Exposure to a mixture of metal(loid)s and sleep quality in pregnant women during early pregnancy: A cross-sectional study.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

The colossal role of H-MnO2-PEG in ischemic stroke.

Stroke is one of the most serious problems that seriously affect people's health and brings huge economic burden to society. The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In recent years, nano drug delivery system has developed rapidly and applied to treat ischemic stroke. Here, we report the synthesis and functionalization of monodisperse hollow structured MnO2 (H-MnO2). The highly monodisperse H-MnO2 with uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. After successive modification of poly ethylene glycol(PEG), we further verified their protective effect on ischemic stroke in our study.

Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway.

INTRODUCTION: Neuroinflammation and oxidative stress are major mechanisms of post-stroke cognitive impairment (PSCI) neural injury and decreased spatial and memory capacity. Enriched environment (EE) is an effective method to improve cognitive dysfunction. However, the regulation by EE of neuroinflammation, oxidative stress and associated mechanisms in animal models remains unclear. MATERIALS AND METHODS: In this study, a rat PSCI model was established by middle cerebral artery occlusion (MCAO). Rats were randomly divided into the control group, standard environment (SE) group and EE group for 28 days. A Morris water-maze test was used to measure cognitive function at 7, 14 and 28 days after MCAO. Rats were sacrificed on the 28th day. Quantitative PCR, immunohistochemistry and ELISA were respectively used to detect mRNA expression of NF-E2-related factor 2 (Nrf2) and Nrf2 response genes, the expression of IL-1ß and levels of proinflammatory cytokines in the hippocampus. RESULTS: EE improved mNSS scores and cognitive ability in PSCI rats. EE increased mRNA expression of the Nrf2 and Nrf2 response genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). EE significantly decreased the level of malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), in the hippocampus of PSCI rats. EE reduced the number of IL-1ß positive cells in the hippocampus, and IL-1ß levels in the hippocampus and serum. EE increased GFAP-positive astrocytes in the hippocampus, and BDNF levels in the hippocampus and serum. CONCLUSIONS: EE can improve cognitive function in PSCI rats by inhibiting neuroinflammation and oxidative stress.

Copeptin is associated with mortality in patients with traumatic brain injury.

BACKGROUND: High serum copeptin levels are associated with injury severity after traumatic brain injury (TBI). However, not much is known regarding its relation with mortality. Thus, we sought to evaluate its relation with disease mortality. METHODS: Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Twenty-six patients (27.7%) died from TBI in a month. After brain injury, plasma copeptin level in patients increased during the 6-hour period immediately, peaked in 24 hours, plateaued at day 2, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma copeptin level (odds ratio, 1.008; 95% confidence interval, 1.002-1.014; p = 0.010) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma copeptin level was negatively associated with Glasgow Coma Scale (GCS) score (t = -7.161; p < 0.001). A receiver operating characteristic curve identified plasma copeptin cutoff level (451.8 pg/mL) that predicted 1-month mortality with the optimal sensitivity (88.5%) and specificity (75.0%) values (area under curve, 0.874; 95% confidence interval, 0.789-0.933; p < 0.001). The area under curve of plasma copeptin level was similar to that of GCS score (p = 0.299). However, copeptin did not statistically significantly improve the area under curve of GCS score (p = 0.413). CONCLUSIONS: Increased plasma copeptin levels are associated with mortality after TBI.

Resistin is associated with mortality in patients with traumatic brain injury.

INTRODUCTION: Recently, we reported that high levels of resistin are present in the peripheral blood of patients with intracerebral hemorrhage and are associated with a poor outcome. However, not much is known regarding the change in plasma resistin and its relation with mortality after traumatic brain injury (TBI). Thus, we sought to investigate change in plasma resistin level after TBI and to evaluate its relation with disease outcome. METHODS: Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5 and 7 after TBI. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Twenty-six patients (27.7%) died from TBI within 1 month. After TBI, plasma resistin level in patients increased during the 6-hour period immediately after TBI, peaked within 24 hours, plateaued at day 2, decreased gradually thereafter and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma resistin level (odds ratio, 1.107; 95% confidence interval, 1.014-1.208; P = 0.023) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma resistin level was negatively associated with Glasgow Coma Scale score (t = -6.567, P < 0.001). A receiver operating characteristic curve identified plasma resistin cutoff level (30.8 ng/mL) that predicted 1-month mortality with the optimal sensitivity (84.6%) and specificity (75.0%) values (area under curve, 0.854; 95% confidence interval, 0.766-0.918; P < 0.001). CONCLUSIONS: Increased plasma resistin level is found and associated with Glasgow Coma Scale score and mortality after TBI.

Apigenin induces apoptosis and counteracts cisplatin-induced chemoresistance via Mcl-1 in ovarian cancer cells.

Ovarian cancer (OC) is one of the prominent causes of mortality in female patients diagnosed with gynecologic malignancies. While it has previously been demonstrated that apigenin inhibits cell growth in colon and breast cancer cells, the effect of apigenin in OC cells is not fully understood. Therefore, the aim of the present study was to investigate the impact of apigenin on cell death and resistance to cisplatin in OC cells. It was found that apigenin inhibited proliferation, hindered cell cycle progression and promoted SKOV3 cell apoptosis. Moreover, these effects were also observed in cisplatin-resistant SKOV3/DDP cells. Furthermore, apigenin reduced the mitochondrial transmembrane potential, and elevated the ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the two cell types. Reverse transcription-quantitative PCR and western blotting results demonstrated that apigenin significantly downregulated Mcl-1 at the transcriptional and translational levels in SKOV3 and SKOV3/DDP cells, which was responsible for its cytotoxic functions and chemosensitizing effects. Collectively, the present results identified the impact of apigenin on OC cell death and resistance to cisplatin, and the potential molecular mechanisms. However, additional studies are required to further elucidate the underlying mechanisms.

A prospective study on serum secreted protein acidic and rich in cysteine-like 1 as a prognostic marker for severe traumatic brain injury.

BACKGROUND: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability with upregulation throughout axonal regeneration. Our study aims to determine the correlation of serum SPARCL1 concentrations with the severity and in-hospital mortality of severe traumatic brain injury (sTBI). METHODS: A total of 102 consecutively recruited patients admitted for sTBI and 102 randomly selected healthy controls were included in this observational prospective study. Serum SPARCL1 concentrations were measured and correlated with Glasgow coma scale (GCS) scores and in-hospital mortality using multivariate analysis. RESULTS: Compared with controls (median, 0.22 ng/ml; interquartile range, 0.19-0.41 ng/ml), patients had significantly higher SPARCL1 concentrations (median, 3.29 ng/ml; interquartile range, 1.88-4.37; P < 0.001). There was an independently correlation between SPARCL1 concentrations and GCS scores (t = -7.011, P < 0.001). We found a high area under receiver operating curve (AUC) of serum SPARCL1 concentrations to predict in-hospital mortality (AUC, 0.822; 95% confidence interval, 0.734-0.891). In the multiple logistic regression analysis, serum SPARCL1 concentrations >3.29 ng/ml was independently associated with in-hospital mortality (odds ratio = 10.052, 95% confidence interval = 1.918-52.686, P = 0.006). CONCLUSIONS: The novel findings of our study are that sTBI patients had an increase of serum SPARCL1 concentrations, and that there is an association between high serum SPARCL1 concentrations and sTBI mortality or trauma severity.

Early Spatiotemporal Patterns and Knee Kinematics during Level Walking in Individuals following Total Knee Arthroplasty.

PURPOSE: With the aim of investigating the spatiotemporal features of early gait pattern and knee kinematics after total knee arthroplasty and analyzing the association between outcomes of gait analyses and knee kinematic parameters, the relationship between walking and dynamic knee deformity at the early period after total knee arthroplasty was assessed in this study. METHODS: Eighteen patients including 14 women and 4 men who underwent total knee arthroplasty were analyzed using three-dimensional gait analysis system to observe gait parameters and values of maximum knee flexion angle (MKFA) during swing phase and knee flexion angle (KFA) and knee valgus angle (KVA) at midstance phase. RESULTS: 3D gait analysis showed that operated side exhibited significantly less total support time and single support time as well as significantly longer swing phase compared with the other side. During walking, the operated side had significantly smaller MKFA and greater KFA and KVA than the nonoperated side. There was moderate to significant correlation between gait pattern and the dynamic knee kinematics. CONCLUSION: The gait abnormality of patients after TKA was associated with inadequate flexion of knees at swing phase and insufficient extension at stance phase as well as increased range of valgus.

Serum lipocalin-2 concentrations and mortality of severe traumatic brain injury.

BACKGROUND: Lipocalin-2 is related to acute brain injury. We assessed the prognostic value of serum lipocalin-2 in head trauma. METHODS: Blood samples were collected from 115 controls and 115 patients with severe traumatic brain injury. Trauma severity was assessed by Glasgow Coma Scale (GCS) scores at baseline. Thirty-day mortality and overall survival time were recorded. RESULTS: Compared with the controls, serum lipocalin-2 concentrations were significantly increased in the patients. Lipocalin-2 concentrations were independently associated with GCS scores (t=-7.271, P<0.001) and serum C-reactive protein concentrations (t=4.325, P<0.001). Under receiver operating characteristic curve for 30-day mortality, sensitivity and specificity were 85.7% and 63.2% respectively for lipocalin-2 concentrations at a cutoff value of 591ng/ml. Additionally, area under curve (AUC) of lipocalin-2 concentrations [AUC, 0.825; 95% confidence interval (95% CI), 0.743-0.889] was equivalent to that of GCS scores (AUC, 0.869; 95% CI, 0.793-0.925; P=0.413). Moreover, serum lipocalin-2 concentrations >591ng/ml emerged as an independent predictor for 30-day mortality (odds ratio, 4.360; 95% CI, 1.908-12.430) and overall survival (hazard ratio, 3.820; 95% CI, 1.935-10.500). CONCLUSIONS: Enhanced serum concentration of lipocalin-2 at admission is associated with trauma severity and neuroinflammation as well as is a predictor of mortality after head trauma.

High plasma adiponectin levels in patients with severe traumatic brain injury.

BACKGROUND: Adiponectin plays an important role in the regulation of tissue inflammation. There is a paucity of data on circulating plasma adiponectin concentrations in human traumatic brain injury. This study is designed to investigate the potential associations between plasma adiponectin levels and clinical outcomes after traumatic brain injury. METHODS: Plasma adiponectin levels of 86 patients with severe traumatic brain injury and 86 healthy subjects were determined. Clinical outcomes included in-hospital mortality, 6-month mortality and 6-month unfavorable outcome (Glasgow Outcome Scale score of 1-3). RESULTS: Plasma adiponectin levels were significantly higher in patients compared to controls (20.5±5.9 vs. 7.7±2.0µg/ml; P<0.001) and emerged as an independent predictor of in-hospital mortality [odds ratio (OR), 1.318; 95% confidence interval (CI), 1.049-1.629; P=0.008], 6-month mortality (OR, 1.328; 95% CI, 1.082-1.657; P=0.007) and 6-month unfavorable outcome (OR, 1.240; 95% CI, 1.066-1.443; P=0.005) in a multivariate analysis. For predicting these clinical outcomes, areas under receiver operating characteristic curve of plasma adiponectin level were similar to those of Glasgow Coma scale scores (all P>0.05). However, adiponectin did not improve predictive values of Glasgow Coma scale scores (all P>0.05). CONCLUSION: Plasma adiponectin level may represent a novel biomarker for predicting clinical outcomes of traumatic brain injury.

Change in plasma gelsolin level after traumatic brain injury.

BACKGROUND: Plasma gelsolin depletion has been associated with poor outcome of critically ill patients. However, there is a paucity of data available on circulating plasma gelsolin concentration in traumatic brain injury (TBI). Thus, we sought to investigate change in plasma gelsolin level after TBI and to evaluate its relation with disease outcome. METHODS: Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Twenty-six patients (27.7%) died from TBI in a month. After TBI, plasma gelsolin level in patients decreased during the 6-hour period immediately, was at the nadir in 24 hours, increased gradually thereafter, and was substantially lower than that in healthy controls during the 7-day period. A multivariate analysis showed plasma gelsolin level was an independent predictor for 1-month mortality (odds ratio, 0.941; 95% confidence interval, 0.895­ 0.989; p = 0.017) and positively associated with Glasgow Coma Scale (GCS) score (t = 6.538, p 0.001). A receiver operating characteristic curve identified that a baseline plasma gelsolin level 52.7 mg/L predicted 1-month mortality with 88.5% sensitivity and 79.4% specificity (area under the curve, 0.869; 95%confidence interval, 0.783­ 0.930). The predictive value of the gelsolin concentration was thus similar to that of GCS scores (p =0.185). However, gelsolin did not statistically significantly improve the area under the curve of GCS scores (p = 0.517). CONCLUSIONS: Decreased plasma gelsolin level is associated with GCS scores and an independent prognostic marker of mortality after TBI. Reversing plasma gelsolin deficiency may be an effective treatment for TBI.