Severe and prolonged myelosuppression during concomitant temozolomide and radiotherapy treatment in a patient with glioblastoma multiforme

Aims: We describe the case of a patient with glioblastoma (GBM) who developed severe and prolonged myelosuppression during concomitant daily temozolomide (TMZ) and radiotherapy (RT) treatment. Analysis of polymorphisms in genes correlated with TMZ-induced myelotoxicity was also performed. Presentation of the Case: A 67–year-old man with diagnosis of GBM undergoing concomitant RT-TMZ treatment developed severe and prolonged pancytopenia that led to discontinuation of TMZ and required frequent platelet and red cells transfusions. Analysis of single nucleotide polymorphisms (SNPs) in the genes NAD(P)H dehydrogenase, quinone 1 (NQO1) and glutathione S-transferase pi 1 (GSTP1) was carried out. Both SNPs were found to be wild-type. Discussion: TMZ is an oral alkylating agent used for the treatment of glioblastoma. TMZ is usually considered well tolerated and safe, with nausea and mild myelosuppression being the most common side effects. However, severe haematologic adverse events have been also reported. Recently, there has been growing interest in gene polymorphisms that might be associated with an increased risk of hematologic toxicity. Conclusion: Myelosuppression is a side effect that can occur relatively early during concomitant TMZ treatment and can negatively impact on patient’s quality of life. Further studies are warranted to find out a correlation between genetic factors and the occurrence of severe hematologic toxicity

Increase in newly diagnosed type 1 diabetes and serological evidence of recent SARS-CoV-2 infection: Is there a connection?

Several studies have investigated the correlation between the COVID-19 pandemic and the onset of type 1 diabetes (T1D) in children, reporting an increased incidence of T1D and severe diabetic ketoacidosis (DKA). This study aimed to investigate the infection by SARS-CoV-2 in children with newly-diagnosed T1D to explore a possible link between SARS-CoV-2 infection, T1D and DKA. Thirty-nine children with a T1D new onset between October 15, 2020, and April 15, 2021, were enrolled. SARS-CoV-2 infection was investigated through a polymerase chain reaction on the nasal swab, dosage of specific antibodies, and an anamnestic question form. Nine (23%) of them had antibodies directed toward SARS-CoV-2, and five (12%) had a history of recent SARS-CoV-2 infection in themselves or in their family. No molecular swabs were positive. Compared to the general pediatric population, the overall incidence of COVID-19 was 5.6 times higher in the T1D patients' group (p < 0.00001). Referring only to the cases in the metropolitan area, we find a net increase in the incidence of T1D compared to the 5 years preceding our study, by 50% compared to the same months in 2016/2017 and 2017/2018, by 69% compared to 2018/2019 and by 77% compared to 2019/2020. The same trend was observed regarding DKA cases. The attributable risk of the pandemic cohort compared to the previous year is 44%. The abnormal disproportion of SARS-CoV-2 infection between children with T1D and the pediatric reference population, with a ratio of 5.6, appears to support the causative role of SARS-CoV-2 in triggering the immune response underlying diabetes, as often described for other viral infections. The difficulty accessing care services during the pandemic, with a consequent diagnosis delay, does not justify the increase in observed T1D cases, which could to be directly linked to the pandemic. The acceleration of the immune process provoked by SARS-CoV-2 may play a suggestive role in the development of T1D with DKA. Multicenter studies are needed to deepen and fully understand the pathophysiological link between SARS-CoV-2 and the onset of T1D in children

ZrO2 phase structure in coating films and powders obtained by sol-gel process

Zirconia coating film and powder obtained by the sol-gel route using zirconium n-propoxide as starting material and acid catalyst were investigated by the Perturbed Angular Correlations method, X-Ray Diffraction and Differential Scanning Calorimetry and Differential Thermal Analyses. The hyperfine interaction, measured after annealing the samples at increasing temperatures up to 1100°C, allowed to distinguish five different zirconium neighborhoods. Two of them describe rather disordered material which, on heating, crystallizes to the tetragonal phase and end finally in monoclinic zirconia. As compared with the powder, the film exhibits a minor fraction of an unidentified ordered form and a higher and more stable fraction of tetragonal phase. In addition, the tetragonal to monoclinic conversion takes place at higher temperatures and with a larger activation energy.Facultad de Ciencias Exacta

Influencia del solvente orgánico en cerámicas de ZrO₂ obtenidas a través del proceso sol-gel

Se prepararon polvos ultrafinos de ZrO₂ por el método sol-gel partiendo de n-propóxido de circonio (ZNP) y usando como solventes etanol, metanol e isopropanol con y sin ácido nítrico como catalizador. Las muestras fueron caracterizadas por Microscopía Electrónica de Barrido (SEM), Difracción de Rayos X (XRD), Análisis Térmico Diferencial (DTA) y Termogravimetría (TG). Una mejor determinación cualitativa y cuantitativa de las fases iniciales y su evolución térmica fueron investigadas mediante el método nuclear de las Correlaciones Angulares Perturbadas (CAP), que mide la interacción hiperfina entre los núcleos sonda ¹⁸¹Hf y los gradientes de campo eléctrico de sus entornos. En este trabajo se pretende conocer el efecto del solvente y el catalizador sobre el contenido de fases y la estabilidad de las muestras estudiadas con el fín de contribuir al diseño de cerámicas de circonio obtenidas por sol-gel. El tipo de alcohol usado como solvente no influye mayormente sobre el producto obtenido; en cambio, el pH en que se realiza la hidrólisis del ZNP tiene un fuerte efecto sobre la morfología y evolución térmica de los polvos obtenidos.Facultad de Ciencias Exacta

Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation

The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression

Phase structure and thermal evolution in coating films and powders obtained by sol-gel process : Part II. ZrO2–2.5 mole% Y2O3

Powders and coatings of zirconia doped with 2.5 mole % yttria have been produced via the sol-gel route. The phase structure and subsequent thermal evolution in heating and cooling cycles have been investigated using mainly perturbed angular correlations spectroscopy. Thermal analyses and XRD as a function of temperature have also been performed to obtain complementary information. Upon heating, the amorphous gels crystallized into the tetragonal structure and showed the same hyperfine pattern and thermal behavior as observed in tetragonal zirconia obtained by the ceramic route: the two configurations of vacancies around zirconium ions denoted as t1 and t2 forms and their mutual t1 → t2 transformation. While the powder sample exhibited an incipient thermal instability above 1000 °C and underwent completely the t2 form to m–ZrO2 transition during subsequent, gradual cooling below 500 °C, the coating retained the tetragonal phase within the whole temperature range investigated. Hyperfine results suggest that the tetragonal phase stabilization is favored by the highly defective nature of the t1 form and consequently hardened by the availability of oxygen. The PAC derived activation energy for the fast diffusion of the oxygen vacancies inherent to the t2 form was determined as 0.54 ± 0.14 eV.Facultad de Ciencias Exacta

Nanostructural study of sol-gel-derived zirconium oxides

Two sol-gel derived zirconia powders were prepared at pH = 0.5 and pH = 5.5. They were investigated as a function of temperature using mainly perturbed angular correlation spectroscopy. The aim was to elucidate the relationship between the nanoscopic configurations around Zr4+ ions and the morphology and structure of the powders. The highly porous material resulting from the solution at higher pH could be described mainly by defective and disordered, very hydrolyzed tetragonal arrays. As temperature increased, the amount of these arrays decreased while they became increasingly asymmetric, thus suggesting their superficial localization. The easy removal of hydroxyls led to the early appearance of the monoclinic phase. The gel obtained from the precursor at pH = 0.5 was entirely described by configurations still involving organic residues. After their calcination, the powder underwent a well-defined two-step hydroxyl removal thermal process leading to the crystallization of the tetragonal and the monoclinic phases. The thermal stability of the metastable tetragonal phase in the investigated powders seems to be controlled by their different capability to absorb oxygen.Facultad de Ciencias Exacta

A importância do exame ultrassonográfico como complementação do BIRADS 0 na mamografia

Introdução: O câncer de mama é uma das principais causas de morbidade e mortalidade entre as mulheres em todo o mundo. Diante desse cenário, estratégias eficazes de rastreamento e diagnóstico precoce tornam-se fundamentais. Objetivo: Explorar de maneira mais aprofundada a importância do exame ultrassonográfico como complementação do BIRADS 0 na mamografia. Metodologia: Trata-se de uma revisão integrativa da literatura. Adotou-se como pergunta norteadora: "Como o exame ultrassonográfico se destaca como uma ferramenta crucial na complementação do BIRADS 0 na mamografia?" Para construção da pesquisa, a coleta e análise de dados foi realizada através do Portal da Biblioteca Virtual em Saúde e das bases de dados Medical Literature Analysis and Retrieval System Online via PubMed e Periódico Capes através dos seguintes Descritores em Ciências da Saúde (DeCS): Mamografia, “Neoplasias da Mama” e “Ultrassonografia Mamária” combinados entre si pelo operador booleano AND com seus respectivos correspondentes no Mesh Terms. Resultados e Discussão: Após o cumprimento dos procedimentos metodológicos, 13 artigos disponíveis no Portal da BVS, na base de dados PubMed e no Periódicos Capes foram selecionados, os quais retratam que a detecção precoce do câncer de mama desempenha um papel crucial na redução da mortalidade e no sucesso do tratamento. No entanto, quando a mamografia apresenta resultados inconclusivos, categorizados como BIRADS 0, é necessário recorrer a métodos complementares. Considerações Finais: A integração do exame ultrassonográfico como complemento ao BIRADS 0 na mamografia representa um avanço significativo no diagnóstico precoce do câncer de mama

Thermal evolution of CaO-doped HfO2 films and powders

Solid solutions of ZrO2 and HfO2 are potential electrolyte materials for intermediate-temperature SOFC because both are oxygen-ion conductors. The main challenge for these compounds is to reduce the relatively high value of the activation energies vacancies diffusion, which is influenced by several factors. In this work the thermal evolution of CaO-HfO2 materials have been investigated. (CaO)y-Hf(1-y)O(2-y) (y 0.06, 0.14 y 0.2) coatings and powders were synthesized by chemical solution deposition (CSD). Films were deposited onto alumina substrates by Dip Coating technique, the burning of organic waste was carried out at 500 °C under normal atmosphere and then the films were thermally treated at intervals of temperature rising to a maximum temperature of 1250 °C. By means Glazing Incidence X-ray Diffraction (ρ-2θ configuration) the phases were studied in the annealed films. On the other hand, the thermal evolution and crystallization process of powders were analyzed in-situ by HT-XRD. The phenomena crystallization occurred in films and powders were analyzed. The activation energies of diffusion of oxygen vacancies of HfO2-14 mole% CaO and HfO2-20 mole% CaO films were measured from the thermal evolution of the relaxation constant measured by Perturbed Angular Correlation Technique.Facultad de Ciencias ExactasFacultad de Ciencias Agrarias y Forestale