Metabolic alterations induced by attenuated Zika virus in glioblastoma cells

Orientador: Rodrigo Ramos CatharinoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: O Zika vírus (ZIKV) tornou-se recentemente um grande motivo de preocupação, uma vez que sua associação com casos de microcefalia em recém-nascidos começou a ser investigada e confirmada. A partir de então, o ZIKV tem sido intensamente estudado e vários dados científicos demonstram o tropismo do vírus por células neurais. Estudos prévios propuseram que o ZIKV induz morte de células de glioblastoma, sugerindo que as moléculas associadas ao ZIKV e o próprio ZIKV seriam capaz de induzir alterações bioquímicas intracelulares e, assim, ser alternativas para o controle do câncer neural. Nesse sentido, o presente trabalho apresenta uma abordagem prospectiva para o manejo do glioblastoma: produzir uma terapia baseada no ZIKV que estimule o controle do glioblastoma. Desenvolvemos um protótipo de Zíka vírus atenuado baseado em vesículas de membrana externa bacteriana (ZVp). O ZIKV atenuado foi aplicado nas células de glioblastoma, onde os efeitos citopáticos e citostáticos foram avaliados. Células de glioblastoma, com e sem tratamento, foram submetidas à análise por espectrometria de massa. Resultados: A análise microscópica mostrou efeitos citopáticos induzidos pelo protótipo ZIKV nas células de glioblastoma após 24 e 48 horas pós-tratamento. Ensaio de fragmentação de DNA e expressão de TNF-alfa foram indicativos de que ZVp induziu dano celular e morte. A investigação metabolômica elegeu 5 diferentes biomarcadores que podem estar associados aos efeitos citopáticos celulares, destacando as modificações bioquímicas intracelulares induzidas pelo ZIKV atenuado. A evidência notável de morte celular no glioblastoma estimulou estudos adicionais que renderam uma triagem preliminar com outras linhagens de células tumorais. Entre os 11 tumores avaliados, os tumores de próstata e ovário foram os mais afetados pelo protótipo ZIKV, e outras 6 linhagens celulares também apresentaram efeitos citostáticos. Conclusões: Os resultados demonstraram que este protótipo não apenas surge como uma possível alternativa para o controle do glioblastoma, mas também pode ser uma ferramenta importante contra outros tumores importantesAbstract: Zika virus (ZIKV) has recently become a major matter of concern since its association with microcephaly cases in newborns was determined. From then on, ZIKV has been untiringly studied, and several scientific data have shown the virus' tropism to neural cells. Previous studies have proposed that ZIKV induced glioblastoma cells death, suggesting that ZIKV and ZIKV-associated molecules might induce intracellular biochemical alterations, and thereby be alternatives for neural cancer management. In this sense, the present contribution presents a prospective approach for glioblastomas management: producing a ZIKV-based therapy that stimulates glioblastoma control. We developed an attenuated ZIKV prototype based on bacterial outer membrane vesicles (OMV). The attenuated ZIKV was applied on glioblastoma cells, where cytopathic and cytostatic effects were evaluated. Glioblastoma cells, with and without treatment, were submitted to mass spectrometry analysis. Results: Microscopic analysis showed cytopathic effects induced by ZIKV prototype on glioblastoma cells after 24 and 48 hours post-treatment. DNA fragmentation assay and TNF-alpha expression were indicative that ZVp induced cell damage and death. The metabolomics investigation elected 5 different biomarkers that might be associated with cell cytopathic effects, highlighting intracellular biochemical modifications induced by the attenuated ZIKV. The remarkable evidence of cell death in glioblastoma stimulated further studies that rendered a preliminary screening with other tumor cell lineages, though anti-proliferative activity test. Among the 11 tumors evaluated, prostate and ovarian tumors were the most affected by ZIKV prototype, and other 6 cell lines also presented cytostatic effects. Conclusions: Results ultimately demonstrated that this prototype not only emerges as a potential alternative for glioblastoma management, but may also be an important tool against other important tumorsMestradoFisiopatologia MédicaMestre em Ciências134522/2016-8CNP

Forest School and its effect on the community: A brief review

Forest School and similar outdoor nature-based education programmes have been spreading across different parts of the world. In this short manuscript, we draw on the literature to shed light on the demarcating characteristics of this distinctive form of outdoor education. Furthermore, we expand on the work by Dabaja (2022a; 2022b) to briefly introduce not only the impact of this educational concept on the involved children, but also the way it affects the educators and their pedagogies as well as the dynamics among the children’s family members and their connection to the outdoors. We then conclude by proposing a set of research-related recommendations to explore the full potentiality of the Forest School concept.&nbsp

Building Research Capacity of Future Teachers: A Canadian Case Study

Since their first day in school, in-service teachers are expected to act professionally, make good judgments, think critically, and problem-solve effectively. The literature suggests that engaging pre-service teachers in research can help them to develop several key skills. In this paper, we present the outcomes from a year and a half long mixed-methods case study that was conducted in two phases (i.e., a pilot and a follow-up study) with two groups of pre-service teachers enrolled in a teacher education programme in a Canadian mid-size university. The purpose of this research was to examine how an in-course research component might have shaped the perceived research capacity of the pre-service teachers and their disposition toward teacher research. The participants reported that the research component had improved their inquiry, reflective, critical thinking, and research-related skills. We conclude by discussing the study outcomes and proposing a set of recommendations for theory and practice

Project #4: The Effects of a Pharmacist-Led Transitions of Care Program after Hospital Discharge

Our program is designed to help facilitate the transitions of care (TOC) of select patients discharged from Henry Ford Hospital (HFH) with the aim of preventing 30-day readmissions, as well as improving cost avoidance measures. TOC, as defined by the Centers of Medicare and Medicaid, is a complex process requiring several actions and multiple disciplines to work together to ensure effective communication and coordination of care. Transitioning from the hospital setting to home, specifically, exposes vulnerability within our health systems, and errors have a high chance of occurring. Medication management and follow-up care are included in “the seven essential elements” needed for successful TOC. According to Burke and colleagues, an ideal framework for establishing successful transitions of care includes 10 domains, amongst which are: medication safety, educating patients to promote self-management, enlisting help of social and community supports, coordinating care among team members and monitoring and managing symptoms after discharge and outpatient follow-up, all of which are embedded into our program.https://scholarlycommons.henryford.com/qualityexpo2022/1000/thumbnail.jp

Activities in nature: how frequent is the contact of contemporary children with the natural world?

The progressive process of industrialization occurring in the world in the last 200 years has increased the urban population. One of its consequences has been the gradual detachment from nature, which negatively affects children’s development. At the same time, several authors state that children play essentially indoors, and outdoor activities are declining not only in nature places but also in urban areas, due to several reasons. The present study aims to check how frequently a myriad of several outdoor activities are performed by a group of 153 urban children, 87 boys and 70 girls, from 6 state primary schools with different social backgrounds (low to high socio-economic status) from the Lisbon area. Differences between boys and girls were also analysed. For this purpose, a questionnaire was administered containing demographic-related items, such as sex, age and school, and the following 11 statements pertaining to different outdoor activities: picking up wild fruits; gardening; climbing trees; catching birds in traps; collecting rocks, minerals and fossils; tracking; visiting farms, zoos and other thematic parks; practising outdoor sports; playing in forested areas; going hunting or fishing with friends and relatives; rappelling and other extreme sports. Children had to select the frequency of their performing of each activity on a four-point scale. A total score for the 11 activities was also calculated. The results show that almost all activities have never or rarely been done by the participants, and only outdoor sports are practised more often (sometimes). Boys and girls statistically significant differences were only for practising outdoor sports and for hunting and fishing with friends and relatives, favouring boys. But the frequency of this latter activity was very low in both genders. The present study confirmed children’s prevalent disconnection with nature alongside the decline in performing different outdoor activities, showing that this trend is at least affecting several western countries. Since the situation is impoverishing children’s development and affecting their knowledge and awareness about the importance of the natural world, implications for parents, teachers and policy makers are discussed to try to invert the present trend.info:eu-repo/semantics/publishedVersio

A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for Acute and Chronic Graft-Versus-Host Disease

Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP) has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD

An Explorative Case Study of the Perceptions and Attitudes of Lebanese School Educators toward the Integration of Outdoor Education in the Teaching of School Curricula

In this era plagued with a detrimental sedentary indoor lifestyle, children are becoming further disconnected from the outdoors, including the natural environment. Many reasons could be causing this prevalent way of life, such as parents’ concerns over their children’s safety and the increase in time spent in front of a screen. One way to counter this harmful trend that can lead to both mental and physical health problems is to implement outdoor education in schools and daycares. Research suggests that outdoor education can not only help students engage in physical activities, but also improve their (a) mental, and emotional wellbeing, (b) personal and interpersonal skills, (c) knowledge about the different curriculum subjects, and (d) an appreciation for and understanding of the natural environment . Despite the many benefits of outdoor education, little has been done to explore this concept in the Middle Eastern Lebanese school context. Thus, the purpose of this multisite mixed methods case study research was to explore the perceptions and attitudes of Lebanese elementary school educators coming from one public and one private school. In total, 30 educators agreed to participate in the study. The sample consisted of 27 classroom teachers and one private school vice principal who completed a questionnaire in addition to the two school principals who were individually interviewed. Findings showed that the majority of participants perceived outdoor education as beneficial. Aligning with this result, 20 educators from the two sectors suggested a several perceived benefits from engaging in outdoor education activities, such as improving the students’ social skills as well as their mental and emotional health which tend to motivate them to better learn. Furthermore, both groups of participants offered several ideas to integrate outdoor education in the teaching of different subject matters along with the guidelines of the Lebanese National Environmental Education strategy. Moreover, educators from both study sites perceived the collaboration between teachers and administration as a crucial factor in the successful implementation of any educational program, including outdoor education. In addition, study participants from the two sectors proposed many implementation challenges which made some of them reluctant to embrace outdoor education. Commonly perceived barriers encompassed (a) maintaining the control and the safety of the students outdoors, (b) covering the curriculum expectations, (c) securing essential resources to facilitate the outdoor education activities, and (d) getting necessary training for educators. One implementation challenge that was solely advanced by the private school educators was “time constraints.” Other contrasting elements that emerged from both cases manifested in the permissions that are needed to engage in outdoor activities and the impact of the socio-economic statuses of the schools on the provision of outdoor education-related activities. Various implications for practice and theory emerged from these findings. One contribution was the adaptation of Knowles’ (1992) and Klausewitz’s (2005) Biographical Transformation Models to fit the theoretical framework and findings of the present study. Finally, a set of recommendations for future research was proposed, including the replication of the present study in urban settings and at a high school level to form a comprehensive picture of outdoor education in the Lebanese context. Furthermore, it is advisable to explore the perspectives of students, parents, the personnel from the Lebanese Ministry of Education and Higher Education as well as other stakeholders, such as professors at the Faculties of Education of different Lebanese universities, toward the integration of outdoor education. These recommended studies could be conducted in Lebanon, the Middle East, Canada, or elsewhere where a need for relevant research is required

Neurogenic Stunned Myocardium Following an Attempt to Pass a Drug Test

Ingestion of a large volume of free water or other hypotonic solution can cause acute hyponatremia, leading to multiorgan dysfunction. Individuals may attempt to generate a false-negative urine drug screen through increased free water consumption leading to acute hyponatremia requiring emergency medical care. We present the case of a 19-year-old male who presented to a community emergency department for altered mental status after an attempt to generate a false-negative urine drug screen. He ingested a large volume of free water and multiple detoxification solutions, causing acute hyponatremia with resultant cerebral edema and neurogenic stunned myocardium. He required extracorporeal membrane oxygenation therapy with complete recovery of neurologic and cardiac function. Acute hyponatremia from excess free water consumption is a well-documented phenomenon that all emergency providers should be aware of. Prompt identification and management of acute hyponatremia are essential to prevent potentially severe, devastating sequelae, including cerebral edema and cardiopulmonary failure.In addition, extracorporeal membrane oxygenation may be considered in patients with cardiopulmonary failure in the setting of reversible cardiomyopathy, as evidenced in our case

Standardizing definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: A report on behalf of the American Society for Transplantation and Cellular Therapy

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized