X-linked adrenal hipoplasia congenita: clinical and follow-up findings of two kindreds, one with a novel NR0B1 mutation

X-linked adrenal hypoplasia congenita typically manifests as primary adrenal insufficiency in the newborn age and hypogonadotropic hypogonadism in males, being caused by mutations in NR0B1 gene. We present the clinical and follow-up findings of two kindreds with NR0B1 mutations. The proband of kindred A had a diagnosis of primary adrenal insufficiency when he was a newborn. Family history was relevant for a maternal uncle death at the newborn age. Beyond 2 year-old steroid measurements rendered undetectable and delayed bone age was noticed. Molecular analysis of NR0B1 gene revealed a previously unreported mutation (c.1084A>T), leading to a premature stop codon, p.Lys362*, in exon 1. His mother and sister were asymptomatic carriers. At 14 year-old he had 3 mL of testicular volume and biochemical surveys (LH < 0.1 UI/L, total testosterone < 10 ng/dL) concordant with hypogonadotrophic hypogonadism. Kindred B had two males diagnosed with adrenal insufficiency at the newborn age. By 3 year-old both siblings had undetectable androgen levels and delayed bone age. NR0B1 molecular analysis identified a nonsense mutation in both cases, c.243C>G; p.Tyr81*, in exon 1. Their mother and sister were asymptomatic carriers. At 14 year-old (Tanner stage 1) hypothalamic-pituitary-gonadal axis evaluation in both males (LH < 0.1UI/L, total testosterone < 10 ng/dL) confirmed hypogonadotropic hypogonadism. In conclusion, biochemical profiles, bone age and an X-linked inheritance led to suspicion of NR0B1 mutations. Two nonsense mutations were detected in both kindreds, one previously unreported (c.1084A>T; p.Lys362*). Mutation identification allowed the timely institution of testosterone in patients at puberty and an appropriate genetic counselling for relatives

Estratégias moleculares para o desenvolvimento de novos antibióticos

Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas MonizCada vez mais surgem novas estirpes bacterianas multirresistentes, resistentes ao arse-nal de antibióticos disponíveis para as combater (Huemer et al., 2020), constituindo uma das maiores ameaças para a saúde pública da atualidade (Hess, 2021). É estimado que até 2050 o número de infeções provocadas por estirpes multirresistentes ultrapassará os 10 milhões mun-dialmente e que estas levarão a um aumento significativo de mortes, ultrapassando o número de mortes provocadas por cancro (The Review, 2014). Diversos fatores podem contribuir para o desenvolvimento de resistências, como a uti-lização incorreta de antibióticos, o que inclui a utilização em excesso de antibióticos de largo espectro, a aquisição de resistências devido a transferência horizontal de genes específicos como também um processo evolutivo por parte das bactérias (Courvalin, 2016). No lado da indústria, o pipeline para novos antibióticos encontra-se escasso por diver-sos motivos, como o elevadíssimo custo de pesquisa e desenvolvimento. A ausência de novos antibióticos deixa poucas opções para o combate contra o aparecimento destas estirpes (Lewis, 2015). Por este motivo é essencial o desenvolvimento de novos antibióticos como também desenvolver estratégias para a ideação de novos antibióticos que se alarguem para além dos convencionais utilizados até hoje. Estas estratégias têm incluído a pesquisa de novos alvos terapêuticos (Lewis, 2015), a inibição dos mecanismos de resistência antibiótica microbiana (Wetzel et al., 2021), a adoção do conceito multi-target (Wetzel et al., 2021), a utilização de péptidos antimicrobianos (Bopa-rai & Sharma, 2019), o desenvolvimento de antibacterianos inorgânicos ou/e organometálicos (Hess, 2021) e a aplicação de bacteriófagos (Song & Chung, 2010).New multidrug resistant bacterial strain s are emerging , resistant to the arsenal of able antibiotics used to treat them (Huemer et al .., 2020), this constitutes one of the greatest threats to public health (Hess, 2021). It’s estimated that by 2050 the number of infections caused by multidrug resistant strains will exceed 10 million worldwide , and these will result in a significant increase in death s, surpassing the number of death s caused by cancer (The view, 2014). Several factors can contribute to the development of antibiotic resistance, like the in- correct use of antibiotics which includes the excessive use of broad spectrum antibiotics, the acquisition of resistance due to the horizontal gene transfer as well as evolutionary process es by bacteria (Courvalin, 2016). On the industry side, the pipeline for new antibiotics is scarce for several reasons, such as the extremely high cost of research and development. The absence of new antibiotics leaves few options to combat the emergence of these drug resistant strains (Lewis, 2015). For this reason, it is essential to develop new antibiotics, as well as to develop strategies for the creation of new antibiotics that go beyond the conventional ones used currently These strategies include the search for new therapeutic targets (Lewis, 2015), the inhi- bition of microbial antibiotic resistance mechanisms (Wetzel et al .., 2021), the implementation of a multi target concept (Wetzel et al .., 2021), the use of antimicrobial peptides (Boparai & Sharma, 2019), the development of inorganic and/or organometallic antibacterials (Hess, 2021) and the application of bacteriophages (Song & Chung, 2010)

Será que o perfil académico e científico dos ministros e secretários de estado da saúde europeus importa para um processo de decisão informado?

ABSTRACT - Background: The impact of health politicians’ qualifications on healthcare quality has not been widely studied. Objectives: To assess whether academic qualifications and scientific output of European health decision makers correlate with healthcare quality, as well as with other developmental and scientific indices. Methods: We assessed the academic qualifications and scientific output of health ministers and state secretaries of EU member states. Based on the highest academic degree held, we created an academic score for each politician, and calculated the average academic score of each country’s health politicians. Associations between the average academic score and public perception of healthcare quality and other developmental and scientific variables were tested by means of simple and multiple linear regression models. Results: Half of the politicians held qualifications in the field of health, followed by economics and management (37%) and social sciences (35%). Over the last 10 years, 28% politicians had authored publications indexed in Web of ScienceTM, mostly in the field of health. The average academic score of health European politicians was negatively correlated with both public perception of healthcare quality (ρ = –0.473; p = 0.011) and with countries’ gross domestic product (GDP) per capita (ρ = –0.664; p < 0.001). In a multiple linear regression model, the GDP per capita was independently and negatively associated with the average academic score (p = 0.038), but the same was not observed for the public perception of healthcare quality (p = 0.722). Conclusions: While correlation does not imply causation, in European countries with higher GDP per capita, health politicians tend to be less qualified.RESUMO - Contexto: O impacto das qualificações académicas dos decisores políticos em saúde não foi ainda amplamente estudado. Objectivos: Avaliar se o perfil académico e científico dos decisores em saúde europeus se relaciona com a qualidade de prestação de cuidados de saúde, bem como com outros índices de desenvolvimento e científicos. Métodos: Efectuámos um levantamento das qualificações académicas e da produção científica dos ministros da saúde e respectivos secretários de estado dos Estadosmembros da União Europeia. Partindo do grau académico mais elevado alcançado, construiu-se um score académico para cada político e calculou-se o score académico médio para cada país. Foram construídos modelos de regressão linear para avaliar associações entre o score académico médio e a percepção pública da qualidade da prestação de cuidados de saúde e outras variáveis de desenvolvimento e científicas. Resultados: Metade dos políticos apresentavam qualificações académicas na área da saúde, seguindo-se economia e gestão (37%), e ciências sociais (35%). Nos últimos 10 anos, 28% dos políticos publicaram em revistas indexadas na Web of ScienceTM, a maioria na área da saúde. O score académico médio dos políticos Europeus em saúde correlaciona-se negativamente quer com a percepção pública da qualidade dos cuidados de saúde prestados (ρ = –0.473; p = 0.011) quer com o Produto Interno Bruto (PIB) per capita (ρ = –0.664; p < 0.001) do respectivo país. No modelo de regressão linear múltipla, o PIB per capita demonstrou uma associação negativa independente com o score académico médio (p = 0.038), mas o mesmo não foi observado para a percepção pública da qualidade da prestação de cuidados de saúde (p = 0.722). Conclusões: Embora correlação não implique causalidade, nos países Europeus com PIB per capita mais elevado, os decisores políticos em saúde tendem a apresentar menos qualificações académicas.info:eu-repo/semantics/publishedVersio

Coincidence or correlation?

Rationale:Multiple Endocrine Neoplasia type 1 (MEN1) is a familial syndrome that results from the disruption of a tumor suppressor protein called MENIN. Its management is challenging, as MEN1 affects different endocrine tissues and predisposes to both benign and malignant tumors. MENIN-deficient cells have recently been recognized to play a role in triggering autoimmunity. Herein, we present a case of MEN1 with multiple endocrine and autoimmune disorders.Patient concerns:A 50 years old female with a 25 years history of complicated nephrolithiasis presented with primary hyperparathyroidism.Diagnoses:Over several decades, she was diagnosed with recurrent primary hyperparathyroidism, autoimmune thyroiditis, multinodular goiter, pernicious anemia, metastatic gastric type 1 neuroendocrine tumor, macroprolactinemia, gonadotropin deficiency, mucosa-associated lymphoid tissue lymphoma of the thyroid gland, positive anti-calcium sensor receptor antibodies, and BRCA 1/2-negative invasive breast cancer. The autoimmune regulator gene was sequenced, but no pathogenic variants were found. Next-generation sequencing revealed both a pathogenic MEN1 mutation and a benign CDC73 gene variant. Familial genetic screening revealed a large kindred with multiple carriers of one or both genetic variants (MEN1 = 19; CDC73 = 7).Interventions:The patient underwent surgical excision of three parathyroid glands, total thyroidectomy and breast tumorectomy plus tamoxifen, and monthly injections of octreotide. The patient and family members with the MEN1 mutation are under a life-long surveillance program for MEN1 prototypic tumors.Outcomes:The patient was stable and alive during a 24-years follow-up period.Lessons:With the present case, the authors highlight a new interplay between MENIN and the immune system, which may have implications for future targeted life-long surveillance and treatment of MEN1 patients.publishersversionpublishe

Local regulation of antral follicle development and ovulation in monovulatory species

The identification of mutations in the genes encoding bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) associated with phenotypes of sterility or increased ovulation rate in sheep aroused interest in the study of the role of local factors in preantral and antral folliculogenesis in different species. An additive mutation in the BMP15 receptor, BMPR1b, which determines an increase in the ovulatory rate, has been introduced in several sheep breeds to increase the number of lambs born. Although these mutations indicate extremely relevant functions of these factors, the literature data on the regulation of the expression and function of these proteins and their receptors are very controversial, possibly due to differences in experimental models. The present review discusses the published data and preliminary results obtained by our group on the participation of local factors in the selection of the dominant follicle, ovulation, and follicular atresia in cattle, focusing on transforming growth factors beta and their receptors. The study of the expression pattern and the functionality of proteins produced by follicular cells and their receptors will allow increasing the knowledge about this local system, known to be involved in ovarian physiopathology and with the potential to promote contraception or increase the ovulation rate in mammals

Estudo epidemiológico das doenças neurodegenerativas na Região da Guarda - Portugal

The aim was to characterize the population with neurodegenerative diseases in the region of Guarda. An epidemiological, descriptive, cross-sectional study was carried out of the user population of the Local Health Unit of Guarda, EPE, located in the Central Region of Portugal, with an active diagnosis of neurodegenerative disease, according to the International Classification of Primary Health Care - ICPC-2 : P70 - Dementia, N86 - Multiple Sclerosis - and N87 - Parkinsonism. The data source was the Regional Health Administrations Information System (SIARS), and the sample consisted of 2500 people with neurodegenerative disease. Dementia is the most prevalent of these diseases (62%), followed by Parkinsonism (32%). The proportion of active diagnoses was 1.66%. Most are women (66%), the average age is 79 (± 11.99) years, with a range of 92 years, minimum 19 and maximum 111 years. The characterization of the population with an active diagnosis of neurodegenerative diseases proves to be an important contribution to delineating specific and targeted intervention strategies for the target population and, thus, proceeding with the study of the quality of life of people with neurodegenerative diseases and their families.Objetivou-se caracterizar a população portadora de doenças neurodegenerativas da Região da Guarda. Realizou-se um estudo epidemiológico, descritivo, transversal da população utilizadora da Unidade Local de Saúde da Guarda, EPE, localizada na Região Centro de Portugal, com diagnóstico ativo de doença neurodegenerativa, segundo a Classificação Internacional de Cuidados de Saúde Primários – ICPC-2: P70 - Demência, N86 - Esclerose Múltipla - e N87 - Parkinsonismo. A fonte de dados foi o Sistema de Informação das Administrações Regionais de Saúde (SIARS), sendo a amostra constituída por 2500 pessoas portadoras de doença neurodegenerativa. A Demência é a mais predominante dessas doenças (62%), seguida do Parkinsonismo (32%). A proporção de diagnósticos ativos foi 1,66%.&nbsp; A maioria são mulheres (66%), a média de idades situa-se nos 79 (± 11,99) anos, com uma amplitude de 92 anos, mínimo 19 e máximo 111 anos. A caracterização da população com diagnóstico ativo de doenças neurodegenerativas, revela-se um importante contributo para delinear estratégias de intervenção especificas e direcionadas para a população-alvo e, assim, prosseguir para o estudo da qualidade de vida da pessoa portadora de doença neurodegenerativa e família

Estudo epidemiológico das doenças neurodegenerativas na Região da Guarda - Portugal

The aim was to characterize the population with neurodegenerative diseases in the region of Guarda. An epidemiological, descriptive, cross-sectional study was carried out of the user population of the Local Health Unit of Guarda, EPE, located in the Central Region of Portugal, with an active diagnosis of neurodegenerative disease, according to the International Classification of Primary Health Care - ICPC-2 : P70 - Dementia, N86 - Multiple Sclerosis - and N87 - Parkinsonism. The data source was the Regional Health Administrations Information System (SIARS), and the sample consisted of 2500 people with neurodegenerative disease. Dementia is the most prevalent of these diseases (62%), followed by Parkinsonism (32%). The proportion of active diagnoses was 1.66%. Most are women (66%), the average age is 79 (± 11.99) years, with a range of 92 years, minimum 19 and maximum 111 years. The characterization of the population with an active diagnosis of neurodegenerative diseases proves to be an important contribution to delineating specific and targeted intervention strategies for the target population and, thus, proceeding with the study of the quality of life of people with neurodegenerative diseases and their families.Objetivou-se caracterizar a população portadora de doenças neurodegenerativas da Região da Guarda. Realizou-se um estudo epidemiológico, descritivo, transversal da população utilizadora da Unidade Local de Saúde da Guarda, EPE, localizada na Região Centro de Portugal, com diagnóstico ativo de doença neurodegenerativa, segundo a Classificação Internacional de Cuidados de Saúde Primários – ICPC-2: P70 - Demência, N86 - Esclerose Múltipla - e N87 - Parkinsonismo. A fonte de dados foi o Sistema de Informação das Administrações Regionais de Saúde (SIARS), sendo a amostra constituída por 2500 pessoas portadoras de doença neurodegenerativa. A Demência é a mais predominante dessas doenças (62%), seguida do Parkinsonismo (32%). A proporção de diagnósticos ativos foi 1,66%.&nbsp; A maioria são mulheres (66%), a média de idades situa-se nos 79 (± 11,99) anos, com uma amplitude de 92 anos, mínimo 19 e máximo 111 anos. A caracterização da população com diagnóstico ativo de doenças neurodegenerativas, revela-se um importante contributo para delinear estratégias de intervenção especificas e direcionadas para a população-alvo e, assim, prosseguir para o estudo da qualidade de vida da pessoa portadora de doença neurodegenerativa e família

A New Perspective for Vineyard Terroir Identity: Looking for Microbial Indicator Species by Long Read Nanopore Sequencing

Grapevine is one of the most important fruit crops worldwide, being Portugal one of the top wine producers. It is well established that wine sensory characteristics from a particular region are defined by the physiological responses of the grapevine to its environment and thus, the concept of terroir in viticulture was established. Among all the factors that contribute to terroir definition, soil microorganisms play a major role from nutrient recycling to a drastic influence on plant fitness (growth and protection) and of course wine production. Soil microbiome from four different terroirs in Quinta dos Murças vineyard was analysed through long-read Oxford Nanopore sequencing. We have developed an analytical pipeline that allows the identification of function, ecologies, and indicator species based on long read sequencing data. The Douro vineyard was used as a case study, and we were able to establish microbiome signatures of each terroir.info:eu-repo/semantics/publishedVersio