Prefrontal Neuromodulation Using rTMS Improves Error Monitoring and Correction Function in Autism

One important executive function known to be compromised in autism spectrum disorder (ASD) is related to response error monitoring and post-error response correction. Several reports indicate that children with ASD show reduced error processing and deficient behavioral correction after an error is committed. Error sensitivity can be readily examined by measuring event-related potentials (ERP) associated with responses to errors, the fronto-central error-related negativity (ERN), and the error-related positivity (Pe). The goal of our study was to investigate whether reaction time (RT), error rate, post-error RT change, ERN, and Pe will show positive changes following 12-week long slow frequency repetitive TMS (rTMS) over dorsolateral prefrontal cortex (DLPFC) in high functioning children with ASD. We hypothesized that 12 sessions of 1 Hz rTMS bilaterally applied over the DLPFC will result in improvements reflected in both behavioral and ERP measures. Participants were randomly assigned to either active rTMS treatment or wait-list (WTL) groups. Baseline and post-TMS/or WTL EEG was collected using 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. ERN in TMS treatment group became significantly more negative. The number of omission errors decreased post-TMS. The RT did not change, but post-error RT became slower. There were no changes in RT, error rate, post-error RT slowing, nor in ERN/Pe measures in the wait-list group. Our results show significant post-TMS differences in the response-locked ERP such as ERN, as well as behavioral response monitoring measures indicative of improved error monitoring and correction function. The ERN and Pe, along with behavioral performance measures, can be used as functional outcome measures to assess the effectiveness of neuromodulation (e.g., rTMS) in children with autism and thus may have important practical implications.     

Oxytocin plasma concentrations in children and adolescents with autism spectrum disorder: correlation with autistic symptomatology

Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 ± 3.8 years), 17 healthy male children (age 13.6 ± 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 ± 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p < 0.001, η ² = 0.285; plasma concentrations ASD 19.61 ± 7.12 pg/ml, ADHD 8.05 ± 5.49 pg/ml, healthy controls 14.43 ± 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in the etiologically and phenotypically overlapping disorder ADHD. Further studies in humans and animal models are warranted to clarify the complex association of the OT system with social impairments as well as stress-related and depressive behavior and whether peripheral findings reflect primary changes of OT synthesis and/or release in relevant areas of the CNS.     

Increasing Performance of Professional Soccer Players and Elite Track and Field Athletes with Peak Performance Training and Biofeedback: A Pilot Study

The aim of this pilot study was to investigate the effects of an intervention consisting of mental coaching combined with either electro encephalogram (EEG) alpha power feedback or heart rate variability (HRV) feedback on HRV, EEG outcomes and self-reported factors related to stress, performance, recovery and sleep quality in elite athletes. A prospective pilot study was performed with two distinct cohorts. Soccer players were provided with four sessions of mental coaching combined with daily HRV biofeedback (Group A); track and field athletes were provided with four sessions of mental coaching in combination with daily neurofeedback (Group B). Measurements were performed at baseline, post intervention and at 5 weeks follow-up. Objective measures: EEG and ECG. Subjective measures: Numeric Rating Scale for performance, Pittsburgh Sleep Quality Index, Rest and Stress Questionnaire and Sports Improvement-60. Group characteristics were too distinct to compare the interventions. Linear mixed models were used to analyze differences within groups over time. In Group A, significant changes over time were present in alpha power at 5 of 7 EEG locations (p < 0.01–0.03). LF/HF ratio significantly increased (p = 0.02) and the concentration (p = 0.02) and emotional scale (p = 0.03) of the SIM-60 increased significantly (p = 0.04). In Group B, the HRV low frequency power and recovery scale of the REST-Q significantly increased (p = 0.02 and <0.01 resp.). Other measures remained stable or improved non-significantly. A mental coaching program combined with either HRV or EEG alpha power feedback may increase HRV and alpha power and may lead to better performance-related outcomes and stress reduction. Further research is needed to elucidate the effects of either type of feedback and to compare effects with a control group.     

Emodin Inhibits Inducible Nitric Oxide Synthase in a Rat Model of Craniocerebral Explosive Injury

To investigate the effects of emodin on blast-induced traumatic brain injury (bTBI) in a rat model. Eighty rats were randomly divided into 2 groups (the control group and the emodin-treated group; N = 40 per group) and were used to establish the model of blast-induced traumatic brain injury. Ten minutes after the explosion, an isotonic saline solution (10 mg/kg) or emodin (10 mg/kg) were administered via an intraperitoneal injection to the control group and the emodin-treated group, respectively. At each time point (pre-explosion, 2, 6, 12, 24 h after explosion), 2 rats were used for the pathological assessment and 6 rats were used for the biochemical assessment. The concentration of nitric oxide (NO) and the expression and activity of inducible nitric oxide synthase (iNOS) were measured at each time point by spectrophotometry and western blot analysis. Light and electron microscopy showed that the brain damage in the emodin-treated group was less serious than that observed in the control group. The concentration of NO in the emodin-treated group was lower compared with the control group (p < 0.05). Western blot analysis showed that protein expression in the emodin-treated group was lower than the control group (p < 0.05). Emodin can alleviate brain damage after bTBI by inhibiting iNOS. These findings suggest that emodin has a protective effect against bTBI. One possible mechanism may occur by inhibiting the expression and activity of iNOS and consequently decreasing the concentration of NO.     

A Pilot Study on the Contribution of Folate Gene Variants in the Cognitive Function of ADHD Probands

Genetic abnormalities in components important for the folate cycle confer risk for various disorders since adequate folate turnover is necessary for normal methylation, gene expression and chromosome structure. However, the system has rarely been studied in children diagnosed with attention deficit hyperactivity disorder (ADHD). We hypothesized that ADHD related cognitive deficit could be attributed to abnormalities in the folate cycle and explored functional single nucleotide polymorphisms in methylenetetrahydrofolate dehydrogenase (rs2236225), reduced folate carrier (rs1051266), and methylenetetrahydrofolate reductase (rs1801131 and rs1801133) in families with ADHD probands (N = 185) and ethnically matched controls (N = 216) recruited following the DSM-IV. After obtaining informed written consent for participation, peripheral blood was collected for genomic DNA isolation and PCR-based analysis of target sites. Data obtained was analyzed by UNPHASED. Interaction between sites was analyzed by the multi dimensionality reduction (MDR) program. Genotypic frequencies of the Indian population were strikingly different from other ethnic groups. rs1801133 “T” allele showed biased transmission in female probands (p < 0.05). Significant difference in genotypic frequencies for female probands was also noticed. rs1801131 and rs1801133 showed an association with low intelligence quotient (IQ). MDR analysis exhibited independent effects and contribution of these sites to IQ, thus indicating a role of these genes in ADHD related cognitive deficit.     

Differentiation between attention-deficit/hyperactivity disorder and autism spectrum disorder by the Social Communication Questionnaire

The differentiation of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) poses a clinical challenge. In children, overlap of psychopathological and cognitive findings has been found for both disorders. In addition, some children suffer from both disorders. The Social Communication Questionnaire (SCQ) is a screening instrument for ASD symptoms which indicates the presence of ASD in a rapid and economic way. However, validity to differentiate ASD and ADHD as differential or comorbid diagnoses has not been studied. Here, the differential validity was compared in groups of children with ASD, ADHD, ASD + ADHD, and typically developing (TD) children and IQ > 70. ROC analyses indicated an excellent differentiation between ASD and TD with ROC–AUC = .941 and between ASD + ADHD with ROC–AUC = .993. The optimal cutoff was below the originally recommended one of 15. The differentiation between children with ASD with (ROC–AUC = .982) or without ADHD (ROC–AUC = .864) and ADHD alone also showed acceptable differential validity, and here, the optimal cutoff corresponded to the recommended. Taken together, the SCQ can be recommended as a screening instrument for a first differentiation between children with ASD and typically developing children as well as children with ADHD.     

The Effects of Individual Upper Alpha Neurofeedback in ADHD: An Open-Label Pilot Study

Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individually determined using the alpha peak frequency as an anchor point. 20 ADHD children underwent 18 training sessions. Clinical and neurophysiological variables were measured pre- and post-training. EEG was recorded pre- and post-training, and pre- and post-training trials within each session, in both eyes closed resting state and eyes open task-related activity. A power EEG analysis assessed long-term and within-session effects, in the trained parameter and in all the sensors in the (1–30) Hz spectral range. Learning curves over sessions were assessed as well. Parents rated a clinical improvement in children regarding inattention and hyperactivity/impulsivity. Neurophysiological tests showed an improvement in working memory, concentration and impulsivity (decreased number of commission errors in a continuous performance test). Relative and absolute upper alpha power showed long-term enhancement in task-related activity, and a positive learning curve over sessions. The analysis of within-session effects showed a power decrease (“rebound” effect) in task-related activity, with no significant effects during training trials. We conclude that the enhancement of the individual upper alpha power is effective in improving several measures of clinical outcome and cognitive performance in ADHD. This is the first NF study evaluating such a protocol in ADHD. A controlled evaluation seems warranted due to the positive results obtained in the current study.     

Therapeutical Effects and Mechanism of Salubrinal Combined with Ulinastatin on Treating Paraquat Poisoning

To explore therapeutic effects and underlying mechanism of Salubrinal combined with Ulinastatin (UTI) on acute Paraquat (PQ) poisoning. Four hundred rats were randomly allocated into UTI group, SAL group, SAL + UTI and control group according to random number table with 100 rats in each group. Acute PQ poisoning models were established, and all rats received UTI, Salubrinal, SAL + UTI and normal saline injection, respectively. Afterward, we analyzed the change of lung tissue and explored the mechanism. Acute PQ poisoning caused significantly damage in rat lung tissue structure, and UTI could effectively repair lung tissue damage. Salubrinal suppressed hemorrhage and fibrosis, but promoted inflammatory infiltration. In contrast, UTI + Salubrinal suppressed hemorrhage, fibrosis and inflammatory infiltration, but could not improve lung tissue damage. Expression of LC3 and Bcl-2 showed statistically significant difference among different groups (p < 0.05). LC3 and Bcl-2 levels in UTI group were much higher than in the other groups, and LC3 and Bcl-2 levels in UTI + SAL group was second higher. LC expression in SAL group was lower than in UTI group and UTI + SAL group with Bcl-2 in control group significantly lower than in the other groups (p < 0.05). Expression of Caspase-3 and Bcl-2/Bax in lung tissue in different groups had statistically significant difference (p < 0.05). Caspase-3 in UTI group was lower than in the other groups; however, Bcl-2/Bax in UTI group was higher than in the other groups (p < 0.05). Acute PQ poisoning can cause endoplasmic reticulum stress–autophagy in rat, and UTI can increase Bcl-2 expression, decrease Caspase-3, which can inhibit progress of lung injury by suppressing apoptosis and exert good therapeutic effects. Although salubrinal has marked effects on protecting lung tissue, it can increase Bcl-2 expression, which is not beneficial to lung tissue protection. The underlying mechanism still needs further exploration.     

Behavioral and Neurochemical Changes Induced by Repetitive Combined Treatments of Ketamine and Amphetamine in Mice

The combined abuse of recreational drugs such as ketamine (Ket) and amphetamine (Amph) should be seriously considered important social and health issues. Numerous studies have documented the behavioral and neurochemical changes associated with polydrug administration; however, most studies have only examined the acute effects. The consequences following chronic repetitive polydrug use are less studied. In the present study, intraperitoneal injections of saline, Amph (5 mg/kg), low dose Ket (LK, 10 mg/kg), high dose Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK) were conducted twice a day for three consecutive days, and one final treatment was administered on day 4. After seven total treatments, animal behaviors, including locomotion, stereotypy and ataxia, were examined in a novel open field. The expression of GAD₆₇ and dopamine (DA) levels were assessed in the striatum and motor-related cortices using immunohistochemistry and high-performance liquid chromatography. Drug-induced hyperactivities and Amph-mediated potentiation of Ket-triggered ataxia manifested after repeated drug treatments. A significant increase in the number of GAD₆₇-positive puncta in the striatum and motor-related cortices was observed, suggesting a neural adaptive change in the GABAergic system. Four hours after the final treatment, while the behavioral hyperactivities had ceased, considerable changes were still evident in the motor-related cortices, suggesting modulation to the DAergic system. Together, our results show the interactive effects of these two drugs in behavioral and neurochemical aspects and neural adaptive changes in the GABAergic and DAergic systems.     

Transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis

Sorafenib in combination with Transarterial chemoembolization (TACE) is increasingly used in patients with unresectable hepatocellular carcinoma (HCC), but the current evidence is still controversial. The aim of this systematic review was to evaluate the effectiveness and safety of TACE plus sorafenib versus TACE alone for unresectable HCC. We searched PubMed, EMBASE and the Cochrane Library for clinical trials comparing TACE plus sorafenib with TACE alone for unresectable HCC. The study outcomes included overall survival (OS), time to progression (TTP), objective response and adverse events (AEs). Six studies including 1,181 patients were included. Meta-analysis of all studies suggested that the combination therapy group had significant longer OS than TACE group [hazard ratio (HR) = 0.64, 95 % confidence interval (CI) = 0.43–0.97], but the pooled HR of randomized controlled trials (RCTs) failed to achieve statistical significance. For TTP, meta-analysis in both RCTs subgroup and retrospective studies subgroup suggested that combination therapy was superior to TACE group. The combination therapy was also associated with better response to treatment (risk ratio = 1.45, 95 % CI = 1.04–2.02) when both RCTs and retrospective studies were pooled. However, the sorafenib associated AEs were more frequent in the combination therapy group. In conclusion, the combination of TACE and sorafenib is likely to improve OS, TTP and response to treatment when compared with TACE monotherapy. The combination group is also associated with more sorafenib-related AEs.     

Effects of Intracavitary Administration of Endostar Combined with Cisplatin in Malignant Pleural Effusion and Ascites

This study evaluated the efficacy and safety of intracavitary administration of recombinant human endostatin (Endostar) combined with cisplatin chemotherapy in treating malignant pleural effusion and ascites. Forty-five patients with malignant pleural effusion and ascites were divided into the EP group (n = 23), who received Endostar and cisplatin intracavitarily, and P group (n = 22), who were intracavitarily treated with cisplatin only. Pleural effusion and ascites were completely drained before treatments. The treatment was administered once a week; two treatments were considered as one course. The outcome quality of life as well as toxicity were evaluated. The objective overall response and disease control rates were, respectively, 78.3 % (18/23) and 87.0 % (20/23) in EP group. In contrast, these parameters were significantly (p < 0.05) lower in P groups: 40.9 % (9/22) and 59.1 % (13/22), respectively. The improvement rate of Karnofsky Performance Status was 87.0 % (20/23) in EP group versus 59.1 % (13/22) in P group (p < 0.05). All patients tolerated the combined treatment well, and no severe adverse effects were observed. Intracavitary injection of Endostar combined with cisplatin is effective and safe to treat malignant pleural effusion and ascites.     

A new method to detect event-related potentials based on Pearson’s correlation

Event-related potentials (ERPs) are widely used in brain-computer interface applications and in neuroscience.  Normal EEG activity is rich in background noise, and therefore, in order to detect ERPs, it is usually necessary to take the average from multiple trials to reduce the effects of this noise.  The noise produced by EEG activity itself is not correlated with the ERP waveform and so, by calculating the average, the noise is decreased by a factor inversely proportional to the square root of N, where N is the number of averaged epochs. This is the easiest strategy currently used to detect ERPs, which is based on calculating the average of all ERP’s waveform, these waveforms being time- and phase-locked.  In this paper, a new method called GW6 is proposed, which calculates the ERP using a mathematical method based only on Pearson’s correlation. The result is a graph with the same time resolution as the classical ERP and which shows only positive peaks representing the increase—in consonance with the stimuli—in EEG signal correlation over all channels.  This new method is also useful for selectively identifying and highlighting some hidden components of the ERP response that are not phase-locked, and that are usually hidden in the standard and simple method based on the averaging of all the epochs.  These hidden components seem to be caused by variations (between each successive stimulus) of the ERP’s inherent phase latency period (jitter), although the same stimulus across all EEG channels produces a reasonably constant phase. For this reason, this new method could be very helpful to investigate these hidden components of the ERP response and to develop applications for scientific and medical purposes. Moreover, this new method is more resistant to EEG artifacts than the standard calculations of the average and could be very useful in research and neurology.  The method we are proposing can be directly used in the form of a process written in the well-known Matlab programming language and can be easily and quickly written in any other software language.     

Behavioral,Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display “motor dyspraxia” or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism.     

The Significance and Mechanism of Propofol on Treatment of Ischemia Reperfusion Induced Lung Injury in Rats

This study is aimed to investigate the efficacy and underlying the mechanism of propofol in treatment of ischemia reperfusion (IR)-induced lung injury in rats, providing a novel insight of therapeutic strategy for IR-induced lung injury. 120 healthy SD rats were selected and randomly divided into sham operation group, IR group, and propofol group (40 rats per group). Bronchoalveolar lavage fluid (BALF) protein content, serum protein content, lung permeability index, lung water content rate, methane dicarboxylic aldehyde (MDA) in lung tissue, superoxide dismutase (SOD), nitric oxide (NO), endothelin (ET-1), toll-like receptor 4 (TLR4), nuclear factor (NF-κB), and tumor necrosis factor-α (TNF-α) were examined and compared among different groups to evaluate the therapeutical effects of propofol on IR-induced lung injury and analyze the mechanism. In sham operation group, neither change in lung tissue nor pulmonary interstitial edema or alveolar wall damage was found under microscope; in IR group, marked pulmonary interstitial edema and alveolar wall damage complicated with inflammatory cell infiltration and hemorrhage were found; in propofol group, alveolar wall widening was observed, however, hemorrhage in alveolar cavity, inflammatory infiltration and tissue damage were less significant than in IR group. At 3 h after reperfusion, BALF protein content, lung permeability index, and lung water content rate were all significantly increased in IR group and propofol group, while the serum protein content was significantly lower than sham operation group (p < 0.05). Moreover, we found that the change of above parameters in propofol group was less significant than in IR group (p < 0.05). No statistically significant difference was found in ET-1 levels in different groups (p > 0.05). In contrast, MDA and NO in IR group and propofol group were significantly increased, while SOD activity was significantly decreased (p < 0.05). Furthermore, the change of above parameters in propofol group was less significant than in IR group (p < 0.05). In addition, mRNAs of TLR4, NF-κB, and TNF-α were significantly increased in IR group and propofol group (p < 0.05) with more significant change in IR group compared with propofol group (p < 0.05). Propofol has protective effects against IR-induced lung injury by improving activity of oxygen radical and restoring NO/ET-1 dynamic balance. Besides, regulation of TLR4, NF-κB, and TNF-α by propofol also play important role in alleviating IR-induced lung injury.     

HRV Biofeedback for Pediatric Irritable Bowel Syndrome and Functional Abdominal Pain: A Clinical Replication Series

Irritable bowel syndrome (IBS) and Functional Abdominal Pain (FAP) are among the most commonly reported Functional Gastrointestinal Disorders. Both have been associated with varying autonomic dysregulation. Heart Rate Variability Biofeedback (HRVB) has recently begun to show efficacy in the treatment of both IBS and FAP. The purpose of this multiple clinical replication series was to analyze the clinical outcomes of utilizing HRVB in a clinical setting. Archival data of twenty-seven consecutive pediatric outpatients diagnosed with IBS or FAP who received HRVB were analyzed. Clinical outcomes were self-report and categorized as full or remission with patient satisfaction, or no improvement. Qualitative reports of patient experiences were also noted. Full remission was achieved by 69.2 % and partial remission was achieved by 30.8 % of IBS patients. Full remission was achieved by 63.6 % and partial remission was achieved by 36.4 % of FAP patients. No patients in either group did not improve to a level of patient satisfaction or >50 %. Patient’s commonly reported feeling validated in their discomfort as a result of psychophysiological education. Results suggest that HRVB is a promising intervention for pediatric outpatients with IBS or FAP. Randomized controlled trials are necessary to accurately determine clinical efficacy of HRVB in the treatment of IBS and FAP.     

Effects of Mild and Moderate Hypothemia Therapy on Expression of Cerebral Neuron Apoptosis Related Proteins and Glial Fiber Acidic Protein After Rat Cardio-pulmonary Resuscitation

To explore the effects of different degrees of hypothermia on brain tissue apoptosis after cardio-pulmonary resuscitation (CPR). Cardiac arrest for 5 min induced by asphyxia method was used to create CPR model. 30 SD rats were randomly divided into control group (normothermia), 33 °C hypothermia group and 30 °C hypothermia group with ten rats in each. Rats in control group received routine treatment at 25 °C room temperature after CPR; Rats in mild hypothermia and moderate hypothermia groups were given hypothermia treatment 0.5 h after CPR. Brain tissue in all groups was taken 24 h after CPR, and immunohistochemistry was used to detect the caspase-3 in cerebral cortex and glial fiber acidic protein (GFAP) expression in astrocyte. Western blotting was used to detect Bcl-2 and Bax protein expression, and histopathological change was observed in brain tissue. Compare to the control group, caspase-3 expression in cerebral neurons in hypothermia group was significantly decreased (p<0.01), which was significantly lower in 30 °C group than that in 33 °C group (p > 0.05); GFAP level in hypothermia groups was significantly increased (p < 0.01), which was higher in 30 °C hypothermia group than that in 33 °C hypothermia group (p < 0.05); Bcl-2 expression level in hypothermia group was significantly increased (p < 0.01), which was higher in 30 °C hypothermia group than that in 33 °C hypothermia group (p < 0.05); The level of Bax had no significant difference among the three groups. Hypothermia-regulated GFAP expression by decreasing caspase-3 expression and increasing Bcl-2 expression to promote brain cell signaling transduction, and further inhibited cell apoptosis and reduced brain injury. Moderate hypothermia therapy is more effective than mild hypothermia in preventing brain injure.     

Effects of Bone Marrow Mesenchymal Stem Cells on Hematopoietic Recovery and Acute Graft-Versus-Host Disease in Murine Allogeneic Umbilical Cord Blood Transplantation Model

To investigate the effect of bone marrow mesenchymal stem cells (MSC) on hematopoietic recovery and acute graft-versus-host disease (GVHD) in a murine allogeneic umbilical cord blood transplantation (allo-UCBT) model. MSCs were obtained from C57/BL mouse bone marrow. The MSC phenotypes were identified by flow cytometry (FCM), and their ability to differentiate into osteoblasts and adipocytes was tested. Once murine allo-UCBT and aGVHD models were established, mice were divided into five groups: (1) total body irradiation (TBI) group, each mouse receiving 0.3 ml sterile saline infusion after TBI and used as control; (2) UCB group, receiving 2 × 10⁶ umbilical cord blood mononuclear cells (UCB-MNC) after TBI; (3) UCB+MSC group, receiving 2 × 10⁶ UCB-MNC and 2 × 10⁷ MSC after TBI; (4) UCB+SC group, receiving 2 × 10⁶ UCB-MNC and 2 × 10⁶ spleen cells after TBI; and (5) UCB+SC+MSC group, receiving 2 × 10⁶ UCB-MNC, 2 × 10⁷ MSC and 2 × 10⁶ spleen cells after TBI. To evaluate the engraftment of HSC, the white blood cells, red blood cells, and platelets counts were tested at different time points after transplantation, and the ratio of chimerism was identified by FCM. The acute GVHD clinical scores, recipient mice survival, and the histopathological analyses were used to evaluate the effect of MSC on acute GVHD. MSCs were successfully obtained in vitro and FCM analysis showed that these cells are highly positive for CD90.2, CD44, and negative for CD34, CD45, and they are capable to differentiate into osteoblasts and adipocytes after being induced. Compared to UCB group, the UCB+MSC mice had shorter duration of myelosuppression and higher percentage of donor-derived cells which was up to 22.87 ± 4.3 % and the white blood cell (WBC), red blood cell (RBC), and platelet counts started to increase by day 6 after transplantation. Moreover, the average survival time for UCB+MSC mice was 25.0 ± 10.55 days, while for the UCB group it was 15.5 ± 12.50 days. The UCB+SC mice showed fatigue, loss of appetite, weight loss, arched back, and hair ruffling on day 13 post transplantation. Approximately 50 % of mice showed skin ulcers, had diarrhea and other manifestations of acute GVHD, and all mice were died within 20 days. Histopathological analysis confirmed grade II–IV GVHD manifestation. In addition to transient weight loss, some UCB+SC+MSC mice developed arched back, hair ruffling, diarrhea and other manifestations of acute GVHD. The clinical scores in UCB+SC+MSC mice with acute GVHD (grade I–II or without GVHD) were lower than UCB+SC group (P < 0.05). Bone marrow MSCs can promote hematopoietic recovery and decrease the incidence of acute GVHD in murine allo-UCBT model.     

Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk factors on psoriasis vulgaris

Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case–control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (≥25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12–2.37), 2.09(95 % CI; 1.44–3.03) and 1.65(95 % CI; 1.15–2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (≥25) increased risk of PV (OR = 2.09; 95 % CI, 1.02–4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37–7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09–6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10–1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.     

Is EEG-biofeedback an Effective Treatment in Autism Spectrum Disorders? A Randomized Controlled Trial

EEG-biofeedback has been reported to reduce symptoms of autism spectrum disorders (ASD) in several studies. However, these studies did not control for nonspecific effects of EEG-biofeedback and did not distinguish between participants who succeeded in influencing their own EEG activity and participants who did not. To overcome these methodological shortcomings, this study evaluated the effects of EEG-biofeedback in ASD in a randomized pretest–posttest control group design with blinded active comparator and six months follow-up. Thirty-eight participants were randomly allocated to the EEG-biofeedback, skin conductance (SC)-biofeedback or waiting list group. EEG- and SC-biofeedback sessions were similar and participants were blinded to the type of feedback they received. Assessments pre-treatment, post-treatment, and after 6 months included parent ratings of symptoms of ASD, executive function tasks, and 19-channel EEG recordings. Fifty-four percent of the participants significantly reduced delta and/or theta power during EEG-biofeedback sessions and were identified as EEG-regulators. In these EEG-regulators, no statistically significant reductions of symptoms of ASD were observed, but they showed significant improvement in cognitive flexibility as compared to participants who managed to regulate SC. EEG-biofeedback seems to be an applicable tool to regulate EEG activity and has specific effects on cognitive flexibility, but it did not result in significant reductions in symptoms of ASD. An important finding was that no nonspecific effects of EEG-biofeedback were demonstrated.     

Analysis of Hair Trace Elements in Children with Autism Spectrum Disorders and Communication Disorders

The primary objective of the present study is analysis of hair trace elements content in children with communication disorder (CD) and autism spectrum disorder (ASD). A total of 99 children from control, CD, and ASD groups (n = 33) were examined. All children were additionally divided into two subgroups according to age. Hair levels of trace elements were assessed using inductively coupled plasma mass spectrometry. The difference was considered significant at p < 0.01. The obtained data demonstrate that children with CD are characterized by significantly increased hair lithium (Li) (96 %; p = 0.008), selenium (Se) (66 %; p < 0.001), arsenic (As) (96 %; p = 0.005), beryllium (Be) (150 %; p < 0.001), and cadmium (Cd) (72 %; p = 0.007) content, being higher than the respective control values. In the ASD group, hair copper (Cu), iodine (I), and Be levels tended to be lower than the control values. In turn, the scalp hair content of Se significantly exceeded the control values (33 %; p = 0.004), whereas the level of iron (Fe) and aluminum (Al) tended to increase. After gradation for age, the most prominent differences in children with CD were detected in the elder group (5–8 years), whereas in the case of ASD—in the younger group (3–4 years old). Taking into account the role of hair as excretory mechanism for certain elements including the toxic ones, it can be proposed that children suffering from ASD are characterized by more profound alteration of metal handling and excretion in comparison to CD.