Morton Brinch (maskiran25)

Traditional cytogenetic testing methodologies, including conventional chromosome analysis and fluorescence in situ hybridization (FISH), are invaluable for the detection or recurrent genetic abnormalities in various hematologic malignancies. However, technological advances, including a novel next-generation sequencing technique termed mate-pair sequencing (MPseq), continue to revolutionize the field of cytogenetics by enabling the characterization of structural variants at a significantly higher resolution compared to traditional methodologies. To illustrate the power of MPseq, we present a 27-year-old male diagnosed with chronic myeloid leukemia in myeloid blast crisis with multiple chromosomal abnormalities observed in all 20 metaphases from a peripheral blood specimen, including t(9;22)(q34;q11.2) and t(4;11)(q12;p15). Suspicious of a novel NUP98/PDGFRA fusion [t(4;11)(q12;p15)], break-apart FISH probe sets for the PDGFRA (4q12) and NUP98 (11p15.4) gene regions were performed and were both positive in approximately 86% of 200 interphase nuclei. However, subsequent MPseq testing revealed breakpoints located within the NUP98 gene and within an intergenic region (4q12) located between the CHIC2 and PDGFRA genes, indicating this 4;11 translocation does not result in the predicted NUP98/PDGFRA gene fusion as inferred from FISH and conventional chromosome results. This case demonstrates the clinical utility of MPseq, particularly for characterizing novel gene fusion events which may ultimately identify a false-positive FISH result. BACKGROUND This study was designed to assess the achievement of a glycated hemoglobin (HbA1c) target in Iraqi type 2 diabetes mellitus (T2DM) patients via retrospective analysis of a tertiary care database over a 9-year period. METHODS A total of 12,869 patients with T2DM with mean (SEM) age 51.4(0.1) years, and 54.4% were females registered into Faiha Specialized Diabetes, Endocrine and Metabolism Center(FDEMC) database between August 2008 and July 2017 were included in this retrospective study. Data were recorded for each patient during routine follow-up visits performed at the center every 3-12 months. RESULTS Patients were under oral antidiabetic drugs (OAD; 45.8%) or insulin+ OAD (54.2%) therapy. Hypertension was evident in 42.0% of patients, while dyslipidemia was noted in 70.5%. Glycemic control (HbA1c 10% at the first visit, presence of dyslipidemia, and insulin treatment as significant determinants of an increased risk of poor glycemic control. Mardepodect clinical trial BMI less then 25 kg/m2 and presence of hypertension were associated with a decreased risk of poor glycemic control. CONCLUSION Using data from the largest cohort of T2DM patients from Iraq to date, this tertiary care database analysis over a 9-year period indicated poor glycemic control. Younger patient age, female gender, longer disease duration, initially high HbA1c levels, dyslipidemia, insulin treatment, overweight and obesity, and lack of hypertension were associated with an increased risk of poor glycemic control in Iraqi T2DM patients. Sepsis is a disease with high mortality rate worldwide and inducible nitric oxide (iNOS) induced vascular hyporeactivity plays a key role in it. There is no effective drug to treat vascular hyporeactivity specifically. Tubeimoside I (TBM) is a triterpenoid saponin isolated from Rhizoma Bolbostemmatis. In this study, we found that 4 mg/kg TBM intraperitoneally injected 1 h before cecal ligation and puncture (CLP) partially improved survival, ameliorated mean arterial pressure (MAP) and enhanced vascular responsiveness to norepinephrine (NE) and KCl in wild-type septic mice. CLP activated TLR4-MyD88-NF-κB-iNOS pathway was also inhibited by TBM both in vitro and in vivo. However, iNOS gene knockout counteracted the protection provided by TBM. We conclude that TBM protects mice in sepsis by reducing excessive NO production through inhibiting the TLR4-MyD88-NF-κB-iNOS pathway. Our stu