Biomonitoring urinary organophosphorus flame retardant metabolites by liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry and their association with oxidative stress.

Organophosphate flame retardants (OPFRs) are widely used as substitutes for traditional brominated flame retardants, necessitating a reliable and sensitive method for biomonitoring their urinary metabolites to assess human exposure. This study conducted biomonitoring of 10 metabolites of OPFRs in 152 adults and assessed their association with oxidative stress biomarkers 8-hydroxydeoxyguanosine and 8-hydroxyguanosine. Urinary metabolites of OPFRs were released via enzymatic deconjugation. The addition of sodium chloride to the urine samples increases the ionic strength, inducing a salting-out effect that reduces the solubility of these compounds, thereby facilitating their extraction with a mixture of ethyl acetate and acetonitrile. Then, the metabolites of OPFRs were quantified by ultra-high performance liquid chromatography-tandem mass spectrometry, and we validated the method for linear range, precision, matrix effect, and method detection limit. The detection limit of the metabolites of OPFRs ranged from 0.01 to 0.2 µg/L, and these metabolites were detected with high frequencies ranging from 25.0 to 98.68% in the urine samples. The concentration of bis (2-chloroethyl) phosphate was significantly higher in males than in females, with the geometric mean concentration of 0.88 µg/L for males and 0.53 µg/L for females, respectively. Spearman correlation analysis revealed weak but statistically significant positive correlations among the urinary metabolites. Bayesian kernel machine regression analysis showed a significant positive association between elevated urinary concentrations of metabolites of OPFRs and increased oxidative stress levels. Di-n-butyl phosphate was identified as the metabolite that significantly contributed to the elevated level of 8-hydroxyguanosine.

Unraveling the contribution of dietary intake to human phthalate internal exposure.

Human exposure to phthalates (PAEs) occurs primarily through diet, but the contribution of dietary exposure to the total internal exposure of PAEs has not been well studied. This work investigated the relationship between dietary exposure and human internal exposure to PAEs. Daily food samples were determined to evaluate the health risk of dietary exposure, and phthalate metabolites (mPAEs) were determined from urine samples of 360 volunteers of Guangzhou to assess their internal exposure. The total mPAEs concentration in the urine samples ranged from 8.43 to 1872 ng/mL, with mono-(2-ethylhexyl) phthalate (MEHP), mono-n-butyl phthalate (MnBP), and mono-isobutyl phthalate (MiBP) being the most predominant mPAEs. The concentration of PAEs in food ranged from n.d-40200 µg/kg, and benzyl butyl phthalate (BBzP), di-n-butyl phthalate (DnBP) and di-(2-ethylhexyl) phthalate (DEHP) were the most prevalent. PAE exposure was significantly associated with age, and children exhibited the highest concentration of mPAEs. Using Monte Carlo simulation to estimate PAE exposure's health risk eliminated uncertainties caused by single-point sampling and provided more reliable statistical results. The hazard quotient (HQ) was used to evaluate PAE exposure health risks. The results showed that 37% of the volunteers had HQ levels higher than 1 based on urinary mPAE concentrations, while 24% of the volunteers had HQ levels greater than 1 because of dietary exposure to PAEs. Dietary intake was the predominant exposure route for PAEs, and accounted for approximately 65% (24% out of 37%) of the cases where HQ levels exceeded 1. The work revealed the correlation between dietary external and internal exposure to PAEs, and further studies are needed to better understand the implications.

Prevalence and risk factors for depression in outpatient departments of three general hospitals in China: a cross-sectional study.

Objectives: To determine the prevalence and risk factors associated with depression of outpatients in three general hospitals in southern China.Methods: This hospital-based, cross-sectional descriptive study was conducted in outpatient departments of Neurology, Gastroenterology, Cardiology and Gynaecology of three general hospitals between March and June 2016. A total of 5294 adult respondents (≥18 years) in clinic waiting rooms were recruited, and 4976 were eligible to participate in the study. The nine-item Patient Health Questionnare-9 (PHQ-9) Scale was used to assess the presence of depressive symptoms. Binary logistic regression analysis was performed to identify the risk factors associated with depressive symptoms.Results: The prevalence of depressive symptoms among outpatients was 26.0% (95% CI: 24.8-27.3%). Risk factors associated with depressive symptoms included younger age (OR = 0.960; 95% CI: 0.95-0.971), social alcohol drinking (OR = 1.339; 95% CI: 1.074-1.668) and sleep disturbance (OR = 3.678; 95% CI: 3.025-4.471).Conclusions: This study provides evidence that depressive symptoms are prevalent among outpatients of general hospitals. Moreover, younger age, alcohol consumption and sleep disturbance may potentially be useful for targeted screening and prevention for outpatients with depression seen in general hospitals.KeypointsThe prevalence of self-reported depressive symptoms is common in outpatients in clinical settings.Younger age, current alcohol drinking and sleep disturbance are the associated risk factors for depression in outpatient population.Alcohol prevention and sleep quality improvement need to be incorporated into strategies aimed at the prevention and management of depression.

Medial temporal lobe atrophy as a predictor of poor cognitive outcomes in general paresis.

BACKGROUND: The effect of penicillin therapy on clinical outcomes vary among patients with general paresis (GP). We sought to explore biomarkers that might serve as predictors of clinical outcomes in GP and identify patients requiring early intervention. METHODS: Thirty-five inpatients with GP were recruited. Each GP patient underwent comprehensive neuropsychological, neuroimaging and laboratory assessments before receiving penicillin therapy, and returned for follow-up evaluations after 6 months. The visual rating of medial temporal lobe atrophy (MTA) and the Fazekas scale was used to analyze the neuroimaging abnormalities. RESULTS: MTA scores were correlated with the pre-treatment cognitive scores and change in Mini Mental State Examination scores. GP patients with a Clinical Dementia Rating Scale (CDR) ≤1 or MTA scores ≤2 achieved significant improvement in neuropsychological test scores, as compared with patients with CDR >1 or MTA scores >2. Fazekas scale scores correlated with the pre-treatment attention scores. Significant improvements in cognitive test scores were observed in GP patients with normalization of serum rapid plasma regain (RPR) titers, but not those without normalization of RPR titers. CONCLUSIONS: Severe MTA may serve as a predictor of poor cognitive outcome and an indicator of severe cognitive impairment in GP patients. Thus, early interventions for improving cognitive function may be considered for GP patients with severe MTA. White matter hyperintensities may associated with attention impairment. Serum RPR titer may serve as a sensitive indicator of therapeutic effect in GP.

Regional differences in the risk of insomnia symptoms among patients from general hospital outpatient clinics.

BACKGROUND: Region-specific differences in the prevalence of insomnia symptoms in outpatient clinics in China have received little systematic study. This study was conducted preliminarily to examine region-specific differences in the risk of insomnia symptoms in Chinese outpatients. METHOD: In total, 4,399 adult outpatients (urban vs rural residents: 1,768 vs 2,631) who completed three questions focusing on insomnia symptoms were included. Their sociodemographic and clinical information were collected with standardized questionnaires. RESULTS: The prevalence of self-reported insomnia symptoms in urban residents (23.4%) was more frequent than the prevalence in rural residents (21.2%). The estimated prevalence of insomnia symptoms was significantly lower in rural than urban residents after adjusting for the potential confounders (P=0.015). Similarly, more urban (22.9%) than rural (13.4%) residents with insomnia symptoms had significantly higher treatment rates (χ 2=14.9, P<0.001). Multiple regression analyses showed that depressive symptoms, old age, and low education level were the most common risk factors for insomnia symptoms in both urban and rural residents. CONCLUSION: Our findings show that the prevalence of insomnia symptoms was relatively lower in rural than urban residents. Longitudinal studies are warranted to confirm the current findings.

Gender differences in the prevalence and clinical correlates of sleep disturbance in general hospital outpatients.

This study investigated gender differences in the prevalence of sleep disturbance and related demographic and clinical characteristics, including quality of life (QOL), in Chinese outpatients. Up to 4399 adult outpatients (2896 females, 1503 males) who visited the neurological, cardiovascular, gastrointestinal, and gynaecological outpatient clinics in four general hospitals were recruited. Demographic and clinical data including QOL were collected by using self-report questionnaires. The prevalence of sleep disturbance in female outpatients (671/2896, 23.2%) was significantly higher than in male outpatients (302/1503, 20.1%) and remained significant after adjusting for significant confounders in the regression analysis. In the regression analysis, divorced/widowed and unemployed status were independently associated with a higher frequency of sleep disturbance in females, while educational level was independently associated with males only. Among these factors, depressive symptoms and older age were the most common risk factors for sleep disturbance in both genders. Sleep disturbance was not associated with the mental domains of the QOL assessments in both genders. This study suggests that sleep disturbance is more frequent in female outpatients and is associated with multiple factors in both genders. A longitudinal study is warranted to confirm the current findings.

Prevalence of insomnia symptoms and their associated factors in patients treated in outpatient clinics of four general hospitals in Guangzhou, China.

BACKGROUND: Data on the prevalence of insomnia symptoms in medical outpatient clinics in China are lacking. This study examined the prevalence of insomnia symptoms and their socio-demographic correlates in patients treated at medical outpatient clinics affiliated with four general hospitals in Guangzhou, a large metropolis in southern China. METHOD: A total of 4399 patients were consecutively invited to participate in the study. Data on insomnia and its socio-demographic correlates were collected with standardized questionnaires. RESULTS: The prevalence of any type of insomnia symptoms was 22.1% (95% confidence interval (CI): 20.9-23.3%); the prevalence of difficulty initiating sleep was 14.3%, difficulty maintaining sleep was 16.2%, and early morning awakening was 12.4%. Only 17.5% of the patients suffering from insomnia received sleeping pills. Multiple logistic regression analysis revealed that male gender, education level, rural residence, and being unemployed or retired were negatively associated with insomnia symptoms, while lacking health insurance, older age and more severe depressive symptoms were positively associated with insomnia symptoms. CONCLUSIONS: Insomnia symptoms are common in patients attending medical outpatient clinics in Guangzhou. Increasing awareness of sleep hygiene measures, regular screening and psychosocial and pharmacological interventions for insomnia are needed in China. TRIAL REGISTRATION: ChiCTR-INR-16008066 . Registered 8 March 2016.

Association of sleep duration with sleep disturbances, quality of life, and sociodemographic factors in general hospital outpatients.

PURPOSE: To examine sleep duration and its demographic and clinical correlates in patients attending outpatient clinics attached to general hospitals. DESIGN AND METHODS: A total of 4,399 outpatients participated in the study. Sleep duration (short sleep, <7 h/day; long sleep, >8 h/day; and medium sleep, 7-8 h/day) was assessed. FINDINGS: The proportions of short and long sleep duration were 39.5% and 10.3%, respectively. Significant associations between short sleep and any type of sleep disturbances, age, education level, depressive symptoms, and rural residence were found. Long sleep was associated with age, education level, being unemployed, and depressive and anxiety symptoms. PRACTICE IMPLICATIONS: Short sleep duration is common among Chinese general hospital outpatients. Due to its negative effects, screening and interventions for short sleep are needed in this population.

Major depressive disorder and suicide risk among adult outpatients at several general hospitals in a Chinese Han population.

BACKGROUND: Somatic complaints are often the presenting symptoms of major depressive disorder (MDD) in the outpatient context, because this may go unrecognized. It is well understood that MDD carries an increased risk of suicide. This study aimed to identify the risk factors and association with both MDD and suicidality among Han Chinese outpatients. METHODS: A multicenter study was carried out in 5189 outpatient adults (≥18 years old) in four general hospitals in Guangzhou, China. The 1392 patients who had the Patient Health Questionnaire-9 (PHQ-9) score ≥ 5, indicating depressive symptoms were offered an interview with a psychiatrist by the Mini International Neuropsychiatric Interview (MINI); 819 patients consented and completed the MINI interview. MINI module B was used to assess suicidality. Stepwise binary logistic models were used to estimate the relationship between a significant risk factor and suicide or MDD. According to with or without MDD, the secondary analysis was performed using the logistic regression model for the risk of suicidility. RESULTS: The current prevalence of MDD and the one month prevalence of suicidality were 3.7% and 2.3% respectively. The odds ratio of suicidality in women was more than twice that in men (OR = 2.62; 95% CI 1.45-4.76). Other risk factors which were significantly associated with suicidality were: living alone, higher education, self-reported depression, getting psychiatric diagnoses (MDD, anxiety disorders, and bipolar disorders). Significant risk factors for MDD were also noticed, such as comorbid anxiety disorders, self-reported anxiety, insomnia, suicidal ideation. LIMITATION: It's a cross-sectional study in outpatient clinics using self-report questionnaires. CONCLUSION: This study provides valuable data about the risk factors and association of MDD and suicide risk in adult outpatients in Han Chinese. Those factors allow better the employment of preventative measures.

1H-proton magnetic resonance spectroscopy differentiates dementia with Lewy bodies from Alzheimer's disease.

FDG-PET and SPECT studies suggest that hypometabolism and hypoperfusion in occipital lobe and posterior cingulate gyrus (PCG) are prominent features of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), respectively. Cerebral blood flow and glucose metabolism are tightly linked to brain energy metabolism. 1H-MRS is a useful tool to directly detect energy metabolism. We aimed to use 1H-MRS to characterize metabolite concentrations in the occipital lobe and PCG in DLB and AD patients, and estimate their usefulness in the diagnosis of DLB. Nineteen DLB, 21 AD, and 18 normal control (NC) subjects underwent 1H-MRS with the voxels placed in bilateral occipital lobes and left PCG. The N-acetylaspartate (NAA) and glutamate (Glu) concentrations in occipital lobe in DLB were lower than those in AD and NC. Concentrations of these two metabolites in PCG in DLB were lower than those in NC, and were the same as those in AD. These results remained robust after correcting for relative gray matter volume in the region of interest. The NAA and Glu concentrations in occipital lobe in DLB were found correlated with global cognitive function. From the ROC curves with Glu concentrations in occipital lobe, the mean areas under the curve were 0.845 for the DLB/control (with sensitivity 83.3% and specificity 84.2%) and 0.773 for the DLB/AD (with sensitivity 66.7% and specificity 84.2%). Our study suggests that 1H-MRS investigation is valuable to detect the characteristic patterns of metabolite concentrations and is helpful in the diagnostic process and assessing dementia severity in DLB.

CSF levels of the neuronal injury biomarker visinin-like protein-1 in Alzheimer's disease and dementia with Lewy bodies.

The overlapping clinical features of Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB) make differentiation difficult in the clinical environment. Evaluating the CSF levels of biomarkers in AD and DLB patients could facilitate clinical diagnosis. CSF Visinin-like protein-1 (VILIP-1), a calcium-mediated neuronal injury biomarker, has been described as a novel biomarker for AD. The aim of this study was to investigate the diagnostic utility of CSF VILIP-1 and VILIP-1/Aß1-42 ratio to distinguish AD from DLB. Levels of CSF VILIP-1, t-tau, p-tau181P , Aß1-42 , and α-synuclein were measured in 61 AD patients, 32 DLB patients, and 40 normal controls using commercial ELISA kits. The results showed that the CSF VILIP-1 level had significantly increased in AD patients compared with both normal controls and DLB patients. The CSF VILIP-1 and VILIP-1/Aß1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. Additionally, CSF VILIP-1 levels were positively correlated with t-tau and p-tau181P within each group and with α-synuclein in the AD and control groups. We conclude that CSF VILIP-1 could be a diagnostic marker for AD, differentiating it from DLB. The analysis of biomarkers, representing different neuropathologies, is an important approach reflecting the heterogeneous features of AD and DLB. Neuronal Ca(2+) -sensor protein VILIP-1 has been implicated in the calcium-mediated neuronal injury and pathological change of AD. The CSF VILIP-1 and VILIP-1/Aß1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. CSF VILIP-1 is a useful biomarker for AD. Evaluating the CSF levels of VILIP-1 in AD and DLB patients could facilitate clinical diagnosis.

Alterations of CSF cystatin C levels and their correlations with CSF Αß40 and Αß42 levels in patients with Alzheimer's disease, dementia with lewy bodies and the atrophic form of general paresis.

Immunohistochemical studies have revealed that cystatin C (CysC) co-localizes with amyloid-ß (Αß) in amyloid-laden vascular walls and in the senile plaque cores of amyloid. In vitro and in vivo animal studies suggest that CysC protects against neurodegeneration by inhibition of cysteine proteases, inhibition of Αß aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aß levels in various types of dementia with characteristic amyloid deposits, such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and the atrophic form of general paresis (AF-GP). We assessed the serum and CSF levels of CysC and the CSF levels of Aß40 and Aß42 in patients with AD (n = 51), DLB (n = 26) and AF-GP (n = 43) and normal controls (n = 30). Using these samples, we explored the correlation between CSF CysC and CSF Aß levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aß42 levels were significantly lower in all three dementia groups (all p<0.001); serum CysC levels were the same in the AD and DLB groups, and were lower in the AF-GP group (p = 0.008). The CSF CysC levels were positively correlated with both the CSF Aß40 and Aß42 levels in the AD, AF-GP and normal control groups (r = 0.306∼0.657, all p<0.05). Lower CSF CysC levels might be a common feature in dementia with characteristic amyloid deposits. Our results provide evidence for the potential role of CysC involvement in Aß metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.