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An amendment to this paper has been published and can be accessed via a link at the top of the paper.Intracerebroventricular (icv) injection of hydrogen peroxide (H2O2) or the increase of endogenous H2O2 centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with H2O2 injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5-10/group) with stainless steel cannulas implanted in the lateral ventricle were used. In freely moving rats, H2O2 (5 μmol/1 μl) or ATZ (5 nmol/1 μl) icv reduced the pressor responses to ANG II (50 ng/1 µl) icv in SHRs (11 ± 3 and 17 ± 4 mmHg, respectively, vs. 35 ± 6 mmHg) and 2K1C hypertensive rats (3 ± 1 and 16 ± 3 mmHg, respectively, vs. 26 ± 2 mmHg). ATZ (3.6 mmol/kg of body weight) iv alone or combined with H2O2 icv also reduced icv ANG II-induced pressor response in SHRs and 2K1C hypertensive rats. Baseline arterial pressure was also reduced (-10 to -15 mmHg) in 2K1C hypertensive rats treated with H2O2 icv and ATZ iv alone or combined and in SHRs treated with H2O2 icv alone or combined with ATZ iv. The results suggest that exogenous or endogenous H2O2 acting centrally produces anti-hypertensive effects impairing central pressor mechanisms activated by ANG II in SHRs or 2K1C hypertensive rats.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) have become an important tool to assess patients' prognosis and guide treatment. We tested the prognostic impact of the 2017 ELN classification in a large cohort of 863 AML patients aged less then 60 years similarly treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology studies. Based on multivariable models within each ELN genetic-risk group, we identified additional gene mutations that may refine the 2017 ELN risk classification. BCOR- or SETBP1-mutated favorable-risk patients with non-core-binding factor AML and IDH-mutated adverse-risk patients had intermediate-risk outcomes. Outcomes of NPM1/WT1 co-mutated patients and those of ZRSR2-mutated patients resembled outcome of adverse-risk patients. Moreover, FLT3-ITDhigh allelic ratio conferred adverse rather than intermediate-risk irrespective of the NPM1 mutation status, and DNMT3A mutations associated with very poor survival. Application of these refinements reclassified 9% of current favorable-risk patients and 53% of current intermediate-risk patients to the adverse-risk group, with similar poor survival as current adverse-risk patients. Furthermore, 4% of current favorable-risk patients and 9% of adverse-risk patients were reclassified to the intermediate-risk group.Population-based studies of classical Hodgkin lymphoma (cHL) in contemporary clinical practice are scarce. PF06821497 The aim of this nationwide population-based study is to assess trends in primary therapy and relative survival (RS) during 1989-2017. We included 9,985 patients with cHL. Radiotherapy alone was virtually not applied as from 2000 among patients aged 18-69 years with stage I/II disease, following the broader application of chemotherapy combined with radiotherapy. Chemotherapy only was the preferred treatment for patients with stage III/IV disease. Throughout the entire study period, around 20% of patients aged ≥70 years across all disease stages received no anti-neoplastic therapy. The most considerable improvements in 5-year RS were confined to patients aged 18-59 years. Five-year RS for patients with stage I/II disease diagnosed during 2010-2017 was 99%, 98%, 100%, 93%, 84%, and 61% for patients aged 18-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years, respectively. The corresponding estimates for stage III/IV disease were 96%, 92%, 90%, 80%, 58%, and 46%. Collectively, the improvements in survival likely relate to advances in cHL management. These achievements, however, do not seem to translate into significant benefits for patients ≥60 years. Therefore, novel therapies are urgently needed to reduce excess mortality in elderly cHL patients.Objective To determine the effect of timing of expression initiation on mother's own milk production and time to secretory activation in mothers of preterm infants. Study design 180 mothers delivering infants ≤1500 grams and ≤32 weeks gestation were randomized to begin expression within 60 (early), 61-180 (intermediate) or 181-360 (late) minutes following delivery. Milk volume was measured on days 1-7 and weekly for 6 weeks. Time to secretory activation was determined through self-report. Results The late group produced more milk than the early group in the first 3 days (p = 0.015-0.031) and over 6 weeks (p = 0.045). The late group had more expressions on day 1 (early p = 0.049; intermediate; p = 0.048). Conclusion Initiation of expression at 181-360 min following delivery was associated with increased milk production for 6 weeks following delivery. Further research is needed to determine the effect of expression frequency on milk production in the first days following birth.Although squamous cell carcinomas (SCC) are the most frequent human solid tumor at many anatomic sites, the driving molecular alterations underlying their progression from precursor lesions are poorly understood, especially in the context of photodamage. Therefore, we used high-depth, targeted next-generation sequencing (NGS) of RNA and DNA from routine tissue samples to characterize the progression of both well- (cutaneous) and poorly (ocular) studied SCCs. We assessed 56 formalin-fixed paraffin-embedded (FFPE) cutaneous lesions (n = 8 actinic keratosis, n = 30 carcinoma in situ [CIS], n = 18 invasive) and 43 FFPE ocular surface lesions (n = 2 conjunctival/corneal intraepithelial neoplasia, n = 20 CIS, n = 21 invasive), from institutions in the US and Brazil. An additional seven cases of advanced cutaneous SCC were profiled by hybrid capture-based NGS of >1500 genes. The cutaneous and ocular squamous neoplasms displayed a predominance of UV-signature mutations. Precursor lesions had highly similar somatic genomic landscapes to SCCs, including chromosomal gains of 3q involving SOX2, and highly recurrent mutations and/or loss of heterozygosity events affecting tumor suppressors TP53 and CDKN2A.