In 2012/2013, the prevalence of child mental illness was estimated to be between 12 and 25% in Ethiopia. The Federal Ministry of Health is currently considering the implementation of the second national mental health strategy guided by the World Health Organization’s pyramid model for an optimal mix of services. This model states self-care as the fundamental concept and practice that can be facilitated by the formal and informal sectors surrounding an individual. Despite this remarkable move toward endorsing contemporary approaches to mental health services, Ethiopia struggles with a limited number of knowledgeable and skilled mental health professionals. This systematic review aims at identifying the main challenges Ethiopia might face while implementing the pyramid model. We will suggest ways to bridge the gap between the need for child/adolescent trained mental health professionals and training mental health professionals informed with the value of integrating the concepts of the pyramid model into the system of mental health care for Ethiopians. The paper also discusses the importance of integrating the Wellness based mental health approach into mental health professionals’ training as a means of developing a culturally responsive approach to child and adolescent services. This review provides implications for further studies and mental health policy, systems and services in Ethiopia. Ethiopia developed its first National Mental Health Strategy (NMHS) in 2012/2013. This NMHS was an initiative by the Federal Ministry of Health (FMOH) intended to be implemented within 5 years : 1–4. Thhttp://www.moh.gov.et/ejcc/am/node/170). However, the report did not include information on specific demographic variables. Although FMOH did not portray its data against the prevalence rates of mental disorders in the other countries, based on a report published in https://www.who.int/health-topics/mental-health#tab=tab_2). The lack of specificity in the data provided by FMOH could be a deterrent in the implementation of the NMHS as well as the provision of preventative and mental health care treatment for Ethiopians.In 2019, as part of a mental health forum, the FMOH identified more specific categories of mental health problems among children and adolescents on its website, i.e., ADHD, oppositional defiant disorders/conduct disorders, anxiety disorders, mood disorders, elimination disorders, and autism spectrum disorders, with prevalence rates of 12–25%.The report showed an increment in suicide rates and the prevalence of alcohol and substance use disorders across a 10-year span. The report also showed a 21.56–27.9% prevalence for “common mental health disorders”  by referring to a meta-analysis [author(s) unspecified] conducted in 2018 . In the literature identification process, for research articles, the search criteria included: research conducted in Ethiopia, research focused on integrating cultural factors into the mental health service provision, mental health among children and adolescents, research that has a framework or a systemic approach to addressing mental health issues and services in Ethiopia, and research studies integrating the concept of a wellness approach. For research articles, studies published between 2014 and 2020 were included. This time period was chosen to include studies conducted following the implementation of the first NMHS in 2012/2013. Research articles were excluded if the study was focused on clinical trials, was non-peer reviewed and focused on non-systemic or framework-oriented research. For other framework and approach-oriented publications, the publication dates were considered between 2000 and 2020. Publications included under the “other framework and approach-oriented publications” were specific to the WHO’s Pyramid model, the Wellness Model and the Indivisible Self-Model. For fundamental conceptual paradigms , original publications were reviewed and their publication year dated back to 2000. During the identification, 28 research articles and 21 other publications were identified. Of these, three articles and five other publications were removed due to duplication.During the screening process, research studies were included that focused on systemic reviews of the mental health systems and policy in Ethiopia, training of mental health professionals, and expanding/alternative approaches to mental health services. Research studies that focused on causes of mental illness, mental health disorders and their consequences, mental health training for professionals, child trafficking, food insecurity and mental health, mental health among women, mental health among college students, and mental health in specific ethnic, economic and ways of life were excluded. For other publications, contents that did not provide general guidance on the framework and approaches to mental health were excluded. Accordingly, 12 research studies and 20 other publications were selected. Of these, 27 articles and other publications were chosen for inclusion in this review.The eligibility process for selecting articles and publications emphasized the first NMHS and the WHO’s pyramid model of optimal mix of mental health services as guiding mental health service approaches for an Ethiopian context. These documents were chosen to be the focus for the following reasons. First, the NMHS was the first of its kind that Ethiopians developed to tackle the barriers identified during the implementation of MDGs. As a result, it provided information on national level directions. Second, the NMHS emphasizes the role of the WHO’s pyramid model of optimal mix of mental health services as a guiding strategy to organize national and local level mental health services. The model is used as a reference for training community-based mental health professionals in Ethiopia. As a result, the pyramid model allows a review of the training of mental health professionals according to the mental health service approach endorsed by FMOH. Third, the emphasis of the WHO’s pyramid model of optimal mix of mental health services on self-care and informal care systems allows the integration of culturally responsive mental health services. As a result, nine articles and 10 other publications were included in the qualitative data synthesis.This systematic review of relevant and timely publications illustrates the WHO’s pyramid model of optimal mix of mental health services, the mental health profile of Ethiopia, mental health professionals practicing in Ethiopia, and ways to bridge the gap between the need for mental health services and integration of a comprehensive approach to such services. The following table shows the type of articles and publications used in the synthesis of this review and the common themes that emerged.In In multiple mental health status reports, it is common to see the lack of specific information on Ethiopia’s systems of assessment and intervention for mental health disorders. The NMHS states cultural factors as reasons contributing to the inability to gather accurate data on the prevalence of mental health problems and providing professional services : 12. Spehttp://www.moh.gov.et/ejcc/am/node/170). Moreover, FMOH, through the NMHS, is still using the WHO’s pyramid model for a combination of services contributing to quality mental health services . The mental health wellbeing approach as a framework for future mental health initiatives and services in Ethiopia was also addressed.After the implementation of the first NMHS, Ethiopia is currently working on the second NMHS, with the intent of incorporating the successes obtained and lessons learned during the implementation of the first NMHS . Most first-generation universities that have undergraduate programs also have graduate level programs in those fields. However, it is not clear how many students graduated from those programs thus far. The lack of national data on the number of mental health graduates from Ethiopian universities and their placements creates a challenge in portraying the work of these professionals. The coordination of services between these mental health professionals and the formal health care system is not well known. It is unclear whether/how these mental health professionals are trained to familiarize themselves with either a wellbeing approach or the WHO’s model of optimal mix of mental health services. In our research, we were able identify that the undergraduate psychology curriculum provides the opportunity for students to learn about child and adolescent developmental milestones but does not address individual well-being as a concept or as an intervention strategy.https://bdu.edu.et/febs/). Graduates of the School Psychology program would be a valuable resource to support the mental health services provided in schools. However, there is no status data that reports the number of graduates from this program thus far or their placement status after graduation. Even with a well-coordinated utilization of all mental health professionals, Ethiopia could still encounter a substantial lack of mental health professionals. The shortage of mental health professionals would be even higher in providing services to children and adolescents since 46.5% of the Ethiopian population is under the age of 14 (https://data.un.org/en/iso/et.html).The WHO’s report depicts a clear picture of the lack of mental health professionals to address the mental health needs of the people in Ethiopia. The report only included one child psychiatrist for the whole country. Most of the outpatient mental health services report no specific categories of services offered or an annual policy/plan for development : 1. ThisDue to low number of adequately trained mental health professionals, Ethiopia largely depends on health extension workers to integrate mental health services into their prevention and intervention work on physical health. “Health extension workers are Ethiopia’s version of a large-scale community health workers (CHWs) program” : 2. HealFMOH, in collaboration with the WHO, has been providing mental health Gap Action Program (mhGAP) trainings to health extension workers, in an attempt to address the lack of trained mental health professionals. The mhGAP is intended to equip primary care providers and their trainers with a model guide to mental health disorders, knowledge and skill on assessment, diagnosis, and intervention . The traDespite the mhGAP training’s brief duration, several findings support the significant improvement in the knowledge, attitude and skill of mental health professionals after the training. However, studies conducted among mental health professionals indicated the perceived challenges in the implementation of culturally sound evidence-based therapeutic techniques. Cultural factors were identified as a challenge in the training of mhGAP for mental health professionals. In a reflection study of 6 years of experience in implementing the mhGAP training in six developing countries including Ethiopia, a study by In a recent study that explored the indigenizing of westernized therapeutic techniques for Ethiopian communities, Diagnostic and Statistical Manual of Mental Disorders, fifth edition  published by the American Psychological Association while the intervention is given less focus. Although the DSM-5 provides guidance in diagnosing mental disorders, the limited representation of cultures like Ethiopia in the process of conducting research to identify symptoms for a particular disorder puts Ethiopian professionals in a difficult position. For instance, the general perception of some symptoms of depression and anxiety among community members as acceptable reactions to life circumstances was one of the challenges identified by mental health professions in their effort to diagnose mental health disorders and deliver interventions for individuals  requires more hours for presenting diagnostic cases than designing interventions. This indicates the emphasis on identifying the psychopathology and becoming equipped with assessment tools and diagnoses based on Western diagnostic criteria, i.e., ividuals : 8. SimiRevision  since thMentorship and supervision are one of the most reliable ways to strengthen the skills of early career professionals as they develop the necessary knowledge, attitude and skill to work effectively. Due to the lack of appropriately trained mental health professionals, Ethiopia also faces a challenge of having a system for supervising front line workers. In the 1980s Myers and Sweeney developed the Wheel of Wellness, based on the Individual Psychology of At the center of the wheel is spirituality, which in most cultural contexts is considered the most significant aspect of overall wellness. In an Ethiopian context, as many studies indicated e.g., , spirituDirectly around spirituality is self-direction, associated with each spoke of the wheel surrounding it. Depending on cultural context, self-direction could include an orientation toward family and community that influences an individual’s self-direction, if part of a collectivist culture as opposed to an individualist culture. Each spoke of the wheel represents tasks associated with achieving balanced wellness and mental health—cultural identity, sense of worth, sense of control, realistic beliefs, emotional awareness and coping, problem solving and creativity, sense of humor, exercise, self-care, stress management and gender identity : 236. ItLife forces that affect personal wellness, such as religion, family, education, business/industry, media, government and community surround the individual in the wheel of wellness, and on a larger scale, global issues and current events are addressed as contributing to overall wellness : 236. FuThe Indivisible Self model includes all of the components of the original Wheel of Wellness, but reduces specific factors influencing overall wellness into more conceptual factors that encompass the many tasks formerly associated with the Wheel of Wellness. In addition, the new model acknowledges cultural contexts, as well as developmental life stages. This new model is accessible to individuals at all stages of the lifespan, in all cultural contexts , 486.The Indivisible Self model represents a framework that can be used to describe the somewhat elusive concept of self-care that the WHO established as the foundation for positive mental health. Not only does the model break down the concept of self-care into specific factors that encompass the whole of human experience, but it brings the focus of attention to strengths an individual, and arguably, family and community system possesses, as opposed to a sole focus on illness and psychopathology. Familiarity with the Indivisible Self model could provide healthcare workers in Ethiopia with a framework to assess mental health issues presenting in their clients, and a direction for providing culturally responsive interventions. Following are some suggestions about how orientation to the Wellness and Indivisible Self models could facilitate services provided to children in Ethiopia.A significant percentage of children and adolescents spend majority of their daytime in schools. For instance, the Ethiopian Ministry of Education stated that the Net Enrollment Ratio (NER) for primary school children (7–14 years-olds) was 94.7% : 34 lookDespite the high prevalence of mental health problems among children in Ethiopia, the FMOH does not have a specific plan or strategy to address mental health issues in children and/or adolescents : 1. ConsThe development of a national strategy would also allow collaboration with mental health professionals, although few, that are already working with children and adolescents in schools. These professionals include applied psychology, school psychology, and social psychology graduates to be counted as mental health service providers. Furthermore, it would allow schools to adopt the strategy and design accountable action plans to promote the overall wellness of their students.DSM-5 as a reference to diagnose mental disorders is valuable, it is paramount that professionals learn about the cultural considerations for each diagnosis. In this regard, The design of mental health professionals’ training curricula should be culturally sensitive to enable trainees to translate their training into practice. It is imperative that international frameworks for assessment, diagnosis and intervention are implemented in accordance with the local contexts of Ethiopian culture. For instance, although using the Introducing a relationship-based wellness model as opposed to the diagnosis-focused medical model would alleviate some of the concerns raised above. Ethiopians believe in establishing and maintaining close relationships with each other. Most people have shared values and consistently work hard to maintain the equilibrium of this status quo. Based on the recommendations of the WHO pyramid model’s mix of mental health services framework, professional helpers should recognize individuals’ self-care strategies that are derived from their values and preferences. Further, they should design interventions that integrate the informal community in to their mental health recovery.Effective integration of the Indivisible Self model to the education and training of mental health professionals can be done in multiple phases. First, continuing education or in-service programs could provide information about overall wellness and the Indivisible Self model to professionals providing services to children and families who were not specifically trained in mental health. Integrating basic knowledge about holistic wellness, recognizing strengths, and enlisting support from families and communities could help to alleviate symptoms that children present. Second, the curriculum design of university programs could be tailored toward promoting the self-care of the individual seeking mental health services. Integrating topics, courses, and experiential learning tasks to the curriculum could enable mental health professionals in training to coordinate the formal and informal systems, self-care, and professional mental health services that their future clients require. These strategies could enable both professionals and the immediate community members to accept the individual with mental health issues as a person first and not as a diagnosis. Third, working with schools, neighborhoods and parents could be an effective strategy to work toward comprehensive mental health services that integrate informal and formal sectors. Developing a system of accountability in schools would also encourage the school system to establish and/or strengthen the mental health systems within schools. Finally, establishing a mentoring and supervision system could provide an opportunity for mental health workers to consult on culturally specific challenges in the process of assessment, diagnosis and intervention for mental disorders among children and adolescents. This mentoring and supervision platform could create an opportunity for integrating and developing culturally responsive strength-based strategies that are supported by the lived experiences of Ethiopian children and adolescents.The potential implementation of the above proposed interventions could enhance the access and quality of mental health services for Ethiopians, especially children and adolescents. Introducing a system that acknowledges the relevance of continuing education will help mental health professionals to be familiar with adaptable contemporary mental health interventions. Consultation among professionals is key to generating ideas that could solve challenges experienced by mental health professionals. It creates the opportunity for psychologists, social workers, and counselors to work across disciplines which might lead to collaborative evidence-based research focusing on culturally sensitive mental health interventions. This systematic review also brings to light the need for ongoing research on the implementation and outcome of the Indivisible Self model specifically within an Ethiopian context. College level mental health programs could pilot introducing the concept and implementation of the wellness approach with the goal of integrating culturally sensitive concepts and interventions into the overall approach to mental health care. On the bases of its applicability, future policies and strategies could integrate the Indivisible Self model in to the WHO’s pyramid model of optimal mix of mental health services.Improving access to culturally relevant intervention strategies to better serve children and adolescents in Ethiopia is at the heart of our purpose in this paper. Systemic change takes time, and perhaps the best place to start is to acknowledge the need for an inclusive and culturally responsive approach to mental health care. Acknowledgment could lead to continuing education for direct care  workers, followed by improved collaboration between health extension workers and mental health professionals. If preliminary outcome data support the inclusion of a wellness approach to mental health care with children and families, perhaps that will provide the impetus for including curricula and practice implementing the wellness approach and the Indivisible Self model into higher education training programs. Promoting the holistic health and wellness of children and adolescents in Ethiopia, and around the world, facilitates wellness in families, communities, and larger social contexts. The world is calling for change, and perhaps honoring cultural contexts in our approach to mental health care is but one way to answer the call.HM is the lead author for this manuscript. HM and VJ consulted on organization and outline and divided tasks. HM conducted literature review on mental health approaches and services in Ethiopia. VJ provided context on the wellness and indivisible self models. Authors worked together to edit and integrate contents in the 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.


The spleen is a secondary lymphoid organ that belongs to the reticular-endothelial system, directly connected to blood circulation. The spleen is greatly involved in the immune response, especially against capsulated bacteria. Splenectomy plays a fundamental role in the treatment of numerous pediatric hematologic disorders. Taking into account all the possible complications  linked to this procedure, alternatives to total splenectomy have been sought. Partial splenectomy has been proposed as a treatment that allows the reduction of infectious risk. This approach has proven safe and feasible in most patients, but multicentric and prospective studies are necessary to more accurately define the indications for performing partial splenectomy. However, vaccinations and antibiotic prophylaxis remain fundamental for preventing serious infections, even in the case of partial splenectomy. We review anatomical and functional properties of the spleen, with a focus on medical or surgical indications to splenectomy, aiming to give practical educational information to patients and their families after splenectomy. Furthermore, we discuss the feasibility of partial splenectomy in children with hematologic diseases who require splenectomy. Currently splenectomy is still fundamental in the treatment of numerous pediatric hematologic and immunological disorders. The main indications for splenectomy are represented by congenital hemolytic anemia , some forms of thalassemia, idiopathic thrombocytopenic purpura not responsive to medical treatment, and some forms of accumulation disease associated with hypersplenism  . There aIn our work, we review anatomical and functional properties of the spleen, performing a focus on medical or surgical indications to splenectomy, with the aim to give a practical educational guide to patients and their families after splenectomy. Furthermore, we discuss the opportunity of partial splenectomy that in recent years has been considered to be a feasible alternative to radical splenectomy in order to obtain a clinical resolution, reducing or eliminating the infectious risks related to the absence of the spleen, which plays an important role in the immune response, especially against capsulated bacteria.The spleen is a secondary lymphoid organ that is part of the reticular-endothelial system. Its peculiarity is given by its faster and more immediate action, because of it is connected to the blood circulation directly and not through the lymphatic vessels like the other lymphoid organs . The splThe spleen is covered by the capsule, a fibrous lining from which some trabeculae branch to form a net that constitutes the splenic stroma. Inside this network there are the red and the white flesh, at the margins of which the fibrous reticulum thickens, forming the marginal zone. The white pulp represents about the 25% of the splenic tissue and consists entirely of lymphoid tissue, which may be divided into three sections: periarteriolar lymphoid sheaths (PALS), germinal centers and marginal zone. Splenic white pulp is organized around central arteries in the form of PALS, which are populated mainly by T lymphocytes. Germinal centers contain lymph follicles with actived B lymphocytes that produce antibodies, following an antigenic stimulus. Finally, the marginal zone develops between the white pulp and red pulp. It contains antigen-presenting cells (APCs), such as macrophages. Splenic arterioles then cross the marginal zone where they thicken macrophages and fibroblasts and finally reach the red pulp, which represents 75% of the spleen. In the red pulp, they form venous sinusoids which are surrounded by a tissue rich in macrophages and are internally covered by endothelial cells. Outside of these venous sinuses, the red flesh is structured in the cords of the spleen, a network of reticular fibers, fibroblasts and macrophages with high phagocytic activity. Numerous body functions are carried out in the spleen, such as phagocytosis, hematopoiesis, deposition and immune response. Splenic macrophages show a high phagocytic capacity, due to the presence of lysosomes rich in enzymes very active in hydrolysis and destruction of tissue debris, corpuscular substances and opsonized infectious agents. In addition to these cells there are numerous mononucleate dendritic phagocytes which are only moderately phagocytic. They perform the function of antigen-presenting cells, by activating the response of T and B lymphocytes, which are present in the white flesh and then migrate in the splenic cords and the bloodstream . The macSplenectomy is a surgical procedure that is performed on about 6.4–7.1 people per 100,000 each year. About 25% of splenectomy interventions are performed as a result of abdominal trauma that causes rupture of the spleen resulting in intraabdominal bleeding and risk of hemodynamic shock. Another 25% of operations are performed for the treatment of hematologic disorders. Less frequent causes of splenectomy are consequent to intrinsic injuries of the spleen, tumors, abdominal surgery, accumulation or vascular disease , as descIn splenectomized patients, a significant problem is represented by overwhelming post-splenectomy infections (OPSI) that are characterized by a sudden and rapid general deterioration that occurs after about 24 h from the onset of the first infectious sign, such as flu, up to the framework of fulminating sepsis with CID and septic shock that can quickly lead to death ,10. The The age of the child (maximum under 2 years and however high up to 5 years), the time elapsed from the splenectomy (greater risk in the first 2–3 years that then decreases without ever zeroing and resurfacing after 60 years), the basic disease  are known as risk factors for OPSI ,13,14. Splenectomy should therefore be avoided up to five years of life, when possible. OPSI are caused mainly by capsulated bacteria  ,16. In aThe OPSI are burdened by a high mortality risk, even if treated appropriately, therefore a prevention program is crucial in splenectomized subjects, based on three pillars: family education, vaccination, and antibiotic prophylaxis . Parents should be informed about the infectious risk and should be made aware of the necessity of always starting quickly an antibiotic therapy at the first signs of infection, and going to the hospital for a rapid medical evaluation at the onset of symptoms. It should also be recommended to avoid areas where malaria is endemic, paying particular attention to dog bites. Several studies showed that splenectomized individuals and their family members have very little awareness about the risks related to their condition. It has also been reported that patients with more comprehensive and adequate information, have a lower risk of presenting OPSI . Table 2Vaccination is the most effective prevention tool for splenectomized patients. Children should be vaccinated two weeks before the splenectomy, when the surgery is planned electively, as in the case of hematologic disorders. In those cases when the splenectomy is performed in an emergency, vaccination should be carried out from 14 days after surgery, although some data suggest that they can be effective even in the immediate peri-operative time .There is a fair variability in the recommendations regarding the type of vaccination and the precise timing to follow, also related to the history of vaccination and the age at the time of splenectomy of the subject. Most of the guidelines indicate vaccinations against the main capsulated germs, such as Pneumococcus, Meningococcus and Hemophilus Influenzae type B, and annual anti-flu vaccination .Conjugated vaccines that seem to provide a better immunological response in splenectomized subjects are generally indicated, since these vaccines stimulate a response mediated by thymic T cells that is not modified by the splenectomy .Concerning anti-pneumococcus vaccination, it is recommended to perform a dose of conjugate vaccine (PCV13) followed by a boost performed with polysaccharide vaccine (PPSV23). The vaccination against meningococcus should include the administration of both the conjugated vaccine quadrivalent (Men A-C-W-Y) and the most recent conjugated vaccine against serotype b (Men B). It has not yet been clarified the indication to perform a recall after the first vaccination, although several recommendations suggest a recall every 3–5 years. For vaccination against Hemophilus Influenzae, a single dose is indicated without any recall in previously vaccinated subjects. Although influenza virus infection does not pose increased risks in splenectomized subjects, annual vaccination is indicated to reduce the risk of any bacterial infection, performed with inactivated vaccines and not with attenuated vaccines .In splenectomized patients, no increased risk of developing severe Sars-Cov2 infections was reported. In a study on asplenic patients in England, the number of deaths from coronavirus disease was not statistically different from the general population ,26.After splenectomy, for children who have performed an adequate administration of vaccines, continuous antibiotic prophylaxis is recommended, which has been shown to reduce the risk of severe infection by 50% and death by about 90% .Adherence to vaccination recommendations has proved very variable and unsatisfactory in most splenectomized subjects . MoreoveZhang et al. performed a systematic review and meta-analysis to explore the association between splenectomy and CTEPH, finding a prevalence of splenectomy in CTEPH of about 4% [Splenectomy may generate a prothrombotic state, with consequent increased risk of venous thromboembolic disease, such as thromboembolic pulmonary hypertension. Thus, splenectomy is recognized as a potential risk factor for chronic thromboembolic pulmonary hypertension (CTEPH) . Recentlabout 4% . From a surgical point of view, the laparoscopic approach is preferable as it reduces intraoperative complications, post-operative pain and hospitalization time. However, the laparotomic approach is however still widely performed and accepted especially in the cases of important splenomegaly. No differences were found in the results of the hematological response, nor in the infectious and thromboembolic complications. In recent years, to reduce the main infectious risks related to total splenectomy, the indication to partial splenectomy has become more important, even though it was performed for the first time in the 60 s. Currently, the improvement of surgical techniques has allowed to extend the laparoscopic approach to this procedure . PartialThe main indications for splenectomy can be medical or surgical. In some cases, as in hereditary spherocytosis, hereditary ellipsocitosis, and some lesions of the spleen, it represents the only therapeutic option. In other diseases, it must be evaluated according to the clinical characteristics of the patient. Splenectomy is considered possible and safe in most children for whom it is indicated, but regarding partial splenectomy, although most of the existing studies are multicentric or performed by single centers, the number of patients is small and it does not allow having clear indications for it. The main advantage of partial splenectomy is the preservation of residual splenic tissue that can maintain the immune function of the spleen, reducing the risk of fulminating sepsis. It is very difficult to extrapolate from the literature to what extent this risk is reduced by subjecting the child to a partial splenectomy, compared to the total one, because there are no trials large enough or with an extended follow-up. In addition, most of these studies were performed before the diffusion of the antistreptococcal vaccine 13-valent and meningitis vaccines, so the actual incidence of post-splenectomy sepsis is difficult to clarify .In some works, the production of total Immunoglobulin G (IgG) and M (IgM) was evaluated and it seems to be stable after the intervention of partial splenectomy. The spleen remains the main antibody production site, so this data suggests the importance of the action of the residual spleen .Sheikha AK et al. collected data from 62 children affected by hereditary spherocytosis, who underwent partial splenectomy. They found a significant improvement in hematologic profiles and symptoms in all patients, briefer in those with a good splenic post-operative regeneration. Moreover, none of them developed sepsis, demonstrating that partial splenectomy may be effective in reducing the OPSI events, becoming an effective alternative in children with hereditary spherocytosis .Regarding the hematologic response to partial splenectomy in patients with spherocytosis, there was a satisfactory improvement in the hemoglobin values, even if lower than that found in patients subjected to total splenectomy (an increase of the hemoglobin of 2.4 g/dl against 4.1 g/dl). Moreover, there was a reduction of the values of reticulocytes and bilirubin overlapped to those obtained from patients who underwent total splenectomy. In drepanocytosis, there was no increase in hemoglobin values, but an improvement in the clinical picture with fewer symptoms related to hypersplenism and splenic size. In subjects with immune thrombocytopenia, there are still no clear data on the short-term and long-term outcomes of partial splenectomy. In such a pathology, the use of partial splenectomy could be limited, considering the hemorrhagic risks related to thrombocytopenia, even if there was no evidence of a different bleeding rate between the partial and total splenectomy. It was necessary to convert the surgery from laparoscopic to laparotomic more often in the partial than in the total splenectomy (30% vs. 1–3%). Apart from this, perioperative complications were minimal and not significantly different from total splenectomy ,39,40,41One aspect to consider is the rate of conversion from partial splenectomy to total splenectomy during surgery, for the following days and even the following months . In the Because of the risk of conversion to total splenectomy and in the absence of clear data about the contribution of the residual splenic tissue to the reduction of the risk of sepsis, the indication to pre-intervention vaccination and post-antibiotic prophylaxis should be assessed in more extensive studies. Furthermore, cholecystectomy is often mandatory after partial splenectomy in patients with spherocytosis. In the work of Hafezi et al., this risk was 39% in patients not previously subjected to cholecystectomy, much higher than in patients who underwent total splenectomy. This suggests that the residual hemolytic splenic activity in the patients with partial splenectomy makes them more susceptible to the onset of gallbladder gallstones [In many studies, a regrowth of the residual spleen was reported after the intervention of partial splenectomy. In the study by Rice et al., among 13 patients that underwent partial splenectomy, the volume of the spleen remained between 15 and 30% of the initial volume after two years, up to 40% after four years. In addition, in four patients where growth was greater than 75%, only two episodes of hemolysis occurred later, suggesting that this event is not related to a return of the disease . FurtherPartial open or laparoscopic splenectomy is a safe procedure associated with a low incidence of morbidity and it has become an important option in children with hematologic disorders that require the removal of the spleen.The possibility of partially preserving splenic tissue seems to ensure a reduction of the main infectious risks related to splenectomy, and an adequate hematologic response, even if such evidence should be supported by more comprehensive future trials. However, although in the absence of reliable data, it is necessary to recommend vaccination and antibiotic prophylaxis also to those patients who undergo partial splenectomy.


BJPsych International focuses on Bangladesh, one of the most densely populated countries in the world and geographically vulnerable to a wide range of natural disasters. Mental health has been deteriorating since the COVID-19 crisis, but few psychiatrists and clinical psychologists are available to manage the consequences.This month's issue of  BJPsych International, so it is of great interest to find out how that country's psychiatric services have developed since then. In this issue we include several articles that will bring us up to date. Back in 2006, Bangladesh had only 73 psychiatrists in a country of 123 million people; just three of them had trained in child mental health.1 Since then, the population has grown by about one-third, indicating that a high proportion of the population is now under 15 years of age. According to the updated country profile by Tasdik Hasan and colleagues, mental health problems in both adults and children are at unprecedently high levels.3 The number of psychiatrists available to provide care to 162 million people has increased to 210 since 2005, but resources devoted to mental health services remain stubbornly low.1 The COVID crisis has made the situation even worse; in particular, there are concerns about the rapidly rising incidence of child mental problems, widely expressed on internet forums.Fifteen years have passed since we last published a country profile on Bangladesh in 2 One promising development has been the provision of a new set of mental health laws, summarised by Mohammad Karim and Sabuj Shaikh.4 In 2018, the colonial era Lunacy Act of 1912 was replaced by a new Mental Health Act. One provision of the Act, which may lead to an improvement in currently inadequate government-run public health facilities , aims to support the development of separate mental health units in medical college and district-level government hospitals. Also, in the future, private entities will be able to establish rehabilitation centres.Hasan et al provide a set of priorities for research and service development, but note that the World Health Organization's (WHO's) Mental Health Gap Action Programme (mhGAP) has yet to be implemented widely in Bangladesh.5 There are no formal psychiatric services available to prisoners provided by the government, although some prisons have third-sector support for prison staff and inmates, aimed at improving employment chances on release and dealing with the problem of drug addiction. Many of the issues discussed would apply equally to prisoners in the UK, where drug misuse and mental health problems are rife. Interestingly, in Bangladesh psychiatrists do not visit prisons, and mentally ill prisoners are brought by staff to attend appointments elsewhere. The authors draw attention to the need for a comprehensive review of prisoner mental health using objective screening methodologies, and suggest that incarceration provides an opportunity to provide therapeutic interventions that may not be available elsewhere.Whether the 2018 Act will improve the fate of prisoners with mental disorders remains to be seen. Al Aditya Khan and colleagues review mental health services in the prisons of Bangladesh.6 This article also draws attention to the poor mental health of many transient Bangladeshi immigrants to the UK, as well as those working in the Persian Gulf states. The country has had to cope with more than its fair share of natural disasters and other stressors, not least of which has been the massive influx of refugees from Myanmar in the past few years. In some ways, these refugees have been better served than the indigenous population because they have received intervention from the WHO mhGAP initiative. Apparently, the consequent provision of psychiatrists and psychological support has caused local resentment because the immigrants are seen as competitors for scarce public service resources. Since the adoption of the country's new Mental Health Act of 2018, there is hope that fresh budgeting and funding will be used productively to improve services nationally, especially in rural areas. Improvements in crisis management are also a priority, given the scale and frequency of natural disasters in this part of the world.Finally, Faruq Alam and co-authors discuss how the provision of mental health services in Bangladesh could be improved in the future.


With the world being amidst the global coronavirus pandemic, the development of vaccines to prevent further transmission was urgently needed, and the response to address this need has been unprecedented. On 21 December 2020, the European Commission (EC), upon a positive scientific recommendation of the European Medicines Agency (EMA), granted the first Conditional Marketing Authorization (CMA) to a vaccine against SARS-CoV-2 (Comirnaty of BioNTech and Pfizer)  Member-States with healthcare and other frontline workers; older adults were identified as priority groups across jurisdictions, while different priority groups were established across different countries. In Greece, January 16 was the first day for the vaccine administration to adults from 85 years of age. Greece introduced a staggered vaccination rollout based on age and exposures. The University Hospital of Heraklion (PAGNI) in Crete was amongst the first healthcare units to participate in this effort. The task was assigned to the PAGNI's Department of Public Health, under the coordination of three university professors and with the participation of 17 residents trained in General Practice/Family Medicine (GP/FM).This perspective article aims to snapshot observations and experiences gathered from the COVID-19 Vaccination Centre (VC) established at the University Hospital of Heraklion in Crete. We also seek to discuss how key practice aspects could be used to inform future interventions and to translate the experiences gained into concrete proposals to improve the role of healthcare practitioners in GP/FM and in primary health care (PHC), to improve the efficiency and effectiveness of future rollouts, as well as to combat similar crises in the future. Finally, We share the first experiences and observations made to date. Furthermore, we formulate our experiences into recommendations aiming to inform the transformation PHC urgently requires in Greece needs to enhance the resilience of the healthcare system, increase preparedness, and improve response.To date , adults, and children from 13 years of age, have been presenting for vaccination to the VC of PAGNI in Crete. During the pre-vaccination consultation, a brief medical history, regarding comorbidities and medications was obtained, along with information on recent episodes of flu or other infections, recent vaccination uptake, and history of contact with any confirmed or suspected COVID-19 case. The first and last author have involved in the providing the services at the VC and supervised the whole process upon the endorsement of the administrative authorities of the University Hospital. Although, it is an audit paper that it has been written as an opinion, the Hospital leaders have fully approved it.To facilitate the flow of the information in this report, we classified the experiences gained from the VC in three time slots and specifically:the first one corresponds to the first 4 months (January–April 2021), i.e., the vaccination of older adults;the second (after April 2021–now) corresponds to the period of the first adverse reactions and hesitancy emerging and resulting in a sustained effect against the COVID-19 vaccination attributed to the reported adverse reactions of Vaxzevria (Astra Zeneca);https://www.ema.europa.eu/en/news/first-covid-19-vaccine-approved-children-aged-12-15-eu). All persons vaccinated were provided with clear instructions about which side effects to expect and how to report them to the VC. According to the available protocol, vaccinated people were advised to stay in the hospital, under close observation for 15 min after the administration of the vaccine. The critical comments are shortly outlined below and, where possible, patients' quotes have been used to vividly support the experiences gained vividly.the third period one corresponds to the period of indication extension and subsequent vaccination rollout to pediatric population following the approval for ages 12–15. (a) Physical function was limited in many of the presenting people and the majority needed assistance. Almost half of them were on wheelchairs, while the presence of frailty was quite apparent in several.It is very frustrating to live in the same building with my six grandchildren and not to be able to see them. I wish this vaccine will end this torture.”(b) Although almost all older people were living with or close to their children, they frequently expressed feeling isolated, potentially because of the measures taken by their children to protect their parents. One lady mentioned: “I wish there were no other people in the waiting room so I could stay more with you and discuss. I felt so lonely, and you are so welcoming…. I wish I knew where to find you when all this ends.”GPs involved in the vaccination rollout set up a plan prior to its initiation so that, apart from vaccination, an empathetic and compassionate approach would be adopted independently of time limitations. If necessary, GPs would provide further consultations. Almost all elderly reacted positively to the empathetic approach of the healthcare professionals and expressed their gratitude for the warm and friendly services they were receiving. A man said: “I am glad that you made us feel so welcome; you remind me the days I was young, and I felt so close to my patients.”Many people also shared stories from when they were younger and more active. A well-known retired medical doctor of 89 years who presented for vaccination said: “The overall experience confirmed that time should be dedicated to really connecting with patients, even presents certain concrete challenges given the limitations in terms of time available for the encounters in the context of vaccine administration at the VC.(c) Older people were almost always accompanied by their children, who were present during consultations. These caregivers asked a lot of questions regarding possible vaccination side effects. Discussions in the context of the encounters at the VC revealed that there might be plenty of room for interventions regarding their own vaccination coverage and several other issues related to disease prevention. This underlined the strong bonds between family members, —a valid characteristic of the Greek society, which has primarly contributed to counteracting the effects of previous crises- and highlighted the need to support family cohesion during the strenuous times of the pandemic.d) The most challenging task was approaching older people with severe mental disorders and dementia, because of the inability to clearly communicate feelings and any potential side effects and given issues of addressing decision-making and autonomy. This challenge had to be managed through close contact with patient caregivers and family, to which GPs explained how to recognize and report side effects.https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-6-9-april-2021). This resulted in a high level of anxiety and uncertainty to the local populations, affecting the vaccination rate, especially in many rural areas where these two vaccines were the only ones available. Furthermore, The lack of active and personal involvement of GPs and PHC professionals in communicating the explicit messages and information as the frontline physicians, with a sporadic role in the vaccination rollout, enhanced the hesitancy, and increased the existing confusion. Several proposals were put forth to local stakeholders and presented in the local media but were not implemented. Among them, the following have been mentioned:In the second period, an increased hesitancy to the vaccinations was reported, as captured in the Pharmacovigilance Risk Assessment Committee (PRAC) regarding the sporadic cases of unusual blood clots with low blood platelets with Vaxzevria (AstraZeneca's COVID-19 vaccine) . Furthermore, safeguarding mobility and autonomy for these people in Greece may be an important area of focus. According to the 2019 OECD report “rs less” , 9.Equally, our observations point out to the impact of social isolation and the need for strong vital networking for people of this age group (over 85 years). In Greece, the role of family is crucial, and it seemed that, in our setting, there was good support provided to the elderly. However, loneliness was very prevalent and the need to see able to see their grandchildren was amongst the people's first wishes and perhaps a reason that motivated them to be vaccinated. We propose that vaccination programmes can be used for opportunistic screening of those elderly that need support in the form of mental and social care interventions, by easily identifying people without family or support/members or those that face other difficulties in accessing healthcare services. In line with the recommendations of the EC Expert Panel on effective ways to invest in health , the neeTo that direction, new healthcare models to respond to the current challenges should be discussed for example. The Italian healthcare system invested locally during the pandemic, and the idea is to keep patients near their families and friends who can take care of them . GP/FPs Our empathy, our capacity to envision that we too could be affected, has been a powerful tool in the public health arsenal” .Health technology has been used in the fight against this pandemic; for example, remote consultations have been extensively used , 14. HowThe high hesitancy to COVID-19 vaccination observed during the second period calls for an effective communication strategy to recover from the pandemic, based on sound evidence and with aligned messages across jurisdictions, communities and, even, across borders. Such a strategy needs to involve and engage stakeholders and community leaders. PHC seems to be the suitable ground to achieve it and there are several positive examples gained from Crete that they can be used as best practices . To thatFinally, the vaccination to children and adolescents in the third period highlights the importance the role of the family-oriented PHC and underlines the needs for further training of GP/FPs in the field of child care.The COVID-19 pandemic has placed health systems under pressure and has led to the introduction of extraordinary, if necessary, measures in Greece and across the world. Older people and patients with pre-existing medical conditions and, in general, with vulnerability are at higher risk of infection and worse outcomes , includiTaking into consideration the critical stage of the pandemic and the PHC reforms lately unfolding in Greece , our expAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Marine ecosystems are hosts to a vast array of organisms, being among the most richly biodiverse locations on the planet. The study of these ecosystems is very important, as they are not only a significant source of food for the world but also have, in recent years, become a prolific source of compounds with therapeutic potential. Studies of aspects of marine life have involved diverse fields of marine science, and the use of metabolomics as an experimental approach has increased in recent years. As part of the “omics” technologies, metabolomics has been used to deepen the understanding of interactions between marine organisms and their environment at a metabolic level and to discover new metabolites produced by these organisms.This review provides an overview of the use of metabolomics in the study of marine organisms. It also explores the use of metabolomics tools common to other fields such as plants and human metabolomics that could potentially contribute to marine organism studies. It deals with the entire process of a metabolomic study, from sample collection considerations, metabolite extraction, analytical techniques, and data analysis. It also includes an overview of recent applications of metabolomics in fields such as marine ecology and drug discovery and future perspectives of its use in the study of marine organisms.The review covers all the steps involved in metabolomic studies of marine organisms including, collection, extraction methods, analytical tools, statistical analysis, and dereplication. It aims to provide insight into all aspects that a newcomer to the field should consider when undertaking marine metabolomics. Oceans cover most of the earth’s surface, and they are a great source of biodiversity  and deep-sea, remote operated vehicles (ROVs) and bottom trawls are often used  or C18 SPE cartridges that retain these highly lipophilic compounds can be used  platform, which uses MS/MS data, has enabled the deduction of structural similarities between metabolites, allowing them to be grouped accordingly , together with methodological approaches such as OSMAC , an important organism in the food industry, was used to evaluate modifications in metabolic pathways related to their survival rates in different preservation conditions. The presence of metabolites indicative of a trade-off between aerobic and anaerobic metabolism detected in live scallops preserved in semi-anhydrous conditions provided essential information for their marketing, since this can affect the final value of the product  have been applied to the analysis of volatile compounds present in marine organisms, such as algae  coupled to mass spectrometry   is usually divided into two categories: unsupervised and supervised methods. For unsupervised MVDA, many approaches have been developed to reduce the dimensionality of the data, out of which principal component analysis (PCA) is currently the most commonly applied in marine metabolomics. PCA aims to collect most of the variance present in a data set using new orthogonal variables, known as principal components . It offers a wide range of options among its search criteria, including spectroscopic data such as UV maximum, NMR chemical shifts, and the exact mass. In the past years, another two open-sourced databases that focus on marine natural products have become available. MarinChem3D is a database that includes the tridimensional structure of over 30,000 marine natural products and some of their physicochemical propierties (MarinChem3D.). The most recently released is the Comprehensive Marine Natural Products Database (CMNPD), based on the annual marine natural products reviews, and includes all marine natural products reported from 1960 until 2018  as an ionization method generates highly reproducible fragmentation patterns that allow reliable identification using databases. In contrast, LC–MS analysis has produced less reproducible fragmentation data. In the past, analyses focused on the mass of adduct ions because of their soft-ionization modes. However, recently the necessity of tandem mass information (MS/MS and MSn) for identification has become evident. Databases such as NIST 20 (NIST 20), MassBank , and Chenomx contain information on the As with any other metabolomics studies, marine metabolomic studies greatly rely on the information available in databases to annotate compounds. As mentioned, the specialized databases MarinLit and AntiBase are particularly useful for the identification of secondary metabolites. However, the use of generic databases should not be dismissed, as several metabolomics studies of marine organisms have revealed changes in primary metabolites that may not be available in specialized libraries. Mass spectrometry databases are continually updated with additions of new information/molecules, making them a powerful tool for the dereplication of compounds, even if differences in experimental parameters and different instrument might greatly influence the mass spectra. In the case of NMR metabolomics, it is important to note that there is a need for the inclusion of more NMR spectroscopic data of marine natural products in the databases to improve the annotation rate of compounds. Moreover, the in silico predictions of NMR spectra, already available in software such as ACD/Labs, could benefit from the addition of more experimental data into the databases. Fortunately, with the increase in public spectroscopic data that is now required in metabolomics studies and the inclusion of this information in the databases, an increase in the annotation of compounds in marine metabolomics studies can be expected.A reasonable approach for identification is to use currently available databases as shown in the previous section. However, the limited number of entities in databases  was an incentive for the development of in silico identification strategies using both NMR and MS based methods. The different nature of the features obtained from NMR and MS data has led to the development of diverse approaches.1H NMR spectra to distinguish which signals belong to the same compound or family of compounds . This method uses the correlation between the intensity of the signals in the nds Fig. . STOCSY nds Fig. . It was nds Fig. . It was Rivularia sp. and Moorea producens  for the dereplication of natural products  is a metabolomics workflow based on MS-data sets, which has emerged in the last few years . After this initial identification, molecular networking analysis allowed the selection of other analogs of this compound, out of which four additional compounds were later isolated and identified .In recent years, and similarly to other fields of life sciences, metabolomics has been increasingly applied to the study of marine natural products as a new holistic tool for metabolic mining. Metabolomics platforms have increased the chances of discovering chemicals with either novel chemical structures or bioactivities. For example, phallusialides A–E, a group of alkaloids, were identified from the marine bacteria Fucus vesiculosus  has been used to identify the optimal culture conditions for different microorganisms, thus increasing the chemical diversity of the extracts obtained. One example of this is a study on fungi associated to the algae Erythropodium caribaeorum produced different diterpenoids of the erythrolides family in three different locations of the Caribbean   of clams Aplysina cavernicola  that uses compounds releases in the urine of its predator, the blue crab , to detect their presence  imaging, direct analysis in real time (DART) and desorption electrospray ionization (DESI) all of which not only provide ecologically relevant information about where compounds are produced and/or stored but can offer the possibility of analyzing samples without extracting them from their matrix  by combing a plaque assay with mass imaging spectrometry , and research submersibles, which allow a study of the environment that could not even be imagined in the past, the study of marine organisms remains an arduous task. The application of metabolomics in marine organism studies provides a new approach for the discovery of compounds that can be used for the benefit of humans in different ways. Perhaps even more importantly, it has increased the understanding of the function that all these metabolites have within the producing organism as well as the interactions of these organisms with their environment.Previous studies have suggested associated of microorganisms to be the real synthesizers of many of the secondary metabolites isolated from marine invertebrates (Gerwick & Moore, The ultimate goal of metabolomics, that is, acquiring a picture of the whole metabolome of an organism, is still a chimera, as none of the existing analytical platforms can detect all metabolites in a single analysis. The addition of new analytical tools, such as CE-MS, SFC-MS, HPTLC, and IR-based metabolomics, is a step in this direction, but even then, the use of more analytical platforms does not necessarily guarantee more useful information. Rather, it is increasingly clear that the solution to this problem may come via the combination of available metabolomics tools in a way that can provide the most useful information about the particular organism under study using bioinformatics tools.Identification of the metabolites of interest continues to be the major restriction in metabolomics studies. Although dereplication can be performed in the initial steps, on many occasions, the compounds cannot be detected within the mixture and have to be isolated for their identification. In the isolation process, the limited amount of sample is always an obstacle, and this has been circumvented in some cases by the implementation of microscale isolation protocols for low amounts of crude extracts. Additionally, other dereplication tools such as in silico MS/MS comparison can be useful for the identification of compounds, as reference compounds needed for identity confirmation are generally very difficult, if not impossible to acquire. The use of these strategies can facilitate metabolomics studies and speed up the process of discovering new compounds and thereby reveal the function of these compounds in the organisms.Until now studies have focused on the metabolites present inside the organisms, ignoring those that are released into the ocean. To achieve a deeper understanding of the interactions occurring in marine organisms, it is crucial to study the metabolites that are released into the water, as it is highly likely that these metabolites are possible mediators in these interactions. However, the study of exuded metabolites represents a major experimental challenge, as they are rapidly diluted in the ocean making their analysis very difficult. As a first approach, studies could be performed in the laboratory, in a controlled environment that reproduces the conditions in the field. In addition, water filtering systems could allow the concentration of the metabolites using methods such as solid-phase extraction. The use of this kind of experiment enables the collection of metabolites in a sufficient quantity to perform further metabolomics analyses. These kinds of studies will become an indispensable tool to understand the transfer of metabolites between organisms, providing valuable information for fields such as aquaculture, marine chemical ecology, and environmental metabolomics.


Background: Eagle syndrome occurs when elongated styloid process or ossification of the stylohyoid ligament interfere with the surrounding anatomical structures giving rise to various symptoms. Watt W. Eagle identified two types: stylo-hyoid classic syndrome and stylo-carotid artery syndrome. The aim of this systematic review of the literature is to evaluate correlations between Eagle syndrome and traumatic events or teeth extractions. Methods: out of 294 articles, the final study allowed the identification of 13 studies focusing on traumatic events. Out of 342 articles, the final study allowed the analysis of two studies regarding extractive dental events. Results: 13 articles showed correlations between the onset of symptoms in Eagle syndrome and traumatic events and highlighted two possibilities: traumatic event could fracture the already elongated styloid process or calcified stylohyoid ligament; trauma itself triggers the pathophysiological mechanisms that lead to lengthening of styloid process or calcification of stylohyoid ligament and therefore the typical symptoms. The only two case reports concerning Eagle syndrome symptoms after extractive dental events describe the onset of classic type. Conclusions: The analyzed articles confirm correlation between traumatic event and onset of typical symptoms of Eagle syndrome. There is not enough literature linking extractive dental events to Eagle syndrome. Trial registration: CRD42020185176. Oro-facial pain is among the most common manifestations of pain reported by patients. In the past, little attention was given to the facial pain and headache resulting from an elongated styloid process .Eagle syndrome (ES) refers to a rare constellation of symptoms caused by an abnormally long styloid process or stylohyoid chain ossification, which is characterized by craniofacial or cervical pain. It was first described by an Italian surgeon, Pietro Marchetti, in 1652; however, the clinical syndrome was definitively outlined by Watt Weems Eagle in 1937 [An elongated process is present in approximately 4% of the population, and the vast majority of these are asymptomatic. Eagle estimated the prevalence of symptoms in patients with elongated styloid processes as 0.16%. The syndrome has a female-to-male predominance of three to one. It generally occurs in adult patients, with the age ranging from 30 to 50 years [-“Stylo-hyoid classic syndrome”, which is characterized by pharyngeal pain aggravated by swallowing and frequently referred to the ear [ the ear . Other t the ear .-“Stylo-carotid artery syndrome” in which its vascular form is attributed to impingement of the internal carotid artery, extracranially, by the styloid process. This can cause a compression when turning the head or in “dissection” of the carotid artery resulting in a transient ischemic accident or stroke.Eagle described two types of the syndrome:In order to recognize and then treat this pathological condition, it is necessary to know the anatomy and embryology of the styloid process and the dynamics that come into play when a traumatic event occurs.Anatomically, the styloid process is a thin, elongated, cylindrical bone projection in an anteromedial position with respect to the mastoid process of the temporal bone. Its length varies between 20 and 30 mm and connects to three muscles and two ligaments. The muscles that originate from it are the styloglossus, the stylohyoid and the stylopharyngeal, which extend to the tongue, the hyoid bone and the pharynx respectively. The styloglossum and stylohyoid are innervated by the hypoglossal and facial nerves while the stylopharyngeal is innervated by the glossopharyngeal nerve. The ligaments that attach to the styloid process are the stylohyoid and the stylomandibular. The stylohyoid ligament originates from the end of the styloid process and extends to the small horn of the hyoid bone. The stylomandibular ligament extends from the styloid process to the posterior edge of the mandible; both are helpful in the movements of the mandible, the hyoid bone, the tongue and the pharynx.Embryologically, the styloid process, stylohyoid ligament, lesser cornu of the hyoid bone and the superior portion of the hyoid body are derived from Reichert’s cartilage, which arises from the second pharyngeal arch. The styloid process begins to ossify at the end of pregnancy and continues to undergo calcification over the first 8 years of life. -Theory of Reactive Hyperplasia.-Theory of Reactive Metaplasia.-Theory of Anatomic Variance .Several theories were proposed by Steinmann between 1968 and 1970 to explain etiopathogenesis, which are considered valid even today:In some cases, Eagle syndrome symptoms occur without an identifiable etiology or they could be consequences of tonsillectomy . The obsSince the symptoms are variable and nonspecific, patients usually seek treatment from several different specialties such as otolaryngology, maxillofacial surgery, neurology, neurosurgery, and finally psychiatry .Clinical manifestations.Digital palpation of the process in the tonsillar fossa.Radiological findings.Lidocaine infiltration test.The diagnosis of Eagle’s syndrome is based on four different parameters:In examining the clinical manifestations it is difficult to reach the correct diagnosis only on the basis of symptoms referred by the patients. It is important for physicians and dentists to consider Eagle’s syndrome in the differential diagnosis, since symptoms such as headache, facial pain, and neck pain, overlap with other clinical conditions such as diseases of nose, ears and throat and other pathologies, ranging from psychosomatic diseases to neoplasms.When carrying out the objective examination we mainly use tonsillar fossa palpation and Eagle himself considered this test as a diagnostic indicator. Digital palpation, in fact, immediately reproduced pain referred by the patients. However, no controlled study has proven the sensitivity or specificity of this indicator. The styloid process can only be palpated in the tonsillar fossa if it is longer than 7.5 cm .-Lateral teleradiography of the head: a disadvantage is that the styloid processes of the two sides may overlap.-Anterolateral modified Towne’s radiograph: this procedure calculates both the medial and lateral deviation of the process.-Panoramic radiograph: using this procedure clinicians can typically consider the styloid process to be elongated if its length is more than 1/3 of the length of the ramus of the mandible. An advantage of the orthopantomograph is that the entire length of the styloid process is visible and its deviation can be measured quite accurately.-Computed tomography: is an effective method for evaluating styloid process length, angulation and other morphological characteristics.-Sagittal computed tomography angiography: in cases of vascular compression, it can also be effective in assessing blood flow disturbance .Confirmation of Eagle syndrome is always radiographic:Saccomanno et al. evaluated different radiographic methods to investigate Eagle syndrome. Validity of panoramic radiograph as a diagnostic method for elongated styloid process and Eagle syndrome was investigated in a systematic review. Panoramic radiograph is a routine exam that gives an overview of the general oral and maxillofacial conditions. It is easy to perform and to interpret, with the advantage of having lower biologic, i.e., radiant dose and economic costs than computed tomography or cone beam computed tomography. For these reasons, it is more appropriate for the first diagnosis and for epidemiological evaluations. Therefore, in symptomatic patients, panoramic radiograph could be of help in the differential diagnosis of other conditions associated with orofacial and neck pain. In fact, the presence of radiographic evidence of styloid process longer than 30 mm, in patients showing pain during mouth opening, deglutition, or head rotation can be suggestive of Eagle’s syndrome .Although plain skull radiographs might be sufficient to reveal the anatomical abnormality, CT of the head/neck and especially 3D-computed tomography scans are considered the gold standard for visualization of the anatomically complex styloid process, as it avoids the problems of obscured overlapping anatomy. Moreover, it underlines the styloid process angulation, which is crucial for the surrounding anatomical relationships .lidocaine infiltration can be used (1 mL 2%) in the tonsillar fossa: if the patient’s symptoms and local sensitivity subside, then the test result is considered positive for a diagnosis of Eagle’s syndrome [Finally, an additional test consisting of sed 1 mL % in the The aim of this work is to investigate literature with a systematic review that evaluates correlation between Eagle syndrome onset and traumatic events. A further aspect that will be examined is the possibility of symptomatic cases of Eagle syndrome following extractive therapies in dentistry. Our work considered only patients who have experienced traumatic events or extractive dental events before Eagle syndrome onset.http://www.crd.york.ac.uk/prospero/; trial registration number: CRD42020185166).This systematic review was conducted following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions . The metThe studies included in the present systematic review were: bibliographic reviews, systematic reviews, meta-analysis and case reports analyzing correlation of Eagle syndrome with traumatic events and extractive dental events. We limited the inclusion criteria solely to English-language publications. Articles with unavailable full-text and articles in which Eagle syndrome and traumatic events were uncorrelated articles were excluded as well.This systematic literature review was carried out by searching articles on: PubMed, Cochrane Library, Campbell Collaboration, Current Contents, Turning Research Into Practice (TRIP) and SciELO. The following key words have been used: “Eagle Syndrome”, “Eagle’s Syndrome”, “Elongated Styloid Process”, “Trauma”, “Dental Procedure”, “Extraction” and “Dentistry”. Eligibility was discussed by authors by screening the title and abstracts of the retrieved articles. Whenever in doubt about the inclusion or exclusion of an abstract, the full text was accessed. The search strategies are reported in The main outcome of this systematic review is that some cases of Eagle syndrome arise after traumatic event and after tooth removal. Patients can be treated in different ways depending on the type and severity of the syndrome with complete remission of symptoms. We collected the data we found on the articles we finally included.We included review articles, systematic reviews, meta-analysis articles and case reports in which patients showed Eagle syndrome typical symptoms after traumatic events and tooth removal as well. After full-text reading we extracted data concerning sex, age, type of traumatic event, symptoms, diagnostic devices, final diagnosis and treatment of the patient. After data extraction we recorded all of them in three tables. Results, .Reviewing different search engines resulted in 294 articles available for consideration. After eliminating duplicate articles, 285 articles remained to be screened. After a first reading we further excluded 253 articles because they were not relevant and we evaluated 32 full-text articles. After evaluation of these 32 full-text articles, we excluded 18 articles because trauma was mentioned among the possible causes of Eagle syndrome, but in the specific reported cases it was not correlated to the patients’ symptoms. We also excluded the article by Balbuena et al. (1997) because it was already mentioned in the 2009 review by Piagkou et al. [Regarding the trauma of tooth extraction, reviewing different search engines resulted in 342 articles available for consideration. After eliminating duplicate articles, 340 articles remained to be screened. After a first reading we excluded 319 articles because they were not relevant and we evaluated 21 full-text articles. After evaluating these 21 full-text articles, we excluded 19 articles because they did not show any correlation between Eagle syndrome and extractive dental events. This left two articles published between 2016 and 2018 in which extractive dental events seemed to be correlated to Eagle syndrome b.The studies were graded under high, uncertain or low risk, based on: Selection bias, Performance bias, Detection bias, Attrition bias and Reporting bias. The quality of individual studies was evaluated based on the categorized ranking by Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.Our systematic review of the literature highlighted 15 articles showing correlations between the onset of symptoms of Eagle syndrome and traumatic events.These articles date from 1978 to 2018 and are mainly case reports ,14,15,16In the case reports included in this systematic review, several traumatic events such as car or motorbike accidents, aggressions, blunt traumas or accidental falls are mentioned and the most commonly found syndromic form is the classic type characterized by symptoms such as headache, dysphagia, cervical pain, pharyngeal pain and foreign body sensation ,15,16,17The diagnosis of Eagle syndrome is based on anamnesis, objective examination and instrumental examination. Through the collection of anamnestic data from patients, it is possible to retrace the traumatic events that led to the manifestation of the pathology: blunt traumas in four articles ,6,11,17,While performing objective examination, in one case it was possible to observe directly the presence of a mass or a bone protrusion due to the elongated styloid process by means of oral observation alone . In otheIn all the articles reviewed, Eagle syndrome was confirmed thanks to instrumental examination: panoramic radiograph ,14,16,17The findings highlighted by these investigations and the treatment of patients described in the studies included in the systematic review have been summarized in the previous Our systematic review of the literature concerning Eagle syndrome symptoms after teeth extraction highlighted only two case reports relevant to what we researched: an article by Sowmya et al.  and one These two studies have similarities, as both patients described are males under 40 years of age (38 and 36 years of age respectively) who began to show symptoms typical of the classic form of Eagle’s syndrome following teeth extraction.In the first article, the patient presented for observation with acute pain on the right side of the face which radiated to the temporal and neck ipsilateral area, also causing a decrease in rotational movements of the neck and head in that direction. He also reported stress and insomnia for about three months, a period during which he underwent lower right jaw third molar extraction.-Objective examination: extraoral palpation of a bony mass at the level of the tonsillar fossa area.-Instrumental examinations: panoramic radiograph and computed tomography scans of the neck.The diagnosis of Eagle syndrome was obtained through:From the examination of the panoramic radiograph the styloid processes were found to be bilaterally elongated and ossified while from the computed tomography display it was possible to measure them: right = 48 mm, left = 40 mm. In this case clinicians opted for drug therapy with diazepam for 5 days, NSAIDs and TENS [In the second article, the patient went in for observation five days after the onset of acute algic symptoms, dysphagia, foreign body sensation with repeated emetic episodes. The patient reported that the symptoms started two hours after the extraction of a dental element (however not specified).The diagnosis of Eagle syndrome was obtained through a computed tomography scan of the neck, which made it possible to examine the bilaterally elongated styloid processes and measure them: right = 46 mm and left = 47 mm. The patient was treated empirically with analgesic drugs and invited to go back for check-ups, to which he did not comply . ResultsEagle syndrome was first described in 1652 by the Italian surgeon Pietro Marchetti, but still there is confusion about this pathological condition because of its various symptoms, which are very common to other diseases.Once the patient with oral-facial pain presents to us, countless scenarios open up that may involve dentists, otolaryngologists, maxillo-facial surgeons, neurologists, neurosurgeons, psychiatrists, sleep disorder specialists and breathing specialists.The symptoms described by patients suffering from Eagle syndrome, and in particular in its classic form, are non-specific and common to other pathological conditions:Headaches: migraine, cluster headache, cervicogenic and chronic tension headaches, carotidynia, atypical facial pain, paroxysmal migraine, SDB, hormonal imbalance, allergies affecting breathing.Facial pain: disorders of the temporomandibular joint including joint clicks; neuralgia affecting the glossopharyngeal, trigeminal, and superior laryngeal nerves, the pterygopalatine ganglion, the intermediate nerve and genicular ganglion; myofascial pain syndrome; third molar disodontiasis; incongruous prostheses; salivary gland disorders.Neck pain: degenerative disc pathology, chronic laryngo-pharyngeal reflux, compensatory postural positions such as forward neck posture, and poor ergonomics.Pathologies of the ear, nose and throat: chronic tonsillitis, tonsillar stones, spasms of the constrictor muscles of the pharynx, otitis, mastoiditis, fracture of the hyoid bone, bursitis of the pterygoid hook.Other pathologies: psychosomatic disorders, foreign bodies, inflammatory and neoplastic processes in the oropharyngeal area, pharyngeal and tongue base tumors, cervical arthritis, temporal arteritis, cellulite and nuchal fibrosis, head and tongue syndrome, granular cell tumors.It also happens that patients with the symptoms mentioned above who have been diagnosed with Eagle syndrome typically have already visited several specialists to try to solve their problems, but without obtaining relief. In the past years, patients affected by Eagle syndrome were not given a specific diagnosis, and the only treatment was pharmacological with analgesics.Nowadays, however, new 3D diagnostic technologies such as CBCT allow us to precisely visualize and analyze the involved anatomical structures. It is possible, for example, visualize and measure the elongated styloid process or the calcified stylohyoid ligament. It is thanks to advances in the field of radiodiagnostics that there is a greater understanding of pathological conditions such as Eagle’s syndrome that has always been difficult to delineate.What we want to underline is the importance of differential diagnosis with the above-mentioned diseases and conditions, especially when the symptoms perceived by the patient cannot be attributed to a known cause. It is important, for this reason, that clinicians and dentists consider this syndrome as a possibility when assessing a patient with cervical-facial or cervical-pharyngeal pain .In this systematic review of the literature, we have collected data on the correlation of Eagle’s syndrome, in both its forms, with traumatic events and extractive dental events and we have focused on the methods used to formulate the diagnosis and the subsequent chosen treatment.What we try to explain through the analysis of the articles is the pathogenetic mechanism by which, following a traumatic event, the styloid process can begin its remodeling giving rise to painful symptoms or how, following a blunt blow or an accidental fall, the styloid process already longer than normal (>30 mm) can fracture and trigger the symptoms.(1)The traumatic fracture of the styloid process causes the proliferation of granulation tissue, which can compress adjacent structures and give rise to typical signs and symptoms.(2)The fractured portion can directly irritate or compress the adjacent noble structures and pharyngeal mucosa.After the analysis of the X-rays, it is possible to identify a first differentiating element, i.e., the presence of a fracture at the level of the styloid process or ossified styloid ligament. In the articles examined there are seven cases (5.2), ,14,15,17(1)Theory of reactive hyperplasia: If the styloid process is properly stimulated by the pharyngeal trauma, ossification can continue from its end towards the stylohyoid ligament. This can occur in the post-trauma healing period and it mainly gives rise to symptoms related to carotid artery impingement.Theory of reactive metaplasia: the traumatic event in this case triggers several metaplastic variations at the level of the stylohyoid ligament that lead to its partial ossification. The eventuality of metaplasia can be attributed to the presence of bone centers, such as bone cells, osteoblasts and osteocytes, between the fibrous formations. In this case the symptoms would originate from the region of the stylohyoid ligament and would affect the soft tissues of the neck giving rise, for example, to dysphagia.In cases in which the styloid process is initially normoconforming, the traumatic event may trigger two mechanisms that determine the lengthening of the styloid process and the ossification of the stylohyoid ligament:(2)In other cases we can, instead, talk about a Theory of anatomical variability: bone and ligament are qualitatively normal and what varies is the lengthening of the styloid process. This theory explains why it is possible to find early radiographic evidence of this type of ossification in children and young adults who have not suffered any prior cervical-pharyngeal trauma. The fact that these anatomical structures are not normal is a risk factor, as traumatic events may trigger the typical symptoms of Eagle syndrome.In the remaining articles considered for this review there was no evident fracture and two distinct scenarios open up, united by trauma, the triggering event. In this case, it is not the fractured portion that causes the symptoms, but the trauma itself that triggers the pathophysiological mechanisms leading to the lengthening of the styloid process or the calcification of the stylohyoid ligament and therefore the typical symptoms. In young patients, on the other hand, these anatomical structures can lengthen without a triggering factor, but they may become additional risk factors in case of traumatic events, thus requiring a differential diagnosis. Therefore we refer back to the hypotheses developed by Steinmann already mentioned in the Introduction:From the systematic review of the literature and the analysis of the described patterns, it is evident that the traumatic event plays a primary role in the pathogenesis of Eagle’s syndrome. The typical symptoms of the syndrome, in fact, can arise following the fracture of already elongated styloid processes or trigger mechanisms that lead to the lengthening or anomalous calcification of the anatomical areas in question that will compress and irritate the surrounding noble structures.In the specific case of extractive dental trauma there is still little documentation to support the hypothesis that would link them to the onset of Eagle syndrome. There is, in fact, little data available and in one of the two articles reviewed there was no follow-up.Certainly, the correlation between traumatic events and Eagle syndrome analyzed in our work must lead to consider the elongated styloid process or calcified stylohyoid ligament as risk factors for the onset of this syndrome following an event such as a car accident or prolonged dental treatments.As this syndrome is often asymptomatic, when such symptoms occur after trauma, the differential diagnosis should include Eagle syndrome in predisposed patients with the above-mentioned anatomical variations.From the moment the diagnosis of Eagle syndrome is confirmed, the problem should be resolved surgically. However, those who should surgically treat these patients, namely otorhinolaryngologists and maxillo-facial surgeons, are reluctant to do so because there is no specific protocol at this time. Hence, the need for a more precise protocol in the future that takes advantage of the multidisciplinary approach and progress in terms of diagnosis.-majority of case reports compared to systematic reviews or meta-analyses.-few works in which the syndrome was correlated with traumatic events.-articles correlating Eagle’s syndrome with tonsillectomy .A further approach, while waiting for specific surgical guidelines, is that of prevention: using CBCT or panoramic radiographs to identify at-risk patients and to make them aware that trauma could lead to symptoms of Eagle syndrome. Similarly, if these patients are subjected to trauma, it will be less complex to diagnose Eagle’s syndrome and attempt a surgical approach. Further studies could explore this aspect. Our work was, in fact, limited by certain aspects:It is clear that the literature on Eagle syndrome has not focused on traumatic events so our aim is to offer insights for further studies.The last aspect we want to focus on is extractive dental events. There is still little literature about it and we think dentists ought to focus on routine examination such as panoramic radiograph to intercept risk factors for Eagle syndrome. From a forensic point of view, awareness of the risk factors for Eagle syndrome following extractive trauma should be added to the informed consent after prolonged dental sessions or in case of oral surgery.This systematic review of the literature makes it clear that Eagle syndrome is a pathology that gives rise to non-specific symptoms that can be traced back to multiple clinical case scenarios and must therefore necessarily be studied and managed by different specialists.In particular, the dentist can assess the presence of altered anatomical structures such as the elongated styloid process and the calcified styloioid ligament by means of panoramic radiograph or computed tomography scans of the head and neck.Anamnesis can also help physicians in the differential diagnosis as past trauma may have caused the fracture of the elongated styloid process and the calcified stylohyoid ligament. At the same time the impact can, instead of fracturing a portion, irritate the adjacent soft structures or the pharyngeal mucosa and cause the classic or stylo-carotid syndrome.The articles found in the literature confirm the strong correlation between traumatic events and the onset of the typical symptoms of Eagle syndrome. As far as the correlation with extractive dental events is concerned, however, there is not enough literature to support a thesis linking this type of dental practice to Eagle syndrome.Further studies are therefore needed to better explore the correlation between Eagle syndrome and traumatic or dental extractive events and to make clinicians aware of this pathological condition and its implications on patients’ everyday life.


The prevalence of food allergies (FA) is increasing worldwide. Generally, the onset of allergies, including FA, begins in early childhood and may persist and/or develop through the life-course. Even though epidemiological studies have focused mainly on children, allergies can also occur for the first-time during adulthood. Within the prolongation of life, it is expected that allergies will be encountered more often even in older people. Recent findings suggest that an early exposure to diverse food antigens may promote the development of immune tolerance. Accordingly, diet diversity during the first year of life or even earlier may have a positive impact on the prevention of allergies. The anti-inflammatory properties of some dietary nutrients may positively contribute to a tolerogenic immune environment too. Diet diversity is associated with a more favorable microbiome, and increasing evidence suggests a promising role of gut microbiota manipulation in inducing immune tolerance. Unjustified avoidance of allergenic foods may expose to intakes of some nutrients below recommended levels through the life-course, even more in cases of self-diagnosis and treatment of presumed forms of food intolerance. Nutritional strategies including the early exposure to a variety of food antigens are a promising area of research for preventive purposes through the life-course possibly extending positive outcomes to older stages. The aim of this paper is to highlight the role of diet diversity in preventing the development of FA starting in early life, as well as to provide an overview of the main strategies to prevent related nutritional issues throughout the life-course. Over the last decades, the presence of allergies such as food allergies (FA), asthma, atopic dermatitis (AD) and eczema has become a prevalent issue for healthcare systems, especially in Western countries , 2. Metaa priori hereditary predisposition of developing allergic reactions, as for the case of children with atopic dermatitis (AD). Indeed, the European Academy of Allergy and Clinical Immunology (EAACI) specifically recommends the “introduction of complementary foods after the age of 4 months for all children irrespective of atopic heredity”  which can occur as early as during the first year of life. Historically, this has led to the hypothesis that the exposition of potentially highly allergenic foods, such as hen's egg, peanuts and cow's milk should be avoided until the end of the first year of life. The basis of such recommendation was the belief that a certain degree of mucosal immunologic immaturity, present in infants, could negatively influence the challenge of the local immune cells with food antigens, ultimately resulting in increase of food allergen sensitization . Howevereredity” . The efferedity” . The inveredity” .An interesting insight on the potential mechanism underlying early development of FA or, on opposite, food tolerance has been provided by the recent “Dual allergen exposure hypothesis,” which proposes that the immune system response to food allergens may differ depending on the allergens first site of exposure during the first year of life  . The hypBesides conditions genetically predisposing to allergies (as for the case of children with AD) the rise of FA in recent years has also been linked to environmental factors, which may affect food tolerance. Specifically, unhealthy lifestyles and diet may negatively influence the intestinal microbiome and immune responses, as well as lead to nutritional imbalances concerning vitamins, antioxidants, fibers and fatty acids dietary intakes . The resde novo sensitization in older people  . TherefoThe term “diet diversity” comprises two possible definitions (1) the variety of food being eaten or, (2) the number of different foods or groups of foods eaten over a reference period of time. Over the last decades, it has been observed that there is a positive association between diet diversity and numerous health outcomes. Most recently the same positive association has been investigated even between diet diversity and the occurrence of allergic diseases, including FA . The conIn the last decades, the rise in allergic diseases, including FA, is becoming a prevalent issue for healthcare systems. Contrary to what is believed, FA are not only an issue mainly related to pediatric ages, as they can also persist or even occur for the first time in adult life. Although the mechanisms involved may differ at the two extremes of life, FA may be more difficult to identify in older people who are characterized by a high clinical complexity with multiple chronic comorbidities and mutually interactive syndromes. Indeed, FA in older life may be observed as a corollary of the aging process which is characterized by mechanisms like as inflamm-aging, immunosenescence and gut microbiota alterations. Diet diversity is emerging as a new strategy to prevent the occurrence of FA in early life with potential implications in later stages of the life too. Additionally, gut microbiota manipulation represents a promising approach in preventing and managing FA despite further evidence is needed.DA and GS equally contributed to conceptualizing and writing the manuscript. CA and MC edited and revised the manuscript. All authors approved the final version of the manuscript.This study was supported by a contribution from the Italian Ministry of Health (Istituto di Ricovero e Cura a Carattere Scientifico- IRCCS grant).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. The handling Editor declared a past co-authorship with one of the authors CA.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.