Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could ...address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures.
Display omitted
•Multi-omic analysis of differentiated C9ORF72 iPSC-derived motor neurons•Network-based integrative computational analysis•Pathogenic versus compensatory pathways elucidated using C9ORF72 Drosophila model•Pathways confirmed with alternative differentiation protocol and postmortem data
Biological sciences; Neuroscience; Systems neuroscience; Systems biology; Omics
Split-thickness skin grafts in the forearm can lead to motion restriction and disability through the dense scarring of the skin and formation of graft-tendon adhesions. Three patients were referred ...for laser treatment of motion-limiting scar-associated split-thickness skin grafts to the forearm. All patients had reached a plateau in range of motion despite aggressive hand therapy and underwent serial laser scar treatments at 6- to 8-week intervals. Treatments were performed in a clinic setting and were initiated 2 to 5 months after reconstructive surgery. Rapid subjective functional and objective improvements in range of motion were noted after laser therapy. Results were cumulative and durable at final follow-up ranging from 10 to 15 months after the initial treatment. No complications were noted. Fractionated carbon dioxide laser therapy is a promising adjunct to hand therapy when the main restraint to motion is superficial skin scarring and skin-tendon adhesions.
Efalizumab, a humanized anti-CD11a monoclonal antibody, has been shown to treat plaque psoriasis. A known association between this drug and autoimmune thrombocytopenia has already been established. ...More recently publicized, however, is efalizumab's ability to affect another cell line—that of the erythrocyte—and cause an autoimmune hemolytic anemia that typically occurs 4 to 6 months after initiating therapy. In this article, we report the case of a patient who developed autoimmune hemolytic anemia after 8 months of successful treatment with efalizumab. His delayed presentation suggests that monitoring of blood cell counts longer than 6 months may be warranted.
JAAD Grand Rounds quiz Lynch, Michael C., MD; Wood, Lance, MD; Anderson, Bryan E., MD ...
Journal of the American Academy of Dermatology,
05/2015, Letnik:
72, Številka:
5
Journal Article
Recenzirano
Learning objectives: At the conclusion of this learning activity, physician participants should be able to assess their own diagnostic and patient management skills and use the results of this ...exercise to help determine personal learning needs. Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence.
PDF
