Expanding the Genetic Spectrum of ANOS1 Mutations in Patients with Congenital Hypogonadotropic Hypogonadism

STUDY QUESTION: What is the prevalence and functional consequence of ANOS1 (KAL1) mutations in a group of men with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Three of forty-two (7.1%) patients presented ANOS1 mutations, including a novel splice site mutation leading to exon skipping and a novel contiguous gene deletion associated with ichthyosis. WHAT IS KNOWN ALREADY: CHH is characterized by lack of pubertal development and infertility, due to deficient production, secretion or action of GnRH, and can be associated with anosmia/hyposmia (Kallmann syndrome, KS) or with a normal sense of smell (normosmic CHH). Mutations in the anosmin-1 (ANOS1) gene are responsible for the X-linked recessive form of KS. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 42 unrelated men with CHH (20 with KS and 22 with normosmic CHH). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were screened for mutations in the ANOS1 gene by DNA sequencing. Identified mutations were further investigated by RT-PCR analysis and multiplex ligation-dependent probe amplification (MLPA) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Hemizygous mutations were identified in three (7.1%) KS cases: a novel splice acceptor site mutation (c.542-1G>C), leading to skipping of exon 5 in the ANOS1 transcript in a patient with self-reported normosmia (but hyposmic upon testing); a recurrent nonsense mutation (c.571C>T, p.Arg191*); and a novel 4.8 Mb deletion involving ANOS1 and eight other genes (VCX3B, VCX2, PNPLA4, VCX, STS, HDHD1, VCX3A and NLGN4X) in KS associated with ichthyosis. LIMITATIONS, REASONS FOR CAUTION: Objective olfactory testing was not performed in all cases of self-reported normosmia and this may have underestimated the olfactory deficits. WIDER IMPLICATIONS OF THE FINDINGS: This study further expands the spectrum of known genetic defects associated with CHH and suggests that patients with self-reported normal olfactory function should not be excluded from ANOS1 genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Portuguese Foundation for Science and Technology. The authors have no conflicts of interest.info:eu-repo/semantics/publishedVersio

Expanding the Genetic Spectrum of ANOS1 Mutations in Patients with Congenital Hypogonadotropic Hypogonadism

STUDY QUESTION: What is the prevalence and functional consequence of ANOS1 (KAL1) mutations in a group of men with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Three of forty-two (7.1%) patients presented ANOS1 mutations, including a novel splice site mutation leading to exon skipping and a novel contiguous gene deletion associated with ichthyosis. WHAT IS KNOWN ALREADY: CHH is characterized by lack of pubertal development and infertility, due to deficient production, secretion or action of GnRH, and can be associated with anosmia/hyposmia (Kallmann syndrome, KS) or with a normal sense of smell (normosmic CHH). Mutations in the anosmin-1 (ANOS1) gene are responsible for the X-linked recessive form of KS. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 42 unrelated men with CHH (20 with KS and 22 with normosmic CHH). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were screened for mutations in the ANOS1 gene by DNA sequencing. Identified mutations were further investigated by RT-PCR analysis and multiplex ligation-dependent probe amplification (MLPA) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Hemizygous mutations were identified in three (7.1%) KS cases: a novel splice acceptor site mutation (c.542-1G>C), leading to skipping of exon 5 in the ANOS1 transcript in a patient with self-reported normosmia (but hyposmic upon testing); a recurrent nonsense mutation (c.571C>T, p.Arg191*); and a novel 4.8 Mb deletion involving ANOS1 and eight other genes (VCX3B, VCX2, PNPLA4, VCX, STS, HDHD1, VCX3A and NLGN4X) in KS associated with ichthyosis. LIMITATIONS, REASONS FOR CAUTION: Objective olfactory testing was not performed in all cases of self-reported normosmia and this may have underestimated the olfactory deficits. WIDER IMPLICATIONS OF THE FINDINGS: This study further expands the spectrum of known genetic defects associated with CHH and suggests that patients with self-reported normal olfactory function should not be excluded from ANOS1 genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Portuguese Foundation for Science and Technology. The authors have no conflicts of interest.info:eu-repo/semantics/publishedVersio

Modeling electrodialysis and a photochemical process for their integration in saline wastewater treatment.

Oxidation processes can be used to treat industrial wastewater containing non-biodegradable organic compounds. However, the presence of dissolved salts may inhibit or retard the treatment process. In this study, wastewater desalination by electrodialysis (ED) associated with an advanced oxidation process (photo-Fenton) was applied to an aqueous NaCl solution containing phenol. The influence of process variables on the demineralization factor was investigated for ED in pilot scale and a correlation was obtained between the phenol, salt and water fluxes with the driving force. The oxidation process was investigated in a laboratory batch reactor and a model based on artificial neural networks was developed by fitting the experimental data describing the reaction rate as a function of the input variables. With the experimental parameters of both processes, a dynamic model was developed for ED and a continuous model, using a plug flow reactor approach, for the oxidation process. Finally, the hybrid model simulation could validate different scenarios of the integrated system and can be used for process optimization

Improving the Knowledge on Seismogenic Sources in the Lower Tagus Valley for Seismic Hazard Purposes

The Lower Tagus Valley, that includes the metropolitan area of Lisbon, has been struck by several earthquakes which produced significant material damage and loss of lives. Their exact location remains unknown. Our goal is to shed some light into the seismogenic sources in the area using seismic reflection and geological data. In areas with no seismic coverage, potential-field data interpretation was carried out. Seismicity was overlaid to the potential seismogenic structures and high-resolution data was acquired in order to confirm which structures have been active into the Quaternary. Three major fault-zones affecting the Neogene were identified: V. F. Xira, Samora-Alcochete and Pinhal Novo. For the first fault, strong evidences suggest it is active. The other two fault-zones and other structures previously unknown can be correlated with several epicentres. Empirical relationships between maximum moment magnitude and fault area indicate that MW > 6.5 earthquakes can be expected for the larger structures

Salmonelose associada ao consumo de leite e produtos lácteos.

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Provocative Tests in the Diagnosis of Childhood Onset Growth Hormone Insufficiency

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

Hypoglycemia in Pregnancy

Hypoglycemia is considered when glycemia values fall below 60 mg/dl and is associated with increased maternal-fetal morbidity and mortality. In a diabetic pregnancy this complication can result from a decrease in caloric ingestion relative to administered insulin. Hypoglycemia can present as a simple adrenergic response or as a neuroglicopenic response that can lead to maternal death and stillbirth. This is the reason why it can rapidly evolve into an obstetric emergency. It is important to possess a pre-defined protocol to guide healthcare professionals regarding the rapid management of this situation. The authors review the scientific literature on the subject of hypoglycemia in pregnancy and propose a protocol to be applied in this situation

Avaliação dos Resultados do Cross-Linking de Colagénio Corneano em Doentes com Queratocone: a Nossa Experiência

Objectivo: Avaliar os resultados visuais e queratométricos do tratamento com cross-linking de colagénio corneano (CXL) no queratocone progressivo realizado no Centro Hospitalar de Entre Douro e Vouga durante o período de 1 ano. Material e Métodos: Estudo retrospetivo no qual foram incluídos 15 olhos (15 doentes) com queratocone progressivo. Todos os pacientes foram submetidos ao tratamento com CXL com riboflavina e luz ultravioleta-A segundo o protocolo de Dresden. 8 olhos completaram 12 meses de seguimento e, 7 olhos completaram 6 meses. Avaliámos a acuidade visual com e sem correcção, cilindro refractivo e equivalente esférico, topografia corneana e paquimetria com Pentacam®, assim como os parâmetros obtidos com o Ocular Response Analyzer®. Resultados: Verificou-se uma melhoria da melhor acuidade visual corrigida média de 0.56 +/- 0.18 para 0.60 +/- 0.18 aos 3 meses, atingindo aos 6 meses 0.69, diferença estatisticamente significativa (p=0.007) e aos 12 meses 0.72 (p=0.003). Os valores do cilindro refractivo e equivalente esférico diminuíram após o procedimento mas sem significado estatístico. Em todos os olhos tratados verificou-se estabilização da progressão. A média da queratometria máxima diminui significativamente de 51.11D pré-operatório para 49.63D (p=0.002) aos 6 meses e para 50.0 D aos 12 meses (p=0.01). Conclusões: O CXL de colagénio é um tratamento promissor para o queratocone evolutivo pois permite atrasar a progressão da doença e, em alguns casos, melhorar os parâmetros visuais, refractivos e topográficos. Os nossos resultados mostram uma melhoria funcional e morfológica, com a estabilização da progressão da doença, sendo necessário, no entanto, resultados a longo prazo.info:eu-repo/semantics/publishedVersio

Hyperthyroidism in Pregnancy - Case Report

Thyroid disease is common in pregnant women.We report a 10 weeks gestation pregnancy with hyperemesis gravidarum, hypertension crisis and hyperthyroidis