Community Engagement is an important ethical imperative in research. Although substantial research emphasizes its real value and strategic importance, much of the available literature focuses primarily on the success of community participation, with little emphasis given to specific community engagement processes, mechanisms and strategies in relation to intended outcomes in research environments. The systematic literature review’s objective was to explore the nature of community engagement processes, strategies and approaches in health research settings in low- and middle-income countries.The systematic literature review design was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for peer-reviewed, English-language literature published between January 2011 and December 2021 through three databases on the internet . The terms "community engagement," "community involvement," "participation," "research settings," and "low- and middle-income countries" were merged in the search.The majority of publications [8/10] were led by authors from low- and middle-income countries, with many of them, [9/10] failing to continuously include important aspects of study quality. Even though consultation and information sessions were less participatory, articles were most likely to describe community engagement in these types of events. The articles covered a wide range of health issues, but the majority were concerned with infectious diseases such as malaria, human immunodeficiency virus, and tuberculosis, followed by studies on the environment and broader health factors. Articles were largely under-theorized.Despite the lack of theoretical underpinnings for various community engagement processes, strategies and approaches, community engagement in research settings was variable. Future studies should go deeper into community engagement theory, acknowledge the power dynamics underpin community engagement, and be more practical about the extent to which communities may participate.The online version contains supplementary material available at 10.1186/s12913-023-09466-9. Bridging the gap between researchers and the researched and linking communities to valuable resources is key to community empowerment. Community Engagement (CE) or Empowerment is increasingly becoming critical across contexts and an integral part of most research endeavours . BroadlyThere have been many studies on community engagement and empowerment in dealing with health issues -8; howevCE in research has been proven to increase the impact of health studies on communities on several occasions. This way, research demonstrates greater sensitivity to the perception, needs and unique circumstances of researched communities. Many studies have pointed out the need to better apply research, disseminate research results more effectively, and synthesize research into evidence-based guidelines and "best practices" for more immediate use by practitioners and community members -15. In lFrom the definitions of CE, it is evident that the concept of “community” is central. However, there are many types of communities . CommuniWhile CE remains an important aspect of research it is one of the most less understood and less funded aspects of the research process . When grStudies on approaches to community engagement and empowerment have mostly focused on aspects of community consultation (decision-making processes) but less on the other crucial, equally important elements: assessing how the community’s capacity is developed; and, ensuring that implementation follows and is in accord with the consultation and decision-making process. The growth in interest and utilization of CE in research, therefore, raises the more compelling question of the actual outcomes of community participation and involvement. What kinds of evidence are there to support the CE's substantive outcomes? What have been social-ecological impacts on local communities where CE has been implemented? These general questions, however, are linked to a more significant question: what are the various CE processes, strategies and approaches that have been adopted in research settings? The purpose of this systematic literature review was to review the literature on the processes, strategies and approaches of community engagement and empowerment that have been adopted by researchers in low-income countries to determine the best practice for community engagement and empowerment. It is noticeable that most CE definitions refers to CE as a process/strategy/approach, and these three concepts are considered to be synonymous; these focus on single specific hypothesised processes drawn from the community engagement framework to identify how one phenomenon influences another. Hence, these concepts were used in this systematic literature review interchangeably as they were also part of the search terms. In line with these pertinent questions, this systematic literature review sought to understand the nature of CE processes in health research environments in Lower Middle-Income Countries (LMICs). LMICs refer to those countries defined by the World Bank based on the countries’ Gross National Income as having “low-income economies,” “lower middle-income economies” or “upper middle-income economies” as may be amended from time to time .This systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Since this was primarily a qualitative systematic review, no specific comparator interventions or demographics were sought, and a wide range of study approaches, whether experimental, descriptive, or exploratory/explanatory, were considered. We predominantly considered qualitative, quantitative, and mixed-methods studies. All of the articles ultimately included in this systematic literature review were based on empirical research. In accordance with our objectives and problem statement, we employed thematic data analysis which is qualitative in its nature. The nature, scale, and intended effects of CE processes, strategies and approaches in research environments were among the domains reviewed. The systematic literature review did not explore all the models that are available in the literature, we limited our scope to certain criteria to achieve the systematic literature review purpose. Due to the limited amount of time that was available to conduct the review and the limited scope of the review, we avoided exploring other existing models. An extensive search of the models was conducted, but we were restricted in what we could access. We only included records that were publicly available. Some of the records in the databases where we were searching for our records were not available for free, limiting our record selection.A literature search was carried out in three electronic databases: PubMed, Web of Science and Google Scholar in December 2021. Each database was searched from January 2011 to December 2021 for articles containing concepts related to community, engagement, research settings and LMICs as shown in Table In Google Forms, a data extraction form was constructed to help extract information from each article on essential components of community engagement processes, strategies, and approaches in research settings, as listed under the research objectives. The study quality was assessed using the Critical Appraisal Skills Program (CASP) and elements of rigour in doing research . Criticawww.vch.ca/ce) which involves five CE distinct stages  e.g., Malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) [40%], which is 4/10, followed by articles presenting studies on the environment [20%] which is, 2/10 as well as those pertaining to other broader health determinants, broader health issues and primary care [20%], which is 2/10. The least health conditions that were investigated and at least involved some degree of CE were found in studies concerned with reproductive and child health  [10%] as well as those concerned with non-communicable disease and other similar conditions [10%].The findings on type of CE strategy used were classified and presented following the Vancouver Coastal College CE framework. The classifications helped us to determine whether each study was able to articulate the 5 stages of the community engagement cycle. Here we state each part of the cycle and the articles that applied each stage/process in their study: (a) community informed about the problems and solutions proposed in the research , 31-33; Photography: Photography was seen as an essential and successful technique for integrating people into health-related research activities . Images Short films and digital story screening: these were also seen as effective means of engaging the community .Communities were also engaged through festivities that involved songs, poems and similar artworks . These aCE through Artwork and Creativity2)CE through Workshops and Focus GroupsThe broad range of methods and approaches for CE were assessed and outlined as mentioned/discussed in surveyed literature. These techniques varied based on whether communities were informed, consulted, involved, collaborated with or empowered. Table 3)CE through forumsWorkshops , 35 and 4)CE through community surveysA forum was seen as a regular meeting of people who represent a group of organizations and were issue or area based. Those involved typically comprised members of civic, political, professional, economic or social groups from a local area. A number of articles , 27, 35 Questionnaire surveys were seen as means of identifying the needs and views of a large number of people in a standard format .Several components of the study quality-examined were clearly unsatisfactory when it came to the interpretation of responses to the quality of study designs and data analysis. Independent of the data collection description, no article fulfilled every requirement for a research article. At least 60% of studies provided basic aspects related to describing study area and selection, data sources and collection, and triangulation across data sources. Despite this, 30 percent of articles did not have declaration of ethical approval from review boards, while 60% of the papers acknowledged limitations Fig. . The quaA distinguishing mark of the CE research literature in health research settings is that more needs to be done at a variety of levels. For community engagement in LMICs as previously de-fined, we have found very few published studies of empirically collected CE processes data , 27, 29,Although our analysis included studies that are simply qualitative, quantitative, or mixed methods, the majority of studies were exploratory in origin, with only a few using probability or experimental designs to evaluate or describe health research in relation to community engagement. Some reviews on community participation have also noted the scarcity of experimental designs that examine the effectiveness of community participation , 37, othSeveral CE approaches were presented in the surveyed literature. However, a deeper discussion on the appropriate contexts where each can be used was lacking across all articles. For instance, the utility of Arts and Creative approaches for CE are very appropriate where local people are involved in expressing their views and generating ideas in a participative approach. They are a useful technique for engaging with people of all ages through education or school programs, local community forums and resident or interest groups. However, they are specifically beneficial at the beginning of a community research project in the planning process to generate interest and raise awareness of the projects. Moreover, this technique often depends on the availability of a large space to exhibit or display results. It may also be difficult to interpret participants’ ideas in this mode of CE. It is significant to understand cultural dynamics in the community engagement discourse as culture provides a sense of belonging in the community, shapes identities, and affects how people interact with one another, define power, and generate meaning . CultureMany of the assessed articles presented creative and socially based approaches to showcase CE. However, utilizing multiple channels of communication is important. Examples of other techniques and channels for CE include the use of soccer clubs, films, community drama, television, songs, Facebook, social events such as weddings, music festivals, and community fairs with prizes. Children were repeatedly mentioned as important change agents and it was recommended that youth groups be mobilized to assist with messaging. This is one way of ensuring that a part of the community actually participates in the role of the research. Mobilizing groups of young people to become citizen scientist or assistant researchers can significantly improve the involvement of young people, it also brings in the element of collaborations especially when young people bring in their ideas and expertise in solving some of the problems as they work with the researchers. CE borders mainly informing, consulting, involving, collaborating and empowering, hence it is important to have an approach that can accommodate all or most of these stages. Drama and creative art facilitate the process of informing, involving but lacks consultation, collaboration and empowerment. Workshops and FGDs bring on the aspect consultation but still lack in collaboration and empowerment unless the workshops take the form of trainings. Peer educators, community forums (such as community advisory boards) and other forms of collaboration including working with community health workers and community research assistants enable the implementation of all the five stages of the CE process framed by the Vancouver Coastal College CE framework .The review shows that the understanding of implementing principles of CE in researching health-related issues is still in its developmental phase, which poses threats to recognising communities from LMICs as knowledge experts. This review demonstrated that there is limited literature on empirical research published on CE processes in relation to health issues in LMICs. Furthermore, the dearth of empirical research in this study subject calls for more measures to conduct empirical studies to close the gaps between a theoretical perspective and its application in the real world to determine the relevance of CE strategies and approaches to address social issues. Some scholars raised great concern by describing CE as less participative and lacking theoretical components that are responsive to the needs of the researched communities in LMICs , 35, 42.This review highlights how crucial it is for researchers conducting community engagement health studies in LMICs to take into consideration the level and the nature of community participation. There is a need for high-quality study designs to better understand the CE processes and approaches in achieving successful community engagement. A key area that emerged from the systematic literature review is that most CE techniques are creative in nature and socially based but the appropriateness, feasibility and value of these techniques are not considered when dealing with health issues in LMICs. Therefore, participatory approaches and strategies, such as community based participatory research (CBPR) being the most established and well-known in the health field should be recognised and adopted in CE. This could provide more in-depth insights into community engagement in health interventions as well as the connections between variables such as power dynamics and their impact on community participation outcomes. Previous studies that adopted CBPR in dealing with health initiatives found CBPR to be one of the most successful strategies for improving community participation in rural settings , 45, 46.We faced limitations during the literature search where some studies that qualified for abstract screening were not available or accessible for free (were available on purchase) and we did not have funding to buy the articles, our institutional library also did not have access to these papers. Because of the unavailability of funds to pay to access these articles, we could not access them or use them in the next stages of the review. The institutional access which our university offered was not covering these journals. Other reasons for not accessing papers included the fact that some papers were listed as citations, but no full papers were available to view them, this could be a problem with wrong referencing or broken links to the source of the articles. In total we failed to access at least 13 papers which impacted the possible outcomes of our review. Another limitation of the review is that grey literature was not looked for. We only focused on peer reviewed and published articles. These limitations slightly reduced the scope of papers included the review and they may have affected the analysis and outcomes in general. Another limitation of the systematic literature review was the use of only the first institutional affiliation, given that two separate affiliations for the first and/or corresponding author were mentioned. This might have resulted in a measurement inaccuracy in terms of determining which economic region to adopt in classifying the study. However, the first author of a publication is typically the student/researcher who conducted the research, while the corresponding author is typically the senior author who gives intellectual input and prepares and approves the procedures to be used in the systematic literature review. We suggest the attribution as provided in this work is fair because it is based on the first or corresponding author of the selected publication.Even though reviewed works were relatively rigorous and appeared balanced, the findings on CE approaches and strategies were inconclusive. While desired change does sometimes occur, overall, the documented research evidence for positive coalition or partnership outcomes is weak. The reviewed publications contain some great examples of CE approaches and strategies, they also contain key cautionary components. Despite the importance of community participation and its history, there is still a lack of general understanding of the concepts, motivations, and social processes that drive it. Many publications are undertheorized and uncritical, with few citations to definitions or frameworks. While this may not appear to be relevant to the social transformation or utilitarian goals that motivate community engagement initiatives, it can help to explain the assumptions that underpin the type of community participation project that is supported, as well as clarify expectations about the scope of change that is expected, and the techniques required to achieve it on multiple levels.Additional file 1: Supplementary Table 1. Study quality assessment and appraisal table.


Over the past 50 years, socioeconomic development has brought a reduction in birth rates, an increase in life expectancy and consequently in the elderly population. For this reason, there has been an increasing focus on physical and mental health of the elderly, promoting the concept of healthy aging. The aim of this study was to explore the associations between perceived physical and mental health of older adults and a variety of determinants, such as demographic factors, physical functional fitness, physical activity level, adherence to the Mediterranean diet and anthropometric indices, through a structural equation modeling (SEM). A cross-sectional observational study involved 208 elderly (24 men and 184 women) over the age of 60, fully independent and autonomous. Perceived physical and mental health were assessed with the Short Form 12 questionnaire. Basic sociodemographic information was collected; anthropometric features were directly measured, functional fitness was assessed with the Senior Fitness Test, and physical activity level was determined through the International Physical Activity Questionnaire; adherence to Mediterranean Diet (MD) was also collected through the MEDAS questionnaire. The SEM analysis revealed that functional fitness, which was a latent variable of the model described by the six administered fitness tests, was a strong predictor both of perceived physical and perceived mental health in the sample of elderly. Physical activity level was as predictor of the perceived physical component, but not of the mental health, while score of metabolic equivalent task did not result a predictor, as well as the sociodemographic factors and adherence to MD. The present findings suggest that it would be strongly recommended for elderly subjects to engage in physical activity specifically targeted to aged populations, in order to enhance their fitness abilities and enable them to improve the perception of their own health status. Over the past 50 years, globally, socioeconomic development has led to a reduction in new births and an increase of life expectancy . This trAging is a natural and irreversible process involving a reduction in the physical and cognitive functions of the human body and the probability of the onset of age-related diseases . The decAging in the elderly is often characterized by a decrease in cognitive function sometimes correlated with the presence of anxiety and depression disorders , 9. It iSeveral studies have also shown that there is a strong association between physical and mental health , 11, betHealthy aging is a multidimensional concept closely related to a healthy lifestyle characterized by the performance of regular physical activity and healthy eating habits in order to preserve physical, social, mental health and well-being and quality of life . RegularPromoting healthy aging may also depend on dietary modification, which can help prevent the onset of age-related diseases and effectively influence their development, thereby improving quality of life . SpecifiIn the literature, the perception of the physical and mental state of the elderly can be influenced by several factors such as the absence of chronic diseases, but also by the degree of functional impairment, personality factors, stress level, and various psychosocial factors, as shown in the study of Knapik .Although the determinants of healthy lifestyle are well known, little is known in the literature about how they interact with each other in order to predict physical and mental health in older people , 23.The aim of this study was to explore the associations between perceived physical and mental health of older adults and a variety of determinants, such as demographic factors, physical functional fitness, physical activity level, adherence to the MD and anthropometric indices, through a Structural Equation Modeling (SEM). This statistical technique is widely used in the literature to modeling the interactions between variables by combining factor analysis and multiple regression analysis, while simultaneously accounting for measurement error . The theThe advantages to the use of SEM are several: it allows observing complex and multidimensional models; the tested relations among factors are theoretically free of measurement error because the error has been estimated and removed, leaving only common variance; the measurement reliability can be accounted for explicitly within the analysis by estimating and removing the measurement error .A cross-sectional observational study was conducted from November 2022 to January 2023, as part of an intervention evaluation within the Physical Activity Promotion & Domestic Accidents Prevention (PAP & DAP) Project, in collaboration with the Azienda Sanitaria Provinciale (ASP) of Palermo.This study involved 208 elderly (24 men and 184 women) over the age of 60, fully independent and autonomous, with no physical and/or mental disabilities and cognitive disorders, from the city of Palermo and its Province. Participants were recruited from September to November 2022 through the ASP contact persons in the various districts of Palermo using posters with adherence on a voluntary basis.Initially, there were 208 participants in the study, but due to various reasons  we had fewer participants who completed the questionnaires or performed the Senior Fitness Test (SFT). SFT was performed by 154 participants, while SF-12, MEDAS, and IPAQ questionnaires were carried out by 126, 110, and 98 subjects respectively.All participants gave their informed consent for the participation to the study, which was approved by the Ethical Board of the University of Palermo (N. 111/2022) and conformed to criteria for the use of persons in research as defined in the Declaration of Helsinki. All older adults participated voluntarily and could withdraw from the study at any time.Participants’ demographic information, i.e. age, gender, living area , and anthropometric measures of weight and height were collected through the completion of a medical history card. BMI calculation is based on the following formula: weight in kilograms divided by height in meters squared. BMI was calculated to classify subjects according to weight status in underweight (below 18.5), normal weight (18.5–24.9), overweight (25.0–29.9), obese (30.0 and above) . SeveralMicrosoft Excel software [http://amsacta.unibo.it/5751/). These two indices were taken as the dependent variables in our modeling study.The Short Form 12 (SF-12) –29 is a software   –33, a baThe physical activity (PA) level of the participants was assessed through the International Physical Activity Questionnaire (IPAQ) that consists of 7 items used to estimate the amount of physical activity performed in the past seven days by the subjects . ParticiMediterranean Diet Adherence Screener (MEDAS) is a 14-item questionnaire assessing adherence to the MD and major eating habits , 40. EacThe software STATA/MP 12.1  was used to analyse all data.2), total MET min/week, MD adherence score, scores of the 6 tests of the SFT to evaluate functional fitness . Qualitative variables were weight status , PA level , MD adherence (yes/no), gender , living area .Quantitative variables used for the analyses included the following: the perceived physical health and perceived mental health measured as scores derived from the SF-12, which represented the dependent variables used in the structural model; BMI  to modelling latent variables and their indicators was conducted.Third, a structural equation model (SEM) was launched to examine predictors of physical and mental health. Both observed and latent variables were included in the model.The following indices and cut-off were used to evaluate the goodness of the model: comparative fit index (CFI) and Tucker-Lewis Index (TLI), with values > = 0.9; root-mean square error of approximation (RMSEA), which tests the fit of the model to the covariance matrix, with value < = 0.06; the standardised root mean squared residual (SRMR), which is the square root of the discrepancy between the sample covariance matrix and the model covariance matrix, with an acceptable fit value of 0.08 or less. Akaike information criteria (AIC) and Bayesian information criteria (BIC) were also reported to compare the different models and choose the one with the smaller AIC and BIC  .The examination of the standardized beta coefficients for hypothesized relationships was performed together with the standard errors. Statistical significance was set at p <0.05.The descriptive analysis of quantitative variables  shows thThe results of the fitness tests are showed both as scores  and cateMore than half participants have lower and upper limb strength in the average (54.6% and 59.3% respectively). The rest of the sample has lower limb strength below average (44.7%), while just one participant is above the average; for the upper limb strength, similar percentages are found both for values above the average (21.4%) and below (19.3%).The flexibility of the lumbar and ischio-crural musculature estimated with the sit and reach test is below average for most participants (56.6%); the rest of the sample has it in the average.The flexibility of the scapulohumeral joint is also below average for most participants (45.5%), but there is a small percentage (13.8%) of persons above the average.The agility and dynamic balance revealed by the timed up-and-go test is for almost all sample (89.6%) above the average.Finally, the aerobic capacity is above the average for most participants (66.9%), while only 2.6% is below the average.The bivariate correlation between the study variables is shown in The perceived physical health is significantly correlated to the agility and dynamic balance measured through the timed up-and-go test , to the leg strength and endurance measured through the chair stand test  and to the total MET and to the physical activity level ; a trend exists for the correlation with the upper limb strength and with the flexibility of the lumbar and ischio-crural muscles .Perceived mental health is correlated to all tests of functional fitness (p<0.01), except sit and reach and back scratch; a trend was identified with Total MET .Other correlations are evident for total MET with upper limb strength  and aerobic resistance ; physical activity level with flexibility of the lumbar and ischio-crural musculature , agility and dynamic balance  and aerobic resistance ; weight status and MD adherence , with those adherents to the MD being less overweight or obese; physical activity level and MD adherence , with those adherents to the MD having a higher level of PA. A trend has been identified for Total MET and weight status , with people overweight/obese having a lower total MET.A first model with three latent variables  did not fit well and wasn’t considered. A second model was analyzed including two latent variables, i.e. functional fitness and physical general status, which was considered better but did not satisfied the cut-points of the indices  .The final model revealing the best fit shown in  includedBoth physical and mental health are positively and significantly predicted by functional fitness. Structural and measurement models are also shown in The physical activity level is only related to physical status: active people have a higher and better perception of their physical status of 0.3 points more compared to inactive people.All the other considered variables were not predictors of perceived physical and mental health.This study explored the relationship between perceived physical and mental health in older adults and several determinants, such as demographic factors, functional fitness, physical activity level, anthropometric indices and adherence to the Mediterranean diet. Correlations between the considered variables were described by an initial bivariate analysis, followed by a structural equation modeling that explained the predictors of perceived physical and mental health.The final obtained model revealed one latent variable, the functional fitness, which was described by the six fitness abilities measured through the SFT and this was confirmed by the highly significant coefficients  showed iRegarding the performances at the fitness tests, our sample generally showed quite good results (in the average or above the average) for the upper body strength, agility/dynamic balance and aerobic capacity/endurance. These values were significantly correlated in the bivariate analysis with the physical activity level, and this result is consistent with the study by Buchman et al.  who showWith concern to the other fitness abilities, most of our sample showed that the flexibility of the lumbar and ischio-crural muscles estimated with the sit-and-reach test, as well as the flexibility of the scapulo-humeral joint were below average. This result could be attributed to the chronic use of these joints, which are the most stressed in the activities of daily living  and not At the bivariate analysis we also found that perceived physical health was significantly correlated with agility and dynamic balance and total MET/physical activity level; for this reason, there is a trend (p<0.10) for correlation with lower and upper limb strength and with flexibility of lumbar and ischio-crural muscles.On the other hand, a study by Pucci et al. showed that there is a positive association between physical activity and Short Form-36 questionnaire domains including "physical functioning", "vitality", "mental health", "role-physical", "role-emotional", "general health" and "physical and mental components". In particular, the domains "physical functioning", "vitality" and "mental health" showed a greater association of these domains with physical activity .The structural model showed the perceived mental health being highly correlated with all tests of functional fitness. To our knowledge, there are not studies in the literature assessing this relationship, but our results can suggest that old people should gradually and constantly build and maintain adequate levels of fitness abilities  in order to perceive a better health status. The bivariate analysis showed this correlation for all tests except the sit and reach and back scratch tests. This is consistent with the work of Hemmeter et al. that physical fitness counteracts the development of depression; in fact, physical fitness is associated with better mental health in the elderly . PhysicaThe structural model in our study confirmed an important role of the physical activity level as predictor of the perceived physical health, but not of the mental health, while MET measured as score did not result a predictor.Despite most participants were overweight/obese, they showed on average a good physical activity level with mean total MET over the average cut-off. This can be considered a good result since higher levels of physical activity have been shown to be linked to lower motor decline in the elderly, while sedentary behavior was associated with impaired physical function . MoreoveOther correlations were evident for physical activity level and all fitness abilities, with the exception of back scratch test. This result could be explained by the type of physical activity that was performed by the study participants. In fact, most of them were engaged in walking or daily activity work such as gardening that did not involve the scapulohumeral joint.Total MET score significantly predicted the upper limb strength and aerobic resistance, while a significant trend was showed for flexibility of the lumbar and ischio-crural musculature, agility and dynamic balance. A review by Lam et al. partially confirmed our results stating that higher levels of physical activity were correlated with higher levels of flexibility and balance .Correlations for age in the bivariate model showed that perceived physical health decreased with aging, and this relationship is mediated by the abilities in some fitness tests. For example, we found that participants’ age was correlated with timed up and go test and arm curl test. In fact, a higher age corresponded to more time to perform the timed up and go test, and a higher age was correlated with lower strength as the repetitions of the arm curl were lower. These findings are consistent with studies by Cadore et al.  who showGender was correlated to sit and reach test, back scratch and minute step tests, with females performing overall better than males. A trend of significance was also found out for females perceiving a worst mental health status than males . In the Our results showed even no correlation between perceived physical and mental health and adherence to the MD. This result appears opposite to the results found by Zaragoza Marti et al.  who founSince different papers confirm the lack of associations between mental health and variables such as age, gender, weight status and diet, focusing more on the psychological aspects such as depression or loneliness that predict mental health, the authors can suppose that the role of these psychological aspects could be stronger and there could be other psychological mediation mechanisms or neuro-metabolic explanations, that are age- and gender-independent or diet-independent, for these relationships.The study has some limitations. Firstly, our sample consisted almost entirely of women (88%) compared to men, so it was difficult to identify differences between genders. Therefore, it is worthwhile to undertake further research that includes a fair number of older men through effective recruitment methods targeted specifically at men.Another limitation could be the use of the IPAQ questionnaire as the only method of measuring physical activity level in the elderly. Although the IPAQ is an internationally recognized questionnaire, whose validity and reliability were assessed in comparison to accelerometer, there are some studies that show some limitations of its use in the elderly population. The study by Tomioka et al.  conducteOur study has various strength points. Firstly, the fitness tests administered were well established and recognized, with the battery in the short form being valid and reliable for older populations. In addition, our sample was recruited from different living areas in the province of Palermo, these allowing comparisons based also on the urban or rural geographical characteristics of the sample.The results of our research can also be applied to the individual because the selection criteria for participants and the evaluation methods used have been defined in detail. Finally, our study provides an important and original contribution to the knowledge of the relationship between perceived mental health and functional fitness in older adults, since there is a lack of this matter in the scientific literature.Referring to our results, the designed structural model was robust to describe predictors of perceived physical and mental health in older adults, which were recognized in the functional fitness both for the physical and mental health, and in the physical activity level for the perceived physical health.Therefore, it would be strongly recommended for elderly subjects to engage in physical activity specifically targeted to older age, in order to improve fitness abilities.Our results may be useful to clinicians and healthcare services for detecting and treating disease or its complications at an early stage, before symptoms or functional losses occur, thereby minimizing morbidity and mortality. In addition, they may be used to plan targeted strategies for promoting healthy lifestyle in elderly.


Several epidemiologic studies have found that consuming fruits and vegetables lowers the risk of getting a variety of chronic illnesses, including several types of cancers, cardiovascular diseases (CVDs), and bowel diseases. Although there is still debate over the bioactive components, various secondary plant metabolites have been linked to these positive health benefits. Many of these features have recently been connected to carotenoids and their metabolites’ effects on intracellular signalling cascades, which influence gene expression and protein translation. Carotenoids are the most prevalent lipid-soluble phytochemicals in the human diet, are found in micromolar amounts in human serum, and are very susceptible to multiple oxidation and isomerisation reactions. The gastrointestinal delivery system, digestion processes, stability, and functionality of carotenoids, as well as their impact on the gut microbiota and how carotenoids may be effective modulators of oxidative stress and inflammatory pathways, are still lacking research advances. Although several pathways involved in carotenoids’ bioactivity have been identified, future studies should focus on the carotenoids’ relationships, related metabolites, and their effects on transcription factors and metabolism. Carotenoids are natural pigments from the tetraterpenes family, characterized by a central chain with 40 atoms of carbon and alternating single and double bonds and various cyclic or acyclic end groups, depending on the carotenoid . In termHumans and animals cannot synthesize carotenoids by themselves, they can be found in their tissues due to the absorption and deposition of the carotenoids ingested in dietary food ,4,5.Carotenoids are natural organic pigmented compounds with structural variations, with more than 750 carotenoids being known, but only 40 of them are present in the human diet and 20 in human blood and tissues ,6,7,8. TIn terms of chemical constituents, these natural pigments can be divided into two categories: carotenes and xanthophylls . If theyCarotenes absorb light energy from chlorophyll and energy from singlet oxygen formed in photosynthesis, being responsible for transmitting this light and protecting the plant tissues . XanthopRegarding functional properties, carotenoids can be classified as primary and secondary carotenoids, with the photosynthetic ones included in the primary group and playing an important role in photosynthesis ,12.These natural organic pigmented compounds, in terms of physicochemical properties, are associated with membrane lipid bilayers and cytosolic lipid droplets, which can affect some properties associated with the permeability and fluidity of the membrane .The principal properties of carotenoids mentioned before are illustrated below, in The regular consumption of fruits and vegetables is widely recommended due to their multiple health benefits such as the lower incidence of chronic diseases  such as Several studies have attributed to bioactive compounds present in the diet , in partSome of the more important biological functions related to human health of the three most known carotenoids are presented in These antioxidant phytochemicals are also important dietary sources of vitamin A and protect cells and tissues from oxidative damage, interacting with other antioxidants ,25. So fVitamin A is important for proper visual, immune, and gastrointestinal functions, growth, and embryonal development . Humans The recent discoveries about the health promotion properties of carotenoids have aroused interest in applying these natural pigments in diversified areas . These nIn nature, the bioavailability of carotenoids is reduced ,20 withoDiet is one of the most important regulators of the intestinal microbiota , but theIn this sense, this review aims to present an overview of the gastrointestinal delivery system for carotenoids, the processes occurring during digestion, from mastication to absorption, and the impact of the gut microbiota and its metabolites on the stability and functionality of carotenoids, and also their ability to modulate inflammatory and oxidative stress pathways.The research articles about carotenoids and intestinal microbiota were searched on Science Direct and on PubMed, using the keywords “carotenoids”, “gut microbiota”, and “interaction”. Therefore, all publications available in these two databases which contained the words mentioned before as author-specified keywords in the title or abstract were considered.Later, the abstracts of all of the articles were analysed and divided into two categories: carotenoids in human health and the interaction of carotenoids with the gut microbiota. There are several articles that mention that phytochemicals/dietary lipids may influence the composition of the intestinal microbiota, the digestion process, and the occurrence or prevention of some diseases, among others. Although carotenoids belong to those categories, the detailed process is focused on other phytochemicals/dietary lipids. For carotenoids, the process is only a supposition, according to the chemical and structural similarities with other dietary lipids, highlighting the lack of information about these natural pigments. For this reason, articles where the role or the process that carotenoids perform is not the main focus were excluded. According to our search through the Science Direct database, only four relevant research articles were published . The oldest article was published in 2018, which reveals that the interaction between carotenoids and the intestinal microbiota is a recent research theme.PubMed than through Science Direct, it corroborates the fact that this topic is a very recent research target and that more research needs to be conducted concerning the interaction between carotenoids and the intestinal microbiota. The articles published were categorized into carotenoids in human health (5 articles) and the interaction of carotenoids with the gut microbiome (7 articles).The search performed on PubMed showed that 18 articles containing the keywords selected by us were published . Although more articles were found through The number of published articles related to carotenoids and their interaction with the intestinal microbiota, according to its year of publication, is represented in Initially, the studies were more related to the role that carotenoids play in human health such as the antioxidant and anti-inflammatory activity and the beneficial effects that they have on the treatment of some cancers and CVDs. It is believed that due to these bioactive properties, the interest in carotenoids has increased exponentially, which is corroborated by the increase in articles about the interaction of carotenoids with the gut microbiome in more recent years. However, it still lacks information related to the impact of digestion and interaction between the carotenoids and the gut microbiome on the stability and functionality of carotenoids. The bioaccessibility of a carotenoid is defined as the maximum quantity of a carotenoid released from the food matrix that is available to be absorbed in the epithelial cells of the intestine . The fraIn nature, the bioavailability of these natural pigments is reduced, since there is a resistance to digestion and degradation from the protein complexes of carotenoids and the cell walls of plants to achieve adequate release from the matrix ,20. In tThe carotenoids’ bioavailability and consequently absorption have some limitations due to factors such as the dietary sources, food composition, cooking temperature, season, the breakup of the food matrix, presence of lipids, dosage, and presence of other soluble compounds/carotenoids ,36. ThesThe release from the food matrix depends on the state of the carotenoid, as natural pigments immersed entirely in lipid droplets are more easily released than ones in the microcrystalline form . This exThe dietary composition also has a significant effect on the bioavailability of carotenoids . CarotenFood thermal processes such as cooking, boiling, and heating disrupt the cellular membrane, allowing the release of carotenoids from the matrix ,20,21, aThe principal factors affecting the carotenoids’ bioavailability, enhancing (left) or decreasing (right) it, are represented below, in Therefore, different extraction technologies are required to increase carotenoids’ solubility and bioavailability . The traIn the last few years, some alternative methods to recover carotenoids have been presented, such as super-critical fluid extraction (SFE), high hydrostatic pressure (HHP), and Ohmic heating (OH).2 mobile phase [SFE is an extraction technique that reduces the toxic solvents used during the process and can generate a solvent-free extract at moderately high selectivity and yield temperatures . Althougle phase ,43,44.2 pressure (180 bar), and at room temperature to obtain phylloquinone [HHP is a simpler and more efficient technique than conventional extraction methods, that contributes to improve the bioaccessibility of bioactive compounds . HHP is oquinone . Howeveroquinone .More recently, Coelho et al.  proposedThe authors  showed tThe main advantages and limitations of OH as an alternative method to recover carotenoids without organic solvents are represented in The carotenoids’ pathway along the GIT starts in the mouth, where they are liberated from the food matrices and, passing through the stomach and intestine, become susceptible to modifications such as solubilization by the intestinal fluids ,49. ThenThe carotenoid absorption mechanism can be divided into release from the food matrix, transfer to the oil phase, formation of mixed micelles, and absorption, as represented below, in The carotenoid absorption mechanism starts with mastication, the physical disruption that leads to the release of carotenoids from the food matrix . This stThe second step consists of the dissolution of carotenoids into the gastric emulsion. The first limiting factor is the digestion from the food matrix: if it is not complete, carotenoids will not have direct contact with the oil and, consequently, will not be transferred to the oily phase .The incorporation of carotenoids into the gastric emulsion also faces several limiting factors, such as soluble proteins, the surface charge of the gastric emulsion, the oil, and the amount of the carotenoid present .In the case of β-carotene, the incorporation of this carotenoid into the gastric emulsion is inhibited by soluble proteins that affect the interfacial characteristics of the digesta. Proteins  have been suggested to help in the bioaccessibility of liposoluble food elements in a variety of ways. Proteins may stabilize oil-in-water (o/w) emulsions in the GI tract after adsorption to lipid droplet surfaces. This is due to the fact that proteins can be highly surface-active molecules, and the formed particles tend to be highly negatively charged, preventing lipid droplet aggregation. However, Qiu et al.  found thHowever, the concentration of soluble proteins decreases and the transfer of β-carotene to oil increases if the pH decreases . β-carotDuring the passage through the small intestine, the release of bile salts occurs that promotes the formation of mixed micelles . These mThe carotenoids’ absorption only occurs if they are in mixed micelles, since the factors that affect the micelle formation also affect the bioavailability of carotenoids in the digestion process . DietaryIn addition to lipids, fibres such as alginate, guar, and pectin are also limiting factors, as in the presence of carotenoids they inhibit the formation of micelles and decrease the bioavailability of carotenoids .The final step of the carotenoids’ absorption starts when the micelles containing the carotenoid come into contact with the apical side of the enterocytes , then enAlthough it was believed that the absorption of carotenoids occured in the same way as dietary lipids, through passive diffusion, it has been discovered that the absorption of carotenoids can be facilitated by transporters present in the membrane, such as the scavenger receptor class B type 1 (SR-BI), the cluster determinant 36 (CD36), and NPC1-like transporter 1 (NPC1L1) ,55. SR-BIn addition, absorption can be affected by the individual’s genetic susceptibility, the dose ingested , and by 14, which is 10 times higher than the number of human cells [The intestinal microbiota consists of a complex community of microorganisms , includian cells . 12 bacterial cells/g of gut content [The intestinal microbiota composition is different along the GIT . The sto content . Almost  content . In The relationship between the intestine and its microorganisms is mutualistic, since the host intestine supplies the bacteria with the conditions for their survival and reproduction and the microbiota has important functions such as digestion, nutrient processing, protection against pathogens, production of different antimicrobial substances , productThe intestinal microbiota has a spatial limitation, which consists of its enclosure within the gastrointestinal lumen, allowing the gut bacteria to translocate and generate a local or/and systemic inflammation ,71. To oNonetheless, the composition and function of the intestinal microbiota can be affected  by indivDietary compounds with low bioavailability or that cannot be absorbed directly , pass thThe intestinal microbiota contains millions of microbial genes  that enaThese plant-derived compounds must be absorbed, transferred to the circulating system, delivered to the site of action in the body, and metabolically converted to the vitamin active form to be biologically effective . The carAfter biological activation, these metabolites can promote a wide range of activities in the host, such as regulating the composition, function, intestinal barrier and motility of the intestinal microbiota, modulating host metabolism, and influencing nutrient absorption, among others . On the In addition to that, dietary compounds can also indirectly interact with the intestinal microbiota through the modulation of gastrointestinal transit time, pH, and the synthesis and release of antimicrobial peptides and secretory immunoglobulins .The typical metabolites generated by the intestinal microbiota and their respective functions and associated diseases are presented in The interaction between carotenoids and the intestinal microbiota is a topic that still lacks associated information and clear evidence. However, some studies have indicated that the intestinal microbiota may be the main factor behind the effectiveness of carotenoids’ action .Jalal et al.  showed tOther studies revealed that the composition of the intestinal microbiota can be regulated through dietary carotenoid supplementation such as lycopene, which inhibits the reproduction of Proteobacteria and promotes the growth of Bifidobacterium and Lactobacillus, maintaining the harmony of intestinal immunity and mitigating the symptoms caused by anxiety and dextran sulfate sodium-induced colitis and depression . AstaxanBifidobacterium and Collinsella strains and high doses increased the abundance of Lactobacillus strains [Supplementation with β-carotene also increased the abundance of Bacteroidetes and Proteobacteria and decreased the abundance of harmful bacteria such as Dialister and Enterobacter, which corroborates the positive effects of this carotenoid in intestinal health . In addi strains .In addition to this, the results obtained by Dai et al.  suggesteTherefore, the results obtained from these studies indicate that carotenoids and the intestinal microbiota have a structure–activity relationship and the latter can be a potential target for carotenoids’ utilization . HoweverCarotenoids have been associated with various health benefits, mainly due to their anti-inflammatory and antioxidant properties that provide protection against lipid peroxidation and damage caused by ROS . 2O2-induced oxidative stress by inducing nuclear localization of Nrf2 and reducing intracellular ROS. However, in other studies, the Nrf2 translocation has been inhibited under different concentrations [In addition to carotenoids’ scavenging function, it is believed that these natural pigments can also act indirectly . This intrations . The efftrations . Despite the scarce number of investigations and the conflicting results obtained, there is also a major research gap related to carotenoid metabolism along the GIT and interactions with the gut microbiota . CarotenSome studies showed that some unknown metabolites were produced during the carotenoids’ pathway through the GIT. These metabolites may include apocarotenoids, that have a shorter chain length and oxygen modification, which increases their aqueous solubility and electrophilicity, and consequently, improves the target of some transcription factors such as NF-κB, giving these metabolites some biological effects ,128. FurSince it has been proved that carotenoids are important for human health, it would be important to understand the mechanisms used by carotenoids to become available for absorption in the host colon, how they are utilized by microbes, and how carotenoids and their metabolites are processed to bring so many human health benefits . This inCarotenoids are natural pigments with important bioactive properties that promote health, becoming more studied and used over the last few years. Carotenoids’ bioavailability in nature is low and little is known about their pathway through the GIT and consequent processes occurring during digestion, as well as the role of the intestinal microbiota and their metabolites on the metabolism and absorption of carotenoids. Traditional methodologies such as SFE and HHP are used to increase carotenoids’ solubility and bioavailability, but the organic solvents used are toxic to human health, necessitating the purification of carotenoids that are to be used in the food industry. More recently, OH has been proposed as a more advantageous methodology that can replace the traditional methods since it is selective, enabling bioactive compounds to be extracted without organic solvents.This review set out to give an overview of the carotenoids’ absorption mechanisms, mentioning the variables that can affect the stability and functionality of carotenoids. The four steps of such a mechanism were explained and the limiting factors that affect the bioavailability of these natural pigments in each phase were indicated. In addition, it was highlighted that the intestinal microbiota can have an important influence on the absorption and metabolism of carotenoids. The change in the composition of the intestinal microbiota can enhance or inhibit the reproduction of some microbial species that can have defensive or damaging effects. The physicochemical structure of these natural pigments, the co-consumption with other compounds, the host variables, and the presence and type of food matrix are examples of other factors that can play important roles in carotenoid efficiency.The intestinal microbiota can synthesise and release a variety of different metabolites that can be produced directly from dietary compounds , produced by hosts and transformed chemically by gut bacteria , or synthesized de novo by gut microbiota . These metabolites are absorbed and transferred into the circulating system and can regulate the composition and function of the host’s intestinal microbiota, as well as play important roles in the development and progression of some pathologies.However, just a few studies have been performed to understand the metabolism and absorption of these bioactive compounds along the GIT and further information and details about the mechanisms they use, as well as their metabolites, that contribute to human health benefits are still lacking. For this reason, more studies are required, since carotenoids have many important biological functions in the human organism, including the prevention of some of the most fatal diseases worldwide.


Studies measuring hair cortisol concentration (HCC) have been increasingly conducted to document stress-related, endocrine changes aggregated over time. Previous studies have shown that HCC reflects abnormalities in the hypothalamic–pituitary-adrenocortical axis (HPA axis) in the context of somatic diseases, such as Cushing’s syndrome. HCC variations also reveal a corresponding alteration in HPA-axis-function in mental disorders, highlighting its potential role as a biomarker for interventions targeting mental health problems.The aim of this study was to investigate the role of HCC in various psychological and neuropsychiatric interventions and to explore the extent to which HCC can serve as a predictive or outcome parameter in such interventions by conducting a PRISMA-compliant review of the literature.Web of Science, Google Scholar, PsychINFO, and ResearchGate were systematically searched using different combinations of relevant keywords. Studies of different types that examined HCC in the context of a wide range of psychological and neuropsychiatric interventions were included. Studies in languages other than English or German and animal studies were excluded. The MMAT tool was used, to assesses the Risk of bias.From May to July 2022, the databases The initial search identified 334 studies. After applying the inclusion and exclusion criteria, 14 publications with a total number of 1,916 participants were identified. An association between HCC and PTSD, depressive disorders, and ongoing social and family stress can be documented. The effect of relaxation techniques, mental training, CBT, or PTSD therapy on HCC has been studied with equivocal results. Some studies found decreased HCC after treatment, while others did not show a clear effect. Baseline HCC appears to be of particular importance. In some studies, higher baseline HCC was associated with increased treatment response, providing a predictive value for HCC.HCC is increasingly being used as a biomarker for the mapping of psychological and neuropsychiatric interventions. However, due to the wide range of study populations and interventions, results are still heterogeneous. Nevertheless, HCC seems to be an encouraging biological parameter to describe the trajectory of different interventions aimed at improving mental health. HCC is increasingly used as trajectory or predictive parameter in psychological interventions.The results do not provide a consistent picture to this point.However, HCC appears to be a promising biomarker to illustrate how biological processes can be modulated by psychological and neuropsychiatric interventions.The methodological gold standard  for psychotherapy studies with determination of HCC should be implemented more consistently in the future.Stress has long been recognized as a risk factor for mental and physical health. The hypothalamic–pituitary–adrenal axis (HPA-axis) plays a critical role in the endocrine regulation of stress. Its activation is required for physical adaptation to any stressor and leads to the release of the hormone cortisol . To dateIn recent years, there has also been an increase in the investigation of cortisol levels in the context of mental disorders, as shown in a meta-analysis from 2018 . The autAs described in another systematic review on the influence of hormones on psychotherapies, it seems plausible that cortisol can influence psycho-affective and emotional functions through physiologically expressed glucocorticoid receptors in the central nervous system. The review attributes some importance to cortisol in the context of psychotherapy . FurtherThe determination of cortisol in scalp hair seems to be a reliable parameter of the HPA axis , 6. In cWith an average hair growth rate of approximately 1 cm per month, the most proximal centimeter represents the previous month’s HCC. Hair samples should be taken from the posterior vertex as close to the scalp as possible , 7. Two As a helpful framework, biomarkers have been classified into diagnostic, prognostic, and intervention-related functions . The stuThe importance of HCC as a biomarker has been widely documented in various fields such as the measurement of stress or in the context of somatic diseases. The relationship between prolonged stress and HCC was demonstrated in a meta-analysis of chronic stress situations . In streIn addition, the measurement of the HCC may be relevant in several somatic diseases. One study showed that mean HCC were significantly increased in patients with Cushing’s syndrome (CS) . CS inflStudies on the relationship between HCC and overweight or obesity found significantly increased HCC levels in children with obesity . FurtherRegarding the association between maternal and infant HCC, several studies have provided interesting and sometimes conflicting results. Studies have shown a positive association between perceived stress and HCC in pregnant women, increased HCC in assisted reproductive technology, and increased HCC in the first trimester when a girl is carried to term –19. RegaGiven the hypothesized critical role of prenatal stress in the early mother–child relationship, mediated by stress responses and subsequent neuroendocrinological changes, in contributing to the etiology of mental disorders in general, these findings suggest further investigation of the association between HCC and psychiatric or psychosomatic disorders . PreviouThus, there is now a consensus in research community that environmental and mental stressors, as well as psychological distress, may ultimately be reflected in variations in HCC. The measurement of hair cortisol therefore seems to be a promising method to map chronic cortisol fluctuations that can occur in the context of psychiatric and psychosomatic diseases and thus also their treatment .Based on the possible association between mental disorders and HCC, it is reasonable to assume that HCC also plays a role in the evaluation of psychological and neuropsychiatric interventions. However, this is still an evolving area of research, which explains the limited nature of the existing data. To date, there has been no review of the literature that classifies the importance of hair cortisol in the context of psychological or neuropsychiatric interventions. This literature review intends to give a first overview of the current state of research on the role of HCC in the context of psychological and neuropsychiatric interventions.On the one hand, this review aims to explore the extent to which HCC is used as a trajectory parameter in research investigating the effects of psychological interventions on people with mental health problems. On the other hand, it is intended to answer the question whether the existing literature provides evidence of the extent to which hair cortisol concentration appears to be suitable as an outcome parameter for psychological and neuropsychiatric interventions by summarizing the existing literature in a structured way. The following research questions, which are formulated in a more general way according to the still preliminary character of the existing literature, shall be answered by the present work:To what extent is HCC used as a predictive or trajectory parameter in psychological and neuropsychiatric intervention studies?How do psychological and neuropsychiatric interventions affect HCC?This paper is a literature review based on the PRISMA statement . AccordiWeb of science, Google Scholar, PsycINFO and ResearchGate for relevant literature from May to July 2022. The primary database utilized in this study was the Web of Science Core Collection. The other databases were employed to fulfill additional search queries, such as retrieving full texts or conducting targeted searches for specific articles. No date limit will be imposed on the search. Studies in languages other than English and German could not be included due to resource limits.To address the research questions, the authors systematically searched the databases hair cortisol AND review or meta-analysis, (2) hair cortisol or hair cortisol concentration or HCC AND psychotherapy or therapy or counseling or psychological therapy or psychosomatic treatment AND response or outcome or predictor or process AND PTSD or posttraumatic stress disorder or depressive disorder or depression or childhood maltreatment or anxiety disorder or somatic symptom disorder or psychosomatic disorder or major depression or fear or borderline disorder or personality disorder.According to the research question, we identified appropriate keywords and linked them by using the Boolean operators “AND” and “OR.” The following combinations were used: (1) Through these selected keywords, we aim to cover as broad a field of mental disorders as possible. However, the studies found in this way mainly examined HCC in the context of psychological and neuropsychiatric interventions in the presence of affective disorders. No relevant literature on hair cortisol and psychological or neuropsychiatric interventions in the context of borderline or other personality disorders could be found.In addition, the reference section of the studies found by automatic search in the databases were manually searched for further relevant publications.The authors also made a cursory search in gray literature. However, no suitable studies were found.Articles that considered the topic of hair cortisol and psychological or neuropsychiatric interventions in the title or abstract were included. The further criteria for studies to be included will be outlined below.Randomized controlled trials (RCTs), cluster RCTs, controlled clinical trials, controlled before-after studies, prospective, retrospective, and case–control studies as well as other forms of clinical trials were included. Time series analysis and different forms of qualitative research were also initially considered. The authors did not include non-empirical research studies, unpublished master-level dissertations, unpublished conference presentations and articles where no full text is available.Studies examining humans of all ages; children and adolescents as well as adults were included. Animal studies were excluded.Different types of psychological interventions were considered for the present work, including widely-applied traditional forms of psychotherapy such as cognitive behavioral therapy (CBT), other forms of behavioral therapy, analytic and psychodynamic therapy, family therapy, or trauma focused therapy, but also interventions from the broader psychotherapeutic or neuropsychiatric spectrum such as stress-reducing therapies, mindfulness-based interventions, and electroconvulsive therapy (ECT). Studies that did not report any form of intervention were excluded.Various comparisons can be of interest for the present study and will be considered in the literature review. Studies that only measured before and after values of HCC are included as well as studies with an untreated control group or other forms of interventions as a control condition.All the included studies need to determine HCC as an outcome parameter. Both ways of quantifying HCC, LC-MS/MS and EIA, will be considered. Studies that did not quantify HCC were excluded.Identification phase shows the total number of articles found by database- and snowball-research, according to the keywords used. Before screening, the duplicates were removed. In the Screening phase, we applied the inclusion criteria to titles and abstracts. The exclusion criteria were then applied during the Eligibility phase. The criteria used in the corresponding phase are listed in the flow diagram. Finally, these steps resulted in 14 articles included in this review. The study selection process was conducted by two of the authors  independently.According to the PRISMA guidelines  a flow cBased on the selected studies, we read each article with particular attention to describe the significance of HCC and the potential predictive value of HCC in psychological and neuropsychiatric interventions. Microsoft Excel was used to manage and organize the relevant extracted information from the studies. Subsequently, these were then transferred into a well-structured table containing the most important data and results of the publications considered. If specified in the publications, the individual hair cortisol values measured are also listed. The table is divided into a part with the studies that mainly focus on the longitudinal changes of HCC in the course of a psychological or neuropsychiatric intervention and a second part with the studies on the predictive power of HCC for the treatment outcome see . The stuTo evaluate the risk of bias and the quality of the studies included, we used the Mixed methods appraisal tool . The MMThe non-randomized studies in general must be assessed with a high risk of bias due to the lack of randomization and the absence of a control group in some of them.In the case of three of the randomized controlled trials, it should be noted negatively that the randomization process was not adequately described. Furthermore, it is not clear whether blinding took place. Another randomized controlled trial did not use blinding of the researchers and participants at all, but this circumstance was clearly described. However, this leads to a high risk of detection bias.Due to the still small number of studies considered and the heterogeneity of their methodological quality, we decided not to conduct a meta-analysis.Find Duplicates function in the literature management program EndNote X9. The remaining 307 articles were then screened by title and abstract. In this process, 265 were found to be ineligible for this review. In a further step, the full texts of the remaining 42 studies were screened and evaluated. This resulted in the exclusion of 32 publications.As shown in In addition, as mentioned above, a hand-search was conducted in the reference section of the previously selected studies. Initially, 15 studies were found to be usable. In the full-text screening, 11 of these results had to be excluded. The exclusion criteria can be found in the methods section and in The selection process thus resulted in a total number of 14 studies, which are considered and described below.The 14 studies reviewed are summarized in The oldest study considered here was published in 2015, the most recent ones are from 2022. The vast majority of the included publications come from Europe . Two were from the USA and one each from Argentina and Jordan.These 14 studies collectively involved a total of 1,916 participants. The number of participants varied significantly and ranged from 30 to 733. The average age of the study population also varied widely, ranging from adolescents to an average age of 60 years. Mostly, however, it was in the range of 30 to 45 years. Accordingly, studies that included only adolescents/children, only adults, or both age groups as participants were included. Only one study included females only. The other study populations were of mixed gender.The 14 studies encompassed in this review followed diverse methodological approaches. One is a meta-analysis, and the others are quantitative trials of various types.Consistent with the defined research questions, the authors included nine studies focusing on longitudinal changes in HCC over the course of a psychological or neuropsychiatric intervention and five studies concentrating on the predictive power of hair cortisol on treatment response.Regarding longitudinal changes in HCC over the course of psychological or neuropsychiatric interventions, one study investigated the effects of CBT, a well-established form of psychotherapy, on HCC. This randomized controlled trial of 78 pregnant women, divided in an experimental and a control group, examined the efficacy of CBT for stress management in reducing psychological stress and HCC. In the therapy group, a reduction in HCC, specific pregnancy stress scores, and general stress levels  was found. According to the authors, the decrease in these psychological and endocrinological stress parameters reflects the effectiveness of CBT in pregnancy .and child HCC was subsequently determined. Interestingly, there was no significant interventional effect on parental HCC. However, the children had lower HCC after their parents’ treatment compared with controls, where concentrations increased  has established itself as a form of neuropsychiatric treatment, especially for severe depression . In one Finally, a meta-analysis examined the effects of meditation on cortisol. However, only two studies quantified HCC. In both, there was no effect of mindfulness-based and focused attention interventions on HCC .predictive value of HCC. In 89 patients with depression and anxiety disorders, it was investigated whether HCC was a predictive parameter for treatment outcome. The treatment included all NICE guideline-recommended treatment approaches for depression and anxiety, including CBT. Non-responders had a lower HCC before the start of therapy (Five studies on this topic could be found. Three of them used variants of cognitive behavioral therapy. One of them provided results indicating a  therapy . In a fu therapy . In addi therapy .predict less improvement in clinical symptoms, but this relationship was no longer statistically significant after adjustment for baseline dissociative symptoms. Thus, there was no clear predictive value of HCC with respect to changes in PTSD symptomatology (In terms of less established psychological interventions, a study examined HCC in the context of multimodal trauma-focused inpatient psychotherapy for PTSD patients. Hair samples from 52 female PTSD patients were analyzed at different examination times. HCC measured at admission and discharge did not differ. Lower HCC before therapy could matology .In another study investigating the association between ECT and HCC, 62 patients with varying degrees of major depression were treated with ECT twice a week for 3 months. Here, HCC was not significantly elevated in the responder group. Increased hair cortisol levels therefore do not appear to be associated with better therapy outcome .The aim of this review was to summarize the current state of research on the effects of different psychological and neuropsychiatric interventions on HCC and to investigate the extent to which hair cortisol can be altered in such types of interventions. Although only a few studies have been published to date, there has been a general trend toward increased relevance of HCC measures in the context of psychological and neuropsychiatric interventions.HCC has been used to assess stress-related interventions such as relaxation training and, in fewer studies, for traditional forms of psychotherapeutic interventions such as CBT.before intervention. Thus, reduced HCC appears to be associated with a lower likelihood of treatment success (Looking at these publications, the reported study results are still rather inhomogeneous. As CBT is a well-established form of psychotherapy, the results of these studies are of particular interest. Two studies showed different associations between CBT and HCC. One study showed a decrease in HCC in the treatment group . In the  success . These s success , 48. ThuData on different relaxation methods, mental training, and ECT are also mixed. Half of the included studies found an association between the different interventions and a predictive potential in form of a longitudinal decrease in HCC.In the context of a multimodal trauma-focused inpatient psychotherapy, there was no predictive value for HCC changes in terms of PTSD symptoms improvement . VariousThe variability of HCC in ECT appears to be puzzling. Therapy responders showed increased HCC in one study . Howeverreduction in HCC with psychological and neuropsychiatric interventions, as no study showed a clear increase in HCC after the intervention, but several found a reduction in cortisol levels. As stress, as reflected by the cortisol levels, is an important underlying factor in the development of mental disorders, a reduction of cortisol levels seems to be of particular importance in alleviating the symptoms of disorders such as depression or PTSD. This highlights the importance of establishing a standard biomarker to measure the impact of psychological interventions.In summary, there is a trend toward a However, the results are still rather inconclusive. The explanation may be complex. One important aspect to consider seems to be that the effects of psychotherapy are not linear. Psychotherapy can often be upsetting and challenging within a given process. Thus, it may have an immediate stress-inducing effect, with the relieving effect coming later. The immediate effect of psychotherapy may also vary depending on the type of therapy and the invasiveness of the therapeutic interventions. The collection of catamnestic data may therefore be of particular importance in mapping the long-term effects of interventions. The lack of effects in some of the reported studies may be explained by the fact that they involved low-intensity stress management training and the like, which did not produce profound changes in the patients that resonated down to the biological level.The most important reason for the heterogeneous data may be the methodology used in the included studies and their varying quality. Due to the quality criteria, only a small number of publications could be included, which underlines the novelty of the research field. Hair cortisol as a biomarker for psychological and neuropsychiatric interventions should be considered as little established in a still evolving research field, which required the inclusion of studies of heterogeneous quality.per se, and hormonal changes, such as pregnancy, influence HCC. Higher hair cortisol levels have been found in young children and older adults (Some methodological limitations of HCC measurement must be kept in mind, which limit the validity and significance of the study results presented above. The comparability of all included studies is limited due to differences in age structure, numbers of participants and type of intervention. In addition, the reported divergent results may be due to different study designs. Additionally, gender differences in HCC, with higher values in adult men, may influence the discrepancy . Age perr adults . Thus, wFurthermore, the different measurement methods of HCC limit the comparability of the reviewed studies. It could be shown that the two methods of measurement were highly correlated with each other, but that immunoassays showed a constant tendency toward higher values . In addiNevertheless, a possible effect of various psychological interventions on HCC as well as some predictive value of hair cortisol in the context of such treatment modalities cannot be excluded. However, these results are still inconclusive and need to be investigated and replicated in further studies.In summary, HCC may be a valuable parameter for monitoring psychological and neuropsychiatric interventions in psychotherapy research. HCC seems to be particularly suitable for this purpose because it consists of aggregated cortisol levels over a defined period of time and represents a stress-related aspect of any psychological intervention or neuropsychiatric treatment. At present, the extent to which HCC can be used for these purposes cannot be clearly determined, not least because of the inconsistent data situation. Thus, the current state of research reflects only a fundamental orientation. However, it indicates that the documentation of changes in HCC during the therapeutic process seems promising and most authors consider it useful to include psychoendocrine biomarkers in psychological and neuropsychiatric intervention studies. Nevertheless, the potential of HCC for true psychological or neuropsychiatric investigations needs to be solidified by further studies with greater consideration of the parameters and study design requirements mentioned above. In the long run, this will hopefully define a clearer direction on the impact of psychological interventions on HCC and thus contribute to the relevance of hair cortisol as a standard psychobiological parameter. Psychopharmacological studies and larger epidemiological surveys of stress in a general population would benefit as well.psychological and somatic parameters to measure the therapeutic effect seems intuitive and highly relevant.The psychoendocrine approach to psychotherapy and psychological interventions may help to compare the effects of different psychotherapeutic methods and to establish differential indications for psychosomatic/psychotherapeutic treatment modalities. Especially for the psychosomatic field, the combination of The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.TB, BB, and EP contributed to conception and design of the study. VH contributed to literature research and wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.


The 7.8 magnitude earthquake that occurred in southern Turkey on February 6, 2023, has resulted in over 40,000 and 5,000 confirmed deaths in Turkey and Syria, respectively, including substantial infrastructure damage. While Turkey has received assistance from various countries and international organizations, the level of support Syria has received remains unclear. The Assad regime has demanded that aid be sent to the capital Damascus, but this may hinder the delivery of assistance to the areas most severely affected by the earthquake because the affected regions were mainly controlled by rebel forces.One of the biggest challenges in providing aid is accessing the affected region, as the earthquake occurred close to the border between Syria and Turkey, where roads and other infrastructure are poorly constructed. Furthermore, the northwest area of Syria shelters many internally displaced people, and more than 50% of medical facilities are not functioning due to the ongoing conflict, making the situation more hazardous.In light of the experience of the Great East Japan Earthquake, securing direct support routes and dispatching medical personnel to the affected areas is crucial for a gradual recovery from the disaster. Therefore, it is essential for the international community, including Japan, to negotiate with the Assad regime to expand direct support routes and provide support for the dispatch of medical personnel who will remain and work in the affected areas. Humanitarian assistance and political issues should be kept separate to avoid further hindrances to aid delivery. In this context, the magnitude 7.8 Turkey-Syria earthquake occurred on February 6, 2023. More than 40,000 people in Turkey and 5,000 in Syria have been confirmed dead. Although Turkey has received assistance from 70 countries, such as the United States, the United Kingdom, and Russia, including 14 international organizations, the situation of support for Syria from the international community is unclear.The need for international cooperation, regardless of the underlying political issues, to save the local people from disasters in countries experiencing internal conflicts is currently being emphasized (2). Furthermore, in Syria, more than 50% of medical facilities are reportedly dysfunctional due to the prolonged internal conflict (3), and the Syrian people are desperate to recover from the disaster on their own. As for international assistance for the earthquake, the Assad regime has demanded that all aid be sent to Damascus’s capital, including aid to areas outside their control. So far, Iran, Egypt, India, and some other countries have sent aid supplies directly to airports under the Assad regime’s control.This is mainly due to the internal conflict within Syria that began in 2011, which has divided the country into several ruling groups and resulted in a lack of domestic coordination. The Assad regime has been internationally criticized and isolated for its thorough suppression of rebel forces and is under severe sanctions. Consequently, the current report revealed that more than 80% of the Syrian people live in poverty, less than US$2 per day and more than 9 million people live in food scarcity (3), thus making the situation much more hazardous.However, some areas most severely affected by the earthquake were regions controlled by rebel forces. Although international aid should be provided based on formal requests from the affected country’s government to protect its sovereignty, delivering aid to the Assad regime by air may prevent timely assistance to victims in rebel-controlled areas, making it increasingly important to provide direct local assistance from abroad. Therefore, access to the area for humanitarian activities has become one of the major challenges since the earthquake occurred near the border between Syria and Turkey, where roads and other infrastructure are not well-developed. Indeed, before the earthquake, only one road in this area could carry supplies directly from Turkey to Syria, as rebel forces controlled this area. This is also an area where many internally displaced people, mainly women and children, have taken shelter from the internal conflict (4). This enabled the direct provision of necessary support and the dispatch of medical professionals from other prefectures, which considerably contributed to promptly improving the health of the affected areas. Despite different backgrounds, it is essential to recover from the disaster to prepare support routes as quickly as possible and to dispatch researchers and medical personnel to the affected areas so that the medical system can be set up promptly (4).Considering the experience of the Great East Japan Earthquake, one of the most critical initial responses was to secure 16 emergency routes to the affected areas by removing obstacles and opening access roads, known as the "teeth of a comb strategy," resulting in 97% of them being passable within one week (5). Thus, considering that the fundamental cause of the difficulty in providing international aid to Syria stems from the ongoing civil war, which has made it challenging to trust the current regime, it is crucial to undertake efforts to dispel tensions between the Assad regime and the international community by continuously implementing peacekeeping activities and long-term support, rather than solely focusing on short-term assistance in the aftermath of an earthquake. We look forward to establishing an international cooperative framework between Turkey and Syria and hope for a rapid reconstruction of both countries.In this context, the continued failure to secure support routes to Syria could lead to more deaths and injuries in the affected areas. Despite the differences in social stability, political, and cultural backgrounds between the current earthquake and the Great East Japan Earthquake, regardless of the political issues, it is crucial for the international community, including Japan, to negotiate with the Assad regime to expand direct support routes and to assist dispatching the medical personnel who will remain and work in the affected areas. Additionally, the purposes of the World Health Organization Emergency Medical Team Initiative include simultaneously enhancing the timeliness and quality of medical services through collaboration among domestic and international emergency medical teams, promoting rapid response capabilities in the immediate aftermath of disasters, outbreaks, and other emergencies, and strengthening the capacity of national health systems to lead coordination efforts NoneConception, designing of the study, and writing this paper; Kaneda YCritical revision of the paper; Akashima SAll authors have read the final draft and approved the submission.


Space has been a critical factor in the growth and development of modern economies –3. Posit8Although the average individual rarely interacts directly with space, almost all aspects of modern economies connect to it. These trends have become particularly prominent over the past few decades, as technology and policy shifts such as reusable rockets, greater computing power, and new contracting mechanisms have led to lower launch prices and increased commercial interest in space . These cAs an economic environment, space is unique. The Outer Space Treaty of 1967 is the predominant international legal framework governing human activity in space. This treaty states that outer space is not subject to national appropriation by claim of sovereignty, complicating the process of establishing property rights in space. The current legal regime poses challenges to economic development in space –15, as d16This Special Feature on “Space Exploration: Economics, Technologies, and Policies” explores key issues in space economics, focusing on the roles of states and firms in technology development, resource management, and economic growth. First, it assesses the implications of significant capital investments in space technologies, both historically and in their potential to combat secular stagnation. Second, it examines the role of the public sector in supporting and regulating the expanding space economy, both identifying promising new institutional structures and characterizing and quantifying their benefits. Finally, it considers the implications of more intensive orbit use and extraction of space mineral resources, outlining salient environmental trade-offs and policy catalysts.Prevailing views emphasize the huge role of government funding in promoting space exploration, against which the modern rise of private funding is an exception. But historical analysis reveals that private funding for space exploration, particularly in the United States, is more a norm than a recent anomaly .The belief that the early years of the “Space Race” led to substantial economic growth in the United States is also widespread , but empTheir main finding is that space activities provide positive spillovers to the economy with different intensities over time. These intensities reached their highest values between the end of the 1960s and the beginning of the 1980s and their lowest values in the 2000s. They consider an exercise that increases space-related production by the same amount under the high and low spillover scenarios and find that the transmission effects on output growth are more than double when associated with the high spillover scenario of the early decades of space activity. Specifically, space sector activity in the 1960s and 1970s had large positive impacts on GDP growth, increasing real GDP by 2.2% on average after 20 y. By contrast, space activity since the 1980s—when public space investment in the United States slowly waned as tasks were outsourced to private industry or simply no longer conducted—has had much smaller 20-y impacts on real GDP, on the order of 0.9%.These results provide lessons for existing and emerging space powers as they look to the historical record for guidance. Positive growth spillovers from space spending may be particularly attractive to policymakers in high-income economies to counterbalance stagnant growth and to use as a tool to fight deep downturns. However, it is not yet clear whether and how the largest effects of the early decades of space activity can be replicated by new space spending. Further research is needed on public space spending, the structure of the sector, and its role in economies at large.The roles of the public and private sectors are rapidly changing in the modern era, with governments paving the way for private corporations to build large, coordinated systems of satellites. These changes are spurred by major technological developments , the region between 100 and 2,000 km above mean sea level. New launch technologies and in-space R&D activities are likely to be spurred by the use of orbital space. The lack of orbital property rights due to the Outer Space Treaty will lead to costly misallocation of orbital space and overproduction of orbital debris and collision risk , 30–32. 30Ref. While there is substantial uncertainty over the scope and magnitude of environmental damages caused by orbit use, it seems clear that the damages are nonzero. Therefore, the authors examine how varying the magnitude of these damages affects optimal policy design. They find that at low levels of environmental damages, economic net benefits are maximized by maintaining more satellites in orbit than the duopoly would, while at high levels of environmental damages, economic net benefits are maximized by maintaining fewer satellites in orbit than the duopoly would. These findings emphasize the importance of studying the implications of competitive behavior in space for space resource use, quantifying the environmental and social costs of different ways of allocating space resources, and developing effective governance and regulatory models to maximize the global economic net benefits of orbit use.Looking ahead, generating sustained economic growth from space will likely require significant levels of capital investment. How might investments in space exploration interact with slowing growth on Earth, particularly in high-income economies? And how might the ability to access mineral resources in space affect growth on Earth, particularly in the face of ongoing environmental degradation? The final two articles in this Special Feature address these questions.Ref. 38Mineral resources naturally sit at the intersection of space exploration and economic growth. The popular press frequently cites the large abundances of minerals like platinum and cobalt in space, often valuing them at current prices. Although economic research points to more complex price dynamics and more muted valuations , the queThis Special Feature deals with several important topics—the economic impact of space investment, innovation-inducing organizational design, competition and optimal use of common pool resources, the potential for cleaner green transitions, and answers to secular stagnation—but it is not the last word on any of them. Rather, by exploring how expanding activities in space have contributed, are contributing, and can contribute to economic growth, these articles are meant to draw attention to the field and identify new and fruitful research directions. In addition to the questions identified throughout this Special Feature, we highlight four areas of study that can have a significant impact on the economics of space exploration and economic growth.First, it is important to remember that the budgetary investment related to space exploration has historically been linked to military objectives, such as the Cold War, which focused on geopolitical and military objectives rather than economics , 21. Tha45Second, while there is great potential for economic growth from space, continuing space development along its current trajectory will also create market failures that limit this potential. These include misallocation of orbital space and overproduction of orbital debris , as wellThird, although space exploration has the potential to boost future economic growth and scientific progress , 37, it 50Finally, effective policies and reliable predictions in the space sector demand comprehensive, high-frequency data. Such specialized statistics are currently scarce, often compelling analysts to rely on industry or government sources not specifically designed for studying the space sector , 23. TheIf managed well, the exploration and utilization of space could present unprecedented opportunities for economic development and sustainability. The articles of this Special Feature emphasize this potential and highlight the need for informed policy-making and international cooperation to govern human expansion into the cosmos.