Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Association of genetic loci for migraine susceptibility in the she people of China.

BACKGROUND: The purpose of this study was to investigate the association of the genotype and allele frequencies of the polymorphisms rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321 in She people of China with migraine headache susceptibility. The five alleles were previously identified as being associated with migraine in a Western population, but it was not known if this association would hold in a She population. rs4379368 is in the succinic HMG coenzyme A transferase (C7orf10) gene; rs10504861 is near the matrix metallopeptidase 16 (MMP16) gene; rs10915437 is near the adherens junctions associated protein 1 (AJAP1) gene; rs12134493 is upstream of the tetraspanin 2 (TSPAN2) gene; and rs13208321 is within the four and a half LIM domains protein 5 (FHL5) gene. METHODS: This was a case-controlled study conducted in She people of Fujian province in China. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were performed. Univariate and multivariate analyses were used to assess the association of the different genotypes of each SNP with migraine. RESULTS: The rs4379368 T allele was not in Hardy-Weinberg equilibrium and was more common than the C allele in subjects with migraine (58.7 %; P = 0.049), possibly suggesting a selection bias for T allele in this population. In support of this, the CT and TT genotypes were more frequent in the migraine compared with the control groups (54.0 % and 31.7 % vs. 48.0 % and 28.7 %, respectively; P = 0.019). These genotypes were also more common in females with migraines than females without migraines (53.8 % and 30.9 % vs. 46.7 % and 27.6 %; P = 0.026). Univariate and multivariate analyses found the CC genotype of rs4379368 and AA or AG genotype of rs13208321 were associated with a reduced risk of migraine (P values ≤0.039). CONCLUSIONS: Our findings suggest that rs4379368 and rs13208321 are potential genetic markers for migraine in this She population. The findings of this study and others indicate important differences between ethnic populations in regard to genetic markers of migraine susceptibility.

Comparative study of surgical and conservative treatments for fifth metatarsal base avulsion fractures (type I) in young adults or athletes.

PURPOSE: This study aimed to investigate the therapeutic effects and complications of minimally invasive surgery in treating displaced avulsion fractures (2-3 mm) of fifth metatarsal base zone I in young adults or athletes. METHODS: Forty-six patients with displaced fifth metatarsal base avulsion fractures were assigned to operative and nonoperative groups by randomization. Patients in nonoperative group were immobilized with plaster, while patients in operative group were treated with closed reduction and fixation with a percutaneous screw. RESULTS: All patients were followed up for 14 months on average (ranging from 12 to 24 months). All cases got primary union except for three patients in nonoperative group with malunion and two with frequent mild to moderate plantar pain. The American Orthopaedic Foot and Ankle Society score was significantly better in operative group at 6 months after treatment ( p < 0.05) but not significantly different at 12 months after treatment ( p > 0.05). The average time of full weight bearing and returning to work was significantly shorter in operative group than nonoperative group ( p < 0.05). CONCLUSION: In young adults or athletes with displaced avulsion fractures of fifth metatarsal base zone I, closed reduction and percutaneous screw fixation provides anatomical stable fixation and early mobilization.

Prevalence of migraine in Han Chinese of Fujian province: An epidemiological study.

Migraine is a relatively common disease that is associated with high disability and reduced quality-of-life. This study aimed to investigate the prevalence, epidemiological characteristics, and risk factors of migraine in Han Chinese from Fujian Province, China.A cross-sectional epidemiological survey study was conducted to evaluate characteristics of migraine in Han Chinese. Demographic and clinical data were collected through a survey administered in face-to-face interviews by trained investigators, and a physical exam and symptom review were performed. Univariate and multivariate regression analyses were performed to assess independent risk factors for migraine.A total of 7860 subjects aged 15 years and older were surveyed, of which 9.1% (n = 717) were diagnosed with migraine. Among these, a higher percentage was female (12.6%) than male (5.3%). Only 114 subjects (15.9%) were diagnosed as having migraine with aura, which was closely associated with family history of migraine. Multivariate regression analysis showed that the odds of migraine were significantly lower in subjects aged ≥50 years compared with those aged <30 years (odds ratio [OR] ranged from 0.40 to 0.64; P ≤.013) and was higher in females compared with males (OR = 2.89, P <.001). The odds of migraine was significantly greater in subjects with a history of alcohol consumption (OR = 1.81, P <.00) and insomnia (OR = 2.77, P <.001).Han Chinese in Fujian province has a relatively high prevalence of migraine, and female gender, <50 years of age, insomnia, and use of alcohol are associated with increased odds of having migraine in this population.

Migraine Susceptibility Genes in Han Chinese of Fujian Province.

BACKGROUND AND PURPOSE: Five single-nucleotide polymorphisms (SNPs) (rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321) were recently identified in a Western population with migraine. These migraine-associated SNPs have not been evaluated in a Han Chinese population. This study investigated the associations of specific SNPs with migraine in a Han population. METHODS: This was a case-control study of Han Chinese residing in Fujian Province. Polymerase chain reaction-restriction-fragment-length polymorphism analysis and direct sequencing were used to characterize the relationships of SNPs in a control group of 200 subjects and in a migraine group of 201 patients. RESULTS: The frequencies of the five SNPs did not differ between patients with migraine and healthy non migraine controls. However, subgroup analysis indicated certain SNPs were more strongly associated with migraine with aura or migraine without aura than with controls. The CT genotype of rs4379368 was more common in migraine patients with aura (75%) than in migraine patients without aura (47.9%) and controls (48.5%) (p<0.05), and the TT genotype of rs10504861 was more common in migraine patients with aura than in controls (8.3% vs. 0.5%) (p<0.05). Meanwhile, the CC genotype of rs12134493 was less common in migraine patients without aura than in controls (80.6% vs. 88%) (p<0.05). CONCLUSIONS: Our findings suggest that the rs4379368 and rs10504861 SNPs are markers for susceptibility to migraine with aura and that rs12134493 is a marker for the risk of migraine without aura in this Han population. Future studies should further explore if these associations vary by ethnicity.

Salusins promote cardiomyocyte growth but does not affect cardiac function in rats.

Salusin-alpha and -beta are newly found polypeptides that stimulate proliferation, hypotension and bradycardia in vascular smooth muscle cells (VSMCs) and fibroblasts. Propresalusin mRNA is widespread, and positive stains for salusins have been observed in many human tissues such as endothelium and ventricular tissue. To investigate the bio-effect of salusins on cardiovascular function, 20 nmol/kg salusin-alpha or 2 nmol/kg salusin-beta was intravenously (i.v.) injected into rats, and isolated rat hearts were perfused with 10(-12) to 10(-7) mol/l salusin-alpha or -beta. (45)Ca(2+) uptake and (3)H-Leucine incorporation were determined in cultured neonatal rat cardiomyocytes. Neither salusin-a nor -beta affected cardiac function in vivo or in vitro but salusin-beta decreased mean arterial blood pressure (MAP). The polypeptides' stimulation of (45)Ca(2+) uptake and (3)H-Leucine incorporation was concentration-dependent, and the incorporation was inhibited by nicardipine (Nic) and FK-506 [FK; an inhibitor of calcineurin (CaN)]. PD(98059) [PD; inhibitor of mitogen-activated protein kinase (MAPK)] and chelerythrine [inhibitor of protein kinase C (PKC)] inhibited salusin-stimulated (3)H-Leucine incorporation. Endothelin-1 (ET) synergistically increased salusin-induced (45)Ca(2+) uptake. Our results suggest that salusin-alpha and -beta did not directly affect cardiac function in the rat heart but that they improved calcium uptake and protein synthesis in neonatal rat cardiomyocytes through the calcium, calcineurin, MAPK and PKC signal pathways. Salusins may be regulatory factors for myocardial growth and hypertrophy.

Assignment of Proton Resonances and Conformational Characterization of Oligodeoxyribonucleic Acid d(CCGTACGG) in Solution.

Lycobetaine prepared from lycorine is a new anticancer agent. The experimental and quantum pharmacological studies revealed that lycobetaine can interact with DNA by intercalation, preferentially into GO base pairs. In order to provide detailed interaction model of lycobetaine-DNA, a self-complementary octanucleotide d(CCGTACGG) was designed and synthesized by using new HELP (high efficiency Liquid phase) According to its nature, the sample was prepared to the desired final concentration by adding salt and buffer solutions. Two-dimensional (1)H-(1)H COSY and NOESY spectra in 99.8% D(2)O and 95% H(2)O were recorded for the duplex, and the NMR techniques of presaturation and WATERGATE were applied to water suppression. Protons of every spin system were identified by their scalar couplings, then through their special couplings all protons in the molecule were assigned except the poorly resolved H5' and H5' ' resonances. The chemical shifts of exchangeable protons and NOE intensities of nonexchangeable protons indicate qualitatively that the d(CCGTACGG) helix is right-handed B-DNA in aqueous solution.

Isolated avulsion fractures of lesser tuberosity humerus: a case report and review of the literature.

In this case, a 31 year-old female was diagnosed of isolated fractures of lesser tuberosity humerus. The patient could take early functional training of shoulder joint two days after operation. Although isolated fractures of lesser tuberosity humerus are rare, when pain of anterior shoulder joint after trauma, doctors should consider isolated fractures of lesser tuberosity humerus. As for the therapy methods, they should be chosen according to time length after injury. Most of the patients had no obvious residual functional disability after treatments.

Epidemiology of migraine in the She ethnic minority group in Fujian province, China.

OBJECTIVES: We examined the prevalence and risk factors of migraine among the She population. The prevalence of migraine among She Chinese in Fujian province is high. METHODS: This study is a cross-sectional survey. Subjects completed a questionnaire that collected demographic and clinical data related to migraine. Physical examination and clinical laboratory tests were performed. Data were analyzed by regression analysis. RESULTS: Of the 5519 subjects enrolled, 2377 were male (43·1%) and 3142 female (56·9%). Of these, 581 (10·53%) experienced migraine annually, including 6·18% of males and 13·82% of females. Highest prevalence rate was among those aged 40-49 years (11·28%). The 141 (24·3%) subjects who had migraine with aura had higher incidence of family history of headache than those without aura (38·5% vs 19·9%, P < 0·0001). CONCLUSION: Female gender and insomnia are possible risk factors for migraine in the She population.

Migraine Susceptibility Genes in Han Chinese of Fujian Province

BACKGROUND AND PURPOSE: Five single-nucleotide polymorphisms (SNPs) (rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321) were recently identified in a Western population with migraine. These migraine-associated SNPs have not been evaluated in a Han Chinese population. This study investigated the associations of specific SNPs with migraine in a Han population. METHODS: This was a case-control study of Han Chinese residing in Fujian Province. Polymerase chain reaction—restriction-fragment-length polymorphism analysis and direct sequencing were used to characterize the relationships of SNPs in a control group of 200 subjects and in a migraine group of 201 patients. RESULTS: The frequencies of the five SNPs did not differ between patients with migraine and healthy non migraine controls. However, subgroup analysis indicated certain SNPs were more strongly associated with migraine with aura or migraine without aura than with controls. The CT genotype of rs4379368 was more common in migraine patients with aura (75%) than in migraine patients without aura (47.9%) and controls (48.5%) (p<0.05), and the TT genotype of rs10504861 was more common in migraine patients with aura than in controls (8.3% vs. 0.5%) (p<0.05). Meanwhile, the CC genotype of rs12134493 was less common in migraine patients without aura than in controls (80.6% vs. 88%) (p<0.05). CONCLUSIONS: Our findings suggest that the rs4379368 and rs10504861 SNPs are markers for susceptibility to migraine with aura and that rs12134493 is a marker for the risk of migraine without aura in this Han population. Future studies should further explore if these associations vary by ethnicity.

Conformation-dependent intermolecular interaction energies of the triphosphate anion with divalent metal cations. Application to the ATP-binding site of a binuclear bacterial enzyme. A parallel quantum chemical and polarizable molecular mechanics investigation.

We have explored the conformation-dependent interaction energy of the triphosphate moiety, a key constituent of ATP and GTP, with a closed-shell divalent cation, Zn2+, used as a probe. This was done using the SIBFA polarizable molecular mechanics procedure. We have resorted to a previously developed approach in which triphosphate is built out from its elementary constitutive fragments, and the intramolecular, interfragment, interaction energies are computed simultaneously with their intermolecular interactions with the divalent cation. This approach has enabled reproduction of the values of the intermolecular interaction energies from ab initio quantum-chemistry with relative errors <3%. It was extended to the complex of a nonhydrolyzable analog of ATP with the active site of a bacterial enzyme having two Mg2+ cations as cofactors. We obtained following energy-minimization a very close overlap of the ATP analog over its position from X-ray crystallography. For models of the ATP analog-enzyme complex encompassing up to 169 atoms, the values of the SIBFA interaction energies were found to match their DFT counterparts with relative errors of <2%.