Sheep anti Human Factor VIII polyclonal antibody [Biotin]

Background Hemophilia B (HB) is an X-linked recessive inherited bleeding disorder caused by mutations in theF9gene that lead to plasma factor IX deficiency. To identify the causative mutations in HB, a molecular analysis of HB pedigrees in China was performed. Methods Using next-generation sequencing (NGS) and an in-house bioinformatics pipeline, 76 unrelated HB pedigrees were analyzed. The mutations identified were validated by comparison with the results of Sanger sequencing or Multiplex Ligation-dependent Probe Amplification assays. The pathogenicity of the causative mutations was classified following the American College of Medical Genetics and Genomics guidelines. Results The mutation detection rate was 94.74% (72/76) using NGS. Of the 76 HB pedigrees analyzed, 59 causative variants were found in 72 pedigrees, with 38 (64.41%) missense mutations, 9 (15.25%) nonsense mutations, 2 (3.39%) splicing mutations, 5 (8.47%) small deletions, 4 (6.78%) large deletions, and 1 intronic mutation (1.69%). Of the 59 differentF9mutations, 10 were novel: c.190T>G, c.199G>T, c.290G>C, c.322T>A, c.350_351insACAATAATTCCTA, c.391+5delG, c.416G>T, c.618_627delAGCTGAAACC, c.863delA, and c.1024_1027delACGA. Of these 10 novel mutations, a mosaic mutation, c.199G>T(p.Glu67Ter), was identified in a sporadic HB pedigree. Usingin-silicoanalysis, these novel variants were predicted to be disease-causing. However, no potentially causative mutations were found in theF9coding sequences of the four remaining HB pedigrees. In addition, two HB pedigrees carrying additionalF8/F9mutations were discovered. Conclusion The identification of these mutations enriches the spectrum ofF9mutations and provides further insights into the pathogenesis of HB in the Chinese population.

BackgroundThe current study aims to systematically assess and compare the antidepressant outcomes of repetitive transcranial magnetic stimulation (rTMS) with the figure-of-eight (F8)-coil and deep transcranial magnetic stimulation (DTMS) with the H1-coil in studies matched on stimulation frequency in unipolar major depressive disorder (MDD).MethodsElectronic search of Medline and PsycInfo identified 19 studies with stimulation frequency of 18-20Hz using F8-coil (k=8 randomised sham-controlled trials, RCTs, k=3 open-label; n=168 patients) or H1-coil (k=1 RCT, k=7 open-label; n=200). Depression severity (the primary outcome) and response/remission rates (the secondary outcomes) were assessed at session 10.ResultsEffects pooled with random-effects meta-analysis showed a large reduction in depression severity, 29% response, and 15% remission rates after 10 sessions of active stimulation with either coil relative to baseline. Reduction in depression severity was greater in studies with younger patients using either coil. The comparison between coils showed a larger reduction in depression severity in H1-coil vs. F8-coil studies (independent of the study design or the concurrent pharmacotherapy) and a trend towards higher remission rates in F8-coil vs. H1-coils studies. These effects are based on a low volume of studies, are not controlled for placebo, and may not be clinically-relevant. The stimulation protocols differed systematically because stimulation was more focal but less intense (80-110% of the resting motor threshold, MT) in the F8-coil studies and less focal but more intense (120% MT) in the H1-coil studies. Two seizures occurred in the H1-coil studies relative to none in the F8-coil studies.ConclusionWhen matched on frequency, the higher-intensity and less focal stimulation with the H1-coil reduces depression more than the lower-intensity and more focal stimulation with the F8-coil. Head-to-head trials should compare the antidepressant outcomes of F8-coil and H1-coil to identify the most optimal stimulation protocols for acute and longer-lasting efficacy.