New potential anti-hepatocellular carcinoma (HCC) agents: in vitro evaluation of anti-HCC activity and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates and QSAR studies

Hepatocellular carcinoma (HCC) is a major health problem with more than 660,000 new cases per year worldwide [1]. HCC is resistant to commonly used treatments like chemotherapy and radiotherapy and new anti-HCC therapies are urgently needed. Sorafenib was the first approved small molecule against HCC and underlines the importance of identifying potential new anti-HCC drugs [2]. Thirty-two 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates, previously prepared by some of us [3,4], were evaluated as potential new anti-HCC agents by studying their in vitro cell growth inhibition on human HepG2 cells, generally regarded as a good HCC model, and hepatotoxicity using a porcine liver primary cell culture (PLP1). The presence of amino groups linked to a benzene moiety on the substituent of the 6-position emerged as the key element for the anti-HCC activity

Lessons from the English auxiliary system

The English auxiliary system exhibits many lexical exceptions and subregularities, and considerable dialectal variation, all of which are frequently omitted from generative analyses and discussions. This paper presents a detailed, movement-free account of the English Auxiliary System within Sign-Based Construction Grammar (Sag 2010, Michaelis 2011, Boas & Sag 2012) that utilizes techniques of lexicalist and construction-based analysis. The resulting conception of linguistic knowledge involves constraints that license hierarchical structures directly (as in context-free grammar), rather than by appeal to mappings over such structures. This allows English auxiliaries to be modeled as a class of verbs whose behavior is governed by general and class-specific constraints. Central to this account is a novel use of the feature aux, which is set both constructionally and lexically, allowing for a complex interplay between various grammatical constraints that captures a wide range of exceptional patterns, most notably the vexing distribution of unstressed do, and the fact that Ellipsis can interact with other aspects of the analysis to produce the feeding and blocking relations that are needed to generate the complex facts of EAS. The present approach, superior both descriptively and theoretically to existing transformational approaches, also serves to undermine views of the biology of language and acquisition such as Berwick et al. (2011), which are centered on mappings that manipulate hierarchical phrase structures in a structure-dependent fashion

Depression and quality of life in Brazilian and Portuguese older people communities

We aimed to compare the association of depression with aspects of quality of life (QoL) among older people users of primary health care (PHC) living in Brazil and Portugal. We carried out an observational, cross-sectional and comparative study with a quantitative approach in the PHC scope in Brazil and Portugal, where we obtained a nonrandom sample of 150 participants aged 65 years or older (100 Brazilians and 50 Portuguese). We used the socioeconomic and health data questionnaire, the Medical Outcomes Short-Form Health Survey QoL (SF-36) questionnaire and the Beck Inventory. Among the socioeconomic profiles, most were females aged between 65 and 80 years in both countries. There was a significant difference between groups in the income variable, with 100.0% of Portuguese people earning up to 1 minimum wage (P value 50.0) within the categorical variables of “absent” and “mild” depression. The Emotional role functioning, Physical role functioning, Physical functioning, Mental health, Total score domains and the Mental health and Physical health summary measures stood out with this behavior in Brazil and in Portugal, where these latter 2 presented moderate to strong correlation values (ρ > 0.400) in Portugal. Greater associations of depression on QoL were revealed in Portugal than in Brazil. Among their most expressive associations, the Physical role functioning (odds ratio [OR] = 4.776; 95.0% confidence interval [CI]: 2.41–9.43), Physical functioning (OR = 3.037; 95.0% CI: 3.037), Vitality (OR = 6.000; 95.0% CI: 1.56–23.07) and Total score (OR = 3.727; 95.0% CI: 2.24–6.17) domains and the Mental health summary measure (OR = 3.870; 95.0% CI: 2.13–7.02) stood out. Aspects related to the emotional, physical, functional and mental health components stood out. The association and correlation with depression were more expressive in Portugal compared to Brazil. However, similar results were obtained in Brazil but with less relevance