Molecular analysis of acid ceramidase deficiency in patients with Farber disease

Farber disease is a rare, autosomal recessively inherited sphingolipid storage disorder due to the deficient activity of lysosomal acid ceramidase, leading to the accumulation of ceramide in cells and tissues. Here we report the identification of six novel mutations in the acid ceramidase gene causing Farber disease: three point mutations resulting in single amino acid substitutions, one intronic splice site mutation resulting in exon skipping, and two point mutations also leading to occasional or complete exon skipping. Of interest, these latter two mutations occurred in adjacent nucleotides and led to abnormal splicing of the same exon. Expression of the mutated acid ceramidase cDNAs in COS-1 cells and subsequent determination of acid ceramidase residual enzyme activity demonstrated that each of these mutations was the direct cause of the acid ceramidase deficiency in the respective patients. In contrast, two known polymorphisms had no effect on acid ceramidase activity. Metabolic labeling studies in fibroblasts of four patients showed that even though acid ceramidase precursor protein was synthesized in these individuals, rapid proteolysis of the mutated, mature acid ceramidase occurred within the lysosome.     

中国医药技术进步的跨越战略

本文对中国医药产业的发展提出了一个大胆设想,即：经由实施技术进步的跨越战略促进中国医药产业在２１世纪实现在质和量上的跳跃性发展。本文系统研究了在中国医药产业实施技术进步跨越战略的时机、可能性和应当创造的配套环境与措施。     

Breakfast-skipping in children and young adolescents in The Netherlands

Background: The objective of this study was to provide nationalfigures on the prevalence of breakfast-skipping and the associationwith sociodemographic variables in 4–15 year old children.Methods: Data of 4,377 children were collected. A food questionnaire(24 h recall) was completed by the parents or by the older childrenthemselves. Results: Five percent of the children in primaryschool and 13% of the children in secondary school skipped breakfastbefore going to school. Breakfast-skipping is more frequentin girls, older children, children of fathers of low educationor living with a single parent and in children attending schoolin a large city. Conclusions: The results of this study pointout the need for preventive programmes to encourage breakfastconsumption in certain groups at risk.     

An investigation of the effectiveness of ready-to-eat breakfast cereals in weight loss: comparison between single and mixed varieties

The present study investigated the effectiveness of ready-to-eat cereals eaten daily for breakfast for six weeks and as a substitute for lunch for two of these six weeks in achieving weight loss. Forty-one overweight and obese subjects (body mass index 25–35 kg/m²) were randomised to either a single cereal (SC) or a variety cereal (VC) group. All subjects consumed their allocated cereal(s) for breakfast and lunch for two weeks followed by ad libitum intake for the rest of the day. For weeks 3–6, subjects continued with their allocated cereal(s) for breakfast only and ate ad libitum for lunch and dinner. Mean weight loss at weeks two and six was −1.1 kg and −1.4 kg, respectively. At the end of week two, 85% of subjects had lost weight, and at the end of the study period (week six), 73% of subjects had achieved weight loss. Greater weight loss was observed in the VC compared with the SC group at weeks two and six. Ready-to-eat cereals eaten daily for breakfast for six weeks and used as a substitute for lunch for the first two weeks resulted in significant weight loss at week two that was sustained at week six. This study has shown that ready-to-eat breakfast cereals eaten daily for breakfast and used as a meal substitute, in particular the provision of a variety of cereals, are an effective method of achieving weight loss.     

The role of breakfast cereals in the UK diet: headline results from the National Diet and Nutrition Survey (NDNS) year 1

The first results from the new rolling programme of the UK's National Diet and Nutrition Survey (NDNS) have been published. The survey found that breakfast cereals were consumed by about 50% of those children and adults taking part, and the average amount eaten was generally in line with the recommendations by the European breakfast cereal association on portion size. Breakfast cereals provided only a small proportion of the total intake of fat, saturated fat, non‐milk extrinsic sugars and sodium, as well as contributing useful amounts of fibre (as measured by non‐starch polysaccharides). Similarities regarding breakfast cereals and their contribution to the UK diet were seen with this survey and the recent Low Income Diet and Nutrition Survey.     

Translational development of splice-modifying antisense oligomers

Introduction: Antisense nucleic acid analogues can interact with pre-mRNA motifs and influence exon or splice site selection and thereby alter gene expression. Design of antisense molecules to target specific motifs can result in either exon exclusion or exon inclusion during splicing. Novel drugs exploiting the antisense concept are targeting rare, life-limiting diseases; however, the potential exists to treat a wide range of conditions by antisense-mediated splice intervention.

Areas covered: In this review, the authors discuss the clinical translation of novel molecular therapeutics to address the fatal neuromuscular disorders Duchenne muscular dystrophy and spinal muscular atrophy. The review also highlights difficulties posed by issues pertaining to restricted participant numbers, variable phenotype and disease progression, and the identification and validation of study endpoints.

Expert opinion: Translation of novel therapeutics for Duchenne muscular dystrophy and spinal muscular atrophy has been greatly advanced by multidisciplinary research, academic-industry partnerships and in particular, the engagement and support of the patient community. Sponsors, supporters and regulators are cooperating to deliver new drugs and identify and define meaningful outcome measures. Non-conventional and adaptive trial design could be particularly suited to clinical evaluation of novel therapeutics and strategies to treat serious, rare diseases that may be problematic to study using more conventional clinical trial structures.     

莆田学院医学院大学生早餐质量及影响因素调查分析

目的 了解大学生早餐就餐质量及其影响因素,为提高大学生早餐质量提供参考依据.方法 采用分层整群抽样的方法从不同年级抽取共273名学生,用自填问卷调查法收集其早餐情况资料,应用SPSS17.0统计软件进行χ2检验和logistic回归分析.结果 早餐质量好的比例仅占25%,其就餐质量与有无医护人员、母亲学历、早餐知识的了解程度有关.结论 大学生早餐质量不佳,早餐营养知识缺乏,很有必要给大学生开展营养健康教育,提高大学生对早餐的认识,从而提高大学生的早餐质量.     

莆田学院医学院学生早餐情况调查分析

目的 以莆田学院医学生为对象,了解大学生早餐就餐情况及其影响因素,为开展大学生营养健康教育提供参考依据.方法 采用分层整群抽样的方法从不同年级抽取共273 名学生,用自填问卷调查法收集其早餐情况资料,应用spss17.0统计软件进行χ2检验、logistic回归分析.结果 早餐的就餐频率与大学生对早餐的态度和认知有密切的关系,而且所调查的医学生中每天吃早餐(7天/周)的人数仅占44.6%,不吃早餐的主要原因是没时间怕迟到.结论 大学生就餐率不容乐观,开展大学生营养健康教育提高大学生对早餐的认识、端正对早餐的态度和制定合理的作息时间表是提高大学生就餐率的有效途径.