Low dose extended exposure to saxitoxin and its potential neurodevelopmental effects: A review

Saxitoxin (STX) and its analogs, the paralytic shellfish toxins (PSTs), are a group of potent neurotoxins well known for their role in acute paralytic poisoning by preventing the generation of action potentials in neuronal cells. They are found in both marine and freshwater environments globally and although acute exposure from the former has previously received more attention, low dose extended exposure from both sources is possible and to date has not been investigated. Given the known role of cellular electrical activity in neurodevelopment this pattern of exposure may be a significant public health concern. Additionally, the presence of PSTs is likely to be an ongoing and possibly increasing problem in the future. This review examines the neurodevelopmental toxicity of STX, the risk of extended or repeated exposure to doses with neurodevelopmental effects, the potential implications of this exposure and briefly, the steps taken and difficulties faced in preventing exposure.     

达芬奇机器人手术系统在我国胸心外科应用的科学性和伦理学系统评价

目的评价达芬奇机器人手术系统（da Vinci Surgical System,dVSS）在我国胸心外科应用的有效性、安全性和伦理性,为其临床应用提供证据。方法检索VIP、CNKI、万方数据库、CBM、国家卫计委官方网站等,PubMed、Cochrane图书馆、Google学术检索引擎、WHO临床试验注册检索平台、ClinicalTrials．gov、中国临床试验注册中心、澳大利亚一新西兰临床试验注册中心、英国ISRCTN,检索时限均为从建库至2014年1月,收集dVSS手术治疗在我国胸心外科疾病的临床研究,用GRADE评价纳入文献质量,对dVSS临床应用有效性、安全性和伦理性的相关指标进行评价。结果共纳入31篇文献,其中病例对照研究4篇,回顾性病例分析27篇,共1037例胸心外科疾病患者,文献质量均为极低级别。dVSS在胸心外科的适应证包括冠状动脉旁路移植术、瓣膜成形术或置换术、胸部肿瘤切除术等。与开放手术及胸腔镜手术相比,dVSS安全性和有效性较佳,但疾病治疗经济负担较重。dVSS能使患者受益,有助于提高胸心外科医疗水平,该系统适用的科目和主体资格合法,但成熟度有待提升,相关措施有待完善。其在研究、引进及应用方面的伦理存在系列问题有待重视。结论dVSS在胸心外科临床应用相对安全、有效,但研究质量有待提升;其在胸心外科临床应用的经济性、伦理学研究有待进一步开展。进一步完善dVSS在胸心外科临床应用的相关防范、追责及保护患者措施,并借助现有临床伦理审查平台体系,进行全程伦理监管。     

Effect of insulin-resistance on circulating and adipose tissue MMP-2 and MMP-9 activity in rats fed a sucrose-rich diet

Background and aimAdipose tissue produces different metalloproteinases (MMPs), involved in adipogenesis and angiogenesis. Different studies have shown that in obesity the behavior of different MMPs may be altered. However there are scarce data about the effect of insulin-resistance (IR) on MMP-2 and MMP-9 activity in adipose tissue. Our aim was to determine whether sucrose induced IR modifies MMP-2 and MMP-9 behavior in expanded visceral adipose tissue and the contribution of this tissue to circulating activity of these gelatinases.Methods and resultsMale Wistar rats were fed with standard diet (Control) or standard diet plus 30% sucrose in the drinking water throughout 12 weeks (SRD). In epididymal adipose tissue vascular density, size and adipocyte density, PPARγ expression and MMP-2 and -9 were measured. Adipose tissue from SRD presented higher adipocyte size (6.32 ± 8.71 vs 4.33 ± 2.17 × 10³ μm², p = 0.001) lower adipocyte density (164 (130–173) vs 190 (170–225) number/mm², p = 0.046) and lower vascular density (16.2 (12.8–23.5) vs 28.1 (22.3–46.5) blood vessels/mm², p = 0.002) than Control. MMP-2 and MMP-9 activity was decreased in SRD (1.93 ± 0.7 vs 3.92 ± 0.9 relative units, p = 0.048 and 1.80 ± 0.8 vs 5.13 ± 1.7 relative units, p = 0.004 respectively) in accordance with lower protein expression (0.35 ± 0.20 vs 2.71 ± 0.48 relative units, p = 0.004 and 1.12 ± 0.21 vs 1.52 ± 0.05 relative units, p = 0.036 respectively). There were no differences in PPARγ expression between groups.ConclusionInsulin resistance induced by SRD decreases MMP-2 and MMP-9 activity in adipose tissue which would not represent an important source for circulating MMP-2 and -9. In this state of IR, PPARγ would not be involved in the negative regulation of adipose tissue gelatinases.     

Data types – The first step to planning your study

This first in the series on clinical research will focus on the basics of data – the types of data (with examples of a rheumatoid arthritis study) and how to numerically and graphically represent these. Knowing the types of data is indeed the first step to planning a study as it leads to a proper planning, entering of data and finally suitable analysis.     

Genetic analysis of matrin 3 gene in French amyotrophic lateral sclerosis patients and frontotemporal lobar degeneration with amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are adult-onset neurodegenerative diseases with overlapping clinical characteristics. They share common genetic causes and pathologic hallmarks such as TDP-43 neuronal accumulations. Recently, exome analysis identified mutations in matrin 3 (MATR3) gene in patients with familial ALS, suggesting a role for this gene in the pathogenesis of the disease. MATR3 is a nuclear matrix protein with DNA and RNA binding domains that interacts with TDP-43. To confirm the contribution of MATR3 to ALS, we studied a French cohort of 153 familial ALS or ALS/FTLD patients, without finding any variant. We conclude that mutations in MATR3 are rare in French familial ALS and ALS with FTLD patients.