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This study identified and discussed principals' perceptions of acceleration and enrichment for gifted students. These areas have proven significant for the teaching of the gifted. The research questions included questions about perceptions of giftedness and how principals organize to allow gifted students to develop and learn based on their conditions and needs. The empirical material consisted of open questions where the informants freely could describe their knowledge and perceptions about gifted students and their education. The principals' mission statement formed the theoretical basis for analysis. The method used was content analysis. Previous research has shown that acceleration and enrichment are significant for teaching and learning for gifted students. It is therefore of importance that principals, responsible for the activities of the schools they are responsible for, are aware of these and enable the teachers to work with acceleration and enrichment based on the different needs of the gifted students. The results showed that the principals in the study believed that (a) acceleration should primarily take place in the gifted students' age-appropriate class, (b) second by studying subjects or courses with higher classes, (c) third, that the teachers enable enrichment for gifted students in their age-appropriate class, (d) fourth, grade skipping is complicated and should be avoided.

To review the longitudinal trajectories -- and the factors influencing their development -- of mental health problems in children with neurodevelopmental disabilities. Systematic review methods were employed. Searches of six databases used keywords and MeSH terms related to children with neurodevelopmental disabilities, mental health problems, and longitudinal research. After the removal of duplicates, reviewers independently screened records for inclusion, extracted data (outcomes and influencing factors), and evaluated the risk of bias. Findings were tabulated and synthesized using graphs and a narrative. Searches identified 94,662 unique records, from which 49 publications were included. The median publication year was 2015. Children with attention deficit hyperactivity disorder were the most commonly included population in retrieved studies. In almost 50% of studies, trajectories of mental health problems changed by < 10% between the first and last time point. Despite multiple studies reporting longitudinal trajectories of mental health problems, greater conceptual clarity and consideration of the measures included in research is needed, along with the inclusion of a more diverse range of populations of children with neurodevelopmental disabilities.

Abstract Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variants associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases. By screening 80 human proteins, we identified 366 mutation-modulated interactions, with half of the mutations diminishing binding, and half enhancing binding or creating novel interaction interfaces. The effects of the mutations were confirmed by affinity measurements. In cellular assays, the effects of motif-disruptive mutations were validated, including loss of a nuclear localisation signal in the cell division control protein CDC45 by a mutation associated with Meier-Gorlin syndrome. The study provides insights into how disease-associated mutations may perturb and rewire the motif-based interactome.

Abstract The study aimed to investigate differences in hypertensive‐ and cardio‐preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men = 1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women.

Abstract The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

Abstract Background Two isoforms of Phosphoinositide 3-kinase (PI3K), p110γ and p110δ, are predominantly expressed in leukocytes and represent attractive therapeutic targets for the treatment of allergic asthma. The study aim was to assess the impact of administration of an inhaled PI3Kγδ inhibitor (AZD8154) in a rat model of asthma. Methods Firstly, we checked that the tool compound, AZD8154, inhibited rat PI3K γ & δ kinases using rat cell-based assays. Subsequently, a time-course study was conducted in a rat model of asthma to assess PI3K activity in the lung and how it is temporally associated with other key transcription pathways and asthma like features of the model. Finally, the impact on lung dosed AZD8154 on target engagement, pathway specificity, airway inflammation and lung function changes was assessed. Results Data showed that AZD8154 could inhibit rat PI3K γ & δ isoforms and, in a rat model of allergic asthma the PI3K pathway was activated in the lung. Intratracheal administration of AZD8154 caused a dose related suppression PI3K pathway activation (reduction in pAkt) and unlike after budesonide treatment, STAT and NF-κB pathways were not affected by AZD8154. The suppression of the PI3K pathway led to a marked inhibition of airway inflammation and reduction in changes in lung function. Conclusion These data show that a dual PI3Kγδ inhibitor suppress key features of disease in a rat model of asthma to a similar degree as budesonide and indicate that dual PI3Kγδ inhibition may be an effective treatment for people suffering from allergic asthma.

IntroductionCampylobacter jejuni gastroenteritis is the most commonly reported zoonosis within the EU, with poultry products regarded as the primary source of transmission to humans. Therefore, finding strategies to reduce Campylobacter colonization in broilers holds importance for public health. Recent studies suggest that supplementation of broiler feed with brown algal extracts, particularly laminarin, can provide beneficial effects on broiler gut health, growth performance, and gut microbiota. However, its effect on gut microbiota development and subsequent reduction of Campylobacter loads in broiler caeca during the later stages of the birds' lives remains unclear.MethodsExperimental colonization of Ross 308 broilers with two different strains of C. jejuni was conducted, with groups fed either a basal diet or the same basal diet supplemented with 725 ppm algal extract from Saccharina latissima to provide 290 ppm laminarin. Fecal samples were collected for bacterial enumeration, and caecal samples were obtained before and after the C. jejuni challenge for the determination of microbiota development.Results and discussionNo significant differences in fecal C. jejuni concentrations between the groups fed different diets or exposed to different C. jejuni strains were observed. This suggests that both strains colonized the birds equally well and that the laminarin rich algal extract did not have any inhibitory effect on C. jejuni colonization. Notably, 16S rRNA amplicon sequencing revealed detailed data on the caecal microbiota development, likely influenced by both bird age and C. jejuni colonization, which can be valuable for further development of broiler feed formulations aimed at promoting gut health.

Abstract Background Older adults have complex medical needs that causes increased use of resources at the emergency department (ED). The prevalence of non-specific complaint (NSC) as a chief-complaint in the ED is common among older adults and is not prioritized even though possibly having worse clinical outcome. The objective was to study hospital admission and mortality for older adults visiting the ED with NSC compared to specific complaints such as dyspnea, chest pain and abdominal pain. Methods A retrospective observational study of older adults visiting the ED with NSC and specific complaints; dyspnea, chest pain and abdominal pain was performed. Chief-complaint were collected from electronic medical records. Fatigue, confusion, non-specific complaints, generalized weakness and risk of falling were defined as non-specific complaint (NSC) when registered as chief-complaint at the ED. Admission rate and 30-days mortality were the primary outcomes. Results A total of 4927 patients were included in the study based on chief-complaint; patients with chest pain 1599 (32%), dyspnea 1343 (27%), abdominal pain 1460 (30%) and NSC 525 (11%). Patients with dyspnea and NSC had the highest hospital admission rate 79% vs 70% compared to patients with chest pain (63%) and abdominal pain (61%) (p =

Abstract Background Light microscopy and rapid diagnostic tests (RDT) have long been the recommended diagnostic methods for malaria. However, in recent years, loop-mediated isothermal amplification (LAMP) techniques have been shown to offer superior performance, in particular concerning low-grade parasitaemia, by delivering higher sensitivity and specificity with low laboratory capacity requirements in little more than an hour. In this study, the diagnostic performance of two LAMP kits were assessed head-to-head, compared to highly sensitive quantitative real time PCR (qPCR), in a non-endemic setting. Methods In this retrospective validation study two LAMP kits; Alethia® Illumigene Malaria kit and HumaTurb Loopamp™ Malaria Pan Detection (PDT) kit, were evaluated head-to-head for detection of Plasmodium-DNA in 133 biobanked blood samples from suspected malaria cases at the Clinical Microbiology Laboratory of Region Skåne, Sweden to determine their diagnostic performance compared to qPCR. Results Of the 133 samples tested, qPCR detected Plasmodium DNA in 41 samples (defined as true positives), and the two LAMP methods detected 41 and 37 of those, respectively. The results from the HumaTurb Loopamp™ Malaria PDT kit were in complete congruence with the qPCR, with a sensitivity of 100% (95% CI 91.40–100%) and specificity of 100% (95% CI 96.07–100%). The Alethia® Illumigene Malaria kit had a sensitivity of 90.24% (95% CI 76.87–97.28) and a specificity of 95.65% (95% CI 89.24–98.80) as compared to qPCR. Conclusions This head-to-head comparison showed higher performance indicators of the HumaTurb Loopamp™ Malaria PDT kit compared to the Alethia® illumigene Malaria kit for detection of malaria.

PurposeThis study aimed to explore whether a meaningful improvement in physical performance following an in-season strength training intervention can be related to external load match parameters at an individual level in professional male football players.MethodsEight male professional football players (25.4 ± 3.1 years, 184.1 ± 3.4 cm, 79.3 ± 2.2 kg) completed a 10-week strength intervention period in addition to football-specific training and matches. Commonly used physical and external load measures were assessed before and after intervention. Physical performance improvements had to exceed the measurement’s typical error and the smallest worthwhile difference (SWD) to be considered meaningful. External load match parameters were assessed before and after the intervention period using SWD and non-overlap of all pairs (NAP) analysis. A Bayesian pairwise correlation analysis was performed to evaluate relationships between changes in physical performance and external load match parameters.ResultsThree players displayed meaningful improvements in two to five physical performance measures. However, positive changes exceeding the SWD and positive effects in NAP results were observed for all players in external load match parameters. Kendall's tau correlation analysis showed evidence (base factor >3) for only one correlation (maximum speed − decelerations, τ = −0.62) between the changes in physical performance and external load measures, while the remaining comparisons exhibited no relation.ConclusionsThe findings suggest that improvements in physical performance may not necessarily translate to improvements in external load match parameters. Further research, with larger sample sizes, is needed to understand potential mechanisms between acute and chronic physical performance changes and football external load parameters during training and matches.

This study explored professional wrestlers’ experiences of the consequences of an anterior cruciate ligament (ACL) injury and their perception of whether the ACL injury could have been prevented. We interviewed 10 professional wrestlers (60% women, age range 21–34) treated with ACL reconstruction with semistructured interviews. Transcripts were analysed using qualitative content analysis: One major theme, ‘Wrestling with a ghost: facing an opponent I can neither see nor clinch’, supported by five main categories, emerged from the collected data. The five main categories were: My ACL injury: bad luck or bad planning?; The way back: a fight to return to sport; Only performance counts; The injury’s impact on life: a wrestling with emotions; In hindsight, personal growth. Professional wrestlers who experienced an ACL injury expressed that not only the injury itself but also the subsequent recovery posed major challenges that they did not know how to deal with and that, in some cases, ended the athletes’ wrestling careers. Professional wrestlers attributed their ACL injuries to bad luck or large training loads and wished that they had more support from the wrestling community when injured.

ABSTRACT: This study examined the effects of including live black soldier fly (BSF, Hermetia illucens) larvae in the diet of laying hens on gut microbiota, and the association between microbiota and fearfulness. A total of 40 Bovans White laying hens were individually housed and fed 1 of 4 dietary treatments that provided 0, 10, 20%, or ad libitum daily dietary portions of live BSF larvae for 12 wk. Cecum microbiota was collected at the end of the experiment and sequenced. Behavioral fear responses to novel objects and open field tests on the same hens were compared against results from gut microbiota analyses. The results showed that the bacteria genera Enterococcus, Parabacteroides, and Ruminococcus torques group were positively associated with increased dietary portion of live larvae, while Lactobacillus, Faecalibacterium, Bifidobacterium, Subdoligranulum, and Butyricicoccus were negatively associated with larvae in the diet. Inclusion of larvae did not affect fear behavior, but the relative abundance of Lachnospiraceae CHKCI001 and Erysipelatoclostridium was associated with fear-related behaviors. Further studies are needed to determine whether the change in gut microbiota affects fearfulness in the long‐term.

Abstract Background Active travel and school settings are considered ideal for promoting physical activity. However, previous research suggests limited effect of school-based interventions on overall physical activity levels among adolescents. The relationship between physical activity in different domains remains inconclusive. In this study, we examined the effects of adding two weekly hours of school-based physical activity on active travel rates. Method We analyzed data from 1370 pupils in the 9th-grade participating in the cluster RCT; the School In Motion (ScIM) project. Intervention schools (n = 19) implemented 120 min of class-scheduled physical activity and physical education, in addition to the normal 2 hours of weekly physical education in the control schools (n = 9), for 9 months. Active travel was defined as pupils who reported walking or cycling to school, while motorized travel was defined as pupils who commuted by bus or car, during the spring/summer half of the year (April–September), or autumn/winter (October–February). The participants were categorized based on their travel mode from pretest to posttest as; maintained active or motorized travel (“No change”), changing to active travel (motorized-active), or changing to motorized travel (active-motorized). Multilevel logistic regression was used to analyze the intervention effect on travel mode. Results During the intervention period, most participants maintained their travel habits. In total, 91% of pupils maintained their travel mode to school. Only 6% of pupils switched to motorized travel and 3% switched to active travel, with small variations according to season and trip direction. The intervention did not seem to influence the likelihood of changing travel mode. The odds ratios for changing travel habits in spring/summer season were from active to motorized travel 1.19 [95%CI: 0.53–2.15] and changing from motorized to active travel 1.18 [0.30–2.62], compared to the “No change” group. These findings were consistent to and from school, and for the autumn/winter season. Conclusion The extra school-based physical activity does not seem to affect rates of active travel among adolescents in the ScIM project. Trial registration Clinicaltrials.gov ID nr: NCT03817047. Registered 01/25/2019′ retrospectively registered’.

Abstract The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions involving eight SARS-CoV-2 protein domains were determined (K D ∼ 7-300 μM). Key specificity residues of the peptides were established for six of the interactions. Two of the peptides, binding Nsp9 and Nsp16, respectively, inhibited viral replication. Our findings demonstrate how high-throughput peptide binding screens simultaneously identify potential host-virus interactions and peptides with antiviral properties. Furthermore, the high number of low-affinity interactions suggest that overexpression of viral proteins during infection may perturb multiple cellular pathways.