Correlation between haemoglobin level and type of erythropoiesis-stimulating agent at initiation of haemodialysis

International Journal of Clinical Pharmacy - Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients...     

Frequent detection and characterization of hepatitis E virus variants in wild rats (Rattus rattus) in Indonesia

One hundred sixteen rats (Rattus rattus) captured in Indonesia from 2011 to 2012 were investigated for the prevalence of hepatitis E virus (HEV)-specific antibodies and HEV RNA. Using an ELISA based on HEV genotype 4 with an ad hoc cutoff value of 0.500, 18.1 % of the rats tested positive for anti-HEV IgG. By nested RT-PCR, 14.7 % of the rats had rat HEV RNA, and none were positive for HEV genotype 1-4. A high HEV prevalence among rats was associated with lower sanitary conditions in areas with a high population density. Sixteen of the 17 HEV isolates obtained from infected rats showed >93.0 % nucleotide sequence identity within the 840-nucleotide ORF1-ORF2 sequence and were most closely related to a Vietnamese strain (85.9-87.9 % identity), while the remaining isolate differed from known rat HEV strains by 18.8-23.3 % and may belong to a novel lineage of rat HEV. These results suggest a wide distribution of rat HEV with divergent genomes.     

Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age.Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy and began to regress at 5 years 10 months and 5 years 6 months of age respectively. They gradually manifested with cerebellar ataxia, dysarthria, pyramidal signs, and dysphasia. Brain MRI revealed T2 high-intensity areas in the cerebellar white matter, bilateral middle cerebellar peduncle, and transverse tracts of the pons, followed by progressive atrophy of these areas.Intriguingly, the ratios of C24:0, C25:0, and C26:0 to C22:0 in plasma, which usually increase in ACOX1 deficiency were within normal ranges in both patients. On the other hand, whole exome sequencing revealed novel compound heterozygous variants in ACOX1: a frameshift variant (c.160delC:p.Leu54Serfs*18) and a missense variant (c.1259 T > C:p.Phe420Ser). The plasma concentration of individual very long chain fatty acids (C24:0, C25:0, and C26:0) was elevated, and we found that peroxisomes in fibroblasts of the patients were larger in size and fewer in number as previously reported in patients with ACOX1 deficiency. Furthermore, the C24:0 β-oxidation activity was dramatically reduced.Our findings suggest that the elevation of individual plasma very long chain fatty acids concentration, genetic analysis including whole exome analysis, and biochemical studies on the patient’s fibroblasts should be considered for the correct diagnosis of ACOX1 deficiency.     

A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder

BackgroundCUL3 encodes cullin-3, a core component of a ubiquitin E3 ligase. CUL3 mutations have recently been associated with autism spectrum disorder (ASD); however, the detailed clinical courses have been described in only a limited number of patients with CUL3 mutations and neurodevelopmental diseases, including ASD.Case reportA 21-month-old Japanese girl presented with febrile status epilepticus and thereafter exhibited developmental regression, including loss of her verbal ability, eye contact, and skills in activities of daily living. Trio-based exome sequencing identified a de novo two-base insertion in CUL3, c.1758_1759insTG, p.(Thr587*).ConclusionWe report a case of a patient with ASD and a stop-gain CUL3 variant. Screening of CUL3 variants is worth considering for patients with ASD, especially those with Rett-like developmental regression.     

Numerical analysis of blood flow distribution in 4- and 3-branch vascular grafts

Trifurcated arch grafts (3-branch grafts) are now being used to repair the thoracic aorta in addition to conventional arch grafts (4-branch grafts). The anatomical shape of the 3-branch graft is different from the original vessel, so it is necessary for clinical application to evaluate blood flow distribution in the graft to assess whether there is adequate blood flow to the target organs. To achieve this, we developed a computational fluid dynamics (CFD) method to evaluate blood flow distribution in the grafts. Aortic blood flow was measured by phase-contrast magnetic resonance imaging (PC-MRI), and flow distribution into the branched vessels was obtained. The MRI image was used to create a patient-specific image model that represents the geometry of the aortic arch. The CFD analysis method was employed to determine a boundary condition of the blood flow analysis in the aorta using a patient-specific image model. We also created simplified models of 4-branch and 3-branch grafts and used our CFD analysis method to compare blood flow distribution among simplified models. It was found that blood flow distribution in the descending aorta was 71.3 % for the 4-branch graft and 67.7 % for the 3-branch graft, indicating that a sum of branching flow in the 3-branch graft was almost the same as the one in the 4-branch graft. Therefore, there is no major concern about implanting a new 3-branch graft. Our CFD analysis method may be applied to estimate blood flow distribution of a newly developed vascular graft prior to its clinical use and provide useful information for safe use of the graft.