Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults.

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aß42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aß42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aß42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aß pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aß pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aß pathology. Fibrinogen was associated with both cognition and Aß pathology. Aß pathology may be a critical mediator for impacts of fibrinogen on cognition.

Associations of the neutrophil to lymphocyte ratio with intracranial artery stenosis and ischemic stroke.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has emerged as an inflammatory marker. However, the associations of NLR with intracranial artery stenosis (ICAS) and ischemic stroke remain unclear. This study aimed to examine the associations of NLR with ICAS and ischemic stroke among a large and high-risk population. METHODS: Participants with records of clinical characteristics were prospectively recruited from the Neurology Department and Health & Physical Examination Center of Qingdao Municipal Hospital. Logistic regression analysis was used to examine the associations of NLR with ICAS and ischemic stroke. Moreover, we also conducted parametric mediation analysis to estimate the effect of NLR on the risk of ischemic stroke mediated through ICAS. RESULTS: A total of 2989 participants were enrolled in this study. After adjusting for covariates, NLR (OR = 1.125, 95%CI 1.070-1.183) and ICAS (OR = 1.638, 95%CI 1.364-1.967) were significantly associated with ischemic stroke. Compared with the first quartile NLR, the second, third and fourth quartiles NLR were independent risk predictors for ischemic stroke (P for trend < 0.001); the third and fourth quartiles were independent predictors for ICAS (P for trend < 0.001). The mediation analysis showed that ICAS partially mediated the association between NLR and ischemic stroke, accounting for 14.4% of the total effect (P < 0.001). CONCLUSIONS: NLR was significantly associated with ICAS and ischemic stroke. Besides, ICAS partially mediated the association between NLR and ischemic stroke.

Associations between cardiometabolic multimorbidity and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: the CABLE study.

BACKGROUND: Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD. METHODS: This study included 1464 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed. RESULTS: A total of 1464 individuals (mean age, 61.80 years; age range, 40-89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: ß = 0.165, P = 0.037) and neuronal injury (CSF T-tau: ß = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aß42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses. CONCLUSIONS: The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.

CAIDE Score, Alzheimer's Disease Pathology, and Cognition in Cognitively Normal Adults: The CABLE Study.

Background: Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. Objective: To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. Methods: In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Results: Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aß42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2%. Conclusions: A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.

Identifying modifiable factors and their joint effect on brain health: an exposome-wide association study.

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

Optimized production of biodiesel from waste cooking oil by lipase immobilized on magnetic nanoparticles.

Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce biodiesel has advantages over common alkaline catalysts such as mild reaction conditions, easy product separation, and use of waste cooking oil as raw material. In this study, Pseudomonas cepacia lipase immobilized onto magnetic nanoparticles (MNP) was used for biodiesel production from waste cooking oil. The optimal dosage of lipase-bound MNP was 40% (w/w of oil) and there was little difference between stepwise addition of methanol at 12 h- and 24 h-intervals. Reaction temperature, substrate molar ratio (methanol/oil), and water content (w/w of oil) were optimized using response surface methodology (RSM). The optimal reaction conditions were 44.2 °C, substrate molar ratio of 5.2, and water content of 12.5%. The predicted and experimental molar conversions of fatty acid methyl esters (FAME) were 80% and 79%, respectively.

Renal function and neurodegenerative diseases : a two-sample Mendelian randomization study.

BACKGROUND: Observational studies showed renal function had associations with Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD) and multiple sclerosis (MS). However, it is unknown whether these associations are causal. METHODS: We use a two-sample Mendelian randomization (MR) analysis to investigate causal relationships between renal function and 6 neurodegenerative diseases (NDDs): AD (including familial AD), PD, LBD, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and MS. Blood urea nitrogen (BUN), chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) were used to measure renal function. The inverse-variance weighted (IVW) was the predominant estimation method. The results were further validated using sensitivity analysis (i.e. MR Egger regression, Cochran Q statistic of IVW, and leave-one-out method). RESULTS: There was no indication of any causative relationship of BUN, CKD, or eGFR with AD, familial AD, PD, LBD, FTD and ALS (all P values >0.05). The IVW analysis demonstrated a causal relationship between eGFR and MS [odds ratio (OR), 4.89; 95% confidence interval (CI), 1.43 to 16.71; P = 0.01] that was not verified in the MR-Egger and weighted median (all P values >0.05). However, no causal association of MS with BUN (OR, 0.91; 95% CI, 0.40-2.07; P = 0.82) and CKD (OR,1.04; 95% CI, 0.88-1.23; P = 0.66) was found. There was no single SNP that affects the overall trend. CONCLUSIONS: Our study showed that reduced eGFR was related to MS. The value of this study is that it provides a direction for further research on the relationship between reduced eGFR and MS.

Cerebral Small Vessel Disease Burden Predicts Neurodegeneration and Clinical Progression in Prodromal Alzheimer's Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). OBJECTIVE: This study aimed to comprehensively investigated the associations of CSVD burden with cognition and AD pathologies. METHODS: A total of 546 non-demented participants (mean age, 72.1 years, range, 55-89; 47.4% female) were included. The longitudinal neuropathological and clinical correlates of CSVD burden were assessed using linear mixed-effects and Cox proportional-hazard models. Partial least squares structural equation model (PLS-SEM) was used to assess the direct and indirect effects of CSVD burden on cognition. RESULTS: We found that higher CSVD burden was associated with worse cognition (MMSE, ß= -0.239, p = 0.006; MoCA, ß= -0.493, p = 0.013), lower cerebrospinal fluid (CSF) Aß level (ß= -0.276, p < 0.001) and increased amyloid burden (ß= 0.048, p = 0.002). In longitudinal, CSVD burden contributed to accelerated rates of hippocampus atrophy, cognitive decline, and higher risk of AD dementia. Furthermore, as the results of PLS-SEM, we observed both significant direct and indirect impact of advanced age (direct, ß= -0.206, p < 0.001; indirect, ß= -0.002, p = 0.043) and CSVD burden (direct, ß= -0.096, p = 0.018; indirect, ß= -0.005, p = 0.040) on cognition by Aß-p-tau-tau pathway. CONCLUSION: CSVD burden could be a prodromal predictor for clinical and pathological progression. Simultaneously, we found that the effects were mediated by the one-direction-only sequence of pathological biomarker changes starting with Aß, through abnormal p-tau, and neurodegeneration.

Recognizing and monitoring infectious sources of schistosomiasis by developing deep learning models with high-resolution remote sensing images.

BACKGROUND: China is progressing towards the goal of schistosomiasis elimination, but there are still some problems, such as difficult management of infection source and snail control. This study aimed to develop deep learning models with high-resolution remote sensing images for recognizing and monitoring livestock bovine, which is an intermediate source of Schistosoma japonicum infection, and to evaluate the effectiveness of the models for real-world application. METHODS: The dataset of livestock bovine's spatial distribution was collected from the Chinese National Platform for Common Geospatial Information Services. The high-resolution remote sensing images were further divided into training data, test data, and validation data for model development. Two recognition models based on deep learning methods (ENVINet5 and Mask R-CNN) were developed with reference to the training datasets. The performance of the developed models was evaluated by the performance metrics of precision, recall, and F1-score. RESULTS: A total of 50 typical image areas were selected, 1125 bovine objectives were labeled by the ENVINet5 model and 1277 bovine objectives were labeled by the Mask R-CNN model. For the ENVINet5 model, a total of 1598 records of bovine distribution were recognized. The model precision and recall were 81.9% and 80.2%, respectively. The F1 score was 0.81. For the Mask R-CNN mode, 1679 records of bovine objectives were identified. The model precision and recall were 87.3% and 85.2%, respectively. The F1 score was 0.87. When applying the developed models to real-world schistosomiasis-endemic regions, there were 63 bovine objectives in the original image, 53 records were extracted using the ENVINet5 model, and 57 records were extracted using the Mask R-CNN model. The successful recognition ratios were 84.1% and 90.5% for the respectively developed models. CONCLUSION: The ENVINet5 model is very feasible when the bovine distribution is low in structure with few samples. The Mask R-CNN model has a good framework design and runs highly efficiently. The livestock recognition models developed using deep learning methods with high-resolution remote sensing images accurately recognize the spatial distribution of livestock, which could enable precise control of schistosomiasis.

Plasma ß2-microglobulin and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: the CABLE study.

BACKGROUND: Previous studies have suggested a correlation between elevated levels of ß2-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and cognition. METHODS: To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M's relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition. RESULTS: We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aß1-42 (P < 0.001) and Aß1-42/Aß1-40 (P = 0.015) as well as increases in T-tau/Aß1-42 (P < 0.001) and P-tau/Aß1-42 (P < 0.001). The subgroup analysis found B2M correlated with Aß1-42 in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aß pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect. CONCLUSIONS: This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aß pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression.

Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study.

Previous observational studies reported that midlife clustering of cardiovascular risk factors and lifestyle behaviors were associated with neurodegenerative disease; however, these findings might be biased by confounding and reverse causality. This study aimed to investigate the causal associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease, using the two-sample Mendelian randomization design. Genetic variants for the modifiable risk factors and neurodegenerative disease were extracted from large-scale genome-wide association studies. The inverse-variance weighted method was used as the main analysis method, and MR-Egger regression and leave-one-out analyses were performed to identify potential violations. Genetically predicted diastolic blood pressure (DBP: OR per 1 mmHg, 0.990 [0.979-1.000]), body mass index (BMI: OR per 1 SD, 0.880 [0.825-0.939]), and educational level (OR per 1 SD, 0.698 [0.602-0.810]) were associated with lower risk of late-onset Alzheimer's disease (LOAD), while genetically predicted low-density lipoprotein (LDL: OR per 1 SD, 1.302 [1.066-1.590]) might increase LOAD risk. Genetically predicted exposures (including LDL and BMI) applied to familial AD showed the same effect. The association of LDL was also found with Amyotrophic lateral sclerosis (ALS) (LDL: OR per 1 SD, 1.180 [1.080-1.289]). This MR analysis showed that LDL, BMI, BP, and educational level were causally related to AD; a significant association between LDL and ALS risk, as well as the potential effect of sleep duration on PD risk, were also revealed. Targeting these modifiable factors was a promising strategy of neurodegenerative disease prevention.

Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes.

Background: Perturbation of lipid metabolism is associated with Alzheimer's disease (AD). Heart fatty acid-binding protein (HFABP) is an adipokine playing an important role in lipid metabolism regulation. Materials and methods: Two datasets separately enrolled 303 and 197 participants. First, we examine the associations of cerebrospinal fluid (CSF) HFABP levels with cognitive measures [including Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of boxes (CDRSB), and the cognitive section of Alzheimer's Disease Assessment Scale] and AD biomarkers (CSF amyloid beta and tau levels). Second, we examine the longitudinal associations of baseline CSF HFABP levels and the variability of HFABP with cognitive measures and AD biomarkers. Structural equation models explored the mediation effects of AD pathologies on cognition. Results: We found a significant relationship between CSF HFABP level and P-tau (dataset 1: ß = 2.04, p < 0.001; dataset 2: ß = 1.51, p < 0.001). We found significant associations of CSF HFABP with longitudinal cognitive measures (dataset 1: ADAS13, ß = 0.09, p = 0.008; CDRSB, ß = 0.10, p = 0.003; MMSE, ß = -0.15, p < 0.001; dataset 2: ADAS13, ß = 0.07, p = 0.004; CDRSB, ß = 0.07, p = 0.005; MMSE, ß = -0.09, p < 0.001) in longitudinal analysis. The variability of HFABP was associated with CSF P-tau (dataset 2: ß = 3.62, p = 0.003). Structural equation modeling indicated that tau pathology mediated the relationship between HFABP and cognition. Conclusion: Our findings demonstrated that HFABP was significantly associated with longitudinal cognitive changes, which might be partially mediated by tau pathology.

Risk of Dementia in Cancer Survivors: A Meta-Analysis of Population-Based Cohort Studies.

BACKGROUND: A negative association between cancer and Alzheimer's disease (AD) was revealed. OBJECTIVE: We aimed to further explore the dementia risk among cancer survivors and then among cancer survivors who received cancer treatment in subsequent subgroup analyses. METHODS: Databases of PubMed, Embase, and Cochrane Library were systematically searched from inception to April 1, 2021, following PRISMA and MOOSE guidelines. Relative risks (RR) of dementia were pooled by a random-effects model stratifying the data by potential confounding factors to explore the heterogeneity. This study is registered with PROSPERO, number CRD42021250654. RESULTS: A total of 36 studies were included in this meta-analysis, of which 16 studies were about the risk of dementia in cancer survivors, and 20 studies were about the risk of dementia in survivors who accepted cancer treatment. The pooled RR reached 0.89 ([95% CI = 0.82-0.97], I2 = 97.9%) for dementia and 0.89 ([0.83-0.95], I2 = 92.6%) for AD in cancer survivors compared with non-cancer controls. Notably, both dementia risk and AD risk significantly decreased in survivors of colon, leukemia, small intestine, and thyroid cancers (RR ranged from 0.64 to 0.92). Furthermore, prostate cancer patients treated with androgen deprivation therapy exhibited a significantly increased risk of dementia (RR:1.18 [1.09-1.27], I2 = 89.5%) and AD (RR:1.17 [1.08-1.25], I2 = 81.3%), with evidence of between-study heterogeneity. CONCLUSION: Currently, available evidence suggests that the risk of dementia among cancer survivors is decreased. However, large-scale prospective cohort studies are warranted to further prove the association.

Association between air pollution and CSF sTREM2 in cognitively normal older adults: The CABLE study.

OBJECTIVES: Ambient air pollution aggravates the process of Alzheimer's disease (AD) pathology. Currently, the exact inflammatory mechanisms underlying these links from clinical research remain largely unclear. METHODS: This study included 1,131 cognitively intact individuals from the Chinese Alzheimer's Biomarker and LifestylE database with data provided on cerebrospinal fluid (CSF) AD biomarkers (amyloid beta-peptide 42 [Aß42], total tau [t-tau], and phosphorylated tau [p-tau]), neuroinflammatory (CSF sTREM2), and systemic inflammatory markers (high sensitivity C-reactive protein and peripheral immune cells). The 2-year averaged levels of ambient fine particulate matter with diameter <2.5 µm (PM2.5 ), nitrogen dioxide (NO2 ), and ozone (O3 ) were estimated at each participant's residence. Multiple-adjusted models were approached to detect associations of air pollution with inflammatory markers and AD-related proteins. RESULTS: Ambient 2-year averaged exposure of PM2.5 was associated with changes of neuroinflammatory markers, that is, CSF sTREM2 (ß = -0.116, p = 0.0002). Similar results were found for O3 exposure among the elderly (ß = -0.111, p = 0.0280) or urban population (ß = -0.090, p = 0.0144). No significant evidence supported NO2 related to CSF sTREM2. For potentially causal associations with accumulated AD pathologies, the total effects of PM2.5 on CSF amyloid-related protein (CSF Aß42 and p-tau/Aß42) were partly mediated by CSF sTREM2, with proportions of 14.22% and 47.15%, respectively. Additional analyses found inverse associations between peripheral inflammatory markers with PM2.5 and NO2 , but a positive correlation with O3 . INTERPRETATION: These findings demonstrated a strong link between PM2.5 exposure and microglial dysfunction. Furthermore, CSF sTREM2 as a key mediator modulated the influences of PM2.5 exposure on AD amyloid pathologies.

Risk Factors for Worsening of Bone Loss in Patients Newly Diagnosed with Inflammatory Bowel Disease.

Background: Bone loss is common in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of metabolic bone disease in patients newly diagnosed with IBD and to identify the risk factors for bone loss over time. Methods: We performed a retrospective, both cross-sectional and longitudinal, study to extract the risk factors of bone loss (including osteopenia and osteoporosis) in patients newly diagnosed with IBD, using dual-energy X-ray absorptiometry (DXA). Results: A total of 639 patients newly diagnosed with IBD that had at least one DXA were included in the cross-sectional study. Osteopenia and osteoporosis were diagnosed in 24.6% and 5.4% of patients, respectively. Age at diagnosis, body mass index, and serum phosphorus were identified as independent factors associated with bone loss at baseline. A total of 380 of the 639 IBD patients (including 212 CD patients and 168 UC patients) with at least a second DXA scan were included in the longitudinal study. 42.6% of the patients presented a worsening of bone loss in the follow-up study. Menopause, albumin, and use of corticosteroids were identified as independent factors associated with worsening of bone loss. Conclusions: Metabolic bone disease is common in IBD patients, and there is a significant increase in prevalence of bone loss over time. Postmenopausal female, malnourished patients, and those requiring corticosteroid treatment are at risk for persistent bone loss. Therefore, BMD measurements and early intervention with supplementation of calcium and vitamin D are recommended in IBD patients with high-risk factors.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Protective Effect and Mechanism of Bone Morphogenetic Protein-4 on Apoptosis of Human Lens Epithelium Cells under Oxidative Stress.

Bone morphogenetic proteins (BMPs), a member of the transforming growth factor ß (TGF-ß) superfamily, are abundant in human ocular tissues and play an important role in lens development. Targeted deletion of BMP-4 in mice results in failure of lens placode formation. Following lens maturation, the formation of senile cataracts is demonstrably associated with free radical-related oxidative stress. Previous studies reported that BMPs play an antiapoptotic role in cells under oxidative stress, and the BMP-4 signal is important in inflammation regulation and homeostasis. BMP-4 evidently suppressed the apoptosis of human lens epithelial cells (HLECS) under oxidative stress induced by H2O2. This protective antiapoptotic effect is partly due to a decrease in caspase-3 activity and reactive oxygen species (ROS) level. Furthermore, the expression of activating transcription factor- (ATF-) 6 and Krüppel-like factor- (KLF-) 6 increased under oxidative stress and decreased after BMP-4 treatment.

Association of Occupational Factors and Dementia or Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: Several existing studies have reported that occupational factors might play an important part in cognitive function with aging. OBJECTIVE: We aim to explore the associations between modifiable occupational factors and risk of dementia or mild cognitive impairment (MCI). METHODS: Adopting random-effect models, this study conducted primary analyses for all occupational factors and subgroup analyses for the effect of occupation type based on prospective cohort and case-control studies searched from PubMed and EMBASE databases up to March 2020. RESULTS: Among the 38,111 identified literatures, 9 studies on occupation type, 4 studies on work complexity, and 30 studies on occupational exposure were included. In terms of occupation type, mental work conferred a 44% reduced risk (95% CI = 0.34-0.94, I²â€Š= 85.00%, p < 0.01) for MCI. In terms of work complexity, higher work complexity conferred a 5% reduced risk (95% CI = 0.91-1.00, I²â€Š= 57.00%, p < 0.01) for dementia. In terms of occupational exposure, high strain and passive job in the longest-held job conferred a 1.21- and 1.15-fold excess risk (95% CI = 1.05-1.39 I²â€Š= 62.00%, p < 0.05; 95% CI = 1.05-1.26 I²â€Š= 31.00%, p = 0.23; respectively) of cognitive decline. Besides, magnetic field exposure conferred a 1.26-fold excess risk (95% CI = 1.01-1.57, I²â€Š= 69.00%, p < 0.01) for dementia. CONCLUSION: Novel prevention strategies based on occupational factors may hold promise against dementia and MCI.

Correction: Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.

[This corrects the article DOI: 10.18632/oncotarget.1628.].

Correction: Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.

[This corrects the article DOI: 10.18632/oncotarget.1628.].