Young Peoples’ Online Science Practices as a Gateway to Higher Education STEM

The purpose of this manuscript is to explore how students perceive that online practices have enabled their participation in university physics programmes. In order to conceptualise how students bridge their science participation across physical and online spaces, we make use of the learning ecology perspective. This perspective is complemented with the notion of science capital, analysing how students have been able to strengthen different aspects of science capital through online participation. Data has been generated through semi-structured interviews guided by a timeline, constructed in collaboration between the interviewer and the interviewee. Twenty-one students enrolled in higher education physics have been interviewed, with a focus on their trajectories into higher education physics. The findings focus on four students who in various ways all have struggled to access science learning resources and found ways to utilise online spaces as a complement to their physical learning ecologies. In the manuscript, we show how online practices have contributed to the students’ learning ecologies, e.g. in terms of building networks and functioning as learning support, and how resources acquired through online science practices have both use and exchange value in the wider science community. Online science participation is thus both curiosity driven and founded in instrumental reasons (using online tutoring to pass school science). Furthermore, we argue that online spaces have the potential to offer opportunities for participation and network building for students who do not have access to science activities and science people in their everyday surroundings.The purpose of this manuscript is to explore how students perceive that online practices have enabled their participation in university physics programmes. In order to conceptualise how students bridge their science participation across physical and online spaces, we make use of the learning ecology perspective. This perspective is complemented with the notion of science capital, analysing how students have been able to strengthen different aspects of science capital through online participation. Data has been generated through semi-structured interviews guided by a timeline, constructed in collaboration between the interviewer and the interviewee. Twenty-one students enrolled in higher education physics have been interviewed, with a focus on their trajectories into higher education physics. The findings focus on four students who in various ways all have struggled to access science learning resources and found ways to utilise online spaces as a complement to their physical learning ecologies. In the manuscript, we show how online practices have contributed to the students’ learning ecologies, e.g. in terms of building networks and functioning as learning support, and how resources acquired through online science practices have both use and exchange value in the wider science community. Online science participation is thus both curiosity driven and founded in instrumental reasons (using online tutoring to pass school science). Furthermore, we argue that online spaces have the potential to offer opportunities for participation and network building for students who do not have access to science activities and science people in their everyday surroundings

Complex lifestyle intervention among inactive older adults with elevated cardiovascular disease risk and obesity: a mixed-method, single-arm feasibility study for RESTART—a randomized controlled trial

Background - Physical inactivity and obesity are global public health challenges. Older adults are important to target for prevention and management of disease and chronic conditions. However, many individuals struggle with maintaining increased physical activity (PA) and improved diet. This feasibility study provides the foundation for the RESTART trial, a randomized controlled trial (RCT) to test a complex intervention to facilitate favourable lifestyle changes older adults can sustain. The primary objective of this study was to investigate study feasibility (recruitment, adherence, side-effects, and logistics) using an interdisciplinary approach. Methods - This 1-year prospective mixed-method single-arm feasibility study was conducted in Tromsø, Norway, from September 2017. We invited by mail randomly selected participants from the seventh survey of the Tromsø Study (2015–2016) aged 55–75 years with sedentary lifestyle, obesity, and elevated cardiovascular risk. Participants attended a 6-month complex lifestyle intervention program, comprising instructor-led high-intensive exercise and nutritionist- and psychologist-led counselling, followed by a 6-month follow-up. All participants used a Polar activity tracker for daily activity monitoring during the intervention. Participants were interviewed three times throughout the study. Primary outcome was study feasibility measures. Results - We invited potential participants (n=75) by mail of which 27 % (n=20) agreed to participate. Telephone screening excluded four participants, and altogether 16 participants completed baseline screening. The intervention and test procedures of primary and secondary outcomes were feasible and acceptable for the participants. There were no exercise-induced injuries, indicating that the intervention program is safe. Participants experienced that the dietary and psychological counselling were delivered too early in the intervention and in too close proximity to the start of the exercise program. Minor logistic improvements were implemented throughout the intervention period. Conclusion - This study indicates that it is feasible to conduct a full-scale RCT of a multi-component randomized intervention trial, based on the model of the present study. No dropouts due to exercise-induced injury indicates that the exercises were safe. While minor improvements in logistics were implemented during the intervention, we will improve recruitment and adherence strategies, rearrange schedule of intervention contents (exercise, diet, and psychology), as well as improve the content of the dietary and behavioural counselling to maximize outcome effects in the RESTART protocol

Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

<p>Abstract</p> <p>Background</p> <p>The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP.</p> <p>Methods</p> <p>Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-γ 200 U/ml and/or tumor necrosis factor (TNF)-α, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC.</p> <p>Results</p> <p>At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-γ and TNF-α treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN-γ, but not TNF-α, treatments.</p> <p>Conclusions</p> <p>All of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation.</p

Complete response to anti-interleukin-5 biologics in a real-life setting:results from the nationwide Danish Severe Asthma Register

BACKGROUND: Phase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma. METHODS: This prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication, i.e. recurrent exacerbations and/or use of mOCS. RESULTS: A total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210 versus 30 mL; p<0.0001 and Δ −1.04 versus −0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e. no mOCS and lower ACQ score) and higher blood eosinophils. CONCLUSIONS: More than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders

Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34 (+)CD38(-) stem and progenitor cells in chronic myeloid leukemia

Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) are remarkably effective inducing deep molecular remission in most patients. However, they are less effective to eradicate the leukemic stem cells (LSC), resulting in disease persistence. Therefore, there is great need to develop novel therapeutic strategies to specifically target the LSC. In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC. Based on these results, the 5-LO inhibitor zileuton has been introduced in clinical trials as a therapeutic option to target the LSC although its effect on primary human CML LSC has not been studied. We have here by using multiplex single cell PCR analyzed the expression of the mediators of the leukotriene pathway in bone marrow (BM) BCR-ABL(+)CD34(+)CD38(-) cells at diagnosis, and found low or undetectable expression of ALOX5. In line with this, zileuton did not exert significant overall growth inhibition in the long-term culture-initiating cell (LTC-IC) and colony (CFU-C) assays of BM CD34(+)CD38(-) cells from 7 CML patients. The majority of the single leukemic BCR-ABL(+)CD34(+)CD38(-) cells expressed cysteinyl leukotriene receptors CYSLTI and CYSLT2. However, montelukast, an inhibitor of CYSLTI, also failed to significantly suppress CFU-C and LTC-IC growth. These findings indicate that targeting ALOX5 or CYSLTI signaling with leukotriene antagonists, introduced into the clinical practice primarily as prophylaxis and treatment for asthma, may not be a promising pharmacological strategy to eradicate persisting LSC in CML patients. (C) 2017 The Author(s). Published by Elsevier Inc.Peer reviewe

Perinatal exposure to the fungicide ketoconazole alters hypothalamic control of puberty in female rats

IntroductionEstrogenic endocrine disrupting chemicals (EDCs) such as diethylstilbestrol (DES) are known to alter the timing of puberty onset and reproductive function in females. Accumulating evidence suggests that steroid synthesis inhibitors such as ketoconazole (KTZ) or phthalates may also affect female reproductive health, however their mode of action is poorly understood. Because hypothalamic activity is very sensitive to sex steroids, we aimed at determining whether and how EDCs with different mode of action can alter the hypothalamic transcriptome and GnRH release in female rats.DesignFemale rats were exposed to KTZ or DES during perinatal (DES 3-6-12μg/kg.d; KTZ 3-6-12mg/kg.d), pubertal or adult periods (DES 3-12-48μg/kg.d; KTZ 3-12-48mg/kg.d).ResultsEx vivo study of GnRH pulsatility revealed that perinatal exposure to the highest doses of KTZ and DES delayed maturation of GnRH secretion before puberty, whereas pubertal or adult exposure had no effect on GnRH pulsatility. Hypothalamic transcriptome, studied by RNAsequencing in the preoptic area and in the mediobasal hypothalamus, was found to be very sensitive to perinatal exposure to all doses of KTZ before puberty with effects persisting until adulthood. Bioinformatic analysis with Ingenuity Pathway Analysis predicted “Creb signaling in Neurons” and “IGF-1 signaling” among the most downregulated pathways by all doses of KTZ and DES before puberty, and “PPARg” as a common upstream regulator driving gene expression changes. Deeper screening ofRNAseq datasets indicated that a high number of genes regulating the activity of the extrinsic GnRH pulse generator were consistently affected by all the doses of DES and KTZ before puberty. Several, including MKRN3, DNMT3 or Cbx7, showed similar alterations in expression at adulthood.ConclusionnRH secretion and the hypothalamic transcriptome are highly sensitive to perinatal exposure to both DES and KTZ. The identified pathways should be exploredfurther to identify biomarkers for future testing strategies for EDC identification and when enhancing the current standard information requirements in regulation

Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause-effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman's reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause-effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.Peer reviewe

Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals : The FREIA Project

Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 825100.Peer reviewedPublisher PD