Resumo O fim da trégua de doze anos (1609-1621) entre a Monarquia Hispânica e as Províncias Unidas da Holanda trouxe Portugal e suas colônias para o centro do conflito europeu. Neste artigo, discutimos o arbítrio do comerciante andaluz Francisco de Retama sobre a tomada holandesa da Bahia em 1624. Figura conhecida da Junta de Comércio e promotor da guerra econômica contra os rebeldes holandeses, Retama escreveu vários arbítrios em matéria de política econômica e, em particular, de comércio, em que era perito. Retama viria a ser conhecido como um dos principais defensores da criação de uma Companhia de Comércio nos moldes holandeses. A sua convicção de que Flandres foi a chave para o sucesso da monarquia dos Habsburgo, colocou os interesses de Portugal numa posição secundária e é um dos primeiros exemplos de propostas políticas que levaram ao crescente descontentamento português. O projeto até então desconhecido que agora publicamos sublinha as contradições e dificuldades de uma monarquia compósita face à necessidade de rentabilidade econômica que, na opinião de Francisco de Retama, era a chave do enriquecimento dos países e da sobrevivência da Monarquia Católica.

Abstract The end of the twelve-year truce (1609-1621) between the Hispanic Monarchy and the United Provinces of the Netherlands brought Portugal and its colonies to the center of the European conflict. In this article we discuss the arbítrio of the Andalusian merchant, Francisco de Retama, on the Dutch seizure of Bahia in 1624. A well-known figure to the Junta de Comercio, and promotor of economic warfare against the Dutch rebels, Retama wrote numerous arbítrios on matters of economic policy and in particular on trade, on which he was an expert. Retama would come to be known as one of the main advocates in favor of the Spanish creation of a Company of Commerce on the Dutch model. His belief that Flanders was the key to the success of the Habsburg monarchy, placed the interests of Portugal in a secondary position, and is an early example of policy proposals that led to growing Portuguese discontent. The previously unknown project that we now publish underlines the contradictions and difficulties of a composite monarchy in the face of the need for economic profitability, which, in the opinion of Francisco de Retama, was the key to the enrichment of countries and the survival of the Catholic Monarchy.

Abstract Lysosomal storage disorders (LSDs) constitute a heterogeneous group of approximately 50 genetic disorders. LSDs diagnosis is challenging due to variability in phenotype penetrance, similar clinical manifestations, and a high allelic heterogeneity. A powerful tool for the diagnosis of the disease could reduce the “diagnostic odyssey” for affected families, leading to an appropriate genetic counseling and a better outcome for current therapies, since enzyme replacement therapies have been approved in Brazil for Gaucher, Fabry, and Pompe diseases, and are under development for Niemann-Pick Type B. However, application of next-generation sequencing (NGS) technology in the clinical diagnostic setting requires a previous validation phase. Here, we assessed the application of this technology as a fast, accurate, and cost-effective method to determine genetic diagnosis in selected LSDs. We have designed two panels for testing simultaneously 11 genes known to harbor casual mutations of LSDs. A cohort of 58 patients was used to validate those two panels, and the clinical utility of these gene panels was tested in four novel cases. We report the assessment of a NGS approach as a new tool in the diagnosis of LSDs in our service.

Abstract Hepatic glycogen storage diseases (GSDs) are genetic diseases associated with fasting hypoglycemia. Periodic intake of uncooked cornstarch is one of the treatment strategies available for those disorders. For reasons that are still not clear, patients with hepatic GSDs may be overweight. Aims: To assess nutritional status and body composition in patients with hepatic GSDs receiving uncooked cornstarch. Methods: The sample included 25 patients with hepatic GSD (type Ia = 14; Ib = 6; III = 3; IX? = 1; IX? = 1), with a median age of 11.0 years (interquartile range [IQR] = 9.0-17.5), matched by age and gender with 25 healthy controls (median age = 12.0 years, IQR = 10.0-17.5). Clinical, biochemical, and treatment-related variables were obtained from medical records. Nutritional status and body composition were prospectively evaluated by bioelectrical impedance. Results: Patients and controls did not differ with regard to age and gender. Height was significantly reduced in patients (median = 1.43 m, IQR = 1.25-1.54) in comparison to controls (median = 1.54 m, IQR = 1.42-1.61; P = .04). Body mass index for age z-score and fat mass percentage were higher in patients (median = 1.84, IQR = 0.55-3.06; and 27.5%, IQR = 22.6-32.0, respectively) than in controls (median = 0.86, IQR = ?0.55 to 1.82; P = .04 and 21.1%, IQR = 13.0-28.3; P = .01, respectively). When patients were stratified by type, those with GSD Ia had significantly higher adiposity (median fat mass = 28.7%, IQR = 25.3-32.9) than those with GSD III and GSD IX?/? (median fat mass = 20.9%, IQR = 14.9-22.6; P = .02). Conclusions: Our findings suggest that patients with hepatic GSD on treatment with cornstarch, especially those with GSD Ia, exhibit abnormalities in nutritional status and body composition, such as short stature and a trend toward overweight and obesity.

Abstract Glycogen storage disease type 1a (GSD 1a) is a rare inborn error of metabolism. It causes severe fasting intolerance and lactic acidosis due to the deficiency of glucose-6-phosphatase enzyme. Blood glucose and lactate concentrations from 2 patients with GSD 1a were retrospectively compared to a control group of patients with familial amyloid polyneuropathy. Carbohydrate intake and infusions were compared to experimental data based on stable isotope studies. Perioperative lactate concentrations were significantly higher in our 2 patients with GSD 1a (median 15.0 mmol/L; range 9.9-22.0 mmol/L) versus 8 controls. In one patient, despite normal blood glucose concentrations, lactate acidosis was probably caused by a combination of the disease itself, insufficient (par)enteral carbohydrate intake, Ringer lactate infusions, and circulatory insufficiency. Patients with GSD 1a carry an increased risk of lactic acidosis during orthotopic liver transplantation compared to non-GSD patients. Multidisciplinary perioperative care is essential to prevent significant complications.

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alph-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ;±20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

Objective: To assess the association of maternal migration to Baja California, body mass index (BMI) status, children's perceived food insecurity, and childhood lifestyle behaviors with overweight (BMI > 85% ile), obesity (BMI > 95% ile) and abdominal obesity (Waist Circumference > 90% ile). Methods: Convenience sampling methods were used to recruit a cross-sectional sample of 4th, 5th and 6th grade children and their parents at Tijuana and Tecate Public Schools. Children's and parents' weights and heights were measured. Children were considered to have migrant parents if parents were not born in Baja California. Results: One hundred and twenty-two children and their parents were recruited. The mean age of the children was 10.1 ± 1.0 years. Forty nine per cent of children were overweight or obese. Children with obese parents (BMI > 30) had greater odds of being obese, Odds Ratio (OR) 4.9 (95% Confidence Interval (CI), 1.2-19, p = 0.03). Children with migrant parents had greater odds of being obese, OR= 3.7 (95% CI, 1.6-8.3), p = 0.01) and of having abdominal obesity, OR = 3.2 (95% CI, 1.4-7.1, p = 0.01). Children from migrant parents have greater risk of higher consumption of potato chips, OR = 8.0 (95% CI, 2.1 -29.1, p = 0.01). Children from non-migrant parents had greater odds of being at risk of hunger. Conclusions: Parental obesity and migration are associated with increased risk of obesity among Mexican children. Children whose parents were born in Baja California have greater odds of being at risk of hunger. Further studies should evaluate the role of migration on risk for childhood obesity.

Objetivo: Determinar la asociación entre la inmigración materna a Baja California, el índice de masa corporal (IMC), la percepción de inseguridad alimentaria de los niños, y los estilos de vida y el sobrepeso, (BMI > 85% ila), la obesidad (BMI > 95% ila) y la obesidad abdominal (Circunferencia de Cintura > 90% ila). Métodos: Se realizó una muestra por conveniencia, en la que se reclutaron niños de 4.º a 6.º grado de primaria y a sus padres, de escuelas públicas de Tijuana y Tecate. Se midió el peso y la estatura de los niños. Los padres que no nacieron en el estado de Baja California se consideraron inmigrantes. Resultados: Fueron reclutados 122 pares de padres y niños. La edad media de los niños fue de 10,1 ± 1,0 años. Cuarenta y nueve por ciento de los niños presentaron sobrepeso u obesidad. Los niños con padres obesos (BMI > 30) presentaron mayor riesgo de obesidad, Razón de Momios (RM) 4,9 (95% Intervalo de confianza (IC) 1,219, p = 0,03). Los niños con padres inmigrantes presentaron mayor riesgo de tener obesidad, RM = 3,7 (95% IC, 1,6-8,3, p = 0,01) y obesidad abdominal, RM = 3,2 (95% IC, 1,4-7,1, p = 0,01). Los niños con padres inmigrantes presentaron mayor riesgo de consumo de patatas fritas, RM = 8,0 (95% CI, 2,1-29,1, p = 0,01). Los niños de padres no inmigrantes presentaron mayor riesgo de hambre. Conclusiones: La obesidad paterna y la inmigración estuvieron asociadas con el aumento de obesidad infantil. Los niños de padres nacidos en Baja California presentaron mayor riesgo de hambre. Se requieren más estudios que valoren el papel de la inmigración sobre el riesgo de obesidad.

O texto trata das relações entre Portugal e Espanha em meados do século XVII, bem como do papel das colônias e do comércio atlântico da prata, do açúcar e dos escravos no fortalecimento do império português. Destaca a importância das estruturas imperiais globais e a centralidade do papel do império no quadro da restauração portuguesa. Por fim, enfoca a importância das colônias e em particular do Brasil nas mudanças que ocorrem ao longo do século.

The present article deals with the relationships forged between Portugal and spain in the mid-17th century and the role in which the trans-Atlantic commerce in slaves, sugar and silver played in strengthening the Portuguese Empire. We salient the importance of global imperial structures, as well as the central role the Empire played in the Portuguese Restoration. Finally, we focus on the importance of the colonies and, in particular, Brazil in the changes which occurred throughout the century.

Le texte étudie les rapports entre le Portugal et l'Espagne au milieu du XVIIème siècle et le rôle joué par les colonies et par le commerce atlantique de l'argent, du sucre et des esclaves dans le renforcement de l'Empire portugais. On souligne l'importance des structures impériales globales et de la centralité du role de l'Empire dans le contexte de la restauration portugaise. Aussi envisage-t-on l'importance des colonies et en particulier du Brésil dans les changements qui prennent place tout au long du siècle.

Plantas estressadas geralmente são mais atacadas por insetos galhadores. Neste estudo investigamos a relação entre abundância populacional e a riqueza de espécies de insetos galhadores na árvore Alchornea castaneaefolia A. JUSS. (Euphorbiaceae), submetida ao estresse induzido pela hemiparasita Psittacanthus sp. (Loranthaceae) na Amazônia, Brasil. Galhos de A. castaneaefolia atacados pela hemiparasita foram mais fortemente infestados por insetos galhadores do que os galhos não atacados. As observações de campo corroboram parcilmente a hipótese de que haveria um nível ótimo de estresse da planta hospedeira para o estabelecimento de insetos galhadores.

Stressed plants are generally more attacked by galling insects. In this study we investigated the relationship between population abundance and species richness of galling insects on the tree Alchornea castaneaefolia A. JUSS. (Euphorbiaceae), submited to stress induced by the hemiparasite Psittacanthus sp. (Loranthaceae) in the Amazon, Brazil. Branches of A. castaneaefolia attacked by the hemiparasite were more heavily infested by galling insects than non-attacked branches. The field observations partially corroborate the hypothesis that there would be an optimal level of host-plant stress for galling insect establishment.

OBJECTIVE: To determine whether the fever module in the WHO/UNICEF guidelines for the integrated management of childhood illness (IMCI) identifies children with bacterial infections in an area of low malaria prevalence. METHODS: Physicians assessed a systematic sample of 669 sick children aged 2-59 months who presented to the outpatient department of Dhaka Shishu Hospital, Bangladesh. FINDINGS: Had IMCI guidelines been used to evaluate the children, 78% of those with bacterial infections would have received antibiotics: the majority of children with meningitis (100%), pneumonia (95%), otitis media (95%) and urinary tract infection (83%); and 50% or less of children with bacteraemia (50%), dysentery (48%), and skin infections (30%). The current fever module identified only one additional case of meningitis. Children with bacteraemia were more likely to be febrile, feel hot, and have a history of fever than those with dysentery and skin infections. Fever combined with parental perception of fast breathing provided a more sensitive fever module for the detection of bacteraemia than the current IMCI module. CONCLUSIONS: In an area of low malaria prevalence, the IMCI guidelines provide antibiotics to the majority of children with bacterial infections, but improvements in the fever module are possible.

OBJETIVO: Determinar si el módulo Fiebre de las directrices OMS/UNICEF para la atención integrada a las enfermedades prevalentes de la infancia (AIEPI) identifica a los niños que presentan infecciones bacterianas en una zona de baja prevalencia de paludismo. MÉTODOS: Los médicos evaluaron una muestra sistemáca de 669 niños enfermos de 2 a 59 meses que acudieron al ambulatorio del Hospital de Dhaka Shishu en Bangladesh. RESULTADOS: Si se hubieran seguido las directrices de la AIEPI para evaluar a los niños, habría recibido antibióticos el 78% de quienes padecían infecciones bacterianas: la mayoría de los niños con meningitis (100%), neumonía (95%), otitis media (95%) e infecciones de las vías urinarias (83%); y el 50% o menos de los niños con bacteriemia (50%), disentería (48%) e infecciones cutáneas (30%). El actual módulo Fiebre identificó sólo un caso adicional de meningitis. En comparación con los que padecían disentería o infecciones cutáneas, entre los niños con bacteriemia eran más frecuentes la febrilidad, la sensación de calor y los antecedentes de fiebre. La combinación de fiebre y percepción parental de respiración rápida resultó ser un criterio más sensible que el actual módulo de la AIEPI para detectar los casos de bacteriemia. CONCLUSIÓN: En una zona de baja prevalencia de paludismo, las directrices de la AIEPI prevén el suministro de antibióticos a la mayoría de los niños con infecciones bacterianas, pero es posible introducir mejoras en el módulo Fiebre.

OBJECTIF: Déterminer si le module Fièvre des directives OMS/UNICEF pour la prise en charge intégrée des maladies de l'enfant (PCIME) permet de reconnaître les enfants atteints d'infections bactériennes dans une région de faible prévalence du paludisme. MÉTHODES: Des médecins ont évalué un échantillon systématique de 669 enfants malades âgés de 2 à 59 mois vus dans le service des consultations externes du Dhaka Shishu Hospital au Bangladesh. RÉSULTATS: Si les directives PCIME avaient été utilisées pour évaluer les enfants, 78 % de ceux qui étaient atteints d'infections bactériennes auraient reçu des antibiotiques : la plupart des enfants atteints de méningite (100 %), de pneumonie (95 %), d'otite moyenne (95 %) et d'infections urinaires (83 %), et au maximum la moitié des enfants atteints de bactériémie (50 %), de dysenterie (48 %) et d'infections cutanées (30 %). L'actuel module Fièvre n'a identifié qu'un cas supplémentaire de méningite. Les enfants bactériémi étaient davantage susceptibles d'être fiévreux, chauds et d'avoir des antécédents de fièvre que ceux qui souffraient de dysenterie et d'infections cutanées. La présence de fièvre associée à l'impression de respiration rapide signalée par les parents constituait un critère plus sensible que l'actuel module Fièvre des directives PCIME pour détecter une bactériémie. CONCLUSION: Dans une zone de faible prévalence du paludisme, les directives PCIME traitent par des antibiotiques la plupart des enfants atteints d'infections bactériennes, mais des améliorations du module Fièvre sont possibles.

A ataxia de Friedreich (FRDA) é a mais frequente das ataxias com herança autossômica recessiva. Em 94 % dos casos, é causada por uma expansão homozigota instável da repetição de trinucleotídeos GAA, localizada no primeiro íntron do gene X25. Esta mutação foi investigada em cinco pacientes brasileiros: quatro com quadro clínico típico de FRDA e um paciente com manifestações atípicas, cujo diagnóstico prévio era o de alguma outra forma de ataxia cerebelar com preservação de reflexos. A investigação foi positiva nos cinco casos. A confirmação do diagnóstico de FRDA no paciente com quadro atípico, assim como em outros casos semelhantes já relatados na literatura, sugere que o espectro de manifestações clínicas da FRDA seja mais amplo do que o classicamente reconhecido, incluindo casos com preservação de reflexos.

Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is caused in 94% of cases by homozygous expansions of an unstable GAA repeat localised in intron 1 of the X25 gene. We have investigated this mutation in five Brazilian patients: four with typical FRDA findings and one patient with atypical manifestations, who was considered to have some other form of cerebellar ataxia with retained reflexes. The GAA expansion was detected in all these patients. The confirmation of FRDA diagnosis in the atypical case may be pointing out, as in other reports, that clinical spectrum of Friedreich's ataxia is broader than previously recognised and includes cases with intact tendon reflexes.

RESUMO Introdução: Toxemia gravídica é uma síndrome caracterizada por hipertensão, proteinúria, edema e ganho de peso, no terceiro trimestre da gravidez. Essa doença sistêmica pode afetar quase todos os órgãos do corpo humano, tendo, potencialmente, conseqüências devastadoras para a mãe e para o feto. O objetivo deste estudo é verificar a importância do exame oftalmológico no diagnóstico da toxemia gravídica, bem como correlacioná-la com os achados de retinopatia hipertensiva e prognóstico fetal. Materiais e métodos: Pacientes gestantes, portadoras de pressão arterial elevada, foram submetidas à fundoscopia e enquadradas na classificação de Gans e na de Keith-Wagener-Barker, (KW). Após o nascimento, os recémnatos (RNs) foram avaliados quanto à idade gestacional (PARKIN), peso e índice de Apgar. Resultados: Foram examinadas 148 gestantes, com idade entre 14 a 48 anos (média 28,67 anos). Destas, 26 (17,6%) eram portadoras de pré-eclâmpsia leve, 35 (23,6%) de pré-eclâmpsia severa, 9 (6,1%) de eclâmpsia e 78 (52,7%) de hipertensão arterial crônica. De acordo com a classificação de KW, 89 (60,1%) tinham retinopatia leve (grau 1), 26 (17,6%) moderada (grau 2), 24 (16,2%) severa e 9 (6,1%) não tinham sinais de retinopatia hipertensiva. Do total de 143 RNs, 55 (38,5%) eram pequenos para a idade gestacional, 90 (62,9%) eram prematuros, 27 (18,2%) foram a óbito, 45 (31,5%) tinham Apgar 1, 2 ou 3 no 1º minuto, e 32 (22,4%) tinham Apgar 1, 2 ou 3, no 5º minuto de vida. Conclusões: Concluiu-se pela análise dos resultados, que, através da fundoscopia, pode-se confirmar o diagnóstico do tipo de toxemia gravídica (p<0,001), entretanto, foi impossível, através desse exame, prever qualquer situação do prognóstico fetal. Concluiu-se, também, que os melhores exames para previsão do prognóstico fetal são: a avaliação da pressão arterial e o próprio diagnóstico clínico feito pelo obstetra, com base em exames laboratoriais (p<0,001).

SUMMARY Introduction: Toxemia of pregnancy is characterized by hypertension, proteinuria, and generalized body edema, which develops during the third trimester of pregnancy. This systemic disease, which can affect almost every organ system in the body, has potentially devastating consequences for both mother and baby. The purpose of this trial is to verify the importance of fundoscopy in the diagnosis of toxemia of pregnancy as well as correlate this findings with hypertensive retinopathy and fetal outcome. Materiais and Methods: We performed a prospective study where pregnant women with high blood pressure, were submitted to fundoscopy and classified according Gans and Keith- Wagener-Barker (KW) classifications. After delivery, the babies were assessed according gestational age (Parkin), weight and Apgar index. Results: We examined 148 pregnant women between 14 and 48 years old (mean = 28,67). From these, 26 (17,6%) had mild preeclampsia, 35 (23,6%) had severe preeclampsia, 9 (6,1 %) had eclampsia and 78 (52,7%) had chronic hypertension. According KW classification, 89 (60,1%) had grade 1 retinopathy, 26 (17,6%) had grade 2 retinopathy, 24 (16,2%) had grade 3 and 4 retinopathy and 9 (6,1%) had no signs of hypertensive retinopathy. Of the 143 babies, 55 (38,5%) were low birth weight infants, 90 (62,9%) were premature, 27 (18,2%) were dead infants, 45 (31,5%) had Apgar 1,2 or 3 in the first minute and 32 (22, 4%) had Apgar 1, 2 or 3 in the fifth minute of life. Conclusions: We concluded that with the fundus examination we could confirm the diagnosis of toxemia of pregnancy (p <0, 001), nevertheless it was impossible with this exam to foresee the fetal prognosis. We also concluded that the best exams to foresee the fetal outcome is the evaluation of blood pressure and the obstetrician 's diagnosis based on exams of labotatory. (p < 0,001);