Childcare competency - an area under development : nurses selfperceived competency in emegency pediatrics

Background: Caring for children with acute illness or injury is one of the most stressful and terror-inspiring scenarios for hospital staff. Yet it is often that nurses who care for these patients feel that they lack the proper competency and training to care for them in the best way related to experience and scientific method. Aim and Method: This study hoped to illustrate how nurses at a hospital close to Mälaren, Sweden perceived their own competence in meeting and caring for a child with acute illness/injury with the use of self-assessment questionnaires. The study included the nurses at a hospital close to Mälaren, Sweden who cared for children with a need for emergency care. The answers were illustrated through descriptive statistical analysis to show nurses self-perceived competence related to their clinical experience in paediatric care. Results: There was a clear correlation and significance between years of clinical experience and parts of the competency of pediatric nurses. There was also a strong need for more pediatric education. Conclusion: The results of this study show that there was a clear correlation between the number of years that the nurses were in clinical practice and the selfperceived competence in care of acute sickness/ injured children. The areas showing the least selfperceived competence were in the areas of medication and handling acute situation. All of the nurses felt that there was a need for more emergency pediatic care.Bakgrund: Att vårda akut sjuka och skadade barn är en av de svåraste situationer som personal i sjukvården ställs inför, ett skräckscenario. Ändå är det ofta sjuksköterskor upplever att de möter akut sjuka/skadade barn utan att ha tillräcklig kompetens och utbildning för att vårda dem på bästa sätt utifrån vetenskap och beprövad erfarenhet. Syfte och Metod: Denna studies syfte var att genom självskattningsformulär undersöka hur sjuksköterskor vid ett sjukhus i Mälartrakten uppfattade den egna kompetensen i mötet med ett akut sjukt/skadat barn. Studien innefattade sjuksköterskor verksamma inom barn och akutsjukvård som mötte barn i behov av akut vård. Svaren analyserades genom deskriptiv statistisk analys för att synliggöra sjuksköterskornas självskattade kompetens relaterat till deras kliniska erfarenhet inom vård av barn. Resultat: Det sågs ett tydligt samband med signifikant korrelation mellan respondenternas kliniska erfarenhet och delar av barnsjuksköterskans kompetensbeskrivning. Även ett stort behov av pediatrisk utbildning framkom i resultatet. Slutsats: Resultatet visade att det fanns en tydlig korrelation mellan antal år som kliniskt verksam sjuksköterska inom barn och ungdomsvård och den självskattade kompetensen. Brister i sjuksköterskornas självskattade kompetens fanns främst i att medicinera barn och hantera akuta situationer. Samtliga sjuksköterskor upplevde att det fanns ett behov av utbildning kring vård av akut sjuka/skadade barn

Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion of cod liver oil: comparison of human and porcine in vitro digestion models

In this work, we investigated lipid oxidation of cod liver oil during gastrointestinal (GI) digestion using two types of in vitro digestion models. In the first type of model, we used human GI juices, while we used digestive enzymes and bile from porcine origin in the second type of model. Human and porcine models were matched with respect to factors important for lipolysis, using a standardized digestion protocol. The digests were analysed for reactive oxidation products: malondialdehyde (MDA), 4-hydroxy-trans-2-nonenal (HNE), and 4-hydroxy-trans-2-hexenal (HHE) by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS), and for free fatty acids (FFA) obtained during the digestion by gas chromatography-mass spectrometry (GC-MS). The formation of the oxidation products MDA, HHE, and HNE was low during the gastric digestion, however, it increased during the duodenal digestion. The formation of the oxidation products reached higher levels when digestive juices of human origin were used (60 μM of MDA, 0.96 μM of HHE, and 1.6 μM of HNE) compared to when using enzymes and bile of porcine origin (9.8, and 0.36 μM of MDA; 0.16, and 0.026 μM of HHE; 0.23, and 0.005 μM of HNE, respectively, in porcine models I and II). In all models, FFA release was only detected during the intestinal step, and reached up to 31% of total fatty acids (FA). The findings in this work may be of importance when designing oxidation oriented lipid digestion studies

Human Health Risk Assessment of Pharmaceuticals in Water: Issues and Challenges Ahead

This study identified existing issues related to quantitative pharmaceutical risk assessment (QPhRA, hereafter) for pharmaceuticals in water and proposed possible solutions by analyzing methodologies and findings of different published QPhRA studies. Retrospective site-specific QPhRA studies from different parts of the world (U.S.A., United Kingdom, Europe, India, etc.) were reviewed in a structured manner to understand different assumptions, outcomes obtained and issues, identified/addressed/raised by the different QPhRA studies. Till date, most of the published studies have concluded that there is no appreciable risk to human health during environmental exposures of pharmaceuticals; however, attention is still required to following identified issues: (1) Use of measured versus predicted pharmaceutical concentration, (2) Identification of pharmaceuticals-of-concern and compounds needing special considerations, (3) Use of source water versus finished drinking water-related exposure scenarios, (4) Selection of representative exposure routes, (5) Valuation of uncertainty factors, and (6) Risk assessment for mixture of chemicals. To close the existing data and methodology gaps, this study proposed possible ways to address and/or incorporation these considerations within the QPhRA framework; however, more research work is still required to address issues, such as incorporation of short-term to long-term extrapolation and mixture effects in the QPhRA framework. Specifically, this study proposed a development of a new “mixture effects-related uncertainty factor” for mixture of chemicals (i.e., mixUFcomposite), similar to an uncertainty factor of a single chemical, within the QPhRA framework. In addition to all five traditionally used uncertainty factors, this uncertainty factor is also proposed to include concentration effects due to presence of different range of concentration levels of pharmaceuticals in a mixture. However, further work is required to determine values of all six uncertainty factors and incorporate them to use during estimation of point-of-departure values within the QPhRA framework

Governing Antimicrobial Resistance (AMR) in a Changing Climate: A Participatory Scenario Planning Approach Applied to Sweden in 2050

Background: Antimicrobial resistance (AMR) is a growing global crisis with long-term and unpredictable health, social and economic impacts, with which climate change is likely to interact. Understanding how to govern AMR amidst evolving climatic changes is critical. Scenario planning offers a suitable approach. By envisioning alternative futures, stakeholders more effectively can identify consequences, anticipate problems, and better determine how to intervene. This study explored future worlds and actions that may successfully address AMR in a changing climate in a high-income country, using Sweden as the case.Methods: We conducted online scenario-building workshops and interviews with eight experts who explored: (1) how promising interventions (taxation of antimicrobials at point of sale, and infection prevention measures) could each combat AMR in 2050 in Sweden given our changing climate; and (2) actions to take starting in 2030 to ensure success in 2050. Transcripts were thematically analyzed to produce a narrative of participant validated alternative futures.Results: Recognizing AMR to be a global problem requiring global solutions, participants looked beyond Sweden to construct three alternative futures: (1) “Tax Burn Out” revealed taxation of antimicrobials as a low-impact intervention that creates inequities and thus would fail to address AMR without other interventions, such as infection prevention measures. (2) “Addressing the Basics” identified infection prevention measures as highly impactful at containing AMR in 2050 because they would contribute to achieving the Sustainable Development Goals (SDGs), which would be essential to tackling inequities underpinning AMR and climate change, and help to stabilize climate-induced mass migration and conflicts; and (3) ”Siloed Nations” described a movement toward nationalism and protectionism that would derail the “Addressing the Basics” scenario, threatening health and wellbeing of all. Several urgent actions were identified to combat AMR long-term regardless which future un-folds, such as global collaboration, and a holistic approach where AMR and climate change are addressed as interlinked issues.Conclusion: Our participatory scenario planning approach enabled participants from different sectors to create shared future visions and identify urgent actions to take that hinge on global collaboration, addressing AMR and climate change together, and achieving the SDGs to combat AMR under a changing climate

The round goby genome provides insights into mechanisms that may facilitate biological invasions

Background: The invasive benthic round goby (Neogobius melanostomus) is the most successful temperate invasive fish and has spread in aquatic ecosystems on both sides of the Atlantic. Invasive species constitute powerful in situ experimental systems to study fast adaptation and directional selection on short ecological timescales and present promising case studies to understand factors involved the impressive ability of some species to colonize novel environments. We seize the unique opportunity presented by the round goby invasion to study genomic substrates potentially involved in colonization success. Results We report a highly contiguous long-read-based genome and analyze gene families that we hypothesize to relate to the ability of these fish to deal with novel environments. The analyses provide novel insights from the large evolutionary scale to the small species-specific scale. We describe expansions in specific cytochrome P450 enzymes, a remarkably diverse innate immune system, an ancient duplication in red light vision accompanied by red skin fluorescence, evolutionary patterns of epigenetic regulators, and the presence of osmoregulatory genes that may have contributed to the round goby's capacity to invade cold and salty waters. A recurring theme across all analyzed gene families is gene expansions. Conclusions: The expanded innate immune system of round goby may potentially contribute to its ability to colonize novel areas. Since other gene families also feature copy number expansions in the round goby, and since other Gobiidae also feature fascinating environmental adaptations and are excellent colonizers, further long-read genome approaches across the goby family may reveal whether gene copy number expansions are more generally related to the ability to conquer new habitats in Gobiidae or in fish

Boganmeldelser

Book review

Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations

Background: Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder caused by mutations in the TSC1 or TSC2 genes, with patients often exhibiting neurodevelopmental (ND) manifestations termed TSC-associated neuropsychiatric disorders (TAND) including autism spectrum disorder (ASD) and intellectual disability. Hamartin (TSC1) and tuberin (TSC2) proteins form a complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. Loss of TSC1 or TSC2 activates mTORC1 that, among several targets, controls protein synthesis by inhibiting translational repressor eIF4E-binding proteins. Using TSC1 patient-derived neural progenitor cells (NPCs), we recently reported early ND phenotypic changes, including increased cell proliferation and altered neurite outgrowth in TSC1-null NPCs, which were unaffected by the mTORC1 inhibitor rapamycin. Methods: Here, we used polysome profiling, which quantifies changes in mRNA abundance and translational efficiencies at a transcriptome-wide level, to compare CRISPR-edited TSC1-null with CRISPR-corrected TSC1-WT NPCs generated from one TSC donor (one clone/genotype). To assess the relevance of identified gene expression alterations, we performed polysome profiling in postmortem brains from ASD donors and age-matched controls. We further compared effects on translation of a subset of transcripts and rescue of early ND phenotypes in NPCs following inhibition of mTORC1 using the allosteric inhibitor rapamycin versus a third-generation bi-steric, mTORC1-selective inhibitor RMC-6272. Results: Polysome profiling of NPCs revealed numerous TSC1-associated alterations in mRNA translation that were largely recapitulated in human ASD brains. Moreover, although rapamycin treatment partially reversed the TSC1-associated alterations in mRNA translation, most genes related to neural activity/synaptic regulation or ASD were rapamycin-insensitive. In contrast, treatment with RMC-6272 inhibited rapamycin-insensitive translation and reversed TSC1-associated early ND phenotypes including proliferation and neurite outgrowth that were unaffected by rapamycin. Conclusions: Our work reveals ample mRNA translation alterations in TSC1 patient-derived NPCs that recapitulate mRNA translation in ASD brain samples. Further, suppression of TSC1-associated but rapamycin-insensitive translation and ND phenotypes by RMC-6272 unveils potential implications for more efficient targeting of mTORC1 as a superior treatment strategy for TAND

Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma

Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF MAPK pathway activation. Here, we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFb Smad signaling which is localised to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BRafV600E or KRASG12D knockin) and TGFb signaling ablation (through Tgfbr1 deletion) in Lgr5+ve stem cells enables rapid cSCC development in the mouse. Mutation of TP53 (which is commonly mutated in sporadic cSCC) coupled with TGFbR1 deletion in Lgr5+ve cells also results in cSCC development. These findings indicate that Lgr5+ve stem cells can act as a cell of origin for cSCC and that RAS-RAF-MAPK pathway hyperactivation or TP53 mutation, coupled with loss of TGFb signaling, are driving events of skin tumorigenesis

DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

<p>Abstract</p> <p>Background</p> <p>The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics.</p> <p>Methods</p> <p>DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA) hydrolysis assay.</p> <p>Results</p> <p>While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin). In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692), or did not exist for gemcitabine.</p> <p>Conclusion</p> <p>The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.</p

The discovAIR project:a roadmap towards the Human Lung Cell Atlas

The Human Cell Atlas (HCA) consortium aims to establish an atlas of all organs in the healthy human body at single-cell resolution to increase our understanding of basic biological processes that govern development, physiology and anatomy, and to accelerate diagnosis and treatment of disease. The lung biological network of the HCA aims to generate the Human Lung Cell Atlas as a reference for the cellular repertoire, molecular cell states and phenotypes, and the cell-cell interactions that characterise normal lung homeostasis in healthy lung tissue. Such a reference atlas of the healthy human lung will facilitate mapping the changes in the cellular landscape in disease. The discovAIR project is one of six pilot actions for the HCA funded by the European Commission in the context of the H2020 framework program. DiscovAIR aims to establish the first draft of an integrated Human Lung Cell Atlas, combining single-cell transcriptional and epigenetic profiling with spatially resolving techniques on matched tissue samples, as well as including a number of chronic and infectious diseases of the lung. The integrated Lung Cell Atlas will be available as a resource for the wider respiratory community, including basic and translational scientists, clinical medicine, and the private sector, as well as for patients with lung disease and the interested lay public. We anticipate that the Lung Cell Atlas will be the founding stone for a more detailed understanding of the pathogenesis of lung diseases, guiding the design of novel diagnostics and preventive or curative interventions