Association between CFL1 gene polymorphisms and spina bifida risk in a California population

BACKGROUND: CFL1 encodes human non-muscle cofilin (n-cofilin), which is an actin-depolymerizing factor and is essential in cytokinesis, endocytosis, and in the development of all embryonic tissues. Cfl1 knockout mice exhibit failure of neural tube closure at E10.5 and die in utero. We hypothesized that genetic variation within the human CFL1 gene may alter the protein's function and result in defective actin depolymerizing and cellular activity during neural tube closure. Such alterations may be associated with an increased risk for neural tube defects (NTDs). METHODS: Having re-sequenced the human CFL1 gene and identified five common single nucleotide polymorphisms (SNPs) in our target population, we investigated whether there existed a possible association between the genetic variations of the CFL1 gene and risk of spina bifida. Samples were obtained from a large population-based case-control study in California. Allele association, genotype association and haplotype association were evaluated in two different ethnicity groups, non-Hispanic white and Hispanic white. RESULTS: Homozygosity for the minor alleles of the SNPs studied (rs652021, rs665306, rs667555, rs4621 and rs11227332) appeared to produce an increased risk for spina bifida. Subjects with the haplotype composed of all minor alleles (CCGGT) appeared to have increased spina bifida risk (OR = 1.6, 95% CI: 0.9~2.9), however, this finding is not statistically significant likely due to limited sample size. CONCLUSION: The sequence variation of human CFL1 gene is a genetic modifier for spina bifida risk in this California population

CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population

BACKGROUND: Neural tube defects (NTDs) are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos. METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989–1991. RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38–0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97–3.67). These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake. CONCLUSION: Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved

High originating radial artery: anatomical study through the use of ultrasound

Typically, the radial artery arises as a branch from the brachial artery at the level of the neck of the radius in the distal antecubital fossa. Anatomical variations in the radial artery are relatively common. Published literature demonstrates a wide variability in the prevalence of high originating radial artery (0.5-14.27%). The literature also shows inconsistent and vague nomenclature when describing the arterial system in cases of high originating radial artery. This study aims to investigate the incidence of a high originating radial artery in vivo through the use of ultrasound. It goes on to propose a classification system utilising precise nomenclature to help in discriminating between the various patterns. METHODS. Fifty-four upper limbs from 27 individuals were investigated using GE LOGIQ e and SonoSite MicroMaxx ultrasound machines with 12L-RS & A L38e 10-5MHz transducer respectively. The radial artery was initially identified and followed proximally to its origin and then distally to the wrist noting its course and relationships to other anatomical structures. SUMMARY. High originating radial arteries were found unilaterally in 4 individuals (4/54, 7.4%). CONCLUSION. Variations in the anatomical course and relationships of the radial artery are pertinent to surgeons, radiologists and anatomists. The presence of a high originating radial artery has both clinical and surgically significance in procedures, such as arterial grafting and cardiac catheterization. Due to its superficial course, it is more vulnerable to injury due to trauma or during cannulation and drug administration. Bedside ultrasound techniques can not only be of benefit in identifying variations prior to such procedures but also for future anatomical studies

プロテアソーム活性化因子PA28ノックアウトマウスの作製と解析

University of Tokyo (東京大学

MRSA Spinal Epidural Abscess as a Neurosurgical and Infectious Disease Emergency with Unresolved Antimicrobial Solution

Spinal epidural abscess caused by MRSA, a life-threatening organism resistant to methicillin and other antibiotics, is a rare but important infectious pathology due to its potential damage to the spinal cord. We present the case of a 74-year-old man who hematogenously seeded his entire epidural spinal canal from C1 to sacrum with MRSA bacteria and remained infected even after maximal treatment with vancomycin and daptomycin. Ceftaroline, a new 5th generation antibiotic with recently described clearance of widespread MRSA infection in epidural complex spine infections, was added to vancomycin as dual therapy for his MRSA infection. A 74-year-old diabetic man with prior right total knee arthroplasty and MRSA infection presented with persistent bacteremia and sepsis. He was transferred to our academic center after diagnosis of entire spine epidural abscesses from C1 to sacral levels with midthoracic MRI T2 hyperintensities of the vertebral bodies and disc concerning for osteomyelitis and discitis. Despite surgery and IV vancomycin with MIC of 1, suggesting extreme susceptibility, the patient’s blood cultures remained persistently bacteremic at day 5 of treatment. After 48 hours of dual antibiotic therapy with vancomycin and ceftaroline, his blood cultures came back showing no growth. The patient’s outcome was unfavorable due to the advanced nature of his infection and multiple comorbidities, but his negative blood cultures after the addition of ceftaroline to his regime require further investigation into this dual therapy. Randomized controlled trials of 5th generation or combinatorial antibiotics should be considered for this disease

Misdiagnosis of Third Nerve Palsy

Third (3rd) nerve palsy is characterized by some combination of ptosis, limited adduction, supraduction, infraduction, and pupillary function. Causes include microvascular ischemia, compression, and aneurysms. Accurate diagnosis is essential to avoid potentially life-threatening consequences and unnecessary testing. We assessed the frequency of 3rd nerve palsy misdiagnosis based upon referrals to two high volume tertiary care neuro-ophthalmology services, and characterized the specific diagnostic errors

High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program.

Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet