En översiktsstudie av Bisphenol A : som ett hormonstörande ämne i livsmedelskontaktmaterial tillverkat av polykarbonat och epoxyresin

Bisphenol A (BPA) is one of the worlds most produced chemicals. This compound is widely employed as an additive in polymers such as polycarbonates and epoxy resins in the manufacturing of plastics to provide transparency, rigidity and resistance to the resins. Because of the suitable properties of these polymers, they are commonly utilized in materials having contact with foods, so called Food Contact Materials (FCMs). Studies in which these materials have been exposed to different kinds of stress, such as heat and long time of exposure, reveal that plastic monomers and additives such as BPA, tend to migrate from the plastic package to the food. This theory, combined with the fact that BPA has been reported as an Endocrine Disrupting Chemical (EDC) with affinity for estrogen receptors (ER), has given rise to the debate regarding the potential adverse health effects of BPA exposure in humans. The aim of this literature study was to examine the prevalence of BPA in FCMs manufactured from polycarbonates and epoxy resins and how this compound tends to migrate as a consequence of common use stress to these materials. Further, it also aimed to compile current research about the potential adverse health effects in humans as a result of exposure. Even though the researchers are divided, a lot of research suggests that high heat and long time of exposure have an impact on the migration of BPA from FCMs. Although, no measured concentrations have exceeded the tolerable daily intake (TDI) and the Specific Migration Limit (SML), which indicate that common use of plastic FCM not should constitute any health risks. Controversially, a lot of research has revealed adverse effects of BPA correlated to various important functions within the body, especially in pregnant women, fetal and young children. However, it should be considered that most documents that have been reviewed in this study are limited and that research on the long-term effects still is underinvestigated. Additionally, most studies have been performed on animals. To be able to draw any definitive conclusions regarding the possible detrimental effects of BPA in humans, more extensive research is needed.Bisphenol A (BPA) är en av nutidens mest producerade kemikalier. Denna förening används i stor utsträckning som tillsats i polykarbonater och epoxyresiner vid tillverkning av plast för att tillföra transparens, spänst och styrka till resinerna. Till följd av dessa polymerers motståndskraftiga egenskaper återfinns de ofta i material som har kontakt med livsmedel, så kallade Food Contact Materials (FCMs). Studier där dessa material utsatts för olika typer av stress, så som värme och lång kontakttid, har visat att monomerer och tillsatser så som BPA, tenderar att migrera till maten de är i kontakt med. Detta faktum, i kombination med att BPA har visat sig vara ett hormonstörande ämne med affinitet för östrogenreceptorer, har väckt en debatt angående dess eventuella hälsorisker hos människan. Syftet med denna litteraturstudie var att undersöka förekomsten av BPA i FCMs tillverkade av polykarbonater och epoxyresiner, samt hur denna förening tenderar att migrera vid vardagligt bruk av sådana material. Vidare syftade den även till att sammanfatta den forskning som finns gällande dess eventuella hälsorisker hos människan. Trots att forskarna är oeniga tyder mycket på att hög värme och lång kontakttid påverkar migrationen av BPA. Inga uppmätta koncentrationer av BPA i mat har däremot överskridit det tolerabla dagliga intaget (TDI) och den specifika migrationsgränsen (SML) vilket indikerar att ett vardagligt bruk av FCM inte bör utgöra några hälsorisker. Trots detta finns studier som pekar på negativa konsekvenser inom flera fysiologiska områden, framförallt i gravida, foster och små barn. I beaktande bör dock medtas att de flesta studier som granskats i denna rapport varit begränsade och därmed saknar belägg för effekterna som kan uppstå vid långvarig exponering. Majoriteten av studierna är dessutom utförda på djur. Av denna anledning krävs mer, extensiv forskning för att styrka påståendet om att BPA från FCMs utgör hälsofara för människan

En röst från Danderyds sjukhus: Hur en offentlig organisation använder podcastmediet i sin varumärkeskommunikation

In this bachelor’s thesis, the branding communication in Danderyd hospital’s podcast Akutsjukhuset is examined, aiming to generate knowledge regarding how a public organisation can use the podcast medium in its branding operations. Thus, the study intends to fill the knowledge gap regarding how public organisations use the podcast medium in their branding communication. An initial understanding of Akutsjukhuset was generated through a first listen of its total 13 episodes, each one consisting of employees from Danderyd hospital acting as lone show-hosts. Through an inductive approach, relevant theories about branding communication were chosen in order to contextualise and generate a deeper understanding of the empirical data. Additionally, we were provided with Danderyd hospital’s policy document regarding external communication, and interviews with two of the hospital’s communication strategists were conducted in order to acquire background information about the podcast. By applying a qualitative content analysis with inspiration from hermeneutics and narrative analysis during our second listen and when analysing the policy document and the interviews, we could interpret and create further understanding regarding the contents of the podcast. The results show that branding strategies such as storytelling, identity building, relationship building and brand ambassadorship are expressed in Akutsjukhuset. To a large degree, the contents consist of the hosts’ personal stories utilising the sound bearing properties of the podcast medium, for example through music and voice variation. These stories can be interpreted as an attempt to humanise the hospital’s brand, which contributes to the creation of the brand’s identity and its stakeholder’s ability to create a relation to the brand. The employer brand is conveyed through frequent positive remarks regarding the workplace and the colleagues, but also in ways that are generalisable for healthcare at large, which can be interpreted as a form of extended employer branding. The podcast also contains attempts of transparency which highlight critique and negative aspects regarding the hospital, which often are extenuated through being mentioned in relation to something positive. Throughout the podcast, a proactive approach towards critique against healthcare is also visible.I föreliggande kandidatuppsats undersöks varumärkeskommunikationen i Danderyds sjukhus podcast Akutsjukhuset med syfte att skapa förståelse för hur en offentlig organisation kan använda podcastmediet i sitt varumärkesarbete. Studien ämnar således fylla kunskapsgapet kring hur offentliga organisationer använder podcastmediet i sin varumärkeskommunikation. En initial förståelse för Akutsjukhuset skapades genom en första genom-lyssning av dess samtliga 13 avsnitt, varje avsnitt bestående av medarbetare från Danderyds sjukhus som ensamma agerar programvärdar. Genom ett induktivt arbetssätt valdes relevanta teorier inom varumärkeskommunikation för att kontextualisera empirin och bidra till en djupare förståelse för den. Dessutom tillhandahölls Danderyds sjukhus policydokument för extern kommunikation, och intervjuer med två av sjukhusets kommunikationsstrateger genomfördes för att erhålla bakgrundsinformation kring podcasten. Genom användandet av en kvalitativ innehållsanalys med inspiration från hermeneutik och narrativ analys vid en andra genomlyssning och vid analysen av policydokumentet och intervjuerna kunde vi tolka och skapa vidare förståelse kring podcastens innehåll. Resultaten visar att varumärkesstrategier såsom storytelling, identitets-skapande, relationsskapande och varumärkesambassadörskap uttrycks i Akutsjukhuset. Innehållet präglas till stor del av programvärdarnas personliga berättelser som utnyttjar podcastmediets ljudbärande egenskaper, till exempel genom musik och röstvariation. Dessa berättelser kan ses som ett försök att mänskliggöra sjukhusets varumärke, vilket bidrar till att skapa varumärkets identitet och förmågan för intressenter att skapa en relation till det. Arbetsgivarvarumärket förmedlas genom att arbetsplatsen och kollegorna omnämns positivt, men även på sätt som är generaliserbara för vården i stort, vilket kan tolkas som en form av förlängd arbetsgivarvarumärkning. Podcastens innehåll präglas också av försök till transparens som framhäver kritik och negativa aspekter gällande sjukhuset, vilka ofta förmildras genom att de framställs i samband med något positivt. Ett genomgående proaktivt förhållningssätt gente¬mot kritik mot vården gör sig också synligt i podcasten

RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo

Fibroblasts are a main player in the tumor-inhibitory microenvironment. Upon tumor initiation and progression, fibroblasts can lose their tumor-inhibitory capacity and promote tumor growth. The molecular mechanisms that underlie this switch have not been defined completely. Previously, we identified four proteins over-expressed in cancer-associated fibroblasts and linked to Rho GTPase signaling. Here, we show that knocking out the Ras homolog family member A (RhoA) gene in normal fibroblasts decreased their tumor-inhibitory capacity, as judged by neighbor suppression in vitro and accompanied by promotion of tumor growth in vivo. This also induced PC3 cancer cell motility and increased colony size in 2D cultures. RhoA knockout in fibroblasts induced vimentin intermediate filament reorganization, accompanied by reduced contractile force and increased stiffness of cells. There was also loss of wide F-actin stress fibers and large focal adhesions. In addition, we observed a significant loss of a-smooth muscle actin, which indicates a difference between RhoA knockout fibroblasts and classic cancer-associated fibroblasts. In 3D collagen matrix, RhoA knockout reduced fibroblast branching and meshwork formation and resulted in more compactly clustered tumor-cell colonies in coculture with PC3 cells, which might boost tumor stem-like properties. Coculturing RhoA knockout fibroblasts and PC3 cells induced expression of proinflammatory genes in both. Inflammatory mediators may induce tumor cell stemness. Network enrichment analysis of transcriptomic changes, however, revealed that the Rho signaling pathway per se was significantly triggered only after coculturing with tumor cells. Taken together, our findings in vivo and in vitro indicate that Rho signaling governs the inhibitory effects by fibroblasts on tumor-cell growth.Peer reviewe

Disease Burden Attributed to Drug use in the Nordic Countries: a Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2019

The Nordic countries share similarities in many social and welfare domains, but drug policies have varied over time and between countries. We wanted to compare differences in mortality and disease burden attributed to drug use over time. Using results from the Global Burden of Disease (GBD) study, we extracted age-standardized estimates of deaths, DALYs, YLLs and YLDs per 100 000 population for Denmark, Finland, Iceland, Norway, and Sweden during the years 1990 to 2019. Among males, DALY rates in 2019 were highest in Finland and lowest in Iceland. Among females, DALY rates in 2019 were highest in Iceland and lowest in Sweden. Sweden have had the highest increase in burden since 1990, from 252 DALYs to 694 among males, and from 111 to 193 among females. Norway had a peak with highest level of all countries in 2001–2004 and thereafter a strong decline. Denmark have had the most constant burden over time, 566–600 DALYs among males from 1990 to 2010 and 210–240 DALYs among females. Strict drug policies in Nordic countries have not prevented an increase in some countries, so policies need to be reviewed.publishedVersio

The human secretome

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019