Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies

The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens

Exercise induced neuroplasticity to enhance therapeutic outcomes of cognitive remediation in schizophrenia: Analyzing the role of brain-derived neurotrophic factor

Cognitive impairment is a major manifestation of schizophrenia and a crucial treatment target as these deficits are closely related to patients' functional outcomes. Cognitive remediation is the gold-standard practice to address cognitive deficits in schizophrenia. There is clear evidence stating that cognitive remediation improves cognitive function and promotes structural neuroplastic changes in patients with schizophrenia, with brain-derived neurotrophic factor (BDNF) expression emerging as a potential biomarker for its efficacy. This is particularly important as there is clear evidence relating atypical BDNF expression to cognitive impairment in patients with schizophrenia. Despite the valuable role of cognitive remediation in the management of schizophrenia, there is still a need to develop methods that allow maximizing its efficacy.info:eu-repo/semantics/publishedVersio

Endotoxin-induced disseminated intravascular coagulation in rabbits: effect of recombinant hirudin on hemostatic parameters, fibrin deposits, and mortality

We evaluated the effect of r-hirudin on an experimental model of disseminated intravascular coagulation (DIC) in rabbits, through the continuous infusion of 100 microg/kg/hr of Escherichia coli endotoxin for a period of 6 hours. r-Hirudin (0.05, 0.3, and 0.6 mg/kg/hr) as treatment, or saline solution as placebo, were administered simultaneously with endotoxin. Severe DIC in the endotoxin control group was shown by impairment in hemostatic parameters, kidney fibrin deposition, and a high mortality rate. Medium and high doses of r-hirudin led to an improvement in such DIC-related parameters as platelet numbers and fibrinogen and protein C concentrations. High-dose r-hirudin also reduced consumption of antithrombin III (ATIII). All doses of r-hirudin prevented decreases in tissue plasminogen activator (t-PA) and reduced the increase in plasminogen activator inhibitor-1 (PAI-1) activity observed at 2 hours after endotoxin administration. A significant reduction in kidney fibrin deposition was seen in medium- and high-dose r-hirudin groups. Additionally, the mortality rate in rabbits receiving medium- and high-dose r-hirudin was 10%, and that in rabbits receiving low-dose r-hirudin was 20%, as compared with a mortality rate of 70% in the control group. Protein C activity was significantly lower (p < 0.001) in nonsurviving rabbits. Moreover, there was a strong positive correlation (r = 0.68, p < 0.001) between protein C consumption and kidney fibrin deposition. We conclude that r-hirudin can be a useful drug in the clinical treatment of DIC

Unlinked rRNA genes are widespread among bacteria and archaea

International audienceRibosomes are essential to cellular life and the genes for their RNA components arethe most conserved and transcribed genes in Bacteria and Archaea. Ribosomal rRNA genes are typically organized into a single operon, an arrangement thought to facilitate gene regulation. In reality, some Bacteria and Archaea do not share this canonical rRNA arrangement - their 16S and 23S rRNA genes are separated across the genome and referred to as "unlinked". This rearrangement has previously been treated as an anomaly or a byproduct of genome degradation in intracellular bacteria. Here, we leverage complete genome and long-read metagenomic data to show that unlinked 16S and 23S rRNA genes are more common than previously thought. Unlinked rRNA genes occur in many phyla, most significantly within Deinococcus-Thermus, Chloroflexi, and Planctomycetes, and occur in differential frequencies across natural environments. We found that up to 41% of rRNA genes in soil were unlinked, in contrast to the human gut, where all sequenced rRNA genes were linked. The frequency of unlinked rRNA genes may reflect meaningful life history traits, as they tend to be associated with a mix of slow-growing free-living species and intracellular species. We speculate that unlinked rRNA genes may confer selective advantages in some environments, though the specific nature of these advantages remains undetermined and worthy of further investigation. More generally, the prevalence of unlinked rRNA genes in poorly-studied taxa serves as a reminder that paradigms derived from model organisms do not necessarily extend to the broader diversity of Bacteria and Archaea

Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? A meta-analysis

We compared the efficacy and safety of low molecular weight heparins (LMWH) and unfractionated heparin (UFH) in the treatement of deep venous thrombosis (DVT). A comparison between two daily subcutaneous injections of LMWH against a single injection was also performed. DESIGN AND METHODS: The study was performed by a meta-analysis. Clot improvement in venography, recurrency, total mortality and major hemorrhages were assessed in 4,472 patients with DVT from 21 studies treated with subcutaneous LMWH or UFH. RESULTS: An improvement in clot reduction (odds ratio 0.73, 95% confidence interval 0.59 to 0.90, p = 0.004), a decrease in total mortality (0. 68, 0.50 to 0.91, p = 0.012) and a lower incidence of hemorrhage (0. 65, 0.43 to 0.98, p = 0.047) were observed in LMWH treated patients. There were no differences in recurrences (0.78, 0.59 to 1.04, p = 0. 10). A single dose of LMWH was better than two in reducing major bleeding (c2 = 4.99, p = 0.025); however, the two dose regimen was more effective in clot reduction (c2 = 8.56, p = 0.004). INTERPRETATION AND CONCLUSIONS: LMWH is superior to UFH in terms of safety and efficacy. A single daily dose of LMWH dose is a suitable therapeutic regimen and could facilitate the outpatient treatment of venous thromboembolism

A ativação da jurisdição do Tribunal Penal Internacional por via do artigo 12.º, n.º 3 do Estatuto de Roma : as declarações de Estados não Parte

Esta dissertação de mestrado tem dois propósitos fundamentais: (1) destacar a importância da jurisdição criminal no âmbito da soberania dos Estados, as teorias que legitimam o seu exercício por parte dos tribunais penais internacionais e a complementaridade do Tribunal Penal Internacional; (2) analisar as condições prévias ao exercício da jurisdição do Tribunal Penal Internacional, com especial enfoque no n.º 3 do artigo 12.º do Estatuto e, partindo de três casos concretos – Costa do Marfim, Uganda e Palestina - , examinar certas questões controversas que se colocam na prática do Tribunal. Em resumo, o autor conclui ser inadmissível a apresentação de declarações “parciais”, isto é, declarações que limitam a jurisdição do TPI a crimes e/ou indivíduos concretos, que é de excluir a hipótese de encarar as declarações apresentadas por Estados não Parte de forma análoga a uma denúncia apresentada por um Estado Parte e, por fim, que não deve ser permitida a denúncia das declarações apresentadas pelos Estados por via do artigo 12.º, n.º 3 do ERTPI.This master’s thesis has two major purposes: (1) to highlight the importance of criminal jurisdiction on state’s sovereignty, the theories invoked to legitimize the operation of international criminal courts and the complementarity of the International Criminal Court; (2) to analyse the preconditions to the exercise of the jurisdiction of the International Criminal Court, with special focus on paragraph 3 of Article 12 of the Statute and, considering three specific cases – Ivory Coast, Uganda and Palestine -, examine certain controversial issues that arise in the practice of the Court. In conclusion, the author states that “partial” declarations, e.g., declarations that limit the jurisdiction of the ICC to specific crimes and/or individuals are inadmissible, that the possibility to treat declarations submitted by States Party analogously to a referral of a State Party is to exclude, and, finally, that the withdrawal of declarations presented by States under Article 12, paragraph 3 of ICC Statute should not be allowed

Downhill Running-based Overtraining Protocol Improves Hepatic Insulin Signaling Pathway Without Concomitant Decrease Of Inflammatory Proteins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The purpose of this study was to verify the effects of overtraining (OT) on insulin, inflammatory and gluconeogenesis signaling pathways in the livers of mice. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). Rotarod, incremental load, exhaustive and grip force tests were used to evaluate performance. Thirty-six hours after a grip force test, the livers were extracted for subsequent protein analyses. The phosphorylation of insulin receptor beta (pIRbeta), glycogen synthase kinase 3 beta (pGSK3beta) and forkhead box O1 (pFoxo1) increased in OTR/down versus CT. pGSK3beta was higher in OTR/up versus CT, and pFoxo1 was higher in OTR/up and OTR versus CT. Phosphorylation of protein kinase B (pAkt) and insulin receptor substrate 1 (pIRS-1) were higher in OTR/up versus CT and OTR/down. The phosphorylation of I kappa B kinase alpha and beta (pIK-Kalpha/beta) was higher in all OT protocols versus CT, and the phosphorylation of stress-activated protein kinases/Jun amino-terminal kinases (pSAPK-JNK) was higher in OTR/ down versus CT. Protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) and hepatocyte nuclear factor 4alpha (HNF-4alpha) were higher in OTR versus CT. In summary, OTR/down improved the major proteins of insulin signaling pathway but up-regulated TRB3, an Akt inhibitor, and its association with Akt.1010Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2013/20591-3, 2014/25459-9, 2013/22737-5, 2013/19985-7

P&D e tamanho da empresa: evidência empírica sobre a indústria brasileira

Este trabalho se propõe a analisar a relação entre o tamanho da firma e atividade de P&amp;D para o caso brasileiro