Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

<p>Abstract</p> <p>Background</p> <p>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.</p> <p>Methods</p> <p>Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.</p> <p>Results</p> <p>In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).</p> <p>Conclusions</p> <p>The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.</p

Science competitions using technology: a study of the behavior of the participating schools in the CNC in Portugal

Neste trabalho investiga-se a dinâmica de escolas do 3º ciclo do Ensino Básico em Portugal, na preparação e participação em uma competição desenvolvida em ambiente computacional sobre conteúdos curriculares de Matemática, Português, Físico-Química e Geologia. Foi realizada uma análise fatorial exploratória de dados empíricos relativos às 143 escolas participantes nas competições realizadas em 2015, analisando-se as suas caraterísticas de atuação. Foram identificados quatro fatores latentes descrevendo o comportamento das escolas: Treino quantitativo, Treino qualitativo, Prestação e Utilizadores, constatando-se que: (i) a participação na competição de Matemática é predominante; (ii) escolas participantes em duas ou três competições apresentam diferentes dinâmicas de preparação; (iii) escolas que participam apenas em Matemática e Físico-Química parecem adotar estratégias pedagógicas mais articuladas e eficientes. Reconhece-se que, embora as escolas participantes desenvolvam trabalhos de preparação, existe uma tendência para as escolas apresentarem estratégias distintas de atuação consoante a combinação de grupos disciplinares presentes nas competições oficiais.In this work we investigate the dynamics of 143 schools of the 3rd cycle of Basic Education in Portugal, regarding the preparation and participation in online science competitions on curricular contents of Mathematics, Portuguese, Physics and Chemistry and Geology. An exploratory factorial analysis of empirical data concerning the competitions in 2015 was carried out, to analyze the characteristics inherent to schools’ performance. Four latent factors describing the schools’ behavior were identified: Quantitative Training, Qualitative Training, Proficiency and Users, which allowed us to verify that: (i) participation in mathematics competition is predominant; (ii) schools participating in two or three competitions present different preparation dynamics; (iii) schools involved only in Mathematics and Physics and Chemistry competitions seem to adopt a more articulated and efficient pedagogical strategy. Although all schools develop a preparatory work before competitions, the strategies used seem to be related to the combination of distinct disciplinary groups participating in the competitions.Trabalho subsidiado por fundos portugueses através do Centro de Investigação e Desenvolvimento em Matemática e Aplicações (CIDMA) da Universidade de Aveiro, e da Fundação para a Ciência e a Tecnologia (FCT), dentro do projeto UID/MAT/04106/2013.publishe

Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cells secretome?

Introduction: The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear. Methods: In the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells. Results: The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome. Conclusions: Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications. © 2015 Teixeira et al.Portuguese Foundation for Science and Technology (FCT) (Ciência 2007 program and IF Development Grant (AJS); and pre-doctoral fellowships to FGT (SFRH/69637/ 2010) and SIA (SFRH/BD/81495/2011); Canada Research Chairs (LAB) and a SSE Postdoctoral Fellowship (KMP); The National Mass Spectrometry Network (RNEM) (REDE/1506/REM/2005); co-funded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), ao abrigo do Quadro de Referência Estratégico Nacional (QREN), através do Fundo Europeu de Desenvolvimento Regional (FEDER).info:eu-repo/semantics/publishedVersio

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016

Fecal Glucocorticoid Metabolites as Biomarkers in Equids: Assay Choice Matters

From Wiley via Jisc Publications RouterHistory: received 2020-05-06, rev-recd 2021-03-29, accepted 2021-04-09, pub-electronic 2021-06-01Article version: VoRPublication status: PublishedFunder: Royal Society; Id: http://dx.doi.org/10.13039/501100000288; Grant(s): UF110641Funder: Chester Zoo; Id: http://dx.doi.org/10.13039/501100005359; Grant(s): Conservation FellowshipABSTRACT: Free ranging animals are exposed to environmental, demographic, and ecological challenges over time, which can affect their health and fitness. Non‐invasive biomarkers can provide insight into how animals cope with these challenges and assess the effectiveness of conservation management strategies. We evaluated how free ranging ponies (Equus ferus caballus) on the Carneddau Mountain range, North Wales respond to 2 stimuli: an acute stressor of an annual roundup event in November 2014, and spatial and temporal variation in ecological factors in 2018. We evaluated fecal glucocorticoid metabolites using 2 enzyme immunoassays (EIAs): an 11‐oxoetiocholanolone EIA (measuring 11,17‐dioxoandrostanes [11,17‐DOAs]) and a corticosterone EIA. The former assay has been validated in equids, whereas there is limited evidence for the suitability of the latter. We used an additional parent testosterone EIA to measure fecal androgen metabolites in response to the ecological challenges. Following the roundup, the metabolite concentrations measured by the 2 glucocorticoid EIAs were not correlated. The 11,17‐DOAs were elevated from the second day following the roundup and then slowly returned to pre‐round levels over the next 2 weeks. In contrast, the metabolites measured by the corticosterone assay showed no response to the roundup. For the ecological data, all 3 assays detected a positive correlation between metabolites and social group size in males but not in females. The metabolite concentrations measured by the testosterone and corticosterone assays were highly correlated and were temporally associated with the onset of the breeding season, whereas the 11,17‐DOAs were not. The co‐variance of metabolites measured by the corticosterone and testosterone assays, and the lack of an acute response in the corticosterone assay to the roundup, suggests that metabolites detected by the corticosterone assay were not primarily associated with increased glucocorticoid production. We recommend using well‐validated fecal biomarker assays of hypothalamus‐pituitary‐adrenal axis activity to evaluate and compare the effect of different management interventions and environmental change. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society

Changes in the salivary proteome of beagle dogs after weight loss

Being overweight or obese represents an important health issue in humans and pets. The aim of this study was to investigate changes in the salivary proteome of overweight beagles after induced weight loss to better understand the physiological changes involved in this process. Five overweight/obese neutered males of pure breed beagles were evaluated. During the 3-mo period of weight loss, each animal received a strictly controlled amount of a low fat commercial diet per day. Body condition scores (BCS), body weight (BW), and serum biochemical parameters (total cholesterol, triglycerides, and C-reactive protein) were assessed weekly. Quantitative proteomics analysis by SWATH was used to evaluate the salivary proteome changes induced by weight loss treatment. BCS, BW, serum total cholesterol concentration, and abundances of 23 salivary proteins differed significantly between before and after treatment. Some of the altered protein amounts, namely of peptidyl-prolyl cis-trans isomerase, fructose-bisphosphate aldolase C, and 78-kDa glucose-regulated protein, increased after weight loss. These proteins are related with the immune system, inflammatory status, oxidative stress, and glucose metabolism. The results obtained suggest a potential use of salivary proteins in monitoring physiological changes in dogs subjected to weight loss. Moreover, the type of changes identified reinforces the postulated physiological improvements, which weight loss induces. Further research is needed to determine whether the changes observed in this study are due to weight loss, dietary changes, or a combination of both