Collateral pial circulation relates to the degree of brain edema on CT 24 hours after ischemic stroke

Background Cerebral edema is frequent in patients with acute ischemic stroke (AIS) who undergo reperfusion therapy and is associated with high mortality. The impact of collateral pial circulation (CPC) status on the development of edema has not yet been determined. Methods We studied consecutive patients with AIS and documented M1-middle cerebral artery (MCA) and/or distal internal carotid artery (ICA) occlusion who underwent reperfusion treatment. Edema was graded on the 24-hour non-contrast computed tomography (NCCT) scan. CPC was evaluated at the acute phase (≤6 hours) by transcranial color-coded Doppler, angiography and/or CT angiography. We performed an ordinal regression model for the effect of CPC on cerebral edema, adjusting for age, baseline National Institutes of Health Stroke Scale, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on admission, NCCT, parenchymal hemorrhagic transformation at 24 hours and complete recanalization at six hours. Results Among the 108 patients included, 49.1% were male and mean age was 74.2 ± 11.6 years. Multivariable analysis showed a significant association between cerebral edema and CPC status (OR 0.22, 95% CI 0.08-0.59, p = 0.003), initial ASPECTS (OR 0.72, 95% CI 0.57-0.92, p = 0.007) and parenchymal hemorrhagic transformation (OR 23.67, 95% CI 4.56-122.8, p < 0.001). Conclusions Poor CPC is independently associated with greater cerebral edema 24 hours after AIS in patients who undergo reperfusion treatment.info:eu-repo/semantics/publishedVersio

Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause

BACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.info:eu-repo/semantics/publishedVersio

Endothelial Progenitor Cells influence acute and subacute stroke hemodynamics

BACKGROUND: Endothelial Progenitor Cells (EPCs) are a circulating stem cell population with in vivo capacity of promoting angiogenesis after ischemic events. Despite the promising preclinical data, their potential integration with reperfusion therapies and hemodynamic evolution of stroke patients is still unknown. Our aim was to determine the association of EPCs with acute, subacute and chronic hemodynamic features. METHODS: In this prospective study, we included consecutive patients with ages between 18 and 80years and non-lacunar ischemic stroke within the territory of a middle cerebral artery. All patients were subject to hemodynamic evaluation by ultrasound at baseline, seven days and three months. We quantified cerebral blood flow (CBF) and assessed early recanalization and collateral flow. Hemorrhagic transformation was graded in Magnetic Resonance imaging performed at seven days. EPCs were isolated from peripheral venous blood collected in the first 24h and seven days, counted and submitted to functional in vitro tests. RESULTS: We included 45 patients with a median age of 70±10years. The angiogenic and migratory capacities of EPCs were associated with increased collateral flow in the acute stage and day seven CBF, without statistically significant associations with recanalization nor haemorrhagic transformation. The number of EPCs was not associated with any hemodynamic variable. CONCLUSIONS: The functional properties of EPCs are associated with acute and subacute stroke hemodynamics, with no effect on haemorrhagic transformation.info:eu-repo/semantics/publishedVersio

Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness.

The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas

Solving the multi-period water distribution network design problem with a hybrid simulated anealling

This work presents an optimization technique based on Simulated Annealing (SA) to solve the Water Distribution Network Design problem, considering multi-period restrictions with time varying demand patterns. The design optimization of this kind of networks is an important issue in modern cities, since a safe, adequate, and accessible supply of potable water is one of the basic necessities of any human being. Given the complexity of this problem, the SA is improved with a local search procedure, yielding a hybrid SA, in order to obtain good quality networks designs. Additionally, four variants of this algorithm based on different cooling schemes are introduced and analyzed. A broad experimentation using different benchmark networks is carried out to test our proposals. Moreover, a comparison with an approach from the literature reveals the goodness to solve this network design problem.Fil: Bermudez, Carlos Alberto. Universidad Nacional de la Pampa. Facultad de Ingeniería; ArgentinaFil: Salto, Carolina. Universidad Nacional de la Pampa. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Minetti, Gabriela Fabiana. Universidad Nacional de la Pampa. Facultad de Ingeniería; Argentin

Blood Pressure Variability in Acute Ischemic Stroke: The Role of Early Recanalization

We performed a retrospective study with the aim of investigating the association between blood pressure (BP) variability in the first 24 h after ischemic stroke and functional outcome, regarding arterial recanalization status. A total of 674 patients diagnosed with acute stroke and treated with revascularization therapies were enrolled. Systolic and diastolic BP values of the first 24 h after stroke were collected and their variation quantified through standard deviation. Recanalization state was evaluated at 6 h and clinical outcome at 3 months was assessed by modified Rankin Scale. In multivariate analyses systolic BP variability in the first 24 h post-stroke showed an association with 3 months clinical outcome in the whole population and non-recanalyzed patients. In recanalyzed patients, BP variability did not show a significant association with functional outcome.info:eu-repo/semantics/publishedVersio

Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio

SOD2 immunoexpression predicts lymph node metastasis in penile cancer

BACKGROUND: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown. METHODS: SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis. RESULTS: SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis. CONCLUSIONS: Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.Dr. Lara Termini (FAPESP 2005/57274-9); Dr. Luisa Lina Villa (FAPESP 2008/57889-1 and CNPq 573799/2008-3)