Overview of Secondary Neurulation

Secondary neurulation is a morphological process described since the second half of the 19th century; it accounts for the formation of the caudal spinal cord in mammals including humans. A similar process takes place in birds. This form of neurulation is caused by the growth of the tail bud region, the most caudal axial region of the embryo. Experimental work in different animal species leads to questioning dogmas widely disseminated in the medical literature. Thus, it is clearly established that the tail bud is not a mass of undifferentiated pluripotent cells but is made up of a juxtaposition of territories whose fate is different. The lumens of the two tubes generated by the two modes of neurulation are continuous. There seem to be multiple cavities in the human embryo, but discrepancies exist according to the authors. Finally, the tissues that generate the secondary neural tube are initially located in the most superficial layer of the embryo. These cells must undergo internalization to generate the secondary neurectoderm. A defect in internalization could lead to an open neural tube defect that contradicts the dogma that a secondary neurulation defect is closed by definition.     

Perspectives : The Role of Clinicians in Understanding Secondary Neurulation

During the last two decades, there have been remarkable advances in knowledge regarding secondary neurulation. An increased number of cases of occult spinal dysraphism and progress in basic embryology research have provoked the continuous discovery of new disease entities and the reclassification of occult spinal dysraphic lesions. Examples of such changes are described. The characteristics of secondary neurulation compared with those of primary neurulation are listed and discussed. Our fundamental questions include what the evolutionary significance of secondary neurulation is and what the advantages of having secondary neurulation are. However, our current data and speculations are insufficient to support scientific inference. The direction of future progress of research in this field is predicted. The role of clinicians in this progress is emphasized.     

Expression of neuronal markers in the secondary neurulation of chick embryos

Objective The goal of our study was to evaluate the expression patterns of neuronal antigens during the process of secondary neurulation. Materials and methods Chick embryos of Hamburger and Hamilton stages 16, 18, 20, 22, 24, 26, 30, 35, 40, and 45 were harvested, and tail sections were processed for neuronal antigen studies. Results and conclusions The areas and periods showing positive reactions for each antigen are as follows: neuronal cell adhesion molecule (N-CAM): the secondary neural tube and notochord from stages 18 to 26 and the germinal and mantle layers from stages 30 to 45; synaptophysin: the caudal cell mass, secondary neural tube, and notochord from stages 22 to 26, the germinal and mantle layers from stages 30 to 45, and the marginal layer at the later stages of development; neurofilament-associated protein (3A10): the dorsal white matter, dorsal root ganglion, and scattered cells around the germinal layer from stages 35 to 45; and neuronal nuclear-specific protein (NeuN): the mantle layer at stage 35, which shows decreased reaction at stages 40 and 45; islet-1: no remarkable staining on the caudal cell mass or on the other neural structures at all stages. Our results indicate that neuronal markers of the secondary neurulation in chick embryos have their own chronological patterns of expression. At early stages of secondary neurulation, N-CAM and synaptophysin are thought to modulate the differentiation of structures derived from the caudal cell mass. At later stages, N-CAM, synaptophysin, 3A10, and NeuN seem to be involved in the maturation of the caudal spinal cord.     

Junctional Neurulation : A Junction between Primary and Secondary Neural Tubes

Recent case reports of junctional neural tube defect (JNTD) which is a peculiar type of spinal anomaly showing the functional disconnection of the primary and secondary neural tubes has risen interest in the process of junctional neurulation (the connection between the two neural tubes) during development. This article summarizes the clinical features of the JNTD and reviews the literature on the basic research on junctional neurulation.     

4001/转染bFGF基因骨髓间充质干细胞在珊瑚骨表面生长状况

目的：将转染bFGF基因的骨髓间充质干细胞与珊瑚骨的复合培养,观察转染bFGF基因的BMSCs在珊瑚支架材料上生长状况。材料和方法：穿刺抽取新西兰大白兔胫骨骨髓,采用密度梯度离心法分离BMSCs,采用贴壁筛选法对分离出的BMSCs进行纯化,利用脂质体转染bFGF-pcDNA3到BMSCs。取生长良好的转染bFGF基因BMSCs和未转染的BMSCs,分别接种于不同珊瑚表面,采用MTT法观察细胞－支架联合培养BMSCs的增殖情况和利用扫描电镜观察珊瑚支架上细胞的生长状况。结果：MTT法检测显示细胞－支架联合培养转染组细胞与联合培养未转染组细胞增殖相比有统计学差异（P﹤0.05）,联合培养转染组细胞生长增殖强于未转染组细胞。而联合培养的转染组细胞同单纯培养转染组细胞增殖相比无统计学差异（P>0.05）。扫描电镜观察显示复合BMSCs细胞贴附在珊瑚上,并在材料上完全铺展,形态多样,细胞向孔内长入或跨越微孔表面,部分区域有细胞外基质形成。 结论：转染bFGF基因的骨髓间充质干细胞在珊瑚支架材料上生长状况较未转染组好,珊瑚人工骨不影响BMSCs的增殖,可以作为BMSCs支架材料构建组织工程骨。     

Cytokinetics of secondary neurulation in chick embryos: Hamburger and Hamilton stages 16–45

Objectives In an attempt to understand the events in the secondary neurulation in embryonic stage, we investigated cytokinetic changes in the tail bud of normal developing chick embryos.Materials and methods We investigated chick embryos of Hamburger and Hamilton stages 16–45 by staining for proliferating cell nuclear antigen (PCNA) and applying the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method.Results and conclusions The cytokinetics of secondary neurulation have several distinctive properties: a general chronological delay compared to primary neurulation; absence of ventrodorsal differences; larger rostrocaudal differences; and degeneration of the distal end of the spinal cord in the later stages of development. These differences in morphogenetic and cytokinetic behavior between primary and secondary neurulation may help to improve our understanding of anomalies originating during secondary neurulation.     

颅脑手术前后继发性癫痫的动态脑电图监测

目的 了解颅脑手术前后继发性癫痫的动态脑电图表现特点及其与手术的关系。方法 选择290例颅内占位性疾病患者,术前1～3d及术后1周、1～3月分别观察其EEG表现。结果 术前有癫痫发作(A组)128例,EEG示痫样放电者117例,痫波检出率为91.4％。术后97例无临床发作,有效率为75.8％;术前无癫痫发作(B组)162例,EEG可见痫样放电者24例。术后新发癫痫19例,均可见痫样放电。结论 开颅手术是治疗继发性癫痫的有效手段,但也可能是导致继发性癫痫的原因之一。     

Increasing Independence in Autism Spectrum Disorders: A Review of Three Focused Interventions

The features of autism that inhibit the independent demonstration of skills, as well as three effective interventions for increasing independence, are explored in this review article. Independent performance may prove difficult for individuals with autism spectrum disorders (ASD) due to the core deficits of the disability, as well as executive function deficits that impact initiation and generalization. These difficulties, coupled with intervention strategies that encourage over-reliance on adult support, contribute to poor long term outcomes for adults with ASD in employment, housing, and relationship development. Self-monitoring, video modeling, and individual work systems each emphasize a shift in stimulus control from continuous adult management to an alternative stimulus and have proven successful in addressing executive function deficits and increasing independence.     

Secondary degeneration of the optic nerve following partial transection: The benefits of lomerizine

Secondary degeneration is a form of ‘bystander’ damage that can affect neural tissue both nearby and remote from an initial injury. Partial optic nerve transection is an excellent model in which to unequivocally differentiate events occurring during secondary degeneration from those resulting from primary CNS injury. We analysed the primary injury site within the optic nerve (ON) and intact areas vulnerable to secondary degeneration. Areas affected by the primary injury showed morphological disruption, loss of β-III tubulin axonal staining, reduced myelinated axon density, greater proteoglycan expression (phosphacan), increased microglia and macrophage numbers and increased oxidative stress. Similar, but less extreme, changes were seen in areas of the optic nerve undergoing secondary degeneration. The CNS-specific L- and T-type calcium channel blocker lomerizine alleviated some of the changes in areas vulnerable to secondary degeneration. Lomerizine reduced morphological disruption, oxidative stress and phosphacan expression, and limited early increases in macrophage numbers. However, lomerizine failed to prevent progressive de-myelination of ON axons. Within the retina, secondary retinal ganglion cell (RGC) death was significant in areas vulnerable to secondary degeneration. Lomerizine protected RGCs from secondary death at 4 weeks but did not fully restore behavioural function (optokinetic nystagmus). We conclude that blockade of calcium channels is neuroprotective and limits secondary degenerative changes following CNS injury. However such an approach may need to be combined with other treatments to ensure long-term maintenance of full visual function.     

Secondary progressive multiple sclerosis: A national consensus paper on diagnostic criteria

BackgroundIn clinical practice, the diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed, retrospective and non-reproducible, as there are no consensus criteria that define the advent of SPMS. Early identification of SPMS is essential to improve patient care.MethodsEight regional board meetings in France involving 56 multiple sclerosis (MS) experts (neurologists) were convened to discuss diagnostic criteria for SPMS. Subsequently, a national board meeting of 13 neurologists (with an expert representing each geographical region) was held to review points of convergence or divergence between regions and to develop a national consensus document.ResultsBased on the discussions from the regional boards, the MS experts at the national board retained the worsening of the EDSS score, with compatible clinical features, as the only consensus criterion for the diagnosis of SPMS in clinical practice. The patient should have experienced during at least the previous 6 months and in the absence of any relapse, a worsening in the EDSS score of +1.0 point (if the previous EDSS was ≤ 5.0) or of +0.5 point (if the previous EDSS was ≥ 5.5), with a pyramidal or cerebellar functional system score ≥ 2 and without setting a minimum EDSS score; or, in case of a stable EDSS score ≥ 4.0, a worsening of a functional score. This worsening should be confirmed within 3 to 6 months. According to the MS experts, the patient's age, duration of illness and a minimal threshold EDSS score are only risk factors for transition to SPMS. Patient reports during consultation and cognitive impairment are important warning signs, which should trigger an objective assessment with specific tests or closer monitoring. Clinical relapse and/or MRI activities are non-discriminatory for making the diagnosis of SPMS.ConclusionsThe experts defined precise diagnostic criteria adapted to clinical practice for earlier identification of SPMS, paving the way for better management of this stage of the disease.     

利多卡因抑制颅脑损伤后继发性脑损害的临床研究

目的：寻找能控制脑外伤后继发性脑损害的发生发展的药物或方法。方法：53例脑外伤病人，随机分为治疗组（A）、对照组（B），A组25例持续应用利多卡因七天。结果：A组25例血中儿茶酚胺，肌酐，血糖以及脑脊液中乳酸脱氢酶，磷酸肌酸激酶，苷露醇和速尿的用量，应激性溃疡发生率，死亡植物生存率均明显低于对照组，结论：利多卡因能抑制颅脑损伤后继发性脑损害的发生发展。     

Secondary verbal memory: a potential endophenotype of schizophrenia

This study aimed at identifying neuropsychological endophenotypes of schizophrenia which met the criteria of stability and sensitivity. Twenty-six non-schizophrenic first-degree relatives together with their affected family members (all simplex-families) underwent assessment with a comprehensive neuropsychological test battery both at baseline and 13 months follow-up. Follow-up patients were in a state of stable remission. Further, 21 unrelated, demographically balanced, non-vulnerable controls were tested one at a time. A principal components analysis of our test battery resulted in four factors: (1) Vigilance, attention, and psychomotor, (2) secondary verbal memory, (3) immediate and working memory, and (3) abstraction and problem solving. At baseline testing our study revealed a pattern of selective cognitive deficits in the relative group that is less pronounced, yet qualitatively similar, to that found in the patient sample. The most severe deficits displayed both the patients and their relatives in the secondary verbal memory domain. The dysfunctions in secondary verbal memory at baseline testing significantly correlated with negative symptoms only. Secondary verbal memory deficits proved to be relatively independent of age at onset of illness, illness duration, and neuroleptic dosage. Longitudinally, dysfunctions in the patients' secondary verbal memory fluctuated over time and with negative symptoms, and persisted in remitted patients at the same level as in their relatives. In conclusion, the secondary verbal memory met the criteria of relative stability and sensitivity in our sample of simplex-families. Thus, the secondary verbal memory seems to be a potential endophenotypic marker of schizophrenia, even for cases with a hypothetically lower genetic loading.     

利多卡因治疗外伤性蛛网膜下腔出血疗效分析

目的探讨早期静脉注射利多卡因对外伤性蛛网膜下腔出血（tsAH）继发性脑损伤的治疗作用。方法重度颅脑损伤后SAH患者60例（GCS评分≤8分）。随机分为治疗组（早期静脉注射利多卡因组）和对照组。在治疗前后对患者均进行GCS评分、颅内压（ICP）测定以及头部CT、发射计算机体层摄影（ECT）、经颅多普勒（TCD）检查。结果利多卡因治疗7d后即出现颅内压降低、挫伤脑组织血流供应改善、脑水肿减轻，与对照组比较，有明显差异（P〈0．01）；GCS评分在利多卡因治疗7d、14d后较对照组明显增加（P〈0．01）。结论早期静脉注射利多卡因能明显减轻颅脑损伤后SAH继发性脑组织损伤的程度，有利于神经功能的早期恢复。     

骨髓间充质干细胞对系统性红斑狼疮患者T细胞活化的影响

背景：骨髓间充质干细胞具有免疫调节作用,可治疗自身免疫性疾病。 目的：探讨在体外人骨髓间充质干细胞对系统性红斑狼疮患者T细胞活化的影响。 方法：分离、培养人骨髓间充质干细胞,培养至第3代以后的细胞胰蛋白酶消化后用流式细胞仪确定其浓度,按照不同浓度将骨髓间充质干细胞设为1×108,1×107L-1两组。取肝素抗凝新鲜27例系统性红斑狼疮患者患者外周血10 mL,分离培养T淋巴细胞,以1×109 L-1的细胞浓度,100 µL/孔,接种两组骨髓间充质干细胞上,以单纯统性红斑狼疮患者的T淋巴细胞作为对照组。通过流式细胞术计算CD3+ T细胞CD25(IL-2R)和CD38细胞的表达率。 结果与结论：与对照组比较,1×108 L-1浓度组的骨髓间充质干细胞对系统性红斑狼疮患者CD25及CD38的表达呈明显抑制作用(P < 0.01),1×107 L-1浓度组,无明显变化。结果表明：骨髓间充质干细胞抑制系统性红斑狼疮患者T细胞的活化,且对这种抑制作用具有数量依赖性。     

The Impact of Emotional Exhaustion on Psychological Factors in Workers with Secondary Traumatic Experiences: A Multi-Group Path Analysis

Objective The objective of the present study was to explore causal pathways to understand how second traumatic experiences could affect the development of emotional exhaustion and psychiatric problems. Methods A total of 582 workers who had jobs vulnerable to secondary traumatic experiences were enrolled for this study. Emotional exhaustion, secondary trauma, resilience, perceived stress, depression, anxiety, and sleep problems were evaluated. A model with pathways from secondary traumatic experience score to depression and anxiety was proposed. The participants were divided into three groups according to the resilience: the low, middle and high resilience group. Results Resilience was a meaningful moderator between secondary traumatic experiences and psychiatric problems. In the path model, the secondary trauma and perceived stress directly and indirectly predicted perceived stress, emotional exhaustion, depression, anxiety, and sleep problems in all three groups. Direct effects of perceived stress on depression and anxiety were the largest in the low resilience group. However, direct effects of secondary trauma on perceived stress and emotional exhaustion were the largest in the high resilience group. Conclusion Understanding the needs of focusing for distinct psychological factors offers a valuable direction for the development of intervention programs to prevent emotional exhaustion among workers with secondary traumatic experiences.     

羟基磷灰石/胶原蛋白复合支架上骨髓间充质干细胞的增殖与分化

摘要 背景：最近胶原蛋白作为细胞体外三维立体支架材料被大量用于组织工程,但胶原蛋白支架材料机械强度低,很难承受较大外力,为此将胶原蛋白与羟基磷灰石制成复合支架材料,探索复合支架的生物相容性和生物活性。 目的：验证大鼠骨髓间充质干细胞在羟基磷灰石/胶原蛋白复合支架上的增殖与分化情况。 方法：贴壁法分离SD大鼠骨髓间充质干细胞,分别在平板、胶原支架、羟基磷灰石/胶原蛋白复合支架上,观察3种条件下细胞的生长状况,四甲基偶氮唑盐法检测其增殖情况。培养14,21 d后,考察细胞碱性磷酸酶活性及胶原蛋白分泌量。 结果与结论：发现骨髓间充质干细胞在羟基磷灰石/胶原蛋白复合支架上铺展良好,其增殖率显著高于纯胶原蛋白支架上培养的细胞,并高于平板培养细胞。骨髓间充质干细胞在羟基磷灰石/胶原蛋白复合支架上的碱性磷酸酶活性及胶原蛋白分泌量明显高于纯胶原蛋白支架,高于平板培养。结果提示,羟基磷灰石/胶原蛋白复合材料能促进骨髓间充质干细胞的增殖和分化,并诱导骨髓间充质干细胞向成骨细胞分化。 关键词：胶原蛋白;羟基磷灰石;骨组织工程;骨髓间充质干细胞;支架 doi:10.3969/j.issn.1673-8225.2010.47.014     

Secondary prevention of coronary heart disease: patient beliefs and health-related behaviour

OBJECTIVE: Coronary heart disease (CHD) is a leading cause of illness and death in Western society. The present study was designed to evaluate the utility of illness perceptions and medication beliefs in predicting secondary preventive behaviour among patients with CHD. An extended version of Leventhal's self-regulatory model (SRM) was used as a theoretical framework for this study [Leventhal H, Nerenz DR, Steele DJ. Illness perceptions and coping with health threat. In: Baum A, Taylor SE, Singer JE, editors. Handbook of psychology and health, Volume IV: social psychological aspects of health. Hillsdale (NJ): Erlbaum, 1984. pp. 219-52; Horne R, Weinman J. Self-regulation and self-management in asthma: exploring the role of illness perceptions and treatment beliefs in explaining non-adherence to preventer medication. Psychol Health 2002;17(1):17-32]. METHOD: Medical and demographic data were gathered from the medical charts of 1611 patients with established CHD from 35 randomly selected general practices. Self-report data about patients' lifestyles (diet, exercise, smoking, alcohol consumption and medication adherence) and information on illness and medication beliefs were provided from postal questionnaire (1084 patients responded; 69% response rate). The relationship between patients' beliefs and their secondary preventive behaviour was examined using regression analyses. RESULTS: Illness perceptions appeared to be only weak predictors of smoking, exercise, diet, alcohol consumption and medication adherence, accounting for about 2% of the variance in these behaviours. Medication beliefs were moderately related to medication adherence, accounting for about 7% of the variance in scores. A strong belief in the necessity of one's medication and a lower level of concern about one's medication were associated with higher levels of adherence. CONCLUSIONS: An illness perception approach did not prove helpful in predicting secondary preventive behaviour among this group of patients. However, beliefs about medications appear to be reasonable predictive of medication adherence.     

Secondary prevention of stroke by a primary health care approach: An open-label cluster randomised trial

Background and aimIncreasing stroke burden in developing countries necessitates measures to strengthen health systems. We aimed to evaluate whether a Community Health Worker (CHW) based educational intervention will improve risk factor control among stroke survivors and enhance behavior change communication.MethodAn open-label, cluster-randomized trial was conducted in rural area of Thiruvananthapuram district, Kerala from December 2017 to December 2018. A CHW-based educational intervention in addition to standard of care was provided in intervention arm and compared to standard clinical care in the control arm with follow-up at three and six months. The primary outcome measures were risk factor control and quality of behavior change communication provided by CHWs.ResultsOf the 234 Stroke/TIA survivors enrolled, the mean age (SD) was 59.43 (11.07) years. At 6-month follow up, all patients with smokeless tobacco consumption had quit in the intervention arm (5 at baseline and 0 at six months) and no relapse in smoking was found (as compared to control arm wherein 9 at baseline and one at 6 months). The control of hypertension and diabetes was not significant at 3 months and 6 months in both intervention and control groups. Home visits as well as health education on risk factors by CHWs in the intervention arm were significantly higher.ConclusionCommunity health worker-based intervention is feasible in resource constrained settings for secondary stroke prevention. Training of CHW on risk factor control and lifestyle modifications for stroke survivors enhances quality of health education provided by health services.     

基因芯片分析成骨生长肽对OPG-/-小鼠骨髓间充质干细胞的作用

背景：合成成骨生长肽在体外可刺激骨髓间充质干细胞增殖和向成骨细胞分化,体内可增加骨密度改善骨质疏松,但具体作用机制尚未明确。 目的：应用小鼠全基因组芯片筛查合成成骨生长肽作用下OPG-/-小鼠骨髓间充质干细胞的差异表达基因,探索成骨生长肽作用下可能影响到的基因与信号传导通路。 方法：应用上海伯豪生物技术有限公司提供的小鼠全基因组Oligo芯片,筛选成骨生长肽干预组与空白对照组OPG-/-小鼠骨髓间充质干细胞差异表达基因,实时定量PCR分析验证部分与增殖分化相关的差异表达基因,并结合聚类分析及通路分析来探索成骨生长肽的作用机制。 结果与结论：芯片结果显示,成骨生长肽作用后使346条基因表达下调,121条基因表达上调。PCR验证结果与芯片结果相符。经BioCarta通路分析,涉及6条通路蛋白;经KEGG通路分析,涉及12条通路。成骨生长肽对OPG-/-小鼠骨髓间充质干细胞的作用涉及多条信号传导通路,其中MAPK信号传导通路可能对其促增殖起着至关重要作用。