Uma oficina de novidades : a implantação de núcleos urbanos na capitania de São Paulo, 1765-1775

Este trabalho apresenta parte dos resultados da tese de doutorado Método e Arte: criação urbana e organização territorial na capitania de São Paulo, 1765-1811, desenvolvida na Faculdade de Arquitetura e Urbanismo da Universidade de São Paulo, com apoio de bolsa da Fundação de Amparo à Pesquisa do Estado de São Paulo.Este artigo acompanha algumas dinâmicas de implantação de núcleos urbanos na capitania de São Paulo durante a administração do governador e capitão-general Morgado de Mateus (1765-1775). Destacam-se momentos significativos do processo de formação de paisagens urbanas, desde o recrutamento de povoadores e a busca de sítios até a definição dos traçados. A intenção é mostrar que a Coroa portuguesa foi tentando organizar determinados modos de conduzir a expansão urbana, ao passo que experiências e circunstâncias locais constantemente exigiram arranjos novos e específicos. A análise fundamenta-se numa seleção da documentação oficial já publicada e também em correspondência, em boa parte inédita, proveniente de agentes locais encarregados de tarefas ligadas ao povoamento. Procura-se tratar da política urbanizadora daquele período como um processo desenvolvido num contexto de conflitos mais do que como produto de um projeto pré-delineado por autoridades metropolitanas ou alheio a realidades do lugar. ______________________________________________________________________________________ ABSTRACTThis article investigates some of the dynamics associated with the establishment of urban nuclei in the captaincy of São Paulo during the administration of the Morgado de Mateus, governor and captain-general of the captaincy from 1765 to 1775. Several significant aspects about the formation process of urban landscapes stand out, from the recruitment of settlers and the search for suitable sites to the definition of urban layouts. The intention of this study is to show that the Portuguese crown made efforts to organize certain processes for conducting urban expansion, whilst local experience and circumstances continually demanded new and specific arrangements. The analysis is based on a selection of previously-published official documents, as well as mostly unpublished correspondence from local agents in charge of settlement-related tasks. The urbanization policy of the period is dealt with as a process that was executed in the context of conflicts, rather than as the product of a project pre-planned by metropolitan authorities or detached from the realities of the place at that time

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Partial left ventriculectomy in a child: 70-month clinical follow up Ventriculectomia parcial esquerda em criança: acompanhamento clínico por 70 meses

We describe the 70- month follow up of a child with idiopathic dilated cardiomyopathy and end-stage congestive heart failure (NYHA III/IV) who underwent partial left ventriculectomy - the Batista operation when he was two and half years old. The clinical follow up was performed in the outpatient clinic by electrocardiography, echocardiography and radionuclide ventriculography to better analyse the left ventricular ejection fraction. The left ventricular diameter increased. Echocardiograms showed enlargement mainly in the systolic left ventricular diameter and slow decrease in fractional shortening (delta D). The child was in class I (NYHA) during the follow-up. His exercise endurance was better than before surgery and hospitalization was not necessary. For these reasons, we believe that this procedure can be considered as a therapeutic option in children with severe dilated cardiomiopathy who are waiting for heart transplantation, as the shortage of donors is a fact.<br>Relatamos a evolução durante 70 meses de uma criança submetida a ventriculectomia parcial esquerda, pela técnica de Batista aos 2 anos e 6 meses de idade, em classe funcional III/IV em decorrência de cardiomiopatia dilatada idiopática, com seguimento clínico ambulatorial. Realizamos eletrocardiogramas, ecocardiogramas seriados e ventriculografia radioisotópica para melhor analisar a fração de ejeção do ventrículo esquerdo. Houve progressivo aumento deste. O ecocardiograma mostrou aumento principalmente do diâmetro sistólico do ventrículo esquerdo com queda progressiva, porém lenta, da fração de ejeção. Apesar da progressão da disfunção miocárdica, a criança manteve-se em classe funcional I durante todo o seguimento, com melhora da tolerância ao exercício e não necessitou de internações. Por isso, achamos que o método pode ser considerado opção terapêutica em crianças com cardiomiopatia dilatada avançada, aguardando a indicação mais tardia de transplante cardíaco, levando-se em conta a dificuldade de órgãos disponíveis para a população pediátrica

Mitral valvuloplasty without support in children - Modified De Vega technique: case reports

We report on three cases of mitral regurgitation in children at ages of 7 months, 5 months and 10 years old. In two of them, the etiology was congenital and the other it was rheumatic. The surgical technique used was valvuloplasty without support using the modified De Vega technique isolated or associated with other procedures. One of the children was re-operated seven years after the first surgery. All the patients were rated New York Association Class III before surgery. Following the surgery they were at Class I with good outcomes. All patients survived, without complications. According with the literature, mitral regurgitation can be treated with mitral valvuloplasty without support or using other surgical techniques, with excellent outcomes. We report here on one more option for its treatment especially in children and adolescents. This technique is easily performed and it permits growth of mitral valve during life

Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease

Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-γ and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-γ mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL-stimulated PBMCs from CAD patients than in corresponding supernatants from controls. Patients with CAD had a higher percentage of constitutive CCR2+ and CXCR3+ cells after stimulation with oxLDL. Among CAD patients, the main differences between the stable (SA) and unstable angina (UA) groups were lower IL-10 mRNA production in the latter group. Altogether, our data suggest that PBMCs from CAD patients are able to produce higher concentrations of chemokines and cytokines involved in the regulation of monocyte and lymphocyte migration and retention in atherosclerotic lesions13611726CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP04/01697-6Não te