The social sciences are essential to include in the fight against both public health challenges of antimicrobial resistance (AMR) and COVID-19. In this scoping review, we document what social science knowledge has been published about the social relationship between COVID-19 and AMR and which social science interventions are suggested to address this social relationship. We analysed 23 peer-reviewed articles published between 2019 and 2021. Results emphasize that changes in antibiotic prescription behaviour, misinformation, over-burdened health systems, financial hardship, environmental impact and gaps in governance might increase the improper access and use of antibiotics during the COVID-19 pandemic, increasing AMR. The identified social sciences transformation strategies include social engagement and sensitisation, misinformation control, health systems strengthening, improved infection prevention and control measures, environmental protection, and better antimicrobial stewardship and infectious diseases governance. The review emphasizes the importance of interdisciplinary research in addressing both AMR and COVID-19. Antimicrobial resistance (AMR) and COVID-19 have many similarities from a public health perspective. Both have a significant demographic and economic impact, both have a lack of medical treatment options and require behavioural changes to prevent their spread, and both need to be addressed through an interdisciplinary approach [Although more and more is known about the relationship between COVID-19 and AMR, most information is biomedical. Social sciences research on AMR remains low , even thwww.sonar-global.eu, accessed on 15 August 2021). In the meeting, we discussed the social dimensions of AMR to generate a curriculum for trainers (SPECIAL SOC AMR) [We define the social dimensions of AMR as the scalar relationship between people , systems , the environment  and policy-making and how they are affected by AMR, and vice versa . The anaSOC AMR) . Thus, tSOC AMR) .People and publics: portraying prescription practices, knowledge about antibiotics, behavioural practices of consumption and access to antibiotics, its impact on vulnerable groups, the social networks and relationships (including user-prescriber relationship), and the role of media on the prescribing and consumption of antibiotics during the pandemic.Systems and environments: framing the dynamics and interactions between AMR and the healthcare, pharmaceutical and food systems. It also includes the economic impact and the role of geography and movement on AMR.Institutions and policies: exploring the AMR policy-making from the local  to the national and the global level.Transformations: integrating the mitigation strategies advised and developed to tackle AMR during pandemic times, the social sciences’ role, and the resulting interventions. These transformations also cover the collaboration between social scientists and non-social scientists.The framework encompasses four main scales, complemented by an action-oriented focus on social science-based transformations: We searched for more recent studies regarding AMR and social sciences to adapt the framework to recent developments within the field. Two recent frameworks were found which address the social dimensions of AMR ,6; they,What evidence is available in peer-reviewed research that addresses the social dimensions of the relationship between AMR and COVID-19?What actions are suggested and generated to deal with these social dimensions?What is the role of the social sciences as a transformation agent during the COVID-19 pandemic?Using this framework, we have answered the following main questions: This review included papers published in peer-review journals between December 2019 and February 2021 in English and Spanish languages. This scoping review followed a methodological framework for scoping studies . BecauseWe searched index terms and selected keywords in MEDLINE, JStor and Google Scholar in February 2021. We limited all searches to full-text articles published in English and Spanish between 2019 and 2021. The search strategy included the following search terms:  AND  AND (“COVID 19” OR “SARS-CoV 2”). These keywords were selected to make sure to find articles that reflected on both antimicrobial resistance and COVID-19, while using a social sciences perspective.The article addresses both topics (AMR and COVID-19) throughout all its content;The article is published in a peer-review journal, including commentaries, review articles, editorials, and viewpoints;The content of the article includes a social sciences perspective.In line with the pre-set research questions in advance of the data extraction process, we determined a set of inclusion and exclusion criteria. These included:n = 20) were published expert opinions, viewpoints, commentaries or editorials. The remaining three (n = 3) presented empirical data, including qualitative methods, questionaries and time-series analysis.The total number of articles found during the initial search was 459 see . After rAll the information about the articles, including name, author, study characteristics and other relevant information following the analytical framework, were extracted using an Excel-based data extraction sheet, coded for all the framework categories. First, the data extraction process was calibrated by all the authors  based on a small sample. Then one author (LT) proceeded to extract the information and conduct the preliminary aggregation of results discussed by the team at several stages.This section provides all the detailed findings of this scoping review. A summary with the key findings can be seen in Literature reports great concern among healthcare workers regarding excessive prescription rates, the use of broad-spectrum antibiotics, prolonged antibiotic treatments without clinical justification, and inappropriate prescribing of antibiotics to patients infected with COVID-19 ,11,12. FWhile consultations via telehealth were used as a tool to treat patients and avoid their presence in the healthcare facilities and the possible spread of COVID-19 infection, its use may have increased antibiotic prescription due to the unavailability of syndromic diagnostic panels, and the challenge for clinicians to determine the nature of the illness, resulting in a potential increase of inappropriate prescriptions of antibiotics . In addiThe COVID-19 challenges combine with ongoing lack of knowledge about proper antibiotic use among health professionals, including a “just-in-case” prescription ,17,18, aDue to postponed healthcare-seeking behaviour during COVID-19 pandemic, antibiotic utilisation increased in response to the delayed presentations of acute infectious conditions, resulting in the prescription of antibiotics used for more severe and complex infections without bacterial confirmation . In addiAn increase in AMR strains is anticipated particularly in low-and-middle-income countries (LMIC) as a result of the disruption of antimicrobial stewardship programmes, limitations on laboratory capacity, and deficient regulation on antibiotic access . In otheSome AMR “positive” outcomes could be seen from the change in the social interaction between healthcare services and people. First, due to the disruption of many routine health services, patients are not receiving elective care, nor are antibiotics prescribed, overall reducing the AMR exposure . Second,Misinformation has been a primary driver in the misuse of antibiotics during the COVID-19 pandemic. In many countries, misinformation included a widespread emphasis by political leaders and media on the potential role of antimicrobials in the prevention and treatment of COVID-19 infection. A notable example was the suggested use of chloroquine  plus azithromycin  to treat COVID-19 disease. The initial media coverage of the COVID-19 outbreak highlighted that there was no “cure” or “treatment” for infection . Later oIn many countries, the politicisation and underestimation of the pandemic by public health stakeholders have turned politicians into a leading source of misinformation, increasing beliefs in conspiracy theories. Widespread misinformation and inconsistency of information have led to public confusion . For exaAnother issue identified is the early posting of preprints which has allowed the fast spread of scientific information of questionable quality, and, with this, the dissemination of inaccurate information among the general population ,23. FurtThe COVID-19 pandemic has had a huge impact on all health systems worldwide. The disruption in routine services such as immunisation, antibiotic treatment, laboratory services, and infectious diseases control and surveillance programmes (as for multi-drug-resistant tuberculosis and HIV) increases the misuse of antibiotics ,24. DisaThe impact of the COVID-19 pandemic on multi-drug-resistant (MDR) tuberculosis and HIV treatment and control may be seen as a result of the increase in the demands of health resources ,24. The The shortages in the health workforce and the limited laboratory capacity induced by the pandemic may delay the diagnosis of other infectious diseases and decrease the capacity to detect AMR microbes, elevating antibiotic use as a consequence . FurtherFor the last 30 years, the lack of development of new antibiotics—referred to as a “discovery void”—has been due to the paucity of research on antimicrobials ,28,29. DThe disruption produced by the COVID-19 pandemic may affect the production chains in several industrial processes, including production, distribution and delivery of vaccines and antimicrobials . FurtherThe global supply chains of antimicrobials and vaccines tend to be affected by the pandemic in several ways, including an increase of the cost due to travel restrictions and disruptions in trade between countries, the shortages of the workforce involved in the production of these vaccines (because of illness or relocation) and the development of protectionist policies (including the relocation of funding for COVID-19 supplies) . This diStrict hygiene and sanitation measures are one of the cornerstones in the prevention of COVID-19. Due to this, the use of biocidal agents for environmental and personal disinfection in healthcare and non-healthcare settings could contribute to the natural selection of drug-resistant bacteria, as these are now increasingly exposed to low levels of biocidal agents ,30. In aUnmeasured until now, the potentially high consumption of antibiotics from prescriptions and self-medication by the general population during the pandemic may lead to a high proportion of bioactive forms being excreted into the wastewater, from where they may enter into natural systems. This consequence might be more prevalent in countries where antibiotics can be easily obtained without a prescription . The preSeveral antimicrobial stewardship (AMS) programmes were established after releasing the Global Action Plan for Antimicrobial Resistance. Unfortunately, after the beginning of the COVID-19 pandemic, many of these programmes were reduced in terms of both workforce and stewardship activities , as COVID-19 was prioritised above AMR ,12,17,24In African countries, where the scarcity of resources allowed only a few countries to have antimicrobial stewardship programmes before the pandemic, all the resources for AMS-related activities were shifted towards the pandemic response . AccordiSurveillance data are likely to be inaccurate due to the unreported amounts of antimicrobials  administrated worldwide during the first moths of pandemic . As expeAntimicrobial resistance legislation showed delays for nationwide implementation, despite the call of the WHO Global Action Plan for Antimicrobial Resistance for an effective and fast implementation phase of the National Action Plans. In this way, due to the pandemic, many national plans and other initiatives against AMR are likely to be delayed, temporarily ceased or postponed . These dThe papers reviewed several social sciences strategies to tackle AMR during the COVID-19 pandemic. For many of the outlined issues, a synergy seems to be achievable while directing attention to the most critical roles social sciences can play in dealing with AMR in the context of the COVID-19 pandemic. A comprehensive overview of all suggested strategies is shown in the Fortunately, new measures implemented to decrease the spread of COVID-19 infections, such as hand washing, physical distancing and quarantining, became part of people’s everyday routine and can also be effective to reduce AMR infections and the spread of AMR microbes . In addiWith increasing awareness, the control of misinformation should be a priority, together with the generation of reliable and trustworthy information about COVID-19 and antimicrobial use, accessible for both healthcare workers and the general population ,18. For Another element highlighted is the strengthening of health systems needed to resist the pandemic’s impact. Investment in expanded capacity building of hospitals and laboratories to face the growing number of patients and the improvement of testing methods for COVID-19 to reduce antibiotic prescription will also help reduce the possibility of increased AMR ,28. FurtThe application of infection prevention and control (IPC) measures learned during the COVID-19 experience might be helpful as leverage to improve IPC measures and decrease AMR . The comThe use of biocides for disinfection to diminish the spread of COVID-19 has become one of the most important measures against the virus. To diminish the environmental impact that biocide products can have, community and healthcare institutions must be cautious with the amount and type of biocides used, as well as their disposal methods .Concerning antimicrobial stewardship programmes, it is crucial to evaluate the impact of the COVID-19 pandemic on antimicrobial use and to strengthen and prioritise the routine AMS programmes in order to prevent the inappropriate prescribing of antimicrobials in COVID-19 patients ,19,28. FThe establishment of a strengthened governance framework with national policies assuring essential public health programmes, improved collaboration between international health agencies and national governments, and transparent reporting and surveillance of AMR during and after COVID-19 times, can help to continue the fight against AMR despite the impact of the pandemic ,19,21,28Overall, the published articles and commentaries included in our scoping review showed a relative biomedical emphasis without much in-depth consideration of how the pandemic affects other spheres, such as social, cultural, economic, environmental and governance dimensions. Details on prescribing practices, health systems challenges, and stewardship programs from the perspective of health care workers are dominant in the articles reviewed. Two other recently published reviews on the same topic confirm this sentiment. A review by Knight et al. analysed how AMR emergence, transmission, and burden is affected by COVID-19 in terms of antimicrobial usage, infection prevention, and health system functioning . RodriguFocusing on the social sphere, we found that the pandemic brought changes in antibiotic prescription practices, antibiotic consumption and health-seeking behaviour. These findings are compatible with the reviewed findings of Knight et al., in so far as they describe how inappropriate prescribing and misdiagnosis, lack of another treatment, and the “desire to try all avenues” has led to the continuing prescription of antibiotics to treat COVID-19 infections by health professionals .In addition, we found that telemedicine might increase the over-prescription of antibiotics due to sub-optimal decision making by physicians. Knight et al. also refer to how telemedicine is not compatible with many settings globally, increasing the over-prescription of antibiotics . One stuAnother social science concern addressed in our scoping review is the impact on vulnerable populations, such as migrants and people living in LMIC during the pandemic. These populations may have a lack of access to antibiotics and infection prevention measures, as well as a higher prevalence of AMR strains in mobile populations and a higher risk of complications due to COVID-19 secondary infections. However, it remains unclear how the pandemic can affect the incidence of AMR in Black, Asian, and minority ethnic (BAME) groups. As studies have shown, socially marginalised populations have been worse affected by COVID-19 ,39,40,41The results also show the high impact of low public awareness on AMR and misinformation around antibiotic use as a preventive measure or treatment for COVID-19, which may have increased the consumption of antibiotics among the general population worldwide. From the HIV pandemic, we have learned how misinformation can lead to mistrust of governmental initiatives, and also how social media facilitates the spread of conspiracy theories creating a state of social paranoia . In the Our findings agree with the review by Knight et al. regarding the economic and environmental dimensions. With respect to economics, the impact of the COVID-19 pandemic on AMR was seen in the increased cost of antimicrobials, the shortages in the workforce and the development of protectionist policies affecting mainly LMICs. Knight et al. describe how financial hardship may affect access to antimicrobials and increase AMR infections and mortality , findingNational and global governance on AMR has been affected by the pandemic by delaying or ceasing the development and implementation of plans and programmes. In its review, Rodriguez-Baño et al. (2021) addressed the difficulty of enforcing regulations on antibiotic use, especially in settings where access to antibiotics without prescription is easy, and counterfeit medicines are openly available . In addiThe transformative social science strategies we found in the reviewed papers aim to decrease the spread of COVID-19 infection and its impact on AMR, and slow the pace of the foreseen consequences of AMR in all aspects. The strategies provided by the authors are mostly generic, lacking sophisticated social science analyses, and aligned with the mainly biomedical “mitigation strategies” and “key recommendations” suggested by Knight et al. and Rodriguez-Baño et al. ,35. ThisFinally, when zooming in on antimicrobial stewardship (AMS), several studies underline that this service could and should be maintained during pandemic times through targeted online training, use of online guidelines, the development of antimicrobial management protocols and integrating AMS activities in the pandemic response ,25,31. Despite the many findings, we note a serious shortage of original research on the social relationship between COVID-19 and AMR. With only three exceptions, this review identified mainly commentaries and editorials which generally only skimmed the surface of this complex relationship and provided little evidence. The two existing review articles on the relationship between COVID-19 and AMR are dominantly focused on biomedical challenges. It is possible that this apparent lack of scholarly studies from the social sciences may be the result of the short history of COVID-19. However, this lack of evidence is not as noticeable in the overall social science attention to COVID-19 with many published papers. However, this state of affairs does echo the findings of Frid-Nielsen, Rubin and Baekkeskov (2019) that there is a dearth of social science scholarship on AMR. Combined with the observed decrease in training and education on AMR due to COVID-19, we believe this is serious cause for concern if we want to address these complex interactions during the current or future epidemics.There is no shortage of future research topics addressing the social, economic, political and cultural dimensions based on the current findings alone: citizen or patient influences on provider treatments and prescriptions; self-medication; the influence on health seeking behaviour in the context of medical pluralism; the ambiguity of telemedicine; social impact on and lived experience of socially marginalised and vulnerable populations; the influence of misinformation, politicisation and even publication cultures on knowledge gaps; the impact of financial hardship on needed access to antibiotics; the need of policies addressing AMR governance during pandemics; etc. Once we look beyond our findings, even more areas of further research could be identified to look at the relationship between COVID-19 and AMR: the One Health interplay between the human, animal and environment in terms of relations, networks, systems and policies; governance issues, including political framing, policy transfer and practices  as well as the role of social scientists in the design, implementation and evaluation of the mitigation strategies brought forward in this scoping review and the impact of social science methods and research behind them.As for the practical implications of our findings, hospital managers should be aware of the need for development and better implementation of AMS policies and programmes, optimized telemedicine use and misinformation control even and maybe especially in times of COVID-19. This could improve the access to health services, availability, quality and affordability of health services, since adapting these services will result in a decrease in the need for and misuse of antimicrobials, and subsequently the healthcare costs even in overcrowded health services and high-pressure situations as during pandemic times. On the other hand, governments and international health agencies should strengthen and continue misinformation control on the lack of evidence of antibiotics used as treatment or prevention measure against COVID-19 as well as patient education on proper antimicrobial use. Moreover, they need to prepare and establish an action plan to prevent and deal with future pandemics that can affect and increase AMR worldwide.We hope this scoping review raises the interest of many social sciences researchers to include AMR in their area and biomedical researchers to understand the non-biomedical side of AMR and COVID-19. It is positive to see that there is some overlap in strategies that reduce the AMR and COVID-19 burden, showing us that by addressing COVID-19 correctly, we can affect and decrease AMR as well. In that way, interdisciplinary work will allow us to face both pandemics from all fronts, making it plausible to overcome these two global threats.


This study presents the design, implementation, and lessons learned from 2 fit-for-purpose online interprofessional faculty development programs for educational practice improvement in the health professions in Chile and the United Kingdom from 2018 to 2021. Both programs were designed to enhance teaching and learning practices in an interprofessional environment based on 4 pillars: professional diversity, egalitarianism, blended/online learning, and active learning strategies. A multidisciplinary mix of educators participated, showing similar results. The 3 main lessons learned were that the following factors facilitated an interprofessional environment: a professions-inclusive teaching style, a flexible learning climate, and interprofessional peer work. These lessons may be transferable to other programs seeking to enhance and support interprofessionality. Faculty development initiatives preparing educators for interprofessional practice should be an integral component of health professions education, as delivering these courses within professional silos is no longer justifiable. As the relevance of interprofessional education grows, an effective way of promoting interprofessonal education is to train the trainers in formal interprofessional settings. Well-designed interprofessional education (IPE) programs among learners in the health professions have been found to foster professional practice, teamwork, communication, and valuing the role of others in the healthcare team ,2. On thUnfortunately, most health professions faculty development programs oriented towards improving educational practices, covering aspects such as instructional design, teaching and learning effectiveness, and evaluation strategies, have been traditionally delivered within uniprofessional or multiprofessional settings, with no evidence-based justification . The conAn additional barrier for faculty development programs is the mode of delivery, as the majority are described as face-to-face, limiting attendance and engagement for busy clinical educators . This isThus, the aim of this paper was to present the design, implementation, and lessons learned from 2 fit-for-purpose online IPE faculty development programs for educational practice improvement in the health professions.This was not a human-subject study; therefore, neither receiving approval from the institutional review board nor obtaining informed consent was required.This study presents a narrative review of curriculum development.The clinical education program  at the University of East Anglia (UK) and the postgraduate diploma in health professions education at the University of the Andes (Chile) were designed to enhance teaching, learning, and assessment in an interprofessional learning environment. Both programs were designed to provide educators with the opportunity to understand the work ethos and professional values of colleagues from other health professions, along with experiencing interprofessional learning and collaborative work. Despite differences in geographical location, language, and culture, the courses exhibit numerous similarities. The interprofessional environment was built on 4 pillars: professional diversity, egalitarianism, blended learning, and active learning strategies. The learning experience was enhanced by the diversity of core academic teams contributing to teaching and by educators from different professional backgrounds and work experience enrolled in the programs, thus reinforcing a culture of interprofessional practice. Both programs were delivered in a way that created a climate within which the contributions of educators from different disciplines were acknowledged and valued.In terms of mode of delivery, the programs used blended and fully online learning to make the courses flexible and available off-campus, acknowledging the busy work schedules and needs of 21st-century health professionals who are unlikely to commit their time for fully face-to-face courses.Regarding teaching and learning strategies, the successful creation of learning communities in faculty development programs has been described as utilizing diverse educational methods grounded in adult learning theories, including experiential learning and peer learning, reflection, and feedback ,8. ThereThe design and delivery of the programs attracted a multidisciplinary mix of educators who participated and interacted with each other throughout the different cohorts. The educators and the core academic teams reported positive feedback across both programs’ internal quality assurance reports and from students’ evaluation surveys. For the postgraduate diploma in health professions education at the University of the Andes, 91% (n=111) of students expressed being overall very satisfied with the course and 86% (n=111) expressed being very satisfied with the course's collaborative and interactive features. For the clinical education program at the University of East Anglia, students’ qualitative comments reflected their satisfaction with the online learning environment, the approachability and presence of the core academic team, and the applicability and interactive nature of the learning activities. The clinical education program also received external validation in the form of being accredited for the Fellowship of the Higher Education Academy and Membership of the Academy of Medical Educators. This shows an alignment with the UK Professional Standards Framework for Teaching and Learning .Program leaders across both courses have jointly reflected and agreed that the creation of an interprofessional environment was mainly facilitated by 3 features: (1) a professions-inclusive teaching and facilitating style, (2) a flexible learning climate, and (3) interprofessional peer work. These constitute the main reflection points and lessons learned from the experience of planning and delivering these online IPE faculty development programs for educational practice improvement, which may well be transferable to other faculty development programs seeking to enhance and support the interprofessionality of their courses.Regarding a professions-inclusive teaching style, the interprofessional setting was facilitated by designing neutral online resources and not favoring any healthcare discipline over the others. Teaching and facilitation were conducted through fully online and blended learning activities, where the core academic teams delivered tutorials using a mix of examples, resources, applications, and guided readings of the literature from different health professions and focused on topics that provided common ground, such as clinical and student-centered teaching. The multidisciplinary core academic teams encouraged educators to appreciate each other’s backgrounds so that all participants gained the best experience from the courses. This constitutes an essential part of the delivery of the interprofessional hidden curriculum, as previous research has shown that learners report clinical faculty behaviors as influencing their own practices and, therefore, could promote interprofessional practices in their own educational settings ,11.Concerning the development of a flexible learning environment, it was essential to implement personalized tutorials, online office hour meetings, and catch-up recordings of sessions to support educators’ needs and personal interests. Furthermore, planning a reasonable workload that suited busy health professionals, flexible attendance and assignment submission, and balanced face-to-face/synchronous and asynchronous contact helped to support the engagement of a mix of clinicians with demanding schedules. These practices have been reported as desirable for online learning programs’ success, especially in light of the abrupt transition to online education as a result of the COVID-19 pandemic ,7.Finally, interprofessional peer work was conducted by employing on-campus and online discussions, debates, and teamwork, with a balance of professional membership in groups, and through different peer-assessment activities in which the core academic teams deliberately conducted interprofessional matching. As IPE involves learning ‘with, from and about’ and it is not just a mix of people acquiring the same knowledge or developing the same educational skills, programs should be designed to include abundant opportunities for interaction and exchange ,2. This The implementation of educational practices incorporating these lessons learned from both faculty development programs is expected to play a unique role in promoting IPE, as these lessons address the major barriers to teaching and learning described above at both the individual and organizational level, with the added value of providing educators with the knowledge and skills needed to design and facilitate IPE as part of their own educational role.Faculty development initiatives that seek to prepare educators for interprofessional learning and collaborative work should be an integral component of health professions education, as delivering these courses within professional silos is no longer justifiable. The successful implementation and delivery of these 2 programs, in culturally diverse settings and with similar experiences across both institutions, showed that IPE was facilitated by creating an environment conducive to collaborative working and learning from each other. Course developers carefully considered the pedagogical approaches used, the learning environment created, and the use of social learning to support communities of learning and interprofessional collaboration. This enabled educators from various professional backgrounds to learn together and from each other, with the support of a flexible and adaptable core academic team able to collaborate and continually learn about, from, and with each other. The latter was possible partly due to the values and practices brought by the multidisciplinary teaching teams and the programs’ structure. Future research should explore and evaluate the perception and effectiveness of these interprofessional settings for educators, along with potential transferability to their teaching practices. As the relevance of IPE grows, an effective way of promoting it is to train the trainers in formal and explicit interprofessional settings.


The United States Centers for Disease Control and Prevention and the World Health Organization broadly categorize mass gathering events as high risk for amplification of coronavirus disease 2019 (COVID-19) spread in a community due to the nature of respiratory diseases and the transmission dynamics. However, various measures and modifications can be put in place to limit or reduce the risk of further spread of COVID-19 for the mass gathering. During this pandemic, the Johns Hopkins University Center for Health Security produced a risk assessment and mitigation tool for decision-makers to assess SARS-CoV-2 transmission risks that may arise as organizations and businesses hold mass gatherings or increase business operations: The JHU Operational Toolkit for Businesses Considering Reopening or Expanding Operations in COVID-19 (Toolkit). This article describes the deployment of a data-informed, risk-reduction strategy that protects local communities, preserves local health-care capacity, and supports democratic processes through the safe execution of the Republican National Convention in Charlotte, North Carolina. The successful use of the Toolkit and the lessons learned from this experience are applicable in a wide range of public health settings, including school reopening, expansion of public services, and even resumption of health-care delivery. The standard approach to Emergency Preparedness is to Prevent, Protect, Mitigate, Respond, and Recover. However, in times of novel or emerging threats, evidence is often scarce and data are frequently so raw as to limit the ability to make objective recommendations. In these times, it is critical to draw on expert opinion and past experience to create adaptive, objective, decision-making tools.1 Pandemic models had large margins of error limiting our ability to predict community disease prevalence or anticipated hospital resource use.3 Existing public health guidance provided only broad, population-based recommendations that did not have robust supporting data. And, there existed no regimented process by which to consolidate the impact of implementing multiple mitigation strategies. In short, existing guidance provided little objective data to conduct objective risk reduction.Our team was tasked with creating an operational medical plan for the Republican National Convention (RNC), a designated National Special Security Event (NSSE) and mass gathering, during the highly infectious novel COVID-19 pandemic. Planning a mass gathering event during a national state of emergency related to the COVID-19 pandemic presented several complex health, medical, operational, public policy, economic, and political risks. We faced a totally novel, poorly understood virus with unclear transmission dynamics.We identified The Johns Hopkins University (JHU) Operational Toolkit (Toolkit) as an objective risk assessment process developed by Global Health and Infectious Disease experts. This toolkit underwent an internal validation process by the Johns Hopkins Center for Health Security to ensure the weighting of risks and mitigation measures were both accurate and comprehensive. The toolkit was then submitted to field tests with a select group of business leaders, allowing for a review process before its publication. Furthermore, our team determined that each individual component and the collective process was consistent with lessons learned from prior pandemics and aligned with current public health guidance. With this understanding, we applied the Toolkit to a complex mass gathering with national security, political, and public policy implications.Risk cannot be eliminated, but it can be mitigated. Robust risk assessment and management tools can reduce risk of disease spread during mass gathering events. The foundation of any COVID-19 mitigation strategy requires understanding the underlying hazard, identifying potential amplifying risks, articulating actions that reduce risk, and creating an iterative process for modifying planning as new recommendations emerge. In addition, for political, religious, or social gatherings of high importance, risk perception, and risk tolerance are influential subjective planning modifiers. As such, planners must incorporate risk communication strategies into the management process to ensure leaders and participants can make an accurate assessment of their personal risks, understand the measures that are being taken operationally to reduce risk, and understand the measures that individuals can take to reduce risk.5 During this pandemic, the JHU Center for Health Security developed a novel risk assessment and mitigation tool for decision-makers to assess SARS-CoV-2 transmission risks that may arise as organizations and businesses hold mass gatherings or increase business operations.6 The JHU development team also contributed to numerous WHO risk assessments designed for broader population health application and specific mass gathering events. During the planning for the RNC, the JHU product was the only publically available toolkit designed specifically for businesses or mass gatherings, and most applicable for the RNC context. The RNC COVID-19 Cross Functional Team (CFT) used the JHU Operational Toolkit for Businesses Considering Reopening or Expanding Operations in COVID-19 (Toolkit) to aid in medical and public health planning for the 2020 RNC.7The United States Centers for Disease Control and Prevention (CDC) and the World Health Organization broadly categorize mass gathering events as high risk for amplification of COVID-19 spread in a community due to the nature of respiratory diseases and the transmission dynamics.The Toolkit quantifies the likelihood that a business or event will amplify community transmission of COVID-19. It also provides a regimented process for identifying risk modification and mitigation measures that organizations can implement to determine a final risk score for the business in light of their inherent risks related to their operations and their efforts to reduce such risks . As partThe initial assessment identifies the inherent risk of an event without intervention and determines the risk score . A critiThe CFT unanimously assessed that the NSSE posed a HIGH risk of COVID-19 amplification in the community.The modification assessment calculates an updated risk score based on changes to event operations . The JHUThe Toolkit modification scores range from low  to high . From a planning standpoint, a HIGH score is desired to allow for greater risk reduction. Based upon initial RNC planning restrictions, the CFT unanimously assessed that the initial modification score was LOWThe Toolkit provides 5 overall scores, ranging from Very Low to Very High. No numerical weight is attributed to these scores as it is impossible to precisely quantify the risk of a business or event due to numerous and constantly changing variables, such as individual risks of participants, epidemiological context, and compliance of mitigation measures. However, a score of VERY HIGH can only be achieved if the original risk of the business or event is considered high and little to no modifications are in place to reduce the risk. The CFT determined that the RNC was HIGH risk with a LOW modification score. As a result, the Toolkit assessed the overall risk of COVID-19 amplification in the community as VERY HIGH.The previous steps focus on the health risks at an operational level and the event modification measures that could reduce overall risk. The mitigation measures focus on decreasing individual risk by promoting personal safety measures. While the mitigation measures do not contribute to the overall score, they should be considered as the foundational element on which planners build a risk and safety strategy. The CFT reviewed the Toolkit mitigation measures and integrated them with an expanded set of additional potential options, such as robust pre-event and daily COVID-19 testing, digital contact tracing technology, and advanced environmental engineering . The absence of data for each of these more aggressive interventions limited the CFT’s ability to calculate a quantifiable risk reduction value or determine a cost-benefit analysis of the recommendations.The CFT added a fifth stage to allow for a more adaptive planning process. In Stage 5, the CFT eliminated the original planning restrictions and completed Stage 2 in an iterative, in-person session. The CFT provided event planners with multiple courses of action that articulated baseline COVID-19 transmission risk and various interventions to reduce overall risk. These recommendations allowed event planners to have an informed conversation about risk tolerance and develop a realistic policy surrounding the viability holding the RNC mass gathering event.Despite the high-profile political nature of the RNC, there were very few hurdles to using the Toolkit. A key to this success was an early iterative process where CFT members articulated individual and agency planning assumptions, consolidated known data surrounding COVID-19 transmission, and created a transparent communication process.Operational and Political ConstraintsThe 3 main general planning hurdles that the Toolkit helped to overcome were:Variable Definitions of RiskThe initial, non-negotiable planning assumptions included no mandatory masking, no restrictions on the numbers of participants, and no mandated physical distancing. Every member of the planning team understood that these requirements ran counter to CDC recommendations and would preclude a safe convention. The scientific rigor of using an objective risk assessment tool and engaging nonmedical professionals, such as engineers and human-centered design experts, was critical for creating an unassailable risk assessment process. The fact that the team used an external assessment tool and found universal agreement on overall risk score was vital for communicating recommendations to the RNC leadership team.Quantifying the Financial Cost of Risk ReductionThe CFT began the process by identifying the categories of risk as individual health, community health, economic impact of resurgence or event cancelation, political, and social disruption. Each category of risk is necessarily interconnected. For some, such as economic or political risk, very little science is available to guide decision-making. Based upon open-source information and current events, the CFT unanimously agreed that COVID-19 amplification would create high risk of economic, political, and social disruption. With this agreement, the CFT was able to focus on using the Toolkit to quantify individual and community health risk.One of the great balancing acts of risk mitigation is aligning the cost of an intervention with the relative impact of that intervention. In this case, reducing the transmission of COVID-19 was paramount and linked to the health, economic, social, and political risk calculations. There was no way to quantify the incremental risk reduction for each advanced intervention. Fortunately, robust funding was available.The deployment of the JHU Toolkit was an operational and quality assurance decision. Publically reported data revealed that using the Toolkit allowed the team to identify four (4) COVID-19-positive individuals before entry into the NSSE and engagement with other attendees. Since the conclusion of the RNC, there are no reports of COVID-19 transmission from the RNC.To our knowledge, this was the first large-scale application of the Toolkit. The post-hoc analysis produced several operational recommendations for successful use of the Toolkit.The first consideration is ensuring multi-specialty representation in the cross-functional team to develop the most comprehensive risk assessment. Diverse representation, including nonmedical personnel, facilitates a more dynamic iterative process, reduces professional blind spots, and strengthens validation of recommendations.The second recommendation is to develop a process for acquisition, analysis, and dissemination of data. During emerging threats, there is often so much data that analysis and transformation of data to information is paralyzed. During periods like these, focused empiricism is a useful strategy, enabling rapid guideline and process development that can be tested and evolved in near real time. The challenge lies in determining valid sources of information and vetting the information while remaining open to nontraditional sources of data. One example was the emerging data on novel air filtration systems. The traditional medical literature had little information on these systems. Fortunately, the CFT engineer had both deep experience with air filtration, knowledge of the cutting-edge research on the topic, and most importantly, understood the valid sources of published data.The third key to success is to conduct familiarization training on toolkit, then ensure anonymous completion of the Toolkit to reduce any potential social influence. The team leader should consolidate CFT responses and review for consensus. The entire team should then determine whether to revise assumptions. Critically, this team ran multiple trials of the toolkit with a variety of initial planning assumptions. This allowed the team to offer leadership multiple courses of action with objective risk profiles.The multi-specialty application of the Toolkit demonstrated a novel process to objectively assess initial risk, evaluate impact of interventions, and rationally advise nonmedical decision-makers. The lessons from this planning process can inform public policy-makers determining re-opening strategies for businesses, schools, and health systems. There are several critical observations. First, the planning team must acknowledge that risk can be mitigated not eliminated. Second, the team must agree upon the definition and core components of the risk to be addressed. Third, building the correct team with broad stakeholder representation is critical to maximize information acquisition, ensure unity of purpose, maintain agreement on planning assumptions, and communicate cohesive recommendations. Finally, during emerging threats, evidence often challenges previous assumptions or recommendations. The planning process must allow for a continuous assessment and refinement of the mass gathering safety plan to integrate new evidence and data.


Multicellular life evolved from simple unicellular organisms that could replicate indefinitely, being essentially ageless. At this point, life split into two fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma, which ages and dies. In this review, we describe the germline as clock-free and the soma as clock-bound and discuss aging with respect to three DNA-based cellular clocks . The ticking of these clocks corresponds to the stepwise progressive limitation of growth and regeneration of somatic cells that we term somatic restriction. Somatic restriction acts in opposition to strategies that ensure continued germline replication and regeneration. We thus consider the plasticity of aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. We further describe how germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backward. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all. Whether or not aging is programmed or is the result of accumulated damage has been the subject of debate for many decades. Early twentieth-century theories favoring programming proposed that aging was a consequence of differentiation as put forth by Minot  or factoPandorina morum consists of a simple ball of identical cells , the gene encoding the catalytic component of the enzyme responsible for telomere maintenance, and by showing that forced expression of hTERT prevented senescence, thus immortalizing the cells . In . In 8].  markers . Indeed, markers . We prop the EFT . The rapInterestingly, the DNAm clock ticks faster following a logarithmic relationship up to the AT and linear relationship to chronological age through adulthood . The telLIN28 (a pre-EFT marker and reprogramming factor) alter the timing of developmental transitions and thus potentially impact regenerative capacity and lifespan. Metamorphosis is an example of developmental processes occurring at various times during the life history as it always involves extensive remodeling of organs and tissues at the histological level, including the growth of new organs and limbs . A. ALIN28,Initial attempts at in vivo reprogramming using 4-factor (OKSM) reprogramming were not encouraging because they resulted in extensive tumor formation ,165. HowThe prospect of reversing organismic aging could potentially reduce or eliminate many age-associated degenerative diseases such as heart disease, cancer, diabetes, osteoporosis, sarcopenia, neurodegenerative disease, and skin aging. Thus, rejuvenation therapies could potentially alleviate many of the social and economic costs that we face globally because of an ever-increasing demographic shift to an older population. However, critical barriers remain to develop rejuvenating therapies that involve germline factor reprogramming. For example, more studies are needed on naturally aged experimental animals to determine the effect of such treatments on lifespan and health span. Moreover, careful control of the timing and dosage of reprogramming factors will need to be developed to minimize the risk of tumor formation. The further development of epigenetic aging clocks in experimental animals and tissue culture will be helpful for screening reprogramming agents and delivery strategies. Strategies for transient expression of reprogramming factors include AAV mediated inducible gene delivery, RNA transfer, and small molecules ,169,170.In this review, we have described three cellular clocks that bind somatic cells to time and compared this with the immortal germline, which in its capacity for indefinite renewal, is uncoupled from time. We have also discussed the plasticity of the aging clocks that tick faster in accelerated aging or slower in decelerated aging. The initiation of the DNAm aging clock, the telomeric clock, and perhaps other clocks at the beginning of development suggests an intimate relationship between development and aging. Indeed, the adaptation of developmental clock rate to environmental pressure could account for the wide variation in lifespan observed between species. For example, humans and mole-rats exhibit neoteny, where slowing the rate of development correlates with an extension of lifespan. The application of germline strategies in somatic stem cells has resulted in the remarkable regenerative capacity of lower life forms that are capable of indefinite lifespans, such as sponges, planarians, and hydra. This regenerative capacity has become increasingly restricted as more complex life forms evolved, being confined to the pre-EFT period in mammals. However, retention of extensive capacity for regeneration is observed in lower vertebrates, including fishes, amphibians, and reptiles, which also exhibit remarkable phenotypic plasticity in their capacity for metamorphosis and in certain cases of remarkable reversals of developmental stage and sexual development. Finally, reprogramming using germline factors can uncover a similar but latent phenotypic plasticity in mammals by reverting both the developmental state and cellular age. Indeed, both natural phenotypic plasticity in the blue wrasse and partial reprogramming involve the repression of DNA methyl transferases (DNMT) and induction of demethylases (TET) which, by a yet-to-be-determined mechanism, may enable the DNAm clock to tick backward. The discovery that partial reprogramming can reverse the aging clock without permanent alteration of cellular identity has led to initial studies that demonstrate the potential to reverse organismic aging. Although there are many challenges ahead, our current understanding of cellular clocks and our ability to reprogram them using germline factors opens the door to many promising therapeutic approaches to slowing down, preventing, or reversing aging itself and thus treating the many age-related diseases that burden society. Indeed, if these approaches can be made practical and scalable, we may find ourselves in a future in which we have no time to age.


The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways, which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possibly due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed and, at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided. A breakthrough in human reproductive medicine was the birth of world’s first in vitro fertilized (IVF) baby, Louise Joy Brown, who was born in 1978. Today, there is widespread use of various assisted reproductive technologies. It is generally accepted that human oocytes have reduced developmental competence and increased aneuploidy with advancing maternal age. Therefore, the outstanding need for adequate biomarkers of oocyte developmental competence has become a high priority for research and fertility clinics around the globe since women’s first attempt at childbearing has increased in the last three decades . The proThe unique gating and permeability of gap-junction channels is defined by their Connexin alignment ,7, wherePANX1 . It. ItGJA1)cription . Granulocription ,41. The ncreased . Studiese (PCOS) . This fes needed .Oocyte maturation reflects the process which is mandatory for the mammalian female gamete to be fertilized by the male gamete . Oocyte PANX1 expression in human oocytes and eight-cell embryos is higher in comparison with cells of somatic tissues [PANX1 were detected, were recently analyzed . A different PANX1 gene mutation has been identified in each family. All four mutations  . It is wIt was found that the interruption of gap-junctional communication within COCs is gonadotropin-dependent and decreases after germinal vesicle break-down (GVBD). The resumption of meiosis was associated with the reduction of Cx43 protein level in porcine and rat cumulus cells ,60,62. ACaenorhabditis elegans, indicating the role of innexins (gap junction proteins in invertebrates) [In the study of Zhou and co-workers , removalebrates) , particuebrates) ,72. Cumuebrates) . It was ebrates) .Connexins are known to play an important role in a variety of biological processes and disturbances in their functioning may cause different pathologies. Several disorders in humans were classified as related to Connexin mutations (reviewed in ). The moAs mentioned previously, the main role of pannexin channels is ATP transfer from the intra- into the extracellular environment in response to activation by calcium or purinergic receptors . PannexiPannexins and Connexins act as essential channel proteins enabling the communication in oocytes to support the processes of oogenesis, folliculogenesis, maturation, fertilization, and embryonic development. As oocytes age, their number, quality, and fertilization outcomes decrease. An increasing number of studies showed that the communication as well as the exchange of molecules and ions via the Pannexin and Connexin pore-forming hemichannels and gap-junctions, are a critical determinant of oocyte developmental competence and fitness. This sparked interest within the reproductive molecular medicine field to better understand how both earlier mentioned channel proteins contribute to the determination of the competence related to oocytes’ growth, development inside of a follicle, and oocytes’ ability to be fertilized. Once the impact of Pannexins and Connexin will be fully elucidated, there will be the possibility of new technologies or treatments to modulate or restore oocyte viability. Technical advances in the three past decades have led to increasingly sophisticated assisted reproductive technologies. Nevertheless, the safe and ethical modulation of channel proteins and oocyte quality requires more comprehensive understanding of their interplay. Taken together, elucidating the molecular mechanisms that contribute to the maturation and fertilization of oocytes, the unique role of Pannexins and Connexins herein, and careful identification of therapeutic targets to improve their function and thereby oocyte health, can contribute to new strategies to enhance and prolong reproductive fitness. Importantly though, our review aimed to stimulate new research ideas on this interesting topic of cell to cell communication, which could aid in the design of novel studies and animal models.


There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates the acute and chronic behavioral responses to addictive drugs. Ghrelin has been shown to activate reward-related behaviors. Moreover, ghrelin enhances, whereas pharmacological or genetic suppression of the ghrelin receptor attenuates the responses to various addictive drugs. Genetic studies and experimental clinical studies further support the associations between ghrelin and addiction processes. Further studies should explore the mechanisms modulating the ability of appetite-regulatory peptides to reduce addiction, and the effects of combination therapies or different diets on substance use are warranted. In summary, these studies provide evidence that appetite-regulatory peptides modulate reward and addiction processes, and deserve to be investigated as potential treatment target for addiction. Addiction/dependence is often referred to as a chronic, relapsing brain disorder which, depending on the drug used, can be divided into alcohol use disorder (AUD) and substance use disorders . These different terms are used interchangeably throughout this overview. In general, addiction develops after the initial acute exposure to an addictive drug followed by more chronic use. It develops as a result of recurring cycles of binge/intoxication followed by withdrawal/negative affect followed by preoccupation/anticipation until the next drug intake session Koob, . The detA diagnosis of AUD/SUD includes behaviors like loss of control over intake, craving and impaired cognitive functioning, and impaired functions like negative social consequences, physical tolerance, and withdrawal symptoms  and the orexigenic peptide ghrelin play dominant roles , which consists of one of two calcitonin receptors (CTRa and CTRb) and one of three receptor activity-modifying proteins (RAMP1-3). The CTRa shifts the selectivity of the AMYR toward amylin over calcitonin. The CTRa/RAMP1-3 protein complex is therefore thought to mediate the physiological properties of amylin. As amylin has a short half-life in blood, other amylinergic compounds are used in research. This includes salmon calcitonin (sCT), an agonist for both the AMYR and CTR   and mesolimbic dopamine release , an intePart of the process of transition from the acute non-addicted phase to chronic use is the consolidation of memories of reward gained from the drug that will drive behavior when opportunities for drug consumption arise in the future. In the memory CPP paradigm, systemic Ex-4 does decrease alcohol reward memory , induces the dopaminergic reward pathway and dopamine release in NAc in rodents  reduces the operant self-administration of alcohol in male rats , Arvid Carlsson foundation, The Swedish brain foundation, and LUA/ALF (Grant No. 148251) from the Sahlgrenska University Hospital. The funding source had no involvement in data collection, analysis and interpretation of data, in the writing of the report; and in the decision to submit the article for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The innate immune system is the oldest protection strategy that is conserved across all organisms. Although having an unspecific action, it is the first and fastest defense mechanism against pathogens. Development of predominantly the adaptive immune system takes place after birth. However, some key components of the innate immune system evolve during the prenatal period of life, which endows the newborn with the ability to mount an immune response against pathogenic invaders directly after birth. Undoubtedly, the crosstalk between maternal immune cells, antibodies, dietary antigens, and microbial metabolites originating from the maternal microbiota are the key players in preparing the neonate’s immunity to the outer world. Birth represents the biggest substantial environmental change in life, where the newborn leaves the protective amniotic sac and is exposed for the first time to a countless variety of microbes. Colonization of all body surfaces commences, including skin, lung, and gastrointestinal tract, leading to the establishment of the commensal microbiota and the maturation of the newborn immune system, and hence lifelong health. Pregnancy, birth, and the consumption of breast milk shape the immune development in coordination with maternal and newborn microbiota. Discrepancies in these fine-tuned microbiota interactions during each developmental stage can have long-term effects on disease susceptibility, such as metabolic syndrome, childhood asthma, or autoimmune type 1 diabetes. In this review, we will give an overview of the recent studies by discussing the multifaceted emergence of the newborn innate immune development in line with the importance of maternal and early life microbiota exposure and breast milk intake. Our understanding of how microbial communities can influence health and disease of their host has significantly improved in the last decades. This boost of scientific discoveries in the microbiome field has been facilitated mainly by the availability and affordability of different techniques, such as gnotobiology, next-generation sequencing (NGS), and metatranscriptomics. Evidence linking the microbiome with the pathophysiology of diseases, for instance, such as inflammatory bowel diseases (IBD) –3, canceEnterococcacae, Clostridiaceae, Lactobacillaceae, Bifidobacteriaceae, and Streptococcaceae. In the first months of life, Bifidobacteriaceae thrive since they feed on oligosaccharides, which are highly abundant in maternal milk, the main energy source of newborn babies. During weaning, when solid food is introduced, the abundance of Bifidobacteriaceae decreases, while Bacteroides, Ruminococcus, and Clostridium become more prevalent . Different hematopoietic cells of the innate immune system can be found in the mucosa including mononuclear phagocytes, intestinal macrophages, intestinal dendritic cells (DCs), eosinophils, mast cells, and innate lymphoid cells (ILCs) Figure 1via fecal transplantation – were of limited success, one reason why much effort is taken to further dissect the causal mechanisms of how such early events can lead to later disease onset. The microbiota certainly is a key player during this window of opportunity. Early colonization during this critical time window by a microbial consortium is crucial for the proper development of the immune system and has been demonstrated in various mouse models  in the offspring and was irreversible after weaning  mediated by acetate resulting in higher gene transcription of Foxp3 in Tregs. They further lowered frequencies of eosinophils and macrophages in the blood and bronchoalveolar lavage fluid as well as serum IgE levels of the offspring  or circulating in the hospital   , 112. Mobacteria . Additiobacteria , 113–116ntangled . In a rentangled . They coposition , 119.via C-section had stunted levels of Tregs in the spleen and MLNs and reduced systemic IL-10 levels until adulthood  is alarming. Not only because NRCS-A is exceptionally disseminating in NICUs, but also due to its probable relevance in LOS pathogenesis  cell differentiation through TNF-α signaling. This process is well-developed in adult mice, in contrast to younger mice, where the threshold for sensitization is decreased. Thus, young mice are more prone to develop asthmatic inflammation due to the weakened response of DCs towards microbial low-dose LPS stimuli, which then insufficiently suppress Th2 cell development -induced colitis later in life. Essentially, blocking GAPs before weaning inhibited Treg development in the colonic lamina propria and resulted in an impaired establishment of early life bacterial-induced tolerance , which is important for stem cell proliferation and regeneration after epithelial damage in the neonatal colon (Bifidobacterium breve strain (UCC2003) was able to boost epithelial regeneration by supporting the stem cell niche and increasing epithelial differentiation in the small intestine. Additionally, upregulation of integrins, tight-junction molecules, and increased mucus production in pups after Bifidobacterium breve treatment supported its role in strengthening the physical intestinal barrier , have immune and antimicrobial properties , and possess the ability to promote growth ). Among all, α-lactalbumin, casein, lysozyme, and sIgA are the most abundant ones , 196. Aseostasis .Generally, milk-derived proteins are considered essential contributors to the first line defense strategy. For instance, lactoferrin, which is part of the innate immune system, has important antimicrobial and immunomodulatory properties that support health and prevent disorders in the neonate . It elicCytokines are essential contributors to the immune response, which stimulate the differentiation and maturation of various immune cells. The cytokine TGF-β is found in breast milk and is ingested by the neonate, where it stimulates mucosal IgA production and inhibits the synthesis of pro-inflammatory cytokines . TGF-β sLast, milk contains EGF, which was shown to prevent the weaning reaction . This fiin vitro studies revealed the uptake of milk-derived exosomes by human macrophages. Nevertheless, their role upon cellular absorption remains to be elucidated  were treated with milk-derived exosomes and stimulated nditions . This coThe presence of immune cells in breast milk, including neutrophils, macrophages, and lymphocytes, is well established. Many animal studies demonstrated the transfer of those maternal cells to the neonate, and it is assumed that they contribute to the maturation of the offspring innate immune system , 242–244Myeloid-derived suppressor cells (MDSCs) have repressing effects on other immune cells of the innate and adaptive immune system, such as monocytes and T cells. There are two main subsets of MDSCs, monocytic MDSCs (MO-MDSCs) and granulocytic MDSCs (GR-MDSCs) . RemarkaA reduction in the frequency of IL-13 producing cells in human milk has been associated with an increased incidence of atopic dermatitis in newborns . This cyin vivo study using wild-type pups that were fostered by GFP+ expressing transgenic mice detected breast milk-derived stem cells in the blood as well as in the brain of the suckling pups, confirming the transfer of milk-derived cells to the offspring. Those cells differentiated into neuronal and glial cells in the pup’s brain, indicating that they play a role in the development of the offspring’s nervous system  or years (human) after birth. Last, we have tried to give an extensive overview on classical and non-classical immunological compounds present in breast milk and how those affect innate immune maturation in the offspring.While evidence for an influence of the maternal microbiota, the neonate’s own microbiota or the breast milk during this critical time window is undoubtedly increasing, many aspects remain to be understood: What are the molecular mechanisms underlying the described phenotypes? How is long-term persistence into adulthood achieved? Why does the window of opportunity close around weaning, could it be reopened later in life, and how? To which extent does the maternal microbiota influence the composition of breast milk and thus immune development in the offspring? Finally, how do the maternal diet and later the offspring’s diet, and additional factors  interact with the microbiota and mutually or independently influence immune maturation in the growing organism?With our current and future research projects, we aim to complement the understanding of the window of opportunity and to use this knowledge in a preventive or therapeutic setting to improve human health from the neonatal age on.CK, NF, SC, and SG-V wrote the manuscript and generated figures. All authors contributed to the article and approved the submitted version.This work was funded through a Peter Hans Hofschneider Professorship provided by the Stiftung Molekulare Biomedizin to SG-V. CK was funded through a European Research Council Starting Grant  provided to Andrew Macpherson. SC received an MD-PhD scholarship of the Swiss National Science Foundation (323530_199385).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


However, the impact of cancer does not end with treatment. The objectives of this review are to (1) provide a broad overview of the supportive care interventions and models of care that have been researched to support Canadian post-treatment cancer survivors; and (2) analyze how these supportive care interventions and/or care models align with the practice recommendations put forth by Cancer Care Ontario (CCO) and the Canadian Association of Psychosocial Oncology/Canadian Partnership Against Cancer (CAPO/CPAC). (2) Methods: An electronic search was completed in MEDLINE, Embase, PsycINFO, and CINAHL in January 2021. Included studies described supportive care interventions or models of care utilized by adult Canadian cancer survivors. (3) Results: Forty-two articles were included. Survivors utilized a multitude of supportive care interventions, with peer support and physical activity programs being most frequently cited. Four models of follow-up care were identified: primary care, oncology care, shared-care, and transition clinics. The supportive care interventions and models of care variably aligned with the recommendations set by CCO and CAPO/CPAC. The most commonly followed recommendation was the promotion of self-management and quality resources for patients. (4) Conclusions: Results indicate an inconsistency in access to supportive care interventions and the delivery of survivorship care for cancer survivors across Canada. Current efforts are being made to implement the recommendations by CCO and CAPO/CPAC; however, provision of these guidelines remains varied. Currently, it is projected that one in two Canadians will be diagnosed with cancer in their lifetime . FortunaWith the increasing incidence and survival rates of cancer, the demand for cancer survivorship care has increased . HoweverIn 2011, the Canadian Association of Psychosocial Oncology (CAPO) and the Canadian Partnership Against Cancer (CPAC) recognized the need for organized cancer survivorship care in Canada and published the Pan-Canadian Guideline on Organization and Structure of Survivorship Services and Psychosocial-Supportive Care Practices for Adult Cancer Survivors . This guEven with these evidence-based guidelines from CCO and CAPO/CPAC, which possess many commonalities in their recommendations ,6, thereThe aim of this scoping review is to provide a description of the current supportive care interventions and transitional care models studied in the context of Canadian cancer survivors and determine how they align with current Canadian guidelines. This will thus illustrate the current landscape of evidence-based post-treatment cancer survivorship care in Canada. Thus, the objectives of this review are (1) to provide a broad overview of the supportive care interventions and models of transitional care that have been researched to support Canadian post-treatment cancer survivors; and (2) to analyze how these supportive care interventions and/or transitional care models align with the practice recommendations by CCO and CAPO/CPAC. The answers to these objectives will illuminate clinical and research areas needed for future post-treatment survivorship care in Canada, as to date, there are no such reviews describing the provision of evidence-based survivorship care in the Canadian context.osf.io/aqhxn/, access on 18 August 2020).The Joanna Briggs Institute scoping review framework was utilized as the guiding methodology to provide a broad overview on what is known about the programs, resources, and models of care to support post-treatment cancer survivors in Canada . To enhaThe population of interest for this review was adult (≥18-years-old) cancer survivors who had completed cancer treatment. The concepts of interest were the supportive care interventions  and/or models of care  that are utilized by cancer survivors as they transition into survivorship care. In identifying these concepts, methods of how the physical and psychosocial supportive care needs of cancer survivors are currently being met in Canada were described. Additionally, this review only included Canadian articles, so as to provide an overview of current cancer survivorship care within the Canadian context specifically. Included material was limited to full text, English language, primary research articles. There was no limit placed on the date of publication to provide a wide image of survivorship care in Canada. This review excluded studies where post-treatment data were not clearly extractable, such as in studies that included both individuals undergoing treatment and those who had completed treatment.A literature search was completed in MEDLINE, Embase, and PsycINFO databases on the Ovid platform, as well as the Cumulative Index of Nursing and Allied Health Literature (CINAHL) on the EBSCOhost platform. Search strategies were adapted to meet the needs of each individual database. The search was completed in June 2020 and updated in January 2021. The search strategy utilized in Ovid MEDLINE is displayed in Following the search, the identified research articles were imported into the reviewing software, Covidence . Two revEach included article was categorized based on whether the extracted content was describing a supportive care intervention or transitional model of care. Thereafter, a thematic grouping of articles within each categorization was conducted to address the first objective of the review.The CCO  and CAPOA total of 732 articles were identified as eligible for screening . After tn = 20) were published since 2003. Most  studies used a quantitative design , 15 (36%) employed qualitative methods, and mixed or multiple methods were utilized in the remaining seven studies (17%). Most studies were completed in Ontario  or Alberta , and another eight (19%) were pan-Canadian or involved multiple provinces. None of the studies explicitly reported on populations from Saskatchewan or the Territories. The most commonly studied cancer survivor population was breast cancer , followed by multiple cancers . One study did not report on the type of cancer. Of the included articles, 22 (52%) were published within the last five years (2016 or later), and the remaining papers ; 3 . T,6. T4,6]This scoping review provides a description of the current supportive care interventions and transitional care models studied in the context of Canadian cancer survivors. It presents an overview of how these interventions align with current Canadian guidelines, thus illustrating the current landscape of evidence-based post-treatment cancer survivorship care in Canada. However, current follow-up care recommendations by CCO and CAPO/CPAC have been met to varying degrees, and implementation is inconsistent from one region to the next. By describing the current landscape of survivorship care, we have identified current gaps and strengths in the provision of cancer survivorship care in Canada, as well as areas for future research. Within this review four models of care were researched in Canada. However, survivors reported a preference for receiving follow-up care from their oncologist at the cancer centre ,25, as tWhile not frequently discussed in the articles included in this review, telehealth is becoming a common care delivery method in the wake of the COVID-19 pandemic. Conversion to telehealth has been shown to increase participation in programs, as this delivery method makes them accessible from home , and redThis review identifies a number of supportive care interventions utilized by cancer survivors. However, cancer survivors report being largely unaware of resources or programs that are available to them ,40,41,42Although most CCO  and CAPOThis review highlights that survivors living in rural settings do not have the same access to care as their metropolitan counterparts ,28. IndeWith one in two individuals expected to be diagnosed with and survive cancer in their lifetime , it is iThe first of these was recommendation B-2, which promotes the use of health behaviour change theories to influence the adoption of healthy lifestyle behaviours in cancer survivors . It is nThe appropriate sharing of surveillance test results with the survivor (CCO-11)  was anotThe last recommendation that was not addressed in the literature of this review was the management of vasomotor symptoms. The CAPO/CPAC recommends that all female cancer survivors have access to cognitive behavioural therapy and lifestyle management programs targeted in alleviating vasomotor symptoms . HoweverThis scoping review is the first to highlight the landscape of survivorship care in the Canadian context, which has important research and practice implications. However, this review is not without limitations. Due to the scoping review methodology, a critical appraisal of the literature was not completed, providing no indication of the quality of the included studies describing the programs, resources, and models of care. However, this was not the intent of the current study. Instead, the authors strove to be inclusive of all peer-reviewed studies conducted in this realm across Canada so as to illuminate the areas researched and in need of further research.While this review included all types of cancers so as to keep the picture of survivorship care in Canada broad, the majority of available Canadian literature focuses on breast cancer survivorship specifically. Forty-one percent of articles included in this review contained breast cancer survivors as their population of interest, and a large proportion of the evidence informing this review is biased towards breast cancer survivorship as discussed above. This limits the generalizability of this review to other cancer types, as it overrepresents the needs and experiences of breast cancer survivors. Similarly, many of the studies were conducted in large urban centres in Ontario, and only a small proportion discussed care of rural cancer survivors; this overrepresents the urban cancer survivor experience. Moreover, the Territories and Saskatchewan were not represented within the review, and only two articles ,47 reporAdditionally, the scope of information available is limited to the content presented in the reviewed articles. Therefore, some of the recommendations by CCO and the CAPO/CPAC may have been adhered to but not reported by authors, and as such not included in the analysis of this review. Furthermore, although population database examinations were useful to underline the supportive care interventions and models of care used by cancer survivors, these types of studies do not permit the examination of the applicability of the guidelines.With the projected increase in the number of individuals surviving cancer , the tra


COVID-19 shocked cities around the world and revealed the vulnerability of urban lives and functions. Most cities experienced a catastrophic disturbance that has lasted for a long time. Planning plays a critical role in responding efficiently to this crisis and enabling rapid functional recovery in the post-disaster era. Cities that have implemented digitalization initiatives and programs are likely to have more capacity to react appropriately. Specifically, digitalized cities could ensure the well-being of their residents and maintain continuity of urban functions. This research aims to analyze the role of technology in crisis management in the last two decades and provide appropriate policy recommendations for dealing with the COVID-19 pandemic. Systematic literature review and subjective content analysis are employed to investigate the effects of technology on community well-being and making cities more resilient in past crises. This study shows that different technology-driven policies and actions enable crisis management, enhance community well-being, and increase urban resilience. Technology has enhanced coping and recovery capacities by increasing participation and social connectedness, enhancing physical and mental health and maintaining the functionality of education and economic systems. These have been achieved through various solutions and technologies such as social media, telehealth, tracking and monitoring systems, sensors and locational applications, teleworking systems, etc. These solutions and technologies have also been used during the COVID-19 pandemic to enhance community well-being and sustain urban functions. However, technology deployment might have adverse effects such as social exclusion, digital divide, privacy and confidentiality violation, political bias and misinformation dissemination, and inefficient remote working and education. It is suggested that to mitigate these side effects, policymakers should liberate the process of digitalization, increase the accessibility to digital services, and enhance digital literacy. Uncertainty, unpredictability, and complexity are prominent features of urban life in the 21st century ,4. IndeeOne of the main planning tools to reduce the risks and vulnerability of populations is using technology to increase preparedness and recovery capacities in the face of crises. In the urban planning domain, such planning tools, efforts, and initiatives are often referred to as smart city solutions . A smartThe term well-being refers to various abstract and objective meanings that philosophically determine an individual’s living space and conditions. These meanings could be different according to the aims and objectives of the researcher or actor ,22. RegaThe main objective of this study is to analyze and understand how technology has been used as an instrument to improve the well-being of citizens during recent crises. The main questions guiding this literature review are how has technology been used to increase participation, transparency, and social connectedness in previous crises? How has technology been used to protect the physical and mental health of residents in previous crises? How has technology been used to keep urban functions and sustain education in previous crises? and how has technology deployment been addressed as an instrument to cope with associated problems of COVID-19? We will use inductive and deductive qualitative content analyses using scientific articles and textbooks published in five selected databases . After dThe systematic literature review is one of the common methods of investigating and analyzing the literature that includes six main steps as shown in In the first step, we used inductive content analysis to find the main areas of well-being and urban functionality that could be affected by the technology or smartness of a city. Then we determined four main questions that should be answered through a systematic literature review. The primary data needed to answer the research questions can be collected from different sources including published papers, reports, books, and newspaper articles. For systematic literature review and deductive qualitative content analysis, we conducted broad searches using six internationally recognized scientific: databases: Science Direct, PubMed, Springer, Sage, Taylor and Francis, and MDPI. In the fields of urban planning and urban studies, these databases are widely known for publishing quality peer-reviewed research. The search string in this study was chosen broadly, including “smart city OR technology OR digitalization” AND “crisis management OR disaster OR pandemic.” The search is only based on documents and cases published in English. We found 1713 documents in databases and 83 other documents from Researchgate, that 53 of them were duplicates. We first manually screened the titles of the retrieved documents and 371 papers that were relevant were selected for detailed screening by reading the abstracts. The main criteria for screening were to have issues related to technology deployment or smart city under crisis situations discussed in the titles. The same criteria were also applied for screening the abstracts. After screening the abstracts, 228 papers were excluded as they were irrelevant. Papers that did not include empirical evidence on the deployment of technology for better crises management and for enhancing community well-being were excluded. We assessed 144 full texts and scrutinized the content of these documents. As we looked for papers with empirical analysis and case studies of crises in previous years, we just chose the articles with the empirical analysis of technology in a specific disaster before the COVID-19 pandemic. As there was a limited number of studies that empirically have analyzed technology deployment during COVID-19 (when this paper was designed and drafted), papers that just mentioned case studies were also included. We finally reviewed 64 papers.Digitalization or smart city approaches strengthen urban resilience through risk reduction strategies and practices . The smaSustainable Development Goals (SDGs) have also emphasized different issues related to urban life , such asCommunity engagement is a central issue in the Sendai Framework for Disaster Risk Reduction to prepare residents and mitigate risks during and after disasters . TechnolSocial media has been used as a new communication method during crises . CommuniBird, et al.  analyzedDisasters threaten people’s well-being and health along with damaging infrastructures ,68,69. PA pilot telemedicine project was implemented in Prayag city in India to reduce the spread of cholera. The project used teleconsultation, telemonitoring of public health and health care facilities, and telehealth education. Additionally, this pilot project processed the gathered data to prevent the spread of the disease. Ayyagari, et al.  analyzedSimilarly, Pasipanodya and Shem  investigMental health problems are also a long-lasting effect of disasters. In the last decade, healthcare systems have used technology to lower these effects. For instance, the 2010 Haiti earthquake caused about 300,000 deaths and more than 1.5 million injuries and displacement. Augusterfer, et al.  analyzedE-learning, remote working, and remote services are common areas that have gained more currency in the last two decades in ordinary days and during disasters. Depending on their magnitude, disasters may have temporary or long-term effects on education systems and employment. However, COVID-19 is a new type of disaster with the characteristics of catastrophic and chronic disasters and has deeply affected local and national economies and education systems . ThroughEmergency remote teaching is a solution for educating people in crisis circumstances by the deployment of technology. These situations need innovative measures to deliver education services to all students regardless of their social and geographical conditions. In South Africa, a private higher education institution that has provided online higher education services has been asked to share its infrastructures to provide services for people exposed to disasters in recent years. It had a blended teaching approach on routine days and extended its programs for emergencies. The institution has two functions: teaching lecturers and then reassuring that students receive education services properly . There aDisasters also affect working systems during and after their occurrence. While there is a lot of research regarding other aspects of disaster risks, little attention has been paid to the nature, conditions, productivity, and other factors related to jobs. Different concepts such as telework, remote work, and mobile working emerged as areas that ICTs enabled to keep urban functioning . PrepariWhile humankind has faced different pandemics in the last century, COVID-19 is one of the most influential human-driven disasters that caused deaths and unprecedented disruptions in urban life ,27. ThisCOVID-19 influenced all personal, social, and political aspects of urban life. So, local authorities and political actors emphasized the deployment of technology to increase the participation of residents in decision-making, particularly regarding COVID-19 decisions, and increase the transparency of these processes. Increasing social connectedness is another objective that is sought through the deployment of technology in cities during COVID-19 see . Social Based on the level of vulnerability of communities and the risk level of disasters, residents’ mental and physical health could be affected ,94,95. TOne of the main features of this pandemic compared to previous disasters is its influence on education systems and working conditions. From the first months of the pandemic, cities around the world imposed restrictions on gatherings, including schools and universities, and shut down unnecessary jobs. Universities and schools canceled all of their face-to-face teachings from laboratories to regular classes to mitigate the associated risks of the COVID-19 outbreak . CountriBeyond the health impacts of COVID-19, businesses have suffered dramatically, and millions of people have lost their jobs. COVID-19 has made workers and employers change working conditions to protect society and the employees. This situation led to more remote working as a solution to reduce the vulnerability of businesses and maintain their functionality . While tAs discussed in the previous section, technology deployment in different ways has empowered local authorities to control the spread and mortality rates of COVID-19. While COVID-19 is an ongoing crisis and judging the effectiveness of this planning approach is problematic, some recent studies have assessed the benefits of implementing smart city projects for controlling COVID-19. Yang and Chong  have quaOne of the significant problems of implementing smart city projects, specifically in less democratic societies, where central government control many aspects of urban life and decision making, is privacy issues. However, since the emergence of COVID-19, the tendency to participate in the research and practice of smart cities has accelerated. The result of research-based projects during COVID has paved the way for the adoption of more technology-based policy-making mechanisms .Although technology deployment to fight COVID-19 is a ubiquitous solution in cities worldwide, there are serious problems and concerns regarding the trustworthiness of these systems. Governments and corporates use geolocational applications and sensors that collect real-time data. Addressing human rights at the digital level is a critical issue that should be considered in digitalization . MoreoveThere are concerns that digitalization may increase inequality and social segregation as all people do not have equal access to technology . The digThe smartness of cities undoubtedly is a positive feature that increases the efficiency of service provision, participation processes, transportation systems, healthcare, etc. However, the digitalization of the city itself may come to action in a nondemocratic process just because it has various benefits , while tThere are strong concerns regarding the use of outcomes in planning and governance processes, including lack of reliable data, poor analysis, misinterpretation, and wrong presentation of decision-making outcomes. These barriers may contribute to less transparency and accountability in urban governance . As new Regarding the deployment of technology to deliver education services, some challenges affect the quality of services. As some institutions have students from different countries and cultures, there might be some language-driven barriers along with other factors of digital inequality . AdditioRegarding teleworking, it provides the employees with a flexible schedule; however, it may lead to diminished boundaries between private and professional life, causing an imbalance between personal concerns and work duties . HoweverTechnology plays a critical role in today’s disaster management. The COVID-19 experience has shown that the smartness of cities could mitigate urban dysfunctionalities and enhance the well-being of communities. This study has reviewed the literature and focused on empirical cases to show how cities’ smartness and technology deployment have affected the resiliency of the city and the well-being of residents. While technology has improved different stages of crisis management, from an urban planning perspective, its tangible effects have been by: firstly, increasing the participation of residents, enhancing the transparency of governmental processes, and social connectedness; secondly, improving the physical and mental health of residents; and lastly, increasing urban functionality in education and employment systems. The result of our literature review showed that technology deployment in all these three areas has increased the well-being of the community and enhanced the functionality of urban systems. Moreover, our analysis in the COVID-19 era revealed that smart cities are more capable and reliable to improve the well-being of their residents and maintain their functionality during pandemics ,113,122.In terms of policy implications, this study revealed that developing smart cities is not achievable by just using technologies to improve urban functions and should also involve considering other aspects and actors such as people and institutions ,44. ThisThis study is not an exhaustive literature review of technology deployment in crisis management due to the broadness of the topic and the interdisciplinary nature of the research. So, there are a number of areas in urban planning that could be investigated in future research, including: first, as Papadopoulos, Baltas and Balta  discuss,