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Mobile assistance systems (MAS) promise to overcome personnel shortages in operating theatres worldwide. A literature review inspired by the PRISMA 2020 method determines the state of the art of MAS, and identifies a lack of application areas for MAS in the operating theatre. Interviews with subject-matter experts aim to investigate application areas for MAS. The results show that most operational tasks refer to material management and patient management. MAS, with their potential to reduce the time needed for material and patient management, and the physical and mental strain of patient management, have great potential in the operating theatre. [ABSTRACT FROM AUTHOR]

This perspective summarises and explains the long-term surveillance framework 2021-2027 for infectious diseases in the European Union/European Economic Area (EU/EEA) published in April 2023. It shows how shortcomings in the areas of public health focus, vigilance and resilience will be addressed through specific strategies in the coming years and how these strategies will lead to stronger surveillance systems for early detection and monitoring of public health threats as well as informing their effective prevention and control. A sharper public health focus is expected from a more targeted list of notifiable diseases, strictly public-health-objective-driven surveillance standards, and consequently, leaner surveillance systems. Vigilance should improve through mandatory event reporting, more automated epidemic intelligence processing and increased use of genomic surveillance. Finally, EU/EEA surveillance systems should become more resilient by modernising the underlying information technology infrastructure, expanding the influenza sentinel surveillance system to other respiratory viruses for better pandemic preparedness, and increasingly exploiting potentially more robust alternative data sources, such as electronic health records and wastewater surveillance. Continued close collaboration across EU/EEA countries will be key to ensuring the full implementation of this surveillance framework and more effective disease prevention and control.

Objective: Parkinson disease (PD) is associated with a predictable decline in motor function and mobility that is commonly managed with exercise. There is a limited understanding of the effects of group exercise compared to individual exercise (IE) and usual care (UC) on motor function and mobility. Our purpose was to investigate the effects of group exercise compared to IE and UC on motor function and mobility for people with PD., Methods: A systematic review and meta-analysis was performed with randomized control trials that investigated the effects of group compared with IE and UC on motor function and mobility for people with PD. A systematic search was performed in PubMed, EBSCO, and Science Direct databases. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach., Results: Twenty-three studies assessed at least 1 mobility-related outcome measure, met our inclusion criteria, and were included in quantitative analysis. There was no significant difference on motor function and mobility between group exercise and IE for all standardized outcome assessment meta-analyses. Motor function and mobility were significantly improved with group exercise compared to UC in 9 of 11 standardized outcome assessment meta-analyses. Results were based upon low to moderate quality of evidence., Conclusion: Based upon low to moderate quality of evidence, group exercise has a similar to larger effect as IE and UC on improving motor function and mobility for people with PD. When used in combination with skilled physical therapy, group exercise may be an appropriate adjunct to individualized physical therapy to maximize mobility and function., Impact: Long-term adherence to exercise is essential to maintain mobility and motor function for people with PD. Our study suggests group exercise is as effective as IE and may be an appropriate option to encourage long-term adherence related to increased access, socialization, and accountability., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In 2023, an increase of OXA-48-producing Klebsiella pneumoniae was noticed by the Lithuanian National Public Health Surveillance Laboratory. Whole genome sequencing (WGS) of 106 OXA-48-producing K. pneumoniae isolates revealed three distinct clusters of carbapenemase-producing K. pneumoniae high-risk clones, including sequence type (ST) 45 (n = 35 isolates), ST392 (n = 32) and ST395 (n = 28), involving six, six and nine hospitals in different regions, respectively. These results enabled targeted investigation and control, and underscore the value of national WGS-based surveillance for antimicrobial resistance.

Purpose: The Promise of Adolescence: Realizing Opportunity for All Youth report recommends several Medicaid policies to increase insurance coverage among adolescents: approve Medicaid expansion; eliminate the 5-year Medicaid waiting period for lawfully present adolescent immigrants; increase Medicaid reimbursement rates for adolescent health services to the level of Medicare; and ensure coverage and sufficient reimbursement of comprehensive health services. We designed this study to identify key advocates and factors relevant to adoption and implementation of the recommended Medicaid policies in Nebraska to highlight opportunities for additional advocacy., Methods: We conducted semistructured interviews January 2022 with 28 adolescent health and health-care access experts in Nebraska, including representatives from health care, education, government, and nonprofit sectors. We recorded the interviews and transcribed them verbatim, then coded data using NVivo software and identified key themes., Results: Participants were unable to identify any Medicaid advocates or advocacy work focused on adolescents, but they did identify 35 organizations working to improve insurance coverage in Nebraska. Coordinated multisector, statewide coalitions secured the adoption of Medicaid expansion through a citizen-supported ballot initiative. Barriers to successful implementation include limited Medicaid outreach to citizens and lawfully present immigrants. Low state government support for increasing Medicaid reimbursement rates and providing comprehensive health services, coupled with the absence of coordinated advocacy, hinder the adoption of these recommendations., Discussion: Advocacy efforts should be implemented to increase adoption and implementation of Medicaid policies recommended to increase adolescents' insurance coverage. These efforts must be built on a foundation of knowledge of state government practices and must utilize sustained partnership among multisector advocates, including adolescent-serving professionals., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

BackgroundPreliminary unpublished results of the survey of carbapenem- and/or colistin-resistant Enterobacterales (CCRE survey) showed the expansion of carbapenemase-producing Klebsiella pneumoniae (CPKP) sequence type (ST) 39 in 12 of 15 participating Greek hospitals in 2019.AimWe conducted a rapid survey to determine the extent of spread of CPKP high-risk clones in Greek hospitals in 2022 and compare the distribution of circulating CPKP clones in these hospitals since 2013.MethodsWe analysed whole genome sequences and epidemiological data of 310 K. pneumoniae isolates that were carbapenem-resistant or 'susceptible, increased exposure' from Greek hospitals that participated in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE, 2013-2014), in the CCRE survey (2019) and in a national follow-up survey (2022) including, for the latter, an estimation of transmission events.ResultsFive K. pneumoniae STs including ST258/512 (n = 101 isolates), ST11 (n = 93), ST39 (n = 56), ST147 (n = 21) and ST323 (n = 13) accounted for more than 90% of CPKP isolates in the dataset. While ST11, ST147 and ST258/512 have been detected in participating hospitals since 2013 and 2014, KPC-2-producing ST39 and ST323 emerged in 2019 and 2022, respectively. Based on the defined genetic relatedness cut-off, 44 within-hospital transmission events were identified in the 2022 survey dataset, with 12 of 15 participating hospitals having at least one within-hospital transmission event.ConclusionThe recent emergence and rapid spread of new high-risk K. pneumoniae clones in the Greek healthcare system related to within-hospital transmission is of concern and highlights the need for molecular surveillance and enhanced infection prevention and control measures.

Analytical treatment interruptions (ATIs) have become a key methodological approach to evaluate the effects of experimental HIV cure-related research interventions. During ATIs, sex partners of trial participants might be at risk of acquiring HIV. This risk raises both ethical and feasibility concerns about ATI trials. We propose a partner protection package (P3) approach to address these concerns. A P3 approach would provide guidance to investigators, sponsors, and those who are designing and implementing context-specific partner protections in HIV cure-related trials involving ATIs. The approach would also help assure institutional review boards, trial participants, and communities that ATI trials with a P3 would provide appropriate partner protections. We offer a prototype P3 framework that delineates three basic considerations for protecting participants' sex partners during ATI trials: (1) ensuring the scientific and social value of the ATI and the trial, (2) reducing the likelihood of unintended HIV transmission, and (3) ensuring prompt management of any acquired HIV infection. We outline possible ways of implementing these basic considerations., Competing Interests: Declaration of interests KD has received funding from Gilead Sciences and Merck & Co, that is not directly related to this manuscript; received support from ethics supplement to R21MH118120 from UM1AI126620, and UM1AI164570 from BEAT-HIV Collaboratory. KD, JAS, and MJP also received support from National Institute of Mental Health R01-MH126768. MJP is supported on K23AI157875 from US National Institute of Mental Health. AR was supported in part by the Clinical Center Department of Bioethics, which is in the Intramural Program of the US National Institutes of Health (NIH). All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fisheries managers stock triploid (i.e., infertile, artificially produced) rainbow trout Oncorhynchus mykiss in North American lakes to support sport fisheries while minimizing the risk of genetic introgression between hatchery and wild trout. In Washington State, the Washington Department of Fish and Wildlife (WDFW) allocates approximately US $3 million annually to stock hatchery-origin rainbow trout in > 600 lakes, yet only about 10% of them are triploids. Many lakes in Washington State drain into waters that support wild anadromous steelhead O. mykiss that are listed as threatened under the U.S. Endangered Species Act. As a result, there is a strong interest in understanding the costs and benefits associated with stocking sterile, triploid rainbow trout as an alternative to traditional diploids. The objectives of this study were to compare triploid and diploid rainbow trout in terms of: (1) contribution to the sport fishery catch, (2) fine-scale movements within the study lakes, (3) rate of emigration from the lake, and (4) natural mortality. Our results demonstrated that triploid and diploid trout had similar day-night distribution patterns, but triploid trout exhibited a lower emigration rate from the lake and lower catch rates in some lakes. Overall, triploid rainbow trout represent a viable alternative to stocking of diploids, especially in lakes draining to rivers, because they are sterile, have comparable home ranges, and less often migrate., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Upon infection by the malaria parasite Plasmodium falciparum, the glycolytic rate of a red blood cell increases up to 100-fold, possibly contributing to lactic acidosis and hypoglycemia in patients with severe malaria. This dramatic increase in glucose uptake and metabolism was correctly predicted by a newly constructed detailed enzyme kinetic model of glucose metabolism in the trophozoite-infected red blood cell. Subsequently, we expanded the model to simulate an infected red blood cell culture, including the different asexual blood-stage forms of the malaria parasite. The model simulations were in good agreement with experimental data, for which the measured parasitic volume was an important parameter. Upon further analysis of the model, we identified glucose transport as a drug target that would specifically affect infected red blood cells, which was confirmed experimentally with inhibitor titrations. This model can be a first step in constructing a whole-body model for glucose metabolism in malaria patients to evaluate the contribution of the parasite's metabolism to the disease state., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A number of psychiatric disorders are defined by persistent or recurrent sleep-wake disturbances alongside disruptions in circadian rhythm and altered clock gene expression. Circadian rhythms are present not only in the hypothalamic suprachiasmatic nucleus but also in peripheral tissues. In this respect, cultures of human derived dermal fibroblasts may serve as a promising new tool to investigate cellular and molecular mechanisms underlying the pathophysiology of mental illness. In this article, we discuss the advantages of fibroblast cultures to study psychiatric disease. More specifically, we provide an update on recent advances in modeling circadian rhythm disorders using human fibroblasts., Competing Interests: Johannes Thome has received financial support from pharmaceutical companies (Actelion, Astra Zeneca, Bristol-Myers Squibb, EVER Neuro Pharma GmbH, Janssen-Cilag, Lilly, Lundbeck, MEDICE, Merz, Novartis, Pfizer, Roche, Servier, Shire, Trommsdorff) some of which manufacture medication used in the treatment of ADHD patients. Frank Faltraco, Golo Kronenberg, Adriana Uzoni, and Denise Palm have no potential conflicts of interest to disclose., (Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany.)

The central oscillator for the inner clock is the suprachiasmatic nuclei of the hypothalamus. Furthermore, many peripheral oscillators are present in tissues such as skin. Human derived fibroblasts provide an advantageous model to study circadian rhythmicity as well as the influence of pharmacological drugs on circadian gene expression. Importantly, the synchronization of the circadian system of fibroblasts can be done by different methods. The review presents an overview of the current knowledge of different synchronization methods mostly used in mice or rat fibroblasts. Furthermore, the review sums up and discusses the role of norepinephrine as a possible synchronizer agent., Competing Interests: Johannes Thome has received financial support from pharmaceutical companies (Actelion, Astra Zeneca, Bristol-Myers Squibb, EVER Neuro Pharma GmbH, Janssen-Cilag, Lilly, Lundbeck, MEDICE, Merz, Novartis, Pfizer, Roche, Servier, Shire, Trommsdorff) some of which manufacture medication used in the treatment of ADHD patients. Frank Faltraco, Adriana Uzoni, Liliia Shevchuk, and Denise Palm have no potential conflict of interest to disclose., (Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany.)

Whole genome sequencing data of 874 Escherichia coli isolates carrying bla NDM-5 from 13 European Union/European Economic Area countries between 2012 and June 2022 showed the predominance of sequence types ST167, ST405, ST410, ST361 and ST648, and an increasing frequency of detection. Nearly a third (30.6%) of these isolates were associated with infections and more than half (58.2%) were predicted to be multidrug-resistant. Further spread of E. coli carrying bla NDM-5 would leave limited treatment options for serious E. coli infections.

To anticipate and adapt to daily recurring events defined by the earth's rotation such as light-dark and temperature cycles, most species have developed internal, so-called circadian clocks. These clocks are involved in the regulation of behaviors such as the sleep-wake cycle and the secretion of hormones and neurotransmitters. Disruptions of the circadian system affect cognitive functions and are associated with various diseases that are characterized by altered neurotransmitter signaling. In this review, we summarize the current knowledge about the interplay of the circadian clock and the regulation of psychiatric health and disease., Competing Interests: Johannes Thome has received financial support from pharmaceutical companies (Actelion, Astra Zeneca, Bristol-Myers Squibb, EVER Neuro Pharma GmbH, Janssen-Cilag, Lilly, Lundbeck, MEDICE, Merz, Novartis, Pfizer, Roche, Servier, Shire, Trommsdorff) some of which manufacture medication used in the treatment of ADHD patients. Jana-Thabea Kiehn, Denise Palm, Frank Faltraco, and Henrik Oster have no potential conflicts of interest to disclose., (Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany.)

Supply chains have evolved into dynamic, interconnected supply networks, which increases the complexity of achieving end-to-end traceability of object flows and their experienced events. With its capability of ensuring a secure, transparent, and immutable environment without relying on a trusted third party, the emerging blockchain technology shows strong potential to enable end-to-end traceability in such complex multitiered supply networks. This paper aims to overcome the limitations of existing blockchain-based traceability architectures regarding their object-related event mapping ability, which involves mapping the creation and deletion of objects, their aggregation and disaggregation, transformation, and transaction, in one holistic architecture. Therefore, this paper proposes a novel 'blueprint-based' token concept, which allows clients to group tokens into different types, where tokens of the same type are non-fungible. Furthermore, blueprints can include minting conditions, which, for example, are necessary when mapping assembly processes. In addition, the token concept contains logic for reflecting all conducted object-related events in an integrated token history. Finally, for validation purposes, this article implements the architecture's components in code and proves its applicability based on the Ethereum blockchain. As a result, the proposed blockchain-based traceability architecture covers all object-related supply chain events and proves its general-purpose end-to-end traceability capabilities of object flows.

The HITECH Act aimed to leverage Electronic Health Records (EHRs) to improve efficiency, quality, and patient safety. Patient safety and EHR use have been understudied, making it difficult to determine if EHRs improve patient safety. The objective of this study was to determine the impact of EHRs and attesting to Meaningful Use (MU) on Patient Safety Indicators (PSIs). A multivariate regression analysis was performed using a generalized linear model method to examine the impact of EHR use on PSIs. Fully implemented EHRs not attesting to MU had a positive impact on three PSIs, and hospitals that attested to MU had a positive impact on two. Attesting to MU or having a fully implemented EHR were not drivers of PSI-90 composite score, suggesting that hospitals may not see significant differences in patient safety with the use of EHR systems as hospitals move towards pay-for-performance models. Policy and practice may want to focus on defining metrics and PSIs that are highly preventable to avoid penalizing hospitals through reimbursement, and work toward adopting advanced analytics to better leverage EHR data. These findings will assist hospital leaders to find strategies to better leverage EHRs, rather than relying on achieving benchmarks of MU objectives.

The AIDS Clinical Trials Group A5345 study (NCT03001128) included an intensively monitored antiretroviral pause (IMAP), during which participants living with HIV temporarily stopped antiretroviral treatment (ART) in an effort to identify biomarkers that could predict HIV rebound. We evaluated the potential impact of the IMAP on A5345 study participants in the United States by questioning them immediately after the IMAP and at the end of the study. We administered longitudinal sociobehavioral questionnaires to participants following the IMAP when they resumed ART and at the end of the study. We summarized descriptive data from the post-IMAP and end-of-study questionnaires. Open-ended responses were analyzed using conventional content analysis. Reactions to pausing ART involved a mixture of curiosity and satisfaction from contributing to science. All participants indicated adherence with the ART interruption. About half (9/17) of post-IMAP questionnaire respondents reported having sexual partner(s) during the IMAP, and of those, nearly all (8/9) did not find it difficult to use measures to prevent HIV transmission to partners. The majority believed that they benefited from the study, yet some had elevated anxiety following the IMAP and at the end of the study. Most (24/29) respondents who completed the end-of-study questionnaire would recommend the study to other people living with HIV. Our findings underscore the relevance of the psychosocial aspects of participating in studies that involve interruptions of ART. Understanding how participants experience this research is invaluable for informing the design of future research aimed at sustained ART-free virologic suppression.

PulseNet International (PNI) is a global network of 88 countries who work together through their regional and national public health laboratories to track foodborne disease around the world. The vision of PNI is to implement globally standardized surveillance using whole genome sequencing (WGS) for real-time identification and subtyping of foodborne pathogens to strengthen preparedness and response and lower the burden of disease. Several countries in North America and Europe have experienced significant benefits in disease mitigation after implementing WGS. To broaden the routine use of WGS around the world, challenges and barriers must be overcome. We conducted this study to determine the challenges and barriers countries are encountering in their attempts to implement WGS and to identify how PNI can provide support to improve and become a better integrated system overall. A survey was designed with a set of qualitative questions to capture the status, challenges, barriers, and successes of countries in the implementation of WGS and was administered to laboratories in Africa, Asia-Pacific, Latin America and the Caribbean, and Middle East. One-third of respondents do not use WGS, and only 8% reported using WGS for routine, real-time surveillance. The main barriers for implementation of WGS were lack of funding, gaps in expertise, and training, especially for data analysis and interpretation. Features of an ideal system to facilitate implementation and global surveillance were identified as an all-in-one software that is free, accessible, standardized and validated. This survey highlights the minimal use of WGS for foodborne disease surveillance outside the United States, Canada, and Europe to date. Although funding remains a major barrier to WGS-based surveillance, critical gaps in expertise and availability of tools must be overcome. Opportunities to seek sustainable funding, provide training, and identify solutions for a globally standardized surveillance platform will accelerate implementation of WGS worldwide.

Abstract: It is unclear if national investments of the HITECH Act have resulted in significant improvements in care processes and outcomes by making "Meaningful Use (MU)" of Electronic Health Record (EHR) systems. The objective of this study is to determine the impact of EHRs and MU on inpatient quality. We used inpatient hospitalization data, American Hospital Association annual survey, and the Centers for Medicare and Medicaid Services attestation records to study the impact of EHRs on inpatient quality composite scores. Agency for Healthcare Research and Quality Inpatient Quality Indicator (IQI) software version 5.0 was used to compute the hospital-level risk-adjusted standardized rates for IQI indicators and composite scores. After adjusting for confounding factors, EHRs that attested to MU had a positive impact on IQI 90 and IQI 91 composite scores with an 8% decrease in composites for mortality for selected procedures and 18% decrease in composites for mortality for selected conditions. Meaningful Use attestation may be an important driver related to inpatient quality. Health care leaders may need to focus on quality improvement initiatives and advanced analytics to better leverage their EHRs to improve IQI 90 composite score for mortality for selected procedures, because we observed a lesser impact on IQI 90 compared with IQI 91., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 National Association for Healthcare Quality.)

In 2017, Public Health 3.0 was introduced, providing recommendations that expand traditional public department functions and programs. Operationalizing the framework requires that local health departments invest in the requisite professional skills to respond to their community's needs. The purpose of this paper is to determine the professional skills that are most important for local health departments to respond to large public health issues and challenges that are having a major impact on their communities. The study used a cross-sectional assessment of the education and training needs of local public health departments in Nebraska following the principles of practice-based systems research. The assessment was designed to assess the training and education needs of local health department staff members. The questions measured the perceived importance of and respondent's capacity across 57 core competencies for public health professionals modified from the Council on Linkages Between Academia and Public Health Practice. A total of 104 staff members from seven local health departments were requested to complete the assessment and 100% of the individuals responded to and completed the assessment. Twenty-eight skills were identified as the most important skills needed for local health departments. The skills were themed and categorized into four domains. (1) Data, Evaluation, and Quality Improvement, (2) Community Engagement and Facilitation, (3) Systems Thinking and Leadership, and (4) Policy and Advocacy. The results from this analysis provide direction to strengthen and transform the public health system into one that is connected, responsive, and nimble. Additionally, it also highlighted a glaring omission that Equity, Diversity, and Inclusion should be included as the fifth domain., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Federal and state policy makers have debated the evolving concept of community benefit and the extent to which nonprofit hospitals are providing benefits to the community in exchange for the tax benefits they receive., Objective: This study compares community benefits spending by nonprofit hospitals in Nebraska and other selected states in both 2012 and 2015. Expenditures are also examined by rural, regional, and urban hospitals within Nebraska., Methods: Community benefit expenditure data were taken from Community Benefit Insight and consolidated into the categories of direct patient care, community health improvement initiatives, and health professions education and research., Results: When community benefit expenditures were compared across 11 states, Nebraska had the highest percentage of expenditures for community health improvement initiatives in both 2012 and 2015. Although community benefit expenditures for the 44 nonprofit hospitals within Nebraska increased from 2012 to 2015, they remained flat as a share of total hospital expenditures. In 2015, 63% of community benefit expenditures were allocated to direct patient care, which represented a 7.3% decrease from 2012. This decline led to greater spending on community health improvement initiatives (3.1%) and health professions education and research (4.2%). Rural, regional, and urban hospitals spent more proportionately on community health improvement initiatives in 2015 than in 2012., Conclusions: The shift in community benefit expenditures from direct patient care to community health improvement initiatives and health professions education and research suggests that hospitals are investing in programs with broader community-wide benefits. Nebraska allocates a significantly larger share of its community benefits spending to community health improvement activities than other Great Plains and Midwestern states. Nebraska is in the process of implementing Medicaid expansion, which may shift future community benefits spending decisions., Competing Interests: The authors have indicated they have no potential conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The internal clock is driven by circadian genes [e.g., Clock, Bmal1, Per1-3, Cry1-2], hormones [e.g., melatonin, cortisol], as well as zeitgeber ['synchronisers']. Chronic disturbances in the circadian rhythm in Objectives: The aim of this review is to summarise the current knowledge and literature regarding circadian rhythms in the context of mood disorders, focussing on the role of circadian genes, hormones, and neurotransmitters., Methods: The review presents the current knowledge and literature regarding circadian rhythms in mood disorders using the Pubmed database. Articles with a focus on circadian rhythms and mood disorders [n=123], particularly from 1973 to 2020, were included., Results: The article suggests a molecular link between disruptions in the circadian rhythm and mood disorders. Circadian disturbances, caused by the dysregulation of circadian genes, hormones, and neurotransmitters, often result in a clinical picture resembling depression., Conclusion: The article suggests a molecular link between disruptions in the circadian rhythm and mood disorders. Circadian disturbances, caused by the dysregulation of circadian genes, hormones, and neurotransmitters, often result in a clinical picture resembling depression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The circadian rhythm is essential for the interaction of all living organisms with their environments. Several processes, such as thermoregulation, metabolism, cognition and memory, are regulated by the internal clock. Disturbances in the circadian rhythm have been shown to lead to the development of neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD). Interestingly, the mechanism of the circadian rhythms has been conserved in many different species, and misalignment between circadian rhythms and the environment results in evolutionary regression and lifespan reduction. This review summarises the conserved mechanism of the internal clock and its major interspecies differences. In addition, it focuses on effects the circadian rhythm disturbances, especially in cases of ADHD, and describes the possibility of recombinant proteins generated by eukaryotic expression systems as therapeutic agents as well as CRISPR/Cas9 technology as a potential tool for research and therapy. The aim is to give an overview about the evolutionary conserved mechanism as well as the changes of the circadian clock. Furthermore, current knowledge about circadian rhythm disturbances and therapeutic approaches is discussed., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Attention-deficit hyperactivity disorder (ADHD) is characterized by changes to the circadian process. Many medications used to treat the condition, influence norepinephrine levels. Several studies have, in addition, reported that norepinephrine itself has an effect on circadian function. The aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after norepinephrine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with an ADHD diagnosis. Circadian preference was evaluated with German Morningness-Eveningness Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different norepinephrine concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. The exposure of 1 µM norepinephrine to confluent cultures of human dermal fibroblasts from participants with a diagnosis of ADHD, was shown to dampen Per1 rhythmicity. The expression of Bmal1, Per1 and Per3 in control subjects was also influenced by incubation with 1 µM norepinephrine. Cultures from the ADHD group revealed no statistically significant overall differences in circadian gene expression, between cultures with and without norepinephrine incubation. Per3 expression showed a significant ZT × group interaction via mixed ANOVA. Per3 expression at ZT4 was significant higher in the group of control samples incubated with 1 µM norepinephrine, compared to the control group without norepinephrine. This effect was also shown in the control samples incubated with 1 µM norepinephrine and cultures from subjects with ADHD without norepinephrine incubation. Per3 expression differed between the healthy control group and the ADHD group without norepinephrine incubation at ZT28. The results of the present study illustrate that norepinephrine impacts on circadian function. In both groups, control group and cultures taken from subjects with ADHD, the expression of the periodic genes (Per1-3) was significantly influenced by incubation with norepinephrine., (© 2021. The Author(s).)

Circadian clocks control immunity and virus replication, as well as pharmacokinetics and efficacy therapeutics. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after remdesivir exposure. In the current study, we analysed circadian gene expression in a cohort of participants without a neuropsychiatric diagnosis. After ex vivo exposure to remdesivir to human dermal fibroblast (HDF) cultures and dexamethasone synchronization, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analysed via qRT-PCR. In this study, D-MEQ scores indicated that participants without a neuropsychiatric diagnosis had no evening preference. Remdesivir leads to a slight phase-shift in Clock, Per1 and Per2. Significant different expressions of Bmal1 and Per3 were detected after remdesivir exposure: Bmal1 at ZT8 (t(22) = 3.26, p = 0.004), ZT24 (t(22) = - 2.66, p = 0.015), ZT28 (t(20) = - 2.14, p = 0.045) and Per3 at ZT8 (t(22) = - 4.27, p < 0.001) and ZT12 (t(22) = - 2.61, p = 0.016). A significant difference between chronotype and circadian gene expression for Bmal1, Cry1 and Per3 was observed. The present study shows that remdesivir has an impact on circadian function. It is well known that the circadian rhythm effects sleep and, moreover, sleep quality. The results suggest that remdesivir medication may alter sleep quality in participants without a neuropsychiatric diagnosis and shifts chronotype to eveningness; similar as prevalent in ADHD., (© 2021. The Author(s).)

Atomoxetine (ATO) is a second line medication for attention-deficit hyperactivity disorder (ADHD). We proposed that part of the therapeutic profile of ATO may be through circadian rhythm modulation. Thus, the aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after ATO exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with a diagnosis of ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different ATO concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. No statistical significant effect of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, sleep WASO and total number of wake bouts was observed. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. ATO induced the rhythmicity of Clock in the ADHD group. This effect, however, was not observed in HDF cultures of healthy controls. Bmal1 and Per2 expression showed a significant ZT × group interaction via mixed ANOVA. Strong positive correlations for chronotype and circadian genes were observed for Bmal1, Cry1 and Per3 among the study participants. Statistical significant different Clock, Bmal1 and Per3 expressions were observed in HDFs exposed to ATO collected from ADHD participants exhibiting neutral and moderate evening preference, as well as healthy participants with morning preferences. The results of the present study illustrate that ATO impacts on circadian function, particularly on Clock, Bmal1 and Per2 gene expression., (© 2021. The Author(s).)