Fish are more sensitive to introduced disturbances from synthetic endocrine disrupting compounds during early life phases compared with mature stages. 17α-Ethinylestradiol (EE2), which is the active ...compound in human oral contraceptives and hormone replacement therapies, is today ever present in the effluents from sewage treatment plants. EE2 targets and interacts with the endogenous biological systems of exposed vertebrates resulting in to large extents unknown short- and long-term effects. We investigated how EE2 exposure affects expression profiles of a large number of target genes during early life of roach (Rutilus rutilus). We exposed fertilized roach eggs collected from a lake in Southern Sweden to EE2 for 12weeks together with 1+-year-old roach in aquaria. We measured the gene expression of the estrogen receptor (esr)1/2a/2b, androgen receptor (ar), vitellogenin, cytochrome P450 (cyp)19a1a/1b in fertilized eggs; newly hatched larvae; 12-week-old fry; and juvenile wild roach (1+-year-old). Results shows that an EE2 concentration as low as 0.5ng/L significantly affects gene expression during early development. Gene expression responses vary both among life stages and molecular receptors. We also show that the gene profile of the estrogen feedback cycle to a large extent depends on the relationship between the three esr genes and the two cyp19a1 genes, which are all up-regulated with age. Results indicate that a disruption of the natural activity of the dominant esr gene could lead to detrimental biological effects if EE2 exposure occurs during development, even if this exposure occurred for only a short period.
Mollusks have received increasing interest in ecotoxicological studies but so far the available scientific analyses of how their genes are affected by anthropogenic pollutants are scarce. The focus ...of this study is to identify an estrogen receptor (er) gene in the common prosobranch snail Bithynia tentaculata and to test a hypothesis that 17α-Ethinylestradiol (EE2) will modulate er gene expression after short-term exposure. We set up exposure experiments with a total of 144 snails, which were collected from a natural population in southern Sweden. Snails were exposed to either 10ng/L or 100ng/L EE2 during 24h and/or 72h. From the isolated B. tentaculata RNA we successfully identified and characterized a novel er gene and phylogenetic analyses strongly indicate that the Bithynia er gene is an ortholog to the human ERα (ESR1, NR3A1). We found a significant interaction between EE2-dose and exposure duration on the er's gene expression (Two-way ANOVA; p=0.04). We also found a significant difference in the gene expression of the er when comparing the control and 100ng/L treatment groups after 72h in female snails (One-way ANOVA; p=0.047). The results from this study should be useful for future field-related studies of estrogen receptors in natural populations of mollusks.
•We successfully isolated the estrogen receptor (er) gene.•Phylogenetic analysis suggest that the er gene is highly conserved in mollusks.•We performed experiments where natural snails were exposed to 17α-ethinylestradiol.
Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to ...vaccine type, dose, timing, participant characteristics and primary immunization regimen received.
Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria.
Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization.
COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.
Endocrine disrupting chemicals (EDCs) have the potential to affect development and reproduction in gastropods. However, one is today lacking basic understanding of the Molluscan endocrine system and ...one can therefore not fully explain these EDC-induced affects. Furthermore, only a few genes that potentially may be connected to the endocrine system have been sequenced in gastropods. An example is the estrogen receptor gene (er) that have been identified in a restricted number of freshwater and marine gastropods. Here, we have identified a new partial coding sequence of an estrogen receptor gene (er) in the European common heterobranch Radix balthica. The following phylogenetic analysis divided the ers of heterobranchs and ceanogastropods in two branches. Furthermore, exposure to the synthetic estrogen 17α-ethinylestradiol (EE2) showed that exposure could significantly affect er expression level in the heterobranch R. balthica. This paper is the first that phylogenetically compares gastropods' er, basal er expression profiles, and transcriptional estrogenic responses in gastropods from two different evolutionary groups.
Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral ...vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines.
Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139.
Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation.
Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.
UK Vaccine Task Force and National Institute for Health Research.
The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a ...substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines.
We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria-with no contraindications to influenza vaccination-were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine Flucelvax Quadrivalent; Seqirus UK, Maidenhead for those aged 18-64 years and adjuvanted trivalent influenza vaccine Fluad; Seqirus UK, Maidenhead for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995.
Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 64·9% of 174 vs 592 53·3% of 1111) or pain (69 39·7% vs 325 29·3%) at injection site, fatigue (48 27·7% vs 215 19·4%), and muscle pain (49 28·3% vs 237 21·4%). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to <65 years) was 87·5% (95% CI -0·2 to 98·4) and in the main study was 89·8% (95% CI 79·7-95·5).
To our knowledge, this substudy is the first to show the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. Our results suggest concomitant vaccination might be a viable immunisation strategy.
Novavax.
Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we ...report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca).
Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33).
Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules.
These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals.
UK Vaccine Taskforce and National Institute for Health and Care Research.
IntroductionSyndromic panel assays, that is, using one test to simultaneously target multiple pathogens with overlapping signs and symptoms, have been integrated into routine paediatric care over the ...past decade, mainly for more severely ill and hospitalised patients. Their wider availability and short turnaround times open the possibility to apply them to non-hospitalised patients as well. In this context, it is important to trial how clinicians make use of pathogen detection data and if their early availability influences management decisions, particularly antibiotic use and hospitalisation.Methods and analysisAdvanced Diagnostics for Enhanced QUality of Antibiotic prescription in respiratory Tract infections in Emergency rooms is an individually randomised, controlled, open-label effectiveness trial comparing the impact of a respiratory pathogen panel assay (BIOFIRE Respiratory Panel 2.1plus) used as a rapid syndromic test on nasopharyngeal swabs in addition to the standard of care versus standard of care alone. The trial will 1:1 randomise 520 participants under the age of 18 at 7 paediatric emergency departments in 5 European countries. Inclusion criteria for the trial consist of two sets, with the first describing respiratory tract infections in paediatric patients and the second describing the situation of potential management uncertainty in which test results may immediately affect management decisions. Enrolment started in July 2021 and is expected to be completed in early 2024. We will perform a two-sample t-test assuming a pooled variance estimate to compare the log-transformed mean time on antibiotic treatment (in hours) and number of days alive out of the hospital within 14 days after study enrolment between the control and intervention arms.Ethics and disseminationThe trial protocol and materials were approved by research ethics committees in all participating countries. The respiratory pathogen panel assay is CE marked (assessed to meet European regulations) and FDA (United States Food and Drug Administration) cleared for diagnostic use. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.Trial registration number NCT04781530.
Bakgrund: I åldersgruppen 16–25 år är internet den starkaste informationskällan. Denna åldersgrupp är även de främsta användarna av sociala medier. Sociala medier kan medföra en hel del positiva ...effekter. Men studier har också visat att användning av vissa sociala medier kan ha negativa hälsoresultat för unga vuxna. Syfte: Syftet med uppsatsen är att studera unga vuxnas reflektioner, tankar och upplevelser kring sociala medier och dess användning. Åldrarna i undersökningen är 15–30 år. Design och metod: Studien utfördes via en kvantitativ tvärsnittsstudie med hjälp av enkäter via Facebook, enkäten var utformad med 16 frågor om hur unga vuxna använder sociala medier, varför och hur mycket. Enkäten låg ute på Facebook i tre dygn och genererad totalt 142 svar. Resultat: Resultaten som framkom utav enkäten visade att alla förutom en använde sig av sociala medier. Det är nästan dubbelt så många kvinnor som män som har svarat på enkäten. De allra flesta använder sig av sociala medier ca en till fyra timmar om dagen. Men de framkommer också attityder och upplevelser kring sociala medier. Slutsats: Många unga vuxna använder sig av sociala medier flera gånger om dagen, där de ständigt får ta del av andras värderingar och normer. Sociala medier berör unga vuxna på olika sätt och i olika utsträckning. De flesta påverkas positivt eller negativt eller till och med både och men trots detta använder de allra flesta sociala medier i alla fall. Denna studie svarar dock inte på varför eller på vilka sätt sociala medier påverkar oss eftersom det inte har varit studiens syfte att undersöka detta.
Background: In the age group 16-25 years, the internet is the strongest source of information. This age group is also the main users of social media. Social media can have a lot of positive effects. But studies have also shown that the use of some social media may have negative health results for young adults.Purpose: The purpose of the paper is to study the reflections, thoughts and experiences of young adults about social media and its use. The ages studied in this study are 15-30 years.Design and method: The study was conducted via a quantitative cross-sectional study using surveys via Facebook, the questionnaire was designed with 16 questions about how young adults use social media, why and how much. The survey was on Facebook for three days and generated a total of 142 responses. Result: The results of the survey showed that all but one used social media. Almost twice as many women as men have answered the questionnaire. The vast majority use social media about one to four hours a day. But they also evoke attitudes and experiences around social media. Conclusion: Many young adults use social media several times a day, where they constantly share other people's values and norms. Social media affects young adults in different ways and to varying degrees. Most people are positively or negatively affected or even both, and yet most of them use social media anyway. However, this study does not answer why or in what way social media affects us because it was not the purpose of the study to investigate this.
Krishantering idag har vidgats i och med sociala mediers uppkomst som medför både möjligheter och hot. Möjligheterna som finns är att det är lättare än någonsin att interagera med en stor målgrupp ...och skapa sömlösa relationer. Å andra sidan skapar det snabb spridning av information vilket kan vara ett hot för en organisation. Kommer falska påståenden ut om ett företag så kan det skapa missnöje men det kan också snabbt bli en sanning som orsakar skada för företaget/varumärket eller organisationen. Syftet med denna studie är att få en bättre inblick i hur kommunerna använder sig av kriskommunikation med dagens kommunikationsteknologi vid en pågående kris. Kris studien undersöker vattenläckor. Kommunikationsteknologin kommer i denna studie avgränsas till sociala medier, mer specifikt Facebook. De tre kommuner som har undersökts är Gävle, Lidingö och Motala kommun. De teoretiska utgångspunkter studien använder sig av är kriskommunikation och strategisk kommunikation. Metoderna som har använts för studien är två kvalitativa, varav en innehållsanalys och intervjuer. Intervjuerna gjordes med de tre kommunikationscheferna i kommunerna för att få en bättre insikt i kommunernas sätt att arbeta med kriskommunikation. Studiens undersökning kom fram till att kommunerna vill utveckla och använda sig mer av Facebook som en kommunikationskanal vid krissituationer för att nå invånarna i kommunen.
Crisis management today has expanded as to social media’s origination, bringing both opportunities and threats. The opportunities available are that it is easier than ever to interact with a large audience and to create seamless relations. However, threats can arise as it creates a rapid dissemination of information which can harm an organization. Moreover false statements being spread out about a company may cause dissatisfaction, additionally rumours can very fast become the truth that cause damage to the company/brand or the organisation. The purpose of this case study is to get a better insight into how three municipalities use their crisis communication with today's communication technology at hand. Communication technology will be defined in this study as social media, and more specifically Facebook. The three municipalities that have been investigated are Gävle, Lidingö and Motala municipality. The theoretical issues this paper is focusing on are crisis communication and strategic communication. Research within other areas is taken into account, as it is relevant for this study and its purpose. The empirical examination consists of a case study of how the three municipalities use their crisis communication. The methods used in this study are a quantitative content analysis of the three municipalities’ Facebook submissions regarding water leaks and a qualitative interview with the person being responsible for each municipality’s communication. The study found that the municipalities want to develop and use more of Facebook as a communication channel in crisis situations to reach residents of the municipality.
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