Thyroid function tests, incongruent internally and with thyroid status, both in a pregnant woman and in her newborn daughter

Introduction: Thyroid function tests (TFT) are extensively used in daily clinical practice. Here, we described a case of incongruent TFT both in a pregnant woman and in her newborn. Case presentation: A 32-year-old woman, diagnosed with autoimmune thyroiditis during her first pregnancy, was monitored during her second gestation. At week 5 + 2 days, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) values (Dimension VISTA 1500, Siemens Healthineers) were within normal limits. At week 19 + 5 days, TSH remained normal while FT4 increased approximately by three-fold. FT4 inconsistency was with both TSH and the clinical status since she continued to be clinically euthyroid. On the same serum sample, thyroid autoantibodies were negative. At week 25 + 4 days, the patient complained of palpitations and dyspnea, with tachycardia. Even though TSH was normal, high levels of both FT4 and free triiodothyronine (FT3) were interpreted as evidence of thyroid overactivity and methimazole was started. TFT of the pregnant woman continued to be monitored throughout gestation. Postpartum FT4 and FT3 gradually returned to normal. TFT, performed on the daughter’s serum, 3 days after birth, showed the same inconsistency as her mother but without clinical signs of congenital hyperthyroidism. Based on the clinical and laboratory setting, the presence of circulating autoantibodies against T3 and T4 (THAb) was suspected and demonstrated by radioimmunoprecipitation. Conclusion: Analytical interferences should be supposed when TFT do not fit with the clinical picture and despite their infrequency, THAb must also be considered. To our knowledge, this is the first case describing the passage of THAb to the newborn

Cognitive and Affective Image: a study of Blumenau, Santa Catarina, Brazil, as a tourism destination

Nos últimos anos, observou-se um aumento considerável de destinos que almejam desenvolver a atividade turística com o objetivo de alavancar a economia local. Concomitante a esta situação, surgiram estudos voltados à competitividade de destinos, englobando as mais diversas temáticas, voltadas principalmente ao marketing e à gestão. A imagem de destinos é abordada com bastante frequência nesses estudos, uma vez que, por meio dela, um destino pode diferenciar-se de seus concorrentes. Em virtude desse cenário, este estudo tem como objetivo realizar uma análise comparativa entre a imagem cognitiva e a imagem afetiva do destino Blumenau (SC, Brasil). A pesquisa caracteriza-se por ser exploratória, descritiva e comparativa, com abordagem qualiquantitativa. Para descrever a imagem cognitiva, realizou-se uma análise morfológica e de conteúdo das 579 palavras e 117 imagens encontradas nos folders e no site promocional da cidade. Posteriormente, aplicou-se aos dados a Modelagem de Equação Estrutural (MEE) e testes de correlação (Coeficiente de Spearman). Para descrever a imagem afetiva, utilizou-se o estudo realizado por Reis et al., que analisa a marca Blumenau a partir da perspectiva dos seus residentes. Os resultados demonstram que a imagem cognitiva corresponde à afetiva, uma vez que a comunicação publicitária de Blumenau promove a cultura germânica, elemento fundamental da autoimagem dos residentes do município.En los últimos años, se observó un aumento considerable de destinos que anhelan desarrollar el turismo con el objetivo de impulsar la economía local. Concomitante a esta situación, empezaron a surgir estudios centrados en la competitividad de los destinos, englobando las más diversas temáticas, pero sobretodo el marketing y la gestión La imagen de destinos se discute con bastante frecuencia en estos estudios, ya que, a través de ella, un destino puede diferenciarse de sus competidores. Bajo este escenario, este estudio tiene como objetivo realizar un análisis comparativo de las imágenes cognitiva y afectiva del destino Blumenau (SC, Brasil). La investigación se caracteriza como exploratoria, descriptiva y comparativa, con abordaje cualicuantitativo. Para describir la imagen cognitiva, se realizó un análisis morfológico y de contenido de 579 palabras y 117 imágenes de folletos promocionales y del sitio web de divulgación de la ciudad. Posteriormente, se aplicó a los datos el Modelo de Ecuaciones Estructurales (MEE) y pruebas de correlación (Coeficiente de Spearman). Para describir la imagen afectiva, se utilizó el estudio de Reis et al., que analiza la marca Blumenau desde la perspectiva de sus residentes. Los resultados demuestran que la imagen cognitiva corresponde a la imagen afectiva, ya que la comunicación publicitaria de Blumenau promueve la cultura alemana, un elemento clave en la autoimagen de los residentes del municipio.In recent years, we have been observed a considerable increase of tourism destinations that aim to develop tourism with the goal of improving local economies. At the same time, new studies have emerged focusing on the competitiveness of these touristic places, addressing the most diverse topics – mainly related to marketing and management. The image of tourism destinations is quite often discussed in these studies, since one can use it to compare touristic cities. Considering this context, this study aims to carry out a comparative analysis between the cognitive and affective image of Blumenau, Santa Catarina, Brazil. The research is exploratory, descriptive and comparative, with quali-quantitative approach. To describe the cognitive image, we conducted a morphological and content analysis of 579 words and 117 images from tourism folders and an analysis of the city website. After this, we used Structural Equation Modeling (SEM) and correlation tests (Spearman’s coefficient) to analyze the data. To describe the affective image, we used the study conducted by Reis et al. in which the researchers analyzed the Blumenau branding from the perspective of its residents. The results show that the cognitive image corresponds to the affective image, since the advertising of Blumenau promotes the German culture, an essential element for the residents’ self-image

Towards Emx2 therapy of Glioblastoma multiforme

The homeodomain-containing transcription factor Emx2 encodes for a homeobox protein essential for territorial specification of rostral CNS as well as for proper spatio-temporal tuning of neural cell growth and differentiation (Gangemi et al. 2006). Previous experiments done in my laboratory demonstrated its role in inhibiting cortico-cerebral astrogenesis, limiting proliferation of astrocytes-committed progenitors upon its overexpression in neural stem cells. This control takes place via a functional cascade, which includes stimulation of Bmp signaling and Sox2 repression, through the downregulation of Egfr and Fgf9 (Falcone et al., 2015). Meanwhile, studies by other labs also reported an inverse correlation between Emx2 expression levels and aggressiveness of several human cancers, including lung, endometrial and gastric tumours (Okamoto et al. 2010) (Li et al. 2012). Inspired by these findings, we activated a research program aimed at exploring the possibility to use Emx2 in therapy of glioblastoma multiforme. This neoplasm is the most common and aggressive malignant primary tumor of the CNS, responsible of 4% of all tumor death in humans. Conventional therapeutic options for it are unfortunately limited: after surgical resection, GBM-affected patients routinely undergo radiotherapy and adjuvant chemotherapy (temozolomide, TMZ); nevertheless, their median survival is no longer than 14 months. In 2016, Carmen Falcone demonstrated that Emx2 overexpression suppresses a number of different glioblastomas in vitro, within 7-10 days, by inducing cell death and inhibiting cell proliferation. Molecular mechanisms underlying this phenomenon resulted to be highly pleiotropic, indeed Emx2 affects different pathways and genes, including RTK cascades, cell cycle control circuitries and other malignancy-related processes (Falcone et al. 2016). Then, given limits of conventional therapies, we decided to score the actual benefit of experimental Emx2 gene therapy, evaluate its possible interaction with standard chemo- and radiotherapy, and explore novel routes for its delivery. These issues were investigated under the framework of this thesis. Results were as follows. First, Emx2 displayed a therapeutically appealing, anti-oncogenic activity in vivo. Indeed the median survival time of mice transplanted with Emx2-GOF tumour cells was twenty days longer compared to the control group (i.e. 35 days), outperforming TMZ. Next, these results were confirmed by in vitro kinetic assays. Here we observed at least an additive effect between TMZ and Emx2-GOF treatments; specifically, in case of the U87 line, Emx2 sensitized GBM cells to chemotherapy. As for X-rays, we found that their association to Emx2 overexpression resulted in an enhanced anti-oncogenic effect. By means of ad hoc calibrated, in vitro kinetic assays, we discovered that Emx2 sensitized GBM cells to radiation. This was predominantly due to an inhibition of homologous recombination-based DNA-repair, likely leading to GBM cell suicide. A pronounced downregulation of SOX2 and FOXG1, two key drivers of GBM malignity, was instrumental to that. Finally, interested in developing new effective and biosafe strategies for in vivo delivery of the therapeutic Emx2 transgene, we collected preliminary proofs of principle, supporting the feasibility of a novel design based on combined use of HSV-1-derived, oncolytic viruses and amplicon vectors

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in context

Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None