As the science of the microbiome advances, social epidemiologists can contribute to understanding how the broader social environment shapes the microbiome over the life course. This review summarizes current research and describes potential mechanisms of the social epidemiology of the microbiome.Most existing literature linking the social environment and the microbiome comes from animal models, focused on the impact of social interactions and psychosocial stress. Suggestive evidence of the importance of early life exposures, health behaviors, and the built environment also point to the importance of the social environment for the microbiome in humans.Social epidemiology as a field is well poised to contribute expertise in theory and measurement of the broader social environment to this new area, and to consider both the upstream and downstream mechanisms by which this environment gets “under the skin” and “into the gut.” As population-level microbiome data becomes increasingly available, we encourage investigation of the multi-level determinants of the microbiome and how the microbiome may link the social environment and health. Social and biological processes interact across the life course to produce health outcomes, including persistent health inequalities by socioeconomic status (SES) . Even whWe underscore the need for robust inquiry into the social epidemiology of the microbiome in the early days of this new scientific area. The mechanisms through which social and demographic factors shape the microbiome over the life course are not well understood, but their importance has been highlighted by recent findings that genetic factors explain little variation in the gut microbiome, leaving “environmental” factors as the predominant determinant •. But whB. longum, while formula-fed infants have elevated levels of the more negatively connotated C. difficile [Birth and early post-partum life are critical periods for microbiome acquisition and development, and periods strongly influenced by one’s social environment. Whether organisms pass into the fetus from the placenta is still an open question, though the most thorough study to date is consistent with placental sterility . Babies ifficile , 21. Theifficile . Using aifficile ••. In thifficile . Breastfifficile . Thus, dA significant body of research implicates the physiologic response to chronic and repeated stressful life events in health inequalities  and one fecal-associated taxa (Roseburia) were relatively more abundant in homes with fewer women, possibly driven by differences in body size and hygiene practices. Lactobacillus, associated with lower risk of allergies and asthma, was more abundant in homes with women. Miletto et al. investigated airborne bacteria in 29 homes in the San Francisco Bay Area, finding that community composition was associated with the number of residents and pets, activity levels, frequency of cooking and vacuum cleaning, ventilation, and abundance and type of vegetation surrounding the building [Beyond the impact of humans on the microbiome of the built environment, differences in geography, ventilation, building design, and even prior flood damage can impact the types of bacteria and fungi found within homes . Barberabuilding . It is pbuilding .Modern environments characterized by increasing urbanization and less exposure to green space have been implicated in changes in exposure to microbes that may be altering human microbiomes over time, as well as contributing to differentials in access to green space by socioeconomic status . Ruiz-CaOverall, studies of built environment and the microbiome consistently find that indoor spaces often harbor unique microbial communities whose source is dominated by humans and pets. Building occupants and surfaces affect each other in both directions, and building design and operation can influence indoor microbial communities •. LittleDifferences in health behaviors such as diet, smoking, and medication use may play an important role in mediating associations between social factors and the microbiome , 74. SucDiet is believed to be a strong determinant of gut microbiome composition and diversity, capable of altering the microbiome both rapidly  and in tThere are strong educational gradients in cigarette smoking that have grown more pronounced over time . NumerouThe relationship between alcohol and SES is complex, such that low SES individuals  and indimore likely than other race/ethnicities to receive antibiotics for a viral infection [Social variation in medication use and how this may impact the microbiome is not yet well characterized. Studies from the USA suggest that non-Hispanic white children are nfection  and thatnfection . Opioidsnfection . Antibionfection ). A studnfection . Numerounfection . Althougnfection , 103.Overall, there is growing evidence that many of the health behaviors already known to be associated with social factors, especially smoking and nutrition, likely have important impacts on the microbiome. Nonetheless, there may be influences on the microbiome such as alcohol consumption and prescription drug use that operate in ways counter to traditional social gradients, with those in more advantaged groups being exposed to more negative impacts on the microbiome. It will therefore be important to understand how the interaction of multiple exposures both influence the microbiome and are shaped by social factors across the life course.Bacteroides and a lower abundance of Prevotella [The evidence presented suggests that markers of socioeconomic status, reflecting access to resources that shape exposures to the physical, social, and psychosocial environments, is likely associated with differences in the composition of the microbiome over the life course. Thus far, two studies have examined sociodemographic factors and the oral microbiome. Belstrom et al. found significant differences in the bacterial profiles of the oral microbiome by area-level socioeconomic status in the Danish Health Examination Survey (DANHES) . Notablyevotella . OverallC. difficile and may have contributed to the upsurge in C. diff hospital infections [. As population-level microbiome data becomes increasingly available, we encourage future investigation of the multi-level determinants of the microbiome and how the microbiome may link the social environment and health.While work establishing the importance of the microbiome for human health continues apace, thus far, research on how the social environment shapes the microbiome, especially in humans, is limited. Social epidemiology as a field is well poised to contribute expertise in theory and measurement of the broader social environment to this new area, and to consider both the upstream and downstream mechanisms by which this environment gets “under the skin,” “into the gut,” and onto every other body site. Social epidemiology can also bring a much needed population perspective  to the sfections . As popu


In order to identify the effects and divergences of the different landscape perception approaches on landscape preference, this study investigated people’s preferences for urban green spaces with different vegetation structures in the early spring through using three approaches, which were on-site survey, photo elicitation and VR technology. The results showed that: (a) There were significant differences among the three approaches for landscape preference, among which there was a significant difference between VR technology and the other two approaches, while no differences between on-site survey and photo elicitation were found. (b) The respondents showed significant differences in their preferences for the urban green spaces with the different vegetation structures through VR technology, and the semi-open green space received the highest preference score. (c) Whatever the approach employed, there were no significant differences in gender and professional background groups for landscape preference. (d) In the comparisons of the three different approaches, the respondents were more willing to choose physical recreational activities to be conducted in the early spring. Based on the above results, the three approaches of landscape perception were divergent and irreplaceable. It is, thus, suggested that the approach of landscape perception should be carefully selected for a specific landscape in a certain season, so as to provide a scientific basis for the evaluation of landscape perception and preference in the future. With the increase of urban population and the acceleration of urbanization, the urban landscape has changed rapidly. People’s perceptions of and preferences for landscape have correspondingly changed as well, which has inspired a greater number of scholars to conduct the study of landscape assessment from the public perspective . HoweverPrevious studies on landscape preference generally emphasized the public perception of and preference for the landscape from the visual perceived sensory dimension. However, the approaches of visual landscape presentation have emerged endlessly to be applied to preference studies with different types of landscape; these approaches include on-site survey, photo elicitation, videos and virtual reality (VR) technology .Since an on-site survey cannot only fully reflect site information and provide participants with the most authentic site experiences, but does maximize the simulation of their touring process, traditional preference studies are usually combined with questionnaires ,5, interFor that reason and with the development of photo image technology, more and more researchers have used photo elicitation as the visual landscape presentation mode due to its strong manipulability, modifiability and easy accessibility. Participants can perceive different landscapes by means of photos, slides or websites, and finally, complete preference examinations by interviews ,11,12, qVR technology is an advanced technology combining a high degree of control and ecological validity, which can simulate experimental conditions that are reasonably similar to those in a real-world setting . At presAlthough there are diversified approaches employed in the studies of landscape perception and preference, several questions arise, such as: Are the approaches being applied the same? Are they replaceable for collecting the information that regards perception and preference?For photo elicitation and on-site surveys, some studies have shown that photos can reflect the real landscape well ,30,31, wSimilarly, the relationship between VR technology and on-site survey has not yet been settled. Some studies have demonstrated that the immersive experience of VR technology is good and can be used as a substitute approach for physically experiencing the real scene . Some stDo the three approaches  have different effects on perceptions and preferences?How do peoples’ preferences vary for different green spaces with different vegetation structures?How do peoples’ preferences vary for activities in different spaces through different perceptual approaches?Due to the complexity of the term landscape, it is necessary to define a clear meaning for the landscapes that were studied in this study. A landscape mentioned in this paper refers to common, urban green spaces of small scale, and based on plants and perceptions and preferences, were examined correspondingly. In previous studies, not only the validity of perception approaches remained to be determined, but the comparison of perceptions of and preferences for different types of urban green spaces was lacking. Moreover, vegetation types (grass and trees) could differently affect perceptions and preferences, which could further influence people’s physiological and psychological well-being . Hence, Three types of urban green spaces were selected based on their similar size and the horizontal structure of vegetation according to the canopy cover ratio of trees and shrubs; the ratios were: open green space with less than 10% canopy of trees and shrubs, semi-open green space with a 30–70% canopy of trees and shrubs, and closed green space with more than 70% canopy of trees and shrubs .This study was conducted around the spring equinox of the Chinese traditional solar terms in March 2019. First, two-dimensional color photos were taken by a digital camera  . In ordeA total of 180 college students studying various subjects were recruited as the participants in this study and were divided into a professional group who studied the subject of landscape architecture and a non-professional group which included students who studied other subjects. The ratio of males to females was 1:1.5 and the ratio of professionals to non-professionals was 3:7. The participants were randomly divided into 9 groups with 20 people in each group, and every participant in a group was asked to use one approach to experience one type of urban green space .In this study, a questionnaire survey was used to identify the participants’ perceptions of and preferences for the selected urban green spaces. The questionnaire consisted of three parts, including basic personal information (gender and profession), preferences and potential engagement in recreational activities. Preference was measured using a five-point Likert scale with the score of 1 to 5 representing “strongly dislike to strongly like”. In order to identify what kind of recreational activity people enjoyed through three perceptual approaches, recreational activities were divided into three categories: physical , social  and mental . Before the beginning of the experiment, participants were provided an explanation of the purpose and the experimental process of this study.Three randomly chosen groups were each taken to one of the three different urban green spaces respectively for perceptions a. In ordThe off-site surveys were conducted in quiet and well-lit classrooms and conference rooms respectively. Another set of three groups perceived the three different urban green spaces through a slide projection b. Each pt-test, were then analyzed to compare the different levels of preference among the three approaches and three green spaces respectively. To determine the significant differences among three approaches emerged in which spaces, the posterior comparisons of different approaches by Duncan’s t-test in each green space, were also conducted. To identify the possible reasons and the detailed aspects of respondents’ preferences, the willingness to visit and potential recreational activities were analyzed by descriptive statistics. All statistical analyses were performed using SAS  software. Qualitative analysis was finally conducted to identify the similarities and divergences of the three approaches on preference for the selected green spaces based on the comments of the participants.Participants in different gender and professional background groups were not evenly distributed between the sites, and accordingly a generalized linear model (GLM) was applied to the whole sample to identify the effects of most decisive factors  on preference. To identify the particular differences among different approaches and different green spaces, the post-hoc tests using Duncan’s p < 0.05), while gender and professional background had no influence  of VR technology application . TherefoThe posterior comparisons among the different approaches in each type of green space showed that VR had the highest preference scores among all the types of the selected green spaces . ParticiFurther analysis of the comments of the semi-open green space showed that nearly half of the participants perceived the tranquility by using VR devices, while noise was experienced by more than a quarter of the participants on the site. Since the selected site was a park where inhabitants often get together to play instruments, sing and chat, the noisier environment could be the reason for the perceptive differences between on-site and off-site approaches.To compare the preferences for different urban green spaces with different structures, the post-hoc test was conducted and the results shown in The attributes of the semi-open environment that attracted participants may concern two aspects: the moderate degree of openness, which means both a certain extent of openness and a certain degree of shade, and the moderate vegetation density along with plant diversity. The former factor may be explained by the prospect-refuge theory, which showed that the ability to see without being seen was important to meet early man’s survival needs , and theAmong the 179 questionnaires, 121 participants were willing to engage in a variety of activities in early spring. The highest frequency of the activities was reported for walking (45.5%), which was followed by picnicking (9.9%) and chatting (9.9%).The results showed that physical activities were the most popular categories that participants were willing to engage in, followed by social activities, while mental activities were the least popular . By realParticipants in the VR technology group were more likely than those in other groups to engage in physical activities . QuietneParticipants in the photo elicitation group preferred social activities in open green space, while they preferred physical activities in semi-open and closed green spaces . Green sParticipants in the on-site survey group preferred physical activities in semi-open green space, while the number of social activities chosen was nearly as large as the number of physical activities in open and closed green spaces . In openThis study was the first to explore the divergences of preferences for different urban green spaces using three approaches and aimed to provide a basis of knowledge for the evaluation of landscape perception and preference. There were some noteworthy conclusions. First, VR technology significantly differed from the other two approaches, especially for the semi-open green space, while no difference between on-site survey and photo elicitation was found. Second, there was a significant difference between preferences for green spaces with different vegetation structure in early spring. Semi-open green space received the highest preference scores. That was followed by closed green space, and open green space was rated the lowest. Finally, physical activities were the most popular activity categories that participants were willing to engage in during the early spring. Based on these results, it is suggested that appropriate approaches should be selected according to the sites’ actual environments, especially for VR technology, which would be cautiously utilized for sites with strong heterogeneity, complex elements and diverse spatial structures of vegetation.However, some weaknesses in this study exist. First, VR technology was only used to provide visual scenes during this study. Since landscape perception is a multi-sensory process, further research could utilize multiple VR devices (a VR helmet and VR headset) to better present the scenery in all sensory dimensions. Second, all participants were college students, so the results might not reflect other social groups. Other varieties of samples should be further examined. Third, the spaces selected in this study were common for the participants. In order to fully explore the divergences in age and professional groups, other types of landscapes, such as natural or semi-natural sites far away from urban areas should be taken into account. Finally, since this study was only conducted in early spring, the participants’ preferences may have been greatly affected by the erratic weather and seasonal plant aspects, especially through on-site survey approach. Further research could be conducted in multiple seasons for comparison.


Background: Cycling is a popular source of recreation and physical activity for children and adults. With regard to the total number of sports injuries, cycling has the highest absolute number of injuries per year in the United States population. Cycling injuries can be classified into bicycle contact, traumatic, or overuse injuries. Aim of this study: The aims of this case report are to report a rare clinical complication of glenohumeral joint anterior dislocation that resulted in a patient experiencing continuous GHJ dislocations secondary to involuntary violent muscular spasms and emphasize the role of the physical therapist’s differential diagnosis and clinical decision-making process in a patient following direct access referral. Case presentation: A professional 23-year-old cyclist presented to a physical therapist with spontaneous multidirectional dislocations to the right shoulder after the recurrence of trauma occurred during a recent cycling race. The dislocations do not occur at night, but occur during the day, randomly, and mostly associated with changes in the patient’s psychological conditions. Directly from the clinical history, the physical therapist identified a neuro-physiological orange flag as well as an orthopedic red flag and, therefore, decided it was appropriate to refer the patient to a neurologist. It was determined by the physical therapist to be a priority to focus on the patient’s neurologic status and then to evaluate the orthopedic problem. The neurological examination revealed a condition of spontaneous multidirectional dislocation associated with recurrent antero-posterior pain spasms of the shoulder joint. The neurologist prescribed medication. Following the second cycle of medication assumption, the patient was able to continue physiotherapy treatment and was referred to the orthopedic specialist to proceed with shoulder stabilization surgery. Discussion and conclusion: Currently, the diagnosis of this unusual clinical condition is still unclear. It is a shared opinion of the authors that the trauma during the past bicycle race awakened an underlying psychological problem of the patient that resulted in a clinical condition of weakness of all the structures of the shoulder, such that these spasms could result in multiple multidirectional dislocations.  Cycling is a popular source of recreation, transportation, and physical activity for children and adults . There aAnterior traumatic shoulder dislocation is a common musculoskeletal condition that physical therapists (PT) and orthopedic surgeons see in practice . This joA number of shoulder girdle injuries in sport are associated with acute anterior GHJ dislocations: Neurological diseases following reduction and either a rotator cuff tear or a greater tuberosity fracture. In terms of prevalence, traumatic anterior shoulder dislocation is common as well as brachial plexus injury  and axilSpecific studies investigating the costs of managing an injury to competitive cyclists have not been conducted even though bicycling is an important mode of transportation in urban environments. For example, San Francisco has seen a 58% increase in the number of observed cyclists in 2009 alone . Of all Differently, in Florida, an estimated 1.7 million youth have Medicaid insurance: The cost of sports injuries in youth was represented by $24 million for inpatient care and $87 million for emergency department care. Youth averaged $6039 for an inpatient visit and $439 for an emergency department visit in costs secondary to injuries from sports. Baseball, basketball, bike riding, American football, roller-skating/skateboarding, and soccer are sports with high costs for both emergency department patients and inpatients. Injuries from non-contact sport participants are few but can have high costs . The aims of this case report are to report a rare clinical complication of GHJ anterior dislocation that resulted in the patient experiencing continuous GHJ dislocations secondary to involuntary violent muscular spasms and emphasize the role of the PT’s differential diagnosis and clinical decision-making process in a patient following direct access referral. To the authors’ knowledge, this is the first case report to describe this presentation.The patient was a 23-year-old Italian male, professional cyclist, non-smoker, 190 cm tall and 82 kg, with a daily training load ranging from three to six hours, six days a week for an upcoming competition. The patient presented with no prior medical record but spontaneous and multidirectional multiple posterior dislocations of the right shoulder. In association with this complaint, the patient stated that he had widespread pain of the GHJ and paresthesias of the entire right hand, but predominantly on the palmar side of the fourth and fifth finger. Moreover, he complained about diffuse spasms (clonic manifestations) occurring around the shoulder, primarily of the pectoralis major and the biceps brachii muscles . After a fall during a cycling race, the athlete went to a medical clinic in March 2017 and was diagnosed with subsequent dislocations of the right shoulder. The fall occurred following contact with a teammate during an international championship while riding on a paved road. The patient was not able to describe the exact traumatic mechanism but remembers his attempt to place his hands toward the ground to avoid the collision. The diagnostic investigation at the time, a magnetic resonance image (MRI), signaled the presence of “intra-articular effusion with non-homogeneity of the antero-inferior portion of the glenoid rim, bone marrow edema on the anterior surface of the humeral head, and an extensive lesion of the subscapularis tendon” . The anaIn June 2018, he returned to the clinic, complaining of a worsening of his clinical presentation and symptoms, characterized by an increase in spasmodic muscles surrounding his right shoulder, resulting in spontaneous multidirectional dislocations. The patient stated that these muscle spasms were associated with constant pain that worsened after the event and caused significant instability, weakness, and temporary tingling of the entire hand that was predominately located in the fourth and fifth finger. The spasms did not occur at night during sleep but appeared randomly and without warning throughout the day without apparent cause according to the patient. The patient also noted that the spasms were influenced by the patient’s mental state (with a reported increase of episodes and worsening following family disputes).By analyzing the patient’s clinical history, family history, and the assessment scales, the PT identified various red and orange flags  during tThe PT had no opportunity to perform any clinical tests as the patient’s passive and active movements immediately set off multidirectional joint dislocations and any type of stimulation increased the spontaneous muscle spasms. Three assessment scales were used by the PT to frame pain presentation (NPRS), disability/psychosocial factors (DASH) , and insThe patient’s NPRS was 8/10. The DASH score was used to evaluate the disability/psychosocial factors: This scale evaluates the patient’s ability to perform a range of daily, work-related, and sports/recreational activities. The DASH reported a 74.6% disability for daily life activities (ADL) and a 100% disability for work/recreational activities. The WOSI was used to evaluate the pathology-specific life quality for the patient with shoulder instability and the patient performed at 5.43%.The PT referred the patient to the orthopedic specialist who recommended medical and diagnostic tests in addition to the X-rays (performed in the emergency room during one of the spasm episodes with dislocation), including another MRI and a computed tomography scan (CT scan). The MRI exam revealed several abnormal findings including an abnormal ACJ, lesion of the pre-insertional bands of the supraspinatus, fluid distension of the subacromial bursa (Sab) with glenoid diastasis, and a slight capsulo-ligamentous thickening on the anterior side. The CT scan and X-ray did not reveal any clinically relevant findings. The orthopedic examinations reported a diagnosis of multidirectional instability and the specialist recommended physical therapy focused on global muscle strengthening prior to surgery. The orthopedic surgeon did not report on the spasmodic related episodes. In consideration of the patient’s clinical presentation and his inability to tolerate any type of physiotherapy treatment, the PT considered it appropriate to further evaluate the associated “spasm” aspect. Therefore, the patient was referred to a neurologist in order to have a complete picture of the condition and to be able to follow the best management approach. The clinical consultation with the neurologist was performed in July 2018 and he noted a condition of multidirectional spontaneous dislocations associated with recurrent antero-posterior painful spasms of the shoulder joint. He advised reinforced physiotherapy in order to maximize the mechanisms of restraining the elusive humeral head as a function for future surgical procedure. The neurologist prescribed Gabapentin two times a day and Thiocolchicoside (TCC) and Alprazolam medications to eliminate episodes of spontaneous spasms. The effects of the medications started to act from the third day of recruitment, both in terms of a reduction of the number of attacks (one attack during the day) and in terms of intensity (less violent spasms and no back block) and duration (a few seconds). After one week of medications, the patient reported a cessation of spontaneous spasms.From that moment, the PT started a rehabilitation program addressing the overall joint reinforcement, progressing from isometric exercises  to graded exposure to increase the intensity of the exercises . The overall program was focused on pain-free exercises and avoidance of dislocations. On August 9th, the patient discontinued the medications and reported only one episode of spasm, which was associated with a family argument with his girlfriend. The spasm episode was described to be of short duration and low intensity. During the physiotherapy sessions, brief spasmodic episodes occurred when the patient was stimulated with ischemic compression techniques, both on the shoulder and at a distance , and also when the PT light touched with the fingertips in sham mode along various parts of the body .On August 20th, 11 days after not taking medications, the spasms re-appeared without any apparent cause (no declared stressful events) with consequent multidirectional multiple painful dislocations with posterior block, that forced the patient to hospitalization. Upon reporting to the hospital, the physicians needed to administer Ketorolac and Apomorphine to reduce the posterior dislocation. Following this second event, the PT was contacted by the patient’s sister and informed that in the patient’s family medical history there was a condition of psychological disorders characterized by temper tantrums associated with temporary loss of consciousness and bipolar disorder. Therefore, the PT contacted the neurologist by telephone, informing him of this new health status information; moreover, the therapist was unable to continue rehabilitation secondary to the frequency, duration, intensity, and general worsening of the spasms. At this point, the physician prescribed 15 days of Gabapentin (twice a day) and then another 15 days once a day (in the evening) to reduce the wash-out effect. This time the pharmacological intake delayed its effects with respect to the first cycle, so that the PT resumed the rehabilitative work as soon as the spasms ceased, on August 29th. The PT noted that the spasms recurred occasionally during changes in mood and were linked to family arguments. On September 6th, the patient reduced the pharmacological treatment of Gabapentin to once a day; four days after the planned pharmacological decrease and, as noted by the patient, during a daily life problem, spasms of high intensity, frequency, and duration recurred and this time was associated with a temporary loss of consciousness. Secondary to these patient complaints, the PT consulted the neurologist, who advised the continuation of full-dose drug therapy (two times a day) and advised for a surgical stabilization procedure . On the The neurologist identified the problem as recurrent antero-posterior spasms that resulted in associated spontaneous multidirectional dislocations and recommended the continuation of physiotherapy associated with drug therapy  to break down the clonus. The neurologist did not provide a precise diagnosis: Using the term “spasm”, he only recognized an objective clinical sign observable during the evaluation. Unfortunately, after 18 days of medications and the subsequent wash-out effect (occurred 11 days later), the spasms recurred, increased in intensity and frequency, secondary to family arguments. The neurologist then prescribed another 15 days of medical therapy with Gabapentin 100 mg and TCC 8 mg twice a day followed by 15 more days of medications once a day to contain the wash-out effect; unluckily even during this second cycle of drug assumption the spasmodic phenomenon recurred at the time of the reduction of pharmacological therapy . These last events led the neurologist to return to a twice a day intake and to plan joint stabilization surgery as soon as possible.The patient had surgery on 25 October 2018 with posterior arthroscopic capsuloplasty. On the advice of the orthopedic specialist, the patient was immobilized with a brace for 30 days and continued the pharmacological treatment with the same dosage, in order to monitor the spasms . Starting from the 30th day of bracing, the patient began the rehabilitation program, as suggested. However, starting from cautious techniques of passive mobilization in abduction, on the scapular plane, the spasms immediately reappeared, predominantly on the pectoralis major, deltoid, and biceps brachii muscles, characterized by low intensity and duration, and frequency linked to the movement. Therefore, the PT instantly called the referring orthopedist, who advised the PT to interrupt rehabilitation in order to avoid these excessive contractions or clonus—as these uncontrolled spasms could harm the results of the surgical intervention. It was also recommended to the patient to keep in touch with the neurologist to update him on the evolution of the clinical conditions. After a telephone interview with the neurologist, the patient was then asked to add Gabapentin 100 mg in the middle of the day, cyclobenzaprine 10 mg . The patient immediately started the new drug dosage; unfortunately, after a few days, side effects appeared (it is still uncertain and unclear whether these effects were determined by the increase of Gabapentin assumption or the addition of cyclobenzaprine), characterized by insomnia, anger attacks, loss of sexual libido, and hair loss. These unwanted consequences, added to his relative’s discouragement, pushed the patient to independently suspend drug therapy on 4 January 2019. Physiotherapy was not interrupted based on the patient’s decision, instead. Physiotherapy then continued essentially with proper attention to the healing processes and in order not to elicit and/or accentuate spasms. Techniques of mobility and muscular strength were associated with manual therapy techniques ; therapeutic exercise was introduced to allow the patient to carry out the main activities of daily life. The rehabilitation program continued for about one month and a half with a frequency of two sessions a week. Due to the persistent presence of uncontrolled spasms that showed themselves with free-movements and/or with pain, the PT could not increase the load and intensity of the exercise therapy necessary to obtain functional improvements (mostly from the point of view of range of motion (ROM) and strength) . At thisThis case report was written following items of the CARE checklist . The disThese spasmodic phenomena influenced the whole rehabilitation process, resulting in some difficulties in the therapeutic approach and during the rehabilitation period. Each therapeutic proposal, passive or active, has been adapted in order to avoid not only structural problems related to shoulder dislocation, but also the onset of phenomena of the central nervous system (spasms). The PT tried to obtain the entire recovery process in a way to avoid treatment complications and to obtain an optimal level of compliance from the patient; the patient’s perception of global management meant that a PT/patient relationship was established immediately. Secondly, each phase of the rehabilitation process was based on literature reviews and solid expert opinions, as written in the latest studies by Cools et al.  and WarbMost recently, the evaluation of orange flags associated with psychiatric disorders  and yellow flags related to maladaptive pain coping strategies  have become fundamental in physical therapy practice. However, the prevalence of psychiatric disorders in patients with movement disorders has increased. In the profession of physical therapy, patients with psychiatric conditions, must be referred for medical interventions such as pharmacological and/or behavioral therapy to facilitate the patient’s rehabilitation process ,10,11. RThe diagnosis of this unusual clinical condition is still unclear. It is a shared opinion of the authors that the trauma of the bicycle race triggered an occult psychological condition that influenced the patient presentation and led to multiple multidirectional shoulder dislocations.The sports PT plays a fundamental role in both preventive and post-injury management for the elite athlete and works as an important part of a team of health care professionals to promote the well-being of the athlete to maximize sporting performance and prevent any type of injury. The PT may act as a manager to address ongoing situations as they arise, which reduces the timing (and therefore the relative costs both in economic terms and in terms of damage from the athlete’s absence in a competition) and the likelihood of a recurrence. In this case report, the authors highlight the PT’s role in a differential diagnosis. The patient in this case report should have been treated for free at the rehabilitation center of the sports club to which he belongs, but he decided to use personal insurance and pay the rehabilitation expenses for around EUR 3000 on his own.Previous literature on a patient like the one in this case report does not exist. Carroll et al. report a patient case of dystonia of the shoulder after trauma in the US military . This paThis paper emphasizes the role of the PT in direct access to identify those patients that are appropriate for referral to another health care provider. Authors have also tried to highlight how a structural problem of the GHJ may underlie an intrinsic psychological framework as a triggering cause, hence the importance of the specialized PT to identify the problem at the base and thus able to carry out a correct referral; moreover, it is important to underline how the teamwork between several health figures (PT–neurologist–orthopedist) allowed the patient to get back to an excellent life condition.


Smartphone-based sensing is becoming a convenient way to collect data in science, especially in environmental research. Recent studies that use smartphone sensing methods focus predominantly on single sensors that provide quantitative measurements. However, interdisciplinary projects call for study designs that connect both, quantitative and qualitative data gathered by smartphone sensors. Therefore, we present a novel open-source task automation solution and its evaluation in a personal exposure study with cyclists. We designed an automation script that advances the sensing process with regard to data collection, management and storage of acoustic noise, geolocation, light level, timestamp, and qualitative user perception. The benefits of this approach are highlighted based on data visualization and user handling evaluation. Even though the automation script is limited by the technical features of the smartphone and the quality of the sensor data, we conclude that task automation is a reliable and smart solution to integrate passive and active smartphone sensing methods that involve data processing and transfer. Such an application is a smart tool gathering data in population studies. Smartphones are nowadays well established and commonly used for private purposes . ThousanThus, smartphones have recently been equipped with smaller and technically advanced sensors to monitor motion, position, temperature, humidity, light, air pressure, noise, or heart rate. These parameters reveal novel possibilities of signal processing for research purposes.ecosystem services in geo- and citizen science ,6,7,human activity, health, and well-being in medicine and sports science ,10,11,12urban microclimate in meteorology ,14,air pollution and noise in geography ,16,17,mobility and human movements in transport planning ,19,20, asocial interaction and behavior in social science ,22,23.Today, there are already publications about smartphone sensing methods (SSMs) on topics ofBased on these publications SSMs can be differentiated in active and passive sensing tasks. Passive SSMs enable automated collection of smartphone generated data, for example, by the accelerometer, GPS data, and ambient noise levels. Active sensing tasks ask for an active user contribution such as taking a picture, tagging a place or entering text. The passive collection is more often used in quantitative and active collection in qualitative research.A special case is citizen-science research that builds on different research subjects with the aim of involving non-professional scientists or the general public in projects to generate collective knowledge through co-production ,24. In tThe aforementioned publications have in common that they use either passive or active SSMs or focus just on single sensor signals. There is a lack of knowledge about the integrated use of multiple smartphone sensor signals with a combination of active and passive SSMs in scientific research. As interdisciplinary research projects tend to work on applied studies were both quantitative and qualitative data are collected, we see substantial needs to advance SSMs for this purpose. Task automation for smartphones could be one valuable solution. Automation applications for smartphones can access all internal and external sensors, as well as audiovisual features to perform user specific tasks. To the best of our knowledge, automation applications for smartphones have not been used or applied in environmental research and participatory sensing to date. Environmental science is a research area where SSMs offer tremendous potential for mobile data collection and monitoring ,29. So fTherefore, our aim was to investigate whether smartphone software can be used to manage multiple sensor signals for the integration of passive and active sensing and to use this data for spatio-temporal context analysis. We designed a script for task automation that stores quantitative records of noise and light-level together with timestamp, geolocation, and a qualitative user feedback.The applicability has been validated through the visualization of measurements and a rating of the users’ handling experiences. We applied the smartphone application in a study about personal exposure of cyclists because they are exposed to several environmental stressors in daily life, like acoustic noise, air pollution, and heat ,32. AsseWe also discuss the application possibilities for environmental research in general and conclude with recommendations for studies that consider using task automation with passive and active SSMs.https://code.mendhak.com/gpslogger/). It was furthermore important to control for (a) outdoor application and (b) wearing compliance. We instructed the participants to use the smartphone being attached to the upper arm only outdoors while cycling. Light levels above a predefined threshold indicate whether the person was in an outdoor environment or not. Finally, an active sensing part was integrated in form of a short survey that appeared on the screen and asked for the user’s feedback. We asked for (a) the purpose of the trip , (b) type of route choice , (c) taken detours , and (d) rating of perceived exposure to noise on this route  that are available for the participatory sensing study with cyclists. As we were interested in the spatio-temporal context of the noise exposure, the location of the cyclists was of major importance. Therefore, we integrated geolocation via GPS coordinates and used the open source application “GPS Logger”  to design a script for the management of the sensor signals. Automate is a basic software that operates using flowcharts (“flows”) of tiles. Each tile will perform a single task and a group of tiles is named “fiber”. All of the fibers together form the flow (a script code) that ends up in the intended output . A basic principle to connect the tiles are logic operations . We used the Automate Version 1.7.1 that is available at the Android Google Play Store.We finally have chosen the open-source task application Except for acoustic noise, all of the sensors were internal features of the smartphone. The sound level was detected by an external microphone with foam windscreen (Edutige ETM-001), as we noticed that the internal microphone would be covered by the bracelet during application, thus causing errors.The final programmed application was evaluated in three ways: based on (1) the operability of the script and correct data output, (2) geographic visual proof of the data, and (3) the ease-of-use rating of cyclists that participated in the exposure study.The correct working script stored all merged sensor signal data of the recorded bike trip in a comma separated file (csv) on the local smartphone memory. Additionally, the file was automatically transferred to a database on a cloud server in near real time.The visual and geographical proof of the data output is of high relevance as data was needed for further spatio-temporal analysis in the exposure study project. It is of importance that the cycling tracks (GPS) are correctly represented and merged with the other sensor data.The ease-of-use rating of the application was performed after the exposure study. Therefore, 66 cyclists used the same study smartphone with the installed automation application for one week during daily cycling in the study period from June to September 2017. The study area was the City of Leipzig, Germany. All of the participants signed written informed consent. The study design was approved by the ethics committee of the Leipzig University (No. 191/17-ek).The smartphones had mobile internet connection to allow for direct data transfer to the cloud server. Before starting the bike trip the users had to press just a start-widget on the smartphone’s homescreen and to attach the device on the left arm. After finishing the bike trip, users simply pressed the stop-widget and answered the appearing questions related to the trip and exposure perception. The final ease-of-use evaluation of the device handling was done via an online survey that the users filled after their study participation. They rated the handling of the application (1 very easy–5 very complicated) and the wearing comfort of the smartphone (1 very high–5 very low).Automate was able to retrieve the desired sensor signals and store them in a predetermined interval (in our case 2 s) with a timestamp in a table. In addition, a text and scoring query was successfully integrated, which makes it possible to retrieve additional information from the user. We inquired about the purpose of the cycle route, possible detours, and the subjectively perceived exposure to noise.The developed script for Therefore, we designed two flowcharts with the software . One forWhen the users pressed the start-widget, the application recorded the current timestamp and the name of the smartphone, what was later used to name the target file. The device name is predefined by a separate text file, which is stored in the mobile phone memory. As soon as satellite signals are connected, the measurement loop starts. This will be reported to the user with a screen notification. At the same time, the target csv-file is created and all of the predefined sensor parameters are stored in intervals using the current timestamp.Arrived at his destination, the user stops the measurement pressing the stop-widget. Subsequently, the GPS application stops tracking and the screen immediately display queries about the purpose of the cycle route, possible detours, and subjective perceived exposure . The interval can be adjusted in the script.While testing the script output, we made some adjustments to improve the data format. For example, in a first version we had just one column for the GPS coordinates. The final version stores latitude and longitude in separate columns with the advantage of easier post processing for visualization with GI-software .As our final aim was the visualization of the data to reveal personal spatio-temporal exposure to environmental stressors (in this case acoustic noise), we imported the original spreadsheet into ArcGIS. The resulting map shows a segment of a study participant’s cycling track .The map on the left hand side shows the noise levels (29–90 dBA) that were registered at the locations (GPS). Here, we plotted the raw data without outlier removal to highlight the usefulness of the recorded light level data. The light sensor, which actually controls the brightness of the screen, can provide information about whether the device is indoors (<1000 lux) or outdoors (>1000 lux). In our study, we benefit from this data as exclusion criteria for indoor recordings, as we are just interested in the cyclists’ outdoor exposure. An exemplified timeframe in which the cyclist went into a building is represented by the white frame on the map , left. TDuring the pilot study with cyclists, we already got direct oral feedback that was generally positive when we picked up the smartphones. The application was used by each cyclist 12 times (12 routes) on average. 59 cyclists  filled the feedback questionnaire online afterwards. Therefore, the ease-of-use evaluation is based on about 708 user-application interactions.The results shown in Automate-script for smartphone task automation demonstrated that multiple sensor signals can be integrated with time and geolocation to collect data in a personal exposure study with cyclists. The resulting data can be used for further spatial analysis and contribute to an improved understanding of the spatio-temporal exposure to environmental stressors. The greatest advantage of our task automation is the integration of active sensing through the request of notifications that enable user feedback after tracking. Thereby, it is possible to compare this subjective data with the objective data from passive sensing in relation to the same timeframe. This is of special interest for studies were complex spatial problems are investigated that need to consider quantitative and qualitative aspects.The developed Automate offers over 300 different task commands to access, combine, store sensor signals, and applications in the smartphone. Furthermore, external sensors can be connected to the device via WLAN, Bluetooth, or NFC.With our script, we showed that task automation is a reliable SSM that has potential to integrate multiple sensor signals. Many combinations of sensor signals are possible and our example to use the light level has shown that the original purpose of the sensor can be utilized as another helpful indicator in a research project. The software Smartphones can be used in many research areas as an advanced tool for data management due to their penetration in society and ongoing evolving technology . This teBeside the relevance of our project to advance SSMs, we emphasize that it is always necessary to consider the accuracy of smartphone sensors. It was not the aim of this article to describe the accuracy of the recorded data, but several articles already confirmed the good sensor performance of smartphones in relation to GPS and noise . FurtherThe article highlighted the process of data collection and showcased a possible visualization scenario. For data storage we used a server database. We see further development needs in the integration of automated cleansing of the data within the database server to forward the data to a Web-GIS application for direct visualization. This possibility would allow for interactive visual user feedback either on a website or on the smartphone. This kind of data processing is already established in the context of different GPS-tracking applications where alternative routing is suggested to the user. The recording, analyzing, mapping, and visualization of multiple smartphone sensor data, including an active user interaction, still needs further experiments and is an emerging field of research .In this paper, we presented a script to automate smartphone task commands for application with sensors in the context of participatory personal exposure studies. The novelty of our script is the integration of active and passive SSMs by means of utilizing time, geolocation, noise level, light level, and a digital questionnaire. An evaluation of this application by cyclists revealed the reliable handling and ease-of-use. According to the trend that data should be available in near real-time, we used a wireless database server storage solution in our script. In future, the real-time data transfer might be integrated and run in parallel to the sensing process; this however depends on the quality and speed of the user’s mobile internet signal that can be poor in rural areas. When considering the limitations of the technology, automated task applications for smartphones are a promising way to advance empirical research involving real-world data collection, especially in the area of environmental science.


International migration of healthcare professionals has increased substantially in recent decades. In order to practice medicine in the recipient country, International Medical Graduates (IMG) are required to fulfil the requirements of their new countries medical registration authorities. The purpose of this project was to compare the final fellowship exit examination in Orthopaedic Surgery for the UK, Australia, Canada and South Africa.The curriculum of the Australian Orthopaedic Association (SET) was selected as a baseline reference. The competencies and technical modules specified in the training syllabus, as well as the specifics of the final fellowship examination as outlined in SET, were then compared between countries.Of the nine competencies outlined in SET, the curricula of the UK, South Africa and Canada were all compatible with the Australian syllabus, and covered 97.7%, 86% and 93%, respectively, of all competencies and sub-items. The final fellowship examinations of Australia, South Africa and the UK were all highly similar in format and content. The examination in Canada was substantially different, and had two written sessions but combined the oral and clinical component into a structured OSCE using standardized patients and the component included unmanned stations. There were no significant differences for completion certificate of training and/or board certification observed between these countries.The results of this study strongly suggest that core and technical competencies outlined in the training and education curriculum and the final fellowship examination in Orthopaedic Surgery in Australia, South Africa and the UK are compatible. Between country reciprocal recognition of these fellowship examinations should not only be considered by the relevant Colleges, but should also be regulated by the individual countries health practitioner registration boards and governing bodies. Common n Canada .In order to practice medicine in the recipient country, IMGs are required to fulfil the requirements of that countries medical registration authorities. For example, for registration in the UK by the General Medical Council (GMC), IMGs from non-European Union member countries have to complete the PLAB  . In AustFor specialist consultants, registration requirements differ from the common registration pathway, and they must become Fellows of the relevant specialist colleges. This generally includes a period of supervision, and may require they sit the final fellowship examination in their specialty ,10. SyedThe purpose of this project was, therefore, to compare the final fellowship examination in Orthopaedic Surgery for the Commonwealth Countries of the UK, Australia, Canada and South Africa. We hypothesized that there would be no significance between country differences, making these examinations comparable.The websites of the Royal Australasian College of Surgeons ,13, AustAll available documents were screened to establish entry criteria into higher orthopaedic surgical training (as an accredited training registrar), and the length and curriculum of required training. These criteria served to establish comparability of the surgical training, and to establish whether there were any significant discrepancies in the training process that could result in the exit examination assessing a different syllabus. This comparison was performed to exclude the possibility that, despite a similarly structured and comparable exit assessment, knowledge of a different syllabus was being tested during the final fellowship examination. For the purpose of comparison of the syllabus and surgical training between the four different countries, the ‘Surgical Education and Training – Orthopaedic Surgery Competency Based Curriculum’ of the Australian Orthopaedic Association was selected as a baseline reference .The Australian curriculum was selected as the baseline based because this syllabus provides a clear and concise list of the competencies that must be achieved during the training period, and provides the most explicit description of the technical modules covered during training. This facilitated a structured search of the other countries’ curricula, with comparison against these criteria. The competencies listed in the Australian syllabus were: medical expertise, technical expertise, judgement-decision making, communication, collaboration, management and leadership, health advocacy, scholar and teacher, and professionalism. These competencies were further subdivided into subcategories; for example ‘medical expertise’ was defined as ‘access & apply relevant knowledge to clinical practice’ and the following criteria were assessed to define competency in this category: maintain currency of knowledge, apply scientific knowledge in practice, recognize and solve real life problems. The technical modules were divided into a common core syllabus of surgery, orthopaedic principles and basic science, paediatrics, spine, shoulder and elbow, hand, hip, knee, arthroplasty, trauma, foot and ankle, tumour and genetic/metabolic/neurological disorders. For example, the arthroplasty module listed clinical competencies for total and unicompartmental knee arthroplasty, total hip arthroplasty, revision arthroplasties, upper limb, and foot and ankle arthroplasties using the following sub-items: knowledge , and skills  .The curricula and syllabuses for the orthopaedic surgery training program in the UK, South Africa and Canada were then also reviewed for all competencies and requisite technical modules. When reviewing the curricula of the other three Commonwealth Countries comparability was not based on finding the identified keywords for the core and technical competencies but to instead identify whether these key-terms were addressed and described in those publications. Comparability was defined if at least 80% of the competencies and technical modules, and their subcategories, for each of these three countries matched those identified in the Australian curriculum. The websites were then searched for details regarding the final fellowship examination in Orthopaedic Surgery for each of these countries and again compared to Australia as the standard, with at least 80% agreement defined as comparable.Similar to assessment of the curricula and syllabus, and to be with consistent with the methodology, the Australian Final Fellowship Examination in Orthopaedic Surgery was used to investigate comparability between countries. Comparability criteria here were defined more strictly, considering the exit examination is regarded as the final hurdle to allow an orthopaedic surgeon to practice independently. While this criterion does not specifically assess the quality of training or examination standards between individual surgeons, it does serve as a reliable tool to assess substantial comparability between international medical graduates as suggested by the policy of the Royal Australasian College of Surgeons .The final fellowship exit examination in Orthopaedic Surgery in Australia is currently comprised of multiple components, beginning with a two hour written multiple-choice test. This is followed by a two hour written exam including both essays and multiple short questions. There are then three viva voce 30-min oral examinations, including one on diagnostic investigations, and a further two operative surgery sessions. Finally, the clinical component consists of two 30-min sessions including up to five clinical cases per session. To be comparable to this Australian standard, the final fellowship examination in the other three countries needed to satisfy the minimum criteria of at least two written components of at least two hours duration, including either multiple choice questions, short essay questions, essays or any combination of these. For the oral component, a minimum of three viva sessions with a minimum of 30-min duration were defined as comparable. Finally, for the clinical component a minimum of three clinical examination sessions of at least 30-min duration were required to accept comparability. For the written and oral component of the fellowship examination to be considered comparable the entire syllabus had to be covered during the examination sessions.Entry criteria for higher surgical training varied between countries . HoweverNine competencies were described in the ‘Surgical Education and Training – Orthopaedic Surgery Competency Based Curriculum’ of the Australian Orthopaedic Association. The curricula of the UK, South Africa and Canada were directly comparable to the Australian syllabus, and mentioned 97.7%, 86% and 93%, respectively, of all competencies and sub-items .10.1080/Thirteen technical modules were described in the ‘Surgical Education and Training – Orthopaedic Surgery Competency Based Curriculum’ of the Australian Orthopaedic Association. The curricula of the UK and South Africa were both highly comparable, and mentioned all 13 modules; Canada mentioned 12 of the 13 modules, but did not mention the common core syllabus of surgery .10.1080/The duration of training was comparable for all four countries . The lonThe final fellowship examinations of Australia, South Africa and the UK were very similar in structure. In comparison to Australia, South Africa required candidates to complete three rather than two written sessions; the UK required candidates to complete four rather than three oral sessions, exceeding the defined criteria for comparability. Canada combined the oral and clinical component into a structured OSCE , with 11 stations of 15 min each. The Canadian College used standardized patients and the component included unmanned stations. This approach was significantly different to the other three countries, and was deemed not comparable with the defined criteria .10.1080/The requirements for completion certificate of training and board certification are outlined in The most important finding of this study was that the entry criteria into higher surgical training, technical modules and competencies , the duration of training, and board certification for all four of these commonwealth countries are comparable. Most importantly, the final fellowship exit examination in the field of Orthopaedic Surgery for South Africa, Australia and the UK are clearly comparable to one other.Migration of medical professionals is part of today’s social, economic and professional globalization trend –5,23. MeRegistration with professional bodies serves several important functions, and helps to assure the registered individuals are fit to practice medicine . MaintaiRegistration as a specialist generally requires a local fellowship within the specialty, and it is uncommon to accept specialist qualification from other countries ,10,12,19The need for an exit examination to provide a common denominator for trainees, and to confirm a high standard of surgical practice, is obvious . HoweverOther modalities may be more useful if the governing and registration authorities see the need for a mechanism to evaluate an overseas trained applicant. Nachbauer reported on the value of an exit assessment in vascular surgery, and reported a prerequisite for assessment should be the completion of training in the home country . Two to The question remains whether these measures are even necessary. The results of this project suggest that they are obsolete for those overseas trained specialists with qualifications from countries with comparable final examinations. Within the specialty of Orthopaedic Surgery, this includes the Commonwealth countries of South Africa, Australia and the UK.Ultimately, political action will be instrumental to drive any such change. In Australia, a recent parliamentary enquiry into registration and support for overseas trained doctors has been concluded, and 45 recommendations were made in the final report . These rThis study has certain limitations. The accuracy of this study relies on the information gained via access to the colleges, other professional bodies and organizations. Orthopaedic surgery fellowship examination and training details may have changed or may not have been published on these websites. This project cannot claim to be a complete qualitative analysis of the training and examination processes involved. However, it can be safely assumed that the provided information on the websites was reliable and valid at the time of access. We, therefore, believe that these comparisons are both reliable and accurate. In contrast to the UK, South Africa and Canada, the Australian training and education curriculum provided a list of competencies which allowed a check of the other curriculi against these specified criteria. As the curricula of other three countries are written in a more narrative fashion, it required intense study to compare these competencies against the Australian curriculum. It is acknowledged that certain criteria may have been missed during the screening which may introduce an element of bias.The results of this study strongly suggest that core cognitive and technical competencies outlined in the training/education curriculum and subjected to scrutiny during the final fellowship examination in Orthopaedic Surgery in Australia, South Africa and the UK are compatible. Between country reciprocal recognition of these fellowship examinations should not only be considered by the relevant Colleges, but should also be regulated by the individual countries health practitioner registration boards and governing bodies.


Depression is the principal cause of illness and disability in the world. Studies charting the prevalence of depression among children and adolescents report high percentages of youngsters in both groups with depressive symptoms. This review analyzes the construct and explanatory theories of depression and offers a succinct overview of the main evaluation instruments used to measure this disorder in children and adolescents, as well as the prevention programs developed for the school environment and the different types of clinical treatment provided. The analysis reveals that in mental classifications, the child depression construct is no different from the adult one, and that multiple explanatory theories must be taken into account in order to arrive at a full understanding of depression. Consequently, both treatment and prevention should also be multifactorial in nature. Although universal programs may be more appropriate due to their broad scope of application, the results are inconclusive and fail to demonstrate any solid long-term efficacy. In conclusion, we can state that: (1) There are biological factors  which strongly influence the appearance of depressive disorders; (2) Currently, negative interpersonal relations and relations with one's environment, coupled with social-cultural changes, may explain the increase observed in the prevalence of depression; (3) Many instruments can be used to evaluate depression, but it is necessary to continue to adapt tests for diagnosing the condition at an early age; (4) Prevention programs should be developed for and implemented at an early age; and (5) The majority of treatments are becoming increasingly rigorous and effective. Given that initial manifestations of depression may occur from a very early age, further and more in-depth research is required into the biological, psychological and social factors that, in an interrelated manner, may explain the appearance, development, and treatment of depression. Depression is the principal cause of illness and disability in the world. The World Health Organization (WHO) has been issuing warnings about this pathology for years, given that it affects over 300 million people all over the world and is characterized by a high risk of suicide (the second most common cause of death in those aged between 15 and 29)  disorders are persistent and usually fluctuating disorders in which the majority of episodes are not sufficiently severe to warrant being diagnosed as hypomanic or mild depressive episodes. Since they last for many years and affect the patient's normal life, they involve considerable distress and disability. This section also includes cyclothymia and dysthymia. Cyclothymia is a persistent instability of mood involving numerous periods of depression and mild elation, none of which are sufficiently prolonged to justify a diagnosis of bipolar affective disorder or recurrent depressive disorder. This disorder is frequently found among the relatives of patients with bipolar affective disorder and some patients with cyclothymia eventually develop bipolar affective disorder. For its part, dysthymia is a chronic depression of mood, lasting at least several years, which is not sufficiently severe, or in which individual episodes are not sufficiently prolonged, to justify a diagnosis of mild, moderate, or severe recurrent depressive disorder.Finally, other mood (affective) disorders include any mood disorders that do not fall into the categories described above because they are not of sufficient severity or duration. They may be single, recurrent (brief), or specified episodes.The manifestations and symptoms of depression vary in accordance with age and level of development. However, it is clear that the DSM-5 and the ICD-10 do not distinguish between adult and child depression, although by including disruptive mood dysregulation disorder, the DSM-5 does take into account the fact that children and young people aged between 7 and 18 may express their distress in other ways, through chronic, severe, and recurrent irritability manifested verbally and/or behaviorally. Similarly, major depressive disorder specifies that in children the mood may be irritable rather than depressed. However, no distinctions of this kind are found in the ICD-10, an absence which may lead to the faulty inference that the characteristics of child and adolescent depression are similar to those of adult depression.Depressive disorders cannot be explained by any single theory, since many different variables are involved in their onset and persistence. The principal biological and psychological theories were therefore taken as the main references for this section. Subsequently, the contributions made by each of these theories regarding depression were studied by conducting searches in PubMed, Web of Science, Science direct, and Google Scholar. With the constant key words being depression, child depression and adolescent depression, the search for information cross-referenced a series of other key words also in accordance with the specific theory in question. Due to the importance of some seminal works in relation to the development of psychological theories of depression, certain authors have remained key references for decades. A total of 64 bibliographical references were used. The following is a summary of the various explanations for the onset of depression, according to the different theoretical frameworks.If a mood disorder cannot be explained by family history or stressful life events, then it may be that the child or adolescent in question is suffering from a neurological disease. In such a case, depressive symptoms may manifest early in children and adolescents as epileptic syndromes, sleep disorders, chronic recurrent cephalalgias, several neurometabolic diseases, and intracranial tumors Narbona, .Serotonin is a monoamine linked to adrenaline, norepinephrine, and dopamine which plays a key role, particularly in the brain, since it is involved in important life regulation functions , as well as many psychiatric pathologies   axis may explain major depression  : secure, anxious-avoidant, and anxious-resistant . These interactions are influenced by cognitions, behaviors and emotions  have all been associated with the onset of depression in childhood , along with changes in people's psychological behavior Casullo, . Some stIn an attempt to better understand the influence of culture and family on depressive symptoms, Lorenzo-Blanco et al.  tested aAnother study carried out with girls aged 7–10 years  biological reasons; (2) insecure attachment; (3) lack of reinforcement of previously-reinforced behaviors; (4) negative interpersonal relations and relations with one's environment and the resulting negative consequences; (5) attributions made by individuals about themselves, the world and their future; and (6) sociocultural changes. It is likely that no single theory can fully explain the genesis and persistence of depression, although currently, negative interpersonal relations and relations with one's environment and sociocultural changes  may explain the observed increase in the prevalence of depression.Many different evaluation instruments can be used to measure child and adolescent depression. As shown in the tables above, there are several self-administered instruments that can be used with children from age 6 to 7 onwards, although their duration should be taken into consideration in order to avoid overtiring subjects. While it is clear that an effort has been made to design shorter measures , the duration of the test should not be the only aspect taken into account when selecting an evaluation instrument.One of the most widely used instruments to measure child depression in the scientific literature is the Children's Depression Inventory-CDI Kovacs, , which iif one wishes to know how a child feels, ask the child” . The inclusion criteria were that the study analyzed all the research subjects of the review study , that study participants were aged between 6 and 18, that the study was published in a peer-reviewed journal and that it was written in either English or Spanish. Review studies and their references were also analyzed. Studies focusing mainly on psychiatric disorders other than depression were excluded.Finally, 39 studies were selected for the review, which explored 8 prevention programs that are outlined in As shown in the table, the results of the various programs outlined are not particularly positive, since on many occasions the effects (if there are any) are not sustained over time or are limited in scope . Nor is the distinction between universal and targeted programs particularly clear as regards their effects, since although targeted programs may initially appear to be more effective, their impact is not found to be sustained in the long term.Greenberg et al.  argue thAs Calear and Christensen  point ouIn order to draft this section, a search was conducted for the most commonly-used therapies with proven efficacy for treating depression. The databases used were PubMed, Web of Science, Science direct, and Google Scholar. The key words used in the search were treatment, depression, child depression, and adolescent depression. A total of 30 bibliographic references were used in the drafting of this summary, including the major contribution made by The American Psychological Association's Society of Clinical Psychology , Although the World Health Organization (WHO)  claims tThe efficacy of treatment with antidepressants has been called into question for some years now. Iruela et al.  claim thOn another hand, Wagner and Ambrosini  analyzedAs regards the effectiveness of psychodynamic treatments, Luyten and Blatt  advocateIn a qualitative study carried out by Brown  on paren– Self-Management/Self-Control Therapy Kanfer, . Depress– Cognitive Therapy Beck, . Individ– Interpersonal Therapy  , – Rational Emotive Behavioral Therapy Ellis, . This sh– Self-System Therapy Higgins, . Depress– Short-Term Psychodynamic Therapy   , have moFerdon and Kaslow , for theThere are other studies also which focus on treatments for depression in childhood. For example, Crowe and McKay  carried Another study carried out in Saudi Arabia concluded that student counseling in schools may help combat and directly reduce anxiety and depression levels among Saudi children and adolescents . Thus, in order for the individual to attain the highest possible level of psychological wellbeing, attention should focus on both these and other related aspects.The present review aims to shed some light on the complex and broad-ranging field of child and adolescent depression, starting with a review of the construct itself and its explanatory theories, before continuing on to analyze existing evaluation instruments, the main prevention programs currently being implemented and the various treatments currently being applied. All these aspects are intrinsically linked: how the concept is defined depends on the explanatory variables upon which said definition is based, and this in turn influences how we measure it and the variables we define as being key elements for its prevention and treatment.It is interesting to note the low level of specificity of both the construct itself and the explanatory theories offered by child and adolescent psychology, which suggest that child depression can be understood on the basis of the adult version of the pathology. This may well be a basic error in our approach to depression among younger age groups. The fact that universal prevention programs specifically designed for children are obtaining only modest results may indicate that we have perhaps failed to correctly identify the key variables involved in the genesis and maintenance of child and adolescent depression.The review of current child and adolescent depression prevention programs revealed that the vast majority coincide in adopting a cognitive-behavioral approach, with contents including social skills and problem solving training, emotional education, cognitive restructuring, and strategies for coping with anxiety. These contents are probably included because they are important elements in the treatment of depression, as shown in this review. But if their inclusion is important and effective in the treatment of depression, why do they not seem to be so effective in preventing this pathology? There are probably many factors linked to prevention programs which, in one way or another, influence their efficacy: who implements the program and what prior training they receive; the characteristics of the target group; group dynamics; how sessions are run; how the program is evaluated; and if the proposed goals are really attained . Moreover, in universal prevention programs carried out in schools, the intervention focuses on students themselves rather than adopting a more holistic approach, as recommended by certain authors such as Greenberg et al. . But, ifThere is therefore still much work to be done in order to fully understand child and adolescent depression and its causes, and so design more effective evaluation instruments and prevention and treatment programs. Given the important social and health implications of this disorder, we need to make a concerted effort to further our research in this field.MG designed the study and wrote the protocol. EB and JJ conducted literature review and provided summaries of previous research studies, and wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This report provides a historical overview of research concerning the endogenous hallucinogen N, N-dimethyltryptamine (DMT), focusing on data regarding its biosynthesis and metabolism in the brain and peripheral tissues, methods and results for DMT detection in body fluids and brain, new sites of action for DMT, and new data regarding its possible physiological and therapeutic roles. Research that further elaborates its consideration as a putative neurotransmitter is also addressed. Taking these studies together, the report proposes several new directions and experiments to ascertain the role of DMT in the brain, including brain mapping of enzymes responsible for the biosynthesis of DMT, further studies to elaborate its presence and role in the pineal gland, a reconsideration of binding site data, and new administration and imaging studies. The need to resolve the “natural” role of an endogenous hallucinogen from the effects observed from peripheral administration are also emphasized. Despite their presence in the human pharmacopeia for millennia, we have yet to resolve the biochemical mechanisms by which the hallucinogens (psychedelics) so dramatically alter perception and consciousness. It is the only class of compounds that efficiently and specifically does so. For that matter, we do not fully understand the biochemistry of perception itself or how we live such a vivid and complex internal life in the absence of external stimulation. We do not understand the basic biochemical mechanisms of some of our most common experiences, such as the many human aspects of creativity, imagination or dream states. This is also true for extraordinary states of consciousness such as “visions” or spontaneous hallucinations or phenomena such as near-death experiences (NDE). And it is troubling that we have not sufficiently turned the scientific method on these latter subjects despite the profound role they have played in the evolution of our science, philosophy, psychology and culture.The experiences derived from the administration of hallucinogens are often compared to dream states. However, the experience of administered hallucinogenic substances is far more intense, robust and overwhelming than the subtlety of mere dreams. By comparison, the natural biochemical processes for our related “hallucinatory” experiences are obviously far more highly regulated, occurring as an orchestrated and inherent function of the “normal” brain. Nonetheless, it is conceivable that attaining an explanation for these related natural human phenomena may lie in resolving the biochemical mechanisms involved in the more dramatic pharmacology of hallucinogens, recognizing that the complexities and intensity of the “administered” experience are, essentially, an overdose relative to corresponding natural regulatory controls. Given their status as “psychedelics” (mind-manifesting substances), increased study of the hallucinogens, particularly with advanced brain imaging and molecular biology approaches, may provide a better understanding of the “common” biochemistry that creates mind.1, Figure Perhaps the science behind the discovery of endogenous opioids offers us a corollary. We came to better understand the common human experience of pain through examining the pharmacology of administered opiates and the subsequent discovery of endogenous opioid ligands, receptors and pathways that are predominantly responsible for and regulate the experience and perception of pain. Such may also be the case for understanding perception and consciousness. With the discovery of the endogenous hallucinogen N, N-dimethyltryptamine  including the medulla, the amygdala, uncus, and frontal cortex  as well, demonstrating its availability for the biosynthesis of DMT is also relevant to a complete elucidation of the overall pathway. Indeed, demonstrating the co-localization of AADC and INMT should be a necessary endeavor in any future research regarding DMT biosynthesis in both the brain and periphery. The colocalization of AADC in discreet brain cells and areas with INMT permits TA and, subsequently, DMT formation locally. With demonstration of colocalization of the necessary biosynthetic machinery in the brain, both AADC and INMT, mechanisms for a rapid biochemical response to signaling and DMT formation may be shown to exist. Furthermore, the demonstration of mechanisms for the protection, storage, release and reuptake of DMT would demonstrate that higher concentrations of DMT could be reached in the synaptic cleft and at neuronal receptors than would have to occur from, based on previous thought, formation and transport from the periphery. Pursuit of research of these mechanisms, as well as detailed mapping of INMT-AADC in the brain, is needed. We should not rule out the possibility that the biosynthesis and transport of DMT can and does occur from the periphery, however. Peripheral DMT, especially if synthesized in tissues that bypass liver metabolism on first pass, may also serve as a signaling compound from the periphery to the brain. Such signaling may occur in maintaining homeostasis or in response to extreme changes in physiology. However, the immediate availability of TA for the biosynthesis of DMT in the periphery should also be demonstrated and studies examining the co-localization of AADC and INMT in the periphery should also be performed. This will require using highly sensitive and well validated antibodies and probes for detection of INMT and/or its mRNA in brain and/or peripheral tissues as well as those for aromatic-L-amino acid decarboxylase (AADC). Demonstration of colocalization with AADC has not been previously conducted in any other study seeking to identify INMT's presence or to demonstrate INMT activity. Such a determination may prove fruitful since a preliminary examination for the possible colocalization of INMT and AADC in the brain is supported by the data provided in the Allen Brain Atlas, mapping INMT and AADC gene expression (brain-map.org).in vitro studies of INMT as it relates to DMT biosynthesis necessarily added TA to their incubations, making TA “artificially” available in regions where natural levels may be absent or at significantly lower levels. Without a source for TA, the hypotheses regarding the formation of DMT in the periphery and its transport to the brain as a mechanism of action/function of endogenous DMT may be seen to be based on a less significant pathway than previously thought. Failure to demonstrate colocalization of INMT and AADC in the periphery would alter, to some degree, the focus of studies of peripheral synthesis and detection for understanding the role of endogenous DMT.A thorough re-examination of possible peripheral DMT biosynthesis is needed. Indeed, INMT actually methylates other substrates, such as histamine  DMT is rapidly metabolized and cleared, with only a small fraction of IV or IM administered DMT subsequently being found in urine. For example, 0.16% of an intramuscular dose of DMT was recovered as the parent compound following a 24 h urine collection  iproniazid as well as other MAOIs  taken from animals pretreated with a MAOI as being 10 and 15 ng/kg. This study's information is unfortunately quite limited in terms of sample number and did not address extraction recoveries, method validation or brain distribution of DMT.Many studies have been conducted to detect and/or quantitate DMT in blood and urine and only a few in the CSF of humans  was used for the analysis, it is still not known how the DMT was distributed in the brain or if the DMT observed actually arose from a discrete brain area or areas alone. The data necessarily expressed the DMT concentration as if it was homogeneously distributed. Rats were also sacrificed at constant times during the study and no accounting was made for possible circadian or ultradian variations.As noted earlier, one study, using rat pups of different ages (1–40 days after birth) and conducted using a validated extraction/gas chromatographic-mass spectrometric analysis of whole-brain extracts  in the Beaton and Morris  study weNichols,  to endogThere is a significant literature correlating the binding affinity of DMT and related hallucinogens for the 5HT2A receptor and its subset of receptors with other hallucinogens and their subsequent behavioral effects  , monocyte-derived macrophages, and dendritic cells, Szabo et al. (2), apparently via its interaction with sigma-1 receptors. A decreased expression and function of the alpha subunit of the hypoxia-inducible factor (HIF-1) was also observed, suggesting that DMT-mediated sigma-1 activation may alleviate hypoxia-induced cellular stress and increase survival via decreased expression and function of the stress factor HIF-1α in severe hypoxia. Such a mechanism has relevance to stroke, myocardial infarct or similar arterial occlusive disorders, cardiac arrest, and perinatal asphyxia, all conditions associated with hypoxic consequences  and mitochondria. In this role, it is involved in the transmission of ER stress to the nucleus  but does, nonetheless, have agonist activity. INMT has been shown to be co-localized with sigma-1 receptors in C-terminals of motor neurons  administered interperitoneally to rats at a dose level of 2.5 and 5.0 mg/kg. The D4DMT was observed to produce, at equivalent doses to DMT itself, a significantly greater disruption of behavior, a longer duration of action and a shorter time to onset than non-deuterated DMT. This potentiation was apparently due to the kinetic isotope effect which, in theory, makes it harder for the MAO enzyme to extract a deuterium (vs. a hydrogen) from the alpha position  the synthetic enzymes and substrates are present in the CNS for the production of DMT, 2) a binding site is present to react with the compound and 3) the compound is found in human CSF and isolated synaptic vesicles from rat brain tissue”  on neuronal plasma membrane  are beginning to show promise in the treatment of addictions  as well as post-traumatic stress (PTSD) and other mental disorders (Bogenschutz and Pommy, Frecska et al.  have sug4DMT is orally active, as previously noted, which would enhance the opportunities to examine its potential as a therapeutic. The use of hallucinogens in psychotherapy is gaining renewed interest and certainly DMT should be among the drugs in the psychiatric pharmacopeia. Any proposal to pursue this avenue will require more than the current combined body of scientific evidence. Both Federal and State laws will have to change in order to make the manufacture and use of such compounds easier and to make conducting the necessary research feasible.At present, the data arguing for the use of DMT as a therapeutic, particularly via administration, is thin. The claimed therapeutic effects for DMT in combination with harmala MAOIs as in ayahuasca or pharmahuasca Ott,  is of inHowever, if DMT is a neurotransmitter and is responsible for modulation of serotonergic or other neurotransmitter systems, it may well be that many existing pharmaceuticals already exert their pharmacology via DMT-related-effect mechanisms. This may be the case for the other hallucinogens, as noted, but may also be true for part of the mode of action of certain serotonergic drugs, such as antidepressants. Further characterization of DMT cellular distribution, receptors and general biochemistry may lead to new targets for more effective pharmaceutical substances and interventions.It has been 86 years since DMT's first synthesis by Manske and 61 years since Szara discovered its hallucinogenic properties. It has been 41 years since Christian et al. characterized DMT as a neurotransmitter. Further research has better defined the latter's characteristics such that a compelling case can be made, at a minimum, to consider DMT as a putative neurotransmitter.Over time, the observations of the hallucinogenic phenomena experienced following the administration of DMT have led to speculation that endogenous DMT is possibly involved in psychosis, normal attributes and experiences such as creativity, imagination and dream states, maintenance of waking reality, altered states of consciousness including religious and/or spiritual phenomena, and NDEs. Even more far reaching and “other worldly” hypotheses have also been offered, suggesting that DMT, as well as other hallucinogens, may provide actual proof of and/or philosophical insights into many of our unanswered questions regarding extraordinary states of consciousness. Regardless of the level and cause of such speculation and hypotheses, it is only scientific research that can inform or refute such thinking. There is no doubt that hallucinogen research has been a forbidden fruit long ripening on the tree of knowledge.Recent research has demonstrated that DMT is present in and is released from the pineal gland of live, freely-moving rodents. Although older data suggested that DMT might not be synthesized to any great extent in brain, studies have now shown that the necessary enzymatic components for the biosynthesis of DMT are present in discreet brain cell types and areas as well as other tissues not previously examined. New receptors for DMT have been identified and a potential role for DMT as a neuroprotectant and/or neuroregenerative agent has been suggested. Hallucinogens have been shown to produce brain patterning resembling dream states, apparently mediated through 5-HT2A receptor activation. DMT's effect in this regard has yet to be examined, but raises speculation as to one of the possible roles of endogenous DMT.As discussed and delineated above, more research is needed on DMT's natural role and function and interaction with other neurotransmitter systems. This will require the recommended future research into DMT biosynthesis, metabolism and binding, new methods for peripheral and central detection and data from administration, imaging and therapeutic trial studies. The data derived from the areas of research addressed above will no doubt suggest several possible new avenues for additional future research on DMT. In order to advance, however, regulatory blockades to hallucinogen research must be removed. Progress in hallucinogen research in these areas has been slowed due to over-regulation. For at least the last 50 years, research on DMT and other hallucinogens has been impeded in the United States by passage of the Congressional Amendment of 1965 and the Controlled Substances Act of 1970 by the United States Congress that classified DMT and other major hallucinogens as Schedule-I substances. Given the endogenous nature of DMT, it deserves a special status for future research.It is evident that we have too long ignored the field of hallucinogen research, in all of its potential aspects. This is especially true if continuing research demonstrates a clear role for one of its more prominent members, DMT, as an endogenous regulator of brain function. It is my opinion that these and many other possible approaches and hypotheses regarding DMT and other psychedelics are research endeavors that have great potential and are worthy of attention and support. Turning the newest technologies to this work, in genetics, analytical chemistry, molecular biology, imaging and others, we will no doubt acquire both new knowledge and ask new questions. If the politics of any one nation forbid it, perhaps others will take up the challenge to further the knowledge of our own potential and the further development and understanding of what we prize as our most unique human characteristic; the untapped possibilities of the mind.The work presented is the sole effort of SB who agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.