Clinicopathological And Immunohistochemical Evaluation Of Oral And Oropharyngeal Squamous Cell Carcinoma In Chilean Population

In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (a-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with a-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). 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Darier Disease: First Molecular Study of a Portuguese Family

Background: Darier disease (DD) is a rare autosomal dominant condition characterized by skin lesions. Additionally, a wide range of neuropsychiatric symptoms is frequently reported in DD patients. This genodermatosis relies on mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2) gene, which encodes an ATPase responsible for pumping Ca2+ from the cytosol to the lumen of the ER. Objective: Herein we studied the molecular aspect of a two-generation Portuguese family with DD history with clinical variability. Methods: All exons and intron-exon borders of genomic ATP2A2, as well as coding ATP2A2, were sequenced. Relative levels of SERCA2 mRNA and protein were quantified by qPCR and western blotting, respectively. Results: The c.1287+1G > T variant was identified in all affected individuals, whereas the unaffected individual was shown to carry the wild-type ATP2A2 sequence in both alleles. This variant leads to the skipping of full exon 10, which consequently generates a frameshift originating a premature STOP codon in exon 11 (p.V395 = fs*19). Although the mutant mRNA seems to partially escape degradation, results suggest synthesis inhibition or immediate degradation of the mutant protein. Neuropsychiatric and other occurrences affecting certain patients are also reported. Conclusion: This is the first study of DD in Portugal, the variant identified, previously described in a single Japanese patient, may be considered a pathogenic mutation, and haploinsufficiency the mechanism underlying DD pathology in these patients. This study also highlights the co-occurrence of neuropsychiatric features in DD.info:eu-repo/semantics/publishedVersio

Distribution and role of benthic diatoms as acid mine drainage indicators in affected water dams

Publicado em "Proceedings of the Energy and Environment Knowledge Week 2014(E2KW2014)". ISBN 978-84-697-1162-

Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing

Quorum sensing (QS) regulates bacterial gene expression and studies suggest quercetin, a flavonol found in onion, as a QS inhibitor. There are no studies showing the anti-QS activity of plants containing quercetin in its native glycosylated forms. This study aimed to evaluate the antimicrobial and anti-QS potential of organic extracts of onion varieties and its representative phenolic compounds quercetin aglycone and quercetin 3-β-D-glucoside in the QS model bacteria Chromobacterium violaceum ATCC 12472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MG1. Three phenolic extracts were obtained: red onion extract in methanol acidified with 2.5% acetic acid (RO-1), white onion extract in methanol (WO-1) and white onion extract in methanol ammonium (WO-2). Quercetin 4-O-glucoside and quercetin 3,4-O-diglucoside were identified as the predominant compounds in both onion varieties using HPLC-DAD and LC-ESI-MS/MS. However, quercetin aglycone, cyanidin 3-O-glucoside and quercetin glycoside were identified only in RO-1. The three extracts showed minimum inhibitory concentration (MIC) values equal to or above 125 μg/ml of dried extract. Violacein production was significantly reduced by RO-1 and quercetin aglycone, but not by quercetin 3-β-D-glucoside. Motility in P. aeruginosa PAO1 was inhibited by RO-1, while WO-2 inhibited S. marcescens MG1 motility only in high concentration. Quercetin aglycone and quercetin 3-β-D-glucoside were effective at inhibiting motility in P. aeruginosa PAO1 and S. marcescens MG1. Surprisingly, biofilm formation was not affected by any extracts or the quercetins tested at sub-MIC concentrations. In silico studies suggested a better interaction and placement of quercetin aglycone in the structures of the CviR protein of C. violaceum ATCC 12472 than the glycosylated compound which corroborates the better inhibitory effect of the former over violacein production. On the other hand, the two quercetins were well placed in the AHLs binding pockets of the LasR protein of P. aeruginosa PAO1. Overall onion extracts and quercetin presented antimicrobial activity, and interference on QS regulated production of violacein and swarming motility

Ordering in the dilute weakly-anisotropic antiferromagnet Mn(0.35)Zn(0.65)F2

The highly diluted antiferromagnet Mn(0.35)Zn(0.65)F2 has been investigated by neutron scattering in zero field. The Bragg peaks observed below the Neel temperature TN (approximately 10.9 K) indicate stable antiferromagnetic long-range ordering at low temperature. The critical behavior is governed by random-exchange Ising model critical exponents (nu approximately 0.69 and gamma approximately 1.31), as reported for Mn(x)Zn(1-x)F2 with higher x and for the isostructural compound Fe(x)Zn(1-x)F2. However, in addition to the Bragg peaks, unusual scattering behavior appears for |q|>0 below a glassy temperature Tg approximately 7.0 K. The glassy region T<Tg corresponds to that of noticeable frequency dependence in earlier zero-field ac susceptibility measurements on this sample. These results indicate that long-range order coexists with short-range nonequilibrium clusters in this highly diluted magnet.Comment: 7 pages, 5 figure

Pyruvate Dehydrogenase Complex Deficiency: Updating the Clinical, Metabolic and Mutational Landscapes in a Cohort of Portuguese Patients

Background: The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype-phenotype correlations. Results: The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants. Conclusion: The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.info:eu-repo/semantics/publishedVersio

Investigação em sistemas e serviços de saúde: novos problemas e objetos, abordagens e estratégias

O artigo discute as tendências atuais das políticas e da organização dos sistemas e serviços de saúde, identificando os problemas que estão a exigir o desenvolvimento de investigações cujos resultados venham a subsidiar a formulação e implementação de propostas de mudança na formação de pessoal e nas práticas de saúde. Identifica áreas temáticas e discute os novos objetos de investigação que estão sendo constituidos, destacando a problemática dos sujeitos políticos em saúde, a redefinição do papel do Estado e a questão dos mercados em saúde, assim como a preocupação com o impacto das políticas, programas e serviços de saúde no contexto do ajuste estrutural das economias latinoamericanas e brasileira, em particular. Analisando as tendências atuais da produção científica no campo dos sistemas e serviços de saúde, aponta o crescimento do interesse pela pesquisa avaliativa e discute as estratégias de articulação entre as instituições de ensino-pesquisa e os serviços, notadamente o estabelecimento de "parcerias" para o desenvolvimento de atividades de cooperação técnica, o que vem colocando novos desafios e oportunidades para a consolidação de núcleos de investigação e da própria Rede de investigações em sistemas e serviços de saúde.The article discusses the present trends of the policies and health system organizations and services. It identifies the problems that at the moment demand the development of investigations with results that may support the formulation and implementation of proposal of changes in the personnel qualification and health practices. The paper also identifies the thematic areas and discusses the new objects of investigation being constituted highlighting the predicament of the political subjects in health, the redefinition of the role of the state and the issues of the health markets another concern is the impact of the policies, programs and health services in the context of economic structural adjustment of Latin America and in special Brazil. Having analyzed the present trends of scientific production in the field of health systems and services it points to the growing interest for the evaluative research. Next it discusses the articulation strategies among the teaching research institutions and the services, notably the establishment of partnerships for the development of activities of technical cooperation. Such strategies have placed new challenges and opportunities for the consolidation of not only the investigation nuclei but also the very Investigation Net system and services

Obscuration beyond the nucleus: infrared quasars can be buried in extreme compact starbursts

In the standard quasar model, the accretion disk obscuration is due to the canonical dusty torus. Here, we argue that a substantial part of the quasar obscuration can come from the interstellar medium (ISM) when the quasars are embedded in compact starbursts. We use an obscuration-unbiased sample of 578 infrared (IR) quasars at $z\approx 1-3$ and archival ALMA submillimeter host galaxy sizes to investigate the ISM contribution to the quasar obscuration. We calculate SFR and ISM column densities for the IR quasars and a control sample of submillimeter galaxies (SMGs) not hosting quasar activity and show that: (1) the quasar obscured fraction is constant up to $\rm SFR\approx 300 \: M_{\odot} \: yr^{-1}$, and then increases towards higher SFR, suggesting that the ISM obscuration plays a significant role in starburst host galaxies, and (2) at $\rm SFR\gtrsim 300 \: M_{\odot} \: yr^{-1}$, the SMGs and IR quasars have similarly compact submillimeter sizes ($R_{\rm e}\approx 0.5-3\rm \: kpc$) and, consequently, the ISM can heavily obscure the quasar, even reaching Compton-thick ($N_{\rm H}>10^{24} \rm \: cm^{-2}$) levels in extreme cases. Based on our results, we infer that $\approx 10-30\%$ of the IR quasars with $\rm SFR\gtrsim 300 \: M_{\odot} \: yr^{-1}$ are obscured solely by the ISM.Comment: Accepted for publication in MNRAS Letter

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201