High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations

To identify cooperating lesions in core-binding factor acute myeloid leukemia, we performed single-nucleotide polymorphism-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). Approximately one-half of the 7q deletions were detectable only by single-nucleotide polymorphism-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single noncoding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region of 1p (NRAS) and 4q (TET2). Analysis of relapse samples identified recurrent MDRs at 3q13.31 (12.2%), 5q (4.9%), and 17p (4.9%), with the 3q13.31 region containing only LSAMP, a putative tumor suppressor. Determining the role of these lesions in leukemogenesis and drug resistance should provide important insights into core-binding factor acute myeloid leukemia.     

Diets containing pistachios reduce systolic blood pressure and peripheral vascular responses to stress in adults with dyslipidemia

Nut consumption reduces cardiovascular risk, and reductions in blood pressure and peripheral vascular resistance may be important mediators of this relationship. We evaluated effects of pistachios on flow-mediated dilation and blood pressure response to acute stress. Twenty-eight adults with dyslipidemia completed a randomized, crossover, controlled-feeding study. All of the meals were provided and calories were controlled. After 2 weeks on a typical Western diet (35% total fat and 11% saturated fat), test diets were presented in counterbalanced order for 4 weeks each, a low-fat control diet (25% total fat and 8% saturated fat), a diet containing 10% of energy from pistachios (on average, 1 serving per day; 30% total fat and 8% saturated fat), and a diet containing 20% of energy from pistachios (on average, 2 servings per day, 34% total fat and 8% saturated fat). None of the resting hemodynamic measures significantly differed from pretreatment values. When resting and stress levels were included in the repeated-measures analysis, average reductions in systolic blood pressure were greater after the diet containing 1 serving per day versus 2 servings per day of pistachios (mean change in systolic blood pressure, -4.8 vs -2.4 mm Hg, respectively; P<0.05). After the higher dose, there were significant reductions in peripheral resistance (-62.1 dyne · s × cm(-5)) and heart rate (-3 bpm) versus the control diet (P<0.0001). These changes were partially offset by increases in cardiac output. There was no effect of diet on fasting flow-mediated dilation. Reductions in peripheral vascular constriction and the resulting decrease in hemodynamic load may be important contributors to lower risk in nut consumers.     

Influence of Periodontal Status and Periodontopathogens on Levels of Oral Human β‐Defensin‐2 in Saliva

Background: Expression patterns of human β‐defensin‐2 (HBD‐2) mRNA or HBD‐2 protein concentration and periodontal diseases have been a focus of scientific research. This study compares the salivary levels of HBD‐2 protein concentration of healthy patients and patients with gingivitis and chronic periodontitis (CP) and correlates these levels with the presence of periodontopathogens. Methods: A total of 89 patients were enrolled in this study: 31 periodontally healthy, 27 with gingivitis, and 31 with CP. Plaque and gingival indices, probing depth, and clinical attachment level were measured. The presence of Campylobacter rectus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Prevotella intermedia was evaluated qualitatively by conventional polymerase chain reaction. HBD‐2 quantification in saliva was performed using an immune enzymatic assay. Frequency of periodontopathogens and HBD‐2 protein concentration was assessed. Association between HBD‐2 protein concentration (≥100 pg/mL) and the simultaneous presence of one to two, three to four, or five to six periodontopathogens was tested. Results: Although periodontally healthy individuals and patients with gingivitis showed similar HBD‐2 levels, the CP group displayed an increased level of HBD‐2. P. gingivalis, P. intermedia, T. forsythia, and T. denticola were more prevalent in CP; however, their mere presence was not related to the increased levels of HBD‐2 (Pearson correlation and multinomial logistic regression model). Conclusions: Salivary HBD‐2 protein concentration was higher in patients with CP compared with healthy individuals or patients with gingivitis. These different protein concentrations were not related to the frequency of periodontopathogens. Clinical inflammatory profile had a higher impact on salivary HBD‐2 levels than bacteria.