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Johanne Sloth Lauszus,1 Peter Lykke Eriksen,1 Mette Mejlby Hansen,1 Lotte Lindgreen Eriksen,1 Debbie Lindsay Shawcross,2,3 Hendrik Vilstrup,1 Karen Louise Thomsen,1 Sidsel Stoy1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, UKCorrespondence: Sidsel StoyDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, Aarhus, DenmarkEmail Sidsel_stoy@clin.au.dkIntroduction: In non-alcoholic fatty liver disease (NAFLD), neutrophils in liver infiltrates are activated, which may contribute to disease progression towards non-alcoholic steatohepatitis (NASH). However, the functional status of the blood neutrophils remains unknown and their role in the disease mechanisms is thus uncertain. We therefore characterized activation and function of blood neutrophils in patients with NAFLD in relation to clinical disease markers and the NAFLD plasma milieu.Methods: We studied 20 patients with NAFLD, among these 6 patients with NASH, and 14 healthy persons. Neutrophil activation, interleukin (IL)-8 production and oxidative burst were measured by flow cytometry on participants´ neutrophils and on healthy neutrophils exposed in vitro to plasma from the study participants.Results: Blood neutrophils from the NASH patients showed a doubling in their expression of the activation marker CD62L. Also, all NAFLD patients had 50– 100% increased expression of CD11b. Functionally, NASH neutrophils had 30% elevated IL-8 production and more than doubled spontaneous oxidative burst. In all NAFLD patients, higher spontaneous oxidative burst was associated with worse liver function. Incubation of healthy neutrophils with NAFLD plasma paradoxically slightly reduced CD62L and CD11b expression, and NASH plasma also reduced the frequency of IL-8-producing neutrophils.Conclusion: In NAFLD, blood neutrophils are activated, and in NASH also functionally primed. This suggests a progressive neutrophil aggressiveness already present with liver fat infiltration. However, NAFLD plasma in vitro, if anything, had the opposite effect on the healthy neutrophils so the NAFLD-related neutrophil activation cannot be attributed to humoral factors and remains unexplained.Keywords: neutrophil, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, oxidative burst, CD11b

The study was designed to characterize the genetics structure of the Adriatic grayling in Slovenia, with particular emphasis on estimating the degree of introgression with non-indigenous stocked grayling. It was revealed that no distinctive Adriatic group is present but rather a dispersed multitude of individuals that cannot be unambiguously distinguished from more homogeneous Danubian population is present.

The author provides a critical overview of three-dimensional (3-D) virtual worlds and "serious gaming" that are currently being developed and used in healthcare professional education and medicine. The relevance of this e-learning innovation for teaching students and professionals is debatable and variables influencing adoption, such as increased knowledge, self-directed learning, and peer collaboration, by academics, healthcare professionals, and business executives are examined while looking at various Web 2.0/3.0 applications. There is a need for more empirical research in order to unearth the pedagogical outcomes and advantages associated with this e-learning technology. A brief description of Roger's Diffusion of Innovations Theory and Siemens' Connectivism Theory for today's learners is presented as potential underlying pedagogical tenets to support the use of virtual 3-D learning environments in higher education and healthcare. [ABSTRACT FROM AUTHOR]

Background: American and European guidelines define hypertension differently and are sex agnostic. Our aim was to assess the impact of different hypertension thresholds at the age of 40 on 30-year stroke risk and to examine sex differences., Methods: We included 2608 stroke-free individuals from the Akershus Cardiac Examination 1950 Study, a Norwegian regional study conducted in 2012-2015 of the 1950 birth cohort, who had previously participated in the Age 40 Program, a nationwide health examination study conducted in 1990-1993. We categorised participants by systolic blood pressure (SBP) at age 40 (<120 mm Hg (reference), 120-129 mm Hg, 130-139 mm Hg and ≥140 mm Hg) and compared stroke risk using Cox proportional hazard regressions adjusted for age, sex, smoking, cholesterol, physical activity, obesity and education. Fatal and non-fatal strokes were obtained from the Norwegian Cardiovascular Disease Registry from 1 January 2012 to 31 December 2020, in addition to self-reported strokes., Results: The mean age was 40.1±0.3 years (50.4% women) and mean SBP was 128.3±13.5 mm Hg (mean±SD). Stroke occurred in 115 (4.4%) individuals (32 (28%) women and 83 (72%) men) during 29.4±2.9 years of follow-up. SBP between 130 and 139 mm Hg was not associated with stroke (adjusted HR 1.71, 95% CI 0.87 to 3.36) while SBP ≥140 mm Hg was associated with increased stroke risk (adjusted HR 3.11, 95% CI 1.62 to 6.00). The adjusted HR of stroke was 4.32 (95% CI 1.66 to 11.26) for women and 2.66 (95% CI 1.03 to 6.89) for men, with non-significant sex interactions., Conclusions: SBP ≥140 mm Hg was significantly associated with 30-year stroke risk in both sexes. A small subgroup of women had SBP ≥140 mm Hg and systolic hypertension was a strong risk factor for stroke in these women., Trial Registration Number: NCT01555411., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The early coronavirus disease 2019 (COVID-19) outbreak inflicted vulnerability on individuals and societies on a completely different scale than we have seen previously. The pandemic developed rapidly from 1 day to the next, and both society and individuals were put to the test. Older people's experiences of the early outbreak were no exception. Using an abductive analytical approach, the study explores the individual experiences of vulnerability as described by older people hospitalised with COVID-19 in the early outbreak. In these older people, we found that the societal context and the individual experiences of vulnerability were inextricable linked. The study demonstrates that despite significant individual stress, informants displayed an interesting ability to also view their situation to reorient their perspective. The experience of vulnerability is both conditional and individual, which imposes a degree of unpredictability that neither they nor others were able to negotiate. The article discusses the phenomenon of unpredictability in light of a modern society with regard to how individuals and society may encounter unexpected events in the future where the potential to reorient will be vital., (© 2024 The Authors. Nursing Inquiry published by John Wiley & Sons Ltd.)

Follicular helper T (Tfh) cells and their interplay with B cells likely contribute to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). Tfh cells are enriched in cerebrospinal fluid (CSF) in RRMS, but effects of anti-CD20 therapy are unknown. We investigated Tfh cells in controls, untreated and anti-CD20-treated patients with RRMS using flow cytometry. CSF Tfh cells were increased in untreated patients. Compared to paired blood samples, CD25 - Tfh cells were enriched in CSF in RRMS, but not in controls. Contrast-enhancing brain MRI lesions and IgG index correlated with CSF CD25 - Tfh cell frequency in untreated patients with RRMS. Anti-CD20 therapy reduced the numbers of circulating PD1 + Tfh cells and CD25 - Tfh cells, and the frequency of CSF CD25 - Tfh cells. The study suggests that CD25 - Tfh cells are recruited to the CSF in RRMS, associated with focal inflammation, and are reduced by anti-CD20 therapy., Competing Interests: Declaration of competing interest Outside the submitted work, SEM has received speaker honoraria and non-financial support for conference participation from Merck. MH has received non-financial support for conference participation from Merck and Sanofi. MBH, VHH and HBS report no conflicting interests. MRM has received non-financial support for conference participation from Merck. JRC has received speaker honoraria from Biogen. FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Lundbeck, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. MRvE has received speaker honoraria from Merck., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting., Methods: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C. difficile test., Results: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%-79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%-82%). The 90-day mortality was 10% (95% CI, 8%-14%)., Conclusion: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival., Clinicaltrials: gov, Number: NCT03712722., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate a new automated retinal oximetry image quality indicator with cataract as a clinical model., Methods: Sixty-one eyes in 61 patients were imaged by the Oxymap T1 Retinal Oximeter at baseline and 25 eyes were also examined 3 weeks after cataract surgery. Image quality (0-10 on a continuous scale) was compared with standardized AREDS cataract grading and Pentacam lens densitometry. Associations with retinal oximetry measurements and visual acuity were examined., Results: Image quality correlated with total, nuclear and posterior subcapsular cataract grades (ANOVA, p < 0.05), tended to be associated with lens densitometry and it improved from 4.3 ± 1.4 to 5.7 ± 1.0 (p < 0.05) after cataract surgery. Very low image quality, below 3, led to vessel detection failure in retinal oximetry images. Higher image qualities were linearly associated with higher measured retinal oxygen saturations (r = 0.52 in arteries and r = 0.46 in veins; p < 0.001)., Conclusion: Retinal oximetry image quality deteriorated with increasing cataract density and improved after cataract surgery, supporting its use as a measure of optical clarity. The numerical quality indicator demonstrated a threshold below which images of poor optical quality should be discarded. Image quality affects the estimates of retinal oximetry parameters and should therefore be included in future analyses., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Population genomics analysis holds great potential for informing conservation of endangered populations. We focused on a controversial case of European whitefish (Coregonus spp.) populations. The endangered North Sea houting is the only coregonid fish that tolerates oceanic salinities and was previously considered a species (C. oxyrhinchus) distinct from European lake whitefish (C. lavaretus). However, no firm evidence for genetic-based salinity adaptation has been available. Also, studies based on microsatellite and mitogenome data suggested surprisingly recent divergence (c. 2500 years bp) between houting and lake whitefish. These data types furthermore have provided no evidence for possible inbreeding. Finally, a controversial taxonomic revision recently classified all whitefish in the region as C. maraena, calling conservation priorities of houting into question. We used whole-genome and ddRAD sequencing to analyse six lake whitefish populations and the only extant indigenous houting population. Demographic inference indicated post-glacial expansion and divergence between lake whitefish and houting occurring not long after the Last Glaciation, implying deeper population histories than previous analyses. Runs of homozygosity analysis suggested not only high inbreeding (F ROH up to 30.6%) in some freshwater populations but also F ROH up to 10.6% in the houting prompting conservation concerns. Finally, outlier scans provided evidence for adaptation to high salinities in the houting. Applying a framework for defining conservation units based on current and historical reproductive isolation and adaptive divergence led us to recommend that the houting be treated as a separate conservation unit regardless of species status. In total, the results underscore the potential of genomics to inform conservation practices, in this case clarifying conservation units and highlighting populations of concern., (© 2024 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Objectives: B cells are important in the pathogenesis of multiple sclerosis. It is yet unknown which subsets may be involved, but atypical B cells have been proposed as mediators of autoimmunity. In this study, we investigated differences in B-cell subsets between controls and patients with untreated and anti-CD20-treated multiple sclerosis., Methods: We recruited 155 participants for an exploratory cohort comprising peripheral blood and cerebrospinal fluid, and a validation cohort comprising peripheral blood. Flow cytometry was used to characterize B-cell phenotypes and effector functions of CD11c + atypical B cells., Results: There were no differences in circulating B cells between controls and untreated multiple sclerosis. As expected, anti-CD20-treated patients had a markedly lower B-cell count. Of B cells remaining after treatment, we observed higher proportions of CD11c + B cells and plasmablasts. CD11c + B cells were expanded in cerebrospinal fluid compared to peripheral blood in controls and untreated multiple sclerosis. Surprisingly, the proportion of CD11c + cerebrospinal fluid B cells was higher in controls and after anti-CD20 therapy than in untreated multiple sclerosis. Apart from the presence of plasmablasts, the cerebrospinal fluid B-cell composition after anti-CD20 therapy resembled that of controls. CD11c + B cells demonstrated a high potential for both proinflammatory and regulatory cytokine production., Interpretation: The study demonstrates that CD11c + B cells and plasmablasts are less efficiently depleted by anti-CD20 therapy, and that CD11c + B cells comprise a phenotypically and functionally distinct, albeit heterogenous, B-cell subset with the capacity of exerting both proinflammatory and regulatory functions., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: This Scoping review (ScR) builds upon the 2017 review conducted by Hansen et al which contributed to evidence base shinrin-yoku (SY), also known as forest bathing (FB), has many positive health effects and is becoming a prescribed dose (specific time spent in nature) by health care providers. Practice and research regarding SY, has been historically based in Asian countries with a recent increase in Europe. The need and call for more research worldwide continues to further the evidence of SY as a health promotion modality. Through this ScR the authors identified programmatic components, health information monitored and screened, time spent in nature, geographical regions, trends, and themes in SY research worldwide., Methods: Following PRISMA-ScR guidelines we searched across 7 electronic databases for SY or FB research articles from 2017 through 2022. PubMed, CINAHL, PsycInfo, ScienceDirect, SCOPUS, Embase, JSTOR were included due to the interdisciplinary nature of SY or FB research. Each database provided unique strengths ensuring a capture of a wide range of articles. The resulting articles were screened and extracted through Covidence., Results: Database searches returned 241 results, with 110 references removed during the deduplication process, 131 were initially screened in the title and abstract review stage. Resulting in 82 unique results deemed relevant and screened in full text. During the final stage of the review, 63 articles met all inclusion criteria and were extracted for data., Conclusions: The practice of SY has physiological (PHYS) and psychological (PSYCH) benefits across age groups. Research findings indicate either the natural or the virtual environment (VW) has significant health benefits. Continued research is encouraged globally for short- and long-term health outcomes for all individuals. The connection with nature benefits the mind, body and soul and is supported by Henry David Thoreau's philosophy: "Our livesneed the relief of where the pine flourishes and the jay still scream.", Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life., Methods: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance., Results: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 μg/mL (range 0.005-0.12 μg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] μg/mL) and without (3.1 [range 0.7-11.0] μg/mL) infections during the first year of life (P = .41)., Conclusions: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To assess the feasibility of delirium screening with the screening tool 4AT conducted by stroke unit nurses., Design: Observational., Methods: Patients with confirmed acute stroke admitted to the stroke unit at Baerum Hospital, Norway, from March to October 2020, were consecutively recruited. Nurses performed delirium screening using the rapid screening tool 4AT within 24 h of admission, at discharge and when delirium was suspected, and filled out a questionnaire assessing their experiences with the delirium screening. A geriatrician validated the delirium diagnosis., Results: In all, 62 patients were included, mean age 73.3 years. 4AT was performed according to protocol in 49 (79.0%) and 39 (62.9%) patients at admission and discharge respectively. Lack of time (40%) was reported as the most common reason for not performing delirium screening. The nurses reported that the felt competent to carry out the 4AT screening, and did not experience it as significant extra workload. Five patients (8%) were diagnosed with delirium. Delirium screening performed by stroke unit nurses seemed feasible and the nurses experienced that 4AT was a useful tool for this purpose., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue., Methods: Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab., Results: Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01)., Conclusion: FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention., Clinical Trial Registration: ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1., (© 2023. The Feinstein Institute for Medical Research.)

Severe illness is often an existential threat that triggers emotions like fear, stress, and anxiousness. Such emotions can affect ill patients' encounters with healthcare personnel. We present a single case study of an older woman who contracted COVID-19 and her challenge to be recognised by healthcare personnel in the early pandemic. Storytelling is vital to understand how patients can create meaning in illness as it gives them the opportunity to reshape and restore their past and to project a future. We used Arthur Frank's dialogical narrative analysis to explore how one patient experienced her encounters with healthcare personnel. Although she felt very ill from COVID-19, she experienced being almost invisible and not being believed by healthcare personnel in a system marked by high stress levels and uncertainty. Despite rejections and illness, she managed to mobilise her resources, even though she depended on significant others. Her story brings forward altered self-understanding and growth. The importance of facilitating dialogical settings for healthcare professionals through patient storytelling also contributes to a broader societal understanding of illness beyond a biological perspective., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background We aimed to explore the predictive value of the carotid plaque score, compared with the Systematic Coronary Risk Evaluation 2 (SCORE2) risk prediction algorithm, on incident ischemic stroke and major adverse cardiovascular events and establish a prognostic cutoff of the carotid plaque score. Methods and Results In the prospective ACE 1950 (Akershus Cardiac Examination 1950 study), carotid plaque score was calculated with ultrasonography at inclusion in 2012 to 2015. The largest plaque diameter in each extracranial segment of the carotid artery on both sides was scored from 0 to 3 points. The sum of points in all segments provided the carotid plaque score. The cohort was followed up by linkage to national registries for incident ischemic stroke and major adverse cardiovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, and cardiovascular death) throughout 2020. Carotid plaque score was available in 3650 (98.5%) participants, with mean±SD age of 63.9±0.64 years at inclusion. Only 462 (12.7%) participants were free of plaque, and and 970 (26.6%) had a carotid plaque score of >3. Carotid plaque score predicted ischemic stroke (hazard ratio [HR], 1.25 [95% CI, 1.15-1.36]) and major adverse cardiovascular events (HR, 1.21 [95% CI, 1.14-1.27]) after adjustment for SCORE2 and provided strong incremental prognostic information to SCORE2. The best cutoff value of carotid plaque score for ischemic stroke was >3, with positive predictive value of 2.5% and negative predictive value of 99.3%. Conclusions The carotid plaque score is a strong predictor of ischemic stroke and major adverse cardiovascular events, and it provides incremental prognostic information to SCORE2 for risk prediction. A cutoff score of >3 seems to be suitable to discriminate high-risk subjects. Registration Information clinicaltrials.gov. Identifier: NCT01555411.

Background: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI), but its effect varies inexplicably., Aims: To optimise the effectiveness of FMT for rCDI and validate determinants for effect METHODS: We conducted a cohort study, including all patients treated with FMT for rCDI between October 2018 and June 2020. Statistical process control was used to evaluate the impact of prospective quality improvement on the effect of single FMT treatments per 10-11 patients. Targeting an 80% effect, optimisations included changes to processing procedures, preparation and clinical application of FMT. The primary outcome was the resolution of Clostridioides difficile-associated diarrhoea at week 8. If CDI recurred, FMT was repeated. All patients were followed for 8 weeks after their latest FMT., Results: 183 patients with rCDI received 290 FMT treatments. A single FMT achieved resolution at week 8 in 127 (69%, 95% CI: 62%-76%), while repeated FMT cumulatively achieved resolution in 167/183 (91%, 95% CI: 86%-95%). The single FMT effect varied between 36% and 100% over time. In a mixed-effect model, patient age above 65 years, non-rCDI antibiotics at week 1 post-FMT, and donor were associated with effect. Neither increasing the dosages of faecal microbes nor standardising the processing improved outcomes., Conclusion: FMT has a high cumulative effectiveness in patients with rCDI following multiple administrations, but the single FMT effect is variable and may be optimised using statistical process control. Optimising FMT by considering patient age, post-FMT antibiotics, donor and multiple administrations may improve the treatment outcomes., Clinicaltrials: gov (Study identifier: NCT03712722)., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Species and populations may adapt to climate change by microevolutionary processes. However, standing genetic variation can be insufficient for this to occur. An interesting new study of a system of rainbowfish species shows that intraspecific hybridization enriches gene pools with adaptive variation that may allow persistence in a changing climate., Competing Interests: Declaration of interests None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Waves of infection have formed the pattern of the COVID-19 pandemic. A wave dominated by the delta variant of the SARS-CoV-2 virus in autumn 2021 was superseded by the omicron variant over the course of a few weeks around Christmas. We describe how this transition affected the population of patients admitted to a Norwegian local hospital with COVID-19., Material and Method: All patients admitted to Bærum Hospital with confirmed SARS-CoV-2 virus were included in a quality study which aimed to describe patient characteristics and clinical course. We present patients admitted in the periods 28 June 2021-31 December 2021 and 1 January 2022-12 June 2022, described here as the delta wave and the omicron wave., Results: The SARS-CoV-2-virus was confirmed in a total of 144 patients who were admitted during the delta wave, and in 261 patients during the omicron wave, where 14/144 (10 %) and 89/261 (34 %) were admitted for reasons other than COVID-19. Patients with COVID-19 during the delta wave were younger on average (59 vs. 69 years) and had a lower Charlson comorbidity index score (2.6 vs. 4.9) and a lower Clinical Frailty Scale score (2.8 vs. 3.7) than patients in the omicron wave. Among 302/405 patients admitted with COVID-19 as the principal diagnosis, 88/130 (68 %) patients had respiratory failure during the delta wave and 59/172 (34 %) during the omicron wave, with a median number of 8 bed days (interquartile range 5-15) and 5 (interquartile range 3-8)., Interpretation: The transition from the wave of infection that was dominated by the delta variant of the SARS-CoV-2 virus to the wave dominated by the omicron variant had a considerable effect on the characteristics and clinical course of patients admitted to hospital with SARS-CoV-2 infection.

Anthropogenic biological invasions represent major concerns but enable us to investigate rapid evolutionary changes and adaptation to novel environments. The goldfish Carassius auratus with sexual diploids and unisexual triploids coexisting in natural waters is one of the most widespread invasive fishes in Tibet, providing an ideal model to study evolutionary processes during invasion in different reproductive forms from the same vertebrate. Here, using whole-genome resequencing data of 151 C. auratus individuals from invasive and native ranges, we found different patterns of genomic responses between diploid and triploid populations during their invasion of Tibet. For diploids, although invasive individuals derived from two different genetically distinct sources had a relative higher diversity (π) at the population level, their individual genetic diversity (genome-wide observed heterozygosity) was significantly lower (21.4%) than that of source individuals. Population structure analysis revealed that the invasive individuals formed a specific genetic cluster distinct from the source populations. Runs of homozygosity analysis showed low inbreeding only in invasive individuals, and only the invasive population experienced a recent decline in effective population size reflecting founder events. For triploids, however, invasive populations showed no loss of individual genetic diversity and no genetic differentiation relative to source populations. Regions of putative selective sweeps between invasive and source populations of diploids mainly involved genes associated with mannosidase activity and embryo development. Our results suggest that invasive diploids deriving from distinct sources still lost individual genetic diversity resulting from recent inbreeding and founder events and selective sweeps, and invasive triploids experienced no change in genetic diversity owing to their reproduction mode of gynogenesis that precludes inbreeding and founder effects and may make them more powerful invaders., (© 2023 John Wiley & Sons Ltd.)

Background: The National Early Warning Score 2 (NEWS2) is a scoring tool predictive of poor outcome in hospitalised patients. Older patients with COVID-19 have increased risk of poor outcome, but it is not known if frailty may impact the predictive performance of NEWS2. We aimed to investigate the impact of frailty on the performance of NEWS2 to predict in-hospital mortality in patients hospitalised due to COVID-19., Methods: We included all patients admitted to a non-university Norwegian hospital due to COVID-19 from 9 March 2020 until 31 December 2021. NEWS2 was scored based on the first vital signs recorded upon hospital admission. Frailty was defined as a Clinical Frailty Scale score ≥ 4. The performance of a NEWS2 score ≥ 5 to predict in-hospital mortality was assessed with sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) according to frailty status., Results: Out of 412 patients, 70 were aged ≥ 65 years and with frailty. They presented less frequently with respiratory symptoms, and more often with acute functional decline or new-onset confusion. In-hospital mortality was 6% in patients without frailty, and 26% in patients with frailty. NEWS2 predicted in-hospital mortality with a sensitivity of 86%, 95% confidence interval (CI) 64%-97% and AUROC 0.73, 95% CI 0.65-0.81 in patients without frailty. In older patients with frailty, sensitivity was 61%, 95% CI 36%-83% and AUROC 0.61, 95% CI 0.48-0.75., Conclusion: A single NEWS2 score at hospital admission performed poorly to predict in-hospital mortality in patients with frailty and COVID-19 and should be used with caution in this patient group. Graphical abstract summing up study design, results and conclusion., (© 2023. The Author(s).)

Objectives: Hypertension in midlife is a risk factor for cognitive impairment. Still, the ideal midlife blood pressure (BP) remains unknown. We examined associations between different systolic blood pressure (SBP) levels at the age of 40-43 years and change in SBP over a 25-year period with cognitive function at age 62-65 years., Methods: We included 2424 individuals born in 1950 who had participated both in the Age 40 Program (1990-1993) and the Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). The exposure was SBP at age 40-43 years and the outcome was cognitive function at age 62-65 years, assessed with Montreal Cognitive Assessment, Delayed recall trial from the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task, and Trail Making Test part B (TMT B)., Results: Participants were 40.1 ± 0.3 years old with mean SPB 128 ± 13 mmHg at the Age 40 Program, and 63.9 ± 0.6 years old with mean SPB 138 ± 18 at the ACE 1950 Study. Adjusted linear regressions showed no associations between SBP and subsequent cognitive function. In logistic regressions, individuals with SBP ≥140 mmHg, compared to individuals with SBP <120 mmHg (odds ratio 2.29, 95% confidence interval 1.28-4.10, P-value 0.005) had increased risk of an abnormal TMT B-score. Change in SBP during the 25-year follow-up was not associated with cognitive function., Conclusions: SBP ≥140 mmHg at age 40-43 was associated with reduced capacity on TMT B, a domain specific cognitive test sensitive to vascular impairment. No other associations were found between SBP, or change in SBP, and cognitive function., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Clostridioides difficile infection is an urgent antibiotic-associated health threat with few treatment options. Microbiota restoration with faecal microbiota transplantation is an effective treatment option for patients with multiple recurring episodes of C difficile. We compared the efficacy and safety of faecal microbiota transplantation compared with placebo after vancomycin for first or second C difficile infection., Methods: We did a randomised, double-blind, placebo-controlled trial (EarlyFMT) at a university hospital in Aarhus, Denmark. Eligible patients were aged 18 years or older with first or second C difficile infection (defined as ≥3 watery stools [Bristol stool chart score 6-7] per day and a positive C difficile PCR test). Patients were randomly assigned (1:1) to faecal microbiota transplantation or placebo administered on day 1 and between day 3 and 7, after they had received 125 mg oral vancomycin four times daily for 10 days. Randomisation was done by investigators using a computer-generated randomisation list provided by independent staff. Patients and investigators were masked to the treatment group. The primary endpoint was resolution of C difficile-associated diarrhoea (CDAD) 8 weeks after treatment. We followed up patients for 8 weeks or until recurrence. We planned to enrol 84 patients with a prespecified interim analysis after 42 patients. The primary outcome and safety outcomes were analysed in the intention-to-treat population, which included all randomly assigned patients. The trial is registered with ClinicalTrials.gov, NCT04885946., Findings: Between June 21, 2021, and April 1, 2022, we consecutively screened 86 patients, of whom 42 were randomly assigned to faecal microbiota transplantation (n=21) or placebo (n=21). The trial was stopped after the interim analysis done on April 7, 2022 for ethical reasons because a significantly lower rate of resolution was identified in the placebo group compared with the faecal microbiota transplantation group (Haybittle-Peto boundary limit p<0·001). 19 (90%; 95% CI 70-99) of 21 patients in the faecal microbiota transplantation group and seven (33%, 95% CI 15-57) of 21 patients in the placebo group had resolution of CDAD at week 8 (p=0·0003). The absolute risk reduction was 57% (95% CI 33-81). Overall, 204 adverse events occurred, with one or more adverse events being reported in 20 of 21 patients in the faecal microbiota transplantation group and all 21 patients in the placebo group. Diarrhoea (n=23 in the faecal microbiota transplantation group; n=14 in the placebo group) and abdominal pain (n=14 in the faecal microbiota transplantation group; n=11 in the placebo group) were the most common adverse events. Three serious adverse events possibly related to study treatment occurred (n=1 in the faecal microbiota transplantation group; n=2 in the placebo group), but no deaths or colectomies during the 8-week follow-up., Interpretation: In patients with first or second C difficile infection, first-line faecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C difficile., Funding: Innovation Fund Denmark., Competing Interests: Declarations of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the association between visual function and ultrastructural characteristics of the retina and optic disc in children operated for cataract and factors influencing this relationship., Methods: We included 56 children aged 7-18 years who had been operated for bilateral or unilateral cataract. Three-dimensional swept source OCT scans of the macula and the optic disc were obtained using the Triton OCT (Topcon, Corporation, Tokyo, Japan). Best corrected distance visual acuity was measured using the HOTV 3 Meter visual chart. Contrast vision was evaluated using the Freiburg Visual Acuity Contrast Test (FrACT). Healthy fellow eyes of the unilateral group were used as control eyes., Results: We did not find any associations between visual acuity or contrast sensitivity and structural retinal parameters. Shorter axial length, the presence of glaucoma and pseudophakia (opposed to aphakia) were all significant predictors of greater mean macular thickness in a multiple regression analysis, (p = 0.039). Two children had foveal hypoplasia, and one child had a right eye with a thin, disorganized retina., Conclusions: Children with pseudophakia have a thicker macula but this does not seem to be related to visual function. Obtaining high quality OCT scans of the macula and optic disc in severely visually impaired children with glaucoma and/or nystagmus is challenging. We found structural macular changes which contributed to poor vision but most eyes with very reduced vision were difficult to image, and the prevalence of structural changes may be underestimated., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The role of methylation in adaptive, developmental and speciation processes has attracted considerable interest, but interpretation of results is complicated by diffuse boundaries between genetic and non-genetic variation. We studied whole genome genetic and methylation variation in the European eel, distributed from subarctic to subtropical environments, but with panmixia precluding genetically based local adaptation beyond single-generation responses. Overall methylation was 70.9%, with hypomethylation predominantly found in promoters and first exons. Redundancy analyses involving juvenile glass eels showed 0.06% and 0.03% of the variance at SNPs to be explained by localities and environmental variables, respectively, with GO terms of genes associated with outliers primarily involving neural system functioning. For CpGs 2.98% and 1.36% of variance was explained by localities and environmental variables. Differentially methylated regions particularly included genes involved in developmental processes, with Hox clusters featuring prominently. Life stage (adult versus glass eels) was the most important source of inter-individual variation in methylation, probably reflecting both ageing and developmental processes. Demethylation of transposable elements relative to pure European eel was observed in European X American eel hybrids, possibly representing postzygotic barriers in this system characterized by prolonged speciation and ongoing gene flow. Whereas the genetic data are consistent with a role of single-generation selective responses, the methylation results underpin the importance of epigenetics in the life cycle of eels and suggest interactions between local environments, development and phenotypic variation mediated by methylation variation. Eels are remarkable by having retained eight Hox clusters, and the results suggest important roles of methylation at Hox genes for adaptive processes., (© 2022 John Wiley & Sons Ltd.)

Background: To report long-term biometric and refractive outcomes in a group of Danish children after surgery for childhood cataract., Methods: Children between 7 and 18 years who had undergone uni- or bilateral cataract surgery at the Department of Ophthalmology, Rigshospitalet, Denmark, were examined in this cross-sectional study. Swept source optical coherence tomography (OCT) based optical biometry (IOLmaster 700) and anterior tomography (Pentacam) was performed. Healthy fellow eyes from those with unilateral cataract were used as controls., Results: We included 56 children in the study with a median age at surgery of 43.8 months (1.6-137.6). The amount of higher order aberrations was significantly increased in operated eyes (median root mean square 0.461 μm [range 0.264-1.484]) compared with non-operated eyes (median root mean square 0.337 μm [range 0.162-0.498], p < 0.001). Younger age at surgery was positively associated with more higher order aberrations at follow-up (p < 0.001), but we found no significant associations between the amount of higher order aberrations and visual acuity or contrast vision. Longer axial length was associated to glaucoma while shorter axial length was associated to strabismus (p < 0.001)., Conclusions: Eyes operated for childhood cataract have higher order aberrations compared with non-operated eyes. Higher order aberrations are complex refractive errors that cannot be corrected by normal lenses and may contribute to poor visual outcomes for the children. We found an association between young age at surgery and higher order aberrations., (© 2022 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: Several of those who have been infected with COVID-19 suffer from the post-COVID-19 condition months after the acute infection. Little is known about how older survivors have experienced the consequences and how these have affected their lives. The aim of this study was to explore how older survivors experienced post-COVID-19 condition and life changes approximately 6 months after hospitalisation for COVID-19., Methods: The study had an explorative and descriptive design. Semi-structured interviews were performed with 17 participants from two local hospitals, 11 men and 6 women, aged 60 years and older (age range 60-96), approximately 6 months after hospitalisation for COVID-19. A thematic descriptive analysis inspired by Braun and Clarke was used., Results: Two main themes and seven subthemes were revealed. The main themes were: From few to various persistent symptoms and Existential thoughts and reflections. Most of the participants experienced various physical and/or cognitive symptoms, such as reduced physical fitness, heavy breathing, fatigue, and 'brain fog'. On the other hand, they also experienced guilt and gratitude for having survived. The recognition of having achieved other life perspectives was also present., Conclusion: Six months after undergone COVID-19 the participants still experienced various distressing symptoms, which were in line with larger studies. The novel findings of this study were connected to the existential area, where the patients' thoughts and reflections of guilt, gratitude, and new life perspectives were revealed. These findings are important for health professionals to consider when treating patients after COVID-19., (© 2022. The Author(s).)

Gene flow shapes spatial genetic structure and the potential for local adaptation. Among marine animals with nonmigratory adults, the presence or absence of a pelagic larval stage is thought to be a key determinant in shaping gene flow and the genetic structure of populations. In addition, the spatial distribution of suitable habitats is expected to influence the distribution of biological populations and their connectivity patterns. We used whole genome sequencing to study demographic history and reduced representation (double-digest restriction associated DNA) sequencing data to analyse spatial genetic structure in broadnosed pipefish (Syngnathus typhle). Its main habitat is eelgrass beds, which are patchily distributed along the study area in southern Norway. Demographic connectivity among populations was inferred from long-term (~30-year) population counts that uncovered a rapid decline in spatial correlations in abundance with distance as short as ~2 km. These findings were contrasted with data for two other fish species that have a pelagic larval stage (corkwing wrasse, Symphodus melops; black goby, Gobius niger). For these latter species, we found wider spatial scales of connectivity and weaker genetic isolation-by-distance patterns, except where both species experienced a strong barrier to gene flow, seemingly due to lack of suitable habitat. Our findings verify expectations that a fragmented habitat and absence of a pelagic larval stage promote genetic structure, while presence of a pelagic larvae stage increases demographic connectivity and gene flow, except perhaps over extensive habitat gaps., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Background: In March 2020, the COVID-19 pandemic challenged both the Norwegian population and healthcare system. In this study we explored how older men and women experienced rehabilitation and recovery after hospitalisation due to severe COVID-19., Methods: Semi-structured interviews with 17 participants aged 60-96 years were performed 6 months after discharge from hospital. A thematic descriptive analysis was conducted., Results: The results revealed that the participants experienced a challenging span between loneliness and companionship in recovering from severe COVID-19. The four subthemes highlighted experiences of being discharged to home and left to themselves, the importance of exercise and companionship at rehabilitation stay, requirement of self-effort and time to recover, and the challenging span between loneliness and companionship when being with family., Conclusion: Among participants, the experiences of loneliness throughout the recovery period were striking. An individualised approach including psychological support should be emphasized in primary healthcare to promote recovery in older survivors after severe COVID-19 and their next-of-kin., (© 2022. The Author(s).)

Context: A memorandum of understanding was reached between the Accreditation Council for Graduate Medical Education (ACGME), the American Osteopathic Association (AOA), and the American Association of Colleges of Osteopathic Medicine (AACOM) in 2014 outlining the course for a single accreditation system for graduate medical education. This process was completed in 2020 and has included the transition of AOA-accredited neuromusculoskeletal and Osteopathic Manipulative Medicine (OMM) programs into programs now termed "Osteopathic Neuromusculoskeletal Medicine" (ONMM) under the single accreditation system. Progress through ONMM residency is evaluated on the basis of 15 ACGME milestones that encompass six core competencies. However, there are no curricular guidelines to help guide the achievement of these milestones., Objectives: The primary purpose of this study was to develop a proposed structure and content for an ONMM residency curriculum that is based on (1) the alignment of residency curriculum with ACGME milestones in one ACGME-accredited ONMM residency program, and (2) the perceived needs of residents and faculty for an ONMM residency curriculum., Methods: A mixed-methods exploratory sequential approach with embedded design was utilized. Qualitative analysis of didactics curriculum content for the past 2 years was coded according to themes identified in the residency curriculum content, which were further coded according to ACGME milestones. Curriculum topics identified in qualitative analysis were utilized to create a questionnaire that was administered to residents and faculty (n=24) in the ONMM residency program to examine the perceived importance of each curriculum topic based on a five-point Likert scale. Open-ended questions were embedded in the questionnaire that asked how faculty and residents define ONMM and what they believe should be the purpose of an ONMM residency curriculum., Results: Five themes were identified in qualitative analysis of curriculum: (1) OMM laboratory topics; (2) faculty-led activities and lecture topics; (3) resident-led activities and lecture topics; (4) research; and (5) training courses and volunteer activities. The most important perceived curriculum topics for faculty and residents were osteopathic structural examination, orthopedic exam, direct and indirect methods, osteopathic cranial manipulative medicine, pediatric OMT, common upper and lower extremity injuries, and low back pain. Each of these topics aligned well with ACGME milestones. Residents reported that integrative medicine topics such as acupuncture were a significantly more important OMM laboratory topic (mean=3.58, SD=0.996) compared to faculty (mean=2.33, SD=0.985), t (22)=-3.091, p=0.005. Study participants most commonly described ONMM in terms of the specialized knowledge required for the discipline (n=19, 79.2%) and the Tenets of Osteopathy (n=17, 70.8%), and they felt that the purpose of an ONMM residency curriculum should be to gain knowledge (n=20, 83.3%) and become a competent physician (n=19, 79.2%)., Conclusions: The present findings were applied to the development of proposed ONMM residency curriculum guidelines and submitted to the American Academy of Osteopathy (AAO) for consideration. They are presented here as a resource for ONMM residencies to develop a program curriculum in alignment with individual program needs., (© 2021 Elizabeth S. Balyakina et al., published by De Gruyter, Berlin/Boston.)

Background: The objective of this article is to summarise the course of illness and treatment for patients with COVID-19 admitted to Bærum Hospital since the start of the pandemic., Material and Method: We present data from a prospective observational study with the aim of systematising knowledge about patients admitted because of COVID-19. All patients admitted to Bærum Hospital up to and including 28 June 2021 were included. The results are presented for three waves of admissions: 9 March-23 June 2020, 21 September 2020-28 February 2021 and 1 March-28 June 2021., Results: A total of 300 patients, divided into 77, 101 and 122 in the three waves respectively, were admitted because of COVID-19. The number of hospital deaths during the three waves was 14 (18 %), 11 (11 %) and 5 (4 %) respectively. The average age of the patients was 67.6 years in the first wave and 53.3 years in the third wave. Altogether 204 patients (68 %) received medical oxygen or ventilation support, and 31 of these (10 % of all the patients) received invasive ventilation support. Non-invasive ventilation support was used as the highest level of treatment in 4 (8 %), 9 (13 %) and 17 (20 %) patients with respiratory failure in the three waves respectively. In the second and third wave, 125 out of 152 patients with respiratory failure (82 %) were treated with dexamethasone., Interpretation: Differences in patient characteristics and changes to treatment methods, such as the use of dexamethasone and non-invasive ventilation support, may have contributed to the apparent fall in mortality from the first to the third wave. Conditions that are not registered in the study, such as vaccination status, may also have impacted on mortality.

Depression is a chronic and debilitating condition that often emerges during adolescence, a period of significant brain maturation. Few studies, however, have examined how mechanisms of neuroplasticity, including myelination, are affected by adolescent-onset depression. Here, we used multimodal MR imaging to characterize myelin, indexed by R1, in white matter tracts previously associated with depression and compare 48 adolescents with lifetime depression (45 with current depression, 3 remitted) and 35 healthy controls in R1. Compared to healthy controls, R1 was higher in adolescents with lifetime depression in the uncinate fasciculus and corpus callosum genu (all βs > 0.42; all ps < 0.037). Sex significantly moderated the association between depression and R1 in the left uncinate fasciculus and corpus callosum genu (all βs > 0.86; all ps < 0.02), such that depressed female adolescents had significantly higher R1 in these tracts than did healthy female adolescents (all βs > 0.82; all ps < 0.0012). In contrast, depressed and non-depressed male adolescents did not differ in R1 in these tracts (all ps > 0.32). While fractional anisotropy (FA), a commonly examined measure of white matter organization based on diffusion-weighted MRI, in the left uncinate was positively associated with lifetime depression in our sample (β = 0.56; p = 0.016), we found no evidence of sex-specific effects of depression in FA. Our results suggest that R1 is more sensitive to sex-specific effects of depression than FA, particularly in female adolescents. Given evidence that myelin inhibits synapse formation and reduces brain plasticity, our findings implicate experience-driven regional myelination as a mechanism underlying depression during periods of significant neural maturation such as adolescence., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background: Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab., Aims: To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life METHODS: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3). Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance., Results: In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring., Conclusions: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe., (© 2021 John Wiley & Sons Ltd.)

Postcopulatory sexual selection is credited as a principal force behind the rapid evolution of reproductive characters, often generating a pattern of correlated evolution between interacting, sex-specific traits. Because the female reproductive tract is the selective environment for sperm, one taxonomically widespread example of this pattern is the co-diversification of sperm length and female sperm-storage organ dimension. In Drosophila , having testes that are longer than the sperm they manufacture was believed to be a universal physiological constraint. Further, the energetic and time costs of developing long testes have been credited with underlying the steep evolutionary allometry of sperm length and constraining sperm length evolution in Drosophila . Here, we report on the discovery of a novel spermatogenic mechanism-sperm cyst looping-that enables males to produce relatively long sperm in short testis. This phenomenon (restricted to members of the saltans and willistoni species groups) begins early during spermatogenesis and is potentially attributable to heterochronic evolution, resulting in growth asynchrony between spermatid tails and the surrounding spermatid and somatic cyst cell membranes. By removing the allometric constraint on sperm length, this evolutionary innovation appears to have enabled males to evolve extremely long sperm for their body mass while evading delays in reproductive maturation time. On the other hand, sperm cyst looping was found to exact a cost by requiring greater total energetic investment in testes and a pronounced reduction in male lifespan. We speculate on the ecological selection pressures underlying the evolutionary origin and maintenance of this unique adaptation.

Background: In species showing partial migration, as is the case for many salmonid fishes, it is important to assess how anthropogenic pressure experienced by migrating individuals affects the total population. We focused on brown trout (Salmo trutta) from the Guddal River in the Norwegian Hardanger Fjord system, which encompasses both resident and anadromous individuals. Aquaculture has led to increased anthropogenic pressure on brown trout during the marine phase in this region. Fish traps in the Guddal River allow for sampling all ascending anadromous spawners and descending smolts. We analyzed microsatellite DNA markers from all individuals ascending in 2006-2016, along with all emigrating smolts in 2017. We investigated (1) if there was evidence for declines in census numbers and effective population size during that period, (2) if there was association between kinship and migration timing in smolts and anadromous adults, and (3) to what extent resident trout were parents of outmigrating smolts., Results: Census counts of anadromous spawners showed no evidence for a decline from 2006 to 2016, but were lower than in 2000-2005. Estimates of effective population size also showed no trends of declines during the study period. Sibship reconstruction of the 2017 smolt run showed significant association between kinship and migration timing, and a similar association was indicated in anadromous spawners. Parentage assignment of 2017 smolts with ascending anadromous trout as candidate parents, and assuming that unknown parents represented resident trout, showed that 70% of smolts had at least one resident parent and 24% had two resident parents., Conclusions: The results bear evidence of a population that after an initial decline has stabilized at a lower number of anadromous spawners. The significant association between kinship and migration timing in smolts suggests that specific episodes of elevated mortality in the sea could disproportionally affect some families and reduce overall effective population size. Finally, the results based on parentage assignment demonstrate a strong buffering effect of resident trout in case of elevated marine mortality affecting anadromous trout, but also highlight that increased mortality of anadromous trout, most of which are females, may lower overall production in the system., (© 2021. The Author(s).)

Background: Previous studies have investigated the natural course of cow's milk allergy (CMA) and development of atopic diseases into adolescence. Studies with long-term follow-up into adulthood are lacking. The aim of this study was to investigate (a) the natural course of CMA in a 1-year birth cohort of Danish children from birth until 15 and 26 years of age and (b) the development of atopic diseases in a group of children with CMA (group A) compared to a random sample of 276 children from the same birth cohort (group B)., Methods: A birth cohort of 1749 newborns was investigated prospectively for the development of CMA and atopic diseases. During the first year of life and at 18 months and 3, 5, 10, 15, and 26 years of age, questionnaire-based interviews, physical examination, skin prick tests, and specific IgE testing, and from 10 years also spirometry, were carried out., Results: Thirty-nine (2.2%) were diagnosed with CMA. The recovery rate was 87%, 92%, and 97% at 3, 5, and 26 years of age. Compared to group B, group A had significantly (P < .05) higher prevalence of asthma and rhinoconjunctivitis at 15 years of age, and at 26 years of age, group A had significantly higher prevalence of asthma and atopic dermatitis. The follow-up rate was 85% (A) and 70% (B)., Conclusion: CMA has a good prognosis regarding recovery rate. However, CMA, especially IgE-mediated, in early childhood predicts a high prevalence of atopic diseases into adulthood., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Environmental DNA (eDNA) provides a promising supplement to traditional sampling methods for population genetic inferences, but current studies have almost entirely focused on short mitochondrial markers. Here, we develop one mitochondrial and one nuclear set of target capture probes for the whale shark (Rhincodon typus) and test them on seawater samples collected in Qatar to investigate the potential of target capture for eDNA-based population studies. The mitochondrial target capture successfully retrieved ~235× (90× - 352× per base position) coverage of the whale shark mitogenome. Using a minor allele frequency of 5%, we find 29 variable sites throughout the mitogenome, indicative of at least five contributing individuals. We also retrieved numerous mitochondrial reads from an abundant nontarget species, mackerel tuna (Euthynnus affinis), showing a clear relationship between sequence similarity to the capture probes and the number of captured reads. The nuclear target capture probes retrieved only a few reads and polymorphic variants from the whale shark, but we successfully obtained millions of reads and thousands of polymorphic variants with different allele frequencies from E. affinis. We demonstrate that target capture of complete mitochondrial genomes and thousands of nuclear loci is possible from aquatic eDNA samples. Our results highlight that careful probe design, taking into account the range of divergence between target and nontarget sequences as well as presence of nontarget species at the sampling site, is crucial to consider. eDNA sampling coupled with target capture approaches provide an efficient means with which to retrieve population genomic data from aggregating and spawning aquatic species., (© 2020 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Background: Older people are particularly vulnerable to severe COVID-19. Little is known about long-term consequences of COVID-19 on health-related quality of life (HR-QoL) and functional status in older people, and the impact of age in this context. We aimed to study age-related change in health-related quality of life, functional decline and mortality among older patients 6 months following hospitalisation due to COVID-19., Methods: This was a cohort study including patients aged 60 years and older admitted to four general hospitals in South-Eastern Norway due to COVID-19, from March 1 up until July 1, 2020. Patients who were still alive were invited to attend a six-month follow-up. Change in HR-QoL and functional status compared to before the COVID-19 hospitalisation were assessed using the EuroQol 5-dimensional-5 levels questionnaire (EQ. 5D-5L). A change in visual analogue scale (VAS) score of 7 or more was considered clinically relevant., Results: Out of 216 patients aged 60 years and older that were admitted to hospital due to COVID-19 during the study period, 171 were still alive 180 days after hospital admission, and 106 patients (62%) attended the six-month follow-up. Mean age was 74.3 years, 27 patients (26%) had experienced severe COVID-19. Fifty-seven participants (54%) reported a decrease in the EQ. 5D-5L VAS score after 6 months, with no significant difference between persons aged 75 years and older compared to younger. Seventy participants (66%) reported a negative change in any of the dimensions of the EQ. 5D-5L, with impaired ability to perform activities of daily life (35%), reduced mobility (33%) and having more pain or discomfort (33%) being the most commonly reported changes. Forty-six participants (43%) reported a negative change in cognitive function compared to before the COVID-19 hospitalisation. Six-month mortality was 21%, and increased with increasing age., Conclusions: More than half of the patients reported a negative change in HR-QoL 6 months following hospitalisation due to COVID-19, and one out of three experienced a persistently impaired mobility and ability to carry out activities of daily living. The results suggest awareness of long-term functional decline in older COVID-19 patients.