Molecular analysis of a Japanese family with Lesch-Nyhan syndrome: identification of mutation and prenatal diagnosis

Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. We examined the HPRT gene mutation for prenatal diagnosis in a Japanese family. A single nucleotide substitution of C to T in exon 3 was identified by direct sequencing analysis of the HPRT gene of a Lesch-Nyhan patient. This substitution resulted in a nonsense mutation, CGA (Arg) to TGA (stop), at codon 51. Utilizing an Xho I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was heterozygous, but the grandmother normal. By the same method, prenatal genetic diagnosis was performed using chorionic villus samples (CVS), and showed that the fetus had the mutant allele.     

Spatial properties of vertical eye movement-related neurons in the region of the interstitial nucleus of Cajal in awake cats

Summary 1. Maximal activation directions of vertical burst-tonic and tonic neurons in the region of the interstitial nucleus of Cajal (INC) were examined in alert cats during vertical vestibulo-ocular reflex induced by sinusoidal rotation (at 0.11 Hz±10 deg, or 0.31 Hz±5 deg) in a variety of vertical planes using a null point analysis. The results were compared with the angles of anatomical and functional planes of vertical canals reported by Blanks et al. (1972) and Robinson (1982), and with the angles of vertical eye muscles measured in this study and by Ezure and Graf (1984). 2. Maximal activation directions of 23 cells (21 burst-tonic and 2 tonic neurons) were determined from their responses during rotation in 4 or more different vertical planes. All cells showed sinusoidal gain curves and virtually constant phase values except near the null regions, suggesting that their responses were evoked primarily by canal inputs. Phase values of 5 cells near the null regions depended on the rotation plane, suggesting additional otolith inputs. We used a measurement error range of ±10 deg for calculating the maximal activation directions from the null regions of individual cells and the values of error ranges of null calculation. Of the 23, the maximal activation directions of 7 cells were outside the measurement error ranges of vertical eye muscle angles and within the ranges of vertical canal angles (class A), those of 5 cells were within the ranges of eye muscle angles and outside the ranges of vertical canal angles (class B), and those of the remaining 11 cells were in the overlapping ranges for both angles (class C). Even if only the cells in which 5 or more measurement points were taken to determine maximal activation directions (n = 15), the results were similar. During vertical rotation with the head orientation +60 deg off the pitch plane, dissociation of cell activity and vertical compensatory eye movement was observed in 5 cells in class A or C that had null angles near +45 deg. These results suggest that the cells in class A and B carried individual vertical canal and oculomotor signals, respectively, although it is difficult to tell for the majority of cells (class C) which signals they reflected. Some cells in class A and C were antidromically activated from the medial longitudinal fasciculus at the level of abducens nucleus, suggesting that the signals carried by these cells may be sent to the lower brainstem. 3. Most burst-tonic neurons did not respond to horizontal rotation; significant responses were obtained in only 3 of 10 cells tested for which the gain was only 14–17% of their maximal vertical gain. There was no clear difference in gain or phase values of the responses to vertical rotation, or in eye position sensitivity (during spontaneous saccades) between cells whose responses coincided with individual vertical canal angles and those matching the angles of vertical recti muscles. The values of phase lag (re head acceleration during pitch rotation) and eye position sensitivity of these cells are still smaller compared to those of extraocular motoneurons reported by Delgado-Garcia et al. (1986), although they were larger than those of secondary vestibulo-ocular neurons (Perlmutter et al. 1988). All these results suggest that the signals carried by burst-tonic and tonic neurons in the INC region are different from oculomotor signals. 4. Similar analysis was done for comparison for 19 other cells that did not show close correlation with spontaneous eye movement but whose activity was clearly modulated by pitch rotation (pitch cells). More than a half (10/19) had maximal activation directions outside the measurement error ranges of individual vertical canal angles, and many shifted towards roll. Horizontal rotation produced responses with higher gain than burst-tonic neurons, suggesting a difference in the spatial response properties of burst-tonic and tonic neurons on one hand and pitch cells on the other.     

Change‐point detection of cognitive states across multiple trials in functional neuroimaging

Many functional neuroimaging‐based studies involve repetitions of a task that may require several phases, or states, of mental activity. An appealing idea is to use relevant brain regions to identify the states. We developed a novel change‐point methodology that adapts to the repeated trial structure of such experiments by assuming the number of states stays fixed across similar trials while allowing the timing of change‐points to change across trials. Model fitting is based on reversible‐jump MCMC. Simulation studies verified its ability to identify change‐points successfully. We applied this technique to data collected via functional magnetic resonance imaging (fMRI) while each of 20 subjects solved unfamiliar arithmetic problems. Our methodology supplies both a summary of state dimensionality and uncertainty assessments about number of states and the timing of state transitions. Copyright © 2016 John Wiley & Sons, Ltd.     

Point estimation in adaptive enrichment designs

Adaptive enrichment designs are an attractive option for clinical trials that aim at demonstrating efficacy of therapies, which may show different benefit for the full patient population and a prespecified subgroup. In these designs, based on interim data, either the subgroup or the full population is selected for further exploration. When selection is based on efficacy data, this introduces bias to the commonly used maximum likelihood estimator. For the situation of two‐stage designs with a single prespecified subgroup, we present six alternative estimators and investigate their performance in a simulation study. The most consistent reduction of bias over the range of scenarios considered was achieved by a method combining the uniformly minimum variance conditionally unbiased estimator with a conditional moment estimator. Application of the methods is illustrated by a clinical trial example.     

酚醛树脂对高软化点沥青的发泡行为及生物挂膜性能的影响

以高软化点沥青为原料,采用自发泡法制备泡沫炭,将其用作生物污水处理固菌载体材料,并通过添加适量的酚醛树脂以提高泡沫炭的开孔率,进而提高其生物挂膜量。研究结果表明：当在高软化点沥青中添加酚醛树脂的质量分数为30%时,所制泡沫炭的开孔率高达100%,生物挂膜量（质量分数）达5.4%;当酚醛树脂的添加质量分数为40%时,所制泡沫炭的压缩强度达5.2 MPa,但其开孔率较低,孔结构的均一性较差。     

温经通督药熥法配合艾灸治疗寒湿闭阻型腰痛临床研究

目的:观察中药包外熥配合艾灸委中穴治疗寒湿闭阻型腰痛的临床疗效,并探讨其效应与作用机制。方法:选取96例确诊为寒湿闭阻型腰痛患者随机分为治疗组和对照组各48例,治疗组采用中药包循经外熥配合艾灸委中穴治疗,对照组给予口服洛索洛芬钠片及腰椎推拿治疗,两组均以10 d为1个疗程,分别于第1个疗程、第2个疗程后观察两组患者腰痛相关症状、体征等改善情况,通过观察两组患者视觉模拟评分法(visual analogue scale,VAS)评分、日本腰椎骨科协会下腰痛(japanese orthopaedic association scores,JOA)评分和Oswestry功能障碍指数问卷表(oswestry disability index,ODI)评分的变化情况对其效应进行分析与评估,于1个月后采用患者自填健康调查表(MOS 36-ltem short form health survey,SF-36)评估生存质量,并分析各组临床疗效,3个月后随访分析各组复发率。结果:两组患者VAS评分和ODI评分均有所减少,较对照组,治疗组减少更为明显(P0.05);两组患者JOA评分中主观症状、临床体征和日常活动受限度比较,其评分均有增加,较对照组,治疗组JOA评分增加更为明显(P0.05),两组膀胱功能比较,差异无统计学意义(P0.05);两组患者SF-36评分均增高,较对照组,治疗组增高更为明显(P0.05);治疗组效率为93.75%,治愈率68.75%,3个月后复发率4.17%,均显著优于对照组(P0.05)。结论:温经通督药熥法配合艾灸委中穴治疗寒湿闭阻型腰痛,疗效显著。     

艾灸肺俞穴治疗儿童哮喘冷哮证急性发作的临床观察

目的 观察艾灸肺俞穴治疗儿童哮喘冷哮证急性发作的临床疗效,为针灸治疗哮喘提供临床证据。方法 选取符合研究标准的哮喘冷哮证患儿87例,随机分为2组,对照组予以常规西药治疗,观察组在常规西药治疗的基础上予以艾灸双侧肺俞穴治疗,观察CRP、IgE、IL-1、IL-6、EOS水平及肺功能和症状积分的变化,对比2组患儿临床疗效。结果 治疗后观察组CRP、IgE、IL-6、EOS等指标水平均明显低于对照组（P＜0.05~0.01）;观察组FEV1、PEF水平明显优于对照组（P＜0.05）;观察组症状积分明显低于对照组（P＜0.05）;观察组显效率（73.81%）明显高于对照组（53.33%,P＜0.05）。结论 艾灸肺俞穴治疗儿童哮喘冷哮证急性发作,可以明显降低患儿CRP、IgE、IL-6、EOS水平,改善肺功能,临床疗效显著。      

应用针刺夹脊穴联合半夏厚朴汤治疗海洛因依赖者稽延性戒断症状的效果及对患者TESS评分的影响

目的:探讨应用针刺夹脊穴联合半夏厚朴汤治疗海洛因依赖者稽延性戒断症状的效果及对患者副反应量表(Treatment Emergent Symptom Scale,TESS)评分的影响。方法:选取2018年8月-2019年8月陕西省某戒毒所进行强制脱毒治疗三个月以上,再次自愿进行康复治疗的海洛因依赖稽延性戒断症患者18例作为研究对象。通过随机选择法将研究对象分为研究组(n=9)和对照组(n=9),研究组采用针刺夹脊穴联合半夏厚朴汤治疗,对照组仅采用针刺夹脊穴治疗。对比两组患者治疗前与治疗后1个月、3个月、6个月的疼痛评分,以及两组患者治疗后第0天、3个月、6个月失眠、情感忧郁、尿液异常、震颤、恶心呕吐、心动过速的TESS评分。结果:两组患者治疗前疼痛评分无明显差异(P>0.05),研究组治疗后1个月、3个月、6个月的疼痛评分均显著低于对照组(P<0.05);两组患者治疗后第0天失眠、情感忧郁、尿液异常、震颤、恶心呕吐、心动过速的TESS评分无明显差异(P>0.05),研究组治疗后3个月、6个月失眠、情感忧郁、尿液异常、震颤、恶心呕吐、心动过速的TESS评分显著低于对照组(P<0.05)。结论:应用针刺夹脊穴联合半夏厚朴汤治疗海洛因依赖者稽延性戒断症状疗效显著,能有效减轻患者的痛苦,值得进一步应用和推广。     

PCOS患者亚临床甲状腺功能减退与代谢异常的相关性研究

目的探讨多囊卵巢综合征(PCOS)患者亚临床甲状腺功能减退(SCH)与内分泌代谢异常的相关性。方法回顾性分析2016年6月～2018年12月在东昌府人民医院就诊的PCOS患者65例,另选取同期就诊的身体健康、月经周期和妇科B超正常的不孕症女性115例作为对照组。按促甲状腺激素(TSH)水平,PCOS患者分为A组(TSH2.5 mIU/L),B组(2.5 mIU/L≤TSH4 mIU/L),C组(TSH4.0 mIU/L),比较各组内分泌代谢特征的差异。结果PCOS组体重指数(BMI)、游离甲状腺素(FT4)、黄体生成素(LH)、LH/卵泡刺激素(FSH)、睾酮(T)及2.5 mIU/L≤TSH4 mIU/L发病率均高于对照组(P0.05),TSH4 mIU/L发病率增高(P0.05)。PCOS组内比较:随着TSH升高,糖类代谢指标均升高(P0.05);C组TSH、胰岛素抵抗β细胞功能指数高于A、B两组(P0.05);B组的FSH比A组略有升高(P0.05)。结论 PCOS患者更容易出现肥胖和代谢异常,TSH4 m IU/L组PCOS患者代谢异常更加明显,可以作为诊断PCOS患者SCH的截点。