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Real-world data on the effectiveness and safety of tildrakizumab, an interleukin 23p19 inhibitor, in Switzerland is limited. The objectives of this analysis were to assess the effectiveness and safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis in Switzerland. Twenty-eight adults from the Swiss Dermatology Network for Targeted Therapies registry (SDNTT), who were on tildrakizumab treatment and had at least 3 months' follow-up, were enrolled in this prospective, multicentre study. No missing data imputation was performed. The median Psoriasis Area and Severity Index (PASI) decreased from 9.5 at baseline to 2.1 and 0.3 (both p < 0.001) after 3 and 18 months, respectively, of tildrakizumab treatment. After 3 months, 76.9%/30.8% patients reached an absolute PASI < 3/ < 1. These rates increased to 85.7%/57.1% after 18 months of treatment. The proportions of patients achieving PASI 90/100 responses were 47.8%/30.4% at month 6 and 42.9%/14.3% at month 18. A significant improvement in quality of life up to 18 months of follow-up was observed as measured by the Dermatology Life Quality Index. There were no treatment discontinuations due to adverse events. This real-world registry provides robust evidence supporting the long-term effectiveness and favourable safety profile of tildrakizumab in treating patients with moderate-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

Sex-specific migration patterns have been revealed in four central Asian populations through analysis and comparisons of mtDNA and.Y-chromosome short tandem repeats. Females seems to have a higher migration rate. A male founder effect appears to exist in the settlement of high-altitude areas. Two lowland populations and two highland populations were sampled. Analysis of molecular variance (AMOVA) brought out a very great degree of genetic difference in the populations. For mtDNA, genetic diversity in the highlands is like that in the lowlands. Haplotype genetic diversity was much lower in high altitudes, especially in Kirghiz.

The origins of Central Asian populations are discussed as they relate to the mingling of genes along the Silk Road and to mtDNA control-region sequences found in peoples including the Kazakh, Uighurs, and both lowland and highland Kirhgiz. Peoples of Europe and eastern Asia have few mtDNA sequences in common, but central Asian peoples have sequences in common with both groups, but sequences found in the study covered here are different from sequences that Europeans and central Asians share, and altitude seems not to exert a major selective pressure in the populations studied.

The hypervariable segment I of the control region of the mtDNA (positions 16024-16383) was amplified from hair roots by PCR and sequenced in 45 unrelated individuals from Anatolia (Asian Turkey). Forty different sequences were found, defined by 56 variable positions, of which only one involves a transversion. The neighbor-joining tree of Kimura’s distance matrix for all sequences shows four main clusters. Cluster D was found to be the most statistically robust of the four, and all the sequences in it shared a mutation that is present only in European and West Asian populations. The variability in cluster D could have originated between 37,000 and 107,000 years ago. No branch is unexpectedly long, denoting the absence of sequences that diverged much before the others. The pairwise difference distribution is bell-shaped, in accordance with a population expansion occurring roughly 35,000 to 100,000 years ago. When compared to other Caucasoid populations through the pairwise difference distribution, there is a pattern from the Middle East (older expansion) to the various European populations, with Turkey in an intermediate position; when Turkish sequences are compared through a neighbor-joining tree on a genetic distance matrix of populations, this position is again evidenced. Although there is a very low level of genetic divergence among Caucasoid populations as shown by mtDNA control region sequences, a geographic pattern of genetic variation emerges, denoting a stepping-stone position of Turkey between the Middle East and Europe, which is in agreement with the hypothesis of a replacement of Neanderthals by modem humans, which could be related to the Upper Paleolithic cultural expansion. [ABSTRACT FROM AUTHOR]