Delecção 1p36 – A Síndrome Não Explica Tudo…

Introdução: A criança com co-morbilidade grave é um premente desafio diagnóstico, cujo sucesso depende de uma abordagem multi-disciplinar. A síndrome de delecção 1p36, microdelecção subtelomérica de apresentação clínica pleiotrópica e multissistémica, pode incluir atraso do desenvolvimento psicomotor, alterações cardíacas, neurológicas e gastrointestinais. Caso Clínico: Filha única de pais não consanguíneos, PNV sem vacinação anti pneumocócica, com múltiplos internamentos: choque cardiogénico com miocardiopatia dilatada (3M), sépsis a S. aureus e Streptococcus do grupo G (5M) e várias intercorrencias infecciosas (varicela, gastrenterite, bronquiolite, febre sem foco). Aos 22 meses é reinternada por choque séptico com falência multi-orgânica por Streptococcus pneumoniae (serotipo 23-F), complicada de osteomielite dos ossos do antebraço e abcesso abdominal com necessidade de cirurgia. Pelos antecedentes e gravidade desta sépsis pneumocócica investigou-se eventual imunodeficiência identificando-se asplenia, confirmada por corpos de Howell-Jolly, TC abdominal e laparotomia. Retrospectivamente, para além da miocardiopatia havia má progressão ponderal com dificuldades alimentares, atraso global do desenvolvimento psicomotor, dermatose eczematosa grave e hipereosinofilia (2.410-5.680/uL), investigada por Genética, Infecciologia e Doenças Metabólicas. O cariotipo revelou monossomia da região distal ao locus 1p36 – delecção 1p36. Cintigrafia com MIBG sem evidência de neuroblastoma (risco aumentado pela síndrome). O estudo metabólico foi negativo, à excepção de défice de L-carnitina, pelo que mantem suplementos estando em curso estudo molecular de CPT2 – gene associado a défice de carnitina, na localização 1p32. Quanto à hipereosinofilia, verificou-se IgE aumentada e biopsia óssea normal pelo que iniciou prednisolona 2mg/Kg/dia com resposta favorável, estando estudo molecular específico em curso. Discussão: No fenótipo da síndrome enquadram-se o atraso global do desenvolvimento, a miocardiopatia e dificuldades alimentares. A asplenia, hipereosinofilia e dermatose eczematosa graves, não associadas a esta síndrome e de etiologia ainda a esclarecer podem-se integrar eventualmente na delecção terminal do cromossoma 1. As alterações no cariotipo carecem ainda de caracterização do ponto de quebra centromérico através de array-CGH, teste com maior especificidade para avaliar a tradução clínica dos efeitos individuais e combinados dos genes envolvidos.

Abnormal spontaneous interleukin 8 receptor expression: a brief report of two cases

Interleukin 8 (CXCL8) is an autocrine chemokine specific for the chemoattraction and activation of granulocytes, NKT cells and T lymphocytes. Patients with tuberculosis and latent Mycobacterium tuberculosis infection were assessed for the spontaneous expression of CXCR1 (CD128) and CXCR2 on lymphocytes and monocytes. Compared with ex vivo profiles, increased spontaneous CXCR2 expression and normal CXCR1 expression were found on lymphocytes in two out of 59 individuals. Monocytes showed normal ex vivo profiles for both receptors. After stimulation with purified protein derivative, the in vitro levels of CXCL8 were below the median levels of all patients with prior tuberculosis. Spontaneous CXCR2 modulation did not cause notable variation in the in vitro levels of CXCL8.

New taxa of Erythroxylum (Erythroxylaceae) from the Amazon basin.

Three new species of Erythroxylumfrom Amazoniaare described: Enythroxylum nelson-rosaePlowman, E. schunkeiPlowman and E. tucuruiendePlowman. An emended des-cription is given for E; ligustrinum DC., previously know from a single collection from French Guiana: its is here cited from Brazil for the first time. A new variety, E. ligustrinum var. carajasensePlowman, is also described. A provisional list of all Erythroxylum species occurring in Amazonia and peripheral areas is appended.

A síntese de um furano-guiano

A síntese de lactonas sesquiterpênicas do tipo guaiano é de interesse devido as atividades biológicas associadas às estruturas complexas deste grupo de produtos naturais. Planejou-se a sua síntese a partir de monoterpenos abundantes isolados de óleos essenciais brasileiros. Assim p-ment-l-eno foi transformado em 2-bromo-6-isopropil-3-metil-ciclohept-2-enona por adição de dibromocarbeno, expansão de anel com rearranjo usado AgNO3, e finalmente oxidação com clorocromato de piridinio. Redução quimioseletiva do bromo com zinco em ácido acético e alquilação termodinâmica em α,β-insaturada. Tratamento com ácido sulfúrico concentrado efetuou hidrólise e desidratação a um furano anelado a um ciclohepteno de estrutura de um oxa-guaiano.

Synthetic biology approaches to shape bacteriophages towards Pseudomonas aeruginosa biofilm control

Dissertation for Ph.D. degree in Biomedical Engineering.

The ear region in Xenarthrans ( = Edentata: Mammalia). Bryan Patterson -- [et al.].

n.s. no.24(1992)

Defining the criteria for the evaluation of self-study multimedia language learning materials: do they facilitate or inhibit learner autonomy?

Durant els darrers anys, s’han publicat un gran nombre de materials multimèdia destinats a l’aprenentatge de llengües, la major part dels quals son CD-ROM dissenyats com a cursos per l’autoaprenentatge. Amb aquests materials, els alumnes poden treballar independentment sense l’assessorament d’un professor, i per aquest motiu s’ha afirmat que promouen i faciliten l’aprenentatge autònom. Aquesta relació, però, no es certa, com Phil Benson i Peter Voller 1997:10) han manifestat encertadament:(…) Such claims are often dubious, however, because of the limited range of options and roles offered to the learner. Nevertheless, technologies of education in the broadest sense can be considered to be either more or less supportive of autonomy. The question is what kind of criteria do we apply in evaluating them? En aquest article presentem una investigació conjunta on es defineixen els criteris que poden ser utilitzats per avaluar materials multimèdia en relació a la seva facilitat per permetre l’aprenentatge autònom. Aquests criteris son la base d’un qüestionari que s’ha emprat per avaluar una selecció de CD-ROM destinats a l’autoaprenentatge de llengües. La estructura d’aquest article és la següent: - Una introducció de l’estudi - Els criteris que s’han utilitzar per la creació del qüestionari - Els resultats generals de l’avaluació - Les conclusions que s’han extret i la seva importància pel disseny instructiu multimèdia

Noves funcions en un entorn de canvis: implicacions de l'accés obert per a les biblioteques

Aquest article examina les possibles implicacions de l'accés obert en la gestió de les biblioteques. Aquesta examinació té lloc en un context en què s'assumeix que el model tradicional d'edició i l'accés obert coexisteixen. L'accés obert presenta nombrosos reptes i oportunitats, però les biblioteques emprenedores trobaran noves formes per servir els usuaris en un nou entorn en el que es combina l'accés obert amb el tradicional (MOA). Per tal de portar-ho a terme, caldrà que aquestes biblioteques redissenyin la seva organització, i això podrà suposar una pressió sobre els recursos econòmics i de personal.

Testing the TASP: An Experimental Investigation of Learning in Games with Unstable Equilibria

We report experiments designed to test between Nash equilibria that are stable and unstable under learning. The “TASP” (Time Average of the Shapley Polygon) gives a precise prediction about what happens when there is divergence from equilibrium under fictitious play like learning processes. We use two 4 x 4 games each with a unique mixed Nash equilibrium; one is stable and one is unstable under learning. Both games are versions of Rock-Paper-Scissors with the addition of a fourth strategy, Dumb. Nash equilibrium places a weight of 1/2 on Dumb in both games, but the TASP places no weight on Dumb when the equilibrium is unstable. We also vary the level of monetary payoffs with higher payoffs predicted to increase instability. We find that the high payoff unstable treatment differs from the others. Frequency of Dumb is lower and play is further from Nash than in the other treatments. That is, we find support for the comparative statics prediction of learning theory, although the frequency of Dumb is substantially greater than zero in the unstable treatments.

Institutions and prosperity

This article reviews ‘Pillars of Prosperity’ by Timothy Besley and Torsten Persson and ‘Why Nations Fail’ by Daron Acemoglu and James Robinson. Both books are focussed on the role of institutions in determining the wealth of nations and the review compares and contrasts the different approaches contained in the two texts. The review also attempts to locate the texts within the broader literature in development and political economics and to link them to other recent work in these areas.

The distribution of intestinal helminth infections in a rural village in Guatemala

Fecal egg count scores were used to investigate the distribution and abundance of intestinal helminths in the population of a rural village. Prevalences of the major helminths were 41% with Ascaris lumbricoides 60% with Trichuris trichiura and 50% with Necator americanus. All three parasites showed a highly aggregated distribution among hosts. Age/prevalence and age/intensity profiles were typical for both A. lumbricoides and T. trichiura with the highest worm burdens in the 50-10 year old children. For hookworm both prevalence and intensity curves were convex in shape with maximum infection levels in the 30-40 year old age class. Infected females had higher burdens of T. trichiura than infected males in all age classes of the population; there were no other effects of host gender. Analysis of associations between parasites within hosts revealed strong correlations between A. lumbricoides and T. lumbricoides and T. trichiura. Individuals with heavy infections of A. lumbricoides and T. trichiura showed highly significant aggregation within households. Associations between a variety of household features and heavy infections with A. lumbricoides and T. trichiura are described.

Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group.

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.

Regulation of adaptive behaviour during fasting by hypothalamic Foxa2.

The lateral hypothalamic area is considered the classic 'feeding centre', regulating food intake, arousal and motivated behaviour through the actions of orexin and melanin-concentrating hormone (MCH). These neuropeptides are inhibited in response to feeding-related signals and are released during fasting. However, the molecular mechanisms that regulate and integrate these signals remain poorly understood. Here we show that the forkhead box transcription factor Foxa2, a downstream target of insulin signalling, regulates the expression of orexin and MCH. During fasting, Foxa2 binds to MCH and orexin promoters and stimulates their expression. In fed and in hyperinsulinemic obese mice, insulin signalling leads to nuclear exclusion of Foxa2 and reduced expression of MCH and orexin. Constitutive activation of Foxa2 in the brain (Nes-Cre/+;Foxa2T156A(flox/flox) genotype) results in increased neuronal MCH and orexin expression and increased food consumption, metabolism and insulin sensitivity. Spontaneous physical activity of these animals in the fed state is significantly increased and is similar to that in fasted mice. Conditional activation of Foxa2 through the T156A mutation expression in the brain of obese mice also resulted in improved glucose homeostasis, decreased fat and increased lean body mass. Our results demonstrate that Foxa2 can act as a metabolic sensor in neurons of the lateral hypothalamic area to integrate metabolic signals, adaptive behaviour and physiological responses.

Did the cooperative start life as a Joint-Stock company? business law and cooperatives in Spain, 1869–1931

Studies of Spanish cooperatives date their spread from the Law on Agrarian Syndicates of 1906. But the first legislative appearance of cooperatives is an 1869 measure that permitted general incorporation for lending companies. The 1931 general law on cooperatives, which was the first act permitting the formation of cooperatives in any activity, reflects the gradual disappearance of the cooperative’s "business" characteristics. In this paper we trace the Spanish cooperative’s legal roots in business law and its connections to broader questions of the freedom of association, the formation of joint-stock enterprises, and the liability of investors in business and cooperative entities. Our account underscores the similarities of the organizational problems approach by cooperatives and business firms, while at the same time respecting the distinctive purposes cooperatives served.