The Minimum Clinically Important Difference in the Repeatable Battery for the Assessment of Neuropsychological Status

Objective: There is no established minimum clinically important difference (MCID) for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) index and total scale scores. This study aimed to estimate the MCID for the RBANS index scores and total scale score. Method: Participants included 1,856 ethnic Chinese, older adults. Distribution- and anchor-based methods were used to estimate values for the MCID. Distribution-based estimates were calculated as the standard error of measurement (SEM) and .5 standard deviations (SD). For anchor-based estimates, we compared RBANS scores between the clinical dementia rating (CDR) scale no dementia and very mild dementia groups and between the clinical assessment of dementia (CAD) cognitively normal and mild cognitive impairment groups using regression models adjusting for demographic characteristics. Results: Estimates from the CDR anchor were 7.79, 8.63, 10.74, 9.74, 5.61, and 3.77 for the total scale score, language, immediate memory, delayed memory, visuospatial/constructional, and the attention index, respectively. Estimates from the distribution-based methods were similar to the estimates based on the CDR, except for the language and attention indexes. Estimates from the CAD anchor were larger. Conclusions: We estimated the MCID for the total scale score, language, immediate memory, delayed memory, visuospatial/constructional, and attention indexes of the RBANS as 8, 9, 10, 10, 6, and 4 points, respectively. These estimates are best suited to discriminate between patient groups, for example, in a clinical trial setting. Further research is needed using longitudinal data to assess their applicability to assess within patient differences.     

Retinoic Acid and Human Olfactory Ensheathing Cells Cooperate to Promote Neural Induction From Human Bone Marrow Stromal Stem Cells

The generation of induced neuronal cells from human bone marrow stromal stem cells (hBMSCs) provides new avenues for basic research and potential transplantation therapies for nerve injury and neurological disorders. However, clinical application must seriously consider the risk of tumor formation by hBMSCs, neural differentiation efficiency and biofunctions resembling neurons. Here, we co-cultured hBMSCs exposed to retinoic acid (RA) with human olfactory ensheathing cells (hOECs) to stimulate its differentiation into neural cells, and found that hBMSCs following 1 and 2 weeks of stimulation promptly lost their immunophenotypical profiles, and gradually acquired neural cell characteristics, as shown by a remarkable up-regulation of expression of neural-specific markers (Tuj-1, GFAP and Galc) and down-regulation of typical hBMSCs markers (CD44 and CD90), as well as a rapid morphological change. Concomitantly, in addition to a drastic decrease in the number of BrdU incorporated cells, there was a more elevated synapse formation (a hallmark for functional neurons) in the differentiated hBMSCs. Compared with OECs alone, this specific combination of RA and hOECs was significantly potentiated neuronal differentiation of hBMSCs. The results suggest that RA can enhance and orchestrate hOECs to neural differentiation of hBMSCs. Therefore, these findings may provide an alternative strategy for the repair of traumatic nerve injury and neurological diseases with application of the optimal combination of RA and OECs for neuronal differentiation of hBMSCs.     

Ceramide is involved in alcohol-induced neural proliferation****

Prenatal alcohol exposure, especially during early pregnancy, can lead to fetal alcohol syndrome. The pharmacological and toxicological mechanisms of ethanol are related to the effects of ceramide. In this study, we established an alcohol exposure model in wild-type mice and in knockout mice for the key enzyme involved in ceramide metabolism, sphingomyelin synthase 2. This model received daily intragastric administration of 25% ethanol, and pups were used at postnatal days 0, 7, 14, 30 for experiments. Serology and immunofluorescence staining found that ethanol exposure dose-dependently reduced blood sphingomyelin levels in two genotypes of pups, and increased neural cell proliferation and the number of new neurons in the hippocampal dentate gyrus. Western blot analysis showed that the relative expression level of protein kinase C α increased in two genotypes of pups after ethanol exposure. Compared with wild-type pups, the expression level of the important activator protein of the ceramide/ceramide-1-phosphate pathway, protein kinase C α, was reduced in the hippocampus of sphingomyelin synthase 2 knockouts. Our findings illustrate that ceramide is involved in alcohol-induced neural proliferation in the hippocampal dentate gyrus of pups after prenatal ethanol exposure, and the mechanism may be associated with increased ex-pression of protein kinase C α activating the ceramide/ceramide-1-phosphate pathway.     

颅骨修补对重型颅脑损伤术后意识恢复的影响

目的探讨颅骨修补对重型脑外伤去骨瓣减压术后长期昏迷病人的影响。方法将47例重型脑外伤去骨瓣减压术后3个月内未清醒(GSC≤8)病人分2组:颅骨修补组20例,对照组27例。颅骨修补组在颅骨修补术后第3个月和第6个月分别进行GOS评分,对照组在对应时间进行随访评估,评估分为有效(GOS 3~5),无效(GOS=2),死亡(GOS=1)。结果颅骨修补组总有效率高于对照组(P<0.05);2组病死率比较无明显差异(P>0.05)。颅骨修补组修补术后第6个月评估,去骨瓣术前一侧瞳孔散大病人有效率高于两侧瞳孔散大病人(P<0.05),两侧颅骨缺损有效率高于一侧颅骨缺损病人(P<0.05),术前GCS评分高的病人有效率高于GCS评分低的病人(P<0.05);性别和修补材料对预后的影响差异无统计学意义(P>0.05)。结论颅骨修补有利于脑外伤术后长期昏迷病人的清醒。     

An optimal dose of tea polyphenols protects against global cerebral ischemia/reperfusion injury

Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral ischemia/reperfusion injury rat model was established using a modified four-vessel occlusion method. Rats were treated with different doses of tea polyphenols (25, 50, 100, 150, 200 mg/kg) via intraperitoneal injection. Results showed that after 2, 6, 12, 24, 48 and 72 hours of reperfusion, peroxide dismutase activity and total antioxidant capacity in brain tissue gradually increased, while malondialdehyde content gradually decreased after tea polyphenol intervention. Tea polyphenols at 200 mg/kg resulted in the most apparent changes. Terminal deoxynucleotidyl transferase-mediated nick end labeling and flow cytometry showed that 200 mg/kg tea polyphenols significantly reduced the number and percentage of apoptotic cells in the hippocampal CA1 region of rats after cerebral ischemia/reperfusion injury. The open field test and elevated plus maze experiments showed that tea polyphenols at 200 mg/kg strengthened exploratory behavior and reduced anxiety of cerebral ischemia/reperfusion injured rats. Experimental findings indicate that tea polyphenols protected rats against cerebral ischemia/ reperfusion injury and 200 mg/kg is regarded as the optimal dose.     

Decreased frontal lobe function in people with Internet addiction disorder

In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in online game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho- line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder.     

Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng’s Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng’s Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.     

Probe substrate and enzyme source-dependent inhibition of UDP-glucuronosyltransferase (UGT) 1A9 by wogonin

Background

Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R&D process of drugs or herbal ingredients.

Objective

To evaluate the inhibition potential of wogonin (an important flavonoid isolated from the root of Scutellaria baicalensis) towards one of the most important phase II DMEs, UDP-glucuronosyltransferase (UGT) 1A9.

Methods

Both recombinant UGT1A9-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and human liver microsomes (HLMs)-catalyzed propofol glucuronidation reaction were used as two different probe reactions.

Results

Wogonin noncompetitively inhibited recombinant UGT1A9-catalyzed 4-MU glucuronidation, and exerted competitive inhibition towards HLMs-catalyzed propofol glucuronidation. The inhibition kinetic parameters (K_i) were calculated to be 3.2 µM and 52.0µM, respectively.

Conclusion

Necessary monitoring was needed when wogonin was co-administered with the clinical drugs mainly undergoing UGT1A9-mediated glucuronidation elimination. Additionally, probe reactions-dependent inhibition of wogonin towards the activity of UGT1A9 should be paid attention when translating these in vitro data into in vivo situation.