Polar Lipids of Marine Microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis Mitigate the LPS-Induced Pro-Inflammatory Response in Macrophages.

Microalgae are recognized as a relevant source of bioactive compounds. Among these bioactive products, lipids, mainly glycolipids, have been shown to present immunomodulatory properties with the potential to mitigate chronic inflammation. This study aimed to evaluate the anti-inflammatory effect of polar lipids isolated from Nannochloropsis oceanica and Chlorococcum amblystomatis. Three fractions enriched in (1) digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG), (2) monogalactosyldiacylglycerol (MGDG), and (3) diacylglyceryl-trimethylhomoserine (DGTS) and phospholipids (PL) were obtained from the total lipid extracts (TE) of N. oceanica and C. amblystomatis, and their anti-inflammatory effect was assessed by analyzing their capacity to counteract nitric oxide (NO) production and transcription of pro-inflammatory genes Nos2, Ptgs2, Tnfa, and Il1b in lipopolysaccharide (LPS)-activated macrophages. For both microalgae, TE and Fractions 1 and 3 strongly inhibited NO production, although to different extents. A strong reduction in the LPS-induced transcription of Nos2, Ptgs2, Tnfa, and Il1b was observed for N. oceanica and C. amblystomatis lipids. The most active fractions were the DGTS-and-PL-enriched fraction from N. oceanica and the DGDG-and-SQDG-enriched fraction from C. amblystomatis. Our results reveal that microalgae lipids have strong anti-inflammatory capacity and may be explored as functional ingredients or nutraceuticals, offering a natural solution to tackle chronic inflammation-associated diseases.

Scenedesmus rubescens Heterotrophic Production Strategies for Added Value Biomass.

Microalgae attract interest worldwide due to their potential for several applications. Scenedesmus is one of the first in vitro cultured algae due to their rapid growth and handling easiness. Within this genus, cells exhibit a highly resistant wall and propagate both auto- and heterotrophically. The main goal of the present work is to find scalable ways to produce a highly concentrated biomass of Scenedesmus rubescens in heterotrophic conditions. Scenedesmus rubescens growth was improved at the lab-scale by 3.2-fold (from 4.1 to 13 g/L of dry weight) through medium optimization by response surface methodology. Afterwards, scale-up was evaluated in 7 L stirred-tank reactor under fed-batch operation. Then, the optimized medium resulted in an overall productivity of 8.63 g/L/day and a maximum biomass concentration of 69.5 g/L. S. rubescens protein content achieved approximately 31% of dry weight, similar to the protein content of Chlorella vulgaris in heterotrophy.

Graves' disease with spontaneous resolution following ocrelizumab in primary progressive multiple sclerosis.

Objectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves' disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an "immune reconstitution syndrome"; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.

Lipoprotein apheresis in the management of severe hypercholesterolemia and hyperlipoproteinemia(a)-The Portuguese experience.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Lipoprotein apheresis is often required for treatment of patients with a high risk for CVD due to hypercholesterolemia and/or hyperlipoproteinemia(a). AIM: To describe our experience with lipoprotein apheresis in patients with severe hypercholesterolemia or with hyperlipoproteinemia(a). METHODS: We retrospectively investigated patients treated with Lipoprotein apheresis using direct adsorption of lipoproteins (DALI) technique, between December 2008 and March 2018, in our center. Adverse events, acute and long term reductions in lipid parameters were analyzed. RESULTS: Between December 2008 and March 2018, a total of 950 treatments were performed in five patients, four with heterozygous familial hypercholesterolemia (HeFH), all on maximally tolerated cholesterol-lowering drug therapy and in one patient with hyperlipoproteinemia(a) and progressive CVD. In the four patients with HeFH we obtained mean acute reductions in LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) of 62.0 ± 7.8% and 60.4 ± 6.8%, respectively. Regarding long-term efficacy we achieved a mean reduction of 43.1% in LDL-C and of 41.2% in non-HDL-C. In the patient with hyperlipoproteinemia(a) we attained mean acute reductions of 60.4 ± 6.4% in Lp(a) and of 75.4 ± 7.3% in LDL-C per session and long term reductions in Lp(a) and LDL-C of 67.4% and 40.5%, respectively. Adverse events were recorded in only 1.2% of treatments. CONCLUSION: Lipoprotein apheresis is an efficient and safe treatment in severely hypercholesterolemic patients who are refractory to conservative lipid-lowering therapy or with hyperlipoproteinemia(a) and progressive CVD.

Psychosocial factors as predictors of quality of life in chronic Portuguese patients.

BACKGROUND: Chronic illnesses are diseases of long duration and generally of slow progression. They cause significant quality of life impairment. The aim of this study was to analyse psychosocial predictors of quality of life and of subjective well-being in chronic Portuguese patients. METHODS: Chronic disease patients (n = 774) were recruited from central Portuguese Hospitals. Participants completed self-reported questionnaires assessing socio-demographic, clinical, psychosocial and outcome variables: quality of life (HRQL) and subjective well-being (SWB). MANCOVA analyses were used to test psychosocial factors as determinants of HRQL and SWB. RESULTS: After controlling for socio-demographic and clinical variables, results showed that dispositional optimism, positive affect, spirituality, social support and treatment adherence are significant predictors of HRQL and SWB. Similar predictors of quality of life, such as positive affect, treatment adherence and spirituality, were found for subgroups of disease classified by medical condition. CONCLUSIONS: The work identifies psychosocial factors associated with quality of life. The predictors for the entire group of different chronic diseases are similar to the ones found in different chronic disease subgroups: positive affect, social support, treatment adherence and spirituality. Patients with more positive affect, additional social support, an adequate treatment adherence and a feel-good spirituality, felt better with the disease conditions and consequently had a better quality of life. This study contributes to understanding and improving the processes associated with quality of life, which is relevant for health care providers and chronic diseases support.

Innovative vs classical methods for drying heterotrophic Chlorella vulgaris: Impact on protein quality and sensory properties.

Drying is a necessary step in the microalgae production chain to reduce microbial load and oxidative degradation of the end product. Depending on the differences in applied temperature and treatment time, the process of drying can have a substantial impact on protein quality and aroma, important characteristics determining the incorporation potential in food products. In this study, we compared the drying of heterotrophic Chorella vulgaris with both innovative (agitated thin film drying (ATFD), pulse combustion drying (PCD) and solar drying (SolD)) and commonly used drying techniques (spray drying (SprD) and freeze drying (FD)). To evaluate the impact on protein quality, we evaluated techno-functional properties, in vitro digestibility (INFOGEST) as well as protein denaturation using differential scanning calorimetry (DSC). A sensory analysis was performed by a trained expert panel, combined with headspace solid-phase microextraction (HS-SPME) - gas chromatography-mass spectrometry (GC-MS) to determine volatile organic compounds (VOCs). ATFD was found to increase techno-functional properties such as gelling, water holding and solubility as well as in vitro protein digestibility. These observations could be related to induced cell disruption and protein denaturation by ATFD. Sensory analysis indicated an increased earthy off-flavor after ATFD. Interestingly, the high-temperature PCD led to an increase in cacao odor while low-temperature FD resulted in lower flavor, odors and VOCs. These results demonstrate that protein quality and sensorial properties of C. vulgaris can be steered through the type of drying, which could help in the selection of application-specific drying methods. Overall, this work could promote the incorporation of microalgal single cell proteins in different innovative food products.

Evaluation of the fertilizer potential of Chlorella vulgaris and Scenedesmus obliquus grown in agricultural drainage water from maize fields.

Producing microalgae with agricultural drainage water (ADW) allows recycling water and nutrients, with the production of a biofertilizer, avoiding receiving waters' contamination. Chlorella vulgaris and Scenedesmus obliquus were cultivated using ADW and standard media supplementation and presented higher productivities, relatively to the control industrial growth medium (using freshwater). Selected strains were grown outdoors in pilot flat panel photobioreactors, reaching 2.20 g L-1 for S. obliquus and 1.15 g L-1 for C. vulgaris, and degrading herbicides in the ADW to non-quantifiable concentrations. The potential of the C. vulgaris and S. obliquus suspensions to replace 50% of nitrogen (N) mineral fertilization of lettuce (0.5 g pot-1) was evaluated through a pot trial, also using a 2-times (1.0 g pot-1) and 5-times (2.5 g pot-1) higher dose, applied 31 days before lettuce transplanting. Even the lower dose of N, applied via C. vulgaris or S. obliquus suspensions, was able to provide significantly higher lettuce fresh matter yield, relatively to the mineral fertilized control. Soil enzymatic activities were improved, with significantly higher dehydrogenase, ß-glucosidase, and acid phosphatase activities for the 2.5 g pot-1 dose, more marked for S. obliquus, which was also able to increase soil organic matter content. Both the non-fertilized control and microalgae fertilized pots led to similar soil electrical conductivities, 3-fold lower than in the N-mineral fertilized pots, evidencing the capacity of microalgae fertilizers to avoid soil secondary salinization. Results suggest benefits from using ADW from maize cultivation to produce C. vulgaris or S. obliquus suspensions, that can be further used as liquid organic slow-release fertilizer.

High prevalence of cardiovascular disease and risk factors among type 2 diabetes patients followed in a hospital setting in Portugal: The PICT2RE observational study.

INTRODUCTION AND OBJECTIVES: Portugal is a country with a high prevalence of type 2 diabetes (T2D) and cardiovascular disease (CVD). The prevalence of CVD and cardiovascular (CV) risk factors among T2D patients followed in hospitals in Portugal is not known. The primary objective of this study was to assess the prevalence of CVD and CV risk factors among T2D patients in a hospital setting in Portugal. The clinical management of CVD in the hospital setting was also assessed. METHODS: We performed a non-interventional, multicenter, cross-sectional study with a retrospective phase. T2D patients were consecutively invited to participate. Data were collected retrospectively. RESULTS: A total of 715 patients were included in the study. Mean age and diabetes duration were 66.6 and 17.4 years, respectively. Of these, 286 patients (40.0%) had been diagnosed with CVD, mostly ischemic heart disease (50.4%). All patients had at least one CV risk factor. CVD was significantly associated with hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol, hypertriglyceridemia and smoking. During the three years prior to study inclusion, the incidence of hyperglycemic episodes and T2D complications increased among patients with established CVD, but the numbers of hospitalization episodes and specialist appointments remained stable. An improvement was observed in key cardiometabolic risk factors. CONCLUSIONS: Our study revealed a high prevalence of CVD and CV risk factors among a sample of T2D patients in a hospital setting. Patients with established CVD seem to be adequately managed but further efforts are needed at the prevention stage for better control of risk factors and morbidity.

Differences and Similarities in Lipid Composition, Nutritional Value, and Bioactive Potential of Four Edible Chlorella vulgaris Strains.

The microalga Chlorella vulgaris is a popular food ingredient widely used in the industry, with an increasing market size and value. Currently, several edible strains of C. vulgaris with different organoleptic characteristics are commercialized to meet consumer needs. This study aimed to compare the fatty acid (FA) and lipid profile of four commercialized strains of C. vulgaris (C-Auto, C-Hetero, C-Honey, and C-White) using gas- and liquid-chromatography coupled to mass-spectrometry approaches, and to evaluate their antioxidant and anti-inflammatory properties. Results showed that C-Auto had a higher lipid content compared to the other strains and higher levels of omega-3 polyunsaturated FAs (PUFAs). However, the C-Hetero, C-Honey, and C-White strains had higher levels of omega-6 PUFAs. The lipidome signature was also different between strains, as C-Auto had a higher content of polar lipids esterified to omega-3 PUFAs, while C-White had a higher content of phospholipids with omega-6 PUFAs. C-Hetero and C-Honey showed a higher content of triacylglycerols. All extracts showed antioxidant and anti-inflammatory activity, highlighting C-Auto with greater potential. Overall, the four strains of C. vulgaris can be selectively chosen as a source of added-value lipids to be used as ingredients in food and nutraceutical applications for different market needs and nutritional requirements.

Diagnostic accuracy of Bilateral Inferior Petrosal Sinus Sampling: The Experience of a Tertiary Centre.

PURPOSE: To assess the accuracy of bilateral inferior petrosal sinus sampling both in the differential diagnosis of adrenocorticotrophic hormone dependent Cushing's syndrome and predicting the localization on the pituitary. METHODS: The authors evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary centre, between January 1995 and March 2018. The probable diagnosis of Cushing's disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with corticotrophin releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated. RESULTS: A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing's disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing's disease - predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization - 70.0%. CONCLUSIONS: Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing's disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited.

Severe symptomatic hyperparathyroidism-Is it carcinoma?-Case report and literature review.

Parathyroid carcinoma is a rare disease, difficult to diagnose and associated with a poor prognosis. It must be suspected preoperatively, based on clinical and imaging grounds, in order to perform the best surgical option and avoid compromising patient's prognosis.

Diagnosis, treatment, and survival analysis of adrenocortical carcinomas: a multicentric study.

INTRODUCTION: Current guidelines specify controversial areas in adrenocortical carcinomas (ACC), such as optimal follow-up time after remission and identification of prognostic markers. We aim to address these topics by analyzing four reference centers in our country. METHODS: Cross-sectional multicentric study of 69 patients (mean age: 51.7 ± 16.7 years-old; women, 72.5%). Kaplan-Meier survival curves and Cox regression analysis were used to calculate overall survival and its predictors. RESULTS: Thirty-eight individuals (55.0%) had hormonal autonomous production, and 40.6% of the patients presented with metastasis. Surgery was performed in 84.1% of them. Most of these patients (72.4%) were then assigned to adjuvant therapy, while 27.6% were actively surveilled. Among patients undergoing surgery, those who achieved transient remission presented a longer survival time (66 months) than those who never reached the disease-free status (21 months) (p = 0.021). One patient presented with recurrence more than 7 years after complete tumor resection. The lowest overall survival was observed in patients (n = 11) assigned to palliative care since diagnosis (9 months). Tumor stage was identified as the only independent predictor of survival in our cohort (p = 0.006). Five-year survival was 67% for tumors confined to the adrenal space (stage I/II), 56% for locally advanced disease (stage III), and 0% for metastatic disease (stage IV). CONCLUSION: This study reinforces the dismal prognosis of ACC, the need for long-term follow-up, and tumor stage as the most important survival predictor. Reviewing medical records in such rare conditions is an opportunity to identify insufficiencies and to improve medical care.

Oxidation of benzoic acid from biomass burning in atmospheric waters.

This work evaluates the degradation of benzoic acid, a tracer from biomass burning, by different oxidation agents (Fe (III); H2O2; sunlight; and combinations of the previous ones) in model solutions and in real atmospheric waters. The extent of reactions was assessed by Ultraviolet-Visible and molecular fluorescence spectroscopies. The oxidation of benzoic acid occurred with the chemical oxidants Fe (III), H2O2, Fe (III) and H2O2 simultaneously in the presence of sunlight, and with Fe (III) and H2O2 simultaneously in the absence of light. The decrease of the pH value from neutral to acid for atmospheric waters generally increased the extent of oxidation. Sunlight was an important oxidation agent, and its combination with chemical oxidants increased the oxidation rate of benzoic acid, possibly due to the photogeneration of hydroxyl radicals. The results also suggested the occurrence of direct and indirect photolysis of benzoic acid in atmospheric waters. Moreover, the oxidation of benzoic acid produced new and more complex chromophoric compounds, which were then degraded. In addition, the nocturnal period is not sufficient for the full degradation of benzoic acid and of the intermediates formed by Fenton-like oxidation. The diurnal period may be enough for their full degradation through photo-Fenton-like oxidation, but this depends on the composition of the atmospheric waters, namely of the chromophoric content. Thus, this study highlights that benzoic acid from biomass burning, and its derivatives, may persist in atmospheric waters for periods of longer than one day, becoming available for other reactions, and may also affect the terrestrial and aquatic ecosystems through the wet depositions.

Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors.

The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components' waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.

[Endocrinology in Portugal - Census 2016. Board of the Portuguese College of Endocrinology and Nutrition of the Portuguese Medical Association]. / A Endocrinologia em Portugal - Censo 2016. Direção do Colégio de Endocrinologia e Nutrição da Ordem dos Médicos.

INTRODUCTION: On September 2016, the Board of the College of Endocrinology and Nutrition of the Portuguese Medical Association carried out a national survey, about all Endocrinology, Diabetes and Metabolism Departments of the public hospitals included in the Portuguese National Health Service and a simplified version of this survey was sent to all endocrinologists working in Portugal and registered with the Portuguese Medical Association. MATERIAL AND METHODS: Data related to organizational and human resources were collected, reporting the situation by the end of year 2015. The census registered 107 individuals and 27 Departments. RESULTS: The ratio of endocrinologists-population was 1.4, much lower than in the other European countries (varies between 2 to 4), resulting in alarming shortages of services in some areas of Portugal and in worse quality indicators. DISCUSSION: These data suggest that actions should be taken to increase the number of endocrinologists and departments in the country. CONCLUSION: In recent years, the number of residents has significantly increased, which will make it possible to correct this situation.

Introdução: A Direção do Colégio de Endocrinologia e Nutrição da Ordem dos Médicos realizou um inquérito nacional em setembro de 2016, a todos os serviços de Endocrinologia, Diabetes e Metabolismo dos hospitais do Serviço Nacional de Saúde e uma versão simplificada do mesmo foi enviada a todos os endocrinologistas a trabalhar em Portugal e inscritos no colégio. Material e Métodos: O censo inclui dados organizacionais e de recursos humanos relativos ao fim do ano de 2015. Registou 107 respostas individuais e 27 serviços. Resultados: O ratio de endocrinologistas por 100 000 habitantes era de 1,4, muito inferior a outros países europeus (varia de 2 a 4), que resulta numa carência grave de serviços em algumas zonas do País e em piores indicadores de qualidade. Discussão: Estes dados indicam que devem ser implementadas medidas para aumentar o número de endocrinologistas e serviços em Portugal. Conclusão: Nos últimos anos, o número de internos tem vindo a aumentar, o que vai permitir melhorar esta situação.

[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: genotype-phenotype correlation]. / Hiperplasia Congénita da Suprarrenal por Deficiência de 21-Hidroxílase: Correlação Genótipo-Fenótipo.

INTRODUCTION: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the most frequent inborn conditions. It is caused by distinct mutations in the CYP21A2 gene and in the majority of cases the disease's severity correlates with CYP21A2 allelic variation Our aim was to describe the mutational spectrum of CYP21A2 and evaluate genotype-phenotype correlation in a cohort of portuguese patients with 21-hydroxylase deficiency. MATERIAL AND METHODS: Retrospective study of 22 patients with clinical diagnosis of 21-hydroxylase deficiency. Molecular analysis of CYP21A2 was performed and genotype-phenotype correlation was then established. RESULTS: Genotyping was performed in 22 unrelated patients: 5 with classic salt-wasting (average age of diagnosis 10,2 days; minimum 1, maximum 20 days), 7 with classic simple virilizing (average age of diagnosis 3,5 years; minimum 0 days, maximum 7 years) and 10 with nonclassical form (average age of diagnosis 5,7 years; minimum 4 years, maximum 8 years). The most frequent genetic defects in the classic forms were I2 splice (24%) and I172N (24%), followed by Q318X (16%) and gene deletions (16%) and in the nonclassical form, the V281L (80%). The overall concordance between genotype and phenotype was 81,8%. Genotype accurately predicted phenotype in 83,3%, 100% and 90% of patients with classic salt-wasting, classic simple virilizing and nonclassical mutations, respectively. DISCUSSION: The frequency of genetic defects in our patients was comparable to similar studies. In most cases there was a good correlation between genotype and phenotype. CONCLUSIONS: Molecular analysis of CYP21A2 provides useful information in terms of prediction of disease severity, genetic and prenatal counseling.

Introdução: A hiperplasia congénita da suprarrenal por deficiência de 21-hidroxílase constitui uma das doenças hereditárias mais comuns. Resulta de diferentes mutações no gene CYP21A2 e, na maioria dos casos, a gravidade da doença correlaciona-se com a variação alélica do CYP21A2. O objetivo deste estudo foi descrever o espectro mutacional do CYP21A2 e avaliar a correlação genótipo-fenótipo numa coorte de doentes portugueses com deficiência de 21-hidroxílase. Material e Métodos: Estudo retrospetivo de 22 doentes com diagnóstico clínico de deficiência de 21-hidroxílase. Foi feita análise molecular do CYP21A2 e estabelecida a correlação genótipo-fenótipo. Resultados: Foi realizada genotipagem em 22 doentes não relacionados: 5 com a forma clássica perdedora de sal (idade média ao diagnóstico de 10,2 dias; mínimo 1, máximo 20 dias), 7 com a forma clássica virilizante simples (idade média ao diagnóstico de 3,5 anos; mínimo 0 dias, máximo 7 anos) e 10 com a forma não clássica (idade média ao diagnóstico de 5,7 anos; mínimo 4 anos, máximo 8 anos). Os defeitos genéticos mais frequentes nas formas clássicas foram o I2 splice (24%) e I172N (24%), seguindo-se o Q318X (16%) e deleções de genes (16%) e, na forma não clássica, o V281L (80%). Verificou-se uma concordância genótipo-fenótipo global de 81,8%. O genótipo permitiu prever adequadamente o fenótipo em 83,3%, 100% e 90% dos doentes com mutações compatíveis com a forma clássica perdedora de sal, clássica virilizante simples e não clássica, respectivamente. Discussão: A frequência de defeitos genéticos observados nos nossos doentes é comparável a estudos semelhantes. Observou-se, na maioria dos casos, uma boa correlação genótipo-fenótipo. Conclusões: A análise molecular do CYP21A2 fornece informação importante relativamente à gravidade da doença e no aconselhamento genético e pré-natal.

Predictors of quality of life in Portuguese obese patients: a structural equation modeling application.

Living with obesity is an experience that may affect multiple aspects of an individual's life. Obesity is considered a relevant public health problem in modern societies. To determine the comparative efficacy of different treatments and to assess their impact on patients' everyday life, it is important to identify factors that are relevant to the quality of life of obese patients. The present study aims to evaluate, in Portuguese obese patients, the simultaneous impact of several psychosocial factors on quality of life. This study also explores the mediating role of stigma in the relationship between positive/negative affect and quality of life. A sample of 215 obese patients selected from the main hospitals in Portugal completed self-report questionnaires to assess sociodemographic, clinical, psychosocial, and quality of life variables. Data were analysed using structural equation modeling. The model fitted the data reasonably well, CFI = 0.9, RMSEA = 0.06. More enthusiastic and more active patients had a better quality of life. Those who reflect lower perception of stigma had a better physical and mental health. Partial mediation effects of stigma between positive affect and mental health and between negative affect and physical health were found. The stigma is pervasive and causes consequences for psychological and physical health.

[Provocative tests in the diagnosis of childhood onset growth hormone insufficiency]. / O Papel dos Testes de Estimulação Farmacológica no Diagnóstico da Deficiência de Hormona do Crescimento em Crianças e Adolescentes.

INTRODUCTION: The incidence of short stature associated with growth hormone deficiency has been estimated to be about 1:4000 to 1:10000. It is the main indication for treatment with recombinant growth hormone. OBJECTIVES: The aims of the study were to evaluate the results of growth hormone stimulation tests and identify the growth hormone deficiency predictors. MATERIAL AND METHODS: A cross-sectional, analytical and observational study was conducted. We studied all the children and adolescents submitted to growth hormone pharmacological stimulation tests between January 2008 and May 2012. Growth hormone deficiency diagnosis was confirmed by two negatives growth hormone stimulation tests (growth hormone peak < 7 ng/ml). The statistical analysis was performed using student t-test, chi-square, Pearson correlation and logistic regression. Statistical significance determined at the 5% level (p ≤ 0.05). RESULTS: Pharmacological stimulation tests were performed in 89 patients, with a median age of 10 [3-17] years. Clonidine (n = 85) and insulin tolerance test (n = 4) were the first growth hormone stimulation tests performed. Growth hormone deficiency was confirmed in 22 cases. In cases with two growth hormone stimulation tests, the growth hormone peak showed a moderate correlation (r = 0.593, p = 0.01). In logistic regression model height (z-score) and the growth hormone peak in first stimulation test were predictors of growth hormone deficiency diagnosis (each one unit increase in z-score decrease the growth hormone deficiency probability). DISCUSSION: Measurement of IGF-1 cannot be used in diagnosing growth hormone deficiency. CONCLUSION: Auxological criteria associated with a positive test seems to be a reliable diagnostic tool for growth hormone deficiency.

Introdução: A incidência da deficiência de hormona do crescimento é de 1:4000 a 1:10000, sendo a principal indicação para tratamento com hormona do crescimento recombinante.Objectivos: Avaliar os resultados dos testes de estimulação da hormona do crescimento e identificar factores preditivos para o diagnóstico da deficiência de hormona do crescimento.Material e Métodos: Estudo observacional, analítico e transversal. Foram analisados dados clínicos e auxológicos e os resultados dos exames de diagnóstico de crianças e adolescentes submetidos a testes de estimulação farmacológica da hormona do crescimento (01/01/2008 a 31/05/2012). O diagnóstico definitivo de deficiência de hormona do crescimento foi efectuado mediante dois testes com estímulos farmacológicos diferentes negativos (pico máximo da hormona do crescimento < 7 ng/mL) ou um teste negativo associado à presença de alterações anatómicas da região hipotálamo-hipofisária, observadas na ressonância magnética cerebral. Para análise estatística, foram realizados o testes de t student, do qui- quadrado, correlação de Pearson e a regressão logística. Foi considerado como nível de significância estatística (p) um valor igual ou menor que 0,05.Resultados: Realizaram-se testes de estimulação em 89 doentes, com mediana de idade igual a 10 [3-17] anos, 67% do sexo masculino e 77% pré-púberes. Os fármacos utilizados no primeiro teste de estimulação foram a clonidina (n = 85) e a insulina (n = 4). Foram diagnosticados 22 casos de deficiência de hormona do crescimento. Nos casos submetidos a dois testes, os valores máximos de hormona do crescimento apresentaram uma correlação moderada entre si (r = 0,593, p = 0,01). Verificou-se que as variáveis estatura (z-score) e pico máximo de hormona do crescimento obtido no primeiro teste têm valor preditivo no diagnóstico de deficiência de hormona do crescimento.Discussão: A determinação do IGF-1 não demonstrou ser preditor de deficiência de hormona do crescimento.Conclusão: Os testes de estimulação são uma ferramenta de diagnóstico da deficiência de hormona do crescimento e que devem ser enquadrados nos parâmetros clínicos e auxológicos.

Optimism on quality of life in Portuguese chronic patients: moderator/mediator?

OBJECTIVE: optimism is an important variable that has consistently been shown to affect adjustment to quality of life in chronic diseases. This study aims to clarify if dispositional optimism exerts a moderating or a mediating influence on the personality traits-quality of life association, in Portuguese chronic patients. METHODS: multiple regression models were used to test the moderation and mediation effects of dispositional optimism in quality of life. A sample of 729 patients was recruited in Portugal's main hospitals and completed self-reported questionnaires assessing socio-demographic and clinical variables, personality, dispositional optimism, quality of life (QoL) and subjective well-being (SWB). RESULTS: the results of the regression models showed that dispositional optimism did not moderate the relationships between personality traits and quality of life. After controlling for gender, age, education level and severity of disease perception, the effects of personality traits on QoL and in SWB were mediated by dispositional optimism (partially and completely), except for the links between neuroticism/openness to experience and physical health. CONCLUSION: dispositional optimism is more likely to play a mediating, rather than a moderating role in personality traits-quality of life pathway in Portuguese chronic patients, suggesting that "the expectation that good things will happen" contributes to a better quality of life and subjective well-being.

Cat eye syndrome and growth hormone deficiency with pituitary anomalies: a case report and review of the literature.

Cat eye syndrome is a rare congenital disease characterized by the existence of a supernumerary chromosome derived from chromosome 22, with a variable phenotype comprising anal atresia, coloboma of the iris and preauricular tags or pits. We report a girl with cat eye syndrome, presenting short stature, with growth hormone deficiency due to posterior pituitary ectopia. Short stature is a common feature of this syndrome, and the association with a structural pituitary anomaly has been described, however growth hormone deficiency and the underlying mechanisms are rarely reported. A review on short stature and growth hormone deficiency in cat eye syndrome is conducted.