Favorable benefit-risk ratio with teriflunomide treatment in relapsing-remitting multiple sclerosis: Results of the 2-year, multicenter, prospective, noninterventional TAURUS MS study in Austria.

Objectives: A prospective, multicenter, open-label, noninterventional study assessed the efficacy, safety, tolerability, and patient satisfaction with teriflunomide therapy over a 24-month follow-up period under real-world conditions in Austria. Methods: An all-comer population aged ≥18 years was followed in clinic and office-based settings. The primary objective of the study was the annualized relapse rate after 12 and 24 months of teriflunomide treatment. Patient-reported outcomes included treatment satisfaction, health-related quality of life, and fatigue, and were assessed based on the Short Form Health-36, Fatigue Severity Scale, and Treatment Satisfaction Questionnaire for Medication (TSQM)-9 questionnaires. Results: Thirty-one patients were included in the analysis, 23 of whom were still on treatment after 24 months. At 12 months (n = 24), the annualized relapse rate was 0.3 (SD, 0.8), which indicated a significant decrease compared to the annualized relapse rate of 1.0 (SD, 0.9) observed during the 12-month reference period prior to treatment initiation (p = 0.009). Similarly, after 24 months of follow-up (n = 23), the annualized relapse rate of 0.2 (SD, 0.8) was significantly lower than that during the last 24 months reference period prior to treatment initiation of 0.7 (SD, 0.8) (p = 0.0003). The Expanded Disability Status Scale score remained stable over 12 and 24 months. This also applied to patient-reported fatigue of the Fatigue Severity Scale, with a mean change of 0.1 (SD, 1.0). Patient treatment satisfaction as assessed by the TSQM-9 increased for all three domains (i.e., effectiveness, convenience, global satisfaction). This was confirmed by the physician and multiple sclerosis nurse ratings of patient treatment satisfaction and ease of use. Adverse events occurred in 38.7%, with hair thinning and diarrhea as the most common. Conclusions: This noninterventional study showed a sustained favorable benefit-risk ratio for this disease-modifying treatment with teriflunomide over 24 months in patients with relapsing-remitting multiple sclerosis. Patient-reported outcomes and ratings performed by physicians and nurses showed overall trends to improvement for patient treatment satisfaction with teriflunomide treatment and its ease of administration.

DXS10011: studies on structure, allele distribution in three populations and genetic linkage to further q-telomeric chromosome X markers.

The hypervariable tetranucleotide STR polymorphism DXS10011 is a powerful marker for forensic purposes. Investigation of this STR led to an allele nomenclature which is in consensus with the ISFG recommendations. DXS10011 is located at Xq28 and genetically closely linked to DXS7423 and DXS8377 but is unlinked to HPRTB and more distant X-chromosomal STRs. DXS10011 is a very complex marker exhibiting some structural variants within alleles of identical length. Two types of repeat structure (regular and inter-alleles) are known and described as types A and B. Two SNPs which are in strong linkage disequilibrium to the different sequence types were found in the repeat flanking region. The type A sequence consists of a long stretch of uninterrupted homogenous repeats which is highly susceptible to slippage mutation during male meiosis.

Cell line DNA typing in forensic genetics--the necessity of reliable standards.

The incorporation of reference DNA is crucial to the validation of any DNA typing protocol. This paper aims to provide a panel of reference DNAs for actual forensic profiling strategies, i.e. autosomal and gonosomal STR typing as well as mtDNA sequencing. We have characterised three human lymphoid cell lines, GM9947, GM9948 and GM3657, and considered 58 autosomal and gonosomal microsatellites as well as the mitochondrial control region sequence. Well-established markers and STRs recently developed for forensic use were involved. K562 DNA samples which we purchased from two different suppliers were also analysed. They revealed conflicting results with regard to the ChrX STR marker genotype. Hence, we suggest that K562 is no longer used for the calibration of profiling techniques. Our investigation establishes a panel of one female and two male DNA samples as an STR allelic ladder calibration tool and offers information on six alleles of each autosome (AS) marker, three alleles of each X chromosome (ChrX) marker and two alleles of each ChrY marker. In addition, sequences of the mitochondrial control region of the three DNAs are communicated in order to provide sequencing quality control.

Detection of fetal DNA in a cell pellet after centrifugation of mountant.

In order to obtain fetal cells (e.g., for paternity cases) after abortion, the centrifugation of mountant (in our case formalin) may be tried when the DNA examination of the fixed tissue itself gives limited or no (or not enough) information. The fixed tissue was microscopically negative for fetal cells and gave no satisfactory results when examined for DNA. Centrifugation of approximately 50 mL of reddish colored formalin resulted in a cell pellet that was examined for DNA, which gave enough information to confirm a case of sexual abuse.