A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients.

Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease-modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein data sets visualized using Gephi, based on protein--protein interactions in the STRING database. The top modules of NDP and RP networks were assessed using Enrichr. Based on the findings, a set of proteins, including ATP binding cassette subfamily C member 1 (ABCC1), neurogenic locus notch homologue protein 1 (NOTCH1), hepatocyte growth factor receptor (MET), RAF proto-oncogene serine/threonine-protein kinase (RAF1) and proto-oncogene vav (VAV1) was found in NDP and was involved in over-represented terms correlated with cell-mediated immunity and cancer. In contrast, transcription factor RelB (RELB), histone acetyltransferase p300 (EP300), acetyl-CoA carboxylase 2 (ACACB), adiponectin (ADIPOQ) and phosphoenolpyruvate carboxykinase 2 mitochondrial (PCK2) had major contributions to viral infections and lipid metabolism as significant events in RP. According to these findings, further research is required to demonstrate the pathogenic roles of such proteins and autoantibodies targeting them in MS and to develop therapeutic agents which can ameliorate disease severity.

Aggressive systemic mastocytosis with the co-occurrence of PRKG2::PDGFRB, KAT6A::NCOA2, and RXRA::NOTCH1 fusion transcripts and a heterozygous RUNX1 frameshift mutation.

Systemic mastocytosis (SM) is a myeloproliferative neoplasm displaying abnormal mast cell proliferation. It is subdivided into different forms, including aggressive systemic mastocytosis (ASM) and systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Oncogenic genetic alterations include point mutations, mainly the KIT D816V, conferring poor prognosis and therapy resistance, and fusion genes, with those involving PDGFRA/PDGFRB as the most recurrent events. We here describe an ASM case negative to the KIT D816V and JAK2 V617F alterations but showing a RUNX1 frameshift heterozygous mutation and the co-occurrence of three fusion transcripts. The first one, PRKG2::PDGFRB, was generated by a balanced t(4;5)(q24;q32) translocation as the sole abnormality. Other two novel chimeras, KAT6A::NCOA2 and RXRA::NOTCH1, originated from cryptic intra-chromosomal abnormalities. The patient rapidly evolved towards SM-AHN, characterized by the persistence of the PRKG2::PDGFRB chimera, due to the presence of an extra copy of the der(5)t(4;5)(q24;q34) chromosome and an increase in the RUNX1 mutation allelic frequency. The results indicated that the transcriptional landscape and the mutational profile of SM deserve attention to predict the evolution and prognosis of this complex disease, whose classification criteria are still a matter of debate.

Prospective comparative study of lower lip defects reconstruction with different local flaps.

Squamous cell carcinoma is the most common malignancy related to the lips (95%), and the lower lip is more commonly involved. Loss of tissue in the lower lip is treated with a variety of techniques, depending on the extension and location of the defect. This was a prospective case series. In this study, 41 patients with squamous cell carcinoma (30 males, 11 females) who were referred to Razi Hospital of Tehran University of Medical Sciences between 2007 and 2008 and underwent lower-lip reconstruction were included. Defects were divided into 4 groups: less than 30%, between 30% and 50%, between 50% and 80%, and more than 80%. Five different local flaps were used for lower-lip reconstruction. Karapandzic flap was used for 9 patients, double reversed-Abbe flap for 6 patients, Abbe-Estlander and step-ladder flaps for 8 patients, and 10 patients underwent reconstruction operation with reversed-Abbe flap. In comparison to reversed-Abbe flap and step-ladder flap, there were no differences functionally and aesthetically except that the step-ladder flap was a single-stage procedure, but the reversed-Abbe flap had 2 stages. There were no functional problems in patients with Estlander flap, but these patients complained of lip asymmetry. There were no functional complaints and aesthetic problems in patients with double reversed-Abbe flap at 3 months after the operation. In patients with 30% to 50% defect of the lower lip, there was no functional and aesthetic difference between Abbe flap and step-ladder flap. Estlander flap is a good choice for reconstruction of lateral or commissural defects of the lower lip. In patients with 50% to 80% defect, it is better to use bilateral reversed-Abbe instead of the Karapandzic flap.

The lipid quality assessment of Schizothorax zarudnyi and Schizocypris altidorsalis by fatty acid analysis.

The proximate and fatty acid composition of two locally important freshwater fish, Schizothorax zarudnyi and Schizocypris altidorsalis, from Sistan Province in Iran were investigated for their nutritional value. The protein and lipid content in the S. zarudnyi were 14.67 and 6.36%, respectively. In S. altidorsalis, protein and lipid content were 13.03 and 4.52%. There was quantitative difference between individual fatty acids of these two fish. Totally 18 fatty acids were found. In S. zarudnyi, DHA was the highest among the poly-unsaturated fatty acids with 42.85%, followed by EPA with 29.62% of the total poly-unsaturated fraction. In S. altidorsalis, EPA was the highest among the poly-unsaturated fatty acids with 45.05%, followed by DHA with 27.87% the total poly-unsaturated fraction. The n-6/n-3 ratio was 0.26 and 0.20 for S. zarudnyi and S. altidorsalis, respectively. High n-3 fatty acids content in these fish revealed that they have high nutritional value. Schizothorax zarudnyi showed better nutritional value in comparison to protein and lipid content of S. altidorsalis.