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Mie Micheelsen Jensen,1 Stine Munk Hald,1,2 Line Marie Buch Kristensen,1 Nils Jensen Boe,1,2 Frederik Severin Gråe Harbo,3 David Gaist1,2,4 1Department of Neurology, Odense University Hospital, Odense, Denmark; 2Neurology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Department of Radiology, Odense University Hospital, Odense, Denmark; 4Open Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, DenmarkCorrespondence: David GaistDepartment of Neurology, Odense University Hospital, J.B. Winsløwsvej 4, Odense C, 5000, DenmarkTel +45 65412485Fax +45 65413389Email dgaist@health.sdu.dkPurpose: Danish registries could be an attractive resource for studies of recurrent intracerebral hemorrhage (re-ICH). We developed and validated algorithms to identify re-ICH in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR).Patients and Methods: Using multiple sources, we followed-up an inception cohort with verified first-ever spontaneous ICH (n = 2528) for their first re-ICH in 2009– 2018 (study period). We used verified cases of re-ICH (n = 124) as the gold standard to assess the performance of register-based algorithms for identifying re-ICH. For each cohort member, we traced events of re-ICH (ICD-10-code I61) in the study period according to DSR and DNPR, respectively. For each registry, we tested algorithms with a blanking period (BP) – ie, a period immediately following the index ICH during which outcome events were ignored – of varying length (7 days– 360 days). The algorithm with the shortest BP that returned a positive predictive value (PPV) of ≥ 80% was considered optimal. We also calculated negative predictive value (NPV), sensitivity, and specificity of each algorithm and [95% confidence intervals] for all proportions.Results: The optimal algorithm for DSR (BP 30 days) had a PPV of 89.5% [82.2– 94.0], NPV 98.8% [98.2– 99.1], sensitivity 75.8% [67.6– 82.5], and specificity 99.5% [99.2– 99.7]. The optimal algorithm for DNPR (BP 120 days) had a PPV of 80.6% [71.7– 87.2], NPV 98.1% [97.5– 98.6], sensitivity 63.7% [55.0– 71.6], and specificity 99.2% [98.8– 99.5].Conclusion: Simple algorithms accurately identified re-ICH in DSR and DNPR. Compared with DNPR, DSR achieved higher PPV and sensitivity with a shorter BP. The proposed algorithms could facilitate valid use of DSR and DNPR for studies of re-ICH.Keywords: stroke, recurrent stroke, intracerebral hemorrhage, epidemiology, validity, register-based research

Sanjay K Gandhi1, Marie M Jensen2, Kathleen M Fox3, Lee Smolen4, Anders G Olsson5, Thomas Paulsson61AstraZeneca LP, Wilmington, DE, USA; 2AstraZeneca, Lund, Sweden; 3Strategic HealthCare Solution, Monkton, MD; 4Medical Decision Modeling Inc, Indianapolis, IN, USA; 5Department of Medical and Health Sciences, Linkoping University, and Stockholm Heart Center, Stockholm; 6AstraZeneca, Sodertalje, SwedenBackground: To assess the long-term cost-effectiveness of rosuvastatin therapy compared with generic simvastatin and generic atorvastatin in reducing the incidence of cardiovascular events and mortality in a Swedish population with Framingham risk ≥20%.Methods: A probabilistic Monte Carlo simulation model based on data from JUPITER (the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was used to estimate the long-term cost-effectiveness of rosuvastatin 20 mg daily versus simvastatin or atorvastatin 40 mg for the prevention of cardiovascular death and morbidity. The three-stage model included cardiovascular event prevention simulating the 4 years of JUPITER, initial prevention beyond the trial, and subsequent cardiovascular event prevention. A Swedish health care payer perspective (direct costs only) was modeled for a lifetime horizon, with 2008/2009 as the costing period. Univariate and probabilistic sensitivity analyses were performed.Results: The incremental cost per quality-adjusted life-year (QALY) gained with rosuvastatin 20 mg over simvastatin or atorvastatin 40 mg ranged from SEK88,113 (rosuvastatin 20 mg versus simvastatin 40 mg; Framingham risk ≥30%; net avoidance of 34 events/1000 patients) to SEK497,542 (versus atorvastatin 40 mg: Framingham risk ≥20%; net avoidance of 11 events/1000 patients) over a lifetime horizon. Probabilistic sensitivity analyses indicated that at a willingness-to-pay threshold of SEK500,000/QALY, rosuvastatin 20 mg would be cost-effective for approximately 75%–85% of simulations relative to atorvastatin or simvastatin 40 mg. Sensitivity analyses indicated the findings to be robust.Conclusion: Rosuvastatin 20 mg is cost-effective over a lifetime horizon compared with generic simvastatin or atorvastatin 40 mg in patients at high cardiovascular risk in Sweden.Keywords: cardiovascular disease, cost-benefit analysis, cost-effectiveness, rosuvastatin, simvastatin, atorvastatin, generic, high risk

Reports on a outpatient developmental services project integrating pediatric psychology with primary medical care for children infected with HIV. Neurodevelopmental and neuropsychological evaluation; Barriers to service provision; Maximization of the benefits of both specialties.

Objective: To investigate patient-reported outcomes following lumbar discectomy in patients with lateral lumbar disc herniation (LDH) compared with patients with paramedian LDH., Methods: Data on patients with lateral and paramedian LDH operated on between 2017 and 2020 at a single public spine unit were extracted from the National Danish Spine Registry, DaneSpine. A propensity score-matched, case-control analysis was conducted to compare the 2 groups. Subgroup analysis was done by further dividing the lateral LDH group into foraminal and extraforaminal groups. Patient demographics, Oswestry Disability Index visual analog scale (VAS) leg and back pain (0-100), EuroQol-5D questionnaire, and measures of patient improvement and satisfaction were collected at baseline and 1 year postoperatively., Results: Of 887 eligible patients, baseline and 1-year follow-up data were available for 525 patients with paramedian LDH and 68 patients with lateral LDH. Following propensity score matching, the 2 groups were similar in terms of all baseline characteristics (P > 0.05). There were no significant differences between groups in Oswestry Disability Index, VAS leg pain, VAS back pain, and EuroQol-5D 1 year postoperatively. Both groups improved in all outcomes from inclusion to follow-up (P < 0.001). Subgroup analysis showed that patients with foraminal LDH compared with extraforaminal LDH had a significantly greater improvement in VAS leg pain (P = 0.016) with a larger number of patients with clinically significant leg pain improvement (P = 0.03)., Conclusions: Patients with lateral and paramedian LDH reported similar postsurgical outcomes. Spine surgeons should be less hesitant to operate on patients with lateral LDH. Patients with extraforaminal LDH experienced the least relief of leg pain., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study is to investigate the effects of acute exercise on appetite control and whether this differs between morning and late afternoon in individuals with overweight/obesity with or without type 2 diabetes (T2D)., Methods and Analysis: The hedonic and homeostatic appetite control in obesity and type 2 diabetes in the context of meal and exercise timing (TIMEX) study is a randomised, controlled, cross-over trial. Fifty-eight women and men (aged 18-75 years) with overweight or obesity (body mass index ≥25 kg/m 2 ) with or without T2D will be recruited. All participants will complete a screening and baseline visit followed by four test visits: two morning visits and two late afternoon visits. The participants will arrive in the fasted state during the visits. During one morning visit and one late afternoon visit, the participants will engage in a 45-min bout of acute high-intensity interval exercise on an ergometer bicycle. The remaining two visits (one morning and one late afternoon visit) will include 45 min of rest. Fifteen minutes after the rest or exercise period, the participants will be presented with an ad libitum meal. Blood samples will be collected and subjective appetite will be assessed using Visual Analogue Scales in the fasted state before exercise/rest, immediately post-exercise/rest and at 15, 30, 45 and 60 min post-exercise/rest. Food reward and food preferences will be assessed using the validated diurnal version of the Steno Biometric Food Preference Task in the fasted state before exercise/rest and 15 min after the ad libitum meal (45 min post-exercise/rest). The primary outcome is the difference in ad libitum energy intake after exercise compared with rest. Secondary outcomes include eating rate; 24-hour energy intake; appetite-related metabolites and hormones, and circulating biomarkers assessed from proteomics, metabolomics and lipidomics analyses; food choice, food attention and reaction time, explicit and implicit liking and wanting for different food categories, subjective appetite; ratings of perceived exertion during exercise. All outcomes will be compared between morning and late afternoon and between participants with and without T2D., Ethics and Dissemination: The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-22019913) and the Capital Region of Denmark's Research Register (Privacy). The study will be conducted in accordance with the Declaration of Helsinki. All results will be published in national and international peer-reviewed journals and will be disseminated at national and international conferences., Trial Registration Number: NCT05768958., Competing Interests: Competing interests: LJ, NPL, MMJ, MBB, LGG and JSQ are employed by Steno Diabetes Center Copenhagen ( SDCC). SDCC is a hospital providing health services for the public health care system. SDCC is funded by the Novo Nordisk Foundation through unrestricted grants. The Novo Nordisk Foundation has no economic interests in the study. The Novo Nordisk Foundation will not have influence on (1) the study design; (2) the collection, analysis and interpretation of data; (3) the writing of the study report or any publication; and (4) the decision to submit the paper for publication. The investigators employed at SDCC will not benefit economically from conducting the study. Co-investigator MKG is employed at Novo Nordisk and will be responsible for exploratory investigations using the data collected in the TIMEX study. Due to the collaborative nature of the study, Novo Nordisk has been involved in designing the study and will be involved in analysing and interpreting data. Novo Nordisk will align with SDCC if and when data and/or biosamples from the study are used for publications. HEP and KF are now employed by Novo Nordisk. iMotions is a collaborator on the project and give advice for the use and analysis of biometric methods in the study design phase. iMotions A/S have no influence on (1) the study design; (2) the collection, analysis and interpretation of data; (3) the writing of the study report or any publication; and (4) the decision to submit the paper for publication. LGG and KF own shares in Novo Nordisk. The sponsor and principal investigator, JSQ, have no economic interest in the results of the study. All other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Loneliness is a public health concern associated with increased morbidity and mortality. Adverse health behaviours and a higher body mass index (BMI) have been proposed as key mechanisms influencing this association. The present study aims to examine the relationship between loneliness, adverse health behaviour and a higher BMI, including daily smoking, high alcohol consumption, physical inactivity, unhealthy dietary habits, and obesity in men and women and across different life stages., Methods: We conducted a cross-sectional study using data from the 2017 Danish National Health Survey (entitled "How are you?"). Loneliness was assessed using the Three-Item Loneliness Scale. Logistic regression models were employed to analyse the association between loneliness, health behaviour and obesity in a sample of 122,258 individuals (16 + years). The models were adjusted for sex, age, educational attainment, country of origin, and partnership status. Stratified analyses were conducted to investigate differences by sex and life stages., Results: Loneliness was associated with an increased risk of daily smoking (Adjusted odds ratio (AOR) = 1.30; 95% CI: 1.21-1.40), physical inactivity (AOR = 1.87; 95% CI: 1.75-1.99), unhealthy diet (AOR = 1.58; 95% CI: 1.47-1.70), and obesity (AOR = 1.60; 95% CI: 1.49-1.72). Conversely, loneliness was associated with a reduced risk of high alcohol consumption in men (AOR = 0.82; 95% CI: 0.74-0.0.91)., Conclusions: Our study provides evidence that loneliness is associated with adverse health behaviour and obesity in both men and women and across the lifespan. These findings suggest that health behaviours and obesity may influence the association between loneliness and poor health outcomes. Longitudinal studies are needed to clarify the causal relationships underlying these associations., Competing Interests: Declarations. Ethical approval: The present study is registered on the Central Denmark Regions’ internal judicial records of data processing activities (record number 1-16-02-334-19). According to Danish law, no further approval is required from an ethics committee or other research oversight when processing data from a survey (§ 14 Sect. 2) [48]. Individuals invited to participate received a letter of invitation which contained the necessary information about the purpose and content of the survey, emphasizing that participation was voluntary. The letter of invitation stated that by answering the survey, participants gave their full consent for their data to be used in accordance with the purpose of the study, ensuring informed consent from all participants. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Groundwater, essential for ecological stability and freshwater supply, faces escalating nitrate contamination. Traditional biological methods struggle with organic carbon scarcity and low temperatures, leading to an urgent need to explore efficient approaches for groundwater remediation. In this work, we proposed an inorganic bioelectric system designed to confront these challenges. At 10 and 4 °C, the system achieved total nitrogen (TN) removal efficiencies of 95.4 ± 2.7% and 90.9 ± 1.9% at 2 h hydraulic retention time (HRT), while maximum TN removal rates were recorded as 206.0 ± 6.3 and 178.3 ± 9.4 g N·m -3 ·d -1 at 1 h HRT. The microbial analysis uncovered shifts in dominant genera across temperatures, with Dechloromonas prevalent at 10 °C and Chryseobacterium at 4 °C, highlighting adaptability to cold-tolerant species. Gene analysis on narG, napA, nirS, nirK, norB, nosZI, nosZII, and nifA examined the nitrate reduction processes, and analysis on mtrC and omcA hinted at electrotrophic processes. Additionally, we demonstrated system resilience to disruptions of power outage and short periods without flow through. These findings establish a foundational understanding of electricity-driven nitrate bioreduction in cold environments, crucial in groundwater remediation strategies and paving the way for future optimization and upscaling efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hydroxylamine, nitrous acid, and nitric oxide are obligate intermediates or side metabolites in different nitrogen-converting microorganisms. These compounds are unstable and susceptible to the formation of highly reactive nitrogen species, including nitrogen dioxide, dinitrogen trioxide, nitroxyl, and peroxynitrite. Due to the high reactivity and cytotoxicity, the buildup of reactive nitrogen can affect the interplay of microorganisms/microbial processes, stimulate the reactions with organic compounds like organic micropollutants (OMP) and act as the precursors of nitrous oxide (N 2 O). However, there is little understanding of the occurrence and significance of reactive nitrogen during biological nitrogen conversions in engineered water systems. In this review, we evaluate the formation and fate of reactive nitrogen produced by microorganisms involved in biological nitrogen removal (BNR) processes, i.e., nitritation/nitrification, denitratation/denitrification, anammox, and the combined processes. While the formation of reactive nitrogen intermediates is entirely controlled by microbial activities, the consumption can be either biological or purely chemical. Changes in environmental conditions, such as redox transition, pH, and substrate availability, can imbalance the production and consumption of these reactive intermediates, thus leading to the transient accumulation of species. Based on previous experimental evidence, environmental relevance of reactive nitrogen in BNR systems, particularly related to abiotic N 2 O production and OMP transformation, is demonstrated.

Aims: Individuals with diminished social connections are at higher risk of mental disorders, dementia, circulatory conditions and musculoskeletal conditions. However, evidence is limited by a disease-specific focus and no systematic examination of sex differences or the role of pre-existing mental disorders., Methods: We conducted a cohort study using data on social disconnectedness (loneliness, social isolation, low social support and a composite measure) from the 2013 and 2017 Danish National Health Survey linked with register data on 11 broad categories of medical conditions through 2021. Poisson regression was applied to estimate incidence rate ratios (IRRs), incidence rate differences (IRDs), and explore sex differences and interaction with pre-existing mental disorders., Results: Among 162,497 survey participants, 7.6%, 3.5% and 14.8% were classified as lonely, socially isolated and with low social support, respectively. Individuals who were lonely and with low social support had a higher incidence rate in all 11 categories of medical conditions (interquartile range [IQR] of IRRs, respectively 1.26-1.49 and 1.10-1.14), whereas this was the case in nine categories among individuals who were socially isolated (IQR of IRRs, 1.01-1.31). Applying the composite measure, the highest IRR was 2.63 for a mental disorder (95% confidence interval [CI], 2.38-2.91), corresponding to an IRD of 54 (95% CI, 47-61) cases per 10,000 person-years. We found sex and age differences in some relative and absolute estimates, but no substantial deviations from additive interaction with pre-existing mental disorders., Conclusions: This study advances our knowledge of the risk of medical conditions faced by individuals who are socially disconnected. In addition to the existing evidence, we found higher incidence rates for a broad range of medical condition categories. Contrary to previous evidence, our findings suggest that loneliness is a stronger determinant for subsequent medical conditions than social isolation and low social support.A preregistered analysis plan and statistical code are available at Open Science Framework (https://osf.io/pycrq).

Candle burning is a considerable contributor to indoor pollutants, while secondary organic aerosols (SOA) from monoterpene ozonolysis represent another type. However, knowledge of the interactions of different indoor pollutants is limited. We investigated physicochemical properties of SOA generated from typical indoor chemistry of the O 3 /α-pinene reaction with and without the presence of particles and gases from a burning candle. Ozonolysis of α-pinene in the presence of candle gaseous emissions yielded a considerably lower particle number, larger particle sizes, and lower particle oxygen-to-carbon ratio compared with experiments without candle emissions. More nitrogen-containing organic compounds were observed in the aerosol phase with candle emissions. Furthermore, concentrations of some typical particle-phase products from the O 3 /α-pinene reaction (i.e., terebic acid, cis -pinic acid, and 3-methyl-1,2,3-butanetricarboxylic acid) were less abundant in the presence of candle emissions. The predicted volatility of particulate organic compounds was higher in experiments with candle emissions. The study demonstrates that candle burning can affect the chemical and physical properties of particles formed from other sources (e.g., α-pinene ozonolysis) by affecting gas-phase chemistry and gas-particle partitioning.

Gastrointestinal function plays a pivotal role in nutrient absorption and overall digestive health. Abnormal gastric emptying is closely linked to type 2 diabetes, impacting blood glucose regulation and causing gastrointestinal symptoms. This study aims to investigate and compare segmental transit times, motility indices, and micromilieu between Greenlandic Inuit and Danish individuals with and without type 2 diabetes. We included forty-four Greenlandic Inuit, twenty-three of whom had type 2 diabetes, and age and gender-matched Danish individuals. Segmental transit time, motility, and luminal environment were measured using the SmartPill®. Greenlandic controls displayed shorter gastric emptying time (GET) (163 min), higher gastric median pH (2.0 pH) and duodenal median contractions (18.2 mm Hg) compared to Greenlanders with type 2 diabetes (GET: 235 min, pH:1.9, median duodenal contraction 18.4 mm Hg) and Danish controls (GET: 190, pH:1.2 median duodenal contraction 17.5 mmHg). Despite similar anti-diabetic management efforts, variations in gastrointestinal physiology were evident, highlighting the complexity of diabetes and its interaction with ethnicity, suggesting potential dietary or even genetic influences, emphasising the necessity for personalised diabetes management approaches. Finally, the study opens possibilities for future research, encouraging investigations into the underlying mechanisms linking genetics, diet, and gastric physiology, as an understanding of factors can lead to more effective, tailored strategies for diabetes care and improved digestive health in diverse populations.

Aims: Sleep problems constitute a significant public health problem due to their high prevalence and impact on mental health and health behaviours, with major consequences for individuals and society. Therefore, the aim of this study was to investigate the association between sleep problems (duration and quality), mental health and health behaviours., Methods: Cross-sectional data was derived from the 2021 health survey 'How are you?' from the Central Denmark Region. The study population was a stratified random sample of 33,925 respondents aged 16 years or older. We used logistic regression models to analyse the associations between sleep problems and indicators of mental health and health behaviour. The models were adjusted for sex, age, educational attainment, labour market attachment, cohabitation, and indicators of mental health and health behaviour., Results: A prevalence of around 10% for both short- and long sleep duration and poor sleep quality was found. All were associated with poor mental health-related quality of life, depression, stress, perceived stressors and obesity. In addition, short sleep duration was associated with daily smoking, and long sleep duration was associated with physical inactivity and daily smoking., Conclusions: Our findings revealed a stronger association between sleep problems and mental health indicators in comparison to health behaviours. We found that sleep duration and sleep quality in broad terms were associated with similar variables within mental health and health behaviour. These findings underline the importance of adopting a comprehensive approach to addressing sleep problems in the context of health promotion, disease prevention, treatment and rehabilitation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Insulin resistance is a risk factor for type 2 diabetes, and exercise can improve insulin sensitivity. However, following exercise, high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a crossover design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemic-euglycemic clamp 5 h after one-legged exercise with 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC activator, dichloroacetate (DCA). Intralipid infusion reduced insulin-stimulated glucose uptake by 19% in the previously exercised leg, which was not observed in the contralateral rested leg. Interestingly, this effect of intralipid in the exercised leg was abolished by DCA, which increased muscle PDC activity (130%) and flux (acetylcarnitine 130%) and decreased inhibitory phosphorylation of PDC on Ser293 (∼40%) and Ser300 (∼80%). Novel insight is provided into the regulatory interaction between glucose and lipid metabolism during exercise recovery. Coupling exercise and PDC flux activation upregulated the capacity for both glucose transport (exercise) and oxidation (DCA), which seems necessary to fully stimulate insulin-stimulated glucose uptake during recovery., (© 2024 by the American Diabetes Association.)

Objective: This secondary analysis investigated the relationship of anxious arousal, as measured by the Tension Anxiety subscale of the Profile of Mood States (TA-POMS), to treatment outcome across diagnoses for each phase of the study. Sequential treatment phases of virtual reality (VR) mindfulness followed by left dorsolateral prefrontal cortex (dlPFC) accelerated transcranial magnetic stimulation (accel-TMS) and then dorsomedial prefrontal cortex (dmPFC) accel-TMS were used to treat dysphoria across diagnoses in an open trial from September 2021 to August 2023., Methods: The change in the TA-POMS subscale was compared to the percent change in primary clinician scale scores using a bivariate analysis. Baseline TA-POMS subscales were compared to treatment response using linear regression models to assess anxious arousal's impact on treatment outcome for the 3 phases. Significance was defined as P < .05, 2-tailed., Results: Twenty-three participants were enrolled in VR mindfulness, 19 in left dlPFC accel-TMS, and 12 in dmPFC accel TMS. Although the change in TA-POMS scores did not significantly correlate with the percent change in primary clinician scale ratings for the VR phase, they did for both the dlPFC ( P = .041) and the dmPFC ( P = .003) accel-TMS treatment phases. Importantly, baseline anxious arousal levels as measured by TA-POMS were not predictive of treatment outcome in any treatment phase., Conclusion: The outcome of accel-TMS treatment was not adversely affected by anxious arousal and similarly improved along with primary rating scales., Trial Registration: ClinicalTrials.gov identifier: NCT05061745., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Objectives: Disease progression, loss to follow-up, and mortality of HIV-2 compared with HIV-1 in children is not well understood. This is the first nationwide study reporting outcomes in children with the two HIV types in Guinea-Bissau., Study Design: Nationwide retrospective follow-up study., Methods: This is a retrospective follow-up study among HIV-infected children <15 years at nine ART centers from 2006 to 2021. Baseline parameters and disease outcomes for children with HIV-2 and HIV-1 were compared., Results: The annual number of children diagnosed with HIV peaked in 2017. HIV-2 (n = 64) and HIV-1 (n = 1945) infected children were different concerning baseline median age (6.5 vs 3.1 years, P < 0.01), but had similar levels of severe immunodeficiency (P = 0.58) and severe anemia (P = 0.26). Within the first year of follow-up, 36.3% were lost, 5.9% died, 2.7% had transferred clinic, and 55.2% remained for follow-up. Mortality (HR = 1.05 95% CI: 0.53-2.08 for HIV-2) and attrition (HR = 0.86 95% CI: 0.62-1.19 for HIV-2) rates were similar for HIV types., Conclusions: The decline in children diagnosed per year since 2017 is possibly due to lower HIV prevalence, lack of HIV tests, and the SARS-CoV-2 epidemic. Children with HIV-2 were twice as old as HIV-1 infected when diagnosed, which suggests a slower disease progression. However, once they develop immunosuppression mortality is similar., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes., Methods: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m 2 ) and concomitant prediabetes (ie, glycated haemoglobin [HbA 1c ] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m 2 ) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656)., Findings: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures., Interpretation: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes., Funding: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark., Competing Interests: Declaration of interests JSQ has received funding for this study from the Novo Nordisk Foundation, Innovation Foundation, and Aalborg University; for other studies from Novo Nordisk; and travel grants from American Diabetes Association, European Association for the Study of Obesity, and Trygfonden Center for Physical Activity Research. HEP is currently employed by Novo Nordisk and is co-investigator on a project partly funded by the Novo Nordisk Foundation and Innovation Fund Denmark. SP is the author of the books The Circadian Code and The Circadian Diabetes Code, which advocate for time-restricted eating. DV is currently employed by Novo Nordisk and has received research grants from Bayer, Sanofi Aventis, Novo Nordisk, and Boehringer Ingelheim and holds shares in Novo Nordisk. SST has received research grants for a study drug and lecture fees from Novo Nordisk. KKBC is currently employed by Novo Nordisk; holds shares in Novo Nordisk; and was co-investigator on this project, for which her salary was covered by a grant from the Novo Nordisk Foundation. MEN has received research grants from Bayer. NJWA has received research grants from Novo Nordisk and Mercodia and has received speaker fees and fees as a member of the advisory board from Merck, Guidepoint, and Boehringer Ingelheim. JJH has received research grants from Novo Nordisk Foundation, Arla Foods, and European Research Council; consulting fees from Alphasights, Arix Bioscience, Eli Lilly, Structure Therapeutics USA, Zealand Pharma, Alcimed, Google Ventures Management, MSD Danmark, and Novo Nordisk; and support for presentations from Eli Lilly, Zealand Pharma, Novo Nordisk, and the Mayo Clinic. MEJ holds shares in Novo Nordisk. JS holds shares in Novo Nordisk. KF is currently employed by Novo Nordisk and has received research grants from Novo Nordisk, Unilever, and AstraZeneca and holds shares in Novo Nordisk and ChemoMetec. MMJ received funding from the Danish Association for the Study of Obesity; is a co-investigator on a project funded by Novo Nordisk; and was co-investigator on this project, for which her salary was covered by grants from the Novo Nordisk Foundation and Aalborg University. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Atrial fibrillation (AF) increases the risk of conditions such as ischemic stroke, dementia, and heart failure, and early detection is crucial. In Greenland, ischemic strokes are common, and the prevalences of AF risk factors are increasing. Studies based on 30-second electrocardiograms (ECGs) and diagnosis codes so far have indicated either a low prevalence of AF or a prevalence comparable to that in other Western countries, such as Denmark. However, using short, single-point ECGs may underestimate the true prevalence, as especially paroxysmal AF can be missed. With this study, we aim to estimate the prevalence of AF using 3-5-day continuous Holter recordings among people in Nuuk, the capital of Greenland., Methods: In this cross-sectional study, we estimated the prevalence of AF among the population aged ≥ 50 years in Greenland's capital, Nuuk. We used an ePatch to record continuous ECGs for 3-5 days, and questionnaires to assess demographic data, comorbidities, medication, symptoms, and risk factors for AF., Results: Of 226 participants (62% women), 21 (33% women) had either self-reported AF, AF on the recording, or both, equivalent to a prevalence of 9.3% (confidence interval [CI] 5.8-13.9). The age-stratified prevalence was 7.2% (CI 2.7-15.1) among those aged 50-59 years; 8.8% (CI 4.1-16.1) among those aged 60-69 years; and 18.2% (CI 7.0-35.5) among those aged ≥ 70 years., Conclusions: This study provides a novel insight into AF prevalence in Nuuk, emphasizing the potential underestimation in previous studies. Continuous ECG monitoring revealed a higher prevalence, especially among the younger age groups, urging a reevaluation of diagnostic practices in this unique population., (© 2024 The Authors.)

Background: Rapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood., Objective: The objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity., Methods: 50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities-sedentary activity (0-100 counts/min), low light activity (101-759 counts/min), high light activity (760-1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times., Results: Median [Q1; Q3] age was 56.5 [46.6-65.5] y, and body mass index (BMI) was 32.1 [28.5-35.1] kg/m 2 . For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed., Conclusions: More time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated., Trial Registration: Clinicaltrials.gov IDs (NCT03894670, NCT03854656)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Aerosol particles with rare specific properties act as nuclei for ice formation. The presence of ice nucleating particles in the atmosphere leads to heterogeneous freezing at warm temperatures and thus these particles play an important role in modulating microphysical properties of clouds. This work presents an ice nucleation cold stage instrument for measuring the concentration of ice nucleating particles in liquids. The cost is ∼ $10 k including an external chiller. Using a lower cost heat sink reduces the cost to ∼ $6 k. The instrument is suitable for studying ambient ice nucleating particle concentrations and laboratory-based process-level studies of ice nucleation. The design plans allow individuals to self-manufacture the cold-stage using 3D printing, off-the-shelf parts, and a handful of standard tools. Software to operate the instrument and analyze the data is also provided. The design is intended to be simple enough that a graduate student can build it as part of a course or thesis project. Costs are kept to a minimum to facilitate use in classroom demonstrations and laboratory classes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Magnetotactic bacteria (MTB) are microorganisms widely inhabiting the oxic-anoxic interface of aquatic environments. Beside biomineralizing magnetic nanocrystals, MTBs are able to sequester various chemical elements (e.g., carbon and phosphorus) for the biogenesis of intracellular granules, like polyhydroxyalkanoate (PHA) and polyphosphate (polyP), making them potentially important in biogeochemical cycling. Yet, the environmental controls of intracellular storage of carbon and phosphorus in MTB remain poorly understood. Here, we investigated the influence of oxic, anoxic and transient oxic-anoxic conditions on intracellular storage of PHA and polyP in Magnetospirillum magneticum strain AMB-1. In the incubations with oxygen, transmission electron microscopy revealed intercellular granules highly rich in carbon and phosphorus, which were further interpreted as PHA and polyP based on chemical and Energy-Dispersive X-ray spectroscopy analysis. Oxygen had a strong effect on PHA and polyP storage in AMB-1 cells, as PHA and polyP granules accounted for up to 47 ± 23% and 5.1 ± 1.7% of the cytoplasmic space, respectively, during continuous oxic conditions, while granules disappeared in anoxic incubations. Poly 3-hydroxybutyrate (PHB) and poly 3-hydroxyvalerate (PHV) accounted for 0.59 ± 0.66% and 0.0033 ± 0.0088% of dry cell weight, respectively, in anoxic incubations, while the values increased by a factor of 7 and 37 after oxygen was introduced. The results highlight a tight link between oxygen, carbon and phosphorus metabolisms in MTB, where favorable oxic growth conditions can lead to metabolic induction of polyP and PHA granule biogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Su, Bazylinski and Jensen.)

Objective: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2., Design: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade., Method: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV., Result: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment., Conclusion: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Survivors of spontaneous (ie, nontraumatic and with no known structural cause) intracerebral hemorrhage (ICH) have an increased risk of major cardiovascular events (MACEs), including recurrent ICH, ischemic stroke (IS), and myocardial infarction (MI). Only limited data are available from large, unselected population studies assessing the risk of MACEs according to index hematoma location., Objective: To examine the risk of MACEs (ie, the composite of ICH, IS, spontaneous intracranial extra-axial hemorrhage, MI, systemic embolism, or vascular death) after ICH based on ICH location (lobar vs nonlobar)., Design, Setting, and Participants: This cohort study identified 2819 patients in southern Denmark (population of 1.2 million) 50 years or older hospitalized with first-ever spontaneous ICH from January 1, 2009, to December 31, 2018. Intracerebral hemorrhage was categorized as lobar or nonlobar, and the cohorts were linked to registry data until the end of 2018 to identify the occurrence of MACEs and separately recurrent ICH, IS, and MI. Outcome events were validated using medical records. Associations were adjusted for potential confounders using inverse probability weighting., Exposure: Location of ICH (lobar vs nonlobar)., Main Outcomes and Measures: The main outcomes were MACEs and separately recurrent ICH, IS, and MI. Crude absolute event rates per 100 person-years and adjusted hazard ratios (aHRs) with 95% CIs were calculated. Data were analyzed from February to September 2022., Results: Compared with patients with nonlobar ICH (n = 1255; 680 [54.2%] men and 575 [45.8%] women; mean [SD] age, 73.5 [11.4] years), those with lobar ICH (n = 1034; 495 [47.9%] men and 539 [52.1%] women, mean [SD] age, 75.2 [10.7] years) had higher rates of MACEs per 100 person-years (10.84 [95% CI, 9.51-12.37] vs 7.91 [95% CI, 6.93-9.03]; aHR, 1.26; 95% CI, 1.10-1.44) and recurrent ICH (3.74 [95% CI, 3.01-4.66] vs 1.24 [95% CI, 0.89-1.73]; aHR, 2.63; 95% CI, 1.97-3.49) but not IS (1.45 [95% CI, 1.02-2.06] vs 1.77 [95% CI, 1.34-2.34]; aHR, 0.81; 95% CI, 0.60-1.10) or MI (0.42 [95% CI, 0.22-0.81] vs 0.64 [95% CI, 0.40-1.01]; aHR, 0.64; 95% CI, 0.38-1.09)., Conclusions and Relevance: In this cohort study, spontaneous lobar ICH was associated with a higher rate of subsequent MACEs than nonlobar ICH, primarily due to a higher rate of recurrent ICH. This study highlights the importance of secondary ICH prevention strategies in patients with lobar ICH.

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production., Competing Interests: The authors have read the journal’s policy and have the following competing interests. The UFM technology described herein has been optioned to Katharos Labs, a company in which Jeffrey M. Karp, Anthony E. Samir, Steven J. Gordon, and Chulho Hyun hold equity and are co-inventors on a patent describing the UFM technology. C.H. performed experiments with masks supplied by Katharos Labs and Katharos Labs supported the cost of the testing instruments. J.M.K. has been a paid consultant and an equity holder for multiple companies including Katharos Labs (listed here https://www.karplab.net/team/jeff-karp). The interests of J.M.K. were reviewed and are subject to a management plan overseen by his institution in accordance with its conflict of interest policies. A.E.S. has served as a compensated consultant for Astra Zeneca, Bracco Diagnostics, Bristol Myers Squibb, General Electric, Gerson Lehman Group, Guidepoint Global Advisors, Supersonic Imagine, Novartis, Pfizer, Philips, Parexel Informatics, and WorldCare Clinical. He holds stock options in Rhino Healthtech Inc. and Ochre Bio Inc. He holds advisory board or committee memberships for General Electric, the Foundation for the National Institutes of Health, and the Sano Center for Computational Personalized Medicine, and is a member of the Board of Governors of the American Institute for Ultrasound in Medicine. His institution has received research grant support and/or equipment for projects that he has led from the Analogic Corporation, Canon, Echosens, General Electric, Hitachi, Philips, Siemens, Supersonic Imagine/Hologic, Toshiba Medical Systems, the US Department of Defense, Fujifilm Healthcare, the Foundation for the National Institutes of Health, Partners Healthcare, Toshiba Medical Systems, and Siemens Medical Systems. He holds equity in Avira Inc., Autonomus Medical Technologies, Inc., Evidence Based Psychology LLC, Klea LLC, Katharos Laboratories LLC, Quantix Bio LLC, and Sonoluminous LLC. A.E.S. receives royalties from Elsevier Inc. and Katharos Laboratories LLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors would like to declare the following patents/patent applications associated with this research: WO2022051476A1., (Copyright: © 2023 Hyun 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 and Objectives: A causal relationship between statin use and intracerebral hemorrhage (ICH) is uncertain. We hypothesized that an association between long-term statin exposure and ICH risk might vary for different ICH locations., Methods: We conducted this analysis using linked Danish nationwide registries. Within the Southern Denmark Region (population 1.2 million), we identified all first-ever cases of ICH between 2009 and 2018 in persons aged ≥55 years. Patients with medical record-verified diagnoses were classified as having a lobar or nonlobar ICH and matched for age, sex, and calendar year to general population controls. We used a nationwide prescription registry to ascertain prior statin and other medication use that we classified for recency, duration, and intensity. Using conditional logistic regression adjusted for potential confounders, we calculated adjusted ORs (aORs) and corresponding 95% CIs for the risk of lobar and nonlobar ICH., Results: We identified 989 patients with lobar ICH (52.2% women, mean age 76.3 years) who we matched to 39,500 controls and 1,175 patients with nonlobar ICH (46.5% women, mean age 75.1 years) who we matched to 46,755 controls. Current statin use was associated with a lower risk of lobar (aOR 0.83; 95% CI, 0.70-0.98) and nonlobar ICH (aOR 0.84; 95% CI, 0.72-0.98). Longer duration of statin use was also associated with a lower risk of lobar (<1 year: aOR 0.89; 95% CI, 0.69-1.14; ≥1 year to <5 years aOR 0.89; 95% CI 0.73-1.09; ≥5 years aOR 0.67; 95% CI, 0.51-0.87; p for trend 0.040) and nonlobar ICH (<1 year: aOR 1.00; 95% CI, 0.80-1.25; ≥1 year to <5 years aOR 0.88; 95% CI 0.73-1.06; ≥5 years aOR 0.62; 95% CI, 0.48-0.80; p for trend <0.001). Estimates stratified by statin intensity were similar to the main estimates for low-medium intensity therapy (lobar aOR 0.82; nonlobar aOR 0.84); the association with high-intensity therapy was neutral., Discussion: We found that statin use was associated with a lower risk of ICH, particularly with longer treatment duration. This association did not vary by hematoma location., (© 2022 American Academy of Neurology.)

Current in the milliampere range can be used for electrochemical inactivation of bacteria. Yet, bacteria-including antibiotic resistant bacteria (ARB) may be subjected to sublethal conditions due to imperfect mixing or energy savings measures during electrochemical disinfection. It is not known whether such sublethal current intensities have the potential to stimulate plasmid transfer from ARB. In this study, conjugal transfer of plasmid pKJK5 was investigated between Pseudomonas putida strains under conditions reflecting electrochemical disinfection. Although the abundance of culturable and membrane-intact donor and recipient cells decreased with applied current (0-60 mA), both transconjugant density and transconjugant frequency increased. Both active chlorine and superoxide radicals were generated electrolytically, and ROS generation was induced. In addition, we detected significant over expression of a core oxidative stress defense gene (ahpCF) with current. Expression of selected conjugation related genes (traE, traI, trbJ, and trbL) also significantly correlated with current intensity. ROS accumulation, SOS response and subsequent derepression of conjugation are therefore the plausible consequence of sublethal current exposure. These findings suggest that sublethal intensities of current can enhance conjugal plasmid transfer, and that it is essential that conditions of electrochemical disinfection (applied voltage, current density, time and mixing) are carefully controlled to avoid conjugal ARG transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Nasopharyngeal swabs (NPS) are considered the gold standard for SARS-CoV-2 testing but are technically challenging to perform and associated with discomfort. Alternative specimens for viral testing, such as oropharyngeal swabs (OPS) and nasal swabs, may be preferable, but strong evidence regarding their diagnostic sensitivity for SARS-CoV-2 testing is still missing. We conducted a head-to-head prospective study to compare the sensitivity of NPS, OPS and nasal swabs specimens for SARS-CoV-2 molecular testing. Adults with an initial positive SARS-CoV-2 test were invited to participate. All participants had OPS, NPS and nasal swab performed by an otorhinolaryngologist. We included 51 confirmed SARS-CoV-2-positive participants in the study. The sensitivity was highest for OPS at 94.1% (95% CI, 87 to 100%) compared to NPS at 92.5% (95% CI, 85 to 99%) ( p = 1.00) and lowest for nasal swabs at 82.4% (95% CI, 72 to 93%) ( p = 0.07). Combined OPS/NPS was detected in 100% of cases, while the combined OPS/nasal swab increased the sensitivity significantly to 96.1% (95% CI, 90 to 100%) compared to that of the nasal swab alone ( p = 0.03). The mean Ct value for NPS was 24.98 compared to 26.63 for OPS ( p = 0.084) and 30.60 for nasal swab ( p = 0.002). OPS achieved a sensitivity comparable to NPS and should be considered an equivalent alternative for SARS-CoV-2 testing.

Background: Olfactory and gustatory dysfunctions are early symptoms of SARS-CoV-2 infection. Between 20-80% of infected individuals report subjective altered sense of smell and/or taste during infection. Up to 2/3 of previously infected experience persistent olfactory and/or gustatory dysfunction after 6 months. The aim of this study was to examine subjective and psychophysical olfactory and gustatory function in non-hospitalized individuals with acute COVID-19 up to 6 months after infection., Methods: Individuals aged 18-80-years with a positive SARS-CoV-2 PCR test no older than 10 days, were eligible. Only individuals able to visit the outpatient examination facilities were included. Gustatory function was tested with the Burgharts Taste Strips and olfactory function was examined with the Brief Smell Identifications test (Danish version). Subjective symptoms were examined through an online questionnaire at inclusion, day 30, 90 and 180 after inclusion., Results: Fifty-eight SARS-CoV-2 positive and 56 negative controls were included. 58.6% (34/58) of SARS-CoV-2 positive individuals vs. 8.9% (5/56) of negative controls reported subjective olfactory dysfunction at inclusion. For gustatory dysfunction, 46.5% (27/58) of positive individuals reported impairment compared to 8.9% (5/56) of negative controls. In psychophysical tests, 75.9% (46/58) had olfactory dysfunction and 43.1% (25/58) had gustatory dysfunction among the SARS-CoV-2 positive individuals at inclusion. Compared to negative controls, SARS-CoV-2 infected had significantly reduced olfaction and gustation. Previously infected individuals continued to report lower subjective sense of smell 30 days after inclusion, whereafter the difference between the groups diminished. However, after 180 days, 20.7% (12/58) positive individuals still reported reduced sense of smell and taste., Conclusion: Olfactory and gustatory dysfunctions are prevalent symptoms of SARS-CoV-2 infection, but there is inconsistency between subjective reporting and psychophysical test assessment of especially olfaction. Most individuals regain normal function after 30 days, but approximately 20% report persistent olfactory and gustatory dysfunction 6 months after infection., Competing Interests: The authors have declared that no competing interests exist.

Cerebral aneurysms (CA), an abnormal bulge in the arteries that supply blood to the brain, are prone to rupture and can cause hemorrhagic stroke. Physicians can treat CA by blocking blood flow to the aneurysmal sac via clipping of the aneurysm neck via open procedure, or endovascular occlusion of the aneurysm with embolic materials to promote thrombus formation to prevent further inflow of blood into the aneurysm. Endovascular treatment options for CA still have significant limitations in terms of safety, usability in coagulopathic patients, and risks of device migration. Bioactive embolic therapies, consisting of non-toxic bioresorbable materials that encourage the growth of neointima across the aneurysm neck, are needed to improve the healing of CA. In this work, the bioinspired silk-elastinlike protein-based polymer (SELP 815K), was used to embolize aneurysms in a rabbit elastase model. SELP 815K effectively embolized the model aneurysms in vivo, achieving &gt;90% occlusion, using commercial microcatheters. No device-associated adverse effects were observed in any of the animals, and SELP 815K showed no cytotoxicity. SELP embolization did not show any deleterious effects to local tissues, and features consistent with reendothelialization of the aneurysm neck were noted in histological examination one-month post-embolization. SELP 815K shows promise as an embolic treatment for unruptured CA. STATEMENT OF SIGNIFICANCE: Unruptured cerebral aneurysms are present in approximately 3% of the population, with a fatality rate of up to 65% upon rupture. In this work a silk-elastinlike protein polymer (SELP) is explored as a liquid embolic for occlusion of cerebral aneurysms. This embolic exists as a liquid at room temperature before rapidly forming a gel at physiological temperature. This shape filling property was used to successfully occlude cerebral aneurysms in rabbits, with stable occlusion persisting for over thirty days. SELP occlusions show evidence for reendothelialization of the aneurysm sac and provide an opportunity for delivery of bioactive agents to further improve treatments., Competing Interests: Declaration of Competing Interest DC, XW and OH were employed by TheraTarget, Inc. DC and HG are founders and hold equity in TheraTarget, Inc. HG serves on the board of TheraTarget, Inc., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Study Design: Systematic Review., Objective: To evaluate the efficacy of available treatment options for patients with persistent coccydynia through a systematic review., Methods: Original peer-reviewed publications on treatment for coccydynia were identified using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines by performing a literature search of relevant databases, from their inception to January 17, 2020, combined with other sources. Data on extracted treatment outcome was pooled based on treatment categories to allow for meta-analysis. All outcomes relevant to the treatment efficacy of coccydynia were extracted. No single measure of outcome was consistently present among the included studies. Numeric Rating Scale, (NRS, 0-10) for pain was used as the primary outcome measure. Studies with treatment outcome on adult patients with chronic primary coccydynia were considered eligible., Results: A total of 1980 patients across 64 studies were identified: five randomized controlled trials, one experimental study, one quasi-experimental study, 11 prospective observational studies, 45 retrospective studies and unpublished data from the DaneSpine registry. The greatest improvement in pain was achieved by patients who underwent radiofrequency therapy (RFT, mean Visual Analog Scale (VAS) decreased by 5.11 cm). A similar mean improvement was achieved from Extracorporeal Shockwave Therapy (ESWT, 5.06), Coccygectomy (4.86) and Injection (4.22). Although improved, the mean change was less for those who received Ganglion block (2.98), Stretching/Manipulation (2.19) and Conservative/Usual Care (1.69)., Conclusion: This study highlights the progressive nature of treatment for coccydynia, starting with noninvasive methods before considering coccygectomy. Non-surgical management provides pain relief for many patients. Coccygectomy is by far the most thoroughly investigated treatment option and may be beneficial for refractory cases. Future randomized controlled trials should be conducted with an aim to compare the efficacy of interventional therapies amongst each other and to coccygectomy.

Background: Arthroscopic distal clavicle resection (DCR) can be offered to patients with persistent acromioclavicular (AC) joint pain who do not benefit from conservative treatment. The aim of this study was to evaluate the outcome of combined arthroscopic DCR and concomitant arthroscopic subacromial decompression in a large consecutive and prospective cohort using patient-reported outcomes., Methods: Consecutive patients were identified from our online database and included based on their primary treatment code. All patients had a diagnosis of shoulder impingement syndrome and persistent AC joint pain resistant to at least six months of conservative treatment. The outcomes from the combined intervention were evaluated by patients through the Oxford Shoulder Score (OSS) questionnaire and EuroQol 5-Dimension 3-Level questionnaire, including a EuroQol visual analog scale score collected preoperatively and at a 2-year follow-up. Patient-reported satisfaction with the procedure was reported at the follow-up. Subgroups were formed to further evaluate outcome based on preoperative OSS (low, moderate, high) and age., Results: 131 patients (75%) were available for analysis at the 2-year follow-up. Sixty seven patients (51%) were female and the mean age was 51 years (range 19-82). A mean OSS change of 12.1 (95% confidence interval, 10.3-14.0; P  < .001) was observed within the entire study group. In both the low and moderate preoperative-OSS (pre-OSS) groups, a mean change of 14 was found with no difference between groups ( P  = .971). A mean change of 7 was found in the high pre-OSS group, which differed from both the moderate ( P  < .001) and low ( P  = .036) pre-OSS groups. A significant change in EuroQol 5-Dimension and EuroQol visual analog scale was observed within all the pre-OSS groups, and 107 patients (82%) replied that they were satisfied or very satisfied with their outcome of surgery at the follow-up., Conclusions: Patients who suffer from persistent AC joint pain largely benefit from arthroscopic DCR with arthroscopic subacromial decompression through relief of symptoms and improved quality of life, including those with a high self-reported and preoperative level of shoulder function., (© 2022 The Authors.)

Therapeutics targeting cell receptors can elicit biological responses in situ. However, the ability to dictate when and where these responses occur is a current challenge. Therapeutic proteins can be combined with stimuli-responsive peptides to increase targeting and stimuli responsive behavior. To this end the authors genetically engineered an elastinlike polypeptide (ELP) fusion protein for selective ELPylation. The addition of a charged, foldable region provides these protein subunits with varied thermoresponsive properties from their parent ELPs. These subunits have responsive secondary structures, dependent on pH, indicating the capability to form coiled-coils with a complementary peptide tag. A Rituximab conjugate is generated herein, containing the complementary peptide. Upon mixing of the ELP and Rituximab subunits, the resulting protein complexes can target CD20 receptors on Raji B cells, resulting in at least twofold increase in mean fluorescent intensities. These ELP subunits fold in vitro with the complimentary generated Rituximab conjugate. This work provides the basis for the design of a therapeutic stimuli-responsive biomacromolecule for targeting receptors., (© 2022 Wiley-VCH GmbH.)

Background: The study aims to investigate the effect of stapedotomy on audiology measurements and the disease-specific health-related quality of life for patients with otosclerosis using the Danish Stapesplasty Outcome Test-25 as a quality of life measuring tool., Methods: In this study, 50 patients who had undergone stapedotomy at our department between September 2017 and December 2020 were included. Data collection was performed by audiometric testing (pure tone and speech audiometry) in the pre- and postoperative settings. Health-related quality of life was assessed pre- and postoperatively in 30 patients using the validated Danish Stapesplasty Outcome Test-25., Results: The mean improvement in air conduction thresholds was 27.7 dB and the mean improvement in air-bone gap was 21.8 dB. Health- related quality of life improved significantly after stapes surgery in all subscores of the Stapesplasty Outcome Test-25 (hearing, mental condition, social restriction, and general), except for "tinnitus." The improvement in the audiometric data correlated significantly with the improvement in "total score" and "hearing function" but not with "tinnitus," "social restrictions," and "mental condition.", Conclusion: Stapedotomy leads to significant improvement in hearing and health-related quality of life. The Stapesplasty Outcome Test-25 can be used as a valuable supplement to the hearing test by assessing health-related quality of life.