Marna Eliana Sakalem

IDH-wildtype glioblastoma, or glioblastoma multiforme (GBM), is the most aggressive primary malignancy of the central nervous system. It is characterized by marked invasiveness, intratumoral heterogeneity, and high recurrence rates, largely driven by intrinsic and acquired resistance to standard temozolomide (TMZ) therapy. TMZ is an oral alkylating agent that methylates nitrogenous bases, mainly forming O ⁶ -methylguanine (O ⁶ -meG) lesions, the main cytotoxic and mutagenic events responsible for its antitumor effects. This review first characterizes gliomas and the mechanism of action of the main GBM treatment drug (TMZ), then critically examines in vitro cell culture models investigating these mechanisms. This review emphasizes the development and application of three-dimensional (3D) culture systems, including tumor spheroids and organoids, which more effectively recapitulate tumor architecture, cell–cell interactions, and drug penetration gradients than conventional two-dimensional models. This review discusses the strengths and limitations of these models and their translational relevance to modeling TMZ sensitivity and resistance in GBM.

Variações anatômicas são um ponto de interesse para o estudo da anatomia, apresentando potencial relevância clínica, o que torna sua identificação crucial para profissionais da saúde. O presente estudo teve como objetivo realizar análises morfométricas dos úmeros e identificar possíveis variações anatômicas em úmeros humanos do acervo do Departamento de Anatomia da Universidade Estadual de Londrina (UEL). Utilizando paquímetro digital e fita métrica, foram avaliadas sete medidas: comprimento do osso; circunferência do ponto médio da diáfise; diâmetro látero-lateral da diáfise; diâmetro ântero posterior da diáfise; diâmetro do colo; diâmetro da tróclea; e diâmetro do capítulo. Durante as medições, constatou-se a presença de forame do olécrano (supratroclear) em alguns espécimes. Quando presente, foram avaliadas e mensuradas sua largura e altura. Um total de 145 úmeros foram avaliados e mensurados (79 esquerdos e 66 direitos). Para reduzir variabilidade devido a tamanhos diferentes, foi realizada uma análise proporcional, dividindo-se cada variável pela medida do comprimento total do osso. O comprimento médio encontrado foi de 31,56±0,2032 cm (média±erro padrão), comprimento do eixo médio 6,37±0,05455 cm, largura látero-lateral 19,11±0,2191 mm e largura anteroposterior 20±0,2027 mm. Dos 145 úmeros, 30 apresentaram forame do olécrano, totalizando 20,7% da amostra. Úmeros com esta variação apresentaram comprimento total inferior aos ossos sem esta variação (p=0,004). Nenhuma outra variação foi observada. Este estudo contribui para a caracterização morfométrica dos úmeros do acervo da UEL.

Introduction: The COVID-19 pandemic has impacted global mental health, but little has been studied about the mental health of health students. This systematic review aims to provide an overview of the mental health of this population and the use of psychotropics in the post-pandemic period. Methods: A data search was conducted using PubMed and SciELO databases using the terms (psychotropics) AND (abuse) AND (health students OR health academics) AND (COVID-19 OR pandemic). Articles that assessed the mental health and use of psychotropics by health students in the post-pandemic period were included, while those published before 2020 and that evaluated other populations were excluded. Four articles were filtered and used. Results and Discussion: Three of the four articles were conducted in Europe, and one in Africa. One article focused on health students, while another separately analyzed different fields of study. The other two studies evaluated students as a whole. A high prevalence of mental symptoms such as anxiety, depression, and suicidal ideation, accompanied by high use of psychoactive substances, was observed. The main reasons for use were recreation and cognition. The transition from remote to in-person teaching and social impact were aggravating factors. Conclusion: The mental health of health students is challenged by the extensive curriculum and high pressure and self-demand. After the pandemic, there was an increased risk of psychotropic abuse. Support strategies and preventive programs are essential to mitigate these effects and promote the well-being of these future health professionals.

Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin (AREG) expression. Materials and methods: We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). A control group (C) received no T3 or inhibitors. Analyses of mRNA and [...] ABSTRACT Objective: Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin (AREG) expression. Materials and methods: We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). A control group (C) received no T3 or inhibitors. Analyses of mRNA and

Human beings have always been fascinated by compounds that could affect their minds, either with the aim of putting the psyche in a comfortable zone or altering consciousness. It was in the beginning of the last century that the word psychopharmacology (derived from the Greek psykhē, i.e. mind, spirit or soul, and farmakon, i.e. poison or drug, and logos, i.e. study or knowledge) was first used. The breakthrough of modern psychopharmacology started in the 1950s, with the synthesis of chlorpromazine, an antipsychotic drug, and continued with the discovery of all psychotropic drug classes. This big start was only possible due to researchers investigating the mechanisms of action of diverse drugs, including several that were at first used for other purposes, but happened to also influence the nervous system. The following decades presented a constant and rapid expansion, which enabled scientists not only to pharmacologically interfere with a dysfunctional brain, but also to use psychotropic drugs to understand how the brain works. More importantly, multiple disorders, such as mood and psychiatric disorders, were finally acknowledged and could be more precisely treated.The World Health Organization (WHO) assumes that untreated mental disorders account for 13% of the total global burden of diseases, and it has been estimated that, by 2030, depression will be one of the leading causes of disability worldwide, surpassing heart disease and cancer. Recently, the pandemic situation led to increased anxiety and fear of uncertainties, all of which have a negative effect on maintaining mental health.Psychiatric conditions and chronic pain can be difficult to manage with conventional pharmacological treatments and it is not uncommon to have patients who do not respond to several pharmacological options. Therefore, there is a need (and even an urgency) for developing new approaches and treatments to medical conditions that affect the central nervous system.The articles selected for this research topic bring compelling information on this matter. Two of them are focused on psychedelic science, a field that has been growing intensively in the past decades, with the publication of many auspicious results when these drugs are administered in a controlled and safe setting. For instance, the popular anaesthetic ketamine is also being used as an antidepressant in cases of treatment-resistant depression. With an intricated study design, the authors state that these effects may be due to the potential of some compounds to act against neuroinflammation and neurodegeneration. On a neuroprotection approach, Hasan et al. performed a review on phytochemicals (from fruits, vegetables, spices, teas and herbs) in the management of traumatic brain injury. They conclude that although the use of phytochemicals in the context of traumatic brain injury seems promising, efficacy and safety studies on human beings are still lacking.The Perspective article by Furqan discusses the recent approval by the US Food and Drug Administration (FDA) of the first drug for the treatment of Rett syndrome. This is a rare sporadic neurodevelopmental disorder characterised by normal early growth and development, followed by regression in previously acquired activities, primarily affecting motor, cognitive and communication skills. From 2 years of age, children who live with this syndrome are now eligible to be treated with trofinetide.Lastly, focusing on efficacy and safety of fospropofol disodium sedation, Zhao et al. describe their study protocol. The authors aim to randomise 256 participants who are scheduled for same-day bidirectional endoscopy under sedation in 2 groups: propofol group (control) and fospropofol group. Their hypothesis is that the efficacy and safety of fospropofol sedation will not be inferior to that of propofol.With this constellation of psychopharmacological topics, we expect to provide the readers with assorted information on this field. The progress is evident; the challenges reside in making this progress safe and accessible to everyone who may need it.

Com o intuito de aproximar estudantes universitários da área da saúde e indivíduos em situação de rua ou carência, foi promovido o The Street Store - uma “loja de rua”. Esse projeto reuniu aproximadamente 120 acadêmicos dos diversos cursos do Centro de Ciências da Saúde de uma instituição acadêmica, e permitiu, além da educação dos voluntários em relação às vulnerabilidades humanas, o acesso à saúde e inclusão social por parte da população atendida. Seguindo as medidas sanitárias necessárias (distanciamento social, uso de máscaras, álcool em gel, limpeza de superfícies, escalonamentos entre os participantes), a atividade contou com dois setores: um de “compra” de roupas e outro de saúde. No primeiro, as pessoas atendidas escolheram peças de roupas a custo zero, enquanto no segundo, realizaram aferição de pressão arterial, verificação de índice glicêmico, medição de saturação de oxigênio, ensino de lavagem correta de mãos e técnica de escovação dos dentes, tiveram acesso a banho, manicure, pedicure e recebimento de kits de higiene pessoal. A ação ocorreu em uma instituição beneficente que atende pessoas em situação de rua e mais de 100 famílias socialmente desfavorecidas da região. Os objetivos do projeto foram alcançados com êxito, uma vez que a intervenção proporcionou educação multidisciplinar e humanizada aos voluntários, além de garantir atendimento técnico e humano, inclusão social e condições mínimas de vida a populações diariamente negligenciadas.