Current UK health policy stresses treating health as an asset to underpin and promote a more inclusive and productive society. The quality of personal relationships is essential for overall quality of life. The social determinants of health (SDH) literature shows that poor mental health and well-being are linked to weaker personal and social connections for individuals, families, and society. The causal impact that mental health has on satisfaction with partners is less understood but requires investigation.The causal relationship between mental health and satisfaction with partners is examined drawing on the United Kingdom’s British Household Panel Survey from 1991 to 2008. A total sample of 9,024 individuals in dyadic couples comprising 42,464 observations was analysed using fixed-effects and instrumental variable fixed-effects panel data estimation.Lower mental health is associated with a lower satisfaction with partners. However, some causal evidence of lower mental health reducing satisfaction with partners is present for males.For females, relationship satisfaction is more likely to influence mental health. For males there is a potential ‘vicious circle’ between satisfaction with partners and mental health.Investment in mental health provision can improve satisfaction with partners which in turn will further enhance health and well-being. This paper investigates the relationship between mental health and satisfaction with partners in the United Kingdom (UK). It finds that lower mental health is associated with a lower satisfaction with partners generally but there is some causal evidence of lower mental health reducing satisfaction with partners for males. The context of the investigation is that the World Health Organisation (WHO) Rio Political Declaration in 2011 called for a global political commitment to address the Social Determinants of Health (SDH) and for national health policies and strategies to reduce the health inequalities deriving from the conditions in which people are born, grow, live, work and age , treatinThere are longstanding theoretical reasons to expect a link between relationships generally, well-being and health –12. RelaTwo strands of empirical work addressing these issues can be identified. One strand focuses on the characteristic of being in a partnership as an implied determinant of health and wellbeing. For example, being married or cohabiting is associated with improved health, lower morbidity and mortality , 20, lesAnother strand of literature focusses directly on satisfaction with the dyadic relationship and its association with health and well-being, exploring potential differences between males and females. It has been found that depression at a later point in time, for both males and females in a couple, can stem from previously experienced marital dissatisfaction , that hiSignificantly, less research has focussed on the implied role of health and well-being as a determinant of satisfaction with partners. Nonetheless, it has been shown that higher levels of depression can predict lower marital satisfaction  and thisFinally, other contextual factors have been shown to be important factors that shape the role of family relationships on well-being and health. These include income , educatiDrawing on the above policy context and literature this study seeks to contribute to better understanding the relationship between mental health and the satisfaction with partners for individuals who are married or in a civil partnership based on nationally representative longitudinal data. More specifically, the paper seeks to make a number of contributions. First, it responds to the call for more longitudinal studies that provide stronger causal inferences on such relationships . The focA longitudinal observational research design is employed based upon data from the British Household Panel Survey (BHPS). The BHPS is a longitudinal social survey of households and individuals living in the UK. It began in 1991 and lasted until 2008, when it was superseded by the Understanding Society Survey (USS). The first set of questions were implemented between late 1991 and early 1992 in Wave 1 and contained approximately 5,500 households with 10,300 individuals from England. In 1999, the survey was rolled out in Scotland and Wales, and in 2001 a sample from Northern Ireland was added. By Wave 11, the panel had grown to 10,500 households. The data cover a wide range of information including household and individual characteristics, socio-demographics, health and education, finances, and social activities. The BHPS is employed in this research as it explicitly investigates satisfaction with partners following the same representative sample of individuals for 10 years between 1998 and 2008. The analysis focusses on a dyadic sample of 9,024 individuals who are either married or in a civil partnership in each wave of the survey, producing a total sample of 42,464 observations.The mental health measure for this study is the 12 item General Health Questionnaire (GHQ12) . The LikSatisfaction with partners is measured in the BHPS through a question that asks individuals to rate explicitly how dissatisfied or satisfied they are with their spouse or partner. The responses range between 1–7, where 1 represents not at all satisfied and 7 represents completely satisfied. This variable measures one aspect of life-satisfaction, as a component of general well-being , and is Confounding variables measuring the individual’s age , level oFinally, because in a dyadic context there is the potential for an individuals’ partner satisfaction with them to influence their satisfaction with their partner, alternative specifications of the analysis were undertaken with the partners satisfaction with their partner included and excluded , 52. AllThe data presented there for dyadic couples is very similar to that for the sample of 65,768 individuals who are either married or in a civil partnership but are not matched across waves of the survey. For example, the mean values for the dyadic and non-dyadic individuals respectively are 6.401 and 6.354 for Satisfaction, 10.877 and 11.071 for GHQ12, 50.121 and 50.124 for Age and 1.773 and 1.749 for Real Family Income. A further consequence of focussing on such dyadic partners in the sample is that analysis distinguishing between the variety of forms of relationship status on satisfaction with partners is not undertaken. The focus is on married couples or those in a civil partnership rather than individuals who are cohabiting, separated, divorced, widowed or never married.To work towards a causal understanding of the effects of mental health on satisfaction with partners, fixed effects, and instrumental variable fixed-effects panel data estimators are employed. The fixed effects control for endogeneity associated with unobserved time invariant personal characteristics, while the instrumental variable fixed-effects panel data estimator is employed to additionally control for reverse causality.To apply the instrumental variable fixed-effects estimator, instrumental variables need to be identified that are correlated with GHQ12 but primarily affect satisfaction with partners indirectly through the mental health variable. Furthermore, the instrumental variables cannot be correlated with the unobserved factors measured by the fixed effects . In thisThe adequacy of the instrumental variables is, thus, tested statistically. Their relevance was examined through F-tests assessing their joint significance in a regression of the measure of mental health on the instrumental variables and other confounding variables. The potential significance of the lag of mental health being directly included in the equation explaining satisfaction with the partner was assessed through t-tests. Finally, the validity of the instrumental variables was tested by the Sargan-Hansen test, which examines the independence of the instrumental variables from the errors of the instrumental variable regression . FinallyTables The regression results in Table The instrumental variable fixed effects panel data analysis reported in Table The instrumental variable results also show that for males and females a partners’ satisfaction with them remains positively associated with their satisfaction with their partner. However, the influence of a partners’ mental health on an individual’s satisfaction with their partner also becomes insignificant. These results suggest that satisfaction with partners is the key conduit with which mental health states can become shared by couples once the causal influence of individuals’ mental health on their satisfaction with partners is identified.The results also demonstrate a ubiquitous negative association between age and satisfaction with partners and the number of children aged greater than three years in the household. Given the mean age of the sample, the former results are consistent with the literature which suggests that middle aged couples experience a dip in their marital quality , while tThe above results identify a ubiquitous influence of cross-partner satisfaction. The potential for a difference between males and females in the influence of mental health on satisfaction with partners, moreover, supports previous evidence in the literature. It has been noted for example that for females marital discord adds more to stress . MoreoveHowever, for males it has also been shown that relationships are affected by their perceived independence and not needing emotional support . For exaThe study adds to the literature, thus, in demonstrating that in a longitudinal context mental health is an important feature of a happy and satisfied personal relationship for dyadic partners in the UK. However, the analysis also reveals that for males, poorer mental health has the potential to exacerbate feelings of lower satisfaction with partners and hence their well-being. These results are important as they offer supporting evidence for the WHO and the recent NHS policy arguments that health can be viewed as an asset that underpins the well-being and flourishing of individuals. The results indicate, thus, that investment in mental health support in the UK could have intersectoral and cross-cutting impacts on other social care domains such as relationship counselling which need to be accounted for in planning , 63. SucThis study has limitations. The analysis is based on the UK and hence the generalisation of the results needs further investigation because it is known that gender differences in mental illness vary internationally . ConstraFuture research might also focus in a more nuanced way on the pathways in which mental health might influence marital quality. As noted above, the GHQ12 is an aggregate measure of mental health to which there are distinct components measuring, for example, depression, confidence, being under strain etc. . MoreoveIt has also been argued, for example, that well-being is highest for married individuals, and successively declines for those that are cohabiting, dating, single, widowed and divorced . MoreoveCurrent UK health policy increasingly seeks to identify health as an asset, playing a role in an integrated care system seeking to promote a more inclusive and productive society, with a focus on the general flourishing of individuals. The literature also recognises the importance of personal relationships in the promotion of health and calls for further longitudinal analysis and causal inference. This study has undertaken the task of addressing causality between mental health and the satisfaction with personal relationship based on a nationally represented longitudinal data in the UK. This is achieved by applying fixed effects instrumental variable panel data estimation.The analysis above shows that investing in mental health as an asset can improve the well-being of individuals through raising satisfaction with partners which can be amplified across partnerships. Such investment, it is shown, is particularly important for males for whom there is some evidence that poorer mental health can reduce satisfaction with personal relationships thus potentially creating a vicious circle of decline.


Gender- and diagnosis-related differences are discussed. Conclusion: Reporting life stressors experienced during childhood or adulthood is strongly associated with IBD. This should be considered in illness management, especially in a severe course of IBD. Background: Stress has been suggested to play a potential role in inflammatory bowel disease (IBD) pathogenesis, but studies focussing on the occurrence of specific life stress events among IBD patients are scarce. Therefore, the aim of the present study was to explore the association between various life stress events and IBD. Methods: Patients with IBD  were compared to a group of healthy controls  originating from a health survey conducted on a representative population sample of Czech adults. The Life Stressor Checklist-Revised (LSC-R) was used to assess the stressors. Results: IBD patients had higher odds of reporting life stressors overall ( Inflammatory bowel disease (IBD) is a group of chronic health conditions with increasing prevalence in the population . Crohn’sStress, chronic and acute, is associated with alterations in systemic immune and inflammatory function, which may be relevant in the pathogenesis of IBD . Many stEarly life events, such as a complicated birth and a lack of breastfeeding, as well as later childhood stressful events are considered to be potential risk factors for IBD . FurtherAlthough a strong relationship between perceived stress and GI symptoms has been determined, a study of Targownik et al.  showed tPatients suffering from IBD experience an increased level of stress in relation to work, family and financial pressure . In a VeOnly a few studies of stress in IBD have used a healthy control group . Given tN = 1800) were collected by trained administrators using face-to-face interviews during September and November 2016. For the purposes of this study, we identified 405 respondents reporting no chronic conditions .Two groups were compared in this study: (1) A control group originating from a health survey conducted on a representative population sample in the Czech Republic. Data on this sample  consisted of 62 patients with Crohn’s disease  and 36 patients with ulcerative colitis . The IBD patients were asked to fill in the same questionnaire battery as the control group. The patients were approached by healthcare professionals who were trained to assist in completing the questionnaire. The patients completed the questionnaires themselves during a visit to the gastroenterological clinic, assisted by a healthcare worker. The clinical sample describes a “non-average” group of IBD patients, because the patients were recruited at gastroenterological centres which concentrate patients with complicated disease course .(2) A group of IBD patients. These patients were selected at random at two Czech IBD centres . Collection of the clinical sample took place in May and June 2017. Of the total number of 110 questionnaires, 98 were completed. The whole clinical sample with IBD .Participants reported gender , age (continuous), living arrangement , education , and economic activity .The Life Stressor Checklist-Revised (LSC-R) is a questionnaire that captures traumatic experiences during childhood and during later life. In the Czech Republic, the questionnaire was validated as a clinically useful tool for detecting life stressors and also for research purposes . The LSCWolfe et al.  recommenThe advantage of the LSC-R is that, in addition to capturing stressors, it measures the personal meaning of stressors in a specific patient. The LSC-R accounts for potential stressors but also captures the participant’s feelings concerning the life event. The LSC-R tool can be one of the options for orientation in a patient’s life. Some items on the questionnaire can be traumatizing for people just to think about, which is why at the end of this study the possibility of a psychotherapeutic intervention was offered.For describing sociodemographic characteristics, means and standard deviations (SD), frequencies and percentages were used. For all other analyses, including logistic regression, the scores of life stressors in total, the stressors before the age of 16 years, events considered to be traumatic stress events and the events comprising interpersonal violence were dichotomised according to their mean + SD value. The differences in the occurrence of life stressors between the groups were assessed using a test of proportions (Z-test).Binary logistic regression was used to model the odds of being in the IBD group, depending on the occurrence of life stressors. All the regression models were adjusted for the age and gender of the respondents. A statistical significance level of α = 0.05 was used in all the tests.All the statistical analyses were performed using the IBM SPSS software, version 21 .The sociodemographic characteristics of the research groups, i.e., the healthy control group (HC) and the IBD patient’s group, are described in p < 0.05).The occurrence of life stressors in general, life stressors before the age of 16 years, life stressors reaching traumatic stress, and interpersonal violence in the research groups are depicted in p < 0.05) of almost all the assessed life stressors, with the exception of experiencing a disaster, accident, financial problem and sudden death of a family member.The occurrence of individual life stress events in the research groups is depicted in p < 0.05) of separation of parents, serious illness, death in the family, robbery, robbery witness and physical abuse before the age of 16 years compared to healthy men. Women with IBD experienced a significantly higher proportion of having a family member in prison, separation, serious illness, abortion, serious illness and nurturing in a family, sudden death in the family, psychical abuse and neglect, violence in the family and physical abuse after 16 years of age.To assess the odds of being in the IBD group, depending on the occurrence of life stressors, a logistic regression was used. The HC respondents were considered as the reference group. The reporting of life stressors in total, life stressors before the age of 16 years, life stressors reaching traumatic stress and life stressors indicating interpersonal violence was significantly associated with IBD , see In a comparison of the UC and CD patient groups, we found that reporting interpersonal violence, physical abuse before the age of 16 years, sexual harassment and a sudden death in the family was significantly associated with UC  and that indicating a serious illness as a life stressor was significantly associated with CD (OR = 0.26).The aim of the study was to explore the association between life stressors and IBD. Our main hypothesis—that the group of patients with a severe course of IBD would report a higher occurrence of stressors throughout their life compared to healthy controls—was supported. In our sample, IBD patients had higher odds of reporting life stressors in total, life stressors before the age of 16 years, life stressors reaching traumatic stress, as well as life stressors indicating interpersonal violence. The differences between men and women and UC and CD are discussed below.In our study, reporting life stress events connected to the family, e.g., one’s own serious illness, serious illness and nurturing in the family, a death in the family, separation of parents, partner separation or the imprisonment of a family member, was strongly associated with IBD. A study by Jakobsen et al.  found thOverall, suffering from a serious illness was reported to be one of the most common stressors by the IBD patients in our study, mostly in men and in CD patients. IBD itself turns out to be a serious stressor . In partA comparison between the UC and CD groups in our study shows that reporting serious illness as a stressor was strongly associated with CD. A German multicentre study of patients with CD and UC  found thIn our study, IBD was associated with a higher occurrence of all life stressors before the age of 16 compared to the healthy controls. Although only limited research on adverse childhood events and IBD has been conducted, there is some evidence of a relationship between them. Thoman, Lis and Raindl  showed tA population-based study also concluded that IBD is strongly related to a generalised anxiety disorder, especially in women suffering from chronic pain and those with a history of childhood sexual abuse . DiffereOur study assessed life stressors reported by patients with a severe course of IBD. It is important to take into consideration that the stressors were evaluated subjectively and that two people who have experienced the same stress event may experience the situation differently, with a different stress level. Perceived stress is a concept which points out that the degree of stress experienced in a specific person can be influenced by various factors, such as personal characteristics, lifestyle, social support and type of life event . The LSCThe results of the logistic regression in our study show that experiencing adverse childhood and adulthood events is associated with a severe form of IBD. Life stress and abuse history have physiological and behavioural effects that amplify the severity of the condition experienced. These effects lead to increased seeking of health care and explain the higher association of abuse histories with GI illness in referral centres and specialty groups when compared with primary care . DiffereThis study provides some valuable information that can help practitioners address their patients’ most frequent stressors. Recalling and talking about difficult life situations can also be a starting point for psychotherapeutic work during treatment of the disease. Patients with IBD often perceive stress as the leading cause of their disease. This can lead to feelings of self-blame, thus causing a relapse. To prevent this vicious circle of stress, gastroenterological practise should be interconnected with mental health practice. Our study indicates that continuous monitoring of IBD patients is very important, because personalised care can help prevent disease flares and the accompanying mental health complications. A recent study recommends asking questions about mental issues, stressors and quality of life in common gastroenterological care . Trying The strength of this study is that only patients with a clinically determined IBD diagnosis coming from IBD centres were involved, i.e., they were not just self-reported. The results may be affected by the fact that patients were receiving biological treatment or have had surgery. This means that these patients had a severe course of the disease and were in a situation when the first choices of conservative cure were not sufficient. On the other hand, the fact that only patients with severe course were involved is in conformity with the need to differentiate the disease severity in subgroups of IBD patients—in our study group those with a severe course of the disease . AnotherA limitation of the study is its cross-sectional character, which does not allow us to assess the causality between stress and exacerbation of the disease. The higher occurrence of stressors in IBD could have been affected by the patients’ severe form of the disease. This means that the results cannot be generalised to all IBD patients. The differences between the severe and mild or average course of the disease should be assessed in future studies. The sample of IBD patients was selected randomly at only two large IBD centres in the Czech Republic, not throughout the Czech Republic. We do not know the onset of the disease in these patients, whether it occurred in childhood or in adulthood.The healthy control group includes respondents who reported being healthy. Even if some respondents could underreport their health problems, the assessment of health status by self-report is a valid option in national multimorbidity studies . We assuOur study shows the connection between a higher occurrence of life stressors and IBD patients with the severe form of the disease. A comparison with healthy controls shows us that patients with severe forms of IBD refer to a higher occurrence of overall life stressors, life stressors before the age 16 years, interpersonal violence and traumatic stress. This should be considered in the management of the illness, especially with severe forms of IBD, when conservative treatment is not sufficient and target psychotherapeutic interventions could be valuable. Possible differences between men and women with IBD and patients with UC and CD in experiencing life stressors should be considered in psychosocial management of the illness as well. The LSC-R is a possible tool for catching stressors and a starting point for communication about the role of adverse life events in a patient’s life.


Current literature recommends online research guides as an easy and effective tool to promote LGBTQ+ health information to both health care providers and the public. This cross-sectional study was designed to determine how extensive LGBTQ+ health guides are among hospital and academic libraries and which features are most prevalent.In order to locate LGBTQ+ health guides for content analysis, we searched for guides on the websites of libraries belonging to the Association of Academic Health Sciences Libraries (AAHSL) and the Canadian Association of Research Libraries (CARL). Additionally, we searched the Springshare interface for LibGuides with the word “health” and either “LGBT” or “transgender.” Content analysis was performed to identify major characteristics of the located guides, including target audience and the information type provided.LGBTQ+ research guides were identified for 74 libraries. Of these, 5 were hospital libraries, and the rest were academic libraries. Of 158 AAHSL member libraries, 48 (30.4%) had LGBTQ+ guides on their websites. Nearly all guides (95.9%) provided general LGBTQ+ health information, and a large majority (87.8%) also had information resources for transgender health. Smaller percentages of guides contained information on HIV/AIDS (48.6%) and women's health (16.2%).Even though literature recommends creating LGBTQ+ health guides, most health sciences libraries are missing an opportunity by not developing and maintaining these guides. Further research may be needed to determine the usage and usefulness of existing guides and to better identify barriers preventing libraries from creating guides. The lesbian, gay, bisexual, transgender, queer, and plus (LGBTQ+) community has a long-recorded history of facing discrimination, social stigma, and issues leading to health disparities. Often classified as a sexual and gender minorities subgroup, research shows that members of the LGBTQ+ community are more likely to have mental health disorders, adverse childhood experiences, increased alcohol/drug use, and an increased risk of sexually transmitted infections (STIs) –3. BeyonWhile the LGBTQ+ community overall faces many difficulties, these stigmas and health disparities are doubled for transgender members of the community due to a lack of legal protections , 7. TranHIV infection remains a health disparity not only for transgender women but also for men who have sex with men (MSM). MSM is a category which encompasses gay men and bisexual men as well as men who may not identify as gay or bisexual but who still engage in sexual activity with men. In 2018, gay and bisexual men represented 69% of new HIV infections despite ongoing HIV prevention efforts through education and PrEP availability . MSM areCisgender individuals within the LGBTQ+ community similarly face a number of health disparities in comparison with the general population. Research shows that lesbians and bisexual women, as compared with heterosexual women, are more likely to be overweight or obese . They arIn part, members of the LGBTQ+ community continue to face these disparities due to the continued discrimination and lack of training of health care professionals. Culturally sensitive physicians, medical students, and other health care providers are needed to prevent many of these barriers to health care. For example, LGBTQ+ patients often do not disclose their experiences to health care providers . More trA review of the library sciences literature reveals a number of articles that discuss guides and other online resources as a way for libraries to reach out to the LGBTQ+ community and provide access to information, including information on health topics. Online library resources for LGBTQ+ information needs have an important role in higher education. Mehra and Braquet 2011) describe the use of an LGBT research guide at a major university library and recommend improved access to LGBTQ information online as a method for university reference librarians to be more engaged with students during the coming-out process . In his 11 descriIn their article on providing health information to the LGBTQ+ community, Hawkins et al. (2017) note that online information resources such as research guides, as well as physical materials in the library itself, can be a means for librarians to disseminate quality consumer health information to the LGBTQ community . Other sMorris and Roberto (2016) suggest that library guides or resource lists on LGBTQ health could be helpful in meeting the information needs of LGBTQ health professionals. They stated that these resources could indicate the subject expertise of the librarian behind them, as well as the availability of the librarian to partner with health care professionals . HawkinsThis previous research highlights the benefits of online resources such as subject guides for LGBTQ+ topics, as well as desire among potential users for these guides. However, a number of these LGBTQ+ guides lack health information addressing the specific needs of the community, which does nothing to help alleviate the need for health information and by extension potentially reduce LGBTQ+ health disparities. LGBTQ+ health guides are by no means universally found on the websites of health sciences libraries in North America, despite the recommendations of numerous authors. The objective of this cross-sectional study was to assess the degree to which academic and health sciences librarians are creating and maintaining LGBTQ+ health LibGuides at US and Canadian colleges and universities.In order to locate as many LGBTQ+ health science research guides as possible, we used a three-part methodology. All of the searches and analyses were conducted in July 2019.First, the website for the Association of Academic Health Sciences Libraries (AAHSL) was accessed, and the organization's membership directory was consulted to provide a standard list of health sciences libraries in the United States . The libAAHSL membership is open to libraries serving medical schools in the United States and Canada that are affiliated with the Association of American Medical Colleges. However, because there were only seven Canadian members of AAHSL at the time of this study, the decision was made that another method should be chosen to identify possible Canadian libraries. There is no equivalent organization to AAHSL in Canada. As a substitute, we used the member list of the Canadian Association of Research Libraries (CARL). In 2018, there were twenty-nine CARL member libraries . Of the Finally, to locate other potential academic libraries with LGBTQ+ health guides but were not members of either AAHSL or CARL, a search was conducted on the LibGuides Community portal . The seaBecause the focus of this study was to find and assess guides to promote health information among health care professionals, health care students, or consumers, a few exclusion criteria were established. Guides were excluded from consideration if the guide or guide page did not focus exclusively on LGBTQ+ health. For example, a page with multiple categories of LGBTQ+ resources, with a box for health resources included, would be excluded because its primary focus was not health. As previously described, guides from public and school libraries were not included. Finally, guides created for specific courses were excluded because they have a specific target audience and are not designed for wider usage.After identification of the guides, we performed content analysis to determine whether certain information categories were present or absent within the guides . We focuLGBTQ+ health research guides were located for a total of 74 institutions . Five ofRegarding the guides' target audiences, just over one-third of the guides  featured consumer health information targeted to the general public. Higher percentages of guides appeared to target health care professionals  and university students , which may be expected considering that the publishing libraries were either academic or hospital libraries.Nearly all of the guides  featured general LGBTQ+ health information, with no particular focus other than the health of the LGBTQ+ community broadly. Most of the guides  had information specific to transgender health. Just under half of the guides  featured HIV/AIDS information, and an even smaller number  contained information specific to women's health. All but one of the guides featured links to websites . Nearly two-thirds of guides  provided book information, and just under half  had links to library databases.Content analysis of the information categories provides some insight into the health priorities of the LGBTQ+ community at present. As one might expect, general health information for the community was found on the vast majority of guides to appeal to the widest number of information seekers. The high percentage of guides featuring transgender health (nearly 88%) is encouraging, as it shows that awareness of the transgender members of the community and their specific health needs is more widespread than it might have been in the past.AIDS Information Sourcebook and HIV/AIDS Internet Information Sources and Resources [More surprising, perhaps, was how few guides featured specific information on two long-time core areas of LGBTQ+ health: women's health and HIV/AIDS. Since the 1980s, HIV/AIDS has dominated discussions of health for the community. Libraries and librarians played a role in providing information on HIV/AIDS to the community during the early decades of the disease, as is reflected in AIDS reference books by librarians from the early 1990s like esources , 34. Howesources . A seconesources . Despiteesources . BecauseAn example of such a guide is the one created by librarians at the Florida International University (FIU) Herbert Wertheim College of Medicine Medical Library. Librarians, in collaboration with researchers from the medical school and school of public health, created a LibGuide on transgender resources based on feedback from a study examining disparities of transgender women of color in South Florida . This stBecause the majority of LGBTQ+ people with HIV/AIDS in the early days of the disease were men, the specific health needs of lesbian and bisexual women were often overlooked. However, there are a number of specific health disparities affecting these women, both in regard to increased risk of certain diseases and in decreased usage of preventative care such as mammography and Pap smears . ConsideThese guides vary not only in their subject areas but also in the types of materials presented. Some are fairly basic, consisting of links to relevant databases, books, and websites. A few guides contained PubMed search strings that were constructed to help the user search for the latest journal articles. Other guides have elements which educate the reader on LGBTQ+ health issues and needs. For example, the University of Arizona's guide for health care providers on working with LGBTQIA+  patients includes a tab on health care–specific recommendations. This page includes descriptions of how specific groups within the community may feel anxious about their interactions with health care providers and suggestions on how providers can communicate more effectively and positively with their patients .Some guides highlighted national, international, and local organizations. Guides published by college and university libraries often connected users to student services organizations on campus, such as gay/straight alliances and medical professional associations. In this regard, the librarian is creating connections between the users and the greater community, which can lead to collaborations between librarians and the greater community. As described in the FIU study, librarians and public health faculty reached outside the university to work with local organizations to improve health knowledge and increase usage of available medical services . The autThe presence or absence of a guide on a library website is most likely the result of the motivations of the librarian creating the guide. Stevens et al. (2019) hypothesize that outreach projects of health sciences librarians supporting the health of the LGBTQ+ community tend to be projects initiated by the librarians themselves rather than top-down initiatives within their libraries or larger institutions. These librarians could be considered early adopters of LGBTQ+ health initiatives and even activists for social justice by promoting health and social equity through access to health information . The guiJust as the presence of these guides leads to speculation on the motivations of the guide creators, the absence of guides leads to a separate but related set of questions. A library without one of these guides does not necessarily indicate that the librarians or their institutions are uninterested in LGBTQ+ health or are antipathetic to the community. While Siegel et al. (2020) report a small number of homophobic librarians in their study, the vast majority of librarians displayed positive or neutral feelings toward the LGBTQ+ community . Based oWhile the health disparities that this study focused on are traditional core areas of LGBTQ+ health, other disparities may appear in the future and could be included in guides. At the time of writing of this article, the United States is dealing with the COVID-19 pandemic. There has been speculation that, as a result of some of the disparities mentioned above, such as smoking, obesity, hypertension, and HIV, the LGBTQ+ population is at an increased risk of the adverse effects of the coronavirus , 41. TheLike many web pages, research guides are always in a state of flux. Our study only provides a snapshot based on an exploratory search in July 2019. It is possible that new guides have been created since this initial work or that guide content has changed. In fact, we hope that more guides have been created since the initial work, making the numbers reported here lower than they actually are at the time of this article's publication. It is also possible that, due to the difficulty in systematically searching Springshare's search engine, some relevant research guides were not retrieved by this method. Also, while the vast majority of libraries use Springshare's LibGuides platform for their research guides, there may be some smaller libraries which opt for another platform. Those libraries, if not members of AAHSL or CARL, would have been missed with the methodology used.An additional limitation of this study was that only four health information categories were selected for coding. Further research could allow for inclusion of some areas not chosen for this basic initial analysis. Deeper coding to allow for subcategories could also be included, such as hormone therapy or mental health under the transgender health category, or PrEP and other HIV prevention measures under the HIV/AIDS category. Further deep coding could also allow for searching for information categories pertaining to specific LGBTQ+ communities. While this study did actively look for transgender health information, it could be possible to search for less recognized groups in the community, such as asexual or intersex.Research guides have been ubiquitous elements of library websites for decades. In academic libraries, these guides are often not used by students, for reasons including ignorance of the guides and a preference for Google searching first . If one Despite the importance of locating quality LGBTQ+ health information, a major unanswered question is exactly how useful these guides are to the end users. Further research should look into how effective they are, perhaps with a cross-institutional study on usage numbers. No matter how often the guides are actually used, though, one could argue that the guides are important no matter the usage data. Considering that it is estimated that 4–5% of the US population identifies as LGBTQ+ , informa


Low education levels of each parent were associated with an increased likelihood of having non-zero carious tooth surfaces . The presence of cavities was predicted by the consumption of carbonated soft drinks , candies , sweetened milk , tea , or cocoa . Furthermore, the non-zero values of the dentinal caries index were more likely in rural schools , and a negative association between the county development index and the fillings/restorations index  was also established. The outcome of this research highlights that the presence of caries  in Romanian schoolchildren is influenced by their socioeconomic background, as well as their specific consumption behaviors.Oral health-related behaviors and living conditions play an important role in general and oral health. This study aimed to evaluate caries prevalence and severity in schoolchildren residing in rural and urban areas of Romania, and to correlate these with oral health-related behaviors. An estimation of the required sample size was conducted (sampling error of ±3% at a 95% confidence level), followed by the stratification of administrative units and then the selection of 49 schools. The Hurdle approach was used to analyze the dataset, requiring two sets of analyses for each outcome variable: a multilevel binary model to predict prevalence, and a multilevel Poisson analysis using only non-zero values. The mean and standard deviation (SD) for the dentinal caries index was 4.96 (5.33). Girls were more likely to have non-zero restoration codes (β = 0.14, SE = 0.08,  Caries is a multi-factorial disease resulting from a series of events that evolve in a chain, lasting for years ,2. It isIn order to benefit from a more comprehensive understanding of how social factors might influence the prevalence of caries, the differences observed between rural and urban areas also constitute a strong factor to be considered. Rural living deprivation has been linked with poorer dental health in several surveys ,9,10. Numerous comprehensive studies in the field have been conducted in countries like Italy, Greece, Hungry, Slovenia, and Croatia, and these have provided valuable insights and future considerations, reporting big differences among countries  ,11,12,13Despite multiple studies being conducted in neighbouring countries, Romania lacks comprehensive national oral health surveys in children or adults. A previous study by Petersen et al. was conducted in the 1990s covering only five major cities and without taking into account rural areas. Some local papers describe a high caries prevalence ,15. OnlyA cross-sectional epidemiological survey “Romanian Oral Health Survey” was designed and conducted in 2019–2020, focusing on two age groups, and this paper was aimed to describe the caries prevalence and severity of carious lesions in 11–14-year-old schoolchildren residing in rural and urban areas of Romania, and to correlate these findings with oral health-related behaviors.The first phase of the research represented the sample selection of the children and the development and validation of questionnaires for the targeted samples. The public schools to be included in the survey were selected based on the number of children registered by the National School Inspectorate in the 42 counties of Romania. Romania is divided into administrative units called counties. Each county is administrated by a major city and gathers together several smaller cities and villages. Rural and urban localities are categorized by the National Administration according to the number of inhabitants. As Romania doesn’t benefit from any source of systemic fluoridation, data regarding fluoridation have never been gathered. Moreover, there are no water or milk fluoridation programs, and sources of fluoride in the soil and water are scarce .An a-priori estimation of the required sample size was conducted assuming a sampling error of plus or minus 3% at a 95% confidence level. The number of children enrolled in the 8th grade National Exam for each Romanian school was established using public information available on the websites of all County School Inspectorates . This process involved the evaluation of publicly available information from 4696 schools, which aided our understanding of the territorial distribution of the target population. The sample was stratified and randomized. The stratification was performed on the administrative units (counties), and on locality type . For each county, the total number of pupils was determined and expressed as a percentage share related to the total number of children. The percentage share was used to estimate how many children would have to be included in each county. The obtained number was then divided based on locality type  and the final target number of evaluations was obtained. MS Excel’s randomization function was used to select an urban and a rural school for each county. As a result, a total of 49 schools distributed in rural and urban areas were selected. At every school, all the students in one class were invited to participate in the study. Although the participation rate was not recorded in detail, it is possible to estimate an inclusion of at least 90% of all children in these 49 schools. School level predictors included also the County Developmental Index, which is a sociological index that combines county-level variables: education stock, life expectancy at birth, medium age of adult population, average living space, number of private cars to 1000 inhabitants, and average household gas consumption. The aggregation of all these different variables was done using factor analysis, and the scores were relevant for assessing the county’s workforce potential, and also the county’s economic potential. Data was collected using the Oral Health Questionnaire for Children developed by the World Health Organization and described in the WHO Oral Health Surveys—Basic Methods, 5th edition, 2013 . The EngChildren were examined in a classroom or any available room, with the teacher present during the procedure, using special lighting sources and examination kits. Each participant came to the examination with the informed consent and questionnaire signed by parents/caregivers. ICDAS criteria were used to classify visual caries lesion severity, and the ICCMS Guide for Practitioners and Educators  was usedExamination was conducted by 10 calibrated dentists. The calibration procedure was carried out by examining 21 subjects displaying an inter-examiner kappa ranging from 0.74–0.86 and intra-examiner kappa ranging from 0.81–0.92. The kappa coefficient for fillings was consistently in the excellent range, while for lesion severity it was in the good to excellent range. None of the children included in the present sample were re-examined. The required calibration of the dentists was performed prior to the data collection, as described.n = 57). Regarding the remaining outcome variables, the over-dispersed multilevel Poisson analysis was used for the dentinal caries index  and the classical multilevel Poisson analysis for the FT index . Because the interpretation of multilevel analyses is eased if the predictors are centered, the median value was used to center each predictor. The analyses focused on studying the relationships between each predictor and the three output variables. For each predictor, two separate regression analyses were conducted: a multilevel logistic regression and a multilevel Poisson regression. These analyses accounted for the nested nature of the data and are equivalent to examining the zero-order correlations between predictors and outcomes. For all multilevel analyses, the HLM version 7.02 was used.ICDAS codes higher than 3 (caries into dentin) were computed as dentinal caries (number of carious tooth surfaces), missing teeth due to complex carious lesions as MT, and number of restored tooth surfaces as FT. By computing these indices, the variables associated with caries  and the variables associated with the treatment of decayed teeth (the MT and FT indices) were analyzed. As children were sampled from 49 schools, a multilevel approach was used to analyze the data. The Hurdle approach was used to analyze the dataset for each outcome variable. The Hurdle approach requires two sets of analyses for each outcome variable: a multilevel binary model (multilevel logistic regression using the Bernouli estimation) to predict the prevalence of each outcome, and so to predict the absence or the presence of caries using the entire sample, and a multilevel Poisson analysis using only the children with non-zero values. Because more than 90% of the sample did not have any missing teeth due to extractions, the Poisson analysis on this outcome was not conducted, as the remaining sample would have been too small . A total of 43.71% of the children resided in rural areas and 56.29% in urban areas, mostly small cities. Almost one third of the parents had high school education . ICDAS caries codes and restoration codes differed by region  and gendp < 0.05). Low education levels of each parents were also associated with the increased likelihood of having non-zero carious teeth surfaces  and non-zero restoration codes   . Interesn level) .p < 0.01), candies , sweetened milk , sweetened tea , or sweetened cocoa . Interestingly, negative relationships can be observed between the existence of restored tooth surfaces (the FT index), the frequent consumption of carbonated soft drinks , and the frequent consumption of sweetened cocoa . In the context of the relationship between the consumption of sweetened products and the outcome variables, a significant association, mostly with the presence of cavities  can be observed. The presence of cavities was predicted by the consumption of carbonated soft drinks , and between the frequent consumption of sweetened cocoa and the FT index  can be observed. A detailed description of nutritional behavior can be found in the The Poisson regression analyses of non-zero count data  suggest p < 0.01). The other significant relationship can be observed as a negative association between the county development index and the RT index .Lastly, it was evaluated whether two school-level variables (place of residence type and the county development index) were also associated with the oral health indices. The results show that the non-zero values of the dentinal caries index were more prevalent in rural schools, in comparison to the schools from urban areas  and in terms of treatment . This could be explained by contextual factors related to the lifestyle and health behavior of the people who live in rural areas . Health disparities have profound social, political, and economic consequences for society. Children living in poverty, or poor housing, who have a poor diet or lack access to high-quality early years education, are more likely to experience chronic adult illnesses and the intergenerational perpetuation of poverty and poor health ,22.The results regarding the living area characteristics highlight that children living in rural areas have a higher probability of developing caries compared to children from urban areas. However, the restoration index is not affected by the rural–urban residency. Furthermore, the number of restorations is negatively impacted by the level of county development and has no influence on the presence of caries or restoration behaviors. Gender, the first variable of the demographic dimension, does not produce any relationship with the presence or absence of caries, as boys and girls appear to have a similar prevalence of caries. Nonetheless, gender is a predictor of restoration behavior, as restoration is more likely to occur in girls. This difference can be explained by a higher level of attention paid by parents, by more requests of girls compared to boys, or by gender differences in attendance to medical services or oral hygiene, leading to more advanced stages of untreated decay in boys’ teeth. The fear factor among girls who prefer to have decayed teeth filled, or even a perceived fear factor from the perspective of the practitioner was also described in Scotland in relation to the presence of restorations . The presence of restoration might be influenced by the lack of dental check-ups among low-income families and by previous negative experiences of service provision among both children and caregivers, as well as logistical difficulties in making and keeping appointments as a result of a lack of transportation, an inability to get time off work, or having to balance responsibilities where, for example, single parents have to care for many children ,25.The demographic dimension of the respondents included the parents’ level of education (both mother and father). These indicators are important predictors for the absence of caries as well as for restoration behaviors. The higher the level of education of parents is, the greater the probability that the child will not have caries. Similar figures were observed about restoration behaviors. Children with highly educated parents have a higher probability to have restoration treatment. Based on this, it could result that the presence of caries in children might be predicted by their parents’ level of education. Furthermore, parents’ level of education might be a useful predictor not only for the presence or absence of caries, but also for the number of caries that children have. The lower the level of education of parents is, the higher number of caries their children have.Socio-demographic patterns in caries were highly influenced by a high education level of the father, suggesting that this parameter should affect caries severity, as previously reported ,25. An aThe survey data show that there is no apparent relationship between the presence of caries and the restoration index of the frequency of tooth brushing. However, there is a statistically significant relationship between the lack of hygienic behaviors and the number of caries lesions. Good oral health behaviors reduce the risk of caries and are thought to have been key factors in the reduction of caries in developed countries observed in the past 20 years . DespiteOne of the limitations of the study resides in the interpretation of the results, which might be biased because of the study’s design, as, in general, a cross-sectional study measures cause and effect at the same point in time, therefore introducing the problem of temporal ambiguity and an inability to establish causal relationships. Among the limitations of this survey, it is possible to recognize some methodological difficulties in organizing and managing the data collection across the 42 counties, and not registering the participation rate can be considered as one of the limitations of this study. Additionally, it is necessary to take into account that the questionnaire data source may not be reliable enough, specifically in relation to socioeconomic data.The validity of the findings is supported by the complex process of the sample selection and data analysis as well as by the thorough calibration process. The present study is the first one carried out in Romania that takes into account caries prevalence and also evaluates the role of the main caries risk factors and oral health-related behaviors, using the STEPS approach as suggested by the WHO guidelines. This ensures the possibility of evaluating national trends as well as comparing these to other countries. The STEPS approach advises the collection of data on a regular and continuing basis. Caries prevalence  in Romanian schoolchildren is strongly influenced by their socioeconomic background, as well as by their specific consumption behaviours. The level of education of the parents, consumption of carbonated soft drinks, milk, candies, tea, and cocoa, as well as rural–urban area residency, influence the prevalence of caries in Romanian schoolchildren. The number of restorations is impacted by gender, parents’ level of education, and the consumption of carbonated soft drinks and cocoa.


Syngamus trachea being one of the most prevalent nematodes that parasitize pheasants. Because it is a highly effective treatment, e.g., 90% effectiveness against S. trachea, and there are very few alternative therapeutic options, this anthelminthic is used in an extra-label manner in the pheasant industry, but few studies have been conducted assessing risks to humans. Therefore, we conducted a risk assessment to evaluate the potential repeat-dose and reproductive, teratogenic, and carcinogenic human risks that may be associated with the consumption of tissues from pheasants that were previously treated with fenbendazole. We conducted a quantitative risk assessment applying both deterministic and stochastic approaches using different fenbendazole sulfone residue limits  established in different poultry species by the Food and Drug Administration, the European Medicines Agency, and other regulatory agencies in Japan, Turkey, and New Zealand. Our results show that fenbendazole poses minimal risk to humans when administered to pheasants in an extra-label manner, and a comparison of different fenbendazole sulfone residue limits can help assess how conservative the withdrawal interval should be after extra-label drug use.Fenbendazole is a benzimidazole-class anthelmintic that is used for the control of immature and adult stages of internal parasites, such as nematodes and trematodes, in domestic food-animal species. It is not approved by the United States Food and Drug Administration for treating pheasants despite  Syngamus trachea (S. trachea. The anthelmintic treatment currently approved for pheasants is thiabendazole (S. trachea in pheasants.According to the United States (US) Food and Drug Administration (FDA), pheasants are considered to be “minor” food-animal species and categorized as game birds. Also, the United States Department of Agriculture census states that 7,790,734 pheasants were sold live in 2017 , such as Safe-Guard®Medication administration through feed, which is considered an effective and practical method of treatment for pheasants. Fenbendazole also seems to have higher efficacy when administered over several days . When coThe US FDA currently approves fenbendazole for use in turkey feed at a dose of 16 parts per million (ppm), but it is not yet approved for game birds in this country. In the United Kingdom, this drug is being used and approved in several game bird species at a dose of 12 ppm orally. In one study, fenbendazole was shown to be safe for Chinese Ring-Necked Pheasants when administered through feed at a dose of 100 ppm for 7 days . HoweverTherefore, according to the Food Animal Residue Avoidance Databank, the marker residue for pheasants has been assumed to be fenbendazole sulfone, and the target tissue is the liver, similar to turkeys , when esHaving FDA-approved fenbendazole-medicated feed for pheasants could minimize the occurrence of resistance to antiparasitics, as it could facilitate the rotation of different antiparasitics. However, commercial pheasants are a relatively small commodity group compared with commercial chickens and turkeys. Therefore, drug sponsors have not pursued the additional label claim for pheasants. Given the common extra-label drug use of using fenbendazole to treat pheasants, there is a need to evaluate the human risks when consuming meat from pheasants treated with fenbendazole. This risk assessment can also help guide how conservative the estimated withdrawal recommendation should be to protect human health while still complying with established regulations to ensure no residue detection.Therefore, the main objective of this study is to estimate the potential risks associated with repeat-dose toxicity, reproductive toxicity, teratogenicity, and carcinogenicity problems in humans that may arise from the prolonged consumption of pheasant meat from animals that were previously treated with fenbendazole. We conducted a quantitative risk assessment applying both deterministic and stochastic approaches and using different fenbendazole sulfone residue limits established in different poultry species by the FDA, the EMA, and other regulatory agencies in Japan, Turkey, and New Zealand.Fenbendazole is an anthelmintic used to treat gastrointestinal nematodes in both small and large animals and is used to treat nematode parasitism in pheasants. Thus, when pheasants are slaughtered, fenbendazole sulfone residues may remain in the tissues. To analyze whether human consumption of pheasant tissues with fenbendazole sulfone residues is safe, we used both deterministic  and stochastic  approaches considering diverse food safety adverse outcomes  and using different limits depending on approval status or if approval is being pursued .We used the same risk assessment approach that is recommended by the World Organization for Animal Health  (OIE) anAccording to the EMA , fenbendAs fenbendazole is a veterinary medication, as indicated by the EMA , this prBecause no data for pheasant meat consumption in the USA are available, the population used for this study were production turkeys consumed in the USA obtained from the National Chicken Council  because in vivo, fenbendazole mainly exists in its oxidized oxfendazole form. The tolerances and MRLs used for our study were liver residue limits from different avian species, as the liver is the target tissue for fenbendazole sulfone in turkeys  in Microsoft Excel. Some results for the stochastic risk assessment were displayed using box plots generated using R-language  and RStuWe first used a deterministic approach to quantify the degree of human risk of repeat-dose toxicity, reproductive toxicity, carcinogenicity, and teratogenicity observed adverse effects by consuming tissue from pheasants previously treated with fenbendazole using the current regulatory values per country and tissue.Several steps were used to calculate how many grams of pheasant tissue with fenbendazole sulfone residues/day a person has to consume to have different observed adverse effects. First, according to the FDA , the accThe repeat-dose, reproductive, carcinogenicity, and teratogenicity NOAELs were used for the deterministic process. Also, three standard uncertainty factors were evaluated: 10, 100, and 1,000. FDA states that a standard uncertainty factor of 100 is recommended. However, Ufs of 10 and 1,000 were also included in the deterministic process to evaluate worst- and best-case scenarios.Taking the FDA assumption of 60 kg of body weight per person , the ADIFinally, we estimated the daily amount of pheasant tissue a person has to consume to have different observed adverse effects due to the presence of fenbendazole sulfone residues in pheasant tissue Equation (3):The nine different limits that were used for the deterministic process are shown in Estimates of grams of pheasant tissue with fenbendazole sulfone residues that would need to be consumed daily to observe adverse effects of repeat-dose toxicity, reproductive, carcinogenicity, and teratogenicity problems, depending on the Ufs and on limits established by different countries in different poultry species and tissues, were determined.After estimating the amount of pheasant tissue with fenbendazole sulfone residues that have to be consumed to have observed adverse effects Equation (3), we evaluated if human consumption of tissue with fenbendazole sulfone residues was safe. To know if the consumption of pheasant tissue from animals that were previously treated with fenbendazole was safe for humans, these calculations were compared with the actual consumption data in the USA and Belgium (EU) and to food consumption values for edible tissues established by the FDA/EMA and using all the fenbendazole sulfone NOAELs   and all In addition to the deterministic approach, we combined geographic regional consumptions and tissues into one single stochastic model to estimate the overall risk associated with consumption of pheasant tissue with fenbendazole sulfone residues independent of the country of origin of the tissue or type of tissue consumed. For this stochastic model, probability distributions were used to capture the variability and uncertainty associated with tissue consumption for different regions and multiple tissues . In addiAccording to the FDA, the Center for Veterinary Medicine, the reference center for animal food and feeds regulation in the USA, has historically applied a safety factor of 100 for an ADI based on the NOAEL ; hence, Thus, applying the mathematical model previously created Equation (3), a range of grams a day of pheasant tissue that has to be consumed to have observed adverse effects was calculated using tolerance, MRL, and LOD distributions.A sensitivity analysis for the LOD distribution and repeat-dose NOAEL was performed to evaluate the impact that changes in input values have on the number of pheasant tissues with fenbendazole sulfone residues a person has to consume a day to have observed adverse effects. Thus, a tornado graph was created, and correlation coefficients applying Spearman rank were calculated to carry out the sensitivity analysis. LOD distribution and repeat-dose NOAEL were chosen, as they were the most conservative parameters not considering the carcinogenicity NOAEL because no evidence for carcinogenicity was found by the EMA .Finally, to evaluate if human consumption of pheasant tissues with fenbendazole sulfone residues is safe, we used the same procedure that was described for the deterministic approach: US and EU consumptions based on the distributions were divided into the range of pheasant tissues a person has to consume daily to have observed adverse effects. Thus, results with a mean <1 were considered safe, and results with a mean ≥1 were considered unsafe.In addition, turkey tissue consumption per capita in the USA was combined with the established consumption for edible tissues according to the FDA and EMA and modeled using a Pert distribution: the most likely value was 119.55 g/day [turkey consumption per capita in the US ], 100 g/We calculated the different amounts of pheasant tissue with fenbendazole sulfone residues that had to be consumed to observe adverse effects based on different limits according to the country, species, and tissues . It can When evaluating all the results obtained after performing the deterministic analysis of the human safety of consuming pheasant tissues with fenbendazole sulfone residues by applying three different Ufs, we found that in very few cases, those values were considered unsafe  . FurtherOur stochastic risk assessment model revealed that the mean amount of tissue consumption per day that a person has to have to observe adverse effects using the pheasant LOD distribution and the repeat-dose NOAEL is 382,965.14 g/day  .Moreover, the highest value of pheasant tissue consumption a person has to eat daily to have observed adverse effects, 2,281,479.10 g/day, corresponds to the pheasant LOD distribution [which has the lowest most likely value for the limit distributions that were analyzed (0.000005 mg/g)] and teratogenicity NOAEL, which is the highest NOAEL (25 ppm) .Also, as the reference limit has a smaller value, tissue consumption may be higher . TherefoA sensitivity analysis was also performed with the pheasant LOD distribution to know which factor has the highest influence on having adverse effects due to repeated dose . As a re2, results ≥100 express that the consumption of pheasant tissues in the USA and the EU is not safe, and results lower than 100 express that it is safe even when having fenbendazole sulfone residues according to the distributions of the tolerances, MRLs, and LODs.Overall, our stochastic model found that the consumption of pheasant tissues with fenbendazole sulfone residues is safe . BecauseAgain, the obtained results after performing the stochastic analysis to determine the human safety of the consumption of pheasant tissue with fenbendazole sulfone residues show that human consumption is safe, applying almost all consumption distributions and limits studied for the different adverse effects that may arise due to the consumption of the different tissues, as the means are lower than 100. However, in the case of possible adverse effects related to carcinogenicity that may arise as a result of the human consumption of these tissues, it is observed that by applying the uniform distribution of the tolerances, this consumption may not be safe. On the one hand, the mean for the safety value of presenting carcinogenicity adverse effects is lower than 100 when applying the distributions of the US and EU consumptions in all the limit distributions. However, applying both consumption distributions (the USA and European consumption), even if the 97.5 percentile is higher than 100, and using the tolerances distribution as a limit, it cannot be concluded that consumption of pheasant tissues with fenbendazole sulfone residues is unsafe, as both confidence intervals include a value lower than 100. Also, it is observed that the lowest numbers, and therefore the safest cases, correspond when applying the distribution of the LODs and the NOAEL of teratogenicity. This seems reasonable, as the limits for the LODs are the lowest, and teratogenicity adverse effects have the highest NOAELs.This study aimed to estimate the risk associated with human consumption of tissues obtained from fenbendazole-treated pheasants. To the best of the authors' knowledge, this is the first study conducted for this drug and this specific species. We evaluated multiple scenarios using both deterministic and stochastic approaches. On the one hand, the deterministic model offers specific results for different countries that establish their own limits for human consumption of pheasant tissues with residues of this drug. Thus, this adds the advantage that, in addition to the ranges already provided with the stochastic process, results from different countries can also be observed, which could also help for safe extra-label drug use of fenbendazole in pheasants in more countries apart from the USA and the EU. Also, our model contributes to consider different Ufs in addition to the 100 Ufs established by the FDA , which iWhen looking at tissue consumption values applying a Ufs of 10 in However, according to the Center for Veterinary Medicine residue tolerances for post-marketing monitoring, the development of safe concentrations values of fenbendazole sulfone in food and withdrawal periods should be established . In thisOur main study limitations were associated with the quality and availability of the data to generate the input values of the model. For example, there were no data on pheasant consumption in the USA, so we extrapolated pheasant consumption based on turkey consumption in the USA. Pheasant consumption in the USA is likely much lower than turkey meat consumption; therefore, our model is likely overestimating the risk for pheasant or representing only the worst-case scenario. Moreover, fenbendazole sulfone residue limits in pheasant meat for human consumption are not established in the USA or in other countries except the EU, which establishes the same limit for all food-producing species except fish. To overcome these two limitations, a stochastic analysis was conducted, taking into account, on the one hand, different consumption of pheasant and turkey meat and, on the other hand, different limits established for poultry, as a similar fenbendazole metabolism is assumed. With this stochastic analysis, we have taken into account the variability and uncertainty that our model has, and those input distributions will likely capture the range of values applicable to pheasants. However, it will be valuable for future studies to have real pheasant consumption data in the USA to more accurately estimate the potential exposure in the USA population and to continue studying other aspects related to drug residues coming from these species.In conclusion, our results suggest that human consumption of products from ring-necked pheasants treated with fenbendazole in an extra-label manner is safe. With this study, after knowing the possible risks that the consumption of pheasant tissue containing fenbendazole sulfone residues can entail, the use of fenbendazole in pheasants can be established in the future. Also, there is a continuing need for monitoring and surveillance to ensure that Food Safety and Inspection Service program goals are met. The extra-label drug use of fenbendazole in pheasants is very important, as it has shown high efficacy against all helminthiasis stages and against a wide range of helminthiasis.The original contributions generated for this study are included in the article/LAT and BM-L contributed to conception and design of the study. MC performed the statistical analysis and wrote the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In 2020, an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths have occurred worldwide, with colorectal cancer ranking as the third most frequently diagnosed (10.0%). Several attempts have been conducted against cancer, including surgery, radiation, monoclonal antibodies, and chemotherapy. Many people choose natural products as alternatives against cancer. These products will not only help in human life preservation but also work as a source of up-to-date information, leading people away from incorrect information. We discuss the current status, distribution, and future implications of protecting populations with natural products as an alternative against colorectal cancer in Indonesia. Thirty-eight studies were included in this review for data extraction. The distribution of natural products in Indonesia that have potential activity against colorectal cancer cells was predominated by terpenoids, followed by phytosterols, phenolics, alkaloids, and polyisoprenoids. The type of cell line utilized in the cytotoxic activity analysis of natural products was the WiDr cell line, followed by HT-29 cells and HCT-116 cells. This review showed that MTT in vitro assay is a general method used to analyze the cytotoxic activity of a natural product against colorectal cancer cells, followed by other in vitro and in vivo methods. The systematic review provided predictions for several secondary metabolites to be utilized as an alternative treatment against colorectal cancer in Indonesia. It also might be a candidate for a future co-chemotherapy agent in safety, quality, and standardization. In addition, computational methods are being developed to predict the drug-likeness of compounds, thus, drug discovery is already on the road towards electronic research and development. Cancer is a deadly disease that has become a burden to everyone. There were 9.8 million cancer deaths reported in 2018. Colorectal cancer (CRC) is the third most common type of cancer globally, with 1.80 million cases, and it ranks second with the highest mortality in the world, i.e., 862,000 deaths . In IndoCancer treatment with chemotherapy agents is still an option, but the multi-drug resistance (MDR) mechanism has resulted in reduced efficacy of chemotherapy drugs . The cheOne of the strategies in the discovery and development of drugs for the prevention of degenerative diseases is by exploring natural products, especially plants, that have the potential to be sources of antioxidants. Plants are known to have an important role in drug discovery . NaturalWhat evidence literature and data exist on the application of natural products from Indonesian plants in colorectal cancer?The systematic review has the following primary review question:What are the available trends and study distribution of colorectal cancer in Indonesia?What are the used approaches and indicators for colorectal cancer derived from natural products in Indonesia?What are the challenges and gaps in the science and application of natural products in colorectal cancer in Indonesia?The secondary review questions are:Population: Colorectal cancer in Indonesia.Intervention: Any secondary metabolites and natural products used for colorectal cancer from Indonesian plants. These common approaches include in vitro and in vivo.Comparator: Any indicators used to monitor the success of anti-colorectal cancer activity by the use of natural products or secondary metabolites.Outcome: Inhibited colorectal cancer or no proliferation activity of colorectal cancer.The systematic review is focused on studies that have reported the utilization of natural products in colorectal cancer in Indonesia. The data was gathered from published literature obtained through preselected bibliographic databases such as Scopus and PubMed, as well as search engines such as Google Scholar. To determine the scope of the review, this study used a globally applied standard approach for systematic review, by first defining the Population, Intervention, Comparator, and Outcome (PICO) of the review . The detMost of the methodological steps in this systematic review follow previous systematic reviews on the health topic or pharmacy practice ,17. In aBefore conducting a literature search in the bibliography database, we composed a search string by identifying the relevant keywords following the defined PICO. However, we only considered keywords from Population and Intervention categories to avoid the narrowed search string and reduce the number of papers. Literature searches in Scopus and PubMed were conducted by using the English search string, while we used both an English and Bahasa Indonesia search string for Google Scholar see . To avoiThe study’s relevance was determined by using the inclusion criteria presented in The reporting and presentation of the results of this systematic review followed a standardized reporting approach for the systematic review of health and pharmacy studies ,17,18. AThe PRISMA flow diagram of the publication screening is presented in As presented in Cancer is the second leading cause of death in the world after cardiovascular disease. Meanwhile, colorectal cancer ranks in the top three in the number of causes of death and is ranked as the second most common cancer type in men and third in women ,59. A coPlants are one of the largest sources of natural products that are used to discover and develop novel chemotherapeutic agents. In particular, several discovered novel compounds from plants have unique mechanisms of action, greater efficacy, or lower adverse effects compared to the conventional chemotherapy drugs currently in use. Bioactive compounds from medicinal plants in Indonesia have also been studied to exhibit anticancer activities in the colorectal, namely terpenoids, phytosterols, alkaloids, phenolics, flavonoids, and polyisoprenoids , induced apoptosis, and through down-regulation mechanisms, i.e., inhibition of PI3K gene expression, AKT1 gene, mTOR gene, and inhibition of EGF receptor expression ,53. The In the current paper, we conducted a systematic review that provided predictions for several secondary metabolites sourced from natural products to be utilized as an alternative treatment against colorectal cancer in Indonesia. They are also prospective candidates for future co-chemotherapy agents in safety, quality, standardization, and efficaciousness. This finding emphasized the potential of several natural products as anticancer agents against colorectal cancer cells.The rich biodiversity of Indonesian plants derived from tropical rainforests provides a diversity of structural compounds that can be used as anti-colorectal cancer agents. At the same time, this review challenged Indonesian researchers of colorectal cancers to support drug-independence programs as these national products can be a part of the competitive multinational market. The utilization of Indonesia’s natural resources, which are rich in plant biodiversity, seems to be less than optimal compared to the number of traditional medicines that have been proven to have benefits and are scientifically proven. Indonesia has more than 30,000 species of plants and animals that have the potential as medicines and 9,600 species of plants and animals that are known to have medicinal properties. This potential can be developed to meet the growing demand for traditional medicines and health supplements based on natural ingredients ,63.Jamu. Jamu is usually used as a plant that has medicinal properties and has served various Indonesian generations for centuries. The Indonesian government categorizes traditional medicinal preparations into three categories, namely Jamu, standardized herbal medicine, and fitofarmaka (phytomedicine). Herbal medicine is categorized as a traditional medicine that has been used empirically but has not yet been scientifically tested; standardized herbal medicine are those plants with medicinal properties that have been proven by preclinical testing; fitofarmaka is a medicinal plant that has been tested to the clinical stage. Until 2019, 23 natural products have been registered and have been proven in clinical trials. Therefore, they are categorized as fitofarmaka in Indonesia [Traditional medicine in Indonesia is popular with the name ndonesia ,64.Jamu as an alternative and additional medicine. The Indonesian government has also established a body under the name Directorate of Traditional, Alternative, and Complementary of Health Care (BINA YANKES TRADKOM) [Herbal medicine has become a part of the culture in Indonesia. This has been done for generations. Its use in the long term has proven its safety and benefits empirically in the community. Despite having been used for centuries, herbal medicine had no place in the formal healthcare system in Indonesia before 1987. Since 1988, the Indonesian government, through the Ministry of Health, has been regulating and encouraging efforts to use scientific TRADKOM) ,66,67. HTRADKOM) . AnotherLeading the discovery is the main component of today’s early pharmaceutical research. The exploration of novel drugs for colorectal cancer therapy that has a fast progression can be a drug repurposing strategy to bypass preclinical steps that usually require laborious and resource-intensive work. In addition, it is also considered that the development of existing agents in the future can be more easily utilized by the community. For those purposes, the exploration of Indonesia’s frequently used natural resources biodiversity is the best choice. In the past, drug development is based on trial and error, so it was costly and time-consuming. Today, molecular modeling, with the aid of computer hardware and software , has reduced the risk and the process of discovery is more effective in cost and time .Jamu which is generally not a pure compound. There is a need to purify and synthesize specific compounds that are originally derived from exotic plants to conserve the environment. Based on the prediction of the active site, compounds can be designed with the expectations to bind to the target protein and have biological activity. These techniques support those novel drug developments which have specific activities by the mechanism of drug-receptor interaction. Computer-aided drug design (CAAD) helps to identify small molecules by orienting and scoring them in the active binding site of a protein [Molecular docking is the computational simulation of a ligand binding to a receptor, which helps to predict binding molecule to the protein target to predict the affinity and activity. The aim of target discovery is the identification and validation of suitable drug targets for therapeutic intervention. Structure-based drug design (SBDD) is responsible for the toxicity and activity of a compound in the body. The SBDD utilizes information from the target protein structure to find the active site of the protein that binds to the drug compound. This is a challenge for a natural product such as  protein .In silico approaches contribute significantly to early pharmaceutical research and are especially important in target discovery and its lead. The need for timely adaptation and application of in silico approaches in pharmaceutical research has been recognized to design and discover novel active substances better than previous compounds and is expected to improve further the overall efficiency of drug discovery .In summary, this review revealed bioactive compounds from natural products of Indonesian plants that have been researched and have potential as anticancer agents that are most commonly experienced in men and women including colorectal cancer. The general method used for the analysis of the cytotoxic activity of colorectal cancer cells is the in vitro method using the MTT assay, the most widely used cell line is WiDr. The most studied bioactive compounds that have any activity against colorectal cancer are terpenoids, phytosterols, phenolics, alkaloids, and polyisoprenoids, but other natural products may have the potential to be developed from this study.