BACKGROUND AND PURPOSE: Whether or not migraine can cause cumulative brain alterations due to frequent migraine-related nociceptive input in patients is largely unclear. The aim of this study was to characterize longitudinal changes in brain activity between repeated observations within a short time interval in a group of female migraine patients, using resting-state functional magnetic resonance imaging. METHODS: Nineteen patients and 20 healthy controls (HC) participated in the study. Regional homogeneity (ReHo) and functional interregional connectivity were assessed to determine the focal and global features of brain dysfunction in migraine. The relationship between changes in headache parameters and longitudinal brain alterations were also investigated. RESULTS: All patients reported that their headache activity increased over time. Abnormal ReHo changes in the patient group relative to the HC were found in the putamen, orbitofrontal cortex, secondary somatosensory cortex, brainstem, and thalamus. Moreover, these brain regions exhibited longitudinal ReHo changes at the 6-week follow-up examination. These headache activity changes were accompanied by disproportionately dysfunctional connectivity in the putamen in the migraine patients, as revealed by functional connectivity analysis, suggesting that the putamen plays an important role in integrating diverse information among other migraine-related brain regions. CONCLUSIONS: The results obtained in this study suggest that progressive brain aberrations in migraine progress as a result of increased headache attacks.
Brain Stem ; Brain* ; Female ; Follow-Up Studies ; Headache ; Humans ; Longitudinal Studies* ; Magnetic Resonance Imaging ; Migraine Disorders* ; Putamen ; Somatosensory Cortex ; Thalamus

OBJECTIVETo evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride (VC)-induced chromosomal damage in peripheral lymphocytes.

METHODSIn this study, 317 workers occupationally exposed to VC were recruited from a factory in Shandong Province, China. The micronucleus (MN) frequency in peripheral lymphocytes was used as an indicator of chromosomal damage. Polymerase chain reaction-restriction fragment length polymorphism and created restriction site combined with restriction fragment length polymorphism were used to determine the five single nucleotide polymorphisms in XRCC1 and APE1 genes in the base excision repair pathway. The association of chromosomal damage with these polymorphisms and the haplotype of XRCC1 was analyzed using Poisson regression and PHASE 2.0.2.

RESULTSIt was found that among the VC-exposed workers, individuals with XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) had a significantly higher MN frequency than those with homozygous wild-type genotypes, with frequency ratios (FR) as follows, respectively: FR = 1.21, 95%CI: 1.05∼1.39 (P < 0.05); FR = 1.14, 95%CI: 1.00∼1.38 (P < 0.05); FR = 1.26, 95%CI: 1.11∼1.44 (P < 0.05); FR = 1.23, 95%CI: 1.08∼1.46 (P < 0.05). APE1 Asp148Glu was found of no significant relationship with MN frequency. Haplotype analysis of XRCC1 demonstrated that the MN frequencies in subjects with CTAA/CTAA and CCAA/CTAA were significantly higher than that in those with TCGG/TCGG (FR = 1.19, 95%CI: 1.02∼1.32, P < 0.05; FR = 1.41, 95%CI: 1.02∼1.87, P < 0.05). Furthermore, association was found between accumulated exposure to VC and XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) after adjustment for age, sex, drinking, and smoking.

CONCLUSIONVC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China (PC-TWA: 10 mg/m(3)); the polymorphisms in XRCC1 and APE1 are associated with chromosomal damage induced by VC.

Adult ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Haplotypes ; Humans ; Male ; Micronuclei, Chromosome-Defective ; Middle Aged ; Occupational Exposure ; adverse effects ; Polymorphism, Restriction Fragment Length ; Vinyl Chloride ; poisoning ; X-ray Repair Cross Complementing Protein 1 ; Young Adult

To identify in vivo-induced gene in Streptococcus pneumoniae (S. pn) through a novel in vivo expression technology (IVET), a large promoter-trap library using galU and lacZ as the reporters was constructed. Based on the suicide vector pEVP3, a new vector pEVP3-galU was constructed with promoterless galU gene as an in vivo reporter. Firstly, promoterless galU gene was directly cloned into pEVP3 fusing with promoterless lacZ gene (an in vitro reporter). Then the random pieces of S. pn chromosomal DNA (200-500 bp), obtained by partial Sau3AI restriction digestion, were subcloned into the Bgl II site of pEVP3-galU. Upon introduction of the ligated plasmid library into E. coli DH5alpha by transformation, about 70,000 recombinants were recovered. Considering insert DNA orientation and insert size, this represents 5 coverage of the 2.2 Mb S. pn genome; 90% of these clones had 250- to 500-bp inserts. Thus, the library retained maximal complexity. Transformation by this plasmid library yield 450,000 S. pn transformants. The library was used to infect animals in intraperitoneal model. Those strains survived in vivo while exhibiting a white colony phenotype on TSA agar containing X-gal would indicate that the DNA fragment upstream of the galU reporter contained an in vivo-induced promoter. The promoter-trap library is suitable for screening in vivo-induced gene of S. pn.
Animals ; Cloning, Molecular ; Female ; Genes, Bacterial ; genetics ; Genes, Reporter ; genetics ; Genomic Library ; Mice ; Mice, Inbred BALB C ; Promoter Regions, Genetic ; genetics ; Streptococcus pneumoniae ; genetics