3 research outputs found
DNA Methylation Signatures within the Human Brain
DNA methylation is a heritable modification of genomic DNA central to development, imprinting, transcriptional regulation, chromatin structure, and overall genomic stability. Aberrant DNA methylation of individual genes is a hallmark of cancer and has been shown to play an important role in neurological disorders such as Rett syndrome. Here, we asked whether normal DNA methylation might distinguish individual brain regions. We determined the quantitative DNA methylation levels of 1,505 CpG sites representing 807 genes with diverse functions, including proliferation and differentiation, previously shown to be implicated in human cancer. We initially analyzed 76 brain samples representing cerebral cortex (n=35), cerebellum (n=34), and pons (n=7), along with liver samples (n=3) from 43 individuals. Unsupervised hierarchical analysis showed clustering of 33 of 35 cerebra distinct from the clustering of 33 of 34 cerebella, 7 of 7 pons, and all 3 livers. By use of comparative marker selection and permutation testing, 156 loci representing 118 genes showed statistically significant differences—a ⩾17% absolute change in DNA methylation (P<.004)—among brain regions. These results were validated for all six genes tested in a replicate set of 57 samples. Our data suggest that DNA methylation signatures distinguish brain regions and may help account for region-specific functional specialization
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Treatment for Central Centrifugal Cicatricial Alopecia - Delphi Consensus Recommendations
There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely.
To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA.
We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed.
In Round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in Round 2. After the final Round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus.
This study included only English-speaking, US-based dermatologists and did not consider non-pharmacological therapies.
Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA