Cancer-Associated Thrombosis in Cirrhotic Patients with Hepatocellular Carcinoma.

It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis

Análise diagnóstica e prospectiva da cadeia produtiva de energia de biomassa de origem florestal.

bitstream/CNPF-2009-09/42554/1/Doc151.pdf1 CD-ROM

Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15–20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents

Albumin uptake in human podocytes: a possible role for the cubilin-amnionless (CUBAM) complex

Abstract Albumin re-uptake is a receptor-mediated pathway located in renal proximal tubuli. There is increasing evidence of glomerular protein handling by podocytes, but little is known about the mechanism behind this process. In this study, we found that human podocytes in vitro are committed to internalizing albumin through a receptor-mediated mechanism even after exposure to low doses of albumin. We show that these cells express cubilin, megalin, ClC-5, amnionless and Dab2, which are partners in the tubular machinery. Exposing human podocytes to albumin overload prompted an increase in CUBILIN, AMNIONLESS and CLCN5 gene expression. Inhibiting cubilin led to a reduction in albumin uptake, highlighting its importance in this mechanism. We demonstrated that human podocytes are committed to performing endocytosis via a receptor-mediated mechanism even in the presence of low doses of albumin. We also disclosed that protein overload first acts on the expression of the cubilin-amnionless (CUBAM) complex in these cells, then involves the ClC-5 channel, providing the first evidence for a possible role of the CUBAM complex in albumin endocytosis in human podocytes

Functioning and disability in multiple sclerosis from the patient perspective

Multiple sclerosis (MS) has a great impact on functioning and disability. The perspective of those who experience the health problem has to be taken into account to obtain an in-depth understanding of functioning and disability. The objective was to describe the areas of functioning and disability and relevant contextual factors in MS from the patient perspective. A qualitative study using focus group methodology was performed. The sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for data analysis. Identified concepts were linked to International Classification of Functioning, Disability and Health (ICF) categories according to established linking rules. Six focus groups with a total of 27 participants were performed. In total, 1327 concepts were identified and linked to 106 ICF categories of the ICF components Body Functions, Activities and Participation and Environmental Factors. This qualitative study reports on the impact of MS on functioning and disability from the patient perspective. The participants in this study provided information about all physical aspects and areas of daily life affected by the disease, as well as the environmental factors influencing their lives

The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters. XIII. ACS/WFC Parallel-Field Catalogues

As part of the Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters, 110 parallel fields were observed with the Wide Field Channel of the Advanced Camera for Surveys, in the outskirts of 48 globular clusters, plus the open cluster NGC 6791. Totalling about $0.3$ square degrees of observed sky, this is the largest homogeneous Hubble Space Telescope photometric survey of Galalctic globular clusters outskirts to date. In particular, two distinct pointings have been obtained for each target on average, all centred at about $6.5$ arcmin from the cluster centre, thus covering a mean area of about $23\,{\rm arcmin^{2}}$ for each globular cluster. For each field, at least one exposure in both F475W and F814W filters was collected. In this work, we publicly release the astrometric and photometric catalogues and the astrometrised atlases for each of these fields.Comment: 30 pages, 23 figures. Accepted by MNRA

Perinatal or neonatal mortality among women who intend at the onset of labour to give birth at home compared to women of low obstetrical risk who intend to give birth in hospital: A systematic review and meta-analyses

Background: More women are choosing to birth at home in well-resourced countries. Concerns persist that out-of-hospital birth contributes to higher perinatal and neonatal mortality. This systematic review and meta-analyses determines if risk of fetal or neonatal loss differs among low-risk women who begin labour intending to give birth at home compared to low-risk women intending to give birth in hospital. Methods: In April 2018 we searched five databases from 1990 onward and used R to obtain pooled estimates of effect. We stratified by study design, study settings and parity. The primary outcome is any perinatal or neonatal death after the onset of labour. The study protocol is peer-reviewed, published and registered (PROSPERO No.CRD42013004046). Findings: We identified 14 studies eligible for meta-analysis including ~ 500,000 intended home births. Among nulliparous women intending a home birth in settings where midwives attending home birth are well-integrated in health services, the odds ratio (OR) of perinatal or neonatal mortality compared to those intending hospital birth was 1.07 (95% Confidence Interval [CI], 0.70 to 1.65); and in less integrated settings 3.17 (95% CI, 0.73 to 13.76). Among multiparous women intending a home birth in well-integrated settings, the estimated OR compared to those intending a hospital birth was 1.08 (95% CI, 0.84 to 1.38); and in less integrated settings was 1.58 (95% CI, 0.50 to 5.03). Interpretation: The risk of perinatal or neonatal mortality was not different when birth was intended at home or in hospital. Funding: Partial funding: Association of Ontario Midwives open peer reviewed grant. Research in Context: Evidence before this study Although there is increasing acceptance for intended home birth as a choice for birthing women, controversy about its safety persists. The varying responses of obstetrical societies to intended home birth provide evidence of contrasting views. A Cochrane review of randomised controlled trials addressing this topic included one small trial and noted that in the absence of adequately sized randomised controlled trials on the topic of intended home compared to intended hospital birth, a peer reviewed protocol be published to guide a systematic review and meta-analysis including observational studies. Reviews to date have been limited by design or methodological issues and none has used a protocol published a priori.Added value of this study Individual studies are underpowered to detect small but potentially important differences in rare outcomes. This study uses a published peer-reviewed protocol and is the largest and most comprehensive meta-analysis comparing outcomes of intended home and hospital birth. We take study design, parity and jurisdictional support for home birth into account. Our study provides much needed information to policy makers, care providers and women and families when planning for birth.Implications of all the available evidence Women who are low risk and who intend to give birth at home do not appear to have a different risk of fetal or neonatal loss compared to a population of similarly low risk women intending to give birth in hospital

The Hubble Space Telescope UV legacy survey of galactic globular clusters - X. The radial distribution of stellar populations in NGC2808

Due to their extreme helium abundance, the multiple stellar populations of the globular cluster NGC 2808 have been widely investigated from a photometric, spectroscopic, and kinematic perspective. The most striking feature of the colour–magnitude diagram of NGC 2808 is the triple main sequence (MS), with the red MS corresponding to a stellar population with primordial helium, and the middle and the blue MS being enhanced in helium up to Y ∼ 0.32 and ∼0.38, respectively. A recent study has revealed that this massive cluster hosts at least five distinct stellar populations (A, B, C, D, and E). Among them populations A, B, and C correspond to the red MS, while populations C and D are connected to the middle and the blue MS. In this paper, we exploit Hubble Space Telescope photometry to investigate the radial distribution of the red, the middle, and the blue MS from the cluster centre out to about 8.5 arcmin. Our analysis shows that the radial distribution of each of the three MSs is different. In particular, as predicted from multiple-population formation models, both the blue MS and the middle MS appears to be more concentrated than the red MS with a significance level for this result which is above 3

Progressive decline of decision-making performances during multiple sclerosis

The purpose of this study was to evaluate longitudinally, using the Iowa Gambling Task (IGT), the dynamics of decision-making capacity at a two-year interval (median: 2.1 years) in a group of patients with multiple sclerosis (MS) (n = 70) and minor neurological disability [Expanded Disability Status Scale (EDSS) ≤ 2.5 at baseline]. Cognition (memory, executive functions, attention), behavior, handicap, and perceived health status were also investigated. Standardized change scores [(score at retest-score at baseline)/standard deviation of baseline score] were computed. Results showed that IGT performances decreased from baseline to retest (from 0.3, SD = 0.4 to 0.1, SD = 0.3, p = .005). MS patients who worsened in the IGT were more likely to show a decreased perceived health status and emotional well-being (SEP-59; p = .05 for both). Relapsing rate, disability progression, cognitive, and behavioral changes were not associated with decreased IGT performances. In conclusion, decline in decision making can appear as an isolated deficit in MS. (JINS, 2009, 15, 291-295.

Pharmacological and partial biochemical characterization of Bmaj-9 isolated from Bothrops marajoensis snake venom

Bmaj-9, a basic PLA2 (13679.33 Da), was isolated from Bothrops marajoensis snake venom through only one chromatographic step in reversed phase HPLC on ¼-Bondapak C-18 column. The amino acid composition showed that Bmaj-9 had a high content of Lys, His, and Arg, typical of a basic PLA2. The sequence of Bmaj-9 contains 124 amino acid residues with a pI value of 8.55, such as DLWQWGQMIL KETGKLPFSY YTAYGCYCGW GGRGGKPKAD TDRCCFVHDC, revealing a high homology with Asp49 PLA2 from other snake venoms. It also exhibited a pronounced phospholipase A2 activity when compared with crude venom. In chick biventer cervicis preparations, the time for 50% and 100% neuromuscular paralysis was respectively (in minutes): 110 ± 10 (1 µg/mL); 40 ± 6 and 90 ± 2 (5 µg/mL); 30 ± 3 and 70 ± 5 (10 µg/mL); 42 ± 1 and 60 ± 2 (20 µg/mL), with no effect on the contractures elicited by either exogenous ACh (110 µM) or KCl (20 mM). Bmaj-9 (10 µg/mL) neither interfered with the muscular response to direct electrical stimulation in curarized preparations nor significantly altered the release of CK at 0, 15, 30 and 60 minutes incubations (27.4 ± 5, 74.2 ± 8, 161.0 ± 21 and 353.0 ± 47, respectively). The histological analysis showed that, even causing blockade at the maximum dosage (5 µg/mL), the toxin does not induce significant morphological alterations such as necrosis or infiltration of inflammatory cells. These results identified Bmaj-9 as a new member of the basic Asp49 PLA2 family able to interact with the motor nerve terminal membrane, thereby inducing a presynaptic neuromuscular blockade181627