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Abstract Background Serotonin (5-HT) is a biogenic monoamine with diverse functions in multiple human organs and tissues. During pregnancy, tightly regulated levels of 5-HT in the fetoplacental unit are critical for proper placental functions, fetal development, and programming. Despite being a non-neuronal organ, the placenta expresses a suite of homeostatic proteins, membrane transporters and metabolizing enzymes, to regulate monoamine levels. We hypothesized that placental 5-HT clearance is important for maintaining 5-HT levels in the fetoplacental unit. We therefore investigated placental 5-HT uptake from the umbilical circulation at physiological and supraphysiological levels as well as placental metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA efflux from trophoblast cells. Methods We employed a systematic approach using advanced organ-, tissue-, and cellular-level models of the human placenta to investigate the transport and metabolism of 5-HT in the fetoplacental unit. Human placentas from uncomplicated term pregnancies were used for perfusion studies, culturing explants, and isolating primary trophoblast cells. Results Using the dually perfused placenta, we observed a high and concentration-dependent placental extraction of 5-HT from the fetal circulation. Subsequently, within the placenta, 5-HT was metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which was then unidirectionally excreted to the maternal circulation. In the explant cultures and primary trophoblast cells, we show concentration- and inhibitor-dependent 5-HT uptake and metabolism and subsequent 5-HIAA release into the media. Droplet digital PCR revealed that the dominant gene in all models was MAO-A, supporting the crucial role of 5-HT metabolism in placental 5-HT clearance. Conclusions Taken together, we present transcriptional and functional evidence that the human placenta has an efficient 5-HT clearance system involving (1) removal of 5-HT from the fetal circulation by OCT3, (2) metabolism to 5-HIAA by MAO-A, and (3) selective 5-HIAA excretion to the maternal circulation via the MRP2 transporter. This synchronized mechanism is critical for regulating 5-HT in the fetoplacental unit; however, it can be compromised by external insults such as antidepressant drugs.

Background BMP10 (bone morphogenic protein 10) has emerged as a novel biomarker associated with the risk of ischemic stroke and other outcomes in patients with atrial fibrillation (AF). The study aimed to determine if repeated BMP10 measurements improve prognostication of cardiovascular events in patients with AF. Methods and Results BMP10 was measured using a prototype Elecsys immunoassay in plasma samples collected at randomization and after 2 months in patients with AF randomized to apixaban or warfarin in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial (n=2878). Adjusted Cox‐regression models were used to evaluate the association between 2‐month BMP10 levels and outcomes. BMP10 levels increased by 7.8% (P

BackgroundThe COVID-19 pandemic and related restrictions may have led to increased stress, particularly in people with mental health problems. Since stress factors play important role in the emergence of suicide attempts (SA) and suicidal ideation (SI), they may have been exacerbated by the pandemic, which could have led to an increased number of suicide attempts. Thus, we first investigated whether the pandemic affected personal stress experiences and appraisal of coping potential in individuals with and without SA and SI. In a second step, we analyzed the frequency and dynamics of SAs by patients admitted to a psychiatric university clinic over a period of four years.MethodsWe examined stress experiences and appraisal of coping resources of inpatients recruited between March 2021 and February 2022 with SA (n=38), SI (n=27), and with mood disorder without SA or SI (n=45). In the second study, we investigated the time course of prospectively recorded patients with a suicide attempt (n=399) between January 1st 2018 and December 31st 2021 using interrupted time-series Poisson regression models.ResultsThere was a significant main effect of group (F[2,107]=6.58, p=0.002) regarding psychological stress levels, which was significantly higher in the SA and SI groups than in the psychiatric control group. No significant differences were found in the appraisal of coping resources or in the frequency of SAs before and during pandemic. However, the pandemic had a significant impact on the seasonal pattern of SAs.ConclusionsThe pandemic increased psychological stress levels in individuals with SA and SI, which may be related to SI and do not necessarily result in SA. The pandemic did not affect the overall frequency of SA between March 2020 and December 2021, but interfered with the seasonal pattern of SA occurrence. Effective intervention strategies during a pandemic should include programs to strengthen the psychological resilience of people who are susceptible to mental health problems.

To succeed in Science on the Move, the nationwide competition for Swiss high school classes, students are requested to work as a team on relevant research topics. The project shapes their notion of science as one of the foundations of our society and as a possible professional field for themselves.

Objectives This study reviewed existing recommendations for virtual mental healthcare services through the quadruple aim framework to create a set of recommendations on virtual healthcare delivery to guide the development of Canadian policies on virtual mental health services.Design We conducted a systematic rapid review with qualitative content analysis of data from included manuscripts. The quadruple aim framework, consisting of improving patient experience and provider satisfaction, reducing costs and enhancing population health, was used to analyse and organise findings.Methods Searches were conducted using seven databases from 1 January 2010 to 22 July 2022. We used qualitative content analysis to generate themes.Results The search yielded 40 articles. Most articles (85%) discussed enhancing patient experiences, 55% addressed provider experiences and population health, and 25% focused on cost reduction. Identified themes included: screen patients for appropriateness of virtual care; obtain emergency contact details; communicate transparently with patients; improve marginalised patients’ access to care; support health equity for all patients; determine the cost-effectiveness of virtual care; inform patients of insurance coverage for virtual care services; increase provider training for virtual care and set professional boundaries between providers and patients.Conclusions This rapid review identified important considerations that can be used to advance virtual care policy to support people living with mental health conditions in a high-income country.

ObjectivesRecently, research on mindfulness and humor has begun to spark interest, both being essential contributors to well-being. This article proposes that forms of humor that share intention and attitudinal foundations with mindfulness, constitute the foundation of a mindful-humorous perspective and mindful humor. Once intention and attitude are in alignment, shared mechanisms underlying a mindful-humorous perspective may lead to synergetic effects (e.g., reinforcing a shift in perspective and attitudinal foundations) as summarized in the proposed mindful humor filter model (MHFM). Based on this theoretical framework, the humor-enriched mindfulness-based program (HEMBP) was developed and evaluated for validity and efficacy in a randomized controlled trial as a first step to test the newly introduced model.MethodsA total of 60 participants were randomly allocated to either the HEMBP or a wait-list control group. Participants' mindfulness, comic styles (e.g., benevolent humor, sarcasm, and cynicism), psychological well-being, life satisfaction, stress, and gelotophobia (fear of being laughed at) were assessed 1 week before and after training, and at a 1-month follow-up. Linear mixed-effects models were fitted to model changes in outcome variables over time.ResultsThe HEMBP was effective in increasing mindfulness, benevolent humor, and psychological well-being, and in reducing sarcasm, cynicism, stress, and gelotophobia, compared to the control group.ConclusionResults support the validity and efficacy of the HEMBP as a promising approach for improving well-being and reducing stress. The HEMBP broadens the scope of existing mindfulness-based programs by cultivating a mindful-humorous outlook on life, facilitating mindfulness practice and insights, and fostering positive emotions and relationships with others through mindful humor. Results are also suggestive of the validity of the mindful humor filter model.

Executing memory-guided behavior requires storage of information about experience and later recall of that information to inform choices. Awake hippocampal replay, when hippocampal neural ensembles briefly reactivate a representation related to prior experience, has been proposed to critically contribute to these memory-related processes. However, it remains unclear whether awake replay contributes to memory function by promoting the storage of past experiences, facilitating planning based on evaluation of those experiences, or both. We designed a dynamic spatial task that promotes replay before a memory-based choice and assessed how the content of replay related to past and future behavior. We found that replay content was decoupled from subsequent choice and instead was enriched for representations of previously rewarded locations and places that had not been visited recently, indicating a role in memory storage rather than in directly guiding subsequent behavior.

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.

Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this phenomenon remains uncertain. Here, we deconstruct the phenomenon of PPI and confirm several limitations of the methodology traditionally utilized to describe PPI, including that the underlying startle response has a non-Gaussian distribution, and that the traditional PPI metric changes with different stimuli. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound processing. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared with wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In contrast, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.

Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this phenomenon remains uncertain. Here, we deconstruct the phenomenon of PPI and confirm several limitations of the methodology traditionally utilized to describe PPI, including that the underlying startle response has a non-Gaussian distribution, and that the traditional PPI metric changes with different stimuli. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound processing. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared with wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In contrast, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.

Abstract Background Persons with hereditary cancer syndromes (carriers) have a higher risk of developing cancer early. They are confronted with decisions regarding prophylactic surgeries, communication within their families, and childbearing. The present study aims to assess distress, anxiety, and depression in adult carriers and identify risk groups and predictors; clinicians can use to screen for particularly distressed persons. Methods N = 223 participants (n = 200 women, n = 23 men) with different hereditary cancer syndromes affected and unaffected by cancer answered questionnaires measuring their distress, anxiety, and depression levels. The sample was compared to the general population using one‐sample t‐tests. The n = 200 women with (n = 111) and without cancer (n = 89) were then compared and predictors for increased levels of anxiety and depression were identified using stepwise linear regression analyses. Results 66% reported clinical relevant distress, 47% reported clinical relevant anxiety, and 37% reported clinical relevant depression. Compared to the general population, carriers experienced increased distress, anxiety, and depression. Additionally, women with cancer suffered from more depressive symptoms than those without cancer. Past psychotherapy for a mental disorder and high distress were identified as predictors for increased anxiety and depression in female carriers. Conclusions The results suggest that the psychosocial consequences of hereditary cancer syndromes are serious. Clinicians could regularly screen carriers regarding anxiety and depression. The NCCN Distress Thermometer can be combined with questions about past psychotherapy to identify especially vulnerable persons. Further studies are needed to develop psychosocial interventions.

Abstract Background To date, little is known about the sustainability and scalability of MyDiabetesPlan, an eHealth innovation designed to facilitate shared decision-making within diabetes care. To avoid the possibility of its short-lived implementation and promote wider adoption so as to promote patient-centred diabetes care, it is critical to understand MyDiabetesPlan’s sustainability and scalability in order to ensure its long-term impact at a greater scale. We sought to identify the sustainability and scalability potential of MyDiabetesPlan and its limiting factors. Methods Using a concurrent triangulation mixed-methods approach, data were collected from 20 individuals involved in the development and implementation of MyDiabetesPlan. The National Health Services Sustainability Model (NHSSM) and the Innovation Scalability Self-administered Questionnaire (ISSaQ) were administered using a ‘think-aloud’ approach and subsequently, short semi-structured interviews were conducted. Mean aggregate scores and stakeholder-specific scores were generated for the NHSSM and ISSaQ, to quantitatively determine facilitating and limiting factors to sustainability and scalability. Content analysis occurred iteratively with qualitative data, to examine commonalities and differences with the quantitative findings. Results The top facilitating factor to sustaining MyDiabetesPlan was “Staff involvement and training to sustain the process.”, whereas the top limiting factors were: “Adaptability of Improved Process”, “Senior Leadership Engagement” and “Infrastructure for Sustainability”. The top three facilitating factors for scale-up were “Acceptability”, “Development with Theory” and “Consistency with Policy Directives.” Conversely, the top three limiting factors were “Financial and Human Resources”, “Achievable Adoption” and “Broad Reach”. Qualitative findings corroborated the limiting/facilitating factors identified. Conclusions Addressing staff involvement throughout the dynamic care contexts, and resource constraints impacting scale-up can enhance the sustainability and scalability of MyDiabetesPlan . As such, future plans will focus on garnering organizational leadership buy-in and support, which may address the resource constraints associated with sustainability and scalability and improve the capacity for adequate staff involvement. eHealth researchers will be able to prioritize these limiting factors from the outset of their tool development to purposefully optimize its sustainability and scalability performance.

Hartnup disease is an autosomal recessive, metabolic disorder caused by mutations of the neutral amino acid transporter, SLC6A19/B0AT1. Reduced absorption in the intestine and kidney results in deficiencies in neutral amino acids and their down-stream metabolites, including niacin, associated with skin lesions and neurological symptoms. The effects on the nervous system such as ataxia have been related to systemic deficiencies of tryptophan (and other neutral amino acids) as no expression of the B0AT1 transporter was found in the brain. In the intestine, SLC6A19 cooperates with ACE2 which has received major attention as the cellular receptor for SARS-CoV-2. When transcriptomics data for ACE2 and its partner proteins were examined, a previously unrecognized expression of Slc6a19 mRNA in the ependymal cells of the mouse brain was encountered that is set into the context of neurological manifestations of Hartnup disease with this communication. A novel role for SLC6A19/B0AT1 in amino acid transport from CSF into ependymal cells is proposed and a role of niacin in ependymal cells highlighted.

Abstract The present multi-study article investigates the subjective experience of professional football (a.k.a. soccer) referees and players during the COVID-19 pandemic and the so-called ghost games (i.e., games without supporters). Referees from the Austrian Football Association completed questionnaires inquiring about self-efficacy, motivation, and general personal observations and perceptions (e.g., arousal or confidence). In addition, two players and one referee in the Austrian Football Bundesliga were interviewed retrospectively regarding their subjective experience during ghost games and the effects of emotions on behavior and performance using semi-structured, video-taped interviews. Results of the referee survey indicate that the most profound differences between regular games and ghost games lie in the domain of intrinsic motivation and multiple aspects of subjective experience. Specifically, the experience in ghost games compared with regular games was reported by referees as being significantly less motivating, less excited/tense, less emotional, less focused, and overall, more negative, despite being easier to referee and the players behaving more positively. Qualitative analyses of the video-taped interview footage indicated (i) substantial inter-individual variability regarding the extent of the effect of the empty stadiums on the subjective experience of emotions, (ii) consequently, different strategies to regulate emotions and arousal from suboptimal to optimal levels, both before and during competition, and (iii) interactions between reported emotions, arousal, motivation, self-confidence, behavior and performance on the pitch. In addition, non-verbal expressions of emotion were captured using fully automated AI-software that coded facial movements during interviews. The results of this exploratory facial expression analysis revealed varying degrees of arousal and valence in relation to the content of the statements during the interviews, demonstrating the convergent validity of our findings. Our findings contribute to the growing literature on the effects of football games without fans during the COVID-19 pandemic and provide insights into the subjective experience of professional football referees. Concerning referees and players alike, emotions are investigated as potential processes related to home-field advantage and performance in professional football by means of a multi-methods approach. Further, the combination of qualitative and quantitative measures—as well as verbal and non-verbal communication channels—can deepen our understanding of the emotional influence of (missing) spectators on the subjective experience and the behavior of sports professionals is discussed.

Over the past 10-20 years, neuroscience witnessed an explosion in the use of non-invasive imaging methods, particularly magnetic resonance imaging (MRI), to study brain structure and function. Simultaneously, with access to MRI in many research institutions, MRI has become an indispensable tool for researchers and veterinarians to guide improvements in surgical procedures and implants and thus, experimental as well as clinical outcomes, given that access to MRI also allows for improved diagnosis and monitoring for brain disease. As part of the PRIMEatE Data Exchange, we gathered expert scientists, veterinarians, and clinicians who treat humans, to provide an overview of the use of non-invasive imaging tools, primarily MRI, to enhance experimental and welfare outcomes for laboratory non-human primates engaged in neuroscientific experiments. We aimed to provide guidance for other researchers, scientists and veterinarians in the use of this powerful imaging technology as well as to foster a larger conversation and community of scientists and veterinarians with a shared goal of improving the well-being and experimental outcomes for laboratory animals.

The years 2021 and 2022 showed that maritime logistics are prone to interruptions. Ports especially turned out to be bottlenecks with long queues of waiting vessels. This leads to the question of whether this can be (at least partly) mitigated by means of better and more flexible terminal operations. Digital Twins have been in use in production and logistics to increase flexibility in operations and to support operational decision-making based on real-time information. However, the true potential of Digital Twins to enhance terminal operations still needs to be further investigated. A Delphi study is conducted to explore the operational pain points, the best practices to counter them, and how these best practices can be supported by Digital Twins. A questionnaire with 16 propositions is developed, and a panel of 17 experts is asked for their degrees of confirmation for each. The results indicate that today’s terminal operations are far from ideal, and leave space for optimisation. The experts see great potential in analysing the past working shift data to identify the reasons for poor terminal performance. Moreover, they agree on the proposed best practices and support the use of emulation for detailed ad hoc simulation studies to improve operational decision-making.

Background: Night shift work is associated with sleep disturbances, obesity, and cardiometabolic diseases. Disruption of the circadian clock system has been suggested to be an independent cause of type 2 diabetes and cardiovascular disease in shift workers. We aimed to improve alignment of circadian timing with social and environmental factors with administration of melatonin. Methods: In a randomized, placebo-controlled, prospective study, we analysed the effects of 2 mg of sustained-release melatonin versus placebo on glucose tolerance, insulin resistance indices, sleep quality, circadian profiles of plasma melatonin and cortisol, and diurnal blood pressure profiles in 24 rotating night shift workers during 12 weeks of treatment, followed by 12 weeks of wash-out. In a novel design, the time of melatonin administration (at night or in the morning) depended upon the shift schedule. We also compared the baseline profiles of the night shift (NS) workers with 12 healthy non-night shift (NNS)-working controls. Results: We found significantly impaired indices of insulin resistance at baseline in NS versus NNS (p