How is neoliberalism implicated in concrete health vulnerabilities? How do macro-level political economy, policy and institutions translate into everyday experiences? Drawing on Marxist, feminist and International Political Economy critiques of everyday life, the article advances an everyday political economy of health focused on four key components: power, agency, intersectionality and the mutual implication of the global and the local. These components enable a nuanced investigation of concrete experiences of health and disease, and of the local implementation of health policies in the context of neoliberalism. The framework is applied to the case of the 2015 public health response to Zika in Brazil, and specifically to the role of community health workers, close-to-community healthcare providers tasked with bridging the health system and vulnerable groups. The everyday practice of these workers, and their working conditions overwhelmingly characterized by precarity and low pay, reveal the presence of global neoliberal dynamics pertaining to the reconfiguration of the Brazilian state as healthcare provider in a context of encroaching austerity, privatization and narrowly-defined cost-efficiency. These dynamics impacted detrimentally upon the effectiveness of the Zika response. In 2015, Brazil declared a war on mosquitoes. An outbreak of Zika virus disease, beginning in April in the northeast of the country, alarmed clinicians, researchers, policymakers, media and the public. Although Zika is a mild illness, causing fever, joint pain and headache, scientists puzzled over unprecedented symptoms in the most affected areas Diniz, . In NoveBecause Zika is transmitted by mosquitoes, from the start the response focused on controlling the mosquito vector Ventura, . Health Zika speaks to academic works connecting health with socioeconomic factors like income, redistribution policies and public investment  to explore the reproduction of ill health in the context of neoliberalism. The framework, drawing on the Marxist and feminist critiques of everyday life and on international political economy (IPE), is applied to the Brazilian response to the 2015 Zika outbreak. Zika is a remarkable case for examining the EPEH because it is a set of interlocking crises in everyday life. It draws attention to bodily matters that are often neglected, such as pregnancy, reproductive rights, disability and the unequal burden of care placed on women. The attention given to Zika as a health emergency obfuscated socioeconomic determinants and the ‘everyday emergencies’ experienced by millions of Brazilians.Community health workers (CHWs) are here an entry-point for analyzing how the response to Zika materialized on the ground. CHWs are close-to-community healthcare providers (sometimes living in the communities they serve) who connect doctors and nurses with remote or hard-to-reach groups in many countries  starts from the assumption that health policy design and implementation are the result of tensions, negotiations and struggles between actors – and are thus traversed by power relations. As Michael Gardiner . It directs the focus to the concrete ways in which power relations are embodied and translated in the diversity of daily experience – an important trope in feminist research. At the same time, in line with its Marxist credentials, EPEH frames the bodily effects of power as part of a broader set of socioeconomic arrangements.The focus on the horizontal aspects of power should not obscure the fact that power relations are often underpinned by significant disparity. The shaping of behavior and the constitution of subjects are embedded within a context of unequal life conditions. Power relations occur in, and are themselves involved in the production of, an uneven environment in which certain groups are systematically placed in a position of subordination in relation to others Young, . NonetheEPEH conceives the horizontal approach of power, according to which the latter circulates between different nodes in society, as intertwined with these hierarchical effects. The Marxist lens is well placed to examine how a society traversed by unequal power relations is one where health vulnerabilities are unevenly distributed and where people can have markedly different capacities to respond to disease. For example, the weakening of public health systems by austerity policies and privatization helps to explain the adverse effects of seemingly horizontal relations underpinned by market-based logics, which in fact place disadvantaged sectors of the population in harm’s way. Moreover, by drawing on feminism, the everyday approach is able to adopt an intersectional perspective to study how power leads to interlocking inequalities. With its focus on everyday practice and bodily experience, EPEH supplements studies that have looked at how class intersects with gender Moss,  and raceThe complex understanding of power afforded by EPEH signals great unevenness in the ability to shape health outcomes – in other words, different capacities to exercise agency. EPEH mobilizes a sophisticated notion of agency, according to which actors are indeed constrained by unequal power relations but are not mere targets or passive recipients. Everyday life is embodied and experienced in the context of constraining structures and relations, but this does not entail powerlessness. As Hobson and Seabrooke , p. 18 rFinally, IPE enables the EPEH perspective to trace the interactions between micro-level of experiences and macro-level dynamics shaping global health. On the one hand, EPEH considers the local effects of the global, that is, how global political and economic arrangements are experienced and embodied. It sheds light upon the concrete effects of neoliberalism: its influence on patterns of health and disease, and on determinants; its impact on the responsibilities and capacity of states, private actors and global institutions as healthcare providers or funders; its role in shaping the working conditions of the health workforce; and its bodily manifestations along class, gender and race lines. On the other hand, EPEH sees everyday practices as essential for the reproduction of neoliberal ideas. For instance, privatization of health services and the commodification of health are supported by the everyday perceptions and behaviors of health system users and health workers, who embody existing arrangements and thereby help to perpetuate them.The argument has laid out an EPEH centered on four interlocking components: an understanding of power as the production of unequal life conditions and chances; a nuanced view of agency; the value of intersectional analysis to unpack the effects of power and the possibilities for agency; and the recognition of the mutual constitution of the local and the global. The remainder of the article shows the added-value of this approach, focusing on the Brazilian response to the 2015 Zika outbreak and the role of the community health workforce therein.agentes comunitários de saúde) are part of the (public) Unified Health System . The origins of the CHW programme can be traced to 1987, when community workers were deployed in the state of Ceará to reduce child mortality and provide employment for women in a period of economic crisis heightened by severe drought , which from the early 1990s was rolled out within the SUS. The ESF supplemented curative medicine in hospitals with close-to-community prevention, health promotion and rehabilitation. Interventions were undertaken by teams comprising general practitioners, dentists, nurses, nursing assistants and CHWs , and simultaneously epitomized the shift towards individual-centered healthcare – one of the mainstays of neoliberalism in health as will be discussed below.CHWs, acting as ‘transmission-belts’ of federal, state and municipal authorities, were instrumental in the implementation of this strategy. They were essential in ensuring the capillary reach of state power, from government offices in Brasília to the most remote backyard. CHWs were heavily involved in mosquito control, identifying vacant buildings, lots or dumpsters where mosquitoes could reproduce and filling in checklists during household visits. These checklists were meant to ensure that homes and backyards did not have mosquito ‘hot-spots’. CHWs checked that empty bottles were turned upside down, that garbage bins and bags were securely shut, and that sand was poured in plant pot saucers to prevent water from accumulating . During the Zika epidemic, mutirões included distribution of leaflets, cleaning of vacant lots, information sessions for the elderly or school children, among others.The everyday practice of CHWs during the Zika epidemic underscored their position as important nodes in the circulation of power at the micro-level of health policy implementation. The checklists enabled state authorities to enhance their reach in the territory through the collection of information, which in turn opened the way for the regular deployment of response teams. Checklists also functioned as templates of ‘good behavior’, through which the health authorities sought to constitute subjects. With the latter purpose in mind, CHWs disseminated information about Zika, its symptoms and effects, and about vector control. This was done door-to-door and through community mobilization in Community mobilization activities signal a broad political function of CHWs, who are more than healthcare providers since they can also play an important role as community organizers . These latter workers are also in close contact with populations and cover the same territories as CHWs. However, they depend upon the Health Surveillance branch of the Ministry of Health, whereas CHWs are tasked with primary healthcare responsibilities. In the territories studied during fieldwork, confusion about roles impaired the effectiveness of the response and added to the frustration of CHWs and communities.Coordination problems impacted upon the everyday work of CHWs during the Zika response. Interviewees expressed confusion about their responsibilities in vector control, particularly regarding their relationship with community workers devoted to endemic diseases , 13 as black and only 5 as white. Moreover, many CHWs are single mothers dealing single-handedly with childcare and household duties. In Buritizeiro, 41 out of 52 had children; 26 were single, 3 were divorced, and only 21 were married; and 31 (60%) were the main/sole provider in the household. Many CHWs, upon which society already places inordinate expectations of care, perceived Zika-related tasks as yet another burden. The stress felt by CHWs because of precarious and difficult working conditions was heightened by the fact that many were women in fertile age, one of the risk groups during the Zika emergency. In Sete Lagoas, 67% of CHWs (183) were under 40 years old; in Buritizeiro, the figure was 83% (43). For some, widespread fears in society about neurological disorders  affecting new-borns as a result of Zika infection made Zika-related work particularly sensitive.The problem with CHW working conditions during the Zika epidemic intersected with gender and race, becoming an acute bodily question. Brazilian CHWs are overwhelmingly poor and vulnerable women, many from non-white backgrounds. In the municipalities studied, 98% of CHWs were women. In Buritizeiro, 51 out of 52 CHWs were women; 32 self-identified as The working conditions of CHWs reflect an understanding of women as carers that permeates Brazil’s highly patriarchal society, with female labor perceived as a natural extension of domestic work  and the circulation of power (the distribution of rewards and punishments to ‘deserving’ and ‘undeserving’ users because of resource scarcity). What happened at the level of communities, individuals and bodies during the response to Zika can be traced back to global economic policies. Simultaneously, global dynamics can only be fully grasped when seen as lived, experienced and embodied in the everyday.The case of Brazilian CHWs thus contributes to a Marxist-inspired interpretation of the contemporary trajectory of global health, illustrating the global neoliberal trend towards privatization, the erosion of public healthcare provision and the precarization of labor, particularly of female labor. The case also confirms the value of (feminist-inspired) intersectional analysis for global health, showing that the success of health policies needs to be assessed alongside a consideration of their bodily effects along gender, race and class lines. Marxism and feminism combined allow us to examine in depth the ways in which inequality may be reproduced through the very processes of implementing health interventions – and not simply by the absence of policy.In addition, the Marxist and feminist lens are relevant in that they point towards possibilities for political change. The everyday perspective presented a complex picture of CHW power and agency as constrained but never fully determined. As an ‘army’ of precarious, easily disposable workers, CHWs can be considered the weakest link the public health system. Nonetheless, as a professional category they are instrumental to realizing the universalist mission of the Brazilian public health system, while meeting the demands of extremely diverse territories and populations. The everyday functioning of the system is reliant upon the agency of CHWs, who engages in informal, power-laden and gender-infused interactions in their everyday practice. EPEH reveals an underlying tension in public healthcare provision in Brazil, showing how it constrains the agency of vulnerable CHWs while remaining heavily dependent on their insider knowledge of communities and on their capacity to make pragmatic decisions , and even to improvise when faced with unforeseen demands and obstacles.This tension constitutes a fault line where ‘top down’ rules and directives can be reinterpreted, reconfigured, resisted and subverted in the everyday. The Brazil case shows that CHWs are embedded in and sometimes help to reproduce the very social and economic arrangements that contribute to their own vulnerabilities and those of their communities. They do so by reproducing inequality through their discretionary power, and by being co-opted in an increasingly segregated system where the poor remain unable to access the full range of health services available. At the same time, because of their unique position in the communities and in the health system, CHWs are well placed to unlock the latter’s transformative possibilities.saúde coletiva), the importance of community-based responses and public participation, the focus on disease determinants, and the engagement with popular and indigenous forms of knowledge. CHWs can play a crucial role in turning these ideas into reality, and their practice can thus potentially challenge global economic structures and their everyday manifestations. Despite the inhospitable environment – which has become even more difficult with Brazil’s shift to the far right after the October 2018 elections – the work of CHWs reveals at times the everyday contestation of the neoliberal model. Everyday acts of resistance and subversion can provide the seeds for broader change. An image sticks to mind from one of the several mutirões organized by CHWs across Brazil during the Zika outbreak: a colorful street parade with festive music, a female CHW disguised as a mosquito, children being alerted to the need to protect their health and that of their loved ones and neighbors. A message of community mobilization and solidarity was transmitted. This happened in Jardim Nazareth, a small neighborhood in São Bernardo do Campo, a city of around 817 thousand people situated in the outskirts of São Paulo, a megalopolis of more than 13 million. The Jardim Nazareth CHWs ironically enacted and subverted the reality of a country at war. No fighting was involved: it was a celebration of life.Emancipatory elements have always been present in the trajectory of Brazilian public health. These include the idea of health as a collective project (


Empowerment is an organisational effort in increasing the willingness and ability of employees to be more independent in performing their duties. Employee leadership empowerment substantially increases motivation, performance, and commitment to the organisation. Leadership empowerment includes self-determination, competence, meaning, and impact. The purpose of this study was to determine the acceptance of leadership empowerment efforts for female employees in three dental hospitals in Bandung.  A descriptive survey was conducted and the study population was dental hospitals in Bandung. The exclusion criteria were dental hospitals which unwillingly followed the research. The inclusion criteria were dental hospitals that have empowered female employees. The data collection technique was performed with total sampling. The research sample amounted to 102 people from three dental hospitals—all data were collected using a validated questionnaire. Data analysis was performed using relative frequency distribution.  Leadership empowerment for female employees in three dental hospitals in Bandung has been given by each. The highest acceptance of empowerment efforts for female employees was shown by employees of Dental Hospital of Jenderal Achmad Yani University, followed by Dental Hospital of Universitas Padjadjaran, and subsequently Dental Hospital of Maranatha Christian University. The level of acceptance of empowerment efforts that need to be improved in three Dental Hospitals in Bandung was self-determination or autonomy at work. Employees must be given more freedom on performing their duties, developing their careers, and acting more independently.  Acceptance of leadership empowerment for female employees in three dental hospitals in Bandung has been demonstrated in each. Acceptance of leadership empowerment efforts in all subdimensions of empowerment needs to be improved, primarily related to self-determination. Some previous researchers have argued that such an environment affects these women's ability to fulfil their family needs. Besides, impoverished women hold responsibility and contribute towards the survival of their impoverished households. Other studies about women and impoverished households also show the importance of women's role as the primary wage earner in their household. Moreover, the result of the study conducted in East Java showed that impoverished women did various works, with a majority of those working in the informal sectors for more than 8 hours per day and earning relatively small wages .Employee empowerment in the form of employee involvement and commitment is a significant success factor in the current organisation. Empowerment increases employees' personal sense of control and motivates them to be more engaged in work, which in turn produces positive managerial and organisational results . EmployeThe empowerment approach for women must be performed through a gender empowerment approach. Gender empowerment should not be misinterpreted as empowering men against women vice versa. Empowerment signifies the transformation of gender relations from a planned sequence of levels or ranks to equality rather than just fiddling with women's positions of power .The next approach is the “Efficiency of Gender Perspective” that focuses on the efficiency of women's role, with an assumption that bringing women into production will automatically serve as a means of achieving gender equality. According to this efficiency approach, the development will only be successful and efficient if women are involved in the development process . HoweverIncrease the status of women to achieve gender equality. The results showed that empowerment, which includes four dimensions of potential, meaningfulness, autonomy, and impact, is more likely to improve organisational performance compared to traditional leadership. The improvement was mainly reflected in employee performance results such as team productivity, proactive quality, and customer service, also towards employee attitudes such as job satisfaction and organisational commitment .Empowering women is beneficial because it can shape behaviour towards and from the organisation. The benefits are as follows: (a) personal: develop confidence and self-capacity and eliminate internalised oppression; (b) rational: develop the ability to negotiate and influence the nature of relationships and decisions made therein; and (c) collective.Empowerment through increased competence, work meaningfulness, autonomy, and impact is beneficial to improve work team efficiency, thus impacts on the performance and working attitude. Implications on performance are increasing productivity, proactivity, and customer service, while on the working attitudes are increasing job satisfaction and organisational commitment. This importance of empowerment encourages us to investigate the acceptance of empowerment in dental hospitals in Bandung. This study was aimed to determine the acceptance of leadership empowerment efforts for female employees in three dental hospitals in Bandung.The research was a descriptive survey . The stuThe data collection technique used was the survey technique. The number of research samples that met the inclusion criteria was at a total of 102 people. The data collection technique was carried out using a questionnaire. Empowerment questionnaires in this study included self-determinants/freedoms, meaningfulness/value of the work done, competence/ability to work, and the impact of self-existence. The research instrument was created by the authors. The validity and reliability of the questionnaire were the results of the validity test in the form of a correlation coefficient above 0.4 (strong correlation) and some that reach above 0.7 (very strong correlation). The reliability test results were in the form of Cronbach's alpha value of 0.842. This value was reliable because it had the value above 0.7 .Scale of data acceptance was calculated using the Likert scale with five categories, which were strongly agree, agree, neither agree, disagree, and strongly disagree. Data analysis was performed using relative frequency distribution in Microsoft® Excel. The study was conducted at the Dental Hospital of Maranatha Christian University, Dental Hospital of Jenderal Achmad Yani University, and Dental Hospital of Universitas Padjadjaran by following the research ethics requirements required by the Research Ethics Committee of Universitas Padjadjaran.The results of the current research are presented in The three tables above show that all three dental hospitals in Bandung have provided leadership empowerment for female employees, with acceptance of the empowerment effort shown variation in the value.p value was in the range of 0.000–0.007, which was lower than 0.05. This value indicated that the variable data above were not normally distributed.The rank value based on the mean for Q1 of meaning: concerned about the quality of my work, Jenderal Achmad Yani University Dental Hospital had the highest value, followed by Universitas Padjadjaran and Maranatha. Regarding the Q2 of meaning: the work is needed by other departments and the entire organisation, Jenderal Achmad Yani University Dental Hospital also had the highest value, followed by Universitas Padjadjaran and Maranatha.The rank value based on the mean for Q1 of competence: the belief that I can do all of my tasks, Jenderal Achmad Yani University Dental Hospital had the highest value, followed by Maranatha and Universitas Padjadjaran, and also, regarding the Q2 of competence: want to learn and be able to solve new challenges at work well and on time, Jenderal Achmad Yani University Dental Hospital also had a slightly higher value than Universitas Padjadjaran and Maranatha Dental Hospital.The rank value based on the mean for the Q1 of impact: actively engaged in all assignments for the advancement of the Dental Hospital organisation, Jenderal Achmad Yani University Dental Hospital had the highest value, followed by Universitas Padjadjaran and Maranatha, and also, regarding the Q2 of impact: all decisions and actions that I take are always taken into consideration of the progress of the Dental Hospital, Jenderal Achmad Yani University Dental Hospital also had a slightly higher value than Universitas Padjadjaran and Maranatha Dental Hospital. All results above are described in p values were higher than 0.05. These values indicated no significant difference in the acceptance of empowerment efforts for female employees in three dental hospitals.Tables 1The results of the current research indicated the necessity for a leadership empowerment approach for female employees, where this effort will have a positive effect on job satisfaction in the form of increasing self-determination. Sharing information regarding goals and performance, providing access to work-related knowledge and skills, and providing wisdom to alter the work processes have a positive and appreciable effect on job satisfaction. Conversely, empowering practices that undermine autonomy, such as offering contingent-based rewards, do not have any significant influence on the job satisfaction .Self-determination is a valuable part of empowerment because it includes the concept of individual autonomy, good behavior competence, and the ability to assess the relationship between behavior and its results . Self-deSelf-determination theory indicates that every individual has an innate tendency towards future development and intrinsic motivation. Intrinsic motivation and well-being are part of three psychological needs related to competence and autonomy. Social rules, including rules at work, external rules, or stimuli including payments, supervision, goals, and direction, are used to encourage desirable behaviour .As long as these three needs are fulfilled, employees will internalize and integrate external rules, meaning they will take values and accept these external rules as their values and self-motivation. This process of internalization and integration forms extrinsically determined behaviors and internal motivation to act on their own accord .Tables 1People have many definitions of work at the same time. However, it usually seems to dominate at specific periods. To be able to see how the meaning of work is built up over time, it is essential to classify people depending on the meaning of work that is dominant to them. Two categorizations were made based on experience. The meaning/function of the main job is to meet the social and economic expectations that are mostly asked by members of their family and relevant community. The meaning of work is considered to be “social” when the meaning/function of the main job is to meet individual needs, aspirations, and interests, and thus, the job can also be considered as having a “personal” meaning. As stated, these categories are not exclusive to each other, and an individual can have both meanings at a certain point. The process of how one meaning dominates another is the subject matter being explored .Such practices also the form of joint control that rewards, recognizes, and values the employee's behavior that can predict employee involvement while providing a higher commitment to their superiors and increasing the level of involvement or participation, which leads to higher learning efforts that will enhance innovation in the workplace. Employees will feel more empowered when they feel that their manager is an empowering leader, which in turn gives motivation and a sense of belonging to the organisation and leads them to be more engaged . The resEmployee involvement consists of three different levels, which are the employee involved, not involved, and unable to get involved. Employees involved are those who work with enthusiasm towards the organisation goals. Employees who are not involved are employees who seem to be participating but not with enthusiasm and energy for achieving the organisation's shared goals. Employees who are unable to get involved are people who are unhappy at work, because of an act of their unhappiness .Involvement also has three different aspects, namely, intellectual involvement, which refers to a dedication to perform better action; effective involvement, which is a positive feeling when performing the job; and social involvement, which is showed through discussing with others regarding improvements in performance related to their work .Efforts to increase the role can be done with career development. Organizations with highly engaged employees will provide many opportunities to learn skills, develop abilities, gain knowledge, and reach their potential. Career development practices will help organizations to retain talented employees and also provide personal development opportunities .Organizations can invest in employees by planning their career development. Career development is a crucial factor in involving employees. Adequate employee career development through training, skills, and learning can result in employees that are more committed to their work and organisation .All three dental hospitals in Bandung have provided leadership empowerment for their female employees. Empowerment access has been recognized by their female employees, which expressed in terms of strongly agree and agree. The most attitude scale stated by employees who have gained access to empowerment is agreed.Empowering women is an important goal in achieving sustainable development throughout the world. Offering access to microfinance services for women is one way to increase women's empowerment. However, empirical evidence gives mixed results concerning its effectiveness .The three-dimensional model of women's empowerment has been developed to integrate previous findings and to gain a deeper understanding of women's empowerment. This model proposes that women's empowerment can occur in three different dimensions: (1) microlevel, referring to personal beliefs and actions, where personal empowerment can be observed; (2) mesolevel, referring to beliefs and actions concerning others relevant, where relational empowerment can be observed; and (3) macrolevel, referring to results in a broader social context where social empowerment can be observed .The results of the current research presented in the three tables above can be intervened in the short term. Previous interventions have proven to be successful in increasing women's incomes and thus should not be underestimated. These interventions benefit women and can have a transformative impact on society by encouraging more significant investment in children welfare, reducing household poverty, and increasing aspirations for the next generation of women and girls .Interventions that can be conducted in the short term, based on the results of previous research, are providing women with business management training, workplace and skills training, and also job vouchers. These are increasingly common interventions aimed at increasing the productivity and income of women entrepreneurs, women farmers, and female wage workers in developing countries .The results of previous studies confirmed significant differences in empowerment and job satisfaction based on demographic factors, which are gender, age, marital status, educational qualifications, appointment, income, and experience. Age, qualifications, and educational background have significant differences in empowerment . Women'sThe results of the present study indicated that an increase in employee empowerment is an urgent need because empowerment is the type of motivational strategy that gives employees a sense of satisfaction with their work and organisation. It can be concluded that employees were satisfied with various factors such as employee training, self-development programs, employee meetings, employee participation in multiple activities, and consideration of their ideas and opinions , 18.Overall, there were no significant differences in the acceptance of empowerment efforts for female employees in three dental hospitals. This result may be caused by each hospital that has advantages in several types of empowerment and has limitations in several types of empowerment as listed in Leadership empowerment in three dental hospitals has been implemented and accepted (recognized) by female employees because of their perceived benefits. Acceptance of leadership empowerment efforts in all subdimensions of empowerment needs to be improved.


Trypanosoma cruzi, a primarily wild mammal parasite, infected humans already long before European colonization of the Americas. T. cruzi heterogeneity remains an unsolved question, and until now, it has still not been possible to associate T. cruzi genotypes with any biological or epidemiological feature. One of the first biochemical attempts to cluster the T. cruzi subpopulations recognized three main subpopulations (zymodemes) that have been associated with the transmission cycles in the wild  and in the domestic environment (Z2). The description of wild mammal species harboring Z2 two decades later challenged this assemblage attempt. Currently, the genotypes of T. cruzi are assembled in seven discrete typing units (DTUs). The biology of T. cruzi still shows novelties such as the description of epimastigotes multiplying and differentiating to metacyclic trypomastigotes in the lumen of the scent glands of Didelphis spp. and the capacity of the true meiosis in parallel to clonal reproduction. The study of the transmission cycle among wild animals has broken paradigms and raised new questions: (i) the interaction of the T. cruzi DTUs with each of its mammalian host species displays peculiarities; (ii) the impact of mixed genotypes and species on the transmissibility of one or another species or on pathogenesis is still unknown; (iii) independent T. cruzi transmission cycles may occur in the same forest fragment; (iv) the capacity to act as a reservoir depends on the peculiarities of the host species and the parasite genotype; and (v) faunistic composition is a defining trait of the T. cruzi transmission cycle profile. The development of models of environmental variables that determine the spatial distribution of the elements that make up T. cruzi transmission by spatial analysis, followed by map algebra and networking, are the next steps toward interpreting and dealing with the new profile of Chagas disease with its many peculiarities. There is no way to solve this neglected disease once and for all if not through a multidisciplinary look that takes into account all kinds of human and animal activities in parallel to environmental variations.Trypanosomatids are ancient parasitic eukaryotes that still maintain prokaryotic characteristics.  T. cruzi presents a very interesting story. It was first observed by Carlos Chagas in 1909 in the digestive tract of a triatomine (Panstrongylus megistus) examined after his attention was drawn to insects that sucked people's blood . Three weeks later, Oswaldo Cruz observed trypomastigote forms in the blood of these animals. In contrast to what was thought by Chagas and Cruz (that the parasites were transmitted by the insects' bites), the marmosets probably became infected by the ingestion of the infected bugs, resulting in the first demonstration of the oral infection of wild mammals  that lived in mudhouse walls  in Brazil that this protozoan parasite started to be considered a primarily wild enzootic organism, maintained by wild mammals and triatomines   were the basis for the first nomenclature consensus proposed in 1999 , which is a hybrid parasite that is the result of a natural product of meiosis recombination between the parentals TcII and TcIII. This T. cruzi genotype was described by its heterozygous profile of the isoenzyme glucose phosphate isomerase, which gave important information long ago  groups, T. cruzi TcI (Z1) and TcII (Z2)  is the most ubiquitous subpopulation and, because of that, is the most frequently detected subpopulation in the wild  was the subpopulation that was consistently isolated from human cases in the formerly endemic areas of Central Brazil, especially maintained by T. infestans in indoor transmission. This subpopulation was therefore associated with the domestic cycle of T. cruzi transmission and with the severe clinical conditions that occurred in 30% of the infected people  and T. cruzi Z2 subpopulations (later confirmed as DTU TcII), that this association was challenged  or host species (as proposed secondly).Since their description, the different zymodemes were associated with different transmission cycles: Z1 and Z3 were associated with the transmission cycles in the wild and Z2 in the domestic environment. The domestic cycle of T. cruzi characterization since the late 1980s, and the most diverse targets proposed, showed that T. cruzi heterogeneity was much higher than the biochemical studies could reveal and made it possible to study the parasite at a much higher level of detail. Soon after the first nomenclature consensus was published, six discrete phylogenetic lineages (later named discrete typing units—DTUs) were proposed  in Didelphis aurita opossum smelling glands  in comparison to the infections caused by the F strain (TcI): opossums were shown to rapidly eliminate the former from the peripheral circulation while maintaining blood-detectable parasitemias when infected by the latter. In other words, it became clear that opossums differ in their infectious potential for TcI and TcII. Moreover, these studies have shown that from an early age, approximately 50 days but still in the marsupial pouch, D. aurita is able to control T. cruzi infection  and involves all mammalian orders. It is worth mentioning that parasitemias are not high. Rarely are positive fresh blood tests reported, and positive blood cultures that also demonstrate infective potential were observed in 8% of 6,587 wild mammals examined , Primates , and Marsupialia  more frequently demonstrate positive hemocultures, i.e., infectious potential, than other taxa  infection route and other factors. Considering that each species  interacts differently with the different subpopulations of T. cruzi, it is possible to conclude that the possibilities of combinations are endless.The already classic reference strains, such as the Y, Colombiana, Esmereldo, CL, and other strains, are highly passaged strains, kept for many years in laboratories, and are therefore subjected to the selective pressures inherent to these methods and hardly represent the diversity of T. cruzi is very likely underestimated, attempts to associate parasite genotypes with host species or environment-related variables should be proposed with caution. Finally, when faced with such a complex model, it is prudent not to dogmatize and to always be open to reviewing concepts.Given that the true diversity of T. cruzi to humans was basically intradomiciliar by T. infestans, an exotic species in Brazil that interestingly never adapted to the wild environment of any Brazilian biome. Therefore, the successful campaign to eliminate indoor T. cruzi transmission by T. infestans was based on single measures that could be taken in all areas of transmission, including the spraying of houses and attachments, educational campaigns and T. infestans collections. Thus, it was possible to use the same vector combat methodology throughout.Although Barretto has drawn attention to the correlation between environmental disruption and the onset of human disease, this knowledge has not been incorporated into the routine of preventive actions. Nor could it be incorporated because the transmission of T. cruzi transmission by T. infestans in Brazil is an issue worth mentioning. This was indeed a very important landmark. In fact, the Chagas Disease Control Program established in Brazil in 1975 achieved, in this continental-sized country, a highly successful campaign, starting from millions of infected people to zero in 25 years , both municipalities displayed good sanitary conditions and the predominance of an urban profile. Humans in those areas did not expose themselves or their food to triatomine bugs. There was never a case or outbreak in these localities again.What makes early detection of Euterpe oleracea) juice was associated with the great majority of current cases in Brazil , and this same instrument was used to cut the palm heart before distributing it to the families. Additionally, in the same state, an outbreak in Ananás municipality in 2012 received attention due to the high number of infected people (12 cases). This latter case was associated with the consumption of bacaba fruit (Oenocarpus bacaba) juice, produced in a similar manner as açai, but with cultural differences associated with its consumption that can directly impact the number of infected people. In this sense, açai fruit juice is consumed daily in some Amazon areas, usually immediately after its preparation and only by the family due to its low income. Contaminated açai juices result in familial Chagas disease outbreaks, usually involving 4 or 5 people. On the other hand, bacaba juice is sporadically consumed and, due to its high output (up to 10 liters), it is usually consumed with friends and for more than 1 day. Contaminated juices, in this feature, can result in an increase in the number of infected people, as was the case of the outbreak reported in Ananás. The most recent outbreak in Brazil occurred in September 2019, resulting in the infection of 16 individuals, and was associated with the consumption of the fruit of the patawa tree (Oenocarpus bataua), a palm tree that reaches 25 m height. This highly appreciated palm tree is found in the Amazon basin, and its fruits are used for several purposes, including juice preparation. Altogether, these cases demonstrate that, more than a specific food, human outbreak cases are the result of poor sanitary education and poor practices of food manipulation.In addition to beverages, Triatoma vitticeps, a triatomine considered to be a secondary vector due to its delay of defecation after a blood meal but that demonstrated to be quite efficient in concomitantly hosting several T. cruzi DTUs and T. dionisii. The boy was infected by handling this T. vitticeps specimen . These distinct epidemiological scenarios throughout Brazil show the necessity of distinct control measures.The definitive control of Chagas disease is possible and, more than that, is urgent. It should not be possible that this parasitosis is still a scourge more than one hundred years after its discovery and so much accumulated knowledge. However, control will be possible only under an integrated multidisciplinary focus and not by the traditional control measures. Spraying in this new epidemiological scenario is the worst control method. The development of an understanding of all cultural, social and economic realities of the outbreak areas and, obviously, all epidemiological features, including fauna composition hosts and vectors, will be the only way to define and adopt the correct measures that must include economic, health and educational improvement.Leishmania infantum  are responsible for controlling transmission  the transmission strategies of the less frequent DTUs; (ii) the fact that these DTUs are detected at extremely distant points; (iii) the lack of association of DTUs with biomes; and (iv) the high diversity of DTUs in a relatively small area of the southeastern Atlantic Forest. Increasing studies of habitats and areas will probably add information that may change this map. All of these questions show that the biological history of T. cruzi is far from complete. Numerous chapters are still to be written about the biological history of T. cruzi that will likely include even more spectacular landmarks than those highlighted here.Philander spp. and Didelphis spp., the coati Nasua nasua, the capuchin monkey Sapajus libidinosus and the golden lion tamarin Leontopithecus rosalia, were the mammalians that demonstrated higher rates of positivity, demonstrating infectious potential  that at some point in the infection, these genotypes had a high circulating blood population; or (ii) other unknown transmission mechanisms warrant transmission in low parasitemias, as is the case in Brazil of the DTUs TcV and TcVI that are rarely found in nature. A plausible explanation can be drawn from a Santa Catarina outbreak in 2005. At that location, the wild mammal fauna was restricted to marsupials of the genus Didelphis whose blood cultures indicated in TcI in contrast to the human cases that were all by TcII. One specimen of Triatoma tibiamaculata had a mixed TcI and TcII infection  clinical manifestations are attributed only to that species or genotype that eventually is detected, and the possible effects of an initial multiple infection are totally ignored; and (ii) associations between the host and parasite (species or genotypes) are established based only on one single finding that is very probably not necessarily representative.A clear demonstration of how biased associations can be established is provided by Guarapari's case of the child who became orally infected by There are still many open questions on this topic, one of which specifically refers to the transmission of these genotypes and species that are so rarely found in nature. Are they becoming extinct, or are they beginning a process of expansion?T. cruzi DTUs or Trypanosoma species were observed in all Brazilian biomes, but the host most frequently associated in these mixed infections varies: bats in the Amazon Forest and Cerrado, opossums also in the Amazon Forest and Atlantic Rainforest, coatis in Pantanal, caviomorph rodents from the Thrichomys genus in Caatinga and triatomines, mainly Triatoma vitticeps, in the Atlantic Rainforest  displayed infections by diverse T. cruzi DTUs. The authors detected the presence of TcI, TcII, TcV, and TcVI in single and mixed infections. In fact, 47% of individuals presented infections due to multiple T. cruzi DTUs  and micro  variables.Studying biological phenomena without considering the scenario in which they occur results in the loss of precious and potentially enlightening information. The determination of the spatial distribution of the elements that compose the epidemiological chain of a parasitic disease is of pivotal importance for the determination of trends and risk evaluation. Moreover, it is worth mentioning that the attempts to control a given multihost parasite that displays a huge intraspecific heterogeneity and a complex transmission cycle as expressed by different epidemiological and enzootiological scenarios employing one single measure will be insufficient. The sustainability of successful control of Chagas in multiple current epidemiological scenarios requires multidisciplinary studies. All of the host species select subpopulations of The study of landscape by the classic methodology of mapping by means of discrete typing units and sharp boundaries does not consider transition areas. Nevertheless, environmental and biological phenomena are typically continuous and exhibit a gradual transition from one to another. The fuzzy logic developed by Zadeh in the 1960s is able to solve the strongly non-linear nature of uncertainty and subjectivity inherent in biological data. Furthermore, the spatial analysis by the fuzzy inference method is a cartographic approach that makes it possible to model the spatial distribution of continuous biological phenomena, representing these distribution levels. Modeling by fuzzy logic allows the incorporation of multidisciplinary expert knowledge into the evaluation process. Despite posing as a paradigm break in comparison to the valuation methodologies based on classic logic, fuzzy theory facilitates dialog between the professionals of exact sciences, responsible for computational implementation, and experts from different biological areas because it allows the use of linguistic variables and simplistic logical rules. Such logic has been vastly used in biological modeling due to its peculiar features, especially the capacity to model complex and non-linear problems in a simple way.T. cruzi transmission in nature. The output data obtained can be used to support decision-making in epidemiological surveillance of Chagas disease and are certainly an example that can be applied to several other parasite infections in distinct areas . The term “map algebra” was established by Dana Tomlin in the early 1980s  were revealed in a few years by Carlos Chagas, the T. cruzi diversity, pathogenesis, peculiar features of the interaction of T. cruzi with its numerous hosts and its multiplication and dispersion strategies still constitute a puzzle. Undoubtedly, the huge technological advance and the consequent stronger analytical power allowed the resolution of many of these issues. However, the current epidemiological profile of Chagas disease, due to the oral route, constitutes a challenge and a scourge, especially for people with less access to adequate sanitary conditions and medical care. One of the possible obstacles to controlling this parasitosis does not depend solely on technology but relies on the conceptual framework of researchers and technicians that is often rigid, poorly resilient and open to the new, disregarding the hyperbolic doubt of René Descartes' (1637) concept about the importance of the need to continually inquire the truth of what is presented as true. This kind of attitude is paralyzing, just as paralyzing as the lack of self-confidence and the hesitation to publish their findings. Science also includes intuition beyond assumptions built on solid foundations. This is exemplified by the pioneering study of an oral outbreak in Nova Teutônia, Santa Catarina State, Southern Brazil. It was a boarding school where several young people became ill and Chagas disease was diagnosed. At the time, all searches for triatomines resulted in vain. The outbreak remained unexplained. One of the authors, Nery-Guimarães, hypothesized that perhaps the ingestion of food that had been contaminated by the urine of T. cruzi-infected opossums could be the cause (Nery-Guimarães et al., T. cruzi in the opossum scent glands of D. aurita (Deane et al., Here, we briefly described some features that have been landmarks in the course of knowledge building on Technological advancement has resulted in new insights into the parasitism phenomenon and consequently in the reformulation of concepts. An example is the definition of what constitutes a reservoir. Carlos Chagas defined the armadillo as a “depositary,” probably disregarding, as expected at that time, that a host receives and exerts selective pressures on the parasites. The very concepts of reservoir and of what is a parasite have been changing since the days of Carlos Chagas. In this sense, the most didactic and clear definition of what is a reservoir does not refer to the number of species or the ability to cause or not to damage but defines reservoir as one animal species or a set of animal species responsible for maintaining the parasite in the wild. This set of animals will be different for each location and time scale (Jansen et al., Trypanosoma spp. associations. A clear understanding of host-parasite interaction and the mechanisms involved in this adaptation process are important from the academic point of view but also for public health, because in times of profound climate change, emerging diseases result precisely from parasitic spillover to unfamiliar hosts. The acquisition and loss of host species are common events in the parasitism phenomenon and can happen independent of a long-term coevolutionary process. Actually, ecological host fitting is a process of spillover that depends on the preexisting attributes of the parasite (Araujo et al., T. cruzi.Parasitic specificity has also been revisited as a consequence of technological innovation, and the awareness of the importance of including wild animals and their parasites in parasitology studies has increased. Trypanosomatids are no exception: reports of the occurrence of trypanosomatids in unfamiliar hosts are increasing, undermining paradigms of host species and T. cruzi biology may be found in its ancient hosts, i.e., the wild mammals in nature.The answers to most of the still open questions of AJ and AR wrote the manuscript. SX performed figures. All authors conceived, designed the manuscript, read, and approved the final manuscript.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.


Background: Oncology patients experience a large number of symptoms and, those referring to cognitive performance has an ever-increasing importance in clinical practice, due to the increase in survival rates and interest in the patient’s quality of life. The studies reviewed showed that chemotherapy-related cognitive impairment might occur in 15 and 50% of oncology patients. The main objective of this research was to study the impact of chemotherapy on the cognitive function of patients with locoregional breast cancer. Method: Analytical, prospective, longitudinal study using three measures, unifactorial intrasubject design, non-probability, and random selection sampling. The sample comprised women newly diagnosed with locoregional breast cancer in stages I, II, IIIA who received chemotherapy at the University Hospital of Salamanca , randomly selected for three years. Semi-structured interviews were conducted, and anxiety and depression ; quality of life  and the following cognitive variables were assessed—processing speed, attention, memory, and executive functions . Results: The final sample size included 151 participants; 23 were excluded. A decline in cognitive performance was observed in patients, which did not completely recover two months after chemotherapy was completed. Additionally, worse cognitive performance was observed in patients with anxious or depressive symptoms. There was a negative impact on the quality of life. Conclusion: Chemotherapy had an impact on the cognitive performance of oncology patients in most cognitive domains studied. The quality of life of oncology patients is one of the aspects of most concern for healthcare professionals in their clinical practice, especially in the last two decades. This increased interest in the impact of oncological treatments on the cognitive functioning of patients.Most research on cognitive functioning was performed on women with breast cancer, as it is a large population, their cognitive functions are in better conditions, and they have fewer symptoms than patients with other oncological pathologies. Additionally, the high survival rates of these patients show the importance of cognitive disorders such as memory loss or attention and learning difficulties. These symptoms can go unnoticed in the pathology of other types of cancer, such as lung cancer, head and neck tumours, or gastric cancer, since there are other priority symptoms.The first studies that were performed did not have well-defined designs, and their small sample size did not allow conclusive outcomes. Most studies were cross-sectional, and the evaluation of cognitive performance was carried out at a single moment in time, during or after chemotherapy . This vaMost studies include the requirement of assessing pre-treatment baseline cognitive performance to compare future results. These first evaluation studies accurately predicted the extent of the change observed after oncological treatment, and at the same time, its development over time. The importance of the first evaluation was evidenced in the study by Wefel , a longiOther studies such as Hurria and Hermelink ,3 also sThis baseline impairment could be explained by the presence of personal or environmental variables, such as emotional state, the hemoglobin level or a low educational level.It is not only necessary to know the baseline cognitive status of the patients before the administration of chemotherapy to have a comparative reference, but it would also be substantial to measure at different times of the treatment, to identify the evolution in the cognitive performance of the patients, since previous studies found that cognitive impairment increases after chemotherapy . Given tThe mechanisms that cause chemotherapy-induced cognitive impairment in cancer patients receiving chemotherapy are not yet well-known, although there exists multiple etiology.-Direct neurotoxic effects—cytostatic drugs that cross the blood–brain barrier can cause cell death .-Induced hormonal changes—these changes can interfere with hormone secretion and activate cognitive problems. It is known that chemotherapy changes the testosterone and estrogen levels, which are considered neuroprotective hormones.-Oxidative stress—chemotherapy decreases the cellular antioxidant capacity and thus increases DNA damage .-Immune system dysregulation caused by cytokine release—inflammatory cytokines cross the blood–brain barrier and can cause a decline in cognitive function, manifested as decreased processing speed, executive function, spatial ability, and reaction time .-Vascular damage—coagulation in small vessels of the central nervous system, vascular damage, and autoimmune phenomena. Both chemotherapy and radiotherapy can damage blood vessels, which reduce blood flow in the small blood vessels in the brain .The factors that the literature proposes as most influential in chemotherapy-induced cognitive impairment areCognitive impairment is the loss of cognitive functions  that occur in normal ageing. Cognitive domains function correctly when the brain structure and function is in an optimal condition. Chemotherapy crosses the blood–brain barrier, alters mental functioning, and causes impairment of some cognitive domains. The cognitive impairment of our brain depends on both physiological and environmental factors and is subject to significant interindividual variability .Hess  also pro-Chemotherapy-related cognitive impairment—toxicity might produce cognitive changes when crossing the blood–brain barrier.-Stress-related cognitive impairment—stress can negatively affect memory as it increases cortisol released by the adrenal glands, and this substance directly affects the hippocampus, which is part of the limbic system dedicated to working and short-term memory .-Anxiety-related cognitive impairment—excessive worry and irrational fear can impair memory by focusing thought on a particular obsession. Memory suffers from anxiety and can cause memory loss .-Depression-related cognitive impairment—depression might be related to attentional problems, which affect the information acquisition and coding phase. The data provided by different scientific studies show adverse neuropsychological effects of chemotherapy .Factors that might speed up the cognitive impairment process are:The meta-analyses focused on this subject have selected some of these studies ,15,16. SA dose-dependent correlation was found ,20 betweThe most positive results assure that after six months, the impairment disappears entirely, or there tends to be a progressive recovery . This suggests that the cognitive impairment of the affected patient is more likely to be transitory in patients treated with fewer cycles of chemotherapy, at lower doses, over a long period. Patients who recently finished their treatment, with a larger number of cycles and high doses of the drug in each cycle, showed significant impairment. The bibliographic review shows that 15 to 50% of oncology patients receiving chemotherapy present some type of neurological complication with regards to cognitive functioning in one or more domains ,23.The studies consulted define some cognitive impairment in oncology patients before the treatment and suggest the possibility of an increase in the impairment, during therapy, as a consequence. It is convenient to explore its influence on cognitive functioning two months after starting the treatment, and also study if the possible impairment is maintained for two to six months after its completion ,24,25.Patients with breast cancer are more susceptible to cognitive impairment, due to their treatments and because their tumour causes fewer symptoms than other cancers, so they are likely to pay more attention to cognitive issues.A longitudinal study was performed that allowed us to verify the pre-treatment cognitive impairment of oncology patients, and increase in impairment post-treatment and after the treatment was completed.Based on the above, the following hypothesis was stated: Patients with locoregional breast cancer present throughout their treatment a cognitive impairment that was preserved at least two months after its completion.The main objective was to study the influence of chemotherapy on the cognitive status of patients with locoregional breast cancer at the University Hospital of Salamanca ).To analyze the impact of chemotherapy on the cognitive domains in the three study periods measured.To assess whether the emotional state affects the cognitive performance of patients.To define if there are changes in the quality of life of the patients during the treatment and if this affects their cognitive performance.Specific objectives:Analytical, prospective, longitudinal study using three measures, unifactorial intrasubject design, non-probability, and random selection sampling. The sample was provided by the Medical Oncology Service of the University Hospital of Salamanca.The scope of the study comprised patients newly diagnosed with locoregional breast cancer in stages I, II, and IIIA, and who are about to receive chemotherapy at the Day Hospital and the Medical Oncology Hospitalisation Unit.All patients were newly diagnosed and received adjuvant or neoadjuvant chemotherapy, and did not receive any previous oncological treatment.The patients were randomly assigned to the study between 2015 and 2017.The following inclusion criteria were established—female; anatomopathological diagnosis of locoregional breast cancer; fit to receive chemotherapy; is a patient who attends the University Hospital of Salamanca; is of legal age and less than 85 years-old; stage I, II, and IIIA breast cancer; and written informed consent stating that participation was voluntary. Additionally, a series of exclusion and withdrawal criteria were stated, as shown in A research project and a viability check by the Salamanca University Assistance Complex’s ethics committee to implement this research was developed. The recruitment of patients started in October 2015, when the research was approved. A baseline was defined at the beginning of the chemotherapy.Those patients who verbally consented to participate in the study were called to the Medical Oncology offices to sign the written informed consent and to explain the objective and procedure of the study.All assessment was performed on the same day the patients received the chemotherapy, between the analysis and the beginning of the chemotherapy cycle.In the first interview, clinical and socio-demographic data were collected from the patients, and the baseline was set using the tests indicated above.The evolution of the patients was followed up during the three months of chemotherapy treatment and within two months of the end of treatment.Therefore, three measurements were established to study the evolution of cognitive performance—at the beginning of chemotherapy, three months after receiving treatment, and finally, two months after the treatment ended.These three measurement moments were established with the aim of evaluating the effect chemotherapy had on the cognitive performance of the patients studied. A total of 613 interventions of approximately one hour were performed.This set of tests was suitable for application in this type of research, specifically in people suffering from an oncological disease, for its selection by relevant psychometric issues, the high incidence of use in similar studies, and its brief and dynamic application. The variables anxiety, depression, and quality of life were studied, as well as their cognitive function, analyzing processing speed, attention, memory, and cognitive functions.-Processing speed—measured by the Symbol Search and Key Search Subtests.-Attention—measured by the Trail Making Test and the Stroop Color and Word Test .-Memory—measured by the Vocabulary Subtest.Anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale (HAD) , qualityThese evaluation tests were considered due to their high use in cancer patients, and also because they are standard tests of choice in the study of cognitive and attentional functions and health-related quality of life.In addition, a semi-structured interview was conducted with all patients for the collection of clinical and socio-demographic data.Data collection took place from October 2015 to January 2017.The study was conducted after the authorization of the Clinical Research Ethics Committee of the Salamanca Health Area, and prior informed consent of the study subjects, following the Declaration of Helsinki. The participants were informed of the objectives and the risks and benefits of the studies (informed consent). Similarly, the confidentiality of the subjects included was guaranteed at all times, following the provisions of the Organic Law 3/2018 of 5 December on the Protection of Personal Data and Guarantee of Digital Rights and the Regulation (EU) 2016/679 of the European Parliament and Council of 27 April 2016, on data protection (GDPR), and the conditions established by Law 14/2007 on biomedical research. Approval number—0000263. Name of the Council—Bioethics Committee of the University of Salamanca. Board Affiliation—University of Salamanca.The statistical analysis was pre-planned, with small modifications once the study was performed. Initially, an exhaustive review and data cleansing was carried out to detect possible errors in the data collection, and to correctly and accurately apply the exclusion criteria established for the study. For this purpose, a descriptive analysis was used, focusing on the maximums and minimums obtained from the quantitative variables.The variables of the study sample were analyzed by the Shapiro–Wilk and Kolmogorov–Smirnov Test for normality, to determine the follow-up. The variables were found to follow a normal distribution and subsequently defined by mean, standard deviation, and interval for values. Cases and percentages defined the discrete variables.Different tests were performed, such as the “analysis of variance ANOVA or the repeated measures ANOVA” to determine if there were significant differences between the three measurements of the patients in the variables that measure cognitive impairment . The data processing was performed using IBM SPSS 23.0.A total of 174 patients were interviewed. Two did not want to participate in the study, and one withdrew the informed consent.A total of 171 patients performed the study. Twenty did not fully complete the self-administered tests and, although in all other measures it was valid, failure to answer some item in a given test nullified the entire study for those patients.The study comprises a total of 151 patients, as shown in the flow chart, The first objective studied, analyzed the impact of chemotherapy on the cognitive domains in the three measurements studied.The analysis of those domains or cognitive functions was as follows—low scores indicate an increase in cognitive impairment, except in the TMT-A and TMT-B tests, where the high scores indicate a significant increase in cognitive impairment.A general pattern was met in most cognitive domains studied—as chemotherapy progressed, the cognitive performance of the patients in the study worsened significantly from the obtained scores at baseline.Regarding memory , we observed a decrease during treatment (M = 26.53) with regards to the start (M = 27.76), and recovery two months after completing chemotherapy, almost reaching the starting data (M = 27.46)In contrast, with regards to the evolution of the processing speed (measured by the Symbol Search Subtest (SS), Key Search Test (KS)), attention (measured by the Trail Making Test (TMT) and the Stroop Test (ST)), a decrease was observed throughout the chemotherapy . The lowest cognitive performance score was obtained two months after the end of treatment .The second objective was to assess whether the emotional state affects cognitive performance throughout the treatment, and to determine if there were significant differences in the tests that measured cognitive impairment, according to the emotional state of the patients . The Analysis of Variance Test for independent samples, ANOVA Inter, was performed to determine if the emotional state of the patients affected cognitive performance. In this case, only the variables with statistically significant differences between the groups are shown. -p < 0.05);Symbol Search before ;Letters and Number before ;Stroop Word before  andStroop Color and Word before Stroop Color and Word during  (1), borderline case (anxiety and depression) (2), and emotional state with a clinical problem (anxiety and depression) (3) : -SymbolSince the Emotional Status Factor had three comparison groups, Scheffé’s Post-Hoc Test was performed to determine which groups presented differences in the tests and which cognitive domains were affected.Therefore, after analyzing the data of the patients’ situation before treatment, the differences were more evident in those whose emotional state (anxiety and depression) was classified as a clinical problem. Additionally, a worsening of cognitive performance was observed in the normal and borderline case. These differences occurred before and during chemotherapy, after which the values tended to normalize, that is, the performance improved.The last objective studied determined if there were changes in the quality of life and if this affected cognitive performance .The statistical analyses performed by the inter ANOVA test did not find significant differences between patients who obtained a bad, regular, or good quality of life in the tests; neither before, during, or after treatment in any of the tests evaluating the cognitive domains. In this case, the classification for each patient, according to the scores obtained in the quality of life assessment (EORTC QLQ BR23), could be a section that was too subjective to find significant differences between those who were classified in one or another category. Therefore, it was complicated to find differences between them when we measured cognitive functions and impairment.The main objective of our research was to determine cognitive impairment in a sample of locoregional breast cancer patients as a consequence of chemotherapy.The results report worsening of cognitive performance in most of the studied domains during chemotherapy. Most studies confirmed that cognitive disorders occurred in 15–50% of patients ,32.The bibliographical review showed that some patients with chemotherapy present memory and concentration problems . This syDuring chemotherapy, the cognitive performance of the patients in the tests decreased regarding the pre-treatment measurement. The performance improved after the end of the treatment, that is, in most cases, the cognitive performance improved with regards to the previous evaluation of the patients. These results were consistent with literature findings in which high levels of cognitive impairment were observed in patients receiving adjuvant chemotherapy, when comparing their performance in the tests with normative data or in patients who did not require chemotherapy or healthy persons. This supports the hypothesis that systemic chemotherapy treatment produces cognitive deficits .Chemotherapy-related cognitive impairment is not a global phenomenon, but rather is specific to certain cognitive domains. Different studies do not agree, but it seems that the most frequently deteriorated domains are—attention span, verbal memory, working memory, processing speed, and motor ,38.In contrast, the executive functions are preserved ,40. FurtThe cognitive domains evaluated in the research were selected based on the literature reviewed, which showed the most affected domains during chemotherapy. After analyzing the results, data showed that all cognitive domains studied were affected during chemotherapy, although not all showed the same impairment. The domains that were most affected in this research were processing speed and working memory. This might be because attention and memory processes are neuroanatomical structures associated with adult hippocampus neurogenesis. The new neurons generated by the hippocampus are essential for memory and learning, and brain-derived neurotrophic factor is required for growth .The optimal functioning of processing speed, which refers to the amount of information that can be processed per unit time, was linked to the diameter of the nerve pathways, the integrity of the myelin sheath, the degree of myelination, the number of ion channels, and the efficiency of the synapses. Some studies linked the use of some chemotherapy drugs used in the treatment of breast cancer to cause toxicity in the Central Nervous System, which could cause cell damage and DNA chain breaks, leading to cell death and consequent synapse loss .In the other cognitive domains studied, a tendency to worsen during chemotherapy was observed, but the results in these domains were not significant.Kesler , performAdditionally, reduced left caudal lateral prefrontal cortex activation significantly correlated with a higher disease severity .The results of this research were similar to those obtained in our study, except for the correlation found between cognitive impairment and disease severity.The emotional state affected cognitive performance, as it increased cognitive impairment of patients during chemotherapy. The patients who had severe levels of anxiety and depression were those who suffered the most from cognitive performance. Some patients in our research showed high levels of anxiety and depression before starting treatment with chemotherapy. This state might be due to the impact of the recent diagnosis on the assessment of their cognitive performance. High levels of anxiety and depression can affect structures related and connected to the hippocampus, which could result in a worsening of patients’ cognitive performance.These results are consistent with the literature reviewed, which states that anxiety and depression affect cognitive function, especially attention, and therefore the way the brain processes and stores information .The study conducted by Jalali  showed aThe impact of cognitive performance on the quality of life of oncological patients in our study showed that cognitive functioning had no impact. As some studies suggest ,46, for Based on the results obtained we can say that the cognitive performance of breast cancer patients decreased throughout chemotherapy treatment. Recovery from this performance is not achieved in its entirety within two months after the end of chemotherapy treatment, which is an important factor in the worsening of cognitive performance and leading to symptomatology of depression or anxiety.


Pediatric biobanks are an indispensable resource for the research needed to bring advances in personalized medicine into pediatric medical care. It is unclear how or when these advances in medical care may reach children, but it is unlikely that research in adults will be adequate. We conducted the screening for a hypothetic problem in various European and American pediatric biobanks based on online surveys through e-mail distribution based on the Biobank Economic Modeling Tool (BEMT) questionnaire model. Participants in the survey had work experience in biobanking for at least 3 years or more. Contact information about the survey participants was confirmed on the social networks profiles (LinkedIn), as well as on generally available websites. First, we tried creating a model which can show the pediatric preclinical and basic clinical phase relationship and demonstrate how pediatric biobanking is linked to this process. Furthermore, we tried to look for new trends, and the final goal is to put the acquired knowledge into practice, so medical experts and patients could gain usable benefit from it. We concluded that leading positions must take into account ethical and legal aspects when considering the decision to include children in the biobank collection. However, communication with parents and children is essential. The biobank characteristics influence the biobank's motives to include children in the consent procedure. Moreover, the motives to include children influence how the children are involved in the consent procedure and the extent to which children are able to make voluntary decisions as part of the consent procedure. The role of biobanks in biological research in general and their impact on medical, societal and economic issues have been discussed in two reports from the Organization for Economic Co-operation and Development. In biomedical research, irreproducible results are increasingly recognized as a major threat for scientists and the public and causing significant losses of private and public investments in research. Recent investigations have revealed that unreliable results are caused to a large extent by poor biological reagents and reference materials –4.Children's biobanks are a new direction, and the level of protection in research involving minors needs to be considered as outlined in the 2010 Secretary's Advisory Committee, Provincial Health Authority. The level and precautions used in clinical trials involving minors (EU Regulation No. 536/2014) differ significantly when examining pediatric biological material in a biobank, which must be taken into account when creating a pediatric repository [The progress of medical and pharmaceutical research in the world, as well as in Ukraine, directly depends on the quality of human bio-samples. Pediatric biobanks are an indispensable resource for the research needed to bring advances in personalized medicine into pediatric medical care. It is not yet clear how or when these advances in medical care may reach children, but it is unlikely that research in adults will be adequate , 10, 11.Today, more than 120 biobanks are known in the world, and at least three global associations and networks are the Middle Eastern and African Society for Biobanking (ESBB), International Society for Biological and Environmental Repositories (ISBER), and Biobanking and BioMolecular Resources Research Infrastructure (BBMRI). However, only 20% of them have biological collections related to pediatrics.For the practice of personalized medicine to be applied to children, genomic research will need to be conducted in children –16. An eIn this study, we explored the opinions and attitudes of biobanks and parents' associations towards the donation of specimens from sick children to a hypothetical biobank.For the tool development, a survey was designed and sent to 230 biobank managers and directors worldwide. We have created a list of about 90 managers, directors in biobanking active individual researchers in developing countries with considerations to ensure wide geographical coverage. The focus was on the active sides for the most accurate evaluation of the survey data. The estimated percentage of respondents was 20–25%.In order to achieve our goals, we conducted a multidisciplinary review of the pediatric biotechnology market to refine and collect information on economic models. We conducted the screening for a hypothetic problem in various European and American pediatric biobanks based on online surveys through e-mail distribution based on the Biobank Economic Modeling Tool (BEMT) questionnaire model .The survey with detailed questions has been divided into five sections:•biobank demographics and structure;•ethical aspects of pediatric biobank;•legal aspects of pediatric biobank;•question of communication biobank-personal/physician and parents’ associations towards the donation of a specimen from sick children;•samples quality control.The managers, directors, researchers of biobanks, and parents of disabled children associations were identified using social networks (LinkedIn), as well as generally available websites. Participants in the survey had work experience in biobanking for at least 3 years or more. The request for a contribution to the survey has been spread by means of blind e-mail, and no personal data of a participant was available to others at this stage. The e-mail comprised a short invitation letter and info about the survey with an attached link to the survey. Responders had the opportunity to save and exit the survey several times and had 4–6 weeks for completion of the survey submission altogether. Three follow-up e-mail reminders were sent to all participants in two-week frequencies. Data were collected from several sources in each biobank after obtaining the permission of officials (managers): websites, information on paper (informed consent forms) that characterize biobanks, and consent policies. Analysis of the collected material made it possible to develop information letters for employees of biobanks, parents, and children. The main direction was the selection of people with sufficient experience in building a children’s protocol and consent procedures in this direction. However, the work experience showed that there was not enough to attract specialists. Therefore, the participating children and parents were also involved –21, 22. We have received only approximately 23% responses; 56 biobanks have responded, and the diversity of biobanks gave an extended profile. For example, in one subgroup, there were differences in operation directions - from collections of one disorder or organ to collections of almost all possible biological samples of human nature in biobanks of medical centers. A total of 56 responses were received. Of the 56 survey responses received, 32 were complete, and 24 were partially complete. Managers, directors, and researchers of pediatric biobanks typically completed the ﬁrst two sections . In contrast, associations of parents of disabled children completed the sections concerned with the legal aspects of the pediatric biobank, questions on the communication between the biobank and individual/physician, and the donation of a specimen from sick children). The majority of the survey responses were from West Europe (44%), developing countries (23%), and North America (11%), with the remaining surveys from Asia, Middle East, South America, and Africa .We found that 12% of biobanks have the A structure model - the collection site and the biobank reside within the same institution, 47% have model B - the biobank is external to the institution collecting the biospecimens and 41% have model C - multiple collection sites . Solid aBased on the survey results, we found that there are no specific regulations in many developing countries to control the creation and management of pediatric biobanks arising from institutional research projects. Also, major ethical concerns need to be met. These reasons are often left to be managed by the local Ethical Committees and their affiliated institution. As a result of the questionnaire, in developing countries, 76% of pediatric biobanks do not have consent forms of exceptional permission for specimen collection.An important component for the management of the pediatric biobank is the process of counseling minors; it is the involvement of children in this issue that is the basis for the management and sustainable development of the pediatric biobank.As a result of the analysis of the respondents’ answers, we established that personal communication and trust are the main factors influencing the donation of samples to the pediatric biobank.The earned trust, and the child’s personalized consent can lead to constant interaction, stability in the research infrastructure, and an increase in feedback among its participants, which is based on respect for minors. Therefore, it is a matter of communication to obtain a child's consent.According to the results of our survey, we developed suggestions for establishing and maintaining communication with children and adolescents:1.Establishing rapport;2.Maintaining rapport;3.Keeping the child in the conversation;4.Maintaining a supportive environment;5.Providing information in an accessible format for the child .Long-term planning with the inclusion of a full range of risks requires working with cell lines, products containing DNA/RNA and biologically active substances.The division into categories when working in a pediatric biobank is as follows: reputation-related risks, ethical risks, financial risks, operative risks, standard lab risks, human resources (HR) risks, infrastructural risks, information technology (IT) risks, strategic risks, natural disasters .Based on the fact that the identification and assessment of risks is a subjective component, we recommend a risk analysis at a seminar with the participation of all employees of the pediatric biobank such as management staff, public relations (PR), HR, financial officers, lab technicians, researchers, IT specialists, ethics specialists, infrastructure specialists, medical doctors and carrier organization members (as strategy makers and stakeholders).We revealed potential risks for pediatric biobanking in developing countries: 1.Children and some parents demonstrated a desire for re-consent and the right to withdraw at age 18;2.Parents often wanted the option of receiving their children’s genetic results, though the return of results was seen as potentially infringing on the privacy and autonomy of the child;3.Despite the rising social expectation that research participants’ voices be heard and an increasing need for pediatric biobanks, there is a paucity of empirical research conducted to date.According to the results of our survey, the main models of the pediatric biobank were model A, where the collection site and the biobank reside within the same institution. In model B, the biobank is external to the institution collecting the biospecimens, but researchers may be internal or external to the collecting institution. In model C, multiple collection sites contribute with biospecimens to a centralized biobank, the biobanking network, which distributes biospecimens to researchers –25. The Interestingly, there was a complete lack of understanding of the pediatric biobanks’ structure in developing countries. There were no regulatory documents necessary for its creation. Scientific, medical and pharmaceutical institutes and clinics have collected, processed and stored biological material without standard operating procedures. Such kind of situation led to a massive number of mistakes in various scientific departments, which caused the reduction of the competitiveness of medical science in developing countries in general –27.Another problem area of the biobanks network in developing countries is connected with the resellers who were involved in the resale of services related to the biological material. They are mainly focused on the movement of tissues and biological samples from primary sources into research groups. The employees of such companies are almost entirely made of people without medical education. This situation led to a greater volume of mistakes. We found that biobanks make “one-time efforts,” namely a one-time collection, only for a specific purpose, as well as in the absence of a clear research motive, and this emphasizes the importance of showing respect for the child, which should be the main goal of biobanks since research interests go hand in hand with the interests of the child. This is the driving force behind the European Pediatric Translational Research Infrastructure (EPTRI), which is a strong incentive to involve children in the consent process .Scientific and medical research that includes children is essential to developing therapies for younger patients . PediatrUndoubtedly, ethical and legal issues based on consultations with stakeholders emphasize the importance of an appropriate framework for practice. The actual parental consent was considered by many to be sufficient, while the undoubted importance of children’s consent for research in the field of biobanks was not studied.The development of biobanks for children requires a deep understanding of many ethical, legal and social issues. This is the solution to the missing sections, and the elimination of gaps at the legislative level, as an example of the lack of attention to the rights of vulnerable subjects in some developing countries, should be considered .We concluded that leading positions must take into account ethical and legal aspects when considering the decision to include children in the biobank collection. However, communication with parents and children is essential. The procedure for including minors in the consent procedure is significantly influenced by the characteristics and purpose of the pediatric biobank. This is what affects the degree of participation in the consent procedure for children. Our study confirms the need for specific policies dedicated to pediatric biobanks by highlighting how the nature of the disease affecting children may influence the parents’ opinions and decisions towards the enrolment of their children in biobank-based research studies.The authors declare that there is no conflict of interest.