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Abstract Background Neurofibromatosis type 1 (NF1) is a genetic condition characterized by various somatic manifestations and cognitive impairments, but the latter are sparsely described in adults. This study aimed at characterizing potential impairments of neurocognitive functions using neuropsychological tests as well as a self-report questionnaire. Methods In a nationwide, population-based study including 103 adults with NF1 and 38 age- and gender-matched NF1-free comparisons, we used a comprehensive neurocognitive test battery to assess intelligence and visual short-term memory, immediate visuospatial recall, reaction time, sustained attention, motor speed, planning, planning time, working memory as well as multitasking and a questionnaire to assess executive functions. Descriptive statistics, multivariate analysis of variance (MANOVA), and general linear models with repeated measure analysis of variance (ANOVA) were used. Results We observed a statistically significant difference in overall performance-based cognitive functioning. Adults with NF1 showed significant, moderate-to-severe impairments in intelligence, visual short-term memory, immediate visuospatial recall, sustained attention (p

Abstract Objectives Emergency Medical Communication Centers (EMCC) have a key role in the prehospital chain-of-stroke-survival by recognizing stroke patients and reducing prehospital delay. However, studies on EMCC stroke recognition report both substantial undertriage and overtriage. Since mis-triage at the EMCC challenges the whole chain-of-stroke-survival, by occupying limited resources for non-stroke patients or failing to recognize the true stroke patients, there is a need to achieve a more comprehensive understanding of the dispatchers’ routines and experiences. The aim of this study was to explore factors affecting EMCC dispatcher’s decision-making in stroke calls. Materials and methods A qualitative exploratory study, based on individual semi-structured interviews of 15 medical dispatchers from EMCC Oslo, Norway. Interviews were conducted during August and October 2022 and analyzed using the principles of thematic analysis. Results We identified four themes: [1] Pronounced stroke symptoms are easy to identify [2]. Non-specific neurological symptoms raise suspicion of acute stroke but are difficult to differentiate from other medical conditions [3]. Consistent use of the Criteria Based Dispatch (CBD) protocol may increase EMCC overtriage [4]. Contextual conditions at EMCC can affect dispatchers’ decision-making process and the ability for experiential learning. Conclusions Medical dispatchers at the EMCC perceive vague and non-specific stroke symptoms, such as dizziness, confusion or altered behaviour, challenging to differentiate from symptoms of other less time-critical medical conditions. They also perceive the current CBD protocol in use as less supportive in assessing such symptoms. High workload and strict EMCC response time interval requirements hinder the gathering of essential patient information and the ability to seek guidance in cases of doubt, potentially exacerbating both EMCC undertriage and overtriage. The absence of feedback loops and other strategies for experiential learning in the EMCC hampers the medical dispatcher’s ability to evaluate their own assessments and improve dispatch accuracy.

Abstract The genus Ilex (holly) in the monotypic family Aquifoliaceae contains more than 600 species distributed worldwide. Pollen fossils and macrofossils of fruits of Ilex are known from the late Cretaceous (90 Ma) and verified leaves from the upper Miocene (10 Ma), but until now only a few more or less incomplete flower fossils have been suggested as referable to this genus. This paper reviews the fossil flowers earlier attributed to Ilex and presents a complete and indisputable staminate Ilex flower from Baltic amber (34–38 Ma) examined in detail with synchrotron X-ray tomography. This finding may challenge the hypothesis of late Neogene dispersal of the genus from a center of origin in subtropical East Asia.

Anita Dyb Linge,1,2,* Irene Øyeflaten,3,* Thomas Johansen,4,5,* Tarjei Urup Helle,6,* Chris Jensen,4,* Anniken Hjellbakk Hole,1,* Randi Jepsen7,8,* 1Muritunet Rehabilitation Centre, Valldal, Norway; 2Faculty of Social Science and History, Volda University College, Volda, Norway; 3Telemark Research Institute, Bø, Norway; 4Norwegian National Advisory Unit on Occupational Rehabilitation, Rauland, Norway; 5Hernes Occupational Rehabilitation Centre, Hernes, Norway; 6The Rehabilitation Centre AiR, Rauland, Norway; 7Red Cross Haugland Rehabilitation Centre, Flekke, Norway; 8Centre for Health Research, Zealand University Hospital, Nykøbing Falster, Denmark*These authors contributed equally to this workCorrespondence: Anita Dyb Linge, Faculty of Social Science and History, Volda University College, Mailbox 500, Volda, 6101, Norway, Tel +47 988 73 835, Email Anita.Linge@hivolda.noBackground: In Norway, individuals who struggle to participate in the workforce can take part in rehabilitation programmes to improve their work ability. The goal is to return to work by working with cognitive, physical, and environmental processes. Virtual Reality (VR) technology has become a popular and common tool in many healthcare and rehabilitation services but has not yet been systematically applied in occupational rehabilitation.Purpose: This study aimed to investigate the experiences of participants who engaged in a game-based, immersive VR activity as part of an occupational rehabilitation program.Material and Methods: Semi-structured interviews were conducted with individuals on long-term sick leave. In total, 12 women and three men (median age 45 years) from three rehabilitation centres (five individuals from each centre) were interviewed before and after discharge from the inpatient stay. The transcripts were analysed using Systematic Text Condensation.Results: When analysing the data material, four themes were consistent. The first and the second theme contained information about how the VR headset and the game influenced the participants. The headset forced them to pay full attention and gave a feeling of protection from external stimuli. The game brought joy, energy, and endurance with its music and rhythm. The third and fourth themes provided information about how the gaming activity influenced the participants. They experienced that it provided a free space and symptom relief. In addition, they got carried away, broke barriers, and challenged themselves.Conclusion: The study results indicated that a gamified VR activity in occupational rehabilitation may be a new and powerful experience, substantially different from other rehabilitation modalities. VR training can facilitate a here-and-now feeling distracted from the outside world. More knowledge is needed on possible synergies between VR and other components of occupational rehabilitation and on how it may influence return to work for individuals on long-term sick leave.Keywords: virtual reality, gaming, occupational rehabilitation, patient experience, qualitative study

Numerous young individuals with various clinical diagnoses and disabilities utilise social media and its aesthetic features to amplify their voices and highlight issues related to disabilities. Like other users of social media, young people with disabilities adapt to the genre conventions of the platforms and discuss significant topics, such as apprehensions about hospitals and societal prejudices linked to disabilities. This article scrutinises the utilisation of social media by young people with disabilities to ascertain how they portray themselves on platforms that have frequently faced criticism for perpetuating not only unhealthy body images but predominantly able-bodied ideals as well. The analysis indicates that young individuals consistently contemplate their portrayal on social media and deliberate over what they reveal and to what extent. Concurrently, they purposefully employ social media to challenge prejudice and stigma, both of which they routinely encounter.

Abstract Macrolides are widely used antibiotics for the treatment of bacterial airway infections. Due to its elevated minimum inhibitory concentration in standardized culture media, Pseudomonas aeruginosa is considered intrinsically resistant and, therefore, antibiotic susceptibility testing against macrolides is not performed. Nevertheless, due to macrolides’ immunomodulatory effect and suppression of virulence factors, they are used for the treatment of persistent P. aeruginosa infections. Here, we demonstrate that macrolides are, instead, effective antibiotics against P. aeruginosa airway infections in an Air-Liquid Interface (ALI) infection model system resembling the human airways. Importantly, macrolide treatment in both people with cystic fibrosis and primary ciliary dyskinesia patients leads to the accumulation of uL4 and uL22 ribosomal protein mutations in P. aeruginosa which causes antibiotic resistance. Consequently, higher concentrations of antibiotics are needed to modulate the macrolide-dependent suppression of virulence. Surprisingly, even in the absence of antibiotics, these mutations also lead to a collateral reduction in growth rate, virulence and pathogenicity in airway ALI infections which are pivotal for the establishment of a persistent infection. Altogether, these results lend further support to the consideration of macrolides as de facto antibiotics against P. aeruginosa and the need for resistance monitoring upon prolonged macrolide treatment.

Abstract The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count

Abstract Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment.

Abstract Background Recent changes in the infant feeding guidelines for women living with HIV from high-income countries recommend a more supportive approach focusing on shared decision-making. Limited information is available on the infant feeding knowledge of women living with HIV and how healthcare providers engage with them in this context. This multicenter, longitudinal, mixed methods study aims to get a comprehensive and nuanced understanding of infant feeding knowledge among women living with HIV of Nordic and non-Nordic origin living in Nordic countries, and their interaction with healthcare providers regarding infant feeding planning. Methods Pregnant women living with HIV in Denmark, Finland, and Sweden were recruited in 2019–2020. The Positive Attitudes Concerning Infant Feeding (PACIFY) questionnaire was completed in the 3rd trimester (T1), three (T2), and six (T3) months postpartum. Women who completed the quantitative survey were also invited to participate in qualitative semi-structured interviews at T1 and T3. Results from the survey and interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the datasets and to draw meta-inferences. Results In total, 44 women living with HIV completed the survey, of whom 31 also participated in the interviews. The merged analyses identified two overarching domains: Knowledge about breastfeeding in the U = U era and Communications with healthcare providers. The women expressed confusion about breastfeeding in the context of undetectable equals untransmittable (U = U). Women of Nordic origin were more unsure about whether breastfeeding was possible in the context of U = U than women of non-Nordic origin. Increased postpartum monitoring with monthly testing of the mother was not seen as a barrier to breastfeeding, but concerns were found regarding infant testing and infant ART exposure. Infant feeding discussions with healthcare providers were welcome but could also question whether breastfeeding was feasible, and many participants highlighted a need for more information. Conclusions Healthcare providers caring for women living with HIV must have up-to-date knowledge of HIV transmission risks during breastfeeding and engage in shared decision-making to optimally support infant feeding choices.

ABSTRACT: Dietary carbohydrate manipulation can be used to reduce enteric CH4 emission, but few studies have focused on the interaction of the different types of carbohydrates that can affect feed intake and ruminal fermentation. Understanding this interaction is necessary to make the most out of CH4 mitigation feeding strategies using different dietary carbohydrates. The aim of this study was to test the effect on enteric CH4 emission, feed intake, and milk production response when cows were fed either grass-clover silage (GCS) or corn silage (CS) as the sole forage source (55% of dry matter, DM), in combination with either barley (BAR) or dried beet pulp (DBP) as a concentrate (21.5% of DM). A total of 24 (half first-parity and half second-parity) cows were used in a crossover design with 2 periods of 21 d each, receiving 2 of 4 diets obtained from a 2 × 2 factorial arrangement of the experimental diet. Feed intake, CH4 emission metrics, and milk production were recorded at the end of the experimental periods. The diets had NDF concentrations between 258 and 340 g/kg of DM and starch concentrations between 340 and 7.45 g/kg of DM (CS-BAR and GCS-DBP, respectively). The effects of silage and concentrate on dry matter intake (DMI) were additive, with the highest feed intake in cows fed CS-BAR, followed by cows fed CS-DBP, GCS-BAR, and GCS-DBP (21.2, 19.9, 19.1, and 18.3 kg/d, respectively). Energy corrected milk (ECM) yield was not affected by silage source in first parity cows, but it was higher for cows fed CS than cows fed GCS in second parity. The effects of silage and concentrate on CH4 production (g/d), yield (g/kg of DMI), and intensity (g/kg of ECM) were not additive, as cows fed GCS had similar responses regardless of the concentrate used, but cows fed CS had lower CH4 production, yield, and intensity when fed BAR instead of DBP. The lower CH4 production, yield, and intensity in cows fed CS-BAR compared with other diets could be partially explained by the nonlinear relationship between ruminal VFA and carbohydrates (NDF and starch) concentration reported in the literature; however, we observed a linear relationship between the acetate/propionate ratio and CH4 yield, suggesting possible other effects. The effects of silage and concentrate on the ruminal VFA were additive in first parity cows, but not in second parity cows. The interaction between dietary carbohydrate type and parity might indicate an effect of feed intake or the energy balance of the cow. Feeding cows silage and concentrate both rich in starch can result in the lowest enteric CH4 emission.

ABSTRACT: Milk production and overall dairy farm economics depend on rearing dairy heifers. This study investigated the presence of a genotype by environment interaction in Holstein (HOL), Nordic Red dairy cattle (RDC), and their F1 crossbreeds (HOL × RDC) when provided different feed rations. The aim of our study was to assess how different energy concentrations in feed rations affect growth, BCS, feed intake, and feed efficiency in the 3 groups during the prepubertal period. The 3 breed groups were randomly allocated to receive either a standard or a low-energy feed ration. Holstein heifers exhibited reduced growth and a lower BCS when they were fed the low-energy feed ration. In contrast, the RDC heifers demonstrated similar growth rates with the different feed rations and maintained similar BCS irrespective of feed energy concentration. The HOL × RDC crossbred heifers performed as an intermediate between the HOL and RDC groups. Significant differences were observed in DMI and energy intake in the HOL and HOL × RDC groups depending on feed ration treatment. The RDC heifers had similar feed intake irrespective of treatment. There were no significant differences in the feed conversion ratio among breeds and feed treatments. These results indicate the presence of a genotype by environment interaction in prepubertal HOL and RDC heifers in response to differences in feed ration treatment. Due to the influence of prepubertal growth on future milk production, reproduction, and health status, it is important to be aware of breed-specific requirements during the prepubertal period, particularly in mixed breed and crossbred groups, to optimize growth rates and production potential.

Abstract Background Cognitive impairment is prevalent across neuropsychiatric disorders but there is a lack of treatment strategies with robust, enduring effects. Emerging evidence indicates that altitude-like hypoxia cognition training may induce long-lasting neuroplasticity and improve cognition. We will investigate whether repeated cognition training under normobaric hypoxia can improve cognitive functions in healthy individuals and patients with affective disorders and the neurobiological underpinnings of such effects. Methods In sub-study 1, 120 healthy participants are randomized to one of four treatment arms in a double-blind manner, allowing for examination of separate and combined effects of three-week repeated moderate hypoxia and cognitive training, respectively. In sub-study 2, 60 remitted patients with major depressive disorder or bipolar disorder are randomized to hypoxia with cognition training or treatment as usual. Assessments of cognition, psychosocial functioning, and quality of life are performed at baseline, end-of-treatment, and at 1-month follow-up. Functional magnetic resonance imaging (fMRI) scans are conducted at baseline and 1-month follow-up, and [11C]UCB-J positron emission tomography (PET) scans are performed at end-of-treatment to quantify the synaptic vesicle glycoprotein 2A (SV2A). The primary outcome is a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference with minimum n = 26 per treatment arm. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data is analyzed with the FMRIB Software Library, while PET data is quantified using the simplified reference tissue model (SRTM) with centrum semiovale as reference region. Discussion The results will provide novel insights into whether repeated hypoxia cognition training increases cognition and brain plasticity, which can aid future treatment development strategies. Trial registration ClinicalTrials.gov, NCT06121206 . Registered on 31 October 2023.