Results from cosmics and first LHC beam with the ALICE HMPID detector

The ALICE HMPID (High Momentum Particle IDentification) detector has been designed to identify charged pions and kaons in the range 1 < p < 3 GeV/c and protons in the range 1.5 < p < 5 GeV/c. It consists of seven identical proximity focusing RICH (Ring Imaging Cherenkov) counters, covering in total 11 m2, which exploit large area MWPC equipped with CsI photocathodes for Cherenkov light imaging emitted in a liquid C6F14 radiator. The ALICE detector has been widely commissioned using cosmics and LHC beam from December 2007 until October 2008. During the cosmics data taking the HMPID detector collected a large set of data, using mainly the trigger provided by the TOF detector. We present here preliminary results of detector alignment using TPC tracking. The HMPID could be operated in a stable way, at a safe HV setting, also during LHC beam injection and circulation tests, when a very large occupancy (up to 50%) was achieved. Resulting gain mapping and overall detector performance will also be discussed.Comment: 4 pages, 5 figures - To appear in the conference proceedings for Quark Matter 2009, March 30 - April 4, Knoxville, Tennessee.

First experimental release of the red-and-green macaw Ara chloropterus in Corrientes, Argentina

In 2015 seven captive-bred red-and-green macaws Ara chloropterus were experimentally released into the Iberá National Park, Corrientes, Argentina. After a month in a pre-release cage, they were hard released. Two birds were preyed upon, three flew beyond our detection range, one transmitter was recovered underwater, and one bird was recaptured. We identify ways in which future releases of captive-bred macaws could be improved.Fil: Volpe, Noelia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; ArgentinaFil: Di Giacomo, Adrian Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; ArgentinaFil: Berkunsky, Igor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto Multidisciplinario sobre Ecosistemas y Desarrollo Sustentable. Grupo de Ecología Matemática; Argentin

C2238/αANP modulates apolipoprotein E through Egr-1/miR199a in vascular smooth muscle cells in vitro

Subjects carrying the T2238C ANP gene variant have a higher risk to suffer a stroke or myocardial infarction. The mechanisms through which T2238C/αANP exerts detrimental vascular effects need to be fully clarified. In the present work we aimed at exploring the impact of C2238/αANP (mutant form) on atherosclerosis-related pathways. As a first step, an atherosclerosis gene expression macroarray analysis was performed in vascular smooth muscle cells (VSMCs) exposed to either T2238/αANP (wild type) or C2238/αANP. The major finding was that apolipoprotein E (ApoE) gene expression was significantly downregulated by C2238/αANP and it was upregulated by T2238/αANP. We subsequently found that C2238/αANP induces ApoE downregulation through type C natriuretic peptide receptor (NPR-C)-dependent mechanisms involving the upregulation of miR199a-3p and miR199a-5p and the downregulation of DNAJA4. In fact, NPR-C knockdown rescued ApoE level. Upregulation of miR199a by NPR-C was mediated by a reactive oxygen species-dependent increase of the early growth response protein-1 (Egr-1) transcription factor. In fact, Egr-1 knockdown abolished the impact of C2238/αANP on ApoE and miR199a. Of note, downregulation of ApoE by C2238/αANP was associated with a significant increase in inflammation, apoptosis and necrosis that was completely rescued by the exogenous administration of recombinant ApoE. In conclusion, our study dissected a novel mechanism of vascular damage exerted by C2238/αANP that is mediated by ApoE downregulation. We provide the first demonstration that C2238/αANP downregulates ApoE in VSMCs through NPR-C-dependent activation of Egr-1 and the consequent upregulation of miR199a. Restoring ApoE levels could represent a potential therapeutic strategy to counteract the harmful effects of C2238/αANP

Role of Arterial Hypertension and Hypertension-Mediated Organ Damage in Cardiotoxicity of Anticancer Therapies

Purpose of the review: Arterial hypertension (AH) is the most common cardiovascular (CV) risk factor in the community and in oncologic patients. It also represents the most important CV condition predisposing to anticancer treatment-related cardiotoxicity. This risk is heightened in the presence of cardiac AH-mediated organ damage (HMOD). Influence of AH and HMOD on the development of cardiotoxicity will be reviewed, with a focus on specific scenarios and implications for management of oncologic patients. Recent findings: Not adequately controlled AH before or during anticancer treatments and/or development of AH during or after completion of such therapies have detrimental effects on the clinical course of oncologic patients, particularly if HMOD is present. As overlooking CV health can jeopardize the success of anticancer treatments, the goal for clinicians caring for the oncologic patient should include the treatment of AH and HMOD

Regulation of the flt3 gene in haematopoietic stem and early progenitor cells

The MYB transcription factor plays critical roles in normal and malignant haematopoiesis. We previously showed that MYB was a direct activator of FLT3 expression within the context of acute myeloid leukaemia. During normal haematopoiesis, increasing levels of FLT3 expression determine a strict hierarchy within the haematopoietic stem and early progenitor compartment, which associates with lymphoid and myeloid commitment potential. We use the conditional deletion of the Myb gene to investigate the influence of MYB in Flt3 transcriptional regulation within the haematopoietic stem cell (HSC) hierarchy. In accordance with previous report, in vivo deletion of Myb resulted in rapid biased differentiation of HSC with concomitant loss of proliferation capacity.We find that loss of MYB activity also coincided with decreased FLT3 expression. At the chromatin level, the Flt3 promoter is primed in immature HSC, but occupancy of further intronic elements determines expression. Binding to these locations, MYB and C/EBPα need functional cooperation to activate transcription of the locus. This cooperation is cell context dependent and indicates that MYB and C/ EBPα activities are inter-dependent in controlling Flt3 expression to influence lineage commitment of multipotential progenitors

Exploring the influence of takotsubo syndrome on oncologic patients' mortality

It has been reported that patients affected by takotsubo syndrome (TTS) with a concurrent diagnosis of cancer suffer from greater mortality as compared to their non-cancer counterpart. It remains unclear whether TTS worsens the prognosis of cancer patients as well. Aim of this study was to compare outcomes of cancer patients with and without TTS. We combined data from two independent cohorts: one consisted of a prospective multicentre TTS registry; the second cohort consisted of all oncologic patients from two Cardio-Oncology Outpatient Clinics, who did not have cardiovascular conditions at the time of the cardio-oncologic visit. From the TTS registry, we selected patients with cancer (cancer-TTS patients). Next, we matched these patients with those from the cardio-oncologic cohort (cancer non-TTS patients) in a 1:2 fashion by age, sex, and type and cancer staging. Study endpoint was all-cause mortality. Among 318 TTS patients, 42 (13%) had a concurrent diagnosis of cancer. Characteristics of cancer-TTS patients and of the 84 matched cancer non-TTS subjects were comparable with the exception of diabetes mellitus, which was more common in cancer non-TTS patients. All-cause mortality was similar between cancer-TTS and cancer non-TTS patients. At Cox regression analysis TTS was not associated with mortality (OR 1.4, 95% CI 0.6-3.3, p = 0.43). Our findings show that even in the presence of acute heart failure due to TTS, the prognosis of oncologic patients is driven by the malignancy itself. Our results may prove useful for integrated management of cardio-oncologic patients

Long QTc in hypertrophic cardiomyopathy. A consequence of structural myocardial damage or a distinct genetic disease?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G &gt; A, p. Arg594Gln; c.532G &gt; A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning

PADUA and R.E.N.A.L. nephrometry scores correlate with perioperative outcomes of robot-assisted partial nephrectomy: analysis of the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database

Objectives: To evaluate and compare the correlations between Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) and R.E.N.A.L. [Radius (tumour size as maximal diameter), Exophytic/endophytic properties of the tumour, Nearness of tumour deepest portion to the collecting system or sinus, Anterior (a)/posterior (p) descriptor and the Location relative to the polar line] nephrometry scores and perioperative outcomes and postoperative complications in a multicentre, international series of patients undergoing robot-assisted partial nephrectomy (RAPN) for masses suspicious for renal cell carcinoma (RCC). Patients and Methods: We retrospectively evaluated the clinical records of patients who underwent RAPN between 2010 and 2013 for clinical N0M0 renal tumours in four international centres that completed all the data required for the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database. All patients underwent preoperative computed tomography or magnetic resonance imaging to define the clinical stage and anatomical characteristics of the tumours. PADUA and R.E.N.A.L. scores were retrospectively assessed in each centre. Univariate and multivariate analyses were used to evaluate the correlations between age, gender, Charlson comorbidity index, clinical tumour size, PADUA and R.E.N.A.L. complexity group categories and warm ischaemia time (WIT) of >20 min, urinary calyceal system closure, and grade of postoperative complications. Results: Overall, 277 patients were evaluated. The median (interquartile range) tumour size was 33.0 (22.0\u201343.0) mm. The median PADUA and R.E.N.A.L. scores were eight and seven, respectively; 112 (40.4%), 86 (31.0%) and 79 (28.5%) patients were classified in the low-, intermediate- or high-complexity group according to PADUA score, while 118 (42.5%), 139 (50.1%) and 20 (7.2%) were classified in the low-, intermediate- or high-complexity group according to R.E.N.A.L. score, respectively. Both nephrometry tools significantly correlated with perioperative outcomes at univariate and multivariate analyses. Conclusion: A precise stratification of patients before PN is recommended to consider both the potential threats and benefits of nephron-sparing surgery. In our present analysis, both PADUA and R.E.N.A.L. were significantly associated with predicting prolonged WIT and high-grade postoperative complications after RAP