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Background: Hailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the ATP2C1 gene, which encodes the secretory Ca2+/Mn2+-ATPase (SPCA1) pump in the Golgi apparatus. Although ATP2C1 is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to ATP2C1 has been associated with heart disease., Objective: To investigate the association between HHD and common heart disease in a Swedish, population-based cohort., Methods: We conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers., Results: Compared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0-2.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6-1.7) or heart failure (RR 1.0, CI 0.6-1.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset., Conclusion: This study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus' Ca2+/Mn2+ homeostasis in common heart disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jebril et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sexually transmitted infections (STIs) have a profound impact on sexual and reproductive health worldwide. Syphilis, gonorrhea, chlamydia, and trichomoniasis are four currently curable STIs. However, most STI cases are asymptomatic and not detected without laboratory diagnostics. Hepatitis B virus, herpes simplex virus, human immunodeficiency virus (HIV), and human papillomavirus (HPV) are four viral and incurable infections, but they can be mitigated by treatment. We investigated the prevalence of selected sexually transmitted pathogens and their relationship with HPV and HIV infection in women from Maputo, the capital of Mozambique. A cross-sectional study was conducted on 233 non-pregnant women seeking health care relating to gynecological symptoms in Mavalane Health facilities in Maputo, between the 1st of February 2018 and the 30th of July 2019. Cervical brush samples were collected and DNA was extracted. Selected STIs including HPV were detected using multiplex STD and HPV Direct Flow Chip Kits through a manual Hybrispot platform (Vitro, Master Diagnostica, Sevilla, Spain). HIV testing was performed using rapid tests: Determine HIV 1/2 test (Alere Abbott Laboratories, Tokyo, Japan) for screening, and UniGold HIV (Trinity Biotech, Ireland) for confirmation. All women (n = 233) were negative for Haemophilus ducreyi and Herpes Simplex Virus-1 (HSV-1). Among the 233 women, a high prevalence of STIs was found (89%), 63% of the women were positive for HPV and 24% were HIV positive. Treponema pallidum (TP), Trichomonas vaginalis (TV), Herpes Simplex Virus-2 (HSV-2), and Chlamydia trachomatis (CT) were detected in 17%, 14%, 8%, and 8% of the women, respectively. As a common phenomenon, vaginal discharge (90%) was the lower genital tract symptom reported by the majority of the women. Co-infection with any STI and HPV was detected in 56% (130/233) while 45% (59/130) of the co-infections were with high-risk HPV (hrHPV) genotypes. Among the HPV-positive participants, infection by TP was the most prevalent (27%). In total, 28% (66/233) of the participants were positive for any hrHPV genotypes. Co-infection with any STI and HIV was found in 15% (34/233) of the study participants. There was a significant association between HPV infection and TP (p = 0.039) and HSV-2 (p = 0.005). TV, TP, and CT-S1-CT-S2 positivity were significantly more prevalent in HIV-positive participants. Pathobionts Ureaplasma urealyticum/parvum and Mycoplasma hominis were detected in 84.0% (195/233) and 45% (105/233), respectively. This present study describes a high prevalence of STIs. Co-infection between HPV and STIs was found in the majority of the study subjects. The high prevalence of HPV emphasizes the need for HPV vaccination to prevent cervical cancer in this population. Management of STIs is also important in women presenting with gynecological symptoms., Competing Interests: No authors have competing interests, (Copyright: © 2024 Maueia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim was to examine the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in cohorts of working age stroke survivors, before and after inpatient rehabilitation., Methods: Stroke patients aged 18-66 years registered in the national quality register WebRehab Sweden were included in the study at hospital admission (n = 256), discharge (n = 223), and 1-year follow-up (n = 313). Classical and modern (Rasch) methods were used for psychometric evaluation., Results: The two-factor HADS model measuring anxiety and depression showed better fit than a single factor measuring emotional distress. The instrument's psychometric stability before and after rehabilitation was satisfactory. The anxiety scale showed good psychometric properties, except for item 7, which is not anxiety-specific. Some concerns were observed for the depression items showing weaker discriminant validity, and item 8 performing poorly as a measure of depression. Cronbach's alpha and McDonald's omega coefficients showed satisfactory internal consistency reliability, whereas Rasch person reliability coefficients indicated weaker reliability, especially for the depression scale. Effect size of change between hospital admission and discharge showed a reduction in anxiety and depression symptoms., Conclusions: HADS showed a stable two-factor structure over the rehabilitation period. Patients' perception of items was not affected by the recovery, allowing relevant comparison of HADS scores between different phases of the rehabilitation process. Measures of responsiveness suggest that HADS is sensitive to capturing improvements in emotional distress following rehabilitation interventions. Overall, despite minor psychometric weaknesses, HADS is a suitable instrument for assessing anxiety and depresssion symptoms in stroke patients aged 18-66 years., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Karlsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: An increasing number of patients receive ambulance care without being conveyed to a definitive care provider. This process has been described as complex, challenging, and lacking in guideline support by EMS clinicians. The use of quality- and outcome measures among non-conveyed patients is an understudied phenomenon., Aim: To identify current quality- and outcome measures for the general population of non-conveyed patients in order to describe major trends and knowledge gaps., Methods: A scoping review of peer-reviewed original articles was conducted to identify quality- and outcome measures for non-conveyance within emergency medical services. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement (PRISMA-ScR) was followed. The PROSPERO and OSF database were checked for pending reviews or protocols. PubMed, CINAHL, Scopus, Web of Science and the Cochrane Library database were searched for relevant articles. Searches were performed in November 2023., Results: Thirty-six studies fulfilled the inclusion criteria and were included in the review. Mortality was the most used outcome measure, reported in 24 (67%) of the articles. Emergency department attendance and hospital admission were the following most used outcome measures. Follow-up durations varied substantially between both measures and studies. Mortality rates were found to have the longest follow-up times, with a median follow-up duration a little bit over one week., Conclusions: This scoping review shows that studies report a wide range of quality and outcome measures in the ambulance setting to measure non-conveyance. Reported quality and outcome measures were also heterogeneous with regard to their follow-up timeframe. The variety of approaches to evaluate non-conveyance poses challenges for future research and quality improvement. A more uniform approach to reporting and measuring non-conveyance is needed to enable comparisons between contexts and formal meta-analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Höglund et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immune checkpoint inhibitors (ICIs) have emerged as an effective treatment for colorectal cancer (CRC). Studies indicate that the composition of gut microbiota could potentially serve as a biomarker for predicting the clinical effectiveness of immune checkpoint inhibitors., Methods: Following PRISMA guidelines, the review was conducted after registering the protocol with PROSPERO. A comprehensive literature search was carried out across five databases: PubMed, Scopus, Web of Science, Embase, and Cochrane Library. Assessment tools from the National Institutes of Health (NIH) were used to gauge the quality of the studies., Results: A total of 5,132 papers were identified, and three studies and one conference abstract published between 2017-2022 met the inclusion criteria and were summarized in a descriptive synthesis table. These four studies were in accord with the following findings, four main phyla, Firmicutes, Bacteroidata, Actinobacteria, and Verrucomicrobiota were associated with CRC patients' clinical response toward ICIs treatment. Ruminococcaceae was predominantly related to CRC patients responding to therapy, while the Micrococcaceae family was more common among the non-responders. Bacterial taxa such as Faecalibacterium and Prevotellaceae were associated with better responses to ICIs and could be predictive biomarkers. The signature of fecal microbiota with Akkermansia muciniphila and Eubacterium rectale enrichment, and Rothia mucilaginosa depletion could independently predict better response to ICIs in patients with CRC., Conclusion: The findings have brought attention to the notable differences in terms of richness and composition of microbiota between patients who responded positively to the treatment and those who did not. Bacterial species and families, such as Faecalibacterium, Bifidobacterium, Lachnospiraceae, Akkermansia sp., Ruminococcaceae, and Prevotellaceae, have consistently surfaced as potential indicators of immunotherapeutic responses. Furthermore, this review also emphasizes the need for additional comprehensive, multi-center studies with larger sample sizes to validate reported microbiota and expand our understanding of the role of gut microbiota in CRC ICIs therapy. PROSPERO ID: CRD42021277691., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ajab et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Pectus excavatum, or funnel chest, causes both physical and psychosocial issues, affecting health-related quality of life. However, the literature on how funnel chest affects daily living prior to corrective surgery is sparse. Therefore, the study aimed to describe the experiences of living with funnel chest prior to correctional surgery., Materials and Methods: The study had a qualitative exploratory design. Consecutive sampling was applied in which all individuals from a single cardiothoracic department scheduled for the minimally invasive repair of pectus excavatum were asked to participate. Nineteen participants, 17 men and two women, participated in the study. Individual telephone interviews were conducted from February 2020 until April 2021. The interviews were analyzed with qualitative content analysis using an inductive approach., Results: The overall theme "To have or not to have a cavity in my chest, it could make a difference" was interpreted as the latent meaning of the participants' experiences. The theme included two subthemes with three categories each. The subtheme "The funnel chest puts a weight on my shoulders" describes the heavy burden the funnel chest places on the participants. The second subtheme, "This is me, but I want to change my future", describes that participants see the funnel chest as a part of themselves; nevertheless, they look forward to surgery and a life without it., Conclusion: The results emphasize the heavy burden funnel chest causes and the great limitations it places on the individual. It also highlights the importance of surgery and the hope for a better future for individuals with funnel chest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Norlander et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cholecystectomy remains the standard management for acute cholecystitis. Given that rates of nonoperative management have increased, we hypothesize the existence of significant hospital-level variability in operative rates. Thus, we characterized patients who were managed nonoperatively at normal and lower operative hospitals (>90th percentile)., Methods: All adult admissions for acute cholecystitis were queried using the 2016-2019 Nationwide Readmissions Database. Centers were ranked by nonoperative rate using multi-level, mixed effects modeling. Hospitals in the top decile of nonoperative rate (>9.4%) were classified as Low Operative Hospitals (LOH; others:nLOH). Separate regression models were created to determine factors associated with nonoperative management at LOH and nLOH., Results: Of an estimated 418,545 patients, 9.9% were managed at 880 LOH. Multilevel modeling demonstrated that 20.6% of the variability was due to hospital factors alone. After adjustment, older age (Adjusted Odds Ratio [AOR] 1.02/year, 95% Confidence Interval [CI] 1.01-1.02) and public insurance (Medicare AOR 1.31, CI 1.21-1.43 and Medicaid AOR 1.43, CI 1.31-1.57; reference: Private Insurance) were associated with nonoperative management at LOH. These were similar at nLOH. At LOH, SNH status (AOR 1.17, CI 1.07-1.28) and small institution size (AOR 1.20, CI 1.09-1.34) were associated with increased odds of nonoperative management., Conclusion: We noted a significant variability in the interhospital variation of the nonoperative management of acute cholecystitis. Nevertheless, comparable clinical and socioeconomic factors contribute to nonoperative management at both LOH and non-LOH. Directed strategies to address persistent non-clinical disparities are necessary to minimize deviation from standard protocol and ensure equitable care., Competing Interests: P. Benharash serves as a proctor for AtriCure. The content of this manuscript is unrelated to this work. The others authors have no disclosures. All authors declare no competing interests., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Parental feeding practices (PFPs) play a key role in fostering preschoolers' dietary habits and in mitigating the risk of childhood obesity. Nevertheless, parents often employ inappropriate feeding practices, leading to children's potential nutrition-related issues. Thus, research is needed to inform interventions that focus on optimizing feeding practices., Methods: This protocol describes the evaluation of a novel intervention-Empowering Parents to Optimize Feeding Practices (EPO-Feeding Program). The program will be evaluated with a two-arm feasibility randomized controlled trial (RCT) in Yangzhou, China. The program includes four weekly group-based training sessions led by healthcare professionals for parents of preschool children. The intervention incorporates sessions, group discussions, motivational interviewing, and supplementary materials (e.g., key messages and educational videos) aimed at enhancing parents' knowledge, skills, and behaviours related to feeding practices. The primary outcomes include i) implementation feasibility, primarily assessed through retention rates; and ii) program acceptability through a survey and qualitative process evaluation. Secondary outcomes encompass the potential impacts on i) PFPs, ii) parental perception of child weight (PPCW), iii) parenting sense of competence, iv) children's eating behaviours, and v) child weight status. Quantitative analyses include descriptive estimates for evaluating the feasibility and linear mixed regression analysis for testing the potential effects. Qualitative valuation will use thematic framework analysis., Discussion: If this study shows this program to be feasible to implement and acceptable to parents, it will be used to inform a fully powered trial to determine its effectiveness. The research will also help inform policy and practices in the context of child nutrition promotion, particularly regarding implementing group-based training sessions by healthcare providers in similar settings., Trial Registration: Clinicaltrials.gov, Protocol #NCT06181773, 20/11/2023., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: There is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics., Methods: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). We will use the Population-Intervention-Comparator-Outcomes-Study design (PICOS) criteria for study inclusion and will search the following database sources for relevant RCTs: Web of Science, Academic Search Complete, CINAHL, APA Psycinfo, SPORTDiscuss, Cochrane. Two independent reviewers will conduct the study selection, data extraction, and quality assessment. Disagreement will be solved by a third reviewer. Primary outcome will be changes in overall depression severity and secondary outcomes will encompass changes in symptoms of depression as defined by the DSM-5, such as sleep quality, fatigue, anxiety, mood, apathy, changes in weight, information processing speed, and executive functions, from baseline until the end of the intervention and to any available intermediary measurement or follow up. Meta-analysis will be undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. Subgroup analysis will investigate the moderating effects of intervention characteristics (frequency, intensity, duration, type of exercise, cognitive demand, social interactions, exercise supervision, behavioral change techniques, compliance, study design, dropout-rate, type of control group) and individual characteristics (age, sex, education, functional capacity, global cognition, population) on primary and secondary outcomes. Additionally, we plan to assess quality of evidence and publication bias, and to carry out sensitivity analysis., Conclusion: The results of the proposed review are anticipated to have a substantial impact on research and clinical practice. On the one hand, the review's conclusions could form the foundation for developing evidence-based recommendations for individualized exercise programs that alleviate depression in older adults. On the other hand, by revealing research gaps, the review results could encourage the formulation of research questions for further RCTs., Protocol Registration Number: This protocol has been published in the Prospero repository (PROSPERO 2022 CRD42022361418, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361418)., Competing Interests: All the authors of this manuscript are members of the COST network PhysAgeNet (CA 20104). The authors have declared that no competing interest exists. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Mack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation., Methods: Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597]., Discussion: To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aburawi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Lower autonomic arousal is a well-known correlate of criminal offending and other risk-taking behaviors in men, but few studies have investigated this association in women., Aim: To test associations between autonomic arousal and criminal offending as well as unintentional injuries among female conscripts., Methods: All women born 1958-1994 in Sweden who participated in voluntary military conscription (n = 12,499) were identified by linking Swedish population-based registers. Predictors were resting heart rate (RHR) and systolic blood pressure (SBP). Covariates were height, weight, and physical energy capacity. Main outcomes were criminal convictions (any, violent, and non-violent) from the National Crime Register. Secondary outcome was unintentional injuries requiring medical treatment or causing death. We used survival analyses to test for associations between predictors and outcomes., Results: Low RHR, relative to high RHR, was associated with an increased risk of any criminal conviction, non-violent criminal convictions, and unintentional injuries. Low SBP, relative to high SBP, was associated with an increased risk of violent criminal convictions., Conclusions: Results support lower autonomic arousal, particularly lower RHR, as a correlate of criminal offending among women that warrants further examination, as the reported findings have potential implications for the prediction of future female crime., Competing Interests: H Larsson has served as a speaker for Evolan Pharma and Shire/Takeda and has received research grants from Shire/Takeda; all outside the submitted work. The other authors report no financial relationships with commercial interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Oskarsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The primary aim of this study was to describe the current practice regarding pain management in relation to tonsil surgery among Ear Nose and Throat (ENT) clinics in Sweden. The secondary aim was to determine the impact of the provider's regime of rescue analgesics on the pain related Patient Reported Outcome Measures (pain-PROMs) from the Swedish Quality Register for Tonsil Surgery (SQTS)., Materials & Methods: A descriptive cross-sectional study originating from a validated web-based questionnaire. The survey enrolled one respondent from each ENT clinic (47/48 participated) nationally. Pain-PROMs from the SQTS, recorded from October 2019 to October 2022, were included (8163 tonsil surgeries)., Results: Paracetamol was used by all enrolled ENT clinics as preemptive analgesia. The addition of COX inhibitors was used in 40% of the clinics. Betamethasone was usually administered, to prevent pain and nausea (92%). All clinics gave postdischarge instructions on multimodal analgesia with COX inhibitors and paracetamol. Rescue analgesics were prescribed after tonsillectomy for 77% of adults, 62% of older children, 43% of young children and less often after tonsillotomy. The most frequently prescribed rescue analgesic was clonidine in children (55%) and oxycodone in adults (72%). A high proportion of patients reported contact with health care services due to postoperative pain (pain-PROMs/ SQTS). Tonsillectomy procedures were associated with the highest rates of contacts (children/adolescents 13-15%; adults 26%), while tonsillotomy were associated with lower rates, (5-7% of children/adolescents). There was no significant difference in the frequency of health care contacts due to pain regarding whether clinics routinely prescribed rescue analgesics or not after tonsillectomy., Conclusion: The Swedish analgesic regimen after tonsil surgery is good overall. Nevertheless, there is a need for increased awareness and knowledge to achieve optimal patient recovery. Pain-PROM data demonstrate the call for improvement in pain management after tonsil surgery., Competing Interests: There was no financial support, no funding and no conflict of interest during the preparation of this article. The authors have declared that no competing interest exist., (Copyright: © 2024 Roskvist et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this cross-sectional study, we aimed to I) investigate the dual-factor model of mental health by forming and describing four participant groups and II) examine associations between mental health status and background factors, school-related factors, stress, and resilience among adolescents in a community population in Sweden. Data were collected through a survey completed by 2,208 students in lower and upper secondary school on the Swedish island of Gotland. After missing data were removed, a total of 1,833 participants were included in the study. The survey included the Mental Health Continuum Short Form (MHC-SF) for the assessment of mental well-being and the Strengths and Difficulties Questionnaire (SDQ) for the assessment of mental health problems. These two measures were combined into a dual-factor model, forming four mental health status subgroups: Vulnerable (47.5%), Complete mental health (36.2%), Troubled (13.9%), and Symptomatic but content (2.5%). Associations between these groups were explored regarding background factors, school-related factors, stress, and resilience through chi-squared tests and logistic regressions. Girls (OR: 1.88) and participants with high stress levels (OR: 2.23) had elevated odds for Vulnerable mental health status, whereas higher resilience (OR: 0.87) and subjective social status in school (OR: 0.76) were factors associated with reduced odds for this mental health status classification. Female gender (OR: 5.02) was also associated with Troubled mental health status. Similarly, a high level of stress (ORs: 4.08 and 11.36) was associated with Symptomatic but content and Troubled mental health status, and participants with higher levels of resilience had decreased odds for being classified into these groups (ORs: 0.88 and 0.81). The findings highlight the importance of interventions to increase resilience, reduce stress, and address stereotypic gender norms as well as social status hierarchies to support adolescents' mental health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hermann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mozambique is a high-prevalence country for HIV and early detection of new HIV infections is crucial for control of the epidemic. We aimed to evaluate the accuracy of the 4th-generation rapid diagnostic test (RDT) AlereTM HIV Combo in detecting acute and seroconverted HIV-infection, among sexually-active women attending three clinical health centers in Maputo, Mozambique., Methods: Women aged 14-55 years (n = 920) seeking care at the Mavalane Health Area, Maputo (February 2018-January 2019) were included, and blood specimens sampled. Sociodemographic and sexual behavior data were collected. Point-of-care HIV testing was performed using Alere DetermineTM HIV-1/2 and Uni-GoldTM HIV-1/2. All samples were also tested using Enzygnost® HIV Integral 4 and Innotest® HIV Antigen mAb in laboratory. The 4th-generation RDT AlereTM HIV Combo was evaluated on serum samples in the laboratory. Finally, Innotest® HIV Antigen mAb, Enzygnost® HIV Integral 4 (Ag/Ab), and HIV RNA quantification acted as gold standard assays in the evaluation of AlereTM HIV Combo test for HIV antigen detection (in clinical samples and in three HIV-1 seroconversion panels)., Results: The antibody component of the 4th generation AlereTM HIV Combo RDT demonstrated a sensitivity and specificity of 100% examining clinical samples. However, the test did not detect HIV p24 antigen in any clinical samples, while Innotest® HIV Antigen mAb, verified by Enzygnost® HIV Integral 4 (Ag/Ab) and/or HIV RNA quantification, detected HIV antigen in six clinical samples. Furthermore, the AlereTM HIV Combo RDT had a low sensitivity in the detection of HIV p24 antigen in seroconversion panels. The HIV prevalence among the examined women was 17.8%., Conclusions: The 4th-generation RDT AlereTM HIV Combo showed similar sensitivity to the 3rd-generation RDTs to detect seroconverted HIV-infections. However, the sensitivity for detection of HIV p24 antigen and diagnosing acute HIV infections, before seroconversion, was low. There is an urgent need to develop and evaluate simple and affordable POC tests with high sensitivity and specificity for diagnosing individuals with acute HIV infection in resource-limited settings with high HIV prevalence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Manjate et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Three billion people in low- and middle-income countries are exposed to household air pollution as they use biomass fuel for cooking. We investigated the associations between solid fuel use and nasopharyngeal (NP) inflammation, as well as the associations between high pneumococcal density and NP inflammation, in mothers and children in rural and urban Ethiopia., Materials and Methods: Sixty pairs of mothers (median age, 30 years; range, 19-45 years) with a child (median age, 9 months; range, 1-24 months) were included from rural Butajira (n = 30) and urban Addis Ababa (n = 30) in Ethiopia. The cohort was randomly selected from a previous study of 545 mother/child pairs included 2016. Questionnaire-based data were collected which included fuel type used (solid: wood, charcoal, dung or crop waste; cleaner: electricity, liquefied petroleum gas). Nasopharyngeal (NP) samples were collected from all mothers and children and analyzed for the levels of 18 cytokines using a Luminex immunoassay. Pneumococcal DNA densities were measured by a real-time multiplex PCR and a high pneumococcal density was defined as a cyclic threshold (Ct) value ≤ 30., Results: Mothers from rural areas had higher median CXCL8 levels in NP secretions than those from urban areas (8000 versus 1900 pg/mL; p < 0.01), while rural children had slightly higher IL-10 levels than those from the urban area (26 vs 13 pg/mL; p = 0.04). No associations between fuel type and cytokine levels were found. However, a high pneumococcal density was associated with higher levels of cytokines in both mothers (CCL4, CXCL8, IL-1β, IL-6 and VEGF-A) and children (CCL4, CXCL8, IL-1β, IL-6 and IL-18)., Conclusions: No significant associations were found between solid fuel use and NP inflammation in Ethiopian mothers and children, but the inflammatory activity was higher in individuals living in the rural compared to the urban area. In addition, high cytokine levels were associated with high pneumococcal density in both mothers and children, indicating a significant impact of NP pathogens on inflammatory mediator levels in upper airways., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Olsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Due to the invasive nature of surgical procedures and the involvement of medical personnel, torture survivors may experience re-traumatization during surgical treatment. This study aimed to explore torture survivors' experiences of re-traumatization during surgical treatment as well as the process by which trauma-related emotions and responses are evoked during surgical treatment for torture survivors. Eight men, aged 45 to 72, from four different countries, who have lived in Norway for 6-40 years, were recruited. We assessed torture and surgical care experiences through in-depth interviews, and the data were analyzed using thematic analysis, resulting in five themes: (1) Interactions with healthcare providers, (2) Reactions during treatment, (3) Triggers causing re-experiences, (4) Avoidance, and (5) Suggestions to healthcare providers. In this study, survivors reported challenges receiving surgical treatment, indicating re-traumatization and difficulty returning to daily life following treatment. Participants reported little collaboration in care-related decision-making processes, lack of recognition of torture by healthcare providers involved in surgical care and experiencing healthcare professionals' attitudes as a source of perplexity, frustration, and despair. Exacerbation of torture memories throughout treatment and re-experiencing of trauma symptoms aggravated these difficulties. Our findings suggest that surgical treatment can remind torture survivors of the traumatic aspects of torture, eliciting strong reactions and feelings like those experienced during torture., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Schippert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Testosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments., Methods: Testosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose., Results: The testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected., Conclusion: The current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women., Competing Interests: “JOS received advisory board fees from Bayer Pharmaceuticals during 2016 and 2019, but the advisory boards were not in any way related to the subject of the current paper. JKP, ISP, ET and EI have no relevant financial or non-financial interests to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2023 Preinbergs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Lay online communication about health-related issues has in recent years largely been associated with the spread of misinformation and decreased trust in healthcare. Such communication has included claims about systemic side effects of the copper IUD. In Sweden, a social media group centered on this issue now gathers around 8,700 members. This study aimed to use the case of reported yet unestablished side effects of the copper IUD to investigate experiences of and reasoning about healthcare encounters between caregivers and patients contesting established medical knowledge., Methods: We conducted qualitative, semi-structured, digital group interviews with members of the social media group (seven groups, n = 23) and with midwives and gynecologists (six groups, n = 15). We also gathered essays written by social media group members (n = 23). The material was analyzed thematically., Results: The participant accounts pointed towards tensions related to principles of evidence-based medicine, i.e., perceived insufficiency of research on the safety of the copper IUD and lack of clarity in routines for reporting and following up suspected side effects, and of patient-centered care, i.e., listening respectfully to patients. Tension between caregivers' obligation to adhere to evidence-based medicine while also providing patient-centered care was noted., Conclusion: Healthcare providers' efforts to assess and address patient claims contesting established medical knowledge should include ensuring and communicating sufficient research, clarifying procedures for reporting suspected side effects, and improving person-centered care. This can increase the quality of care while contributing to the mitigation of distrust in healthcare and the spreading of health-related misinformation., Competing Interests: The authors have no conflicts of interests to report., (Copyright: © 2023 Wemrell, Gunnarsson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Brown bears (Ursus arctos) prepare for winter by overeating and increasing adipose stores, before hibernating for up to six months without eating, drinking, and with minimal movement. In spring, the bears exit the den without any damage to organs or physiology. Recent clinical research has shown that specific lipids and lipid profiles are of special interest for diseases such as diabetes type 1 and 2. Furthermore, rodent experiments show that lipids such as sulfatide protects rodents against diabetes. As free-ranging bears experience fat accumulation and month-long physical inactivity without developing diabetes, they could possibly be affected by similar protective measures. In this study, we investigated whether lipid profiles of brown bears are related to protection against hibernation-induced damage. We sampled plasma from 10 free-ranging Scandinavian brown bears during winter hibernation and repeated sampling during active state in the summer period. With quantitative shotgun lipidomics and liquid chromatography-mass spectrometry, we profiled 314 lipid species from 26 lipid classes. A principal component analysis revealed that active and hibernation samples could be distinguished from each other based on their lipid profiles. Six lipid classes were significantly altered when comparing plasma from active state and hibernation: Hexosylceramide, phosphatidylglycerol, and lysophosphatidylglycerol were higher during hibernation, while phosphatidylcholine ether, phosphatidylethanolamine ether, and phosphatidylinositol were lower. Additionally, sulfatide species with shorter chain lengths were lower, while longer chain length sulfatides were higher during hibernation. Lipids that are altered in bears are described by others as relevant for and associated with diabetes, which strengthens their position as potential effectors during hibernation. From this analysis, a range of lipids are suggested as potential protectors of bear physiology, and of potential importance in diabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tekin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate individual effects of a three-week sleep robot intervention in adults with ADHD and insomnia, and to explore participants' experiences with the intervention., Methods: A proof-of-concept study with a mixed-methods design (n = 6, female = 4) where a repeated ABA single-case study was combined with interviews. Data were collected with the Consensus Sleep Diary, wrist actigraphy, questionnaires on symptoms of insomnia, arousal, emotional distress, and ADHD, and through individual interviews., Results: Visual analysis of the sleep diary and actigraphy variables did not support any effects from the robot intervention. Half of participants reported clinically relevant reductions on the Insomnia Severity Index from pre- to post-intervention. No changes regarding ADHD or arousal. Thematic analysis of the interviews resulted in three themes: (1) A pleasant companion, (2) Too much/not enough, and (3) A new routine., Conclusion: Adjustments of the intervention ought to be made to match the needs of patients with both ADHD and insomnia before the next trial is conducted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Støre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although recent technological developments in the field of bionic upper limb prostheses, their rejection rate remains excessively high. The reasons are diverse (e.g. lack of functionality, control complexity, and comfortability) and most of these are reported only through self-rated questionnaires. Indeed, there is no quantitative evaluation of the extent to which a novel prosthetic solution can effectively address users' needs compared to other technologies. This manuscript discusses the challenges and limitations of current upper limb prosthetic devices and evaluates their functionality through a standard functional assessment, the Assessment of Capacity for Myoelectric Control (ACMC). To include a good representation of technologies, the authors collect information from participants in the Cybathlon Powered Arm Prostheses Race 2016 and 2020. The article analyzes 7 hour and 41 min of video footage to evaluate the performance of different prosthetic devices in various tasks inspired by activities of daily living (ADL). The results show that commercially-available rigid hands perform well in dexterous grasping, while body-powered solutions are more reliable and convenient for competitive environments. The article also highlights the importance of wrist design and control modality for successful execution of ADL. Moreover, we discuss the limitations of the evaluation methodology and suggest improvements for future assessments. With regard to future development, this work highlights the need for research in intuitive control of multiple degrees of freedom, adaptive solutions, and the integration of sensory feedback., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Capsi-Morales et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Family involvement in care can be seen as a prerequisite for high-quality family-centered care. It has been identified to improve both patient safety and the quality of care by reducing patient complications and hospital length of stay., Objective: To develop and evaluate the content validity of a questionnaire measuring family involvement in inpatient care., Methods: The study followed a systematic approach in building a rigorous questionnaire: identification of domain, item generation, and assessment of content validity. The content validity index was calculated based on ratings of item relevance by an expert group consisting of seven senior nurses. Subsequently, 19 online cognitive interviews using the Think-aloud method were conducted with family members of former patients who had undergone open-heart surgery., Results: Five aspects of family involvement were identified, and the initial pool of items were selected from two preexisting questionnaires. The experts' ratings resulted in item content validity of 0.71-1.00, and the scale content validity/averaging was 0.90, leading to rewording, exclusion, and addition of items. The pretesting of items through two rounds of cognitive interviews with family members resulted in the identification of three main problem areas: defining family involvement, misinterpretation of different terms, and underuse of the not relevant response option. The problems were adjusted in the final version of the questionnaire, which consists of 16 items with a four-point Likert scale and two open-ended items., Conclusions: The Family Involvement in Care Questionnaire has demonstrated potential in evaluating family involvement in inpatient care. Further psychometric properties regarding reliability and validity need to be established., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Drakenberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Strandvik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Given the predominance of the theory of planned behaviour (TPB) to represent the psychological determinants underlying people's charitable decisions, the present study synthesised the model's key relationships, using meta-analysis, and tested the predictive utility of the model for charitable giving encompassing donations of blood, organs, time, and money. Given its relevance to altruistic decisions, the impact of moral norm was assessed also. A systematic literature review identified 117 samples (from 104 studies) examining donation intentions and/or prospective behaviour using TPB measures. The sample-weighted average effects for all associations were moderate-to-strong with perceived behavioural control (PBC) most strongly associated with intention (r+ = 0.562), followed by moral norm (r+ = 0.537), attitude (r+ = 0.507), and subjective norm (r+ = 0.472). Intention (r+ = 0.424) showed stronger associations with prospective behaviour than PBC (r+ = 0.301). The standard TPB predictors explained 44% of variance in intention (52% including moral norm). Intention and PBC explained 19% of variance in behaviour. A number of TPB associations showed differences when analysed for moderator variables such as length of follow-up for prospective behaviour and type of target behaviour. Stronger associations were found for the (subjective and moral) norm-intention associations among some of the different types of giving behaviours, especially for donating organs and time. Overall, the large proportion of variance explained by the TPB predictors especially for intention highlights those cognitions associated with people's plans to give, informative for charities reliant on people's propensity to give., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 White et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The personal economic impact of bariatric surgery is not well-described., Objectives: To examine earnings and work loss from 5 years before to 5 years after bariatric surgery compared with the general population., Setting: Nationwide matched cohort study in the Swedish health care system., Methods: Patients undergoing primary bariatric surgery (n = 15,828) and an equal number of comparators from the Swedish general population were identified and matched on age, sex, place of residence, and educational level. Annual taxable earnings (primary outcome) and annual work loss (secondary outcome combining months with sick leave and disability pension) were retrieved from Statistics Sweden. Participants were included in the analysis until the year of study end, emigration or death., Results: From 5 years before to 5 years after bariatric surgery, earnings increased for patients overall and in subgroups defined by education level and sex, while work loss remained relatively constant. Bariatric patients and matched comparators from the general population increased their earnings in a near parallel fashion, from 5 years before (mean difference -$3,489 [95%CI -3,918 to -3,060]) to 5 years after surgery (-$4,164 [-4,709 to -3,619]). Work loss was relatively stable within both groups but with large absolute differences both at 5 years before (1.09 months, [95%CI 1.01 to 1.17]) and 5 years after surgery (1.25 months, [1.11 to 1.40])., Conclusions: Five years after treatment, bariatric surgery had not reduced the gap in earnings and work loss between surgery patients and matched comparators from the general population., Competing Interests: Dr. Neovius reports receipt of advisory board fees from Itrim (a commercial vendor for lifestyle interventions) and Ethicon Johnson & Johnson. Dr. Näslund reports personal fees, outside the submitted work, from Baricol Bariatrics AB, Sweden, personal fees from Ethicon, Johnson & Johnson, and personal fees from AstraZenica A/S Denmark. Dr. Näslund is the previous director of the Scandinavian Obesity Surgery Registry. Dr. Ottosson reports personal fees as advisory board member for Ethicon Johnson & Johnson and for Vifor Pharma, and is the current director of the Scandinavian Obesity Surgery Registry. Dr. Norrbäck and Dr. Bruze declare that they have no conflict of interests., (Copyright: © 2023 Norrbäck et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Business angels dominate early-stage investment in firms, but research on their effects on firms is scarce and limited by sample selection. To address sample selection, we propose using population data and we develop an algorithm for identifying business angel investments in such data. We illustrate this novel approach by applying it to detailed and longitudinal total population data for individuals and firms in Sweden. In our application, we focus on a subset of business angels-active business angels who are themselves successful entrepreneurs with a profitable exit. We then study active business angels' effects on firm performance, using population data. Employing a quasi-experimental estimator, we find that the business angels invest in firms that already perform above par. There is also a positive effect on subsequent growth compared with control firms. However, contrary to previous research on business angels, we cannot find any impact on firm survival. Overall, the paper underlines the need to address sample selection when studying business angels and suggests using population data for identification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lodefalk, Andersson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Intravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes., Methods: We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015-2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models., Results: The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis., Conclusions: Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liedberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of the study was to explore and describe how workers in communication-intense workplaces in health care and preschools experience the sound environment. The dependence on vocal communication and social interaction poses a challenge using hearing protection in these working environments., Method: A qualitative method was used, more specifically inductive thematic analysis was used, as this approach was deemed suitable to explore the staff's experiences of the sound environment. Data were collected by interviews and to increase trustworthiness, several researchers were involved in the data collection and analysis., Study Sample: Workers from two preschools, one obstetrics ward and one intensive care unit took part in the study., Results: Four main themes emerged from the thematic analysis: A challenging and harmful sound environment; Health-related effects of a challenging and harmful sound environment; A good sound environment is not prioritised; and Resourceful and motivated staff., Conclusions: Workers in communication-intense workplaces in preschools, obstetrics care and intensive care reported that there was a relationship between the sound environment and negative health effects. In addition, the results suggests that the high motivation for change among staff should be utilised together with an increased prioritization from the management to reach innovative context specific improvements to the sound environment in communication intense working environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gyllensten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) in early stages is challenging. The aim of this study was therefore to investigate whether electrocardiographic imaging (ECGI) can detect epicardial conduction changes in ARVC patients and healthy mutation-carriers (M-carriers)., Method: Twelve ARVC patients, 20 M-carriers and 8 controls underwent 12-lead ECG, signal-averaged ECG, 2-dimensional echocardiography, 24-hours Holter monitoring and ECGI (body surface mapping and computer tomography with offline analysis of reconstructed epicardial signals). Total and Right Ventricular Activation Time (tVAT and RVAT respectively), area of Ventricular Activation during the terminal 20 milliseconds (aVAte20) and the activation patterns were compared between groups., Results: In ARVC patients the locations of aVAte20 were scattered or limited to smaller parts of the right ventricle (RV) versus in controls, in whom aVAte20 was confined to right ventricular outflow tract (RVOT) and left ventricle (LV) base (+/- RV base). ARVC patients had smaller aVAte20 (35cm2 vs 87cm2, p<0.05), longer tVAT (99msec vs 58msec, p<0.05) and longer RVAT (66msec vs 43msec, p<0.05) versus controls. In 10 M-carriers (50%), the locations of aVAte20 were also eccentric. This sub-group presented smaller aVAte20 (53cm2 vs 87cm2, p = 0.009), longer RVAT (55msec vs 48msec, p = 0.043), but similar tVAT (65msec vs 60msec, p = 0.529) compared with the M-carriers with normal activation pattern., Conclusions: ECGI can detect epicardial conduction abnormalities in ARVC patients. Moreover, the observation of localized delayed RV epicardial conduction in M-carriers suggests an early stage of ARVC and may be a useful diagnostic marker enhancing an early detection of the disease., Competing Interests: Due to ethical considerations, the data are available upon request. This does not alter, though, our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kommata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time consuming process and that viruses constantly mutate and render the vaccine ineffective. Antimicrobial peptides (AMP), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 αβ, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 αβ is thought to have high safety profile by specifically targeting viral envelopes without effecting host cell membranes. In this study, we have tested the antiviral effects of PLNC8 αβ against the flaviviruses Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and human immunodeficiency virus-1 (HIV-1). The concentration of PLNC8 αβ that is required to eliminate all the infective virus particles is in the range of nanomolar (nM) to micromolar (μM), which is surprisingly efficient considering the high content of cholesterol (8-35%) in their lipid envelopes. We found that viruses replicating in the endoplasmic reticulum (ER)/Golgi complex, e.g. SARS-CoV-2 and flaviviruses, are considerably more susceptible to PLNC8 αβ, compared to viruses that acquire their lipid envelope from the plasma membrane, such as IAV and HIV-1. Development of novel broad-spectrum antiviral agents can significantly benefit human health by rapidly and efficiently eliminating infectious virions and thereby limit virus dissemination and spreading between individuals. PLNC8 αβ can potentially be developed into an effective and safe antiviral agent that targets the lipid compartments of viral envelopes of extracellular virions, more or less independent of virus antigenic mutations, which faces many antiviral drugs and vaccines., Competing Interests: A patent application has been submitted to the Swedish Patent and Registration Office by Hazem Khalaf, Torbjörn Bengtsson, Jorma Hinkula, Wessam Melik, Daniel Aili, and Robert Selegård. The authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Omer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Increased physical activity (PA) has positive effects on health and longevity. In Swedish healthcare, the physical activity on prescription (PAP) method reportedly increases patients' PA levels for up to 12 months, but long-term follow ups are lacking. As it remains difficult to maintain lifestyle changes, our aim was to evaluate adherence and clinical effects at a 5-year follow-up of PAP treatment in primary healthcare., Methods: This longitudinal, prospective cohort study included 444 patients, (56% female), aged 27-85 years, with at least one metabolic risk factor. Participants were offered PAP by nurses or physiotherapists. The PAP intervention included an individualised dialogue, a PA recommendation by written prescription, and individually adjusted follow-up over 5 years, according to the Swedish PAP model. Patient PA level, metabolic risk factors, and health related quality of life (HRQoL) were measured at baseline and at the 6-month, 1.5-year, 2.5-year, 3.5-year, and 5-year follow-ups. Estimated latent growth curves were used to examine levels and rates of change in the outcomes., Results: The study dropout rate was 52%, with 215 of 444 patients completing the 5-year follow-up. At follow-up, the mean PA level had increased by 730 MET-minutes per week or 3 hours of moderate-intensity PA/week when compared to baseline. During the 5-year intervention, we observed significant positive changes (p ≤ 0.05) in 9 of 11 metabolic risk factors and HRQoL parameters: body mass index, waist circumference, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, cholesterol, high-density lipoprotein, and mental component summary., Conclusion: This first evaluation of a 5-year PAP intervention in primary care demonstrated positive long-term (5 years) effects regarding PA level, metabolic health, and HRQoL. The recorded long-term adherence was ~50%, which is in line with medical treatment. Despite limitations, PAP can have long-term effects in an ordinary primary care setting., Competing Interests: The authors have declared that no competing interests exist.

The present study aimed to compare men and women with gambling disorder (GD) regarding presence of psychiatric comorbidity and socio-economic vulnerability, and to examine whether these factors appear before or after the gambling disorder. This is a retrospective case-control study, based on registers from The National Board of Health and Welfare and Statistics Sweden. A total of 3592 adults with GD were matched with two controls based on age and gender, including a total of 10776 individuals in the study. The study included psychiatric comorbidity through the presence of relevant diagnostic codes or pharmacological codes, and socio-economic vulnerability data through the presence of unemployment, social welfare payments and sickness/activity/rehabilitation compensation. Time between GD and psychiatric comorbidity/socio-economic vulnerability was calculated by subtracting dates between diagnoses/first incidence of socio-economic vulnerability factor and GD diagnosis. Women with GD were more likely to have a psychiatric comorbidity, compared to men. Overall, women were also more likely to receive their psychiatric diagnosis prior to GD diagnosis, while men were more likely to receive the diagnoses concurrently. Social welfare payments, and sickness support were more common among women, while there was no difference in unemployment between genders. Women were also more likely to receive sickness/activity/rehabilitation compensation prior to GD, than men who were more likely to receive these types of support after GD diagnosis. In conclusion, women appear to be at higher risk of psychiatric comorbidity and socio-economic vulnerability alongside GD. They are in general also more likely to receive have their psychiatric and psycho-social problems identified prior to GD, than men who are more likely to receive diagnoses concurrently., Competing Interests: Håkansson’s employment at Lund University, and parts of his research activities, are financially supported by AB Svenska Spel, which is the gambling operator owned entirely by the Swedish government, and he also has research funding obtained, in competition with other researchers, from the independent research council of Svenska Spel, as well as from the corresponding research council of Systembolaget, which is the alcohol monopoly of Sweden, owned by the Swedish government. Larsson has no specific conflicts of interest to report. None of the organizations mentioned above had any role in - or any influence on - the present research.

Background: A wish for improved health or avoidance of ill health is often given as reason for wanting to undergo bariatric surgery. How such reasons relate to postoperative outcome is unclear., Objective: The aim was to explore Swedish patients' reasons for undergoing bariatric surgery. Also, we wanted to analyze if there were sex and age differences and associations with weight loss and health-related quality of life (HRQoL)., Settings: This was a single-center study conducted at a university hospital., Method: Data on 688 patients (528 women and 160 men) including a free text response was analyzed inductively and deductively using predefined statements and was merged with data from the Scandinavian Obesity Surgery Registry. All data was analyzed using descriptive and analytic statistics., Result: The most common reason for undergoing bariatric surgery was pain in different body parts. A wish for an improved medical condition was reported by most patients (59%, n = 408), followed by physical limitations making daily life difficult (42%, n = 288). Men and women reported similar reasons. Younger patients were more distressed about physical appearance (p = 0.001) and older patients wanted to improve their medical condition (p = 0.013). Health-related quality of life improved irrespective of reasons for undergoing surgery., Conclusion: The most reported reasons for undergoing bariatric surgery were a wish for improved medical condition and to make daily life easier. Factors associated with the decision for surgery showed that there were few sex differences, but age seemed to be a factor. The HRQoL trajectory showed improvement regardless of reasons for undergoing surgery., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer., Aim: We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample., Methods: We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years., Results: Overall survival and survival from causes other than bladder cancer estimated with Kaplan-Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up., Conclusion: The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding., Competing Interests: The authors have declared that no competing interests exist.

Currently, cervical cancer prevention is undergoing comprehensive development regarding human papillomavirus (HPV) vaccination and cervical cancer screening. In Sweden and many other countries, high coverage vaccinated cohorts are entering screening within the next few years. This entails demands for baseline HPV genotype data across the screening age range for surveillance and a basis for screening program adjustment. In 2016, Örebro County, Sweden, changed to primary HPV screening using HPV mRNA testing followed by cytology triage. An alternative triage method to cytology could allow for a fully molecular screening algorithm and be implemented in a screening program where self-sampling is included. Hypermethylation analysis of the human genes FAM19A4/miR124-2 has been suggested as a promising triage method. HPV mRNA-positive screening samples (n = 529) were included and subjected to genotyping targeting a broad range of both low-risk and high-risk genotypes in addition to hypermethylation analysis of the two human genes FAM19A4/miR124-2. Data were connected to cytological and histological status and age. The most commonly detected genotypes were HPV31, 16, and 52. In addition, HPV18 was one of the most common genotypes in high-grade squamous intraepithelial lesions (HSILs) samples. In relation to available vaccines, 26% of the women with histological HSIL or cancer (≥HSIL) tested positive for only hrHPV included in the quadrivalent vaccine and 77% of the genotypes in the nonavalent vaccine. According to these figures, a relatively large proportion of the HSILs will probably remain, even after age cohorts vaccinated with the quadrivalent vaccine enter the screening program. Hypermethylation positivity was associated with increasing age, but no HPV-related independently predictive factors were found. Accordingly, age needs to be considered in development of future screening algorithms including triage with hypermethylation methodology., Competing Interests: The authors have declared that no competing interests exist.

Background: There is little research on high frequency emergency department users (HEDU) in Sweden. We aim to determine the prevalence and costs of HEDU compared to non-HEDU at Örebro University Hospital (ÖUH). Additionally, we will determine the factors and outcomes associated with being a HEDU., Methods: This was a retrospective, observational cohort study of ED patients presenting to ÖUH, Sweden between 2018-19. Analyses used electronic registry, ambulance, and cost data. The definition for HEDU was ≥4 visits/year. HEDUs were categorized further into Repeat, High and Super HEDU with 4-7, 8-18 and ≥19 visits/year, respectively. We used multivariable logistic regression to determine the adjusted odds ratios for factors and outcomes between HEDU and non-HEDU., Findings: Of all ÖUH ED patients, 6.1% were HEDU and accounted for 22.4% of ED visits and associated costs. Compared to the mean cost of non-HEDU, the Repeat, High and Super HEDU were more costly by factors of 4, 8 and 27, respectively. The HEDUs were more likely to be male, self-referred, present with abdominal pain, arrive by ambulance, at night and from the Örebro municipal region. Super HEDU were more likely to be of adult age and assigned lower acuity scores. HEDU were more likely to be directed to the surgical zone, less likely to receive radiologic imaging or achieve a 4-hr time target. In contrast to the Repeat and High HEDU, Super HEDU were less likely to be admitted, but more likely to leave without being seen., Conclusion: ÖUH has a HEDU population with associated factors and outcomes. They account for a substantial proportion of ED costs compared to non-HEDU., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Breast and prostate cancer survivors can experience impaired quality of life (QoL) in several QoL domains. The current strategy to support cancer survivors with impaired QoL is suboptimal, leading to unmet patient needs. ASCAPE aims to provide personalized- and artificial intelligence (AI)-based predictions for QoL issues in breast- and prostate cancer patients as well as to suggest potential interventions to their physicians to offer a more modern and holistic approach on cancer rehabilitation., Methods and Analyses: An AI-based platform aiming to predict QoL issues and suggest appropriate interventions to clinicians will be built based on patient data gathered through medical records, questionnaires, apps, and wearables. This platform will be prospectively evaluated through a longitudinal study where breast and prostate cancer survivors from four different study sites across the Europe will be enrolled. The evaluation of the AI-based follow-up strategy through the ASCAPE platform will be based on patients' experience, engagement, and potential improvement in QoL during the study as well as on clinicians' view on how ASCAPE platform impacts their clinical practice and doctor-patient relationship, and their experience in using the platform., Ethics and Dissemination: ASCAPE is the first research project that will prospectively investigate an AI-based approach for an individualized follow-up strategy for patients with breast- or prostate cancer focusing on patients' QoL issues. ASCAPE represents a paradigm shift both in terms of a more individualized approach for follow-up based on QoL issues, which is an unmet need for cancer survivors, and in terms of how to use Big Data in cancer care through democratizing the knowledge and the access to AI and Big Data related innovations., Trial Registration: Trial Registration on clinicaltrials.gov: NCT04879563., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Covid-19 can cause chronic hypoxic respiratory failure, but the impact on the need for long-term oxygen therapy (LTOT) is unknown. The aim was to investigate change in incidence and characteristics of patients starting LTOT in Sweden 2020 after the outbreak of the pandemic., Material and Methods: Population-based observational study using data from the National Registry for Respiratory Failure (Swedevox) and from a survey to all centres prescribing LTOT in Sweden. Swedevox data provided information on incidence of LTOT and characteristics of patients starting LTOT during 2015-2020., Results: Between March-Dec 2020, 131 patients started LTOT due to covid-19, corresponding to 20.5% of incident LTOT in Sweden. Compared with 2015-19, the total number of patients starting LTOT did not increase. No significant differences in patient characteristics or underlying causes of hypoxemia were found between patients starting LTOT during 2020 compared 2015-2019. The majority of the LTOT centres estimated that, since the start of the pandemic, the incidence of LTOT was unchanged and the time devoted for LTOT work was the same or slightly less., Conclusions: Covid-19 caused one fifth of all LTOT starts during the pandemic in 2020. The LTOT incidence overall did not increase possibly due to reduction in other infections., Competing Interests: The authors have no conflicts of interest related to the study.

Soluble B and T lymphocyte attenuator (sBTLA) has been shown to be associated with severity and outcome, in critically ill septic patients. We aimed to assess the dynamic expression of sBTLA, as a prognostic biomarker of long-term mortality in patients with bloodstream infection (BSI) and sepsis, and to evaluate its association with biomarkers indicative of inflammation and immune dysregulation. Secondarily, sBTLA was evaluated in association with severity and bacterial etiology. Patients with BSI (n = 108) were prospectively included, and serially sampled from admission to day 28. Blood and plasma donors (n = 31), sampled twice 28 days apart, served as controls. sBTLA concentration in plasma was determined with enzyme-linked immunosorbent assay. Associations between sBTLA on day 1-2 and 7, and mortality at 90 days and 1 year, were determined with unadjusted, and adjusted Cox regression. Differences related to severity was assessed with linear regression. Mixed model was used to assess sBTLA dynamics over time, and sBTLA associations with bacterial etiology and other biomarkers. sBTLA on day 1-2 and 7 was associated with mortality, in particular failure to normalize sBTLA by day 7 was associated with an increased risk of death before day 90, adjusted HR 17 (95% CI 1.8-160), and one year, adjusted HR 15 (95% CI 2.8-76). sBTLA was positively associated with CRP, and negatively with lymphocyte count. sBTLA on day 1-2 was not linearly associated with baseline SOFA score increase. High SOFA (≥4) was however associated with higher mean sBTLA than SOFA ≤3. sBTLA was not associated with bacterial etiology. We show that sustained elevation of sBTLA one week after hospital admission is associated with late mortality in patients with BSI and sepsis, and that sBTLA concentration is associated with CRP and decreased lymphocyte count. This suggests that sBTLA might be an indicator of sustained immune-dysregulation, and a prognostic tool in sepsis., Competing Interests: The authors have declared that no competing interests exist.

Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR., Competing Interests: The authors have declared that no competing interests exist.

Patients with chronic venous disease (CVD) have elevated levels of leucocyte elastase (LE) released from the activation of leucocytes. In acute deep venous thrombosis (DVT), LE can degrade fibrin from the thrombus resulting in cross-linked fibrin degradation products (E-XDP) being released into the bloodstream. In patients with CVD the levels and significance of circulating E-XDP are unknown. We aimed to investigate the association between plasma E-XDP concentration and severity of CVD. Levels of E-XDP were quantified with a specific enzyme-linked immunosorbent assay (ELISA) in plasma from 142 consecutively recruited CVD patients (mean age 64 years, (range 23-89), 81 were females and 61 males). Patients were also divided into three groups based on CVD severity using the C-class of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification, with C 0-1 class as the reference group, C 2-3 as the second group and C 4-6 as the third group with the most severely affected patients. We found significantly elevated levels of E-XDP in patients with C 4-6 compared with patients with C 0-1 (p = 0.007) and increased with increasing disease severity across the groups (p = 0.02). Significant independent association was observed between levels of E-XDP and the classes C 4-6 after adjustment for age and sex (p < 0.05), but the association was no longer significant after further adjustment for use of statins, use of anticoagulants and history of DVT (p = 0.247). This exploratory study shows that E-XDP levels are elevated in patients with CVD, encouraging further studies on the role of E-XDP in CVD., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1(83-119), D2, and B´/B epitopes., Objectives: The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D183-119, D2, B´/B, and B´/BCOOH in co-vaccination with IFN-γ or IL-10 in a murine model of lupus induced by pristane., Material and Methods: To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D183-119, D2, B´/B, B´/BCOOH, IFN-γ, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with 35S and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-γ from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy., Results: The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048)., Conclusion: The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with Rheumatoid Arthritis (RA) often report impaired health-related quality of life (HrQoL) such as difficulties in daily life, pain, fatigue and an affected social life. Even when lowering disease activity, pharmacological treatment does not always resolve these factors., Objective: To investigate if a proposed anti-inflammatory diet improves HrQoL in patients with RA., Design: In this controlled crossover trial, 50 patients were randomized to start with either an intervention diet (anti-inflammatory) or a control diet (usual Swedish intake) for ten weeks followed by a wash out period before switching to the other diet. Participants received food equivalent to ~1100 kcal/day, five days/week, and instructions to consume similarly for the remaining meals. HrQoL was evaluated using Health Assessment Questionnaire (HAQ), 36-item Short Form Survey (SF-36), Visual Analogue Scales (VAS) for pain, fatigue and morning stiffness, and a time scale for morning stiffness., Results: Forty-seven participants completed ≥1 diet period and were included in the main analyses. No significant difference between intervention and control diet at end of diet periods was observed for any outcome. However, significant improvements were obtained for SF-36 Physical Functioning (mean:5.79, SE: 2.12, 95% CI: 1.58, 10.01) during the intervention diet period. When excluding participants with anti-rheumatic medication changes, the differences between diet periods increased for most outcomes, favoring the intervention diet period, and the difference for SF-36 Physical Functioning became significant (n = 25, mean:7.90, 95% CI:0.56, 15.24, p = 0.036)., Conclusions: In main analyses, the proposed anti-inflammatory diet did not significantly improve HrQoL for patients with RA compared to control diet. In sub-analyses, significant improvements in physical functioning were detected. Larger studies with consistent medication use and in populations more affected by the disease may be needed to obtain conclusive evidence., Competing Interests: The authors have declared that no competing interests exist.

Background: Previous studies have shown that a high body mass index (BMI) is a risk factor for severe COVID-19. The aim of the present study was to assess whether a high BMI affects the risk of death or prolonged length of stay (LOS) in patients with COVID-19 during intensive care in Sweden., Methods and Findings: In this observational, register-based study, we included patients with COVID-19 from the Swedish Intensive Care Registry admitted to intensive care units (ICUs) in Sweden. Outcomes assessed were death during intensive care and ICU LOS ≥14 days. We used logistic regression models to evaluate the association (odds ratio [OR] and 95% confidence interval [CI]) between BMI and the outcomes. Valid weight and height information could be retrieved in 1,649 patients (1,227 (74.4%) males) with COVID-19. We found a significant association between BMI and the risk of the composite outcome death or LOS ≥14 days in survivors (OR per standard deviation [SD] increase 1.30, 95%CI 1.16-1.44, adjusted for sex, age and comorbidities), and this association remained after further adjustment for severity of illness (simplified acute physiology score; SAPS3) at ICU admission (OR 1.30 per SD, 95%CI 1.17-1.45). Individuals with a BMI ≥ 35 kg/m2 had a doubled risk of the composite outcome. A high BMI was also associated with death during intensive care and a prolonged LOS in survivors assessed as separate outcomes. The main limitations were the restriction to the first wave of the pandemic, and the lack of information on socioeconomic status as well as smoking., Conclusions: In this large cohort of Swedish ICU patients with COVID-19, a high BMI was associated with increasing risk of death and prolonged length of stay in the ICU. Based on our findings, we suggest that individuals with obesity should be more closely monitored when hospitalized for COVID-19., Competing Interests: LS, MT, JM, CR, VW, TO, JMK have no conflicts of interest. ES received lecturing fees from Johnson & Johnson Medical.

Due to the COVID-19 pandemic, higher educational institutions worldwide switched to emergency distance learning in early 2020. The less structured environment of distance learning forced students to regulate their learning and motivation more independently. According to self-determination theory (SDT), satisfaction of the three basic psychological needs for autonomy, competence and social relatedness affects intrinsic motivation, which in turn relates to more active or passive learning behavior. As the social context plays a major role for basic need satisfaction, distance learning may impair basic need satisfaction and thus intrinsic motivation and learning behavior. The aim of this study was to investigate the relationship between basic need satisfaction and procrastination and persistence in the context of emergency distance learning during the COVID-19 pandemic in a cross-sectional study. We also investigated the mediating role of intrinsic motivation in this relationship. Furthermore, to test the universal importance of SDT for intrinsic motivation and learning behavior under these circumstances in different countries, we collected data in Europe, Asia and North America. A total of N = 15,462 participants from Albania, Austria, China, Croatia, Estonia, Finland, Germany, Iceland, Japan, Kosovo, Lithuania, Poland, Malta, North Macedonia, Romania, Sweden, and the US answered questions regarding perceived competence, autonomy, social relatedness, intrinsic motivation, procrastination, persistence, and sociodemographic background. Our results support SDT's claim of universality regarding the relation between basic psychological need fulfilment, intrinsic motivation, procrastination, and persistence. However, whereas perceived competence had the highest direct effect on procrastination and persistence, social relatedness was mainly influential via intrinsic motivation., Competing Interests: The authors have declared that no competing interests exist.

Background: Low resting heart rate (RHR) and low systolic blood pressure (SBP) are associated with criminal behavior. However, knowledge is lacking about their predictive value for reoffending., Aim: We aimed to examine associations of RHR and SBP with reoffending in a large population-based sample., Methods: We conducted a cohort study of all convicted male conscripts born in Sweden 1958-1990 (N = 407,533). We obtained data by linking Swedish population-based registers. Predictor variables were RHR and SBP, measured at conscription which was mandatory until 2010 for men at age 18. The outcome variable was reoffending, defined as criminal convictions (any crime, violent crime and non-violent crime), obtained from the National Crime Register. We used survival analyses to test for associations of RHR and SBP with reoffending, adjusting for pertinent covariates such as socioeconomic status, height, weight and physical energy capacity., Results: In fully adjusted Cox regression models, men with lower RHR (≤60 bpm) had higher risk of reoffending (any crime: HR = 1.17, 95% CI: 1.14, 1.19, violent crime: HR = 1.23, 95% CI: 1.17, 1.29, non-violent crime: HR = 1.16, 95% CI: 1.14, 1.19), compared to men with higher RHR (≥ 82 bpm). Men with lower SBP (≤80 mmHg) had higher risk of reoffending (any crime: HR = 1.19, 95% CI: 1.17, 1.21, violent crime: HR = 1.16, 95% CI: 1.12, 1.20, non-violent crime: HR = 1.20, 95% CI: 1.18, 1.22), compared to men with higher SBP (≥138 mmHg)., Conclusions: Low autonomic arousal is associated with increased risk of reoffending. RHR and SBP should be investigated further as potential predictors for reoffending as they each may have predictive value in risk assessment protocols., Competing Interests: H Larsson has served as a speaker for Evolan Pharma and Shire/Takeda and has received research grants from Shire/Takeda; all outside the submitted work. The other authors report no financial relationships with commercial interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Aim: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function., Materials and Methods: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018., Results: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes., Discussion: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor., Competing Interests: The authors have declared that no competing interests exist.

Aims: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population., Methods: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086)., Results: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals., Conclusions: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality., Competing Interests: I have read the journal´s policy and the authors of this manuscript have the following competing interests: AH holds a position at Lund University which is sponsored by the Swedish state-owned gambling operator AB Svenska Spel. He also disposes research grants from the research councils of AB Svenska Spel, the state-owned alcohol monopoly Systembolaget, and from the research council of the Swedish Enforcement Agency and the Swedish Sports Federation. He is involved in a clinical research study receiving non-financial support from the commercial body Kontigo Care in the area of digital follow-up tools in the treatment of addictive disorders. He is also the national principal investigator of a prior pharmaco-epidemiological survey study conducted by the US research institute Research Triangle Institute and sponsored by the pharmaceutical company Shire, which supported the conduct of the study but did not provide personal fees to the individual researcher. The present competing interests are not involved in – and did not have any influence on – the present research project. OD has received research funding from Abbvie, MSD, and Gilead. MK has received honoraria for lectures/consultancy from AbbVie, Gilead, MSD, and has received research grants from Gilead. AD has given lectures with honoraria and/or been consultant for AbbVie, Gilead, and MSD. SA has received honoraria for lectures/consultancy from AbbVie, BMS, Gilead, MSD, and has received research grants from AbbVie and Gilead. CG, AJ, and HH declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Sensitization requires exposure to an allergen with subsequent production of a "danger "signal. In the skin, keratinocytes are the main producers of these signals., Objective: To compare dose- and time-effects of cobalt on the viability of and cytokine release from HaCaT cells cultured at low or high calcium., Method: To model two separate states of differentiation of keratinocytes, HaCaT cells were cultured under low or high calcium conditions. HaCaT were exposed to different concentrations of cobalt chloride (10 μm to 5 mM) over time (30 minutes- 48 hours). Cell viability was measured with the Cell-Titer Blue Viability assay. Cytokine production was measured using a bead-based immunoassay and flow cytometry. Gene expression was quantified using qPCR. Data was analyzed by ANOVA and linear mixed model., Results: Viability of the cells was dose- and time-dependent. A linear mixed statistical model showed that cobalt exposure induces increase in IL-6, CXCL8 and CCL2 production over time and whereas increase of IL-6 and a decrease of CCL2 was associated with increasing cobalt chloride concentrations. When comparing the cells incubated under high and low calcium conditions, the more differentiated cells in the high concentration were found to exert a stronger response in terms of IL-6 release., Conclusions: Our data suggest that cobalt chloride triggered an alarm system in HaCaT cells, and proinflammatory cytokines/chemokines were secreted in a dose- and time-dependent manner. When high and low calcium incubations were compared, the difference was seen only for IL-6. These findings indicate that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Over time, ambulance assignments have increased in number both nationally and internationally, and a substantial proportion of patients encountered by emergency medical services are assessed as not being in need of services. Non-conveying patients has become a way for emergency medical services clinicians to meet this increasing workload. It has been shown that ambulances can be made available sooner if patients are non-conveyed, but there is no previous research describing the factors that influence the non-conveyance time., Study Objective: To describe ambulance time consumption and the factors that influence time consumption when patients are non-conveyed., Methods: A prospective observational review of 2615 non-conveyed patients' ambulance and hospital medical records was conducted using a consecutive sample. Data were analysed with the Kruskal-Wallis test, Mann-Whitney U test and Spearman's rank correlation (rho) for linear correlations., Results: The mean NC time for all ambulance assignments during the study period was 26 minutes, with a median of 25 minutes. The shortest NC time was 4 minutes, and the longest NC time was 73 minutes. NC times were significantly faster during the day than at night., Conclusions: This study provides new knowledge about time consumption when patients are non-conveyed. Although there are time differences when patients are non-conveyed, the differences observed in this study are small and not of clinical value. Ambulances will most often become available sooner if patients are non-conveyed. Although patients might be eligible for non-conveyance, policy-makers might have to decide when it is appropriate to non-convey patients from time, resource, patient safety and patient-centred care perspectives., Competing Interests: The authors have declared that no competing interests exist.