Bartter Syndrome Presenting as Arginine-Vasopressin Resistance: A Report of 2 Cases.

BACKGROUND Bartter syndrome is a rare, inherited salt-wasting tubulopathy caused by mutations in 1 of 6 genes that express ion transport channels in the thick ascending limb of nephrons. Excessive prostaglandin E2 and associated hyperreninemic hyperaldosteronism occurs, causing polyhydramnios, polyuria, prematurity, failure to thrive, and characteristic physical features. Hypokalemia, hypochloremic metabolic alkalosis, and, depending on the affected gene, hypercalciuria and nephrocalcinosis are hallmarks of Bartter syndrome. CASE REPORT A 9-month-old male infant, born prematurely due to polyhydramnios, presented in the Emergency Department with dehydration due to incoercible vomiting and significant polyuria. A 6-year-old male infant with a previous history of prematurity due to polyhydramnios was referred to the Pediatric Endocrinology Department due to short stature and notable polydipsia and polyuria. Considering these marked symptoms, both cases triggered suspicion and started workup for arginine-vasopressin insufficiency/resistance. However, during the investigations, a broader clinical revision revealed that both had dysmorphic physical features (triangularly shaped face, prominent forehead, protruding ears, drooping mouth), poor growth, impaired weight gain, and typical biochemical findings (hypokalemic metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism) of Bartter syndrome. Genetic testing confirmed the diagnosis of Bartter syndrome types 1 and type 2, respectively, and this diagnosis allowed proper treatment and significant clinical improvements, personalized follow-up, and genetic counseling for parents desiring further healthy pregnancies. CONCLUSIONS Here, we present clinical and follow-up findings of 2 patients with Bartter syndrome types 1 and 2 discovered upon a broader clinical revision of suspected arginine-vasopressin insufficiency/resistance. We also review pertinent data on diagnosis and management of this challenging syndrome.

Heterologous expression of fungal L-asparaginase: a systematic review.

Aim: To review the available literature about heterologous expression of fungal L-asparaginase (L-ASNase). Materials & methods: A search was conducted across PubMed, Science Direct, Scopus and Web of Science databases; 4172 citations were identified and seven articles were selected. Results: The results showed that heterologous expression of fungal L-ASNase was performed mostly in bacterial expression systems, except for a study that expressed L-ASNase in a yeast system. Only three publications reported the purification and characterization of the enzyme. Conclusion: The information reported in this systematic review can contribute significantly to the recognition of the importance of biotechnological techniques for L-ASNase production.

Asparaginase is a common treatment for the most common type of leukemia in children. These treatments generally use asparaginase sourced from bacteria. Some people can experience bad reactions to these treatments. One way that has been explored to avoid this is to use asparaginase sourced from fungi because they are more similar to humans. However, fungi produce less asparaginase than bacteria. This review looks into ways that the production of fungal asparaginases can be made more productive.

Thermoluminescence Studies of Proton-Irradiated Cr-, Mg-Codoped ß-Ga2O3.

Chromium-doped Ga2O3, with intense Cr3+-related red-infrared light emission, is a promising semiconductor material for optical sensors. This work constitutes a comprehensive study of the thermoluminescence properties of Cr-, Mg-codoped ß-Ga2O3 single crystals, both prior to and after proton irradiation. The thermoluminescence investigation includes a thorough analysis of measurements with different ß- irradiation doses used to populate the trap levels, with preheating steps to disentangle overlapping peaks (TM-TSTOP and initial rise methods) and finally by computationally fitting to a theoretical expression. At least three traps with activation energies of 0.84, 1.0, and 1.1 eV were detected. By comparison with literature reports, they can be assigned to different defect complexes involving oxygen vacancies and/or common contaminants/dopants. Interestingly, the thermoluminescence signal is enhanced by the proton irradiation while the type of traps is maintained. Finally, the pristine glow curve was recovered on the irradiated samples after an annealing step at 923 K for 10 s. These results contribute to a better understanding of the defect levels in Cr-, Mg-codoped ß-Ga2O3 and show that electrons released from these traps lead to Cr3+-related light emission that can be exploited in dosimetry applications.

Rare earth elements as statistical sentinels of pollution and paleoenvironments?: Application to a highly polluted estuary in southwestern Spain.

Multivariate analyses have been applied to the REE contents of three cores collected in the Tinto estuary, SW Spain, an extremely polluted area. Results indicate an extremely correlation between all REE, which behave as a single variable. A slight natural pollution peak and three anthropogenic pollution peaks are identified, related with the first mining activities, the Roman period and a recent intensive mining accompanied by a heavy industrial pollution. In all these peaks, the increase of Cu is parallel to that of MREE, which are configured as the best indicators of pollution among REE. Statistical analyses clearly differentiate four groups, each consisting of samples from different environments. Although grain size and this strong pollution alter the study of REE as environmental indicators, it is possible to recognise groups of samples with a common origin or to identify the surface extent of a given pollution peak.

Quality of Life, Sexual Functioning and Chronic Disease: A Comparative Study with Portuguese Women without Chronic Disease, and Women with Diabetes Type 1 and 2, and Arterial Hypertension.

Aims: Previous research has focused on the impact of chronic diseases on men's sexual functioning and quality of life; however, little is known about the association between chronic disease and women's sexual functioning and quality of life. Current study aimed at exploring the differences in quality of life and sexual functioning between women without chronic disease, and women with type 1 diabetes, with type 2 diabetes, and with arterial hypertension. Methods: A web-survey was completed by 313 Portuguese women (167 without chronic disease, 48 with type 1 diabetes, 48 with type 2 diabetes, and 50 with arterial hypertension). Results: Women without chronic disease scored significantly higher than women with chronic disease in quality of life and sexual functioning, adjusting for age. Conclusions: Quality of life and sexual functioning in women with chronic diseases is impaired.

Utilização da cirurgia de mohs no tratamento de neoplasias malignas não melanocíticas da pele ­ uma revisão sistemática / Mohs micrographic surgery in the treatment of non-melanocytic skin neoplasms ­ a systematic review

Objetivo: Averiguar a efetividade da utilização da cirurgia de MOHS no manejo de tumores cutâneos tipo não melanoma em comparação a outros métodos de terapia. Métodos: O estudo consiste em uma revisão sistemática, cuja coleta de artigos ocorreu nas bases de dados MEDLINE, PubMed Central (PMC), LILACS e SciELO, utilizando os termos "Cirurgia de MOHS", "Câncer de pele", "Ensaio clínico", excluindo "melanoma". Resultados: Do total de 132 artigos identificados, foram considerados elegíveis 11. A análise dos artigos demonstrou que a CMM, comparada a outros métodos, apresentou resultados estéticos melhores, além de menor grau de complicações em tumores recorrentes e um custo/benefício variável com o país onde foi feita operação. A CMM também apresentou menores índices de recorrência em todos os estudos. Conclusão: No geral, a cirurgia de MOHS se mostrou um método terapêutico promissor. No entanto, existem ainda poucos estudos comparativos sobre a eficácia da CMM e os que existem se concentram em poucas regiões do mundo. (AU)

Objective: Evaluating the effectiveness of using MOHS surgery in the management of non-melanoma skin tumors compared to other therapy methods. Methods: The study consists of a systematic review, whose search for articles was performed using databases MEDLINE, PubMed Central (PMC), LILACS and SciELO, using the terms "MOHS surgery", "Skin cancer", "Clinical trial", excluding "melanoma". Results: from a total of 132 identified articles, 11 were considered eligible. The analysis of the articles showed that MMS, compared to other methods, presented better cosmetic results, in addition to a lower grade of complications in recurrent tumors and a variable cost/benefit according to the country where the surgery was performed. MMS also had lower recurrence rates in all studies. Conclusion:Overall, MOHS surgery has shown promising therapeutic results. However, there are still few comparative studies on the effectiveness of MMS and those that exist are concentrated in a few regions of the world. (AU)

Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients.

BACKGROUND: The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype-phenotype correlations. RESULTS: The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants. CONCLUSION: The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.

Acrodermatitis dysmetabolica as a sign of methylmalonic aciduria decompensation.

Methylmalonic aciduria children must follow an adequate diet with low protein intake and should be regularly monitored to prevent complications. Although skin lesions like acrodermatitis enteropathica are rare in this disease, their appearance should be correlated with possible low plasma isoleucine level and it can be a sign of decompensation.

Outbreak of laboratory-acquired Brucella abortus in Brazil: a case report

Human brucellosis is an occupational disease affecting workers in slaughterhouses, butcher shops and the milk and dairy product industry as well as individuals who work in clinical or research laboratories. We report the first outbreak of a Brucella abortus infection in a Brazilian laboratory and compare the data obtained with reports available in the literature. Exposure was a result of damage to a biological safety cabinet and failure of the unidirectional airflow ventilation system. An epidemiological investigation identified 3 seroconverted individuals, 1 of whom had clinical manifestations and laboratory results compatible with infection at the time of exposure (n=11; attack rate=9.1%).

A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract.

BACKGROUND: Although thyroid dysgenesis is the most common cause of congenital hypothyroidism (CH), its molecular basis remains largely elusive. Indeed, in only a minority of cases with thyroid dysgenesis (2%-3%) was it possible to identify an underlying genetic defect. The objective of this study was to screen the PAX8 gene and the PAX2 gene in a family with six cases of CH spanning three generations and presenting urogenital malformations. Herein, we report a case series and in vitro characterization of the PAX8 gene mutation. METHODS: Investigations were conducted at a tertiary care referral center. The index case was diagnosed to have congenital hypothyroidism at 7 months of age when he presented with severe impairment of suckling, constipation, and poor development. Treatment with levothyroxine corrected the symptoms and was associated with catch-up growth. His progeny, including two sons, one daughter, and two granddaughters, were affected by CH, and three of them received the diagnosis at neonatal screening. Ultrasound demonstrated normally located thyroid glands with reduced volumes. Five of the six affected family members, including the index case, had urogenital malformations, including incomplete horseshoe kidney, undescended testicles, hydrocele, and ureterocele. Strabismus was found in three out of six affected patients. No other somatic malformations were found. RESULTS: Direct sequencing of the PAX8 gene revealed a new heterozygous mutation (c.74C > G) in all affected individuals. This mutation leads to substitution of proline with arginine at codon 25 (P25R). Fluorescence microscopy showed that P25R is normally located in the nucleus. In transient transfection studies, this mutation causes reduced transcriptional activation ability when using a luciferase reporter construct under the control of a thyroglobulin promoter. This diminished transactivation ability is due to loss of DNA binding capability as shown in electrophoresis mobility shift assay. The sequencing analysis of the PAX2 gene was normal. CONCLUSIONS: We conclude that this novel PAX8 mutation is responsible for a severe form of dominantly inherited CH. The mutation seems to be associated with abnormalities of the urogenital tract.

Outbreak of laboratory-acquired Brucella abortus in Brazil: a case report.

Human brucellosis is an occupational disease affecting workers in slaughterhouses, butcher shops and the milk and dairy product industry as well as individuals who work in clinical or research laboratories. We report the first outbreak of a Brucella abortus infection in a Brazilian laboratory and compare the data obtained with reports available in the literature. Exposure was a result of damage to a biological safety cabinet and failure of the unidirectional airflow ventilation system. An epidemiological investigation identified 3 seroconverted individuals, 1 of whom had clinical manifestations and laboratory results compatible with infection at the time of exposure (n=11; attack rate=9.1%).

[Eosinophilic esophagitis: clinical expression at pediatric age]. / Esofagite eosinofílica: diversidade de expressão clínica em idade pediátrica.

Eosinophilic esophagitis is an emerging chronic oesophageal inflammatory disease, increasingly recognized both in children and in adults. It is presently accepted that this entity has a chronic course with persistent or relapsing symptoms and a wide range of clinical manifestations at different age groups: in children it is responsible for feeding disorders, vomiting or abdominal pain; in teenagers and adults it causes dysphagia and oesophageal food impaction. The etiopathogenesis of eosinophilic esophagitis has not been yet well established, but immuno-allergic mechanisms associated with a Th2 immune response have been proposed. Diagnosis is based both on clinical and histological grounds, requiring that oesophageal mucosal biopsy specimens obtained from different oesophageal locations contain more than 15 intraepithelial eosinophils per high power field and the exclusion of gastroesophageal reflux disease. Currently proposed effective treatments rely on eviction of putative allergens through dietary exclusion and on treatment with swallowed steroids. We describe two cases (a young child and a teenager) illustrative of the clinical spectrum and course variability of eosinophilic esophagitis at pediatric age. A brief review of current knowledge concerning this puzzling clinical entity is presented, emphasizing specific diagnostic dilemmas and questions concerning its long-term follow-up.