An outbreak of Portuguese man-of-war (Physalia physalis - Linnaeus, 1758) envenoming in Southeastern Brazil

Introduction Portuguese man-of-war, Physalia physalis (Linnaeus, 1758), are cnidarians capable of discharging intracellular organelles filled with venom, resulting in severe envenomation in humans. Methods We report the clinical and therapeutic aspects of 331 accidents involving Portuguese man-of-war in an outbreak on the coast of the State of São Paulo, Brazil. Results The clinical manifestations of envenomation were rare and mild and mostly local, systemic reactions; there was a low rate of late complications. Conclusions The consequences of envenomation were of moderate severity, and first aid measures were effective in controlling the pain. Outbreaks of accidents involving Portuguese man-of-war occur periodically in the area without a clear explanation.

Conception and first results of a cross-sectional national study on the demography, disease characteristics and socioeconomics status of the Portuguese patients with multiple sclerosis : the PORT-MS study

RESUMO: Introdu����o e objetivos: N��o existia um estudo multic��ntrico que descrevesse as caracter��sticas dos doentes com EM, da doen��a em si, ou do seu tratamento, em Portugal.M��todos: Doentes McDonald 2010 positivos foram sequencialmente recrutados em 7 centros entre Maio e Novembro 2014. Aplicou-se um Caderno de Recolha de Dados incidindo na demografia, doen��a, educa����o e emprego (estudo PORT-MS). Resultados: 561 doentes inclu��dos. Primeiros sintomas aos 30,2��10,5 anos (RRMS 29,2��10, PPMS 39,4��11,7, p<0,001); diagn��stico 3,2��5,3 anos depois (RRMS 3,0��5,1, PPMS 4,9��2,5, p=0,002); tempo de doen��a ap��s diagn��stico 9,4��7,2 anos (semelhante RRMS no diagn��stico e PPMS); idade atual 42,9��12,4 anos (grupo RRMS no diagn��stico 42,0��12,1, PPMS 52,5��11,3, p<0,001); EDSS atual 2,5 (RRMS 2.0, PPMS 6.0); propor����o feminino:masculino �� 2,5:1 (RRMS semelhante, PPMS 1,1:1, p<0,05); no diagn��stico RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% dos RRMS encontravam-se em SP na inclus��o (nomeadamente os com mais idade no diagn��stico e/ou atualidade ou tempo de doen��a mais prolongado). PPMS mais frequente em doentes diagnosticados mais tardiamente (p<0,001), onde aumenta tamb��m ligeiramente a propor����o de mulheres na PPMS. Nas ��ltimas d��cadas: novos casos mostram estabilidade na propor����o de g��neros e tipos de doen��a; idade nos primeiros sintomas e no diagn��stico aumentou ligeiramente, tempo entre eles diminuiu ligeiramente. Propor����o sob DMT (Maio 2014): global 84,5%; atualmente RRMS 90,4%; SPMS 70,8%; PPMS 36,8%; progressivas agregadas 48%. Tipo de DMT, amostra global: interfer��es 56,5%, GA 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Global: economicamente ativos 61,5%, desemprego 13,5%, 74,1% dos n��o activos est��o reformados por doen��a. Gravidezes ap��s diagn��stico em 15% mulheres. Casos com hist��ria familiar positiva 7,8%. Discuss��o e conclus��es: Inclu��da cerca de 10% da popula����o portuguesa. Resultados congruentes com dados internacionais. Elevada propor����o sob DMT, mesmo EDSS alto e formas progressivas. Terap��uticas de segunda linha sub representadas. Doentes jovens e com doen��a ligeira com vida econ��mica ativa; restantes essencialmente reformados por doen��a.---------------- ABSTRACT : Background/aims: In Portugal, there wasn���t a multicentric study on the general characteristics (demography, disease milestones, DMT, socioeconomic status) of Multiple Sclerosis patients. Methods: Patients fulfilling McDonald 2010 criteria were sequentially recruited from May to November 2014 in 7 centers and data was systematically collected. Results: 561 patients included. First symptoms occurred at 30,2��10,5 years-old (RRMS 29,2��10, PPMS 39,4��11,7, p<0,001); diagnosis 3,2��5,3 years later (RRMS 3,0��5,1, PPMS 4,9��2,5, p=0,002); 9,4��7,2 years elapsed since diagnosis (similar for those is RRMS at diagnosis and PPMS); current age 42,9��12,4 years-old (group RRMS at diagnosis 42,0��12,1, PPMS 52,5��11,3, p<0,001); current EDSS 2,5 (RRMS 2.0, PPMS 6.0); females to males 2,5:1 (RRMS similar, PPMS 1,1:1, p<0,05); at diagnosis RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% of RRMS reached SP at inclusion (those older at diagnosis, in actuality, or with longer follow-up). PPMS more frequente in patients diagnosed at older ages (p<0,001), also slight increase in females. Along the last decades: new cases have showed stable proportions of gender and disease types; age at first symptoms and diagnosis slightly increased, time between them slightly decreased. Proportion on DMT (May 2014): 84,5% of all; 90,4% of currently in RRMS; 70,8% of SPMS; 36,8% of PPMS; 48% of progressive forms together. Type of DMT, all patients: interferons 56,5%, Glatiramer Acetate 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Economically active 61,5% of all, unemployment 13,5%, 74,1% of non-active are retired due to disease. Females pregnant after diagnosis 15%. Positive family cases in 7,8%. Discussion/Conclusions: 10% of the national MS population collected. Data generally consistente with international reports. Proportion under DMT relatively high in all disease types, but second line therapies underrepresented. Young patients with mild disease have an active economic life. Those not active are essentially retired due to disease.

Classifica����o Internacional de Funcionalidade, Incapacidade e Sa��de : uma dimens��o do neurodesenvolvimento

RESUMO: Objetivo Principal ��� Determinar a consist��ncia da utiliza����o dos instrumentos de avalia����o da capacidade intelectual ��� escalas de Griffiths e WISC III ��� no enquadramento dos dom��nios e dos qualificadores da CIF-CJ, restrita ��s fun����es mentais do corpo. Objetivo secund��rio: ��� Estudar a efetividade e concord��ncia inter-observador da aplica����o da CIF, com base na leitura dos dados obtidos em avalia����o efetuada com os instrumentos referidos, por duas observadoras independentes, em contexto de articula����o sa��de, respetivamente educa����o e seguran��a social M��todos ��� Estudo observacional, descritivo, transversal e prospetivo. ��� Foi estudada uma amostra de conveni��ncia 355 crian��as, num per��odo de tr��s anos (Maio de 2010 a 30 de Abril de 2013), com patologia da ��rea da pediatria do neurodesenvolvimento (total de 4000 consultas) no Centro de Desenvolvimento (CD) do Hospital de Dona Estef��nia (HDE), Centro Hospitalar de Lisboa Central, EPE (CHLC, EPE). ��� Crit��rios de inclus��o: crian��as de ambos os sexos, observadas no CD do HDE, CHLC (primeiras consultas e consultas de reavalia����o) com idade ���12 meses e ���17 anos e incapacidade intelectual definida de acordo com os crit��rios da DSM-IV-TR, DSM 5 e CID-10. ��� Crit��rios de exclus��o: crian��as com autismo, perturba����es espec��ficas da linguagem, hiperatividade, d��fice de aten����o e concentra����o, d��fices sensoriais cong��nitos (baixa vis��o e ou audi����o), ou com outros diagn��sticos de perturba����es de neurodesenvolvimento. ��� O estudo teve duas fases: na primeira, a investigadora principal colheu ou atualizou a hist��ria cl��nica, observou clinicamente as crian��as solicitando os exames complementares considerados necess��rios e foi efetuada avalia����o psicol��gica com os instrumentos adiante descritos, pela mesma psic��loga cl��nica, devidamente credenciada, e com larga experi��ncia nas escalas referidas. Com base nos dados colhidos, quer por observa����o direta, quer atrav��s dos resultados das escalas Griffiths e WISC ��� III, a investigadora aplicou a CIF-CJ, circunscrita aos dom��nios e fun����es (vari��veis): 1. FUN����ESMENTAIS GLOBAIS (b110- Fun����es da consci��ncia, b114- Fun����es da orienta����o no espa��o e no tempo, b117 ��� Fun����es intelectuais, b122- Fun����es psicossociais globais, b125- Fun����es intrapessoais, b126- Fun����es do temperamento e da personalidade); 2.FUN����ES MENTAIS ESPEC��FICAS (b140- fun����es da aten����o, b147- Fun����es psicomotoras, b152- Fun����es emocionais, b156- Fun����es da perce����o, b163- Fun����es cognitivas b��sicas, b164- Fun����es cognitivas de n��vel superior, b167- Fun����es mentais da linguagem 3. FUN����ES DA VOZ E DA FALA (b320- Fun����es da articula����o, b330- Fun����es da flu��ncia e do ritmo da fala). Numa segunda fase, foi solicitada a colabora����o de duas co-investigadoras, com forma����o espec��fica nas escalas utilizadas e na CIF-CJ, a aplica����o da CIF nos mesmos dom��nios e fun����es. Estas observadoras n��o efetuaram observa����es diretas das crian��as envolvidas. ��� Para efetuar a an��lise estat��stica e analisar a rela����o entre os qualificadores (0 a 4) das vari��veis da CIF em estudo (b117, b122, b147, b163, b164, b167, b320 e b330) e os instrumentos psicom��tricos (escalas de Griffiths e WISC III), que constitui a primeira parte do estudo, recorreu-se �� t��cnica estat��stica n��o param��trica do coeficiente de correla����o de Spearman, que quantifica a intensidade e sinal da eventual correla����o existente entre as vari��veis em estudo. ��� Para determinar as correla����es referentes �� segunda parte do estudo, foram utilizados os programas SPSS��, (IBM SPSS Statistics) e Statistica�� (StatSoft, Inc., 2011). STATISTICA (data analysis software system, version 10. www.statsoft.com.), tendo-se dado prefer��ncia aos gr��ficos deste ��ltimo. Resultados 1. Observou-se um predom��nio do sexo masculino (rela����o de 1:1,9); relativamente �� idade no momento de avalia����o, 242 crian��as (68,1%) tinham entre zero e seis anos e, dentro destas, a maioria (189) situava-se entre os tr��s e os seis anos. 2. De acordo com a DSM-IV e DSM-5, 261 (73,4%) crian��as apresentavam incapacidade intelectual ligeira. 3. A avalia����o da compet��ncia intelectual pelas escalas de Ruth Griffiths e WISC III (QI), revelaram correla����o negativa predominantemente forte e muito forte (��ndice de Spearman) com os qualificadores das fun����es do corpo estudadas (fun����es mentais, mentais espec��ficas e da voz). Os resultados obtidos pela co-investigadora A foram sobrepon��veis aos da investigadora principal. Os resultados obtidos pela co-investigadora B revelaram correla����o negativa moderada e forte, correla����o inferior �� da investigadora principal; Conclus��es Os resultados permitem inferir que as escalas de Ruth Griffiths e WISC-III s��o instrumentos adequados para caracterizar a incapacidade intelectual na CIF-CJ; a concord��ncia inter-observador, moderada, nos qualificadores atribu��dos nas fun����es em an��lise pela investigadora e co-investigadoras, permite concluir que as escalas de Ruth Griffiths e WISC IIIl s��o bons instrumentos para caracterizar os qualificadores nos dom��nios e fun����es estudados, por diferentes grupos de profissionais ligados �� inf��ncia. Subsistem dificuldades na diferencia����o entre qualificadores, designadamente entre os qualificadores 1 e 2, o que tem necessariamente implica����es na elegibilidade das crian��as para os apoios preconizados pelo DL 3/2008. ------------------------ ABSTRACT: Main objective ��� To determine the consistency of the use of assessment tools for intellectual ability - Griffiths and WISC III scales - in the context of domains and qualifiers for the ICF-CY, restricted to the mental functions of the body. Secondary objective ��� Studying the effectiveness and inter-observer concordance concerning the application of the ICF, based on the data recovered from the assessment made with the mentioned instruments, carried out by two independent observers including their perspective on health, education and social security. Methods ��� Observational, descriptive, cross-sectional and prospective study. ��� A convenience sample of 355 children was studied over a period of three years (May 2010 to April 2013), with a pathology in the area of pediatric neurodevelopment ��� intellectual disability (total of 4000 consultations, including first consultations and revaluations) were observed in the Development Centre (CD) in Hospital de Dona Estef��nia (HDE), Centro Hospitalar de Lisboa Central, EPE (CHLC). ��� Inclusion criteria: children of both sexes aged ���12 months and years ���17 and intellectual disability defined according to the criteria in the DSM-IV-TR, DSM 5 and ICD-10. ��� Exclusion criteria: children with autism; specific language impairment, hyperactivity; attention deficit disorder; severe birth sensory deficits (eg, impaired vision and hearing); amongst other diagnoses for neurodevelopmental disorders. ��� The study was conducted in two phases: in the first phase the principal investigator collected or updated medical history, clinically observed children requesting additional investigations if she deemed necessary. Psychological evaluation was performed by a single, duly licensed clinical psychologist with extensive experience in the referred scales using the instruments described below. Based on data collected, either by direct observation or through the results of Griffiths scales and WISC - III, the researcher applied the ICF-CY confined to the following fields and functions (variables): 1. GLOBAL MENTAL FUNCTIONS (b110- functions of consciousness, b114- Functions referring to space and time orientation , b117 - intellectual functions, b122- global psychosocial functions, b125- intrapersonal functions, b126- functions related to temperament and personality); 2. SPECIFIC MENTAL FUNCTIONS ( b140- attention functions, b147-psychomotor functions, b152- Emotional functions, b156- perception functions, b163- basic cognitive functions and cognitive functions b164- top level b167- language related mental functions. ) 3. VOICE AND SPEECH FUNCTIONS (b320-articulation functions, b330- fluency and rhythm of speech functions). ��� In the second phase, two co-investigators, with specific training on the scales used and the ICF-CY have applied the ICF in the domains and functions mentioned above, based on the scales results. These co-investigators did not make any direct observation of the studied children. ��� To perform the statistical analysis and analyze the relationship between the qualifiers (0-4) of the variables in the ICF study (b117, b122, b147, B163, B164, b167, b320 and B330) and psychometric instruments (Griffiths scale and WISC III), which is the first part of the study, the statistical technique of non-parametric Spearman correlation coefficient was used, which quantifies the strength and sign of the possible correlation between the variables under study. ��� For submission of correlations related to the second part of the study, SPSS (IBM SPSS) and Statistica (StatSoft, Inc., 2011) programs were used. STATISTICA (data analysis software system, version 10 www.statsoft.com.). Preference was given to graphs computed in Statistica. Results ��� Male predominated (ratio of 1: 1.9). 242 children (68.1% of the sample) were aged between zero and six years and, among these, the majority (189) was aged largest number between three and six years. ��� According to the DSM-IV and DSM-5, 261 (73.4%) children had mild intellectual disability. The correlation between the assessment of intellectual competence by Ruth Griffiths scales and WISC III (QI), was predominantly negative strong and very strong correlation with the qualifiers of body functions studied (specific mental functions, mental and voice functions using Spearman index). The levels of correlation obtained by the co-investigatores were in agreeance with the results from the principal investigator. The results obtained by co-investigator B showed moderate to strong negative correlation, levels that were lower to the those registered by the principal investigator; Conclusions These results indicate that Ruth Griffiths and WISC-III scales are adequate tools to characterize intellectual disability in the ICF-CY; moderate inter-observer agreement in the qualifiers assigned the functions under analysis by the researcher and co-researchers, shows that the scales are also good tools to measure CIF qualifyers by diferent technicians with different professional orientations, related to children. However, there are still difficulties in differentiating qualifiers, namely between qualifiers 1/2 and 3/4, which necessarily has implications for the eligibility of children for the state support advocated by the Portuguese Decret Law 3/2008.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Evaluation of the cytokine mannose-binding lectin as a mediator of periportal fibrosis progression in patients with schistosomiasis

INTRODUCTION : We hypothesized higher mannose-binding lectin level and classic factors (i.e., age, sex, alcohol consumption, exposure, and specific treatment) are associated with the severity of periportal fibrosis in schistosomiasis. METHODS : This cross-sectional study involved 79 patients infected with Schistosoma mansoni with severe or mild/moderate periportal fibrosis. Serum concentrations of mannose-binding lectin were obtained by enzyme-linked immunosorbent assay (ELISA). RESULTS: Higher serum level of mannose-binding lectin was significantly associated with advanced periportal fibrosis. CONCLUSIONS: Mannose-binding lectin may contribute to liver pathology in schistosomiasis and may represent a risk factor for advanced periportal fibrosis in the Brazilian population studied.

Historical trajectories of currently shrinking Portuguese cities: A typology of urban shrinkage

Cities develop according to different patterns, undergoing population growth during some periods and decline (shrinkage) during others. Theories attempting to understand these behaviours include: 1) shrinkage is a natural process in the life cycle of a city, alternating with periods of growth, or 2) shrinkage is an extreme event that places cities into a continuous decline process with no return to population growth. We use retrospective data over a period of 130 years to study 25 Portuguese cities currently facing population decline, and show that both theories coexist in time and space. Five types of shrinking city are revealed: ���Persistent Early Shrinkage��� due to exodus fromthe rural periphery, ���Metropolitan Shrinkage��� due to the challenges of urban sprawl, ���Recent Shrinkage��� in de-industrialisation hotspots, ���Cyclic Shrinkage��� occurring in political transformation cores, and ���Mild Shrinkage��� due to life-style disamenity. As diversity of city population trajectories appears to be the norm in both Portugal and other Western European countries, the incorporation of this range into the management of urban transitions is recommended in order to reinforce city resilience.

Fractional state space analysis of economic systems

This paper examines modern economic growth according to the multidimensional scaling (MDS) method and state space portrait (SSP) analysis. Electing GDP per capita as the main indicator for economic growth and prosperity, the long-run perspective from 1870 to 2010 identifies the main similarities among 34 world partners��� modern economic growth and exemplifies the historical waving mechanics of the largest world economy, the USA. MDS reveals two main clusters among the European countries and their old offshore territories, and SSP identifies the Great Depression as a mild challenge to the American global performance, when compared to the Second World War and the 2008 crisis.

Gold nanoprobes for assessing expression of critical genes in the infection pathway of MRSA

Staphylococcus aureus is an important opportunistic pathogen that can cause a wide variety of diseases from mild to life-threatening conditions. S. aureus can colonize many parts of the human body but the anterior nares are the primary ecological niche. Its clinical importance is due to its ability to resist almost all classes of antibiotics available together with its large number of virulence factores. MRSA (Methicillin-Resistant S. aureus) strains are particularly important in the hospital settings, being the major cause of nosocomial infections worldwide. MRSA resistance to ��-lactam antibiotics involves the acquisition of the exogenous mecA gene, part of the SCCmec cassette. Fast and reliable diagnostic techniques are needed to reduce the mortality and morbidity associated with MRSA infections, through the early identification of MRSA strains. The current identification techniques are time-consuming as they usually involves culturing steps, taking up to five days to determine the antibiotic resistance profile. Several amplification-based techniques have been developed to accelerate the diagnosis. The aim of this project was to develop an even faster methodology that bypasses the DNA amplification step. Gold-nanoprobes were developed and used to detect the presence of mecA gene in S. aureus genome, associated with resistance traits, for colorimetric assays based on non-crosslinking method. Our results showed that the mecA and mecA_V2 gold-nanoprobes were sensitive enough to discriminate the presence of mecA gene in PCR products and genomic DNA (gDNA) samples for target concentrations of 10 ng/��L and 20 ng/��L, respectively. As our main objective was to avoid the amplification step, we concluded that the best strategy for the early identification of MRSA infection relies on colorimetric assays based on non-crosslinking method with gDNA samples that can be extracted directly from blood samples.

Factors affecting Helicobacter pylori eradication using a seven-day triple therapy with a proton pump inhibitor, tinidazole and clarithromycin, in brazilian patients with peptic ulcer

Triple therapy is accepted as the treatment of choice for H. pylori eradication. In industrialized countries, a proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole have shown the best results. Our aims were: 1. To study the eradication rate of the association of a proton pump inhibitor plus tinidazole and clarithromycin on H. pylori infection in our population. 2. To determine if previous treatments, gender, age, tobacco, alcohol use, and non-steroidal anti-inflammatory drugs (NSAIDs) change the response to therapy. METHODS: Two hundred patients with peptic ulcer (upper endoscopy) and H. pylori infection (histology and rapid urease test - RUT) were included. A proton pump inhibitor (lansoprazole 30 mg or omeprazole 20 mg), tinidazole 500 mg, and clarithromycin 250 mg were dispensed twice a day for a seven-day period. Eradication was assessed after 10 to 12 weeks of treatment through histology and RUT. RESULTS: The eradication rate of H. pylori per protocol was 65% (128/196 patients). This rate was 53% for previously treated patients, rising to 76% for not previously treated patients, with a statistical difference p<0.01. No significant difference was observed regarding sex, tobacco use, alcohol consumption, and NSAID use, but for elderly patients the difference was p = 0.05. Adherence to treatment was good, and side effects were mild. CONCLUSIONS: A proton pump inhibitor, tinidazole, and clarithromycin bid for seven days resulted in H. pylori eradication in 65% of the patients. Previous treatments were the main cause of treatment failure.

Prevention of respiratory syncytial virus infections

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

Hemolytic disease of the newborn due to anti-U

Anti-U is a rare red blood cell alloantibody that has been found exclusively in blacks. It can cause hemolytic disease of the newborn and hemolytic transfusion reactions. We describe the case of a female newborn presenting a strongly positive direct antiglobulin test due to an IgG antibody in cord blood. Anti-U was recovered from cord blood using acid eluate technique. Her mother presented positive screening of antibodies with anti-U identified at delivery. It was of IgG1 and IgG3 subclasses and showed a titer of 32. Monocyte monolayer assay showed moderate interaction of Fc receptors with maternal serum with a positive result (3.1%). The newborn was treated only with 48 hours of phototherapy for mild hemolytic disease. She recovered well and was discharged on the 4th day of life. We conclude that whenever an antibody against a high frequency erythrocyte antigen is identified in brown and black pregnant women, anti-U must be investigated.

Pulmonary function and aerobic capacity in asymptomatic bariatric candidates with very severe morbid obesity

PURPOSE: Aerobic capacity and respiratory function may be compromised in obesity, but few studies have been done in highly obese bariatric candidates. In a prospective study, these variables were documented in the preoperative period, aiming to define possible physiologic limitations in a apparently healthy and asymptomatic population. METHOD: Forty-six consecutively enrolled adults (age 39.6 &plusmn; 8.4 years, 87.0% females, body mass index /BMI 49.6 &plusmn; 6.3 kg/m�� ) were analyzed. Ventilatory variables were investigated by automated spirometry, aerobic capacity was estimated by a modified Bruce test in an ergometric treadmill, and body composition was determined by bioimpedance analysis. RESULTS: Total fat was greatly increased (46.4 &plusmn; 4.6% of body weight) and body water reduced (47.3 &plusmn; 4.6 % body weight), as expected for such obese group. Spirometric findings including forced vital capacity of 3.3 &plusmn; 0.8 L and forced expiratory volume-1 second of 2.6 &plusmn; 0.6 L were usually acceptable for age and gender, but mild restrictive pulmonary insufficiency was diagnosed in 20.9%. Aerobic capacity was more markedly diminished, as reflected by very modest maximal time (4.5 &plusmn; 1.1 min) and distance (322 &plusmn;142 m) along with proportionally elevated maximal oxygen consumption (23.4 &plusmn; 9.5 mL/kg/min) achieved by these subjects during test exercise. CONCLUSIONS: 1) Cardiopulmonary evaluation was feasible and well-tolerated in this severely obese population; 2) Mean spirometric variables were not diminished in this study, but part of the population displayed mild restrictive changes; 3) Exercise tolerance was very negatively influenced by obesity, resulting in reduced endurance and excessive metabolic cost for the treadmill run; 4) More attention to fitness and aerobic capacity is recommended for seriously obese bariatric candidates;

Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy

PURPOSE: The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS: Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS: Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 �� 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). CONCLUSIONS: Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.

Therapeutics bioconjugates: evaluation of iminoboronates as payload delivery system for cancer

The advent of bioconjugation impacted deeply the world of sciences and technology. New biomolecules were found, biological processes were understood, and novel methodologies were formed due to the fast expansion of this area. The possibility of creating new effective therapies for diseases like cancer is one of big applications of this now big area of study. Off target toxicity was always the problem of potent small molecules with high activity towards specific tumour targets. However, chemotherapy is now selective due to powerful linkers that connect targeting molecules with affinity to interesting biological receptors and cytotoxic drugs. This linkers must have very specific properties, such as high stability in plasma, no toxicity, no interference with ligand affinity nor drug potency, and at the same time, be able to lyse once inside the target molecule to release the therapeutic warhead. Bipolar environments between tumour intracellular and extracellular medias are usually exploited by this linkers in order to complete this goal. The work done in this thesis explores a new model for that same task, specific cancer drug delivery. Iminoboronates were studied due to its remarkable selective stability towards a wide pH range and endogenous molecules. A fluorescence probe was design to validate this model by creating an Off/On system and determine the payload release location in situ. A process was optimized to synthetize the probe 8-(1-aminoethyl)-7-hydroxy-coumarin (1) through a reductive amination reaction in a microwave reactor with 61 % yield. A method to conjugate this probe to ABBA was also optimized, obtaining the iminoboronate in good yields in mild conditions. The iminoboronate model was studied regarding its stability in several simulated biological environments and each half-life time was determined, showing the conjugate is stable most of the cases except in tumour intracellular systems. The construction of folate-ABBA-coumarin bioconjugate have been made to complete this evaluation. The ability to be uptaken by a cancer cell through endocytosis process and the conjugation delivery of coumarin fluorescence payload are two features to hope for in this construct.

The role of arl13b in cilia length regulation and in zebrafish development

RESUMO: Arl13b �� uma importante prote��na ciliar, presente em c��lios prim��rios e c��lios m��veis. Ratinhos mutantes para Arl13b t��m comprimento dos c��lios reduzido e defeitos nos B-t��bulos dos c��lios. Como consequ��ncia destes fen��tipos, defici��ncias na Arl13b originam, em modelos animais, v��rias doen��as cong��nitas, incluindo problemas no estabelecimento do eixo esquerda-direita, malforma����es cerebrais e deforma����es corporais. Nos seres humanos, defici��ncias na Arl13b levam a uma doen��a cr��nica cong��nita chamada S��ndrome de Joubert. Por outro lado, a sobreexpress��o de Arl13b origina c��lios mais longos, no entanto existe uma aus��ncia da caracteriza����o dos fen��tipos celulares e durante o desenvolvimento embrion��rio. Neste trabalho, quisemos explorar o efeito da sobre-express��o de Arl13b em embri��es de peixezebra. Descobrimos que, ao n��vel ciliar, a sobre-express��o de Arl13b nas c��lulas aumenta o comprimento ciliar em c��lios prim��rios e m��veis, no entanto, a esses c��lios falta adequada acetila����o da alfa-tubulina no citoesqueleto feito por microt��bulos. Os nossos resultados mostraram que esse efeito �� espec��fico de Arl13b sobre-express��o e quando se manipularam as enzimas respons��veis pela acetila����o (Mec17) e pela de-acetila����o (HDAC6) encontr��mos uma sinergia potencial com ambas. Test��mos ainda, que o aumento no comprimento ciliar n��o estava causalmente relacionado com a falta de acetila����o, ou seja, os c��lios com menos acetila����o n��o eram necessariamente os mais longos. Tamb��m mostr��mos que a sobre-express��o de Arl13b �� capaz de restaurar o comprimento dos c��lios em mutantes com c��lios curtos e como isso pode ser explorado para um futuro potencial papel terap��utico para Arl13b. Em seguida, foi avaliado o impacto do aumento da quantidade de Arl13b no desenvolvimento embrion��rio do peixe-zebra. Observou-se que a sobre-express��o de Arl13b apresentava fen��tipos muito fracos, quando comparados com a perda de fun����o dos mutantes de Arl13b. Focados no inesperado fen��tipo leve no estabelecimento do eixo esquerda-direita abord��mos a quest��o atrav��s do estabelecimento de uma colabora����o com matem��ticos, descobrimos que os c��lios mais longos que potencialmente t��m a capacidade de movimentar mais fluido s��o atenuados por amplitudes de batimento menores, e, como resultado, estes longos c��lios n��o prejudicam o movimento do fluido e consequentemente n��o afetam o estabelecimento dos padr��es de esquerda-direita. Sugerimos assim que a Arl13b �� um regulador chave, do comprimento ciliar. Descobrimos uma nova intera����o com as enzimas de acetila����o/de-acetila����o e levantamos novas hip��teses quanto aos mecanismos moleculares da fun����o da Arl13b. Propomos um novo modelo para o mecanismo molecular da Arl13b na regula����o do comprimento dos c��lios onde podemos integrar os nossos resultados com os relatados na literatura. Este trabalho adiciona mais conhecimento para o mecanismo de a����o da Arl13b e, portanto, fornece uma importante contribui����o para o campo da investiga����o em c��lios.---------------------------------------------------------------------------------------------------------------------- ABSTRACT: Arl13b is an important ciliary protein, present in primary and motile cilia. arl13b-/- mouse mutants have reduced cilia length and cilia B-tubule defects. As a consequence of these phenotypes, Arl13b loss of function animal models suffer from several congenital disorders including left-right problems, brain malformations and body deformations. In humans Arl13b depletion leads to a congenital chronic disease called Joubert Syndrome. On the other hand, overexpressing Arl13b leads to longer cilia but the characterization of the cellular and developmental phenotypes was missing. In this work we explore the effect of Arl13b overexpression in zebrafish embryos. We found that, at the ciliary level, Arl13b overexpression from 1 cell stage produces longer primary and motile cilia, but these cilia lack proper alpha tubulin acetylation of their microtubule cytoskeleton. Our results showed that this effect is specific from Arl13b overexpression and when we manipulated the enzymes responsible for acetylation, Mec17, and de-acetylation, HDAC6, we found a potential synergy of both mec17 knockdown and HDAC6 activity with Arl13b overexpression. We tested that the ciliary increase in length was not causally related to the lack of acetylation, meaning the more de-acetylated cilia were not necessarily the longer ones. We also showed that Arl13b overexpression is able to restore cilia length in short cilia mutants and how that may be explored to a potential future therapeutic role for Arl13b. Next, we evaluated the impact of increasing the amount of Arl13b in zebrafish embryonic development. We observed that Arl13b overexpression presented very mild phenotypes when compared to the loss of function mutants. We focused on the unexpected left-right mild phenotype and by establishing a mathematical modeling collaboration, we found out that the longer cilia generated force was attenuated by smaller beating amplitudes, and as a result, these long cilia were not impairing the cilia generated flow and the establishment of left-right patterning. We suggest that Arl13b is one key cilia length regulator. We disclosed a novel interaction with the acetylation / de-acetylation enzymes and raised new hypothesis as to the mechanisms of Arl13b function. We propose a new model for the Arl13b molecular mechanism of cilia length regulation where we integrate our findings with those reported in the literature. This work adds more knowledge to the Arl13b mechanism of action and therefore provides an important contribution to the cilia research field.