Disorders of Sex Development of Adrenal Origin

Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.Fil: Finkielstain, Gabriela Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Vieites, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

Caracterização morfológica dos otólitos sagitta das espécies portuguesas da família Triglidae

Tese de mestrado. Biologia (Ecologia Marinha). Universidade de Lisboa, Faculdade de Ciências, 2013Desde há várias décadas, vários autores têm usado as características morfológicas dos otólitos sagitta dos peixes para inferir relações de proximidade ou distanciamento filogenético entre taxa, confirmando ou propondo alterações, mais ou menos drásticas, às classificações vigentes. O presente trabalho tem como alvo as espécies Nordeste Atlânticas da família Triglidae, cuja sistemática tem estado envolta numa certa controvérsia. Com este estudo pretende-se verificar se a caracterização e descrição morfológica detalhada dos otólitos sagitta das espécies em causa fornecem suporte para corroborar alguma das classificações existentes ou apresentar uma alternativa. Com este objectivo em vista, efectua-se uma caracterização e descrição detalhadas dos otólitos sagitta das oito espécies portuguesas da família Triglidae (Chelidonichthys cuculus, Chelidonichthys lucernus, Chelidonichthys obscurus, Eutrigla gurnardus, Lepidotrigla cavillone, Lepitotrigla dieuzeidei, Trigla lyra e Trigloporus lastoviza) com o intuito de determinar a extensão da variabilidade intraespecífica e se a mesma permite a identificação segura das espécies com base na caracterização morfológica dos seus otólitos. O teste de Qui-quadrado permitiu a identificação imediata de algumas características diagnosticantes das espécies C. lucernus, E. gurnardus, L. cavillone e T. lyra e uma Análise de Correspondências Múltiplas (ACM) permitiu determinar as combinações de características que diagnosticam as restantes quatro espécies em estudo. Do estudo realizado conclui-se, através de um caso prático, que a morfologia dos otólitos é uma ferramenta muito útil na identificação de indivíduos até à espécie e na inferência de relações filogenéticas entre eles.Since several decades ago, many authors have used the morphological characteristics of the otoliths sagitta of fish to infer proximity or phylogenetic relationships between taxa, confirming or proposing more or less drastic changes in the current classifications. This work targets the Northeast Atlantic species of the family Triglidae, which have been systematically involved in some controversy. This study intends to verify if the characterization and detailed morphological description of the otoliths sagitta of the species concerned provides support to corroborate some of the existing classifications or to propose an alternative arrangement for the species of the family. With this in mind, a detailed description and characterization of the sagitta otoliths of the eight Portuguese species of the Triglidae family (Chelidonichthys cuculus, Chelidonichthys lucernus, Chelidonichthys obscurus, Eutrigla gurnardus, Lepidotrigla cavillone, Lepitotrigla dieuzeidei, Trigla lyra and Trigloporus lastoviza) is made, in order to determine the extent of intraspecific variability and if it allows a reliable identification of species based on the morphological characterization of their otoliths. The Chi-square test immediately allowed the identification of some diagnostic features of the species C. lucernus, E. gurnardus, L. cavillone and T. lyra and a Multiple Correspondence Analysis (MCA) test allowed the determination of characteristic combinations that diagnose the remaining four species under study. In general it can be concluded that the morphology of otoliths is a useful tool in the identification of individuals down to species and in the inference of phylogenetic relations among them

Caracterización de la respuesta citotóxica de la pectenotoxina-2 (PTX-2) en dos modelos celulares humanos: células de neuroblastoma y células Caco-2

[ESP] La presencia de pectenotoxinas (PTX) en los moluscos fue descubierta debido a su elevada toxicidad aguda en el bioensayo en ratón mediante inyección intraperitoneal de extractos lipofílicos. Los estudios en animales indican que son mucho menos potentes vía oral y que no inducen diarrea. En este trabajo, hemos caracterizado la respuesta citotóxica de la PTX-2 in vitro en dos líneas celulares, las células de Caco-2 y las células de neuroblastoma, incluyendo marcadores de citotoxicidad y de apoptosis. Hemos evaluado los potentes cambios estructurales que provoca la PTX-2 sobre ambos modelos celulares, el desprendimiento del sustrato, el redondeamiento celular y los cambios en el citoesqueleto, así como la integridad de la membrana plasmática que no se ve afectada por la PTX-2 en ninguna de las líneas celulares estudiadas. Por otro lado, hemos abordado el estudio de distintos marcadores de apoptosis: potencial de membrana de mitocondria, fragmentación del DNA y activación de caspasas. Entre ellos el que más se ve afectado por el tratamiento celular con la PTX-2 es el potencial de membrana de mitocondria, mientras que otros marcadores o no se ven afectados o el efecto es poco relevante.Este trabajo se financió con fondos de los proyectos AGL-2004- 08268-C02-01/ALI y REN-2003-06598-C02-02 del Ministerio de Ciencia y Teconologí

Disminución del contenido en ácido domoico en vieiras (Pecten maximus) mediante un proceso fácilmente aplicable en la industria transformadora

[ESP] La incidencia económica de las mareas rojas con toxicidad ASP (Amnesic Shellfish Poisoning) es especialmente trágica en el sector de la vieira (Pecten maximus) debido a su baja tasa de detoxificación natural. El ácido domoico se acumula mayoritariamente en el hepatopáncreas de este molusco. Por ello, la normativa comunitaria actual permite la ablación del hepatopáncreas para disminuir la toxicidad, si bien exige garantías de que este procedimiento consiga disminuir la concentración de toxina en la parte comestible hasta niveles tolerables. Por otra parte, existe normativa específica para la disminución de la toxicidad PSP (Paralytic Shellfish Poisoning) en el corruco o langostillo (Acanthocardia tubercu- latum). En este trabajo hemos estudiado el efecto de la combinación de ambos procedimientos sobre la toxicidad ASP en vieiras. Los resultados obtenidos sugieren que la combinación de ambos métodos es más efectiva que la ablación por sí sola y que puede suponer una alternativa para disminuir el efecto económico negativo de la toxicidad ASP sobre el sector de la vieira.Este trabajo se financió con los fondos del proyecto PGIDIT06RMA00804CT de la Xunta de Galicia

Pheochromocytoma: new insights in diagnosis and monitoring

La hipertensión arterial es una patología de menor frecuencia en pediatría que en la edad adulta, sin embargo existen diversas etiologías que la pueden originar y es fundamental realizar diagnóstico certero de las mismas. El feocromocitoma es un tumor endócrino, originado en el tejido cromafin y constituye una importante causa de hipertensión secundaria. Puede ser esporádico o formar parte de diversos síndromes familiares, como la enfermedad de von Hippel Lindau, la Neoplasia Endócrina Múltiple tipo 2, los síndromes de Feocromocitoma/ Paraganglioma Familiar tipo 1, 2, 3 y 4, y la Neurofibromatosis tipo 1. Además, en la actualidad se han descrito más de 15 genes susceptibles que han sido implicados en casos familiares. Siendo tumores altamente heredables, se recomienda realizar pruebas genéticas en todos los pacientes, incluso en aquellos con una historia familiar comprobable. El diagnóstico de la enfermedad hereditaria mejora la atención del paciente y permite el diagnóstico precoz en familiares.Arterial hypertension is a less frequent condition in paediatrics than in adulthood, but due to the high proportion of secondary causes, the search for the aetiology is crucial for an adequate diagnosis and treatment. Pheochromocytoma is an endocrine tumor originated in the chromaffin tissue. It is an important cause of secondary hypertension. It can be sporadic or part of several hereditary syndromes, such as von Hippel Lindau disease, Multiple Endocrine Neoplasia type 2, Pheochromocytoma/Familiar Paraganglioma syndromes type 1, 2, 3 and 4, and type 1 Neurofibromatosis. In addition, more than 15 susceptible genes have been described in familial pheochromocytoma. Being highly heritable tumors, genetic testing of tumor susceptibility is recommended in all patients, even in absence of a family history. The diagnosis of the hereditary disease improves the patient’s attention and allows early diagnosis in relatives.Fil: Vieites, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Sanso, Elsa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Barontini, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

A narrative video game for adults with subjective and objective cognitive impairment. Design and preliminary results on user-interaction and efficacy

The design of a narrative video game for cognitive training of memory and executive functions in older adults with subjective and objective cognitive impairment is reported along with preliminary results on preferences (Study 1), user interaction experience (Study 2), and efficacy of the game (Study 3). A study of aesthetic preferences in backgrounds and avatars was implemented in 13 older adults, who were asked for their opinion on the acceptability of the plot. After completion of the design, a user interaction study was conducted in a sample of 19 older adults. In addition, a Matched Paired Experimental Design (MPED) was implemented as a preliminary test of the efficacy of the narrative video game in a sample of 22 participants with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Preferences for free violence content in videogames was supported in our sample of low-frequency adult gamers and acceptability of the plot was high. The video game was rated favourably by the older adults in terms of user preferences and acceptability. The results of the preliminary MPED study suggest that the video game could be a useful tool for cognitive training in SCD and MCI older adults.This work was financially supported through FEDER founds (‘A way to make Europe’) by the Spanish AEI (Doi: 10.13039/501100011033; Refs. PID2020-114521RB-C21 and PSI2017-89389-C2-1-R) and by the Galician Government (Consellería de Cultura, Educación e Ordenación Universitaria; axudas para a consolidación e estruturación de unidades de investigación competitivas do Sistema Universitario de Galicia; GI-1807-USC: Ref. ED431C 2021/04).S

Impact of the COVID-19 Lockdown on a Long-Term Care Facility: The Role of Social Contact

(1) Background: Long-term care facilities (LTCFs) have been harmed by the coronavirus, and older adults have remained isolated for a long time with many restrictions. The aim of this study was to measure the decline in cognitive, functional, and affective status in a care facility after the lockdown in the first wave of the COVID-19 pandemic and to compare it with previous measures in order to determine if this decline was accelerated. (2) Methods: Ninety-eight participants were recruited. Data from three retrospective pre-lockdown assessments and an additional post-lockdown assessment were analyzed. Mixed ANOVA analyses were performed according to the Clinical Dementia Rating levels, considering social-contact frequency during the lockdown as a covariate. (3) Results: The cognitive and functional scores were lower and depression scores were higher after the strict lockdown, accelerating a general pattern of decline that was already present in LTCF residents. The frequency of social contact eliminated the measurement differences in the cognitive and functional scores and the group differences in depression scores. (4) Conclusions: The effects of the SARS-CoV-2 lockdown in an LTCF were mediated by the frequency of contact. Clinical implications: Preventive measures must be taken to ensure social contact with relatives and friends and reduce the negative consequences of social isolation in LTCFsS

Does empirically derived classification of individuals with subjective cognitive complaints predict dementia?

Background: Early identification of mild cognitive impairment (MCI) in people reporting subjective cognitive complaints (SCC) and the study of progression of cognitive decline are important issues in dementia research. This paper examines whether empirically derived procedures predict progression from MCI to dementia. (2) Methods: At baseline, 192 participants with SCC were diagnosed according to clinical criteria as cognitively unimpaired (70), single-domain amnestic MCI (65), multiple-domain amnestic MCI (33) and multiple-domain non-amnestic MCI (24). A two-stage hierarchical cluster analysis was performed for empirical classification. Categorical regression analysis was then used to assess the predictive value of the clusters obtained. Participants were re-assessed after 36 months. (3) Results: Participants were grouped into four empirically derived clusters: Cluster 1, similar to multiple-domain amnestic MCI; Cluster 2, characterized by subjective cognitive decline (SCD) but with low scores in language and working memory; Cluster 3, with specific deterioration in episodic memory, similar to single-domain amnestic MCI; and Cluster 4, with SCD but with scores above the mean in all domains. The majority of participants who progressed to dementia were included in Cluster 1. (4) Conclusions: Cluster analysis differentiated between MCI and SCD in a sample of people with SCC and empirical criteria were more closely associated with progression to dementia than standard criteria.This work was financially supported by the Spanish Directorate General of Scientific and Technical Research (Project PSI2014- 55316-C3-1-R) and by the Galician Government (Consellería de Cultura, Educación e Ordenación Universitaria; axudas para a consolidación e Estruturación de unidades de investigación competitivas do Sistema universitario de Galicia; GRC (GI-1807-USC); Ref: ED431-2017/27) through FEDER fundsS

VHL-P138R and VHL-L163R Novel Variants: Mechanisms of VHL Pathogenicity Involving HIF-Dependent and HIF-Independent Actions

The von Hippel–Lindau (VHL) disease is an autosomal dominant cancer syndrome caused by mutations in the VHL tumor suppressor gene. VHL protein (pVHL) forms a complex (VBC) with Elongins B-C, Cullin2, and Rbx1. Although other functions have been discovered, the most described function of pVHL is to recognize and target hypoxia-inducible factor (HIF) for degradation. This work comprises the functional characterization of two novel variants of the VHL gene (P138R and L163R) that have been described in our center in patients with VHL disease by in vitro, in vivo, and in silico approaches. In vitro, we found that these variants have a significantly shorter half-life compared to wild-type VHL but still form a functional VBC complex. Altered fibronectin deposition was evidenced for both variants using immunofluorescence. In vivo studies revealed that both variants failed to suppress tumor growth. By means of molecular dynamics simulations, we inspected in silico the nature of the changes introduced by each variant in the VBC complex. We have demonstrated the pathogenicity of P138R and L163R novel variants, involving HIF-dependent and HIF-independent mechanisms. These results provide the basis for future studies regarding the impact of structural alterations on posttranslational modifications that drive pVHL’s fate and functions.Fil: Mathó Pacielo, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Fernández, María Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Bonanata, Jenner. Universidad de la República; UruguayFil: Liu, Xian-De. Md Anderson Cancer Center ; University Of Texas;Fil: Martin, Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Vieites, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Sanso, Elsa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Barontini, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Jonasch, Eric. Md Anderson Cancer Center ; University Of Texas;Fil: Coitiño, E. Laura. Universidad de la Republica; UruguayFil: Pennisi, Patricia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin