Cannabis use Disorder and Complications After Anterior Cervical Diskectomy and Fusion.

OBJECTIVE: The aim of this study, a retrospective database analysis, was to assess the impact of baseline cannabis use disorder (CUD) on perioperative complication outcomes in patients undergoing primary 1- to 2-level anterior cervical diskectomy and fusion (ACDF) surgery. METHODS: The PearlDiver Database was queried from January 2010 to December 2021 for patients who underwent primary 1- to 2-level ACDF surgery for degenerative spine disease. Patients with CUD diagnosis 6 months before the index ACDF surgery (i.e., CUD) were propensity matched with patients without CUD (i.e., control in a ratio of 1:1, employing age, gender, and Charlson Comorbidity Index as matching covariates). Univariate and multivariable analysis models with adjustment of confounding variables were used to evaluate the risk of CUD on perioperative complications between the propensity-matched cohorts. RESULTS: The 1:1 matched cohort included 838 patients in each group. Following multivariate analysis, CUD was demonstrated to be associated with an increased incidence of hospital readmission at 90 days (odds ratio [OR] = 2.64, 95% confidence interval: [1.19 to 6.78], [P = 0.027]) and revision surgery at 1 year postoperative (OR = 3.36, 95% confidence interval: [1.17 to 14.18], [P = 0.049]). CUD was additionally associated with reduced risk of overall medical complications at both 6 months and 1 year postoperative (OR = 0.55, [P = 0.021], and OR = 0.54, [P = 0.015], respectively). CONCLUSIONS: These findings indicate that isolated baseline CUD is associated with an increased risk of hospital readmission at 90 days postoperative and cervical spine reoperation at 1 year after primary 1- to 2-level ACDF surgery with a decrease in overall medical complications, cardiac arrhythmias, and acute renal failure.

Postoperative complications following Schwab-grade-I versus Schwab-grade-II PCO in treating severe rigid kyphoscoliosis patients: comparative matched-group outcomes with minimum 2-year follow-up.

BACKGROUND CONTEXT: Standard partial facetectomies, (Smith-Petersen Osteotomy, (SPO), (Schwab-grade-I) and complete facet resection also known as Ponte osteotomy, (PO), (Schwab-grade-II) are narrowly akin and collectively appreciated as posterior column shortening osteotomies (PCOs). The former is considered a gentler osteotomy grade than the latter. The spine literature provides very little information on their comparison regarding perioperative complications and major curve correction rate outcomes. PURPOSE: To determine whether Schwab-grade-I PCO (SPO) and Schwab-grade-II PCO (PO) are comparably safe in the surgical management of severe rigid scoliosis or kyphoscoliosis patients. STUDY DESIGN/SETTING: Retrospective single-center comparative clinical study. PATIENT SAMPLE: A total of 38 patients with severe rigid scoliosis or kyphoscoliosis were propensity score matched in this study, (SPO-treated); n=21 (55.30%) and (PO-treated); n=17 (44.70%), who underwent primary spinal deformity corrective surgery, respectively. OUTCOME MEASURES: Outcomes included demographics, baseline pulmonary functional outcomes, perioperative complications incidence, hospital costs, Oswestry disability index (ODI), and the Scoliosis Research Society-22 (SRS-22) questionnaire scores. METHODS: Following approval by the Institutional Review Board (IRB) of Beijing Chaoyang Hospital-Affiliated Capital Medical University in Beijing, out of a total of 82 consecutive surgical patients with complete data demonstrating severe and/or rigid spinal deformity, a pool of 38 of the 82 (46.3%) propensity-matched adult (≥18 years) patients with severe rigid scoliosis or kyphoscoliosis defined with a preoperative major curve magnitude of ≥80° on anteroposterior plain radiographs, and flexibility of <25% on bending plain radiographs who underwent primary spinal deformity corrective surgery were retrospectively evaluated. The patients were dichotomized into two osteotomy groups: standard (partial) facetectomy (SPO-treated), n=21 with an average age of 24.67 years, (Schwab-grade-I PCO) and complete facet excision, (PO-treated), (ie, Schwab-grade-II PCO), n=17 with an average age of 23.12 years. The minimum follow-up period was 2 years. Primary outcomes included baseline demographics and clinical features. Secondary outcomes included perioperative [intraoperative, immediate, and 2-year postoperative] complication rates. Tertiary outcomes included perioperative ODI and SRS-22 scores. Statistical analyses were carried out by Student t-test and Pearson's Chi-square test (Fisher's Exact Test), through Python statistical software package. Statistical significance was set at (p<.05). RESULTS: Of the 38 matched severe rigid scoliosis or kyphoscoliosis patients, 55.30% (n=21) were SPO-treated and 44.70% (n=17) were PO-treated patients, respectively. The overall average age of patients was 23.97 years, with a female incidence of 76.32%. Major curve correction rates were 49.19% and 57.40% in SPO-treated and PO-treated patients, respectively, (p>.05). Immediately following surgery, comparable overall complication rates of 28.57% (n=6/21) versus 29.41% (n=5/17) were observed in the SPO-treated and PO-treated patients, respectively, (p=.726). We observed incidences of 9.52%, (n=2/21) versus 5.88%, (n=1/17) for surgical intensive care unit (SICU) admission, and incidences of 4.76%, (n=1/21) versus 5.88%, (n=1/17) for cardiopulmonary events in SPO-treated versus PO-treated patients following corrective surgery, respectively, (p>.05). The incidences of neurological deficits in the SPO-treated and PO-treated patients were respectively, 14.29%, (n=3/21) versus 17.65%, (n=3/17) immediately following surgery, (p>.05), and 0.00%, (n=0/21) in SPO-treated versus 14.28%, (n=3/21) in PO-treated patients at ≥2 years postoperative, (p<.05). Among the three patients that reported neurological deficits in the PO-treated group at ≥2 years postoperative, two patients had pre-existing baseline neurological deficits. The ODI score in the PO-treated group was significantly inferior at a minimum 2-year follow-up, (p<.05). CONCLUSIONS: In the current study, both SPO-treated and PO-treated patients demonstrated statistically comparable surgical complications immediately following corrective surgery. Severe rigid kyphoscoliosis patients with preexisting baseline neurological deficits were more inclined to sustain neurological morbidity following corrective surgery. PCO corrective techniques are warranted as safe options for treating patients with severe rigid spine deformity phenotypes.

Efficacy and Clinical Outcomes of Minimally Invasive Direct Thoracic Interbody Fusion: A Retrospective Analysis.

INTRODUCTION: A unique surgical approach - the minimally invasive direct interbody fusion (MIS-DTIF) - was previously introduced in our proof-of-concept study, which included four patients who underwent thoracic interbody fusion below the scapula at the T6/7 vertebral level. However, due to the novelty of this method, a report of associated operative parameters such as pain, function, and clinical outcomes from an expanded patient cohort was needed to assess the validity of our results. MATERIALS AND METHODS: Following IRB approval, data were analyzed retrospectively from electronic health records between 2014 and 2021. Inclusion criteria were patients ≥18 years old who underwent minimally invasive thoracic interbody fusion using the MIS-DTIF technique for at least one vertebral level. The primary outcomes included demographic/radiographic features (e.g., age). Secondary outcomes included perioperative clinical features (e.g., preoperative and ≥1-year final follow-up (FFU)). Tertiary outcomes included perioperative complications. Both preoperative and FFU patient-reported pain and functional outcomes (ODI scores) were analyzed using t-tests to establish significance.  Results: A total of 13 patients who underwent MIS-DTIF surgery were observed, with eight male patients and five female patients. The average age was 49.2 years, with an average BMI of 30.5 kg/m2. Of the surgeries included, the majority (69.23%) were 1-level thoracic vertebrae fusions - with 2-level fusions and ≥ 3-level fusions accounting for 15.38% and 15.38% of cases, respectively. The mean operative time was 58.9 ± 19.9 minutes, with an average fluoroscopy time of 285.7 ± 126.8 seconds and an average actual blood loss volume of 109.0 ± 79.0 mL. The average hospital length of stay was 1.1 (±1.7) days, and no clinically significant perioperative complications were observed in this patient cohort. The average follow-up period was 12.1 ± 9.6 months, with preoperative and FFU back pain visual analog scale (VAS) scores showing highly significant improvement (p<0.001). In addition to pain reduction, quality of life improvements was noted, with significant differences in some of the ODI domains between preoperative and FFU scores (p<0.05), as well as the overall total score between preoperative and FFU ODI assessment (p<0.001) - both of which reflect increased patient function and decreased disability. CONCLUSION: This study provides further evidence for the safety and efficacy of the MIS-DTIF approach for surgical management of symptomatically refractory patients with thoracic disc herniation or stenosis owing to degenerative disc disease or compression fractures. Additionally, the data gathered suggests that this minimally invasive procedure offers many clinical benefits, including less tissue damage, decreased intraoperative blood loss, shortened surgery time, and shortened hospital length of stay. Finally, in addition to significant pain intensity improvement, this study showed that treated patients highly benefited from 'sleeping' and 'return-to-work' domains and other ODI functional domains in activities of daily living (ADLs). More clinical studies are recommended in larger patient cohorts to ascertain the findings reported in this study.

Comparison of Overall Complication Rates in VCR-Based vs Non-VCR-Based Corrective Techniques in Severe Rigid Kyphoscoliosis Patients: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Compilation of complication outcomes data from the surgical management of severe rigid kyphoscoliosis patients using VCR-based vs non-VCR-based corrective maneuvers is lacking. This meta-analysis aimed to compare complication outcomes between those classified osteotomy approaches. METHODS: Thorough literature review and meta-analysis were conducted between January 2000 and September 2021. The selection criteria were studies: i) reporting major curve Cobb angle of ≥80° and flexibility of <25% or 30%; ii) comparing VCR or ≥ Type V Schwab osteotomy defined as VCR-based vs [non-VCR-based] techniques, (any osteotomy or technique other than VCR); iii) published in English with ≥10 patients; iv) reporting complication rates; and v) having minimum of 2-year follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Significance level was set at (P < .05). RESULTS: Of the 174 patients included, 52.30% (n = 91) and 47.70% (n = 83) were VCR-based and non-VCR-based, respectively. The incidence of dural tears/nerve injuries/significant intraoperative-neuromonitoring changes was significantly higher; [OR = 6.78, CI= (1.75 to 26.17), I2 = 0%, (P = .006)] in the VCR-based group than the non-VCR-based group. The 'overall surgical and medical' complication rate was significantly higher in the VCR-based group, [OR = 1.94, CI= (1.02 to 3.67), I2 = 31%, (P = .04)]. CONCLUSION: Both VCR-based and non-VCR-based surgical techniques for management of severe rigid scoliosis and kyphoscoliosis patients pose comparable overall surgical complication rates, while a significantly higher perioperative neurological complication incidence was associated with VCR-based technique compared to the non-VCR-based techniques. The VCR-based technique was associated with 6.78 times higher incidence of neurological complications compared to non-VCR-based techniques.

Discrepant modulating effects of dietary docosahexaenoic acid on cerebral lipids, fatty acid transporter expression and soluble beta-amyloid levels in ApoE-/- and C57BL/6J mice.

AIMS: The study was designed to explore the role of apolipoprotein E (ApoE) deficiency concomitant with dietary docosahexaenoic acid (DHA) treatment on brain ß-amyloid (Aß) and lipid levels. METHOD: A 5-month dietary DHA intervention was conducted in ApoE-deficient (ApoE-/- ) mice and wild-type C57BL/6J (C57 wt) mice. The Morris water maze test was performed to assess the behaviour of the animals. The cortical contents of soluble Aß1-40 and Aß1-42 were detected by enzyme-linked immunosorbent assay (ELISA). Cortical fatty acid levels were detected by gas chromatography. Gene and protein expression of molecules associated with cerebral Aß and lipid metabolism were measured using real-time polymerase chain reaction (PCR), Western blot and histological methods. RESULTS: DHA treatment increased the content of cortical DHA and n-3 polyunsaturated fatty acids (n-3 PUFAs) but decreased the ratio of n-6/n-3 PUFAs in ApoE-/- mice; whereas the content of cortical DHA and n-3 PUFAs in C57 wt mice remained unchanged after DHA treatment. Cerebral Fabp5 and Cd36 gene expression were significantly downregulated in DHA-fed C57 wt mice; cerebral Cd36 and Scarb1 gene expression were significantly upregulated, whereas Fabp5 gene expression was downregulated in DHA-fed ApoE-/- mice. In comparison with C57 wt mice, the content of cortical soluble Aß1-42 , total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased, whereas the level of high-density lipoprotein cholesterol (HDL-C) decreased in ApoE-/- mice. Interestingly, these differences were significantly reversed by DHA dietary treatment. CONCLUSION: DHA intervention has discrepant impacts on cerebral lipids, fatty acid transporter expression and soluble Aß levels in ApoE-/- and C57 wt mice, suggesting the modifying role of ApoE status on the responses of cerebral lipids and Aß metabolism to DHA treatment.

Effects of distinct n-6 to n-3 polyunsaturated fatty acid ratios on insulin resistant and AD-like phenotypes in high-fat diets-fed APP/PS1 mice.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are prevalent diseases with similar pathophysiological characteristics and genetic predispositions. Polyunsaturated fatty acids (PUFAs) are essential in maintaining normal brain function. However, little is known about the effect of dietary n-6/n-3 PUFA ratio on AD-like pathology, particularly in high-fat diet (HFD)-fed AD model mice. In the present study, the APP/PS1 mice were fed with 60 % HFD for 3.5 months to induce insulin resistance. After that, 45 % HFD with various n-6/n-3 PUFA ratios (n-6/n-3 = 1:1, 5:1 or 16:1) was applied for an additional 3.5 months of treatment. The behavior of mice was observed using the water maze after dietary intervention. The animals were euthanized after behavioral testing, and serum and tissue samples were collected for biochemical, histological, and pathological tests and evaluation. HFD caused insulin resistance, increased serum IL-6 and TNF-α levels, cortical soluble Aß1-40, Aß1-42 content, and cortical n-6/n-3 PUFA ratio in APP/PS1 mice. Increased APP and BACE1 protein expression and p-IR/IR ratio but decreased pro-inflammatory cytokines mRNA expression was detected in the cortex of 60 % HFD-fed APP/PS1 mice. N-3 PUFAs-rich diet (n-6/n-3 = 1:1) alleviated insulin resistance and hyperlipidemia caused by 60 % HFD. Cortical soluble Aß1-40 and Aß1-42 contents, as well as the expression of cortical APP, GLUT1, GLUT3, insulin metabolism-related molecules, and NF-κB pathway downstream pro-inflammatory cytokines, were found to be n-6/n-3 PUFAs ratio-dependent, indicating that dietary n-6/n-3 PUFA ratio plays a critical role in modifying the responses of serum inflammatory cytokines, AD pathology, cortical n-6/n-3 PUFAs ratio, insulin signaling, and neuroinflammation to HFD treatment.

Study on the Association of Dietary Fatty Acid Intake and Serum Lipid Profiles With Cognition in Aged Subjects With Type 2 Diabetes Mellitus.

Background: The correlation between dietary fatty acid (FA) intake and serum lipid profile levels with cognition in the aged population has been reported by previous studies. However, the association of dietary FA intake and serum lipid profile levels with cognition in subjects with type 2 diabetes mellitus (T2DM) is seldom reported. Objective: A cross-sectional study was conducted to explore the correlation between dietary FA intake and serum lipid profiles with cognition in the aged Chinese population with T2DM. Methods: A total of 1,526 aged Chinese subjects were recruited from communities. Fasting blood samples were collected for parameter measurement. The food frequency questionnaire (FFQ) method was applied for a dietary survey. Cognition was assessed using the Montreal Cognitive Assessment (MoCA) test. Dietary FA intake and serum lipid levels were compared between subjects with T2DM and control subjects. A logistic regression analysis was carried out for analyzing the association of FA intake and serum lipid levels with the risk of mild cognitive impairment (MCI) in subjects with T2DM and control subjects. Results: There was a significant difference in the serum lipid level between the T2DM group and the control group. Results of the logistic regression analysis demonstrated the potential associations of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and dietary n-3 polyunsaturated fatty acids (PUFAs) intake with the risk of MCI in subjects with T2DM, but the associations were not observed in control subjects. Conclusion: The T2DM phenotype might affect the relationship between dietary FA intake, circulating lipids, and cognitive performance. Large prospective cohort studies are needed to uncover the underlying mechanism of how dietary FA intake and serum lipid levels affect cognition in aged subjects with T2DM.

Comparison of reference distributions acquired by direct and indirect sampling techniques: exemplified with the Pediatric Reference Interval in China (PRINCE) study.

BACKGROUND: Our study aimed to compare the reference distributions of serum creatinine and urea obtained by direct sampling technique and two indirect sampling techniques including the Gaussian Mixture Model (GMM) and the Self-Organizing Map (SOM) clustering based on clinical laboratory records, so that the feasibility as well as the potential limitations of indirect sampling techniques could be clarified. METHODS: The direct sampling technique was used in the Pediatric Reference Interval in China (PRINCE) study, in which 15,150 healthy volunteers aged 0 to 19 years were recruited from 11 provinces across China from January 2017 to December 2018. The indirect sampling techniques were used in the Laboratory Information System (LIS) database of Beijing Children's Hospital, in which 164,710 outpatients were included for partitioning of potential healthy individuals by GMM or SOM from January to December 2016. The reference distributions of creatinine and urea that were established by the PRINCE study and the LIS database were compared. RESULTS: The density curves of creatinine and urea based on the PRINCE data and the GMM and SOM partitioned LIS data showed a large overlap. However, deviations were found in reference intervals among the three populations. CONCLUSIONS: Both GMM and SOM can identify potential healthy individuals from the LIS data. The performance of GMM is consistent and stable. However, GMM relies on Gaussian fitting, and thus is not suitable for skewed data. SOM is applicable for high-dimensional data, and is adaptable to data distribution. But it is susceptible to sample size and outlier detection strategy.

Association Between ApoE Status, Circulating Vitamin A and Vitamin E Levels with Dyslipidemia in Aging Adults.

BACKGROUND: The influence of ApoE or lipid-soluble vitamins on lipid profile has been well documented. However, the association between ApoE status, vitamin A (VA) and vitamin E (VE) with dyslipidemia has been seldom reported. The aim of the present study was to investigate the impact of ApoE status on circulating VA and VE in aging adults with dyslipidemia. METHODS: A total of 1754 Chinese aged 55-75 was recruited from community health centers. They were interviewed to obtain demographic information. Food frequency questionnaire (FFQ) was used to investigate daily food intakes of the participants. Fasting venous blood samples were taken and used for serum lipid profile measurement and ApoE genotyping. Serum VA and VE concentrations were determined by using high-performance liquid chromatography (HPLC). RESULTS: Serum VE and VA concentrations were circulating lipids and ApoE status dependent. Dyslipidemia subjects showed higher serum TC, TG, HDL-c/LDL-c ratio, VE and lipid-adjusted VE levels than normal subjects. ApoE genotype-dependent differences in serum lipid profile, VE and VA levels were observed in both normal and dyslipidemia subjects. The relationship between circulating VA with dyslipidemia is modifiable by lipid status. CONCLUSION: Higher serum VE and lipid adjusted VE levels associated with increased risk of dyslipidemia in aging Chinese adults, especially in ApoE4 carriers. Large scale longitudinal study is required to determine the optimal circulating VE levels in the elderly based on different lipid profiles and ApoE status.

Clinical Effectiveness of Interlaminar Epidural Injections of Local Anesthetic with or without Steroids for Managing Chronic Neck Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic neck pain is reportedly considered the fourth leading cause of disability. Cervical interlaminar epidural injections are among the commonly administered nonsurgical interventions for managing chronic neck pain, secondary to disc herniation and radiculitis, spinal stenosis, or chronic neck pain of discogenic origin. OBJECTIVES: To systematically review the differences in the effectiveness of cervical epidural injections with local anesthetics with or without steroids for the management of chronic neck pain. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive search of the literature of randomized controlled trials (RCTs) that compared epidural injections with local anesthetic with or without steroids was performed, including a search of PubMed, EMBASE, and Cochrane databases for all years up to May 2019. Meta-analysis was done for pain relief based on the Numeric Rating Scale, functional status based on the Neck Disability Index, and opioid intake dosage. RESULTS: Four studies met the inclusion criteria. A total of 370 patients were divided into 2 groups: the experimental group received cervical epidural injection with steroid and local anesthetic, and the control group received injection with local anesthetic only. Regrading pain relief, no significant difference was observed between both groups (weighted mean difference [WMD], -0.006; 95% confidence interval (CI), -0.275 to 0.263; P = 0.963; I² = 0.0% at 12 months). There was also no significant difference in the improvement of the functional status (WMD, 0.159; 95% CI, -1.231 to 1.549; P = 0.823; I² = 9.8% at 12 months). Similarly, there was no significant difference in opioid dosage (WMD, -0.093; 95% CI, -5.952 to 5.766; P = 0.975; I² = 0.0% at 12 months). LIMITATIONS: Only a few studies on this premise were found in the literature. There was also a lack of heterogeneity of the included RCT studies. CONCLUSIONS: The addition of steroids to anesthetic injectates was not associated with better pain and functional score outcomes compared with anesthetic injectate alone in patients with chronic neck pain. KEY WORDS: Chronic neck pain, cervical radiculopathy, cervical disc disease, spinal stenosis, facet joint pathology, cervical epidural injections, steroid injections, local anesthetic injections, systematic review, meta-analysis, randomized control trial.

PDZ Scaffold Protein CAL Couples with Metabotropic Glutamate Receptor 5 to Protect Against Cell Apoptosis and Is a Potential Target in the Treatment of Parkinson's Disease.

Targeting mGluR5 has been an attractive strategy to modulate glutamate excitotoxicity for neuroprotection. Although human clinical trials using mGluR5 negative allosteric modulators (NAMs) have included some disappointments, recent investigations have added several more attractive small molecules to this field, providing a promise that the identification of more additional strategies to modulate mGluR5 activity might be potentially beneficial for the advancement of PD treatment. Here, we determined the role of the interacting partner CAL (cystic fibrosis transmembrane conductance regulator-associated ligand) in mGluR5-mediated protection in vitro and in vivo. In astroglial C6 cells, CAL deficiency blocked (S)-3, 5-dihydroxyphenylglycine (DHPG)-elicited p-AKT and p-ERK1/2, subsequently prevented group I mGluRs-mediated anti-apoptotic protection, which was blocked by receptor antagonist 1-aminoindan-1, 5-dicarboxylic acid (AIDA), and PI3K or MEK inhibitor LY294002 or U0126. In rotenone-treated MN9D cells, both CAL and mGluR5 expressions were decreased in a time- and dose-dependent manner, and the correlation between these 2 proteins was confirmed by lentivirus-delivered CAL overexpression and knockdown. Moreover, CAL coupled with mGluR5 upregulated mGluR5 protein expression by inhibition of ubiquitin-proteasome-dependent degradation to suppress mGluR5-mediated p-JNK and to protect against cell apoptosis. Additionally, CAL also inhibited rotenone-induced glutamate release to modulate mGluR5 activity. Furthermore, in the rotenone-induced rat model of PD, AAV-delivered CAL overexpression attenuated behavioral deficits and dopaminergic neuronal death, while CAL deficiency aggravated rotenone toxicity. On the other hand, the protective effect of the mGluR5 antagonist MPEP was weakened by knocking down CAL. In vivo experiments also confirmed that CAL inhibited ubiquitination-proteasome-dependent degradation to modulate mGluR5 expression and JNK phosphorylation. Our findings show that CAL protects against cell apoptosis via modulating mGluR5 activity, and may be a new molecular target for an effective therapeutic strategy for PD.

DHA and vitamin E antagonized the Aß25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells.

The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 µmol L-1 Aß25-35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets' gene and protein expression. Our results indicated that the Aß25-35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aß25-35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aß25-35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aß25-35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.

Short-term PM10 and emergency department admissions for selective cardiovascular and respiratory diseases in Beijing, China.

BACKGROUND: Few studies have explored PM10's connection with specific respiratory and cardiovascular emergency department admissions (EDAs). This study aimed to examine the overall effects of PM10 on EDAs for cardiovascular and respiratory diseases, including specifically, cerebrovascular events (CVE), ischemic heart disease (IHD), arrhythmia, heart failure (HF), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), chronic obstructive pulmonary disease (COPD) and asthma. METHODS: We collected daily data for EDAs from the 10 largest hospitals in Beijing, between January 2013 and December 2013 as well as daily measurements of PM10 from 17 stations in Beijing. The generalized-additive model was utilized to evaluate the associations between daily PM10 and cardio-pulmonary disease admissions. Differences in gender, age, and season groups were also examined by models. Relative risks (RR) with 95% confidence interval (CI) were calculated based on subtype, age, gender and seasonal groups. In all, there were approximately 56,212 cardiovascular and 92,464 respiratory emergency admissions presented in this study. RESULTS: The largest estimate effects in EDAs of total cardiovascular disease, CVE, IHD, total respiratory diseases, URTI, LRTI and COPD were found for PM10 at day 4 (accumulative) moving average, were 0.29% (95% CI:0.12%, 0.46%), 0.36% (95% CI:0.11%, 0.61%), 0.68% (95% CI:0.25%, 1.10%), 0.34% (95% CI:0.22%, 0.47%), 0.35% (95% CI:0.18%, 0.51%), 0.34% (95% CI:0.14%, 0.55%), 2.75% (95% CI:1.38%, 4.12%) respectively. In two-pollutant models and full-pollutant model modified confounding factors, the positive correlation remained unchanged. The elderly (age ≥ 65 years) and male subjects were more susceptible to specific respiratory diseases. PM10's impact on EDAs for HF was found higher during the hot season however, EDAs for COPD peaked during the cold season. CONCLUSION: The study markedly informed that PM10 pollution was strongly associated with EDAs for cardio-pulmonary diseases. The effects of PM10 pollution on COPD and heart failure EDAs were clearly determined by seasonal-temperatures.

Diminished circulating retinol and elevated α-TOH/retinol ratio predict an increased risk of cognitive decline in aging Chinese adults, especially in subjects with ApoE2 or ApoE4 genotype.

OBJECTIVE: The current study evaluated the relationship between circulating fat soluble vitamin status and cognition in aging Chinese population. METHODS: A cross-sectional study was carried out in 1754 community residents aged 55-80 years aiming to evaluate the relationship between circulating α-tocopherol and retinol status and cognition. The effect of ApoE genetic polymorphism on the relationship between vitamins and cognition was also explored. RESULTS: Our results indicated that serum retinol status positively correlated with cognitive performance; while, serum α-tocopherol (α-TOH)/retinol ratio negatively correlated with cognitive performance. Mild cognitive impairment (MCI) subject demonstrated higher serum α-TOH status (P < 0.05), α-TOH/retinol ratio (P < 0.01) and lower retinol status (P < 0.01) than normal subjects. Subjects with ApoE4 genotype have lower serum retinol level (P < 0.05) and higher α-TOH/retinol ratio (P < 0.01) than subjects with ApoE3 genotype. MCI-ApoE4 carriers demonstrated the worst cognitive performance (P < 0.05) and exhibited higher serum TC, α-TOH and α-TOH/retinol ratio levels (P < 0.05), and lower LDL-C, retinol and lipid-adjusted retinol status (P < 0.05). MCI-ApoE2 subjects showed higher serum TC, HDL-C content and α-TOH/retinol ratio (P < 0.05); and lower serum retinol and lipid-adjusted retinol status (P < 0.05). CONCLUSION: Lower circulating retinol and higher α-TOH/retinol ratio potentially predicts an increased risk for the development of cognitive decline in aging Chinese adults. ApoE2 or E4 carriers with higher circulating α-TOH/retinol ratio infer poor cognitive performance and an increased risk of developing MCI.

Brain Structure Alterations in Respect to Tobacco Consumption and Nicotine Dependence: A Comparative Voxel-Based Morphometry Study.

The main purpose of this study is to examine the lifetime tobacco consumption and the degree of nicotine dependence related gray matter (GM) and white matter (WM) volume alterations in young adult-male smokers. Fifty-three long-term male smokers and 53 well-matched male healthy non-smokers participated in the study, and the smokers were respectively categorized into light and heavy tobacco consumption subgroups by pack-years and into moderate and severe nicotine dependence subgroups using the Fagerström Test for Nicotine Dependence (FTND). Voxel-based morphometry analysis was then performed, and ANCOVA analysis combined with subsequent post hoc test were used to explore the between-group brain volume abnormalities related to the smoking amount and nicotine dependence. Light and heavy smokers displayed smaller GM and WM volumes than non-smokers, while heavy smokers were found with more significant brain atrophy than light smokers in GM areas of precuneus, inferior and middle frontal gyrus, superior temporal gyrus, cerebellum anterior lobe and insula, and in WM areas of cerebellum anterior lobe. However, the contrary trend was observed regarding alterations associated with severity of nicotine dependence. Severe nicotine dependence smokers rather demonstrated less atrophy levels compared to moderate nicotine dependence smokers, especially in GM areas of precuneus, superior and middle temporal gyrus, middle occipital gyrus, posterior cingulate and insula, and in WM areas of precuneus, posterior cingulate, cerebellum anterior lobe and midbrain. The results reveal that the nicotine dependence displays a dissimilar effect on the brain volume in comparison to the cigarette consumption. Our study could provide new evidences to understand the adverse effects of smoking on the brain structure, which is helpful for further treatment of smokers.

Dietary Vitamin E Status Dictates Oxidative Stress Outcomes by Modulating Effects of Fish Oil Supplementation in Alzheimer Disease Model APPswe/PS1dE9 Mice.

Quite a number of studies have examined the effects of fish oil supplementation on cognitive performance in different transgenic animal models of Alzheimer's disease (AD). However, inconsistent and controversial outcomes have been derived from these experiments. In order to investigate whether the beneficial effect of fish oil supplementation on cognition was dietary VE status associated, fish oil dietary intervention was carried out in transgenic APPswe/PS1dE9 (APP/PS1) mice. Control mice (C57BL/6J mice) were fed a normal control diet. APP/PS1 mice were assigned to a normal control diet group and low VE diet + fish oil supplement, normal VE diet + fish oil supplement, and high VE diet + fish oil supplement groups, respectively. After 7 months of dietary intervention, we found that fish oil supplementation improved behavioral performance, alleviated brain beta-amyloid (Aß) plaque burden, and attenuated the oxidative stress in APP/PS1 mice by increasing cortical GSH content and total antioxidant capacity, as well as by decreasing MDA level. Fish oil treatment increased cortical n-3 PUFA concentration and decreased n-6/n-3 PUFA ratio in APP/PS1 mice. Fatty acid transporters, Nrf2 and downstream targets involved in cortical and hippocampal antioxidant system were also modulated by fish oil-supplemented diet. Our data demonstrate that fish oil supplementation exerts an enhanced modulatory effect on the antioxidant system and fatty acid concentrations in APP/PS1 mice fed on lowly or averagely concentrated level of VE-containing diet than in mice fed with VE-rich diet. The current data do support previous findings that already dictate the beneficial effect of n-3 PUFAs on cognitive function. Moreover, the cognition promoting effects of n-3 PUFAs may be dietary VE status related.

Time-dependent depressive symptoms and risk of cardiovascular and all-cause mortality among the Chinese elderly: The Beijing Longitudinal Study of Aging.

BACKGROUND: Depressive symptoms tend to fluctuate over time. Data on the relationship between time-dependent depressive symptoms and the risk of cardiovascular and all-cause mortality among the elderly in China are lacking. METHODS AND RESULTS: A prospective cohort of 1999 subjects aged ≥55 years were enrolled in the Beijing Longitudinal Study of Aging since 1992. Depressive symptoms were assessed at baseline (0 years) and after 2, 5, 8, and 12 years, defined as a score of ≥16 on the 20-item Center for Epidemiological Studies Depression Scale. Mortality status was obtained from the local death registry until December 31st, 2012. Hazard ratio (HR) for all-cause mortality and sub-distribution HR (SHR) for cardiovascular mortality were respectively deduced from time-dependent Cox and competing risk models. During 19,658 person-years of follow-up, 1127 (55.65%) deaths were recorded, of which 483 (23.85%) were attributable to cardiovascular inclinations. Baseline depressive symptoms were neither associated with all-cause mortality (adjusted HR: 1.12, 95% confident interval, CI: 0.94-1.33) nor cardiovascular mortality (adjusted SHR: 1.10, 95% CI: 0.82-1.46) after adjustment of potential cardiac-risk factors. When depressive symptoms were used as time-dependent variable updated from 1992 to 2004, the associations were significant for both all-cause mortality (adjusted HR: 1.48, 95% CI: 1.26-1.73) and cardiovascular mortality (adjusted SHR: 1.40, 95% CI: 1.08-1.82) in the full adjusted model. CONCLUSIONS: Time-dependent depressive symptoms increased the risk of all-cause and cardiovascular mortality among the elderly in China.

The Role of ApoE Polymorphism in the Relationship between Serum Steroid Hormone Levels and Cognition in Older Chinese Adults: A Cross-Sectional Study.

BACKGROUND: Epidemiology studies have indicated an association of apolipoprotein E (ApoE) genetic polymorphism and circulating steroid hormone levels with the risk of Alzheimer's disease. The established physiologic relationship between apolipoproteins and steroid hormone indicate an important role of ApoE polymorphism in impacting the relationship between serum steroid hormones and cognition in the elderly. STUDY DESIGN: A total of 500 Chinese adults aged between 50 and 75 participated in this community-based cross-sectional study. Blood samples were collected in the morning for ApoE genotyping and serum parameter assessment. Cognitive performance of participants was evaluated by Montreal Cognitive Assessment test. RESULTS: Age, gender, educational level, smoking, and physical activity levels are factors associated with cognitive performance in this older Chinese adults. Compared to the control subjects, MCI subjects demonstrated higher serum total cholesterol, HDL-C, and estradiol status (P < 0.05). ApoE genotype difference of serum lipid profile was observed with a relatively higher mean serum triglyceride levels in ApoE2 and ApoE4 carriers (P < 0.05), and lower mean serum HDL-C level in ApoE4 carriers (P < 0.05). Memory and delayed recall ability was serum estradiol level related; and subjects with higher circulating estradiol concentration exhibited lower memory and delayed recall ability (P < 0.05). The association of serum estradiol and cortisol concentration with cognitive performance was ApoE genotypes dependent. Poor cognitive performance was observed in ApoE2 and ApoE4 carriers with higher serum estradiol level (P < 0.05). Moreover, ApoE2 and ApoE4 carriers with higher serum cortisol status demonstrated decreased language ability (P < 0.05). Multiple logistic regression analysis indicates that subjects with higher serum estradiol status may have an increased risk for MCI [OR = 2.004, 95% confidence interval (CI): 1.135, 3.540; P = 0.017]. ApoE2 carriers with higher serum steroid levels may be potentially predisposed to an increased risk of MCI (OR = 3.353; 95% CI: 1.135, 9.907; P = 0.029). CONCLUSION: Cognitive outcomes in older Chinese adults are associated with serum steroid hormone status. Higher serum steroid levels in ApoE2 carriers might pose an increased risk of MCI in the elderly.

The cold effect of ambient temperature on ischemic and hemorrhagic stroke hospital admissions: A large database study in Beijing, China between years 2013 and 2014-Utilizing a distributed lag non-linear analysis.

The effects of ambient temperature on stroke death in China have been well addressed. However, few studies are focused on the attributable burden for the incident of different types of stroke due to ambient temperature, especially in Beijing, China. We purpose to assess the influence of ambient temperature on hospital stroke admissions in Beijing, China. Data on daily temperature, air pollution, and relative humidity measurements and stroke admissions in Beijing were obtained between 2013 and 2014. Distributed lag non-linear model was employed to determine the association between daily ambient temperature and stroke admissions. Relative risk (RR) with 95% confidence interval (CI) and Attribution fraction (AF) with 95% CI were calculated based on stroke subtype, gender and age group. A total number of 147, 624 stroke admitted cases (including hemorrhagic and ischemic types of stroke) were documented. A non-linear acute effect of cold temperature on ischemic and hemorrhagic stroke hospital admissions was evaluated. Compared with the 25th percentile of temperature (1.2 °C), the cumulative RR of extreme cold temperature (first percentile of temperature, -9.6 °C) was 1.51 (95% CI: 1.08-2.10) over lag 0-14 days for ischemic type and 1.28 (95% CI: 1.03-1.59) for hemorrhagic stroke over lag 0-3 days. Overall, 1.57% (95% CI: 0.06%-2.88%) of ischemic stroke and 1.90% (95% CI: 0.40%-3.41%) of hemorrhagic stroke was attributed to the extreme cold temperature over lag 0-7 days and lag 0-3 days, respectively. The cold temperature's impact on stroke admissions was found to be more obvious in male gender and the youth compared to female gender and the elderly. Exposure to extreme cold temperature is associated with increasing both ischemic and hemorrhagic stroke admissions in Beijing, China.