) was used to assess the impact of neck pain on daily life, and functional disability was graded by the index of impaired neck function; a self-designed questionnaire was adopted to evaluate potential workload-related risk factors (working time, postural load, and force load) of neck-shoulder pain after a Delphi expert consultation. A total of 1 161 valid questionnaires were returned, and χ２test and logistic regression model were used to screen the potential risk factors for neck-shoulder pain. Results The prevalence rate of neck-shoulder pain in the past 1 month was 87.5% (1 016/1 161) and varied by different characteristics of the nursing staff, ranging from 76.9% to 91.2%. The scores of the 10 items of the NDI ranged from 0 to 5, but most of them were 0, 1, and 2; of the 10 items, neck pain had the greatest impact on sleep (1.30±1.21) and the least impact on self-care behaviors (0.35±0.65). The index of impaired neck function showed that the majority (65.4%) of nurses had mild cervical spine dysfunction and 30.1% had moderate cervical spine dysfunction. The univariate analysis results revealed that 24 out of the 31 workload-related risk factors had significant differences, and further multiple analysis results showed that three variables entered the logistic regression model. Under the same conditions, nurses with ≥5 h of cumulative head-down tasks per shift had 3.03 times higher neck-shoulder pain risks compared with those with ＜1 h. Compared with "occasionally or never", nurses who "sometimes" and "often" tilted their necks back and maintained this posture for a long time showed 2.36 and 2.94 times higher risks for neck-shoulder pain respectively. The nurses who reported "sometimes" and "often" having difficulty using their force at work due to unnatural posture had 2.78 times and 7.08 times higher neck-shoulder pain risks than those who "occasionally or never" respectively. Conclusion The reported rate of neck-shoulder pain among nurses in tertiary general hospitals in Hunan Province is high, but most of them are mild dysfunction. Working hours and posture load may affect the risk of neck-shoulder pain.
Aims
This work aims to analyse the current state of the professional identity of Chinese nurses; examine the relationship amongst regulatory focus, organizational silence and professional identity ...and determine how regulatory focus affects the relationship between professional identity and organizational silence.
Design
This study conducted a cross‐sectional survey.
Methods
From June to August 2023, 420 nurses from six hospitals in Hunan Province, China, were selected through convenience sampling and surveyed by using a general information questionnaire, the regulatory focus scale, the organizational silence scale and the professional identity scale. The relationship amongst the regulatory focus, organizational silence and professional identity of nurses was examined by utilizing SPSS 25.0 and the mediating role of regulatory focus between organizational silence and nurses' professional identity was examined by applying AMOS 24.0.
Results
Nurses had a moderate level of professional identity. Professional identity was positively correlated with regulatory focus and negatively correlated with organizational silence. Regulatory focus was negatively correlated with organizational silence. Mediation effect studies revealed that organizational silence and professional identity were partially mediated by regulatory focus.
Conclusion
In accordance with research showing that nurses' organizational silence can indirectly affect professional identity via regulatory focus, clinical nursing managers should concentrate on the interaction amongst these three variables to strengthen professional identity.
Impact
The results of this study serve as a reminder to nurses to select a preventive or promotive focus based on their career objectives and to effectively express their views to enhance their professional identity. This also reminds nursing managers assess nurse‐led regulatory focus, identify their underlying qualities and understand their professional aspirations and career orientation, create a good atmosphere for advice and encourage nurses to express their views, so as to improve nurses ‘professional identity.
Patient or Public Contribution
No patient or public contribution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Nanoparticles (NPs) represent an important advance for delivering diagnostic and therapeutic agents across the blood-brain barrier. However, NP clearance is critical for safety and therapeutic ...applicability. Here we report on a study of the clearance of model organic and inorganic NPs from the brain. We find that microglial extracellular vesicles (EVs) play a crucial role in the clearance of inorganic and organic NPs from the brain. Inorganic NPs, unlike organic NPs, perturb the biogenesis of microglial EVs through the inhibition of ERK1/2 signalling. This increases the accumulation of inorganic NPs in microglia, hindering their elimination via the paravascular route. We also demonstrate that stimulating the release of microglial EVs by an ERK1/2 activator increased the paravascular glymphatic pathway-mediated brain clearance of inorganic NPs. These findings highlight the modulatory role of microglial EVs on the distinct patterns of the clearance of organic and inorganic NPs from the brain and provide a strategy for modulating the intracerebral fate of NPs.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
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