Association between lifestyle factors and headache

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required

Cyclic Peptides to Improve Delivery and Exon Skipping of Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy

Item does not contain fulltex

Guidelines for Antisense Oligonucleotide Design and Insight Into Splice-modulating Mechanisms

Antisense oligonucleotides (AONs) can interfere with mRNA processing through RNase H–mediated degradation, translational arrest, or modulation of splicing. The antisense approach relies on AONs to efficiently bind to target sequences and depends on AON length, sequence content, secondary structure, thermodynamic properties, and target accessibility. We here performed a retrospective analysis of a series of 156 AONs (104 effective, 52 ineffective) previously designed and evaluated for splice modulation of the dystrophin transcript. This showed that the guanine-cytosine content and the binding energies of AON-target and AON–AON complexes were significantly higher for effective AONs. Effective AONs were also located significantly closer to the acceptor splice site (SS). All analyzed AONs are exon-internal and may act through steric hindrance of Ser-Arg-rich (SR) proteins to exonic splicing enhancer (ESE) sites. Indeed, effective AONs were significantly enriched for ESEs predicted by ESE software programs, except for predicted binding sites of SR protein Tra2β, which were significantly enriched in ineffective AONs. These findings compile guidelines for development of AONs and provide more insight into the mechanism of antisense-mediated exon skipping. On the basis of only four parameters, we could correctly classify 79% of all AONs as effective or ineffective, suggesting these parameters can be used to more optimally design splice-modulating AONs