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The relationship between social participation and cognitive function early after surgery of glioma patients

Objective Social Participation (SP) is known to benefit cognitive function. However, whether this positive relationship holds across the people with glioma has not been studied. The present study aimed to investigate the current status of SP and cognitive function of patients early after surgery with glioma, and therefore, explore the associations between cognitive function and SP. Methods This study included 179 postoperative patients with gliomas within 6 months of surgery. Cognitive functioning was measured by the Montreal Cognitive Assessment (MoCA) including orientation, attention, learning and memory, executive functioning and verbal fluency. Social participation was obtained also by questionnaire survey with the Impact on Participation and Autonomy Questionnaire (IPA). The Pearson correlation analysis was used to explore the relation between cognitive functioning and social participation, and the efficacy of social participation in predicting cognitive functioning was evaluated using the receiver operating characteristic (ROC). Results The prevalence of cognitive impairment in early postoperative glioma patients was 77.65%. The mean level of social participation was 37.96 ± 26.85 points, with poorer scores in the autonomy participation of family role and outdoor engagement dimensions. Patients’ cognitive functioning was positively correlated with social participation (r = −0.64, P < 0.001). And The areas under the ROC curve for social participation predicting cognitive function were 0.884. Conclusion Early post-operative cognitive impairment was more common in glioma patients, which was positively correlated with social participation. Social rehabilitation programs for glioma patients should be actively constructed to promote the social participation of patients early after surgery in order to protect their cognitive function.

Coronary CT Anatomy-Based Prediction of Invasively Assessed Hemodynamic Significance in Middle-Aged Patients With Right Coronary Artery Anomaly: The NARCO Study

A life course study of genetic and environmental influences on sustainable working life

Genetics plays a role in short- and long-term sustainable working life (i.e., not having interruptions due to sickness absences (SA), disability pensions (DP), or unemployment), but the life course effects are not known. Thus, we aimed to investigate the age-specific genetic and environmental influences on sustainable working life from young adulthood until old-age pension. We used classical twin modeling based on the genetic relatedness of mono- and dizygotic twins in a longitudinal design. The final sample (n =  49 372) of Swedish same-sex twins with known zygosity born between 1929 and 1990 (52.8% women) with detailed national register data of employment, SA, DP, unemployment, old-age pension, emigration, and death. Genetic influences for sustainable working life were 54% at ages 18–27 years, 59% at 28–37 years, 37% at 38–47 years, 69% at 48–57 years, and 34% at 58–65 years. We observed genetic influences transferred from 18–27 years to 28–37 years and to 38–47 years explaining 28% and 17% of the variance, respectively, from 28–37 years to 38–47 years 60%, and from 48–57 years to 58–65 years 47%. Unique environmental influences were 57–72% in five age groups. Age group-specific common environment explained 63% of the variance for 18–27 years, 27% for 28–37 years, 12% for 48–57 years, and 25% for 58–65 years (none for 38–47 years). From age 48–57 years, the common environment explained 24% of the variance among those aged 58–67. To conclude, stability and change in genetic effects are important for a sustainable working life across the life course. The unique environmental effects were important for the middle age groups between 28 and 57 years. Thus, society and workplaces should support health and well-being to promote a sustainable working life.

Declining Trend of Sudden Cardiac Death in Younger Individuals: A 20-Year Nationwide Study

BACKGROUND: Declining cardiovascular mortality rates have been well-documented, yet temporal trends of sudden cardiac death (SCD) in young individuals remain unclear. We provide contemporary nationwide estimates of the temporal trends of SCD in young individuals (1–35 years of age) from 2000 through 2019 and correlate these trends to changes in out-of-hospital cardiac arrest (OHCA) patterns, rates of inherited cardiac diseases, and implantations of implantable cardioverter defibrillators (ICD). METHODS: All individuals between 1 and 35 years of age living in Denmark from 2000 through 2019 were included, with annual re-evaluation of the at-risk population in regard to age. Adjudication of SCD cases relied on multiple sources, including death certificates, medical files, and autopsy reports. Information on OHCA, diagnostic rates, and ICD implantations were captured from nationwide administrative registries. Annual incidence rates of SCD were calculated, and temporal trends in SCD incidence were computed as percentage change annualized. Trends in OHCA survival and characteristics, diagnostic rates of inherited cardiac diseases, and ICD implantations were assessed. RESULTS: During the 20-year study period (47.5 million person-years), 1057 SCDs were identified (median age, 29 years; 69% male). The overall incidence of SCD was 2.2 per 100 000 person-years and declined by 3.31% (95% CI, 2.42–4.20) annually, corresponding to a 49% (95% CI, 38.7–57.6) reduction during the study. Rates of witnessed SCD declined markedly (percentage change annualized −7.03% [95% CI, −8.57 to −5.48]), but we observed no changes in the rate of unwitnessed SCD (percentage change annualized −0.09% [95% CI, −1.48 to 1.31]). Therefore, the proportion of unwitnessed SCD increased by 79% ( P <0.001). Survival after OHCA in young individuals (1 to 35 years of age) increased from 3.9% to 28%, mainly because of increased bystander cardiopulmonary resuscitation and defibrillation rates. Diagnostic rates of inherited cardiac diseases increased 10-fold (incidence rate ratio, 10.4 [95% CI, 8.46–12.90]) and the ICD implantation rate increased 2-fold (incidence rate ratio, 1.97 [95% CI, 1.51–2.60]). CONCLUSIONS: SCD incidence rates in young individuals declined by 49% over the past 2 decades. The decline was paralleled by improved survival of OHCA, higher diagnostic rates of inherited cardiac diseases, and higher ICD implantation rates. However, rates of unwitnessed SCD were unchanged, which calls for new perspectives in preventive strategies.

Vocational rehabilitation for people with multiple sclerosis in the national health service of the United Kingdom: A realist evaluation

Background There is limited evidence about how vocational rehabilitation (VR) for people with multiple sclerosis (MS) can be delivered through the United Kingdom’s (UK) National Health Service (NHS) and how it works. Aim To understand the mechanisms and context for implementing a VR intervention for people with MS in the NHS and develop an explanatory programme theory. Methods A realist evaluation, including a review of evidence followed by semi-structured interviews. A realist review about VR for people with MS in the NHS was conducted on six electronic databases (PubMed, MEDLINE, PsychINFO, Web of Science, CINAHL, and EMBASE) with secondary purposive searches. Included studies were assessed for relevance and rigour. Semi-structured interviews with people with MS, employers, and healthcare professionals, were conducted remotely. Data were extracted, analysed, and synthesised to refine the programme theory and produce a logic model. Results Data from 13 studies, and 19 interviews (10 people with MS, five employers, and four healthcare professionals) contributed to producing the programme theory. The resulting programme theory explains the implementation of VR in the NHS for MS populations, uncovering the complex interplay between the healthcare and employment sectors to influence health and employment outcomes. VR programmes that offer timely support, tailored to the needs of the person with MS, and that support and empower the employee beyond the healthcare context are most likely associated with improved employment outcomes, for example, job retention. Conclusion Embedding VR support within the NHS requires substantial cultural and organisational change (e.g., increased staff numbers, training, and awareness about the benefits of work). This study emphasises the need to routinely identify people with MS at risk of job loss and follow a collaborative approach to address employment issues. This realist evaluation provides insight on how to improve the quality of care available to people with MS.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models

BACKGROUND: The EF-hand Ca 2+ sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca 2+ ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75–94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts. METHODS: We applied an integrative translational research pipeline ranging from in silico computational molecular modeling and in vitro biochemical molecular assays as well as isolated rodent and human cardiomyocyte performance assessments to in vivo safety and efficacy studies in small and large animal cardiac disease models. RESULTS: We characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardium in vitro and in vivo. This activity translates into improved contractile performance and survival in preclinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca 2+ cycling and prevents β-adrenergic receptor–triggered Ca 2+ imbalances by targeting SERCA2a and RyR2 activity. In line with the S100A1ct-mediated enhancement of SERCA2a activity, modeling suggests an interaction of the peptide with the transmembrane segments of the sarcoplasmic Ca 2+ pump. Incorporation of a cardiomyocyte-targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potency in vitro and in vivo. CONCLUSIONS: S100A1ct is a promising lead for the development of novel peptide-based therapeutics against heart failure with reduced ejection fraction.

Self-rehabilitation strategy for rural community-dwelling stroke survivors in a lower-middle income country: a modified Delphi study

Background More than half of stroke survivors in lower-middle income countries lack access to stroke rehabilitation services. The promotion of self-rehabilitation could be promising for addressing stroke rehabilitation inadequacies in lower-middle income countries. Self-rehabilitation interventions are more readily acceptable to community-dwelling stroke survivors, and therefore, have the potential to boost the successful realization of the Sustainable Development Goals and other WHO rehabilitation goals. We report a consensus-building process that sought to identify which task trainings are relevant to include in a task-specific self-rehabilitation strategy for rural community-dwelling stroke survivors. Methods An iterative two-stage mixed-method consensus-building approach was used: (1) focus group discussions (n =  5) with rural community-dwelling chronic stroke survivors were conducted to explore personal life experiences in performing daily activities, and the results were used to develop a list of candidate task trainings that could be included in a task-specific self-rehabilitation intervention model for improving functional ability of survivors; (2) a three-round Delphi exercise with a panel of stroke rehabilitation experts to establish consensus on the importance/relevance of the developed task trainings. Consensus was pre-defined to be the point where the proportion of items given a rating of 3 (quite relevant) or 4 (highly relevant) by expert panellists is ≥  0.8. Kendall’s coefficient of concordance (W) was used to assess the level of agreement among the expert panellists. Results A list of 74 task trainings was generated from the results of the focus group discussions involving 29 chronic stroke survivors. The tasks were classified as follows: training for the upper extremity (37); lower extremity training (21); trunk training (7); and balance training (9). A panel of 13 stroke rehabilitation experts reviewed these task trainings using the Delphi method and consensus was reached on keeping 28 task trainings in the first round (Kendall’s W =  0.252, p <  0.001) and an additional 7 in the second round (Kendall’s W =  0.409, p <  0.001). In the study team’s analysis of open text responses, several areas of debate were identified and some task trainings were modified. The exercise yielded 49 task trainings (66% of 74) on which there was consensus (the mean proportion of items given a rating of 3 or 4 by panellists was 0.93; Kendall’s W =  0.291, p <  0.001) to keep 3 task training groups relating to: upper extremity (27), lower extremity/balance (8), trunk strength (4) as well as warm up exercises (10). Conclusion The study provides a consensus-based view of the features of a task-specific self-rehabilitation training strategy to improve outcomes following a stroke. This self-rehabilitation training strategy can be used as an intervention approach to augment and promote stroke rehabilitation among rural community-dwelling stroke survivors, especially in sub-Saharan Africa.

Digital Twins: The Future for Ventricular Tachycardia Ablation?

Quantifying variation of non-point source pollution and its impact factors: A study of Nansi Lake Basin

Agricultural non-point source (NPS) pollution directly affects the quality of soil and water, ecological balance and human health, and is a key challenge to achieve sustainable environmental development and efficient resource management. Taking the Nansi Lake Basin (NLB) as the study area, this study explores the main sources of agricultural NPS pollution and its influencing factors, aiming to provide scientific basis for the management of water resources in the basin. Current studies usually use the runoff pollution partitioning method to estimate agricultural NPS pollution loads in runoff, but the accuracy of the analyses is limited by the incompleteness of water quality monitoring data, especially the lack of complete runoff records in some years. To compensate for this deficiency, this study simulated the river runoff based on the Long-Term Hydrological Impact Assessment (L-THIA) model, and applied the simulation results to the quantitative calculation of agricultural NPS pollution loads after verifying the model reliability through accuracy calibration. Based on L-THIA model, the spatial and temporal distribution data of agricultural NPS pollution in the basin from 2010 to 2020 were obtained, the distribution characteristics of chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) were quantitatively assessed, and the impacts of natural and socio-economic factors on them were analyzed. A regression model was developed to simulate future agricultural NPS pollution through multiple regression analysis. The results showed that the total agricultural NPS pollution in the NLB showed an increasing trend during the study period. In particular, among the socio-economic factors, COD and NH3-N were significantly correlated with fertilizer application, pesticide use, rural employment and total population. Among the natural factors, topographic index, watershed area and gully density were positively correlated with pollutants, while slope and soil organic matter were negatively correlated. The results of this study raise awareness of the contribution of influencing factors and allow researchers and planners to focus on the most important NPS pollution sources and influencing factors. The study provides an important reference for the prevention and control of agricultural NPS pollution in the NLB, which is of great practical importance.

How to develop a good writing style

New Definition of Elevated Blood Pressure in the 2024 ESC Guidelines: Increased Prevalence, Uncertain Evidence

FAM50A as a novel prognostic marker modulates the proliferation of colorectal cancer cells via CylinA2/CDK2 pathway

Objective Colorectal cancer (CRC) is the third most prevalent malignant tumor type and the second leading cause of cancer-related death. Sequence similarity family 50 member A (FAM50A) plays a vital role in numerous disease processes, including tumor progression. This study aimed to evaluate the prognostic significance of FAM50A in CRC and to explore its role in CRC cell proliferation. Methods TCGA and GTEX databases and immunohistochemical staining (IHC) was used to study the expression of FAM50A in CRC tissues. Patient survival data were used to assess the prognostic significance of FAM50A in CRC using Kaplan–Meier analysis and Cox regression analysis. The Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and colony-formation assays were employed to assess the impact of FAM50A on tumor cell proliferation. Flow cytometry was used to detect the changes of cell cycle. The cell cycle and cycle-related proteins were measured via western blotting (WB) to explore the potential mechanisms involving in cancer progresses. Results The results of IHC revealed a notable upregulation of FAM50A expression levels in CRC tissue compared with adjacent normal tissue. Moreover, FAM50A expression was positively correlated with N and TNM stages in 145 patients with CRC. Cox regression analysis and construction of a nomogram revealed that high FAM50A expression was a prognostic indicator for poor overall survival in patients with CRC. Knockdown of FAM50A decreased cell proliferation ability, the proportion of EdU positive cells, and the number of CRC cell colonies, whereas overexpressing FAM50A promoted proliferative phenotypes. Knocking down FAM50A induced a significant increase in the number of cells in the S phase. Meanwhile, CyclinA2 and CDK2 were significantly reduced after FAM50A knocking down. Conclusion FAM50A may be a novel prognostic marker for CRC, and may participate in regulating tumor progression by targeting the CyclinA2/CDK2 signal pathway.

Sudden cardiac death after coronary artery bypass graft surgery and role of antiplatelet therapy

Background While coronary artery bypass grafting (CABG) surgery is effective in reducing the risk of myocardial infarction and subsequent cardiac events by improving myocardial perfusion, the risk of sudden cardiac death (SCD) remains notable. Methods This retrospective observational study evaluated the efficacy of dual antiplatelet therapy (DAPT) in preventing sudden cardiac death (SCD) among patients undergoing CABG surgery at a major U.S. cardiac center (2012–2015). Data was manually extracted from electronic medical records between 23/04/2017 to 30/03/ 2018 and verified for accuracy, with patients categorized into DAPT or aspirin monotherapy groups based on discharge prescriptions. Results Of 2,476 patients followed in this post-CABG study, the analysis included 1,005 patients who received aspirin monotherapy (AMT) and 1,458 patients who received dual antiplatelet therapy (DAPT). AMT group had a significantly higher incidence of SCD compared to those on DAPT (3.1% vs 0.8%; OR = 3.831, 95% CI: 1.961–7.519; p < 0.001). The binary regression model indicated that a higher BMI was associated with an increased risk of SCD (HR = 1.064, 95% CI: 1.012–1.118, p = 0.014). However, patients prescribed P2Y12 antagonists (HR = 0.285, 95% CI: 0.135–0.603, p < 0.001), those with a GFR >  60 ml/min (HR = 0.314, 95% CI: 0.158–0.624, p < 0.001), and those with a higher ejection fraction (HR = 0.962, 95% CI: 0.939–0.986, p = 0.002) were less likely to experience SCD following CABG. A 1 kg/m2 increase in BMI is associated with a 6.4% increase in the risk of SCD. Morbidly obese patients with BMI >  35 were more likely to have experienced SCD than those with BMI < 35 (HR = 2.400, 95% CI: 1.204–4,787; p =  0.013). Similarly, patients with EF > 40% had decreased incidence of SCD compared to those with EF < 40% (HR 0.347, 95% CI:0.158–0.763; p = 0.008). Patients on AMT had higher all-cause (OR = 2.136, 95% CI 1.502–3.038; p < 0.001) and CV mortality (OR = 3.731, 95% CI 2.233–6.235; p < 0.001) but had lower incidence of major bleeding (by drop in hemoglobin criteria) (OR = 0.704, 95% CI: 0.595–0.833; p < 0.001) compared to the DAPT group. Conclusion DAPT prescription after CABG improves survival and lowers risk of sudden cardiac death.

Daily briefing: Postdocs and PhD students hit hard by Trump’s crackdown on science

L-shaped relationship between dietary niacin intake and hearing loss in United States adults: National health and nutrition examination survey

Hearing loss poses a significant threat to human health, with its prevalence increasing annually. Niacin (vitamin B3) is an essential B vitamin that plays a crucial role in energy metabolism and cellular repair in the body. Additionally, it exerts a protective influence on the cells of the inner ear. A correlation between dietary niacin and hearing loss has been reported; however, the results remain controversial, requiring further investigation. This study aimed to examine the potential association between dietary niacin intake and hearing loss in United States (U.S.) adults, providing a reference for dietary preventive management of hearing loss. In this cross-sectional study, data derived from the National Health and Nutrition Survey for U.S. adults aged 20 to 69 years, spanning the 2011–2012 and 2015–2016 cycles, were used. Logistic regression, restricted cubic spline models, subgroup analyses, and sensitivity analyses were used to assess the stability of the results. A total of 7675 participants were included, of whom 772 (10.1%) exhibited low-frequency hearing loss (LFHL), 1165 (15.2%) had speech-frequency hearing loss (SFHL), and 2816 (36.7%) had high-frequency hearing loss (HFHL). In the final model, the adjusted odds ratios of dietary niacin intake and LFHL, SFHL, and HFHL in Q2 (16.97–23.40 mg/day) were compared with those in Q1 (≤16.96 mg/day) and were 0.73 (0.57–0.92), 0.76 (0.61–0.94), and 0.80 (0.67–0.96), respectively. The relationship between dietary niacin intake and hearing loss (HL) was illustrated via an L-shaped curve in the restricted cubic spline with an inflection point of approximately 23.26 mg/day. The odds ratios for HL in individuals with niacin intake less than 23.26 mg/day were as follows: 0.950 (0.917–0.984) for LFHL, 0.951 (0.921–0.982) for SFHL, and 0.965 (0.939–0.992) for HFHL. To summarize, an “L”-shaped correlation between dietary niacin intake and the occurrence of HL in U.S. adults with an inflection point estimated at approximately 23.26 mg/day was revealed in the present study.

Key factors in supporting adolescents to achieve high self-esteem and a positive body image: A qualitative community-based study

Introduction Body dissatisfaction can be affect adolescents’ mental health, leading to issues with body weight control, low self-esteem, and poor school performance. Methods A total of 24 interviews with adolescents, parents, and teachers in Spain were conducted for this study. The study aimed to explore and compare the views of adolescents, parents, and teachers regarding interventions to improve self-esteem and positive body image in school-aged adolescents. A generic qualitative study design with purposive sampling was used, and the data was thematically analyzed. Results Key barriers identified included lack of family communication, unfavourable family environments, and insufficient training. Social media and gender stereotypes, along with social rejection, were major challenges for adolescents. Facilitators included family involvement and using role models as a strategy. Proposed interventions focused on individual and group recreational activities starting at an early age, engaging adolescents in activities of interest, and promoting collaboration with families. Conclusion This study identified barriers and facilitators proposing multi-level interventions that engage adolescents, families, educational institutions, and the community. Strengthening facilitators and reducing barriers should guide future public health policies. Public contribution These findings may be useful for developing multilevel interventions aimed at improving body image and self-esteem, which could, in turn, prevent and reduce the severity of clinical disorders during adolescence.

Early colonization of the deep-sea bottom—The protracted build-up of an ecosystem

Our understanding of the patterns and processes behind the evolution of deep-marine ecosystems is limited because the body-fossil record of the deep sea is poor. However, that gap in knowledge may be filled as deposits are host to diverse and abundant trace fossils that record the activities of benthic deep-marine organisms. Here, we built a global dataset of trace-fossil occurrences from a comprehensive survey of 720 Ediacaran–Devonian units and show that the establishment of a modern-style deep-marine benthic ecosystem was protracted and coincident with global cooling and increase in oxygenation during the Ordovician. The formation of open burrows may have increased bioirrigation in the uppermost sediment zone, promoting ventilation and generating an ecosystem engineering feedback loop between bioturbation and pore-water oxygenation. Sharp changes in deep-marine bioturbation during the Devonian may have originated from oxygen variations resulting from climate-controlled oceanic circulation.

Trustworthy diagnosis of Electrocardiography signals based on out-of-distribution detection

Cardiovascular disease is one of the most dangerous conditions, posing a significant threat to daily health. Electrocardiography (ECG) is crucial for heart health monitoring. It plays a pivotal role in early heart disease detection, heart function assessment, and guiding treatments. Thus, refining ECG diagnostic methods is vital for timely and accurate heart disease diagnosis. Recently, deep learning has significantly advanced in ECG signal classification and recognition. However, these methods struggle with new or Out-of-Distribution (OOD) heart diseases. The deep learning model performs well on existing heart diseases but falters on unknown types, which leads to less reliable diagnoses. To address this challenge, we propose a novel trustworthy diagnosis method for ECG signals based on OOD detection. The proposed model integrates Convolutional Neural Networks (CNN) and Attention mechanisms to enhance feature extraction. Meanwhile, Energy and ReAct techniques are used to recognize OOD heart diseases and its generalization capacity for trustworthy diagnosis. Empirical validation using both the MIT-BIH Arrhythmia Database and the INCART 12-lead Arrhythmia Database demonstrated our method’s high sensitivity and specificity in diagnosing both known and out-of-distribution (OOD) heart diseases, thus verifying the model’s diagnostic trustworthiness. The results not only validate the effectiveness of our approach but also highlight its potential application value in cardiac health diagnostics.

Revisiting Pearl’s influenza studies by bootstrapping for forward variable selection with a null factor

In 1919 and 1921 Raymond Pearl published four empirical studies on the Spanish Flu epidemic in which he explored the factors that might explain the explosiveness and destructiveness of the epidemic in America’s largest cities. Using partial correlation coefficients he tried to isolate the net effects of the possible explanatory factors, such as general demographic characteristics of the cities and death rates for various diseases, on the variables measuring the severity of the epidemic. Instead of Pearl’s correlation analysis, we apply a bootstrap simulation to forward variable selection with a null factor for generalized linear regression with AICc validation. The null factor or pseudo-variable is a random variable that is independent of the response. The number of times it is included in the model selection simulation provides an important metric for deciding which terms should remain in the model. Our results are largely consistent with Pearl’s conclusions in that the pre-pandemic death rates from organic heart disease and from all causes are most predictive of pandemic explosiveness or severity. However, our results also contain substantive nuances. Our paper contributes to the literature showing that state-of-the-art methodology for variable selection proves useful for historical epidemiology.

Clinical safety and pharmacokinetics of a novel oral niclosamide formulation compared with marketed niclosamide chewing tablets in healthy volunteers: A three-part randomized, double-blind, placebo-controlled trial

Aim Niclosamide is an established anthelmintic substance and a promising candidate for treating cancer, viral infections, and other diseases. However, its solubility in aqueous media is low, and the systemic bioavailability of the commercially available chewing tablet is poor, limiting the use of niclosamide for systemic treatment. A liquid oral formulation using polyethylene glycol 400 was developed and investigated in healthy volunteers to assess safety, tolerability, and pharmacokinetics in comparison to the marketed tablet. (ClinicalTrials.gov: NCT04644705). Methods The study consisted of three parts: Part A was a double-blind placebo-controlled single ascending dose trial in three dose groups (200, 600, and 1600 mg) with four participants receiving either the investigational niclosamide formulation or placebo (3:1) under fasted and/or fed conditions. Part B was a crossover study comparing 1600 mg investigational niclosamide solution with the marketed 2000 mg chewing tablet in four healthy volunteers. Part C was a double-blind placebo-controlled multiple-dose trial comparing 1200 mg and 1600 mg (verum: placebo 4:2) in two dose groups with six subjects each, who received daily doses for seven days. Results No serious or severe adverse events occurred. The most frequent adverse events were mild to moderate gastrointestinal reactions. There was also no apparent dependence between drug exposure levels (AUC, Cmax) and the severity and incidence of adverse events detectable. A relevant food effect was observed with a mean AUC last about 2-fold higher in fed condition compared to fasted condition. In Part B, dose-normalized C max and AUC last were similar for niclosamide solution and tablet. Absorption of niclosamide solution was highly variable. Some individuals showed high absorption (C max > 2µg/ml) whereas others did absorb only marginally. Importantly, there was no dose linearity in the range of 200 mg – 1600 mg. No signs of relevant systemic drug accumulation after multiple administrations were observed. Conclusion Overall safety and tolerability observed in healthy subjects were benign. This is also true for individuals with high absorption (C max > 2µg/ml), encouraging further research into niclosamide as a potential therapeutic agent. Galenic optimization, however, will remain challenging as evident from the observed exposure variability and non-linear PK. Non-linearity, if confirmed by additional data, might make niclosamide more suitable for multi-dose rather than high single dose regimens. The observed food effect should also be considered when further investigating systemic niclosamide exposures. Trial registration ClinicalTrials.gov NCT04644705