Multiscale Entropy of Electroencephalogram as a Potential Predictor for the Prognosis of Neonatal Seizures

Objective

Increasing animal studies supported the harmful effects of prolonged or frequent neonatal seizures in developing brain, including increased risk of later epilepsy. Various nonlinear analytic measures had been applied to investigate the change of brain complexity with age. This study focuses on clarifying the relationship between later epilepsy and the changes of electroencephalogram (EEG) complexity in neonatal seizures.

Methods

EEG signals from 19 channels of the whole brain from 32 neonates below 2 months old were acquired. The neonates were classified into 3 groups: 9 were normal controls, 9 were neonatal seizures without later epilepsy, and 14 were neonatal seizures with later epilepsy. Sample entropy (SamEn), multiscale entropy (MSE) and complexity index (CI) were analyzed.

Results

Although there was no significant change in SamEn, the CI values showed significantly decreased over Channels C3, C4, and Cz in patients with neonatal seizures and later epilepsy compared with control group. More multifocal epileptiform discharges in EEG, more abnormal neuroimaging findings, and higher incidence of future developmental delay were noted in the group with later epilepsy.

Conclusions

Decreased MSE and CI values in patients with neonatal seizures and later epilepsy may reflect the mixed effects of acute insults, underlying brain immaturity, and prolonged seizures-related injuries. The analysis of MSE and CI can therefore provide a quantifiable and accurate way to decrypt the mystery of neonatal seizures, and could be a promising predictor.     

Tyroserleutide tripeptide affects calcium homeostasis of human hepatocarcinoma BEL-7402 cells

This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg-kg^-1 · d^-1, 160 μg·kg^-1 ·d^-1 and 320 μg · kg^-1 · d^-1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium overload. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (P< 0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.     

Six new species of the spider genus Spiricoelotes species (Araneae,Agelenidae) from caves in Jiangxi,China

Six new species of the spider genus Spiricoelotes Wang, 2002 are described, Spiricoelotes anshiensis Chen & Li, sp. n. (♂♀), Spiricoelotes chufengensis Chen & Li, sp. n. (♂♀), Spiricoelotes nansheensis Chen & Li, sp. n. (♂♀), Spiricoelotes taipingensis Chen & Li, sp. n. (♂♀), Spiricoelotes xianheensis Chen & Li, sp. n. (♂♀) and Spiricoelotes xiongxinensis Chen & Li, sp. n. (♀). All new species were collected from caves in Jiangxi Province, China.     

Phosphoinositide-Dependent Kinase 1 and mTORC2 Synergistically Maintain Postnatal Heart Growth and Heart Function in Mice

The protein kinase Akt plays a critical role in heart function and is activated by phosphorylation of threonine 308 (T308) and serine 473 (S473). While phosphoinositide-dependent kinase 1 (PDK1) is responsible for Akt T308 phosphorylation, the identities of the kinases for Akt S473 phosphorylation in the heart remain controversial. Here, we disrupted mTOR complex 2 (mTORC2) through deletion of Rictor in the heart and found normal heart growth and function. Rictor deletion caused significant reduction of Akt S473 phosphorylation but enhanced Akt T308 phosphorylation, suggesting that a high level of Akt T308 phosphorylation maintains Akt activity and heart function. Deletion of Pdk1 in the heart caused significantly enhanced Akt S473 phosphorylation that was suppressed by removal of Rictor, leading to worsened dilated cardiomyopathy (DCM) and accelerated heart failure in Pdk1-deficient mice. In addition, we found that increasing Akt S473 phosphorylation through deletion of Pten or chemical inhibition of PTEN reversed DCM and heart failure in Pdk1-deficient mice. Investigation of heart samples from human DCM patients revealed changes similar to those in the mouse models. These results demonstrated that PDK1 and mTORC2 synergistically promote postnatal heart growth and maintain heart function in postnatal mice.     

Evaluation of Finnish Diabetes Risk Score in Screening Undiagnosed Diabetes and Prediabetes among U.S. Adults by Gender and Race: NHANES 1999-2010

Objective

To evaluate the performance of Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes and prediabetes among U.S. adults by gender and race.

Methods

This cross-sectional analysis included participants (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) 1999–2010. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve and the optimal cutoff points for identifying undiagnosed diabetes and prediabetes were calculated for FINDRISC by gender and race/ethnicity.

Results

Among the 20,633 adults (≥20 years), 49.8% were women and 53.0% were non-Hispanic White. The prevalence of undiagnosed diabetes and prediabetes was 4.1% and 35.6%, respectively. FINDRISC was positively associated with the prevalence of diabetes (OR = 1.48 for 1 unit increase, p<0.001) and prediabetes (OR = 1.15 for 1 unit increase, p<0.001). The area under ROC for detecting undiagnosed diabetes was 0.75 for total population, 0.74 for men and 0.78 for women (p = 0.04); 0.76 for White, 0.76 for Black and 0.72 for Hispanics (p = 0.03 for White vs. Hispanics). The area under ROC for detecting prediabetes was 0.67 for total population, 0.66 for men and 0.70 for women (p<0.001); 0.68 for White, 0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs. Hispanics). The optimal cutoff point was 10 (sensitivity = 0.75) for men and 12 (sensitivity = 0.72) for women for detecting undiagnosed diabetes; 9 (sensitivity = 0.61) for men and 10 (sensitivity = 0.69) for women for detecting prediabetes.

Conclusions

FINDRISC is a simple and non-invasive screening tool to identify individuals at high risk for diabetes in the U.S. adults.     

COMP-Angiopoietin1 Potentiates the Effects of Bone Morphogenic Protein-2 on Ischemic Necrosis of the Femoral Head in Rats

Angiogenesis is considered essential for proper bone regeneration. The purpose of this investigation was to determine if a combined therapy of bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) can potentiate the therapeutic effect of BMP-2 in a rat model of ischemic necrosis of the femoral head (INFH). INFH was surgically induced in the femoral head of rats, and the animals were divided into the following groups: 1) a sham-operated group (sham group), 2) a bovine serum albumin-injected group (BSA group), 3) a BMP-2-injected group (BMP-2 group), and 4) a COMP-Ang1 and BMP-2-injected group (COMP-Ang1 + BMP-2 group) (n = 20/group). Radiologic, histologic, and histomorphometric assessments were performed to assess femoral head morphology, vascular density, and bone resorption activity. Western blots and immunohistochemical staining were performed to evaluate production of BMP-related signaling proteins in C3H10T1/2 cells and tissues. Real-time RT-PCR was performed to investigate expression of the target integrin gene, and the effect of integrin on C3H10T1/2 cells was determined using a cell adhesion assay. Radiographs obtained six weeks after injection revealed better preservation of the architecture of the femoral head in the COMP-Ang1 + BMP-2 group compared with the BSA and BMP-2 groups. Histological findings indicated increased trabecular bone and vascularity and decreased osteoclast bone resorption activity in the COMP-Ang1 + BMP-2 group compared with those in the BSA and BMP-2 groups. The combination of COMP-Ang1 and BMP-2 increased phosphorylation of Smad1/3/5, p38, and Akt. Increased integrin α3 and β1 mRNA expression in the COMP-Ang1 + BMP-2 group promoted cell adhesion. These results suggest that COMP-Ang1 preserved the necrotic femoral head through the potentiation of BMP-2 signaling pathways and angiogenesis. Combination treatment with COMP-Ang1 and BMP-2 may be a clinically useful therapeutic application in INFH.     

Chinese Proprietary Herbal Medicine Listed in ‘China National Essential Drug List’ for Common Cold: A Systematic Literature Review

Objective

Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the ‘China national essential drug list’ by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation.

Methods

We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the ‘China national essential drug list’ for common cold. There was no restriction on study design.

Results

A total of 33 CPHMs were listed in ‘China national essential drug list 2012’ for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality.

Conclusions

The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs.     

Improving the Secretion of a Methyl Parathion Hydrolase in Pichia pastoris by Modifying Its N-Terminal Sequence

Pichia pastoris is commonly used to express and secrete target proteins, although not all recombinant proteins can be successfully produced. In this study, we used methyl parathion hydrolase (MPH) from Ochrobactrum sp. M231 as a model to study the importance of the N-terminus of the protein for its secretion. While MPH can be efficiently expressed intracellularly in P. pastoris, it is not secreted into the extracellular environment. Three MPH mutants (N₆₆-MPH, D₁₀-MPH, and N₉-MPH) were constructed through modification of its N-terminus, and the secretion of each by P. pastoris was improved when compared to wild-type MPH. The level of secreted D₁₀-MPH was increased to 0.21 U/mL, while that of N₉-MPH was enhanced to 0.16 U/mL. Although N₆₆-MPH was not enzymatically active, it was secreted efficiently, and was identified by SDS-PAGE. These results demonstrate that the secretion of heterologous proteins in P. pastoris may be improved by modifying their N-terminal structures.