Congenital iodide transport defect: recent advances and future perspectives

Iodide is an irreplaceable component of thyroid hormones; therefore, a key requirement for thyroid hormone synthesis is that iodide is actively accumulated in the thyroid. The ability of thyroid follicular cell to concentrate iodide relies on the functional expression of the sodium/iodide symporter (SIS) at the plasma membrane. Underscoring the significance of SIS for thyroid physiology, naturally occurring loss-of-function SIS mutations cause iodide transport defect (ITD) autosomalrecessive disorders in which iodide accumulation is severely or totally impaired, leading to dyshormonogenic congenital hypothyroidism. Up to date, sixteen different loss-of-function mutations in the gene encoding SIS have been reported. Surprisingly, marked clinical heterogeneity between patients harboring the different (or even the same) SIS mutation without a clear genotype–phenotype correlation has been observed. Residual mutant SIS activity and iodide intake levels have been proposed to explain the difference in the age of onset on hypothyroidism and the development of goiter. Significantly, genetic screening is highly recommended in patients with severely reduced radioiodide accumulation even in the absence of goiter. The identification of mutations in SIS may allow subsequent preclinical diagnoses of younger members of the family as patients with delayed onset on hypothyroidism had already signs of developmental delay at time of diagnosis. Moreover, iodide supplementation can improve thyroid function in patients with residual SIS activity and should be considered. This review summarizes the current knowledge regarding the molecular basis of ITD, as well as the clinical and biochemical presentation of patients with ITD. Moreover, we explore the latest advances in the molecular characterization of ITD-causing slc5a5 mutants whose study has yielded invaluable information into the molecular mechaSISm of SIS and the perspectives of understanding naturally occurring SIS mutants to improve radioiodide therapy in thyroid cancer as well as SIS-based gene therapy.Fil: Martín, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Validation of a new portable metabolic system during an incremental running test

We tested a new portable metabolic system, the Jaeger Oxycon Mobile (OM) at a range of running speeds. Six subjects carried out, in random order, two incremental tests on a treadmill, one of them using the OM, and the other using the Jaeger Oxycon Pro (OP). There are systematic errors in the measurements of oxygen consumption (VO2) and respiratory exchange ratio (RER) with the OM. Production of CO2 (VCO2) tends to be overestimated by the OM, although the differences are not significant. Ventilation (VE) showed very similar values in both analyzers. Data of VO2 and RER were corrected with a regression equation which minimised the differences among the devices. The portable metabolic system OM makes systematic errors in measurements of VO2 and RER which can be adjusted with a regression analysis to obtain data comparable to those obtained by fixed system

Pleomorphic adenoma of the palate: Two cases report and literature review.

Abstract: Pleomorphic adenoma (PA) is the most common neoplasm encountered  in major and minor salivary glands. Intraorally, it is most frequently developed in the palatal glands. Histologically, it is characterized by a diverse architecture comprised of epithelial stromal elements mixed with mucoid, myxoid, or chondroid fibrohyaline. A PA does not generally present gender bias and can occur at any age with the same clinical behavior. It is usually a round, slow-growing, painless tumor, which is firm upon palpation. We reported two cases of adult patients who were treated using transoral resection at San Juan de Dios Hospital in La Serena.Keywords: Pleomorphic Adenoma, Salivary Glands, Tumor.Adenoma pleomorfo palatino: Reporte de 2 casos y revisión de la literatura.Abstract: El Adenoma Pleomorfo es la neoplasia más común de las glándulas salivales mayores y menores. Intraoralmente las glándulas del paladar son las más afectadas. Histológicamente se caracteriza por una arquitectura variada que comprende elementos epiteliales mezclados con estroma mucoide, mixoide, fibrohialino o condroide,  Los AP no suelen presentar predisposición por sexos, pudiendo aparecer a cualquier edad, con el mismo comportamiento clínico. Se presentan habitualmente como una tumoración redondeada de crecimiento lento, indolora y firme a la palpación. Presentamos dos casos de pacientes adultos, quienes fueron tratados mediante resección transoral en el hospital de la Serena.Palabras clave: Adenoma Pleomorfo, Glándulas salivales, Tumor

Economic stress at work: Its impact over absenteeism and innovation

Economic stress has been recognized as a major threat to the well-being and performance of workers, especially during times of global economic crisis. An interesting and relatively unexplored research topic concerns the associations between economic stress and employee job outcomes such as innovative behaviors, indispensable for business survival. The aim of the present study was to investigate the relationship between economic stress, absenteeism and innovation. We considered both a direct and a mediation hypothesis and hypothesized that economic stress can have a negative influence on innovation directly and indirectly through increased absenteeism. A cross-sectional study was performed during 2018 and 2019 in an Italian food factory. A sample of 578 employees completed the Stress Questionnaire, the Janssen’s nine-item scale and a single-item regarding absenteeism. All relationships are supported by empirical data. As expected, the results indicated that economic stress is negatively related to innovation and positively related to absenteeism, which, in turn, plays a mediating role in the relationship between economic stress and innovative behavior. Herewith, those employees with higher levels of economic stress show higher levels of absenteeism contributing at the same time to a decrease in innovative behaviors. These findings show the importance of economic stress in understanding individual work outcomes and highlight the need to promote adequate intervention programs

Implications of Na+/I- Symporter transport to the plasma membrane for thyroid hormonogenesis and radioiodide therapy

Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I2) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I2 is ultimately dependent on functional Na+/ I2 symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I2 transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I2 accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I2 transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field.Fil: Martín, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Geysels, Romina Celeste. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Peyret, Victoria. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernal Barquero, Carlos Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Masini-Repiso, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

A comparison of para, meta, and ortho-carborane centred non-fullerene acceptors for organic solar cells

[Abstract]: We report the first examples of carborane-containing non-fullerene acceptors (NFAs), and their use in organic photovoltaic (OPV) devices. NFAs employing an A–D–A′–D–A type design centred around a central electron withdrawing carborane unit (A′), using either para, meta, or ortho-carborane isomers are reported. We demonstrate that the nature of the isomer has a major impact on device performance, despite minor differences in optoelectronic and morphological properties, with the use of ortho-carborane resulting in the highest device efficiencies. We further show that end-group fluorination is an efficient strategy to modulate energy levels and improve device performance of such NFAs.Reino Unido. Physics Science Research Council; EP/V048686/1Reino Unido. Physics Science Research Council; EP/T028513/1Arabia Saudí. King Abdullah University of Science and Technology; OSR-2019-CRG8-409

Development of mental health first-aid guidelines for depression: a Delphi expert consensus study in Argentina and Chile

Background: Depression is one of the most common mental health problems worldwide and, while prevalence rates in Latin America are relatively high, most people who meet the criteria for diagnosis do not receive treatment. Family and friends of a person with depression can play an important role in supporting a person to seek and engage with treatment. However, many people do not have the necessary skills or confidence to help. English-language mental health first aid guidelines have been developed to support people to provide such help. The aim of this study was to culturally adapt these guidelines for Chile and Argentina. Methods: A Delphi expert consensus study was conducted with two expert panels, one of people with lived experience of depression (either their own or as a carer; n = 26) and one of health professionals (n = 29). Overall, 172 statements from the English-language guidelines were translated and compiled into a questionnaire. Participants were asked to rate statements based on how essential or important those statements were for Chile and Argentina and to suggest new statements if necessary. Results: Data were obtained over two survey rounds. Consensus was achieved on 172 statements. A total of 137 statements were adopted from the English-language guidelines, whereas 35 new endorsed statements were generated from panel suggestions. There were similarities between the English-language guidelines and those for Chile and Argentina. The adapted guidelines did not include some of the items from the English-language guidelines related to commenting on a person’s strengths or making judgements about their character, and also incorporated new items related to the incorporation of sociocultural considerations as causes of depression and attention to inequities in mental health. Conclusions: The significant number of new items underscores the importance of undertaking a careful process of cultural adaptation. Further research on dissemination and incorporation of the guidelines into the Mental Health First Aid training course for Chile and Argentina is still required.Fil: Encina Zúñiga, Esteban. Universidad de Chile; ChileFil: Agrest, Martín. No especifíca;Fil: Tapia Munoz, Thamara. University College London; Estados UnidosFil: Vidal-Zamora, Isidora. Universidad de Chile.; ChileFil: Ardila Gómez, Sara Elena. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alvarado, Rubén. Universidad de Valparaíso; ChileFil: Leiderman, Eduardo A.. Universidad de Palermo. Facultad de Ciencias Sociales; ArgentinaFil: Reavley, Nicola. University of Melbourne; Australi

Vulnerability Assessment of Buildings due to Land Subsidence using InSAR Data in the Ancient Historical City of Pistoia (Italy)

The launch of the medium resolution Synthetic Aperture Radar (SAR) Sentinel-1 constellation in 2014 has allowed public and private organizations to introduce SAR interferometry (InSAR) products as a valuable option in their monitoring systems. The massive stacks of displacement data resulting from the processing of large C-B and radar images can be used to highlight temporal and spatial deformation anomalies, and their detailed analysis and postprocessing to generate operative products for final users. In this work, the wide-area mapping capability of Sentinel-1 was used in synergy with the COSMO-SkyMed high resolution SAR data to characterize ground subsidence affecting the urban fabric of the city of Pistoia (Tuscany Region, central Italy). Line of sight velocities were decomposed on vertical and E–W components, observing slight horizontal movements towards the center of the subsidence area. Vertical displacements and damage field surveys allowed for the calculation of the probability of damage depending on the displacement velocity by means of fragility curves. Finally, these data were translated to damage probability and potential loss maps. These products are useful for urban planning and geohazard management, focusing on the identification of the most hazardous areas on which to concentrate efforts and resources.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), the State Agency of Research (AEI) and European Funds for Regional Development (FEDER) under projects AQUARISK (ESP2013-47780-C2-2-R) and TEMUSA (TEC2017-85244-C2-1-P) and STAR-EO (TIN2014-55413-C2-2-P). The first author shows gratitude for the PhD student contract BES-2014-069076. The work was conceived during the research stay of P. Ezquerro and R. Tomás in the Università degli Studi di Firenze and the research stay of G. Herrera in the IGOT Lisbon University, supported by the Spanish Ministry of Education, Culture and Sport under fellowships EEBB-I-18-13014, PRX17/00439 and PRX19/00065, respectively. The S-1 monitoring activity is funded and supported by the Tuscany Region under the agreement “Monitoring ground deformation in the Tuscany Region with satellite radar data.” The authors also gratefully acknowledge TRE ALTAMIRA for having processed the S-1 data. The project was carried out using CSK® Products, © ASI (Italian Space Agency), delivered under the ASI Project Id Science 678 - “High resolution Subsidence investigation in the urban area of Pistoia (Tuscany Region, central Italy). The work is under the framework of the e-shape project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement 820852. This paper is also supported by the PRIMA programme under grant agreement No 1924, project RESERVOIR. The PRIMA programme is supported by the European Union

Physical Exercise and Alzheimer's Disease: Effects on Pathophysiological Molecular Pathways of the Disease

Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD