The scope of the dataset allows to examine undergraduate hospitality and tourism students’ intentions towards environmental sustainability. Moreover, it is possible to compare factors  towards environmental sustainability between hospitality and tourism students based on different socio-demographic characteristics. To fulfill these objectives, data was collected through a bilingual questionnaire containing 312 valid responses from undergraduate students studying towards a business degree. The questionnaire was administered at the Prince of Songkla University in Phuket, Thailand in the fourth quarter of 2021. Moreover, the data collection adhered to the NESH principles applicable for Social Science Research. The data collection instrument was validated for international consistency and reliability through a three-person panel of research experts and validated using the IOC method. Furthermore, the questionnaire was tested with a targeted sample consisting of ten students prior to its implementation. The dataset serves as an insightful reference for practitioners and policymakers in higher education to adjust their pedagogy, in addition to, as a secondary data source for educational researchers to examine undergraduate hospitality and tourism students’ intentions towards environmental sustainability. Based on eligible responses, the representative demographic profile in The questionnaire was administered with a bilingual option, i.e. Thai and English. Moreover, the questionnaire was administered at the Prince of Songkla University in Phuket, Thailand in the fourth quarter of 2021. After screening the collected data, 9 inconclusive/incomplete responses were discarded from inclusion. The sample size included was 312 to represent the population in data analysis. The confidence level of accurate sampling was estimated at 95% (2.2The adaptation of seven (7) instead of five (5) points on the original Likert-type scale is described as a universal instrument to efficiently measure and evaluate the attitudes of respondents n = 10), although these responses were not included in the analysis.Moreover, the index of item-objective congruence (IOC) is a tool used to improve the validity and reliability of administered surveys and was used as the basis for screening the item quality. The survey was evaluated by three impartial research experts for content validity using an adapted version of the IOC index developed by Turner and Carlson Institutional approval was obtained prior to collecting the data and before answering the survey, written informed consent was a precondition for participation. The participants were informed about the research and its purpose, that they had the right to withdraw at any stage, and that the data collected would be treated as confidential . For ethical considerations and to protect the identity of the participants, some specific information in the socio-demographic profile was generalized before disclosure in this paper, namely some specific minority nationalities were labeled as “foreign” instead of displaying the particular nationality as this could potentially allow exposing the identity of the participant. The foundation for ethical considerations is based on the principles formulated by the Norwegian National Research Ethics Committees Kevin Fuchs: Conceptualization, Methodology, Data curation, Writing – original draft.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The aim of this collection is to provide information on recent advances and current thinking in selected areas of Neonatal Endocrinology, as we believe that this area can be challenging in presentation and management for both neonatologists and pediatric endocrinologists. To this end, we invited several leaders in the field to contribute. In addition, we have included 3 manuscripts submitted to Frontiers that fell within the remit of our topic.The collection focuses on selected conditions presenting in the newborn consisting of a series of 10 mini-reviews, including some which may be considered the “go to” article for up-to-date science and management of various conditions.The neonatal period is complicated by unique physiology, because of the transition from intrauterine life including the influence of maternal and placental hormones, and “normal” values for hormone levels can be difficult to define, and many change with increasing postnatal age. The measurement of hormone levels is further complicated by numerous additional circulating steroids which may interfere with assays, and the challenges of small sample size. In the context of this milieu the collection of articles ranges from common neonatal problems such as hypoglycemia to rare disorders such as neonatal bone disease. The content of all the articles in the collection is summarized below.Bosch i Ara et al. provide an extensive review of congenital hypopituitarism, with a thorough review of the science, including the known genetics, phenotype-genotype correlations, syndromic, and non-syndromic hypopituitarism with helpful accompanying tables. They also provide a comprehensive guide to the clinical presentation including red-flag symptoms and signs, diagnosis, assessment and management of pituitary hormone deficiencies.Di Dalmazi et al. present a study on the effect of maternal and neonatal factors on neonatal TSH levels, using retrospective data from screening for congenital hypothyroidism in 62,132 infants in Abruzzo, Italy, a relatively iodine deficient area. As both sex and postnatal age at collection affected the TSH level, they advocate the use of locally derived TSH cut-offs for both and provide local percentile charts for TSH based on their data. Effects of maternal and neonatal factors were modest, but the study was limited by data routinely collected in the screening programme and the unknown contribution that iodine deficiency may have played in this population.Buonocore et al. describe causes of adrenal insufficiency, with a focus on genetic conditions that present in the first few months of life. This superb overview provides clear and concise information on complex pathways and conditions, identifying seminal features of presentation in a manner that is easy to read. Testing for adrenal insufficiency was not in the remit of this invited review, but assessment of the HPA axis can be found in the review of congenital hypopituitarism by Bosch i Ara et al..Balsamo et al. explore the breadth of conditions presenting as congenital adrenal hyperplasia in the newborn period, and provide insight into some of the rarer conditions. They describe how clinical characteristics and diagnostic tests may be used to distinguish between these, and how steroidogenic biochemistry is evolving in this field. Therapeutic approaches are also included.Li et al. from China present a systematic review and meta-analysis of the screening results for congenital adrenal hyperplasia involving 7.85 million newborns. The incidence of 1/23,024 was higher in males than females, possibly as a result of the gender imbalance in China, the greater attention paid to male infants resulting in a higher recall rate, or the diagnosis of ambiguous genitalia before or after birth in females, making screening unnecessary in girls.Bertelloni et al. outline a different approach to the investigation of 46XY DSD to the extensive, often repeated and invasive laboratory testing, by using advanced genetic technologies  as the first line test after karyotyping and salt-loss exclusion which may result in a molecular diagnosis and guide more targeted biochemical investigations. A causative genetic diagnosis allows for accurate prognosis and recurrence risk.With advancement in the genetic diagnosis of disorders of sex development, Lucaccioni et al. review the current understanding of minipuberty and using this window as an opportunity for the diagnosis, and potentially treatment, of babies with DSD which could alter the natural history. They highlight the hormonal changes that occur and how minipuberty modulates neurobehavioral development.Edwards and Harding review clinical aspects of transient neonatal hypoglycemia. They discuss pathophysiology, controversy over definitions of hypoglycemia, when and how to make blood glucose measurements, and use of glucose gel to prevent hypoglycemia. They highlight the need for evidence as to whether transient asymptomatic hypoglycemia is associated with brain injury, and if so, at what level or duration.Chandran et al. report a family with a novel HNF4A mutation presenting with differing phenotypic presentations of glucose dysregulation. They describe an infant with diazoxide responsive hyperinsulinaemic hypoglycemia, who shares a novel HNF4A mutation with a sister who had transient neonatal hypoglycemia, and his father who developed diabetes at the age of 15. Implications of the genetic diagnosis on treatment and prognosis are discussed.Beardsall reviews hyperglycemia with a focus on the preterm infant, and discusses pathogenesis, glucose insensitivity and insulin resistance, relative insulin deficiency, the clinical consequences of hyperglycemia, and its clinical management. The review provides a wealth of information on underlying mechanisms, which may be of particular value for neonatologists.Beltrand et al. describe how the recent advances in neonatal diabetes mellitus can guide management and how the known genetic mutations define the pathophysiology by causing either abnormal β-cell function or abnormal pancreatic morphology. The authors provide a detailed clinical description of both the permanent and transient forms. The challenge of insulin therapy in maintaining normoglycaemia is discussed, as is the management of those with mutations in the KATP channel with suphonylureas to which the channel remain sensitive in 90% of cases. A helpful appendix provides practical advice on switching from insulin to glibenclamide, the oral suspension of which is licensed for children in the European Union.Taylor-Miller and Allgrove examine the current understanding of fetal-to-neonatal mineral homeostasis mechanisms  as well as vitamin D. Recent genetic discoveries have shed light on the pathophysiology of some causes of neonatal hypo and hypercalcemia. The presentation and management of bone fragility is discussed as well as the investigation and management of disorders of calcium and phosphorus homeostasis.In the review of current insights into disorders of calcium and phosphate in the newborn, Saraff et al. describe an approach to neonatal bone disorders for clinicians, highlighting that early and accurate diagnosis in these rare disorders can be important for potentially life-saving treatment. The review includes structural bone defects, and bone mineralization defects, and an approach to diagnosis and management. This practical approach could be extremely useful for neonatal clinicians.This series of articles was conceived with Dr. Paolo Ghirri, Associate Professor of Pediatrics at the University of Pisa, where he was the director of Neonatology at the Santa Chiara. Following his sudden and untimely death during the planning stage, we decided to dedicate the series to his life and work and made our contributors aware of this at the time of invitation.Both authors contributed equally to this editorial and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Phaseolus vulgaris L.), maize, and squash were described by explorers as early as 1492. The illustration of common bean recognized as the first in Europe is in Fuchs’ Di Historias Stirpium, published in 1542 and a half-century after beans were observed in the Caribbean. Besides herbals and herbarium specimens, the sources of information on the introduction of New World crops are paintings and illustrations. Two early sources of images of maize and squash are the Grandes Heures d’Anne de Bretagne and the Loggia di Amore e Psiche in the Villa Farnesina, Rome. The former was illustrated between 1507 and 1508 and has an image identified as the common bean. The Villa Farnesina Loggia was decorated in 1515–1518, with festoons containing three instances of bean pods. Our first objective was to evaluate these images to determine whether they represented depictions of common bean earlier than the illustration by Fuchs. Neither image appears to be a common bean based on a combination of botanical characters and size. Folio 194 of the Grandes Heures d’Anne de Bretagne is most likely a Vigna species in the Ceratotropis subgenus. In the Loggia, one set of pods appears to be a species in the Mimosoideae subfamily and the second and third sets of pods most closely resemble Canavalia gladiata. Neither image likely represents common beans and are probably Old-World species. Secondly, illustrations of common beans from ten early herbals were analyzed for traits that are characteristic of the centers of domestication and races of common beans. Our objective was to characterize the diversity observed among herbals and determine whether beans from both centers of domestication were present. We potentially identified both Middle American, race Mesoamerica and Andean, race Nueva Granada types. We posit that both Middle American and Andean types were in the Caribbean at the time of the Columbian exchange and that beans from both centers were informally introduced into Europe early on. This review of 16th-century manuscripts and illustrations has provided some answers to the questions of what and when common beans reached Europe and provide new hypotheses for researchers studying the origins, diversity, and distribution of this crop.Common bean ( Zea mays), squash (Cucurbita spp.), and beans (Phaseolus spp.). The 4th of November 1492 entry in Columbus’ navigation journal (Vigna unguiculata) whereas “habas” was probably the larger, flatter-seeded lima bean that is more similar in size and shape to broad beans (Vicia faba)  . A seconia faba) .There are many questions about the introduction of New World beans into Europe including when and where were they introduced and where did they come from? What were the characteristics of these beans? What center of domestication did they represent? Some of these questions can be investigated by examining the iconography of the food crops produced after the Columbian exchange began.The first definite evidence of the introduction of common beans into Europe is found in the mid-16th century. This is roughly 40 years after the Columbian exchange began, so it is not clear exactly when it was introduced or how quickly it diffused through Europe after 1492.Prior studies of the first images of New World Vegetables in Europe have focused on maize and squash . Maize iPhaseolus species out of a genus of about 70 species that must be considered in the context of the introduction of New World grain legumes into Europe. The other domesticates are tepary bean (Phaseolus acutifolius), runner bean (P. coccineus), year or year-long bean (P. dumosus), and lima bean (P. lunatus). P. vulgaris, P. acutifolius, P. coccineus, and P. dumosus (formerly P. polyanthus) belong to the Vulgaris group within sister clade B whereas P. lunatus in the Lunatus group is more distantly related (vulgaris), the common bean was and is the one most widely distributed throughout North and South America. It is a predominantly autogamous annual adapted to moderate temperatures and precipitation. Of the other domesticated Phaseolus species, these have a combination of more specific environmental adaptation and a limited region of production. P. dumosus (year or year-long bean) is highly photoperiod sensitive and is rarely seen outside of a narrow zone in the cool, humid tropical highlands of Guatemala. Likewise, the distribution of P. acutifolius (tepary bean) is restricted to the hot and dry environments of northern Mexico and the southwest United States. Two species showing wider distributions and more likely to have occurred with common beans in the Latin America-Caribbean region at the time of the Columbian Exchange are lima beans and runner beans. Runner bean is a predominantly allogamous perennial species with tuberous roots that is adapted to the cool and humid tropical highlands  as well as general adaptation to warm and humid tropics. The two gene pools differ in that the large-seeded Andean “Big Lima” types were traditionally found along the mid- to southern Andes above 1,600 masl whereas the small-seeded types were found along the northern Caribbean coast and valleys of South America below 1,200 masl , the material may be arranged for aesthetic rather than documentary purposes, and the objects in an illustration may not be all be of the same scale.De Historia Stirpium, and have been suggested to be the earliest images of common beans in Europe (Grandes Heures d’Anne de Bretagne (Book of Hours of Anne of Brittany)   and the rittany) . An objeGrandes Heures d’Anne de Bretagne is catalogued as Ms. Latin 9474 at the Bibliothèque Nationale de France and can be viewed online in its entirety , Welch-, Welsch-, or Welsche-Bonen, Phaseolus (German), and Faba or Haba, Frijol, Frijole, and Faxones (Spanish).In the last decade, a number of old European herbals from the 15th century onward have been digitized and made publicly available. We systematically searched for digitized herbals of the prominent herbalists of the 16th century, using Whereas most other vegetables and fruits are morphologically distinct, many legume pods look superficially similar, and distinguishing the pods of various cultivated large-seeded grain legumes can be problematic. If pictures are sufficiently detailed and enough plant parts are visible, then identification at least to the genus level is possible. Our approach to analyzing the images was to first determine the size of the images, then thoroughly describe the material, looking for key diagnostic features. We subjected pods to analysis using the Intkey Legume Fruits and Seeds electronic-based key . Genus-sPhaseolus spp., and not Vigna or Dolichos spp. Unlike the Grandes Heures d’Anne de Bretagne or Villa Farnesina images, morphometric scaling was not possible but images were compared for the relative size of plant parts , colors of flowers and seeds, as well as growth habit and various morphological characteristics. To distinguish Phaseolus species from other grain legumes, we looked for the absence or greatly reduced stipules, the presence of stipels on the petiole, absence of a prominent calyx, and presence of bracteoles attached to the base of the corolla. The domesticates from the Middle American and Andean centers of domestication are morphologically distinct, and morphology can help separate the three Andean and four Middle American races. Cultivars within races share certain morphological characteristics which can be used to differentiate them from other races  often borrowed illustrations from other authors and these were sometimes mixed with new and original ones. This is particularly the case with Fuchs’ herbals where a number of authors reused his woodcuts . We initGrandes Heures d’Anne de Bretagne was illustrated in Tours, France between 1503 and 1508 and shortly after the discovery of the New World. Many pages contain a prayer surrounded by a vertically oriented image of a plant with some animals present. Over 300 species of plants are depicted and include examples of native flora from the Touraine region in northwestern France as well as ornamental and food plants from the Royal Gardens of Tours and Blois  Duchess of Brittany and twice queen of France, commissioned the artist, Jean Bourdichon (1457–1521), to create a prayer book for her personal use . The Grand Blois . The aniGrandes Heures d’Anne de Bretagne was described by P. vulgaris. The image is in a reverse C shape surrounding the text, with the inscription in Latin “Faberole” above, and the vernacular French “Faverolles” below the image  are quite accurate and easily recognizable. Perhaps the artist was unable to see the plant in all stages of its lifecycle and borrowed from other legume species to fill in the blanks. The lack of conspicuous stipules on the stems is consistent with Phaseolus, but also with some Old World species. A lack of stipels on the leaves would argue against Phaseolus, but this detail is often left off in illustrations of this species. The presence of a prominent calyx and the absence of bracteoles also argue against Phaseolus. The exaggerated bumpiness over the ovules in the pods is not consistent with any cultivated grain legume. For some traits, there appears to be a blending of characters from different species. The trifoliate leaves and determinate habit are consistent with both Phaseolus and Vigna spp., but the flowers, pods, and glabrous vegetative appearance more closely resemble that of Pisum sativum rather than any warm-season legume. None of the cultivated Phaseolus species have yellow flowers; rather, they are white to purple in color. Among grain legumes, only those species belonging to the subgenus Ceratotropis of the genus Vigna possess solid yellow flowers. These include cultivated Asian species Vigna aconitifolia, V. angularis, V. glabrescens, V. mungo, V. radiata, and V. umbellata). The flowers and pods of V. angularis (adzuki bean) are shown in Overall, the image depicted in Folio 194 is not completely consistent with any single grain legume species. This is somewhat surprising because other grain legumes depicted in the Grandes Heures d’Anne de Bretagne specimen keys out to the genus Vigna , the us Vigna . Assumin legumes . The oneConstruction for the Villa Farnesina was initiated in 1505 for Angostino Chigi, a wealthy and well-connected financier. The interior was decorated between 1515 and 1518 . On the Vicia faba in association with pods are also present. None of the legume pods appear to have leaves of that species associated with them. Cucumis melo fruit in the festoons to the right of the panel showing Cupid with the Attributes of Jupiter  which illustrates various seed colors , the plant is named Ayecohitli but a second image in the Codex  shows P. coccineus with the name Cimatl . While V. unguiculata may also be considered a candidate, it belongs to the subgenus Vigna and accessions of this subgenus have white to pink flower colors. Yellow nectar guides may be found on the banner petal, but solid yellow flowers are not found within this subgenus. The illustration may have been painted without the benefit of the fresh plant material, or another yellow-flowered legume species may have been used as a model to flesh out the memory of a particular grain legume for which a living material was unavailable. Assuming that Folio 194 was based on a real plant, and is not a chimeric mix of various legume species, the best candidate is a subgenus Ceratotropis Vigna species.Folio 194 of the vulgaris . Apparenvulgaris , and BonCucurbita pepo, C. moschata, and C. maxima) were illustrated. Although we agree that Cucurbita species are present in the Loggia, we question whether C. maxima was present as it was unlikely to have been found in the Caribbean at the beginning of the Columbian exchange  were growing concurrently in the Caribbean. Encounters by explorers with P. coccineus would have been less likely because this species is adapted to cooler tropical production zones, and would most likely have been only grown at high altitudes in Latin American and interior uplands on the Caribbean islands. In addition to common beans, lima beans were prevalent in the Caribbean because of their adaptation to the hot, humid lowland tropics. Both species would have been taken back to Europe, but common bean would have been better able to transition to a new temperate environment at a higher latitude  small-seeded beans found on the islands of Cuba and Hispaniola will be most closely related to small-seeded accessions from Mesoamerica and not to those from northern South America and Brazil. (2) Large seeded Nueva Granada landraces from the Caribbean will be most closely related to landraces from Spain and Portugal, with a gradient of increasing genetic distance as one moves east and north across Europe. (3) Landraces of Italy will show the greatest affinity to those from the western slopes of the Andes and not the Caribbean. (4) Beans may have been introduced into Africa directly from the New World through the slave trade as well as indirectly from Europe. A caveat is that repeated introductions may obscure the relationship between regions, but utilization of the oldest landraces may be able to overcome this obstacle.The original contributions presented in the study are included in the article/JM and JJ conceived of the manuscript. JM conducted the analysis of images and wrote the first draft of the manuscript. JM, AF, and JJ researched the topic, obtained historical documents, contributed to revisions of the manuscript, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The survey included basic sociodemographic questionnaire and validated Hospital Depression and Anxiety Scale. And was distributed via the Internet. The results were statistically analyzed. High school degree was the most commonly held education (46%), large city was the most popular place of living (33%) and majority of the respondents have a full-time job (53%). Only 19% of the respondents consult their doctor or pharmacists about taking CBD. On the group of psychiatric patients, only 49% of respondents tell their psychiatrist about using the compound. Psychiatrists should be aware of CBD use in their patients during their daily practice, as CBD use can be found within people from all walks of life, and due to public interest, there is a need for education and research on the efficacy and safety of CBD use for mental disorders.Cannabis sativa, whose flowers are also known as marijuana or marihuana, is a recreational plant that contains many chemicals that are constantly being studied by scientists around the world. One of these substances is cannabidiol (CBD), which has gained widespread popularity on the internet as a cure for mental health problems, leading many people to use CBD to self-treat depression and anxiety. This article presents an exploratory cohort study ( Cannabis sativa, commonly known as marijuana or marihuana, is a plant with psychoactive properties used primarily for recreational purposes. However, in recent years, numerous studies have been conducted that have found its beneficial effects in the treatment of many diseases . MarijuaCBD appears to be relatively safe substance in preliminary studies, but there are several side effects that should be mentioned. CBD is one of the better tolerated substances compared to THC, mainly due to its lower addictive potential . In the The public is very interested in natural methods to treat depression. Scientists are focusing on the study of dimethyltryptamine (DMT), a psychedelic substance found in many plants, and psilocybin, a psychedelic that occurs naturally in mushrooms such as psilocybin cubensis . The popThe study was designed by psychiatrists from the Department of Psychiatry at the Medical University of Silesia in Katowice and was conducted according to the guide-lines of the Declaration of Helsinki and Good Clinical Practice. It included 23 questions in Polish in the areas of: general sociodemographic parameters, general psychiatric interview of patients, questions related to CBD intake: frequency, dosage and form of consumption, improvement of wellbeing after CBD intake and additionally included the Hospital Anxiety and Depression Scale (HADS) questionnaire. The HADS is one of the most widely used self-assessment questionnaires for screening anxiety/depression symptoms and focuses mainly on the cognitive and psychological aspects. It is used in both the general medical population and the healthy population. The HADS consists of a total of 14 items on 2 separate subscales: Anxiety (HADS-A) and Depression (HADS-D), and the total score ranges from 0 to 42 points. Currently, the categorization system includes several groups: 0–7, normal; 8–10, mild; 11–15, moderate; over 16, severe . Qualitative variables were tested using the chi-square test. The Shapiro-Wilk test was used to check whether quantitative variables conformed to the normal distribution. The test revealed that not all variables conformed to the normal distribution. In case of non-normal distribution, Mann-Whitney U test was used to compare two independent groups, while Kruskal-Wallis test was used to compare multiple independent samples. Spearman's rank order correlation test was used to test the relationship between the variables. Statistical significance was assumed at We collected 90 correctly completed questionnaires from the respondents. The study comprised a group of males and females of comparable size who did not differ significantly in age, education and type of occupation. One person reported being non-binary and was excluded from the statistical analysis. The youngest respondent was 16 years old and the oldest was 69 years old. High school degree was the most commonly held education (46%), large city was the most popular place of living (33%) and majority of the respondents have a full-time job (53%). Majority of the respondents claim that they either trust or probably trust the psychiatrists. The detailed characteristics of the study population are shown in Majority of the respondents were or still are treated by a psychiatrist (55%) and started using CBD for depressed mood (69%). The most commonly consumed other psychoactive substance was caffeine (47%). Only 19% of respondents consulted a doctor or pharmacists about taking CBD, and most respondents (59%) consume CBD daily. Majority of the respondents (57%) are currently under the supervision of a psychiatrist and a little over half (51%) do not tell their psychiatrists about their use of CBD. Majority of respondents said they felt better after CBD treatment (86%). The detailed characteristics of CBD use for self-treatment of mental disorders are shown in 2 =; 6.19 p = 0.01; chi-square test). Among the psychiatric disorders treated, men were significantly more likely to be diagnosed with anxiety disorders . No significant difference was found between genders for the other disorders. Women were significantly more likely than men to take CBD due to insomnia  and energy depletion ; chi-square test). Men were significantly more likely than women to use THC  and alcohol .Women were more likely to be diagnosed or treated by a psychiatrist compared to men . Respondents most frequently purchased CBD from online stores, while the most common form of CBD consumption was CBD oil, which was significantly more frequently consumed by women .Men were significantly more likely than women to learn about CBD from the Internet, while women learned from friends and family . There were no significant differences between genders in frequency of use, amount of dose taken, or reported improvement in wellbeing after taking CBD.The older the individuals were, the more frequently CBD was consumed (Majority of the respondents (53%) claim that CBD made them feel overall better and 88% of the respondents would more likely take CBD than a prescription drug from a psychiatrist. r = −0.22; p < 0.02; Spearman's rank-order correlation). There was no correlation between reported improvement in wellbeing after CBD use and: (1) frequency of CBD use, (2) amount of CBD dose taken, or (3) form of CBD use.Out of respondents who are or were treated by a psychiatrist, the most commonly drugs prescribed were selective serotonin reuptake inhibitors (16%). r = −0.27; p < 0.01; vs. HADS-D: r = -. 26; p < 0, 01; Spearman's Rank-Order Correlation). A very strong correlation was found be-tween scores on the HADS Anxiety subscale and the HADS Depression subscale .The greater the reported improvement in wellbeing after CBD use, the lower the HADS score in both subscales , while in the case of the HADS sub-scale, 47% exceeded this cut-off point.93% of the respondents did not observe any negative effects of CBD consumption. Two respondents reported the occurrence of anxiety disorders during therapy, while 1 respondent reported the following symptoms: depressed mood, addiction, diarrhea, xerostomia.p < 0.0001; Mann Whitney U test).Only 17% of respondents reported that they were currently taking psychotropic drugs. This group is too small to perform a statistical analysis using the above statistical tests. 49% of respondents admit to having taken the above drugs in their lifetime. Individuals who admit to taking psychotropic drugs in the past are significantly more likely to trust psychiatrists . Scores on the HADS anxiety and HADS depression subscales were significantly lower among psychiatrist-untreated respondents . Nicotine use was significantly more common among psychiatric patients , while THC use was more popular among the untreated . Patients who did not receive psychiatric treatment were significantly less likely to consult a physician or pharmacist about CBD . There was no significant difference between groups in terms of: Frequency, dose and form of CBD use, age of respondents, reported improvement in wellbeing after taking CBD, use of alcohol, caffeine, psychostimulants and hallucinogens.A comparison was made between the groups of respondents divided into diagnosed/treated psychiatry and under-diagnosed/untreated psychiatry. Non-treated respondents were found to have significantly lower trust toward psychiatrists , with different levels of education, and living in both rural and urban communities, which means that the use of CBD for self-treatment of depression is not limited to certain social groups. This information may be useful in further planning of scientific and educational activities in this area.When analyzing the above responses, it should first be noted that only 19% of respondents consulted their doctor or pharmacist about taking CBD. At the same time, in the group of psychiatric patients, only 49% of respondents informed their psychiatrist about the use of CBD during psychiatric treatment. This situation is potentially dangerous because when patients buy CBD outside the pharmacy, this sale escapes the control of the pharmaceutical regulatory authority, which may encourage the accidental ingestion of other substances than intended, because when sales are outside the control of pharmaceutical regulators, consumers need to trust the honesty of the sellers. The situation of physicians and pharmacists being informed by the patient of the use of a psychoactive substance that is not an approved drug for the condition being treated is also extremely difficult. Categorical prohibition is unlikely to be effective, but it will limit the patient's honesty at subsequent visits, and acceptance of this state of affairs means that the patient accepts responsibility-at least in part - for the possible adverse effects of taking a psychoactive substance. The situation of physicians and pharmacists will not improve until they have accurate knowledge of the effects of CBD in various clinical situations and of interactions with the most common psychotropic drugs. There is an urgent need to complete this knowledge.An important element in the mystery of the CBD phenomenon is the chemical composition of the oil itself or the dried fruit you buy. You should keep in mind that in addition to CBD and other cannabinoids, there are substances from other chemical groups, such as terpenoids, flavonoids, and alkaloids. It is possible that these substances may have an impact on the patient's wellbeing . It is iAs mentioned in the introduction, the media is eagerly interested in the topic of using CBD to treat depression, and society is picking up on the topic in social media. In public discourse, healthcare professionals should stick to facts. There is not enough data to conclusively confirm or rule out the claim that CBD is useful in treating mental illness. Given the social aspect of CBD use, further research by interdisciplinary teams made up of psychiatrists and pharmacists seems well warranted.The responses collected shed light on another aspect. When planning further research on the use of CBD to improve symptoms of depressive disorders, it is important to pay attention to validated instruments that help in the diagnosis of depression. The responses to the question about reasons for starting CBD use may suggest that although we asked about self-treatment of depression, and this was clearly explained in the survey instructions and in the first question, some of the public may not fully understand the nature of this disorder. Patients could be suffering from major depressive disorder or mixed depression-anxiety disorder, and since it makes a difference in terms of the proper medical solutions offered byphysicians, it may not make a difference to patients. They might just call both disorders “depression,” whereas according to our HADS-A and HADS-D results, anxiety is actually more prevalent in our study group. Differentiating the causes of depressive disorders on the basis of the currently used International Statistical Classification of Diseases and Related Health Problems will make it possible to reduce methodological errors, contribute to a more rapid resolution of scientific problems and avoid inaccuracy in providing data to other scientists.This study is probably the only study to examine the extent of self-treatment of depression with CBD, but it is not free of limitations. The data was collected during COVID-19 pandemic, which could have an impact on the respondents wellbeing in terms of depressive and anxiety symptoms. Due to anonymity of the study, the study was anonymous and was not prospective, therefore, we could not explain if CBD actually helps people who use the substance. The survey was conducted over the Internet, which limits the ability to rule out respondent error in completing the survey and prevents intentional bias from being ruled out. A small group of respondents does not allow for indepth statistical analysis and it is not necessarily representative for the population; furthermore, the selection of the group depends on activity on the Internet. However, the exploratory nature of this study provides solid justification for further research and analysis in this area.Psychiatrists should be aware of CBD use in their patients during their daily practice, as CBD use can be found within people from all walks of life for self-treatment of depression due to depressed mood. Due to public interest, there is a need for education and research on the efficacy and safety of CBD use for mental disorders.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.GW: conceptualization, project administration, and visualization. GW and MS: methodology and software. GW and RP: validation and writing—review and editing. GW, IS, and MS: formal analysis, investigation, and writing—original draft preparation. GW and IS: resources. MS: data curation. PG and RP: supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cytoplasmic ribonucleoproteins called stress granules (SGs) are considered as one of the main cellular solutions against stress. Their temporary presence ends with stress relief. Any factor such as chronic stress or mutations in the structure of the components of SGs that lead to their permanent presence can affect their interactions with pathological aggregations and increase the degenerative effects. SGs involved in RNA mechanisms are important factors in the pathophysiology of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and Alzheimer's diseases (AD). Although many studies have been performed in the field of SGs and neurodegenerative disorders, so far, no systematic studies have been executed in this field. The purpose of this study is to provide a comprehensive perspective of all studies about the role of SGs in the pathogenesis of neurodegenerative disorders with a focus on the protein ingredients of these granules. This scoping review is based on a six-stage methodology structure and the PRISMA guideline. A systematic search of seven databases for qualified articles was conducted until December 2020. Publications were screened independently by two reviewers and quantitative and qualitative analysis was performed on the extracted data. Bioinformatics analysis was used to plot the network and predict interprotein interactions. In addition, GO analysis was performed. A total of 48 articles were identified that comply the inclusion criteria. Most studies on neurodegenerative diseases have been conducted on ALS, AD, and FTD using human post mortem tissues. Human derived cell line studies have been used only in ALS. A total 29 genes of protein components of SGs have been studied, the most important of which are TDP-43, TIA-1, PABP-1. Bioinformatics studies have predicted 15 proteins to interact with the protein components of SGs, which may be the constituents of SGs. Understanding the interactions between SGs and pathological aggregations in neurodegenerative diseases can provide new targets for treatment of these disorders. Cell function is divided between the organelles sited inside the cell. Based on the presence of lipid membrane, organelles can be divided into main two groups. Nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus are the major membranous organelles. Membraneless organelles are ribosomes  have the ability to phosphorylate the α subunit in the eIF2 factor  used in search strategy if available. PubMed and Embase related search strategies are shown in Studies in neurodegenerative diseases in relation to SGs in humans or in human-derived cell lines were screened from publications obtained during the search process. All types of publications were reviewed, including journal articles, conference presentations, conference abstracts and reports. Non-English articles with English abstracts were also included. Screening was done in two stages. At first, both researchers  screened articles separately based on title and abstract, according to the inclusion criteria mentioned above. In the next step, full texts of the selected articles were investigated to measure its relevance to the research question. Finally, appropriate articles were selected based on the eligibility criteria. Any contradiction was resolved in agreement with the opinion of the third person.Two separate charts were designed for human samples and human-derived cell lines in Microsoft Excel to help extracting the data. Chart related to human sample articles included author's name, year of publication, diagnosed neurodegenerative disease (number of patients), age and country, sample and method of analysis, protein component of SGs and major findings. The chart related to human-derived cell lines articles included the author's name, year of publication, origin of cell lines, age at biopsy, country, sample, method of analysis, mutation, and major findings. Two researchers  separately extracted data from articles based on charts.Quantitative and qualitative analysis was performed on the data obtained from the publications. In the quantitative analysis section, a descriptive numerical summary of the extent, nature and distribution of the studies were reviewed. In the qualitative analysis section, based on the research question mentioned earlier, a narrative review was performed on the available information with affirmation on the broader context suggested by Levac et al. .p < 0.05.Two disease-protein interaction networks were designed using Cytoscape v3.8.0 software , and with progressive loss of upper MNs (UMN) in the motor cortex of the brain and lower MNs (LMN) in the brain stem and the spinal cord , product of the TARDBP gene, plays the largest role in the formation of pathological aggregations. Most of the changes observed in this protein in aggregations include phosphorylation  is present in pathological aggregations with a lower percentage than TDP-43 and its association and effects on SGs have been studied. The mechanism of FUS toxicity is not fully understood, but due to its cytoplasmic localization, loss of nuclear activity and acquisition of cytoplasmic function might be involved  is another common mutation in ALS that is associated with an increase in the number of G4C2 repeats in the C9orf72 gene. The number of repeats in normal people are between 20 and 30, but in people with mutations, the number of repeats increases to hundreds   (Mori et al., FTD is one of the most common types of dementia that affects people under the age of 65 (Bird et al., AD is a chronic neurodegenerative disease that is accompanied by death of neurons and loss of synapses in the cerebral cortex and certain subcortical regions of the brain (Tiraboschi et al., Tau can act as a negative regulator of protein translation by binding to ribosomes and reducing protein synthesis (Meier et al., MS is a demyelinating disease in which the cover of nerve cells in the brain and spinal cord is damaged (Noyes and Weinstock-Guttman, GO classifies relationships between genes by annotating and categorizing them into three levels: biological process, molecular function, and cellular component. Biological process describes the cellular or physiological role performed on a larger scale by a gene in relation to other genes. The molecular function describes the molecular activity of the desired gene, and the cellular component determines where the gene product executes its function (The Gene Ontology Consortium., Equilibrium is the most important point in SGs. SGs are in the nature of the cell and are considered as cell solutions to stress. They are temporary constructions and when the stress is relieved, they are disassembled and reduced in number, and the cell condition returns to normal. If under any circumstances the presence of SGs becomes permanent and leads to disequilibrium, in interaction with pathological aggregations such as TDP and FUS aggregations, they can lead to pathological conditions such as neuron degeneration. SGs have been studied in many neurodegenerative diseases in humans, including ALS, FTD, AD, and MS. These studies have indicated common features in SG biology among neurodegenerative diseases. At least 15 proteins have been predicted to interact with the protein components of SGs in mentioned neurodegenerative disorders. Therefore, it seems that SG biology is common between these disorders. Yet, some components of SGs might be specific to these disorders. Based on the rarity of comparative analysis between these disorders, it is not possible to male conclusive interpretations in this regard. We have tried to provide a comprehensive summary of these studies and an overview of SGs in neurodegenerative diseases. To conclude, more studies can be done in diseases such as AD and MS and the association of the Tau protein with other protein components of SGs or the association of inflammatory pathways with the formation of SGs could also be assessed.MT, SG-F, and MR wrote the manuscript and contributed in study design. MA, MS, HS, and AJ contributed in the data collection, designed the tables and figures. All authors approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The Republic of Burundi first reported cholera cases in 1978 and outbreaks have been occurring nearly every year since then. From 2008–2020, 6949 cases and 43 deaths were officially reported. To evaluate Burundi’s potential to eliminate cholera, we identified hotspots using cholera incidence and disease persistence as suggested by the Global Task Force for Cholera Control. The mean annual incidence for each district that reported cholera ranged from 0.29 to 563.14 cases per 100,000 population per year from 2014–2020. Ten of 12 Health Districts which recorded cholera cases reported a mean annual incidence ≥5 per 100,000 for this time period. Cholera cases occur during the second half of the year in the areas near Lake Tanganyika and along the Ruzizi River, with the highest risk district being Bujumbura Centre. Additional research is needed to understand the role of Lake Tanganyika; risks associated with fishing; migration patterns; and other factors that may explain cholera’s seasonality. Due to the consistent epidemiological pattern and the relatively small area affected by cholera, control and elimination are feasible with an integrated program of campaigns using oral cholera vaccine over the short term and community-based interventions including WASH activities for sustained control. The Republic of Burundi is a landlocked country in the Great Lakes region of Africa which has outbreaks of cholera regularly every year. It lies between Rwanda to the north, Tanzania to the south and east, the Democratic Republic of the Congo (DRC) to the northwest, and Lake Tanganyika to the southwest. The Ruzizi River , which flows into Lake Tanganyika from Lake Kivu, serves as the border between the DRC and Burundi. The capital of the country, Bujumbura, is located near the northern part of Lake Tanganyika. The total land area is 27,830 sq km, and the country is divided into 18 provinces which are further divided into 47 districts and 119 communes. The smallest subdivision is the colline, of which there are 2638.Some of the factors in Burundi that relate to cholera patterns include seasonality, population density, insufficient water-sanitation infrastructure, considerable internal and external migration, poverty, and the relationship of people to Lake Tanganyika.Burundi has two rainy seasons, a major one from February to May and a lesser one between September and November. The dry seasons are from June to August and December to January. Minimum monthly temperatures appear to be constant throughout the year, but higher maximal temperatures occur from July to October .While the country is geographically small, it is among the top five most densely populated countries in Africa with 463 inhabitants per square kilometers . It has Indicators of water and sanitation for Burundi demonstrate the need for major improvements. According to the Joint Monitoring Project of the WHO and UNICEF , 20% of Burundi has a long history of both natural disasters and civil conflict, both of which have contributed to its high degree of migration. Within Burundi, people are often displaced because of natural disasters such as landslides, flooding and high winds . When peMigration to and from neighboring countries arise due to violent conflicts, but sometimes are related to the search for employment. As of 31 January 2021, 306,000 people have fled Burundi , with over half of the refugees traveling to Tanzania 148,000) and many others traveling to Rwanda , the DRC , and Uganda  [,000 and V. cholerae was isolated from the water of Lake Tanganyika and cholera cases were associated with exposure to or drinking lake water in case control studies [Lake Tanganyika plays a critical role in the life and economy of Burundi. The lake is an extremely large, deep, freshwater lake with an alkaline pH pH 8.5–9); the surface temperature ranges between 25 and 28 °C ; the sur without  studies . In East and Central Africa, Burundi is one of the countries where cholera is endemic. Burundi first reported cholera cases to the World Health Organization (WHO) in 1978 and cases have been reported in Burundi every year, except during 1986–1989 . CompareCholera cases that were reported to the World Health Organization (WHO) from 2008 through 2018 are shown in Vibrio cholerae O1 or O139 (Serotype O139 has never been isolated in Burundi). Generally, the National Reference Laboratory in Bujumbura is the laboratory that confirms the case. One case of suspected cholera signifies the alert threshold, while a case must be confirmed before declaring an outbreak, signifying the “action threshold.” The first ten suspected cases are to be cultured, but after one or more are culture-confirmed, it is not necessary to confirm each case.Cases of cholera, both suspected and confirmed, are recorded using Burundi’s Integrated Disease Surveillance and Response (IDSR) system . AccordiThis epidemiological analysis is intended to provide an overview of the burden of cholera. A principal objective of this analysis was to identify cholera hotspots in Burundi since these are the areas where interventions should focus. A secondary objective was the identification of other factors that may assist in informing intervention and cholera control decisions. Per the GTFCC guidance on developing a national cholera control plan, countries should conduct a situational analysis to include an assessment of the country’s cholera epidemiological situation. This includes the review of historical cholera burden data to identify cholera hotspots and to review contextual factors of hotspots, including population mobility, vulnerability, weather patterns, access to WaSH, among potential other contextual factors . BurundiWeekly reported suspected cholera case data from Burundi for the years 2014–2020 were obtained from the IDSR surveillance system conducted by the Ministry of Public Health of Burundi (MOPH). Cholera cases are reported at the Health District level. Burundi is divided into 47 Health Districts, and each Health District consists of 2–4 communes. The names of these Health Districts were matched with the names in the reference mapping file. The duration of each outbreak was calculated by comparing the start and end week of reported cases in each Health District. Outbreaks that might have continued across Health District borders were considered as two separate outbreaks.The population data were obtained at the commune level from the most recent census, in 2008. Although the population has increased since then, we assumed this growth was occurring at a similar rate in the different commune . The Heahttp://geokov.com/education/utm.aspx, accessed on 16 February 2021). Data for cholera hotspots were analyzed using the second administrative boundary level as the geographic unit of analysis.The Health District boundary map of Burundi was obtained from the United Nations Office for the coordination of Human Affairs. The maps were projected in WGS84 UTM coordinates system Zone 37S , which is based on the mean annual incidence of cholera cases and the persistence of the disease . IdeallyThe end of a discrete outbreak is defined, per the GTFCC, as the point when two weeks have passed with no further suspected cases . PersistEthical Considerations: As this study only uses secondary, aggregated, de-identified data, the Ministry of Public Health of Burundi determined that ethical approval was unnecessary. Additionally, the IRB at the Johns Hopkins Bloomberg School of Public Health Institutional Review Board determined that this activity was exempt.Cholera cases were reported every year between 2008 and 2020. Over this 13-year span, 6949 cases and 43 deaths were reported. A more detailed analysis was conducted for two five-year periods for which we had data at district level to facilitate the use of the GTFCC tool. The 7 years of total data were divided into two 5-year periods of analysis, overlapping in years 2016–2018, but facilitating the assessment of whether the hotspots were consistent over time. From 2014 to 2018, 575, 423, 434, 344, and 92 cases were reported for these years, respectively, for a total of 1868 cases and 14 deaths. The second analysis was from 2016–2020, during which 1195 cases and 3 deaths, and 139 cases and 1 death, were reported in 2019 and 2020, respectively. These cases were reported from 12 Health Districts, all on the western side of the country near Lake Tanganyika, or along the Ruzizi River near the border with the DRC.Cases occurred during discrete outbreaks within individual districts experiencing from one to eleven such outbreaks during the 7 years (median of 4.5 outbreaks). The outbreaks lasted from 1 to 24 weeks, with most lasting fewer than 3 weeks. The distribution of the number of outbreaks per district is shown in The weekly number of cases during the surveillance period showed a seasonal pattern, with most cases occurring during the second half of the year . The patCholera occurred annually in Burundi during the timeframe of this analysis . The meaOf 12 Health Districts that reported cholera, ten reported a mean annual incidence ≥5 per 100,000 during the time period of 2014–2020. The cutoff values for determining the magnitude of the cholera risk include applying the median annual incidence  and the median proportion (percentage) of weeks with cholera, defined as persistence (8%), among the nine districts included in the analysis for 2014–2018. For the time period of 2016–2020, the median annual incidence was 13/100,000 and persistence was 5% among the nine districts included in the analysis for this time period. The districts reporting cholera were subsequently grouped into high, medium, and lower risk among the identified hotspots according to the criteria in When applying the combination of the two cutoffs in This analysis demonstrates that cholera occurred every year in Burundi from 2014 through 2020 and the hotspot pattern proved to be consistent during the period 2014 to 2020. Although there was some variability between the districts in their rank order, the same areas along Lake Tanganyika and along the Ruzizi River, bordering the DRC, were the districts which reported cholera. Other parts of Burundi away from the Lake or the River rarely reported cholera. The designation of high, medium and lower risk hotspots are designations suggested by the GTFCC, and national policy makers will use this information, along with other factors, as they develop plans for cholera control.Since cholera was first reported in Burundi in 1978, it has remained consistent with very few exceptions. The regular pattern of yearly outbreaks is highlighted further by the striking seasonal pattern in which cholera outbreaks start in the second half of the calendar year and by the consistent locations where the outbreaks occur. The outbreaks occur along the edge of Lake Tanganyika or north of the Lake along the Ruzizi River, which forms the border with the DRC. During these outbreaks, several hundred cases are reported. These numbers are smaller than the numbers of cases in neighboring countries with much larger populations, such as the DRC or Tanzania, but they do constitute a great threat to the people of Burundi. Cholera outbreaks require many resources and require the need for very rapid and vigorous response limited health workers to avoid cholera deaths. The two time periods of hotspot analysis identified three of the same Health Districts with consistent high priority risk, with a fourth identified in the 2014–2018 time period which remained medium risk in the most recent time period. Both analyses identified additional Health Districts with heightened risk but at a somewhat lower level. The identification of these districts and the predictable nature of the time and place of the outbreaks provide valuable information with which to focus prevention efforts. Such preventive efforts should, of course, include improving water and sanitation infrastructure. For the short term, campaigns to provide oral cholera vaccine to the people living in the highest risk health districts might quickly eliminate these seasonal outbreaks. As the cholera pattern is so consistent, the effectiveness of the OCV campaigns could quickly be evaluated. Being a relatively small country, this would require vaccinating about 1.6 million people living in the districts at risk, or if one were to be more selective, 728,000 living in the highest risk districts identified in either time period. While the maps identify the districts at highest risk, additional local knowledge should be added to provide a more comprehensive understanding of the actual areas at risk. For example, if cases from Bujumbura Centre are actually from the urban area, specific evaluations may be needed to address municipal water and sanitation needs and also consider the specific neighborhoods from which cases arise.Vaccination campaigns in Burundi would be logistically feasible because the high-risk districts are geographically close to the capital, Bujumbura, where the vaccine could be stored and teams mobilized. The national laboratory is also located in Bujumbura, which simplifies the confirmation of cases following the vaccine campaign; this is important to document the vaccine’s effectiveness.With financial support from GAVI , OCV campaigns have been carried out in several African countries including Malawi ,20,21, UOCV is recommended as a two-dose vaccine with an interval of about 2 to 4 weeks between vaccine rounds. Campaigns using a two-week immunization strategy are possible in Burundi; however, cholera’s unique epidemiology in Burundi suggests consideration of other vaccination strategies. Specifically, the first round should be given prior to the expected cholera season . The second round could be given two weeks later, but another option is to wait until the following May to give the second round. The consideration of a delayed second round relates to the protection provided by a single dose ,28 and tIn addition to using OCV to prevent cholera, enhanced surveillance would improve the understanding of cholera’s epidemiology in Burundi and would be needed to monitor and evaluate the effectiveness of interventions such as vaccine campaigns and WASH improvements. Rapid diagnostic tests (RDTs) are now available that allow the detection of a case within 15 min. If these were made available in the health facilities in the hotspot districts, outbreaks could be detected rapidly, and samples could be sent to the National Laboratory to declare the outbreak even more quickly. The RDTs can then be used to monitor the course of the outbreak while determining the proportion of cases which are true cases and determine when the outbreak is over. Isolates that are detected at the National Lab should be saved so that molecular testing can confirm their relation to isolates from neighboring countries, especially the DRC and Tanzania.Reasons for the consistent cholera season in Burundi were not identified. The association of the hotspots being adjacent to Lake Tanganyika and to the border with the DRC suggests the infection may be transmitted from the DRC where cholera is known to be endemic . During V. cholerae, having an alkaline pH, and V. cholerae has been recovered from lake water in the past during an outbreak. If so, it is possible that the domestic use of lake water may be a vehicle of transmission, but this does not explain cholera’s seasonality in Burundi.Some suggest that a high-risk group are the fishermen who often travel back and forth across the lake. Certainly, fishing villages have been identified as having a higher cholera risk in Uganda  and MalaThe strong seasonality suggests that climate changes may also be related to the timing of outbreaks. During most years, the outbreaks start during the hotter drier months, but then accelerate during the rainy season. It may be that certain climate factors help to initiate an outbreak, but then the rainy season leads to more environmental contamination leading to increased transmission. In endemic areas of Bangladesh and West Bengal, cholera rates have a strong seasonality . Safe water and improved sanitation will be critical for cholera control, and certainly the national indicators for water and sanitation demonstrate the need for much improvement. We did not, however, identify specific WASH indicators that would explain the higher risk observed in the hotspot districts. Nevertheless, if RDT and OCV are used in these districts, increased emphasis for improving safe water and sanitation should focus on these districts. The lack of correlation between WASH indicators and cholera risk suggests that data on these risk factors need to be collected from specific subgroups who have had cholera rather than a representative sample of households in the district, most of whom have not had cholera.V. cholerae. If rapid tests were used in the field, these might detect outbreaks more quickly. Finally, we used population data from the 2008 census, and we assumed that the increase in numbers would be similar in the different Health Areas. Plans for interventions will need to use updated population numbers when determining the requirements for vaccines and for WASH interventions in these Health Districts. This analysis had certain limitations. Since this analysis assumes that each district is distinct, the spread of outbreaks between Health Districts is not easily shown and likely under-estimates the true duration of the outbreaks. In fact, many outbreaks did occur simultaneously in different districts and their duration would have extended if the spread between districts was considered. Secondly, only some of the cases were confirmed; however, this method of confirming initial cases and then counting clinically determined cases is consistent with WHO recommendations. Thirdly, we did not have migration histories of the cases to understand where the infection may have been acquired, nor was DNA from Burundian strains available to determine their relation to strains from the DRC or Tanzania. Fourthly, the analysis of hotspots would have benefited if precise GIS points of the actual cases were available. This would have been especially helpful to differentiate urban and rural cases. Fifthly, declaring an outbreak depends on sending samples to the lab in Bujumbura to confirm Several factors suggest that cholera could be quickly eliminated as a public health problem in Burundi using an integrated program with OCV for the short term and WASH interventions for the longer term. (1) The country and specifically the hotspot districts are of sufficient size to vaccinate in an organized campaign; (2) the hotspot districts demonstrate consistent cholera persistence over an extended time period; and (3) they are geographically close to the capital of Bujumbura, simplifying logistical requirements for OCV campaigns and follow-up evaluations. The GTFCC has set a goal of eliminating cholera from at least 20 countries by 2030, and Burundi should be included on this list. Due to the consistency of cholera patterns, Burundi is unique in that the impact of such an integrated intervention will be apparent very quickly. This epidemiological analysis of Burundi includes the assessment of hotspots and an overview of contextual/risk factors, based on the data available, which may be used in concert with the GTFCC’s framework to update Burundi’s national cholera control plan and plan for elimination .


Children with attention-deficit/hyperactivity disorder (ADHD) are commonly affected by medical illness. The aim of the present study was to explore the risks of contracting respiratory infectious diseases (RIDs), including upper and lower RIDs and influenza, in children with ADHD. We also examined whether methylphenidate has a protective effect regarding the risk of contracting RIDs among children with ADHD who have a history of methylphenidate treatment. Children in the Taiwan Maternal and Child Health Database from 2004 to 2016 were included in the present study. Upper and lower RIDs, influenza, ADHD, age, sex, and records of methylphenidate prescription were identified. A Cox proportional hazards regression model was used to estimate the significance of the risk of RIDs among children with ADHD in comparison with that among children without ADHD after adjustment for sex and age. The self-controlled case series analysis was conducted to examine the protective effect of methylphenidate treatment against RIDs. In total, 85,853 children with ADHD and 1,458,750 children without ADHD were included in the study. After controlling for sociodemographic variables, we observed that children with ADHD had significantly higher risks of upper RIDs, lower RIDs, and influenza infection than did those without ADHD. Among the children with ADHD who had a history of methylphenidate treatment, the risk of contracting RIDs was lower during the methylphenidate treatment period than during the nontreatment period. Children with ADHD had a higher RID risk than those without ADHD. Methylphenidate might reduce the risk of RIDs among children with ADHD who have a history of methylphenidate treatment. Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder and manifests as hyperactivity, inattentiveness, and impulsivity ,2. ADHD Research has shown that children with ADHD have predominantly higher rates of allergic sensitization and allergic rhinitis than the general population, indicating the shared etiology of ADHD and immunological diseases ,16. HoweMethylphenidate is the most commonly used stimulant that is effective for reducing not only the severity of ADHD symptoms and ADHD-related dysfunction ,22 but aThe first aim of this population-based study was to investigate the risks of contracting upper RIDs, lower RIDs, and influenza among children with ADHD in comparison with those without ADHD. We hypothesized that compared with children without ADHD, children with ADHD would be more likely to contract upper and lower RIDs and influenza. The second aim of the study was to examine the effect of methylphenidate on reducing the risk of contracting RIDs among children with ADHD who received methylphenidate treatment. We hypothesized that for the children with ADHD who had received methylphenidate treatment, the risk of contracting RIDs would be significantly lower during the treatment period than during the nontreatment period.The present study included liveborn children with information regarding gestational age at birth in the Taiwan Maternal and Child Health Database (TMCHD), which covered 99.78% of births , from 20In the current study, the primary exposure was the diagnosis of ADHD. Children were identified as having a diagnosis of ADHD if they received more than three outpatient diagnoses of ADHD  or one inpatient diagnosis of ADHD during the study period ,For children with ADHD, we further examined whether they received methylphenidate treatment after ADHD diagnosis according to dispensed prescriptions recorded in the prescribed drug register with the Anatomical Therapeutic Chemical classification of methylphenidate (N06BA04).For all of the children in the TMCHD, the main outcomes included upper RIDs, lower RIDs, and influenza according to ICD-10 and ICD-9 in the 2 test was applied to compare categorical variables and an independent t test was used to compare continuous variables. To determine the risk of incident RIDs in children with and without ADHD, the Cox proportional hazards regression model was applied, with adjustment for age and sex. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to verify the risk and statistical significance of differences in incidence rates of upper RIDs, lower RIDs, and influenza. Children without ADHD served as the reference. An HR value greater than 1 indicated an increased risk of RIDs in children with ADHD compared with those without ADHD. If the 95% CI of the HR included the null value of 1, then no significant difference existed in the risk of RIDs between the groups.For the descriptive statistics, continuous variables and categorical variables were recorded as the mean with standard deviation and frequency with proportion, respectively. To estimate the difference between children with and without ADHD, the Pearson’s χTo determine the beneficial effect of methylphenidate on RIDs, we performed a self-controlled case series (SCCS) analysis for within-individual comparisons. For individuals with ADHD, we divided the entire follow-up period into the nontreatment period and treatment period from the first date of ADHD diagnosis to the end of the research period , and the RIDs were treated as a recurrent event in the SCCS analysis. On the basis of previous studies ,28, the In total, 85,853 children with ADHD and 1,458,750 children without ADHD were included in the study. The characteristics of demographic variables in children with and without ADHD are presented in p < 0.001), with the highest risk noted for influenza. Protective effect of methylphenidate against RIDs in children with ADHD. Based on the SCCS analysis with a conditional Poisson regression model, we discovered that the children with ADHD had lower average risks for upper RIDs , as well as for lower RIDs , influenza , and all types of RIDs  during the methylphenidate treatment period compared with during the nontreatment period . Second, the TMCHD is a database including naturalistic and clinical information, and possible confounding factors could not be controlled for to the same extent as they can be in clinical trials. For instance, prescription of methylphenidate is not randomized to groups of comparison. However, naturalistic studies can include representative individuals, enabling the results to be more reflective of real situations. Third, medication records were based on prescription data rather than actual consumption, resulting in potential misclassification because of common imperfect medication adherence. However, this may have had little impact on our results. Because of the limited drug regulations for methylphenidate and the young age of the children in this study, it is less likely that children who were not prescribed methylphenidate actually consumed it. Instead, it is more likely that children who were prescribed the medication were not adherent to it. In this case, the misclassified effect period should actually be attributed to the non-effect period, which is a bias in favor of nonmedication, and we observed a significant protective effect of methylphenidate against RIDs; thus, the true effect of methylphenidate should be more profound.The present study reveals that children with ADHD have increased risks of contracting upper RIDs, lower RIDs, and influenza compared with those without ADHD. Regular treatment with methylphenidate is beneficial for reducing the risk of RIDs among children with ADHD. Establishing adequate interventions for infection control among children with ADHD is crucial, such as hygiene education, proper behavioral modification, and adjustments to school environments for social distancing purposes. Moreover, parents can adopt specialized parenting strategies to reduce the defiant and disruptive behaviors of children with ADHD, as recommended by the European ADHD Guidelines Group for preventing the spread of COVID-19 . The res


According to official statistics in Iran, there were 17000 fatalities in road traffic crashes in 2018 that 25% of all crash fatalities belong to pedestrians. In most of the researches related to pedestrians’ safety, one aspect of the traffic crash (e.g. the injury or crash severity) is almost considered for the investigation. In order to perform a complete study of the crash, accident size can be utilized which involves different aspects of the crash. Accident size is described in terms of the number of fatalities and injured individuals and the number of dam-aged and involved vehicles in a crash. According to the fact that accident size has multiple indicators and it is not measured directly, traditional methodologies cannot be applied. So, in the present study the effective factors on the accident size of pedestrian crashes are investigated through structural equation modeling. For the purpose of this study, 3718 pedestrian-involved crash data occurred in Isfahan province is used for the modeling. The independent variables are weather conditions, road surface conditions, time, horizontal and vertical alignments, road type and location, driver’s gender and age, vehicle type, pedestrian’s age, gender and clothing color.The results indicated that highways, the pedestrians’ invisibility, female and old-aged pedestrians, heavy vehicles, old-aged and female drivers are related to the increase of the accident size in pedestrian crashes. These results denote that the mentioned variables are associated with the higher number of injuries, fatalities, the higher number of involved and damaged vehicles in a crash.Present study shows the importance of considering safety improvement measures in highways, educating the people in the society about the traffic safety, the separation of pedestrian and motor vehicle traffic flow and considering the old people in policies and programs for mitigating the accident size. Among these statistics, pedestrians show noticeable susceptibility in severe crashes that approximately 25% of all crash fatalities belong to them. Because of their light and fragile bodies and low travel speeds, pedestrians involved in collisions are at a definite disadvantage relative to drivers or vehicle occupants.2 The investigation of influential factors on crashes enables engineers to carry out calculations in order to reduce crash severity3 which is an essential process in pedestrian crashes.Pedestrians are among the most vulnerable road users who often experience serious injuries in traffic crashes.2 which involves one aspect of the crash. However, other aspects of the crash such as the number of involved vehicles and the number of damaged vehicles can also be the representatives of the crash severity.9 Considering the variables related to the vehicle and injury severity simultaneously can help the researcher investigate the crash more accurately. Thus, the concept of accident size can be defined here for a thorough investigation, the indicators of which are the number of injured individuals, the number of fatalities, the number of involved vehicles and the number of damaged vehicles.9There are several studies addressing the safety of pedestrians in traffic crashes that in most of them the crash severity or the pedestrians’ injury severity is taken into account,Therefore, for performing a comprehensive study of the pedestrian crashes and their obvious susceptibility in the event of a crash, the objective of this study is to investigate the influential factors on the accident size of pedestrian crashes considering the factors related to road, environment, driver, pedestrian and vehicle.Literature review11 Logit14 and Probit 17 models. Prior studies have reported that drivers’ and pedestrians’ age and gender,19 vehicle type19 road characteristics like road type and alignments,19 and environmental characteristics such as time and weather conditions19 significantly affect pedestrians’ safety in road traffic crashes. In previous studies, different analytical methods are employed for investigating the factors influencing the pedestrian crashes which involves Logistic regression,20 In a recent study, Yuan et al. (2019) studied the accident size of fatal accidents involving trucks that the results indicated that main indicators affecting accident severity are: environmental and roadway factors such as weather and surface conditions; vehicle factors such as truck weight and body type; and driver factors such as age, driving experience, and history of crashes or convictions.21The concept of accident size was first developed by Lee et al. (2008) that was defined using the variables of the number of injured individuals, fatalities, involved vehicles and damaged vehicles in a traffic crash. Lee et al., (2008) used 2649 accident data occurred on highways in Korea and estimated relationship among different factors and traffic accident size. The model suggested that road factors, driver factors and environment factors are strongly related to the accident size. Then, accident size was used by Hassan et al. (2013) for investigating the accident size of fatal and injury traffic crashes and the results showed that road factor was the most significant factor affecting the size of the crash followed by the driver and environment factors.According to previous studies, researchers have mainly focused on the pedestrian crashes by using different methodologies and by focusing on one feature of the crash at a time. Although there are numerous studies in the severity of pedestrian crashes, there are few studies addressing the accident size of pedestrians. So, in the present study, for investigating the crash severity more comprehensively, the relationships of human, environment, road factors and accident size are studied.22 Observed variables are the measured variables in the data collection process and latent variables are the variables measured by connecting to the observed variables, because they cannot be directly measured. SEM has some advantages over traditional statistical methods  that some of them are: the ability to model multiple dependent variables simultaneously; the ability to test overall model fit, complicated and specific hypotheses, and the ability to handle difficult data .22 For this reason, it can be said that structural equation modeling is more suitable for testing the hypothesis than other methods.23The goal of this study is to investigate the effects of different factors on the accident size. The accident size is considered as a representative of the crash severity which cannot be measured directly. As accident size is a linear combination of four indicators , the most proper modelling technique is the structural equation modeling (SEM). In SEM, unobservable latent variables are estimated from observed indicator variables, and the focus is on the estimation of the relations among the latent variables free of the influence of measurement errors.24 There are some rules of thumb for choosing between CB-SEM and PLS-SEM, some of which are worth mentioning here that when the structural model is complex, sample size is small, the data are non-normally distributed or the feature of the study is exploratory the researcher should use the later one.24 Regardless of the approach used, an SEM is validated in three steps: the assessment of the measurement models, the assessment of the path model and the assessment of the goodness of fit of the overall model that the commonly used criteria for assessing the PLS-SEMs are provided in 25There are two types of SEM: covariance-based SEM (CB-SEM) and partial least squares SEM . CB-SEM is primarily used to confirm (or reject) theories  is measured by four defining variables: number of damaged vehicles, number of involved vehicles, total number of injured people and total number of fatalities. So, SEM was developed for specifying the relationships between observed and latent variables. The results of assessing the reflective measurement models are provided in 1 higher than 0.7 and AVE2 higher than 0.5 are required.25 Therefore, the reliability and the validity of the measurement models are approved. Finally, for the assessment of structural model, the values of R2 and goodness of fit are 0.83 and 0.68 respectively that meet the requirements.According to the values of measurement models’ assessment in 25 As the standardized coefficients are discussed here, the effect of each latent variable on accident size can be compared. Thus, it is indicated that the most effective factors are vehicle, road, pedestrian and environment, respectively. Hence, in order to decrease the accident size of pedestrian crashes some improvement measures dealing with vehicle and road factor can be implemented. In addition, in the measurement models of road, vehicle and pedestrian the most indicative variables are location, vehicle type and pedestrian’s clothing color, respectively. The coefficients of the study illustrate that these factors are associated with the increase of accident size.19 Kim et al., (2008) have shown that two-way divided roads have better geometric design, but if a pedestrian–vehicle crash happens, a pedestrian is more likely to suffer from fatal injury most likely due to higher speed on two-way divided roads. In another study, the results illustrate that high-speed urban roadways were associated with greater severe injury probability and these roads found to be more dangerous for pedestrians, especially for pedestrians crossing the roadways.13 Therefore, minimizing the conflict between pedestrians and vehicles in highways through the physical design can be one of the measures for reducing the accident size of pedestrian crashes.It is illustrated that in the road factor the most influential variable is road location, which shows that highways  influence the accident size positively. This result is in agreement with previous studies.19 According to the study of Haleem et al. (2015), this can be mainly due to their weak physical conditions. Kemnitzer et al. (2019) have concluded that the youngest pedestrians (0–4 years old) were associated with the lowest odds of injury, whereas the oldest pedestrians (aged 65 and older) were associated with the highest odds compared to pedestrians aged 26–64. The variable of pedestrian’s gender shows that females are involved in more severe crashes other than males which is in accordance with other studies27 and this may be attributed largely to the greater fragility of females than males due to their physiological differences, in terms of height and weight, as well as differences in resistance of the body to withstand impact.27Considering the pedestrian characteristics, the variables of clothing color, gender and age are the most effective variables, respectively. So, for controlling the accident size, educating the people and considering the old people in designing the road infrastructures (e.g. pedestrian bridges) can be some of the effective measures. The clothing color has negative influence on the accident size , showing that having a contrasting clothing color leads to lower accident sizes. In a study conducted by Pour-Rouholamin et al. (2016), it is represented that pedestrians who wear not contrasting clothing are more vulnerable to severe injuries compared to others who wear contrasting clothing. It is believed that wearing bright or contrasting clothes makes pedestrians more visible to drivers. According to the study of Zavareh et al. (2015) , being seen on the road is a fundamental requirement for safety of all road users, particularly vulnerable road users. On the other hand, the results of present study show that old pedestrians are more vulnerable in the event of a crash which is compatible with the results of other researches.29 the old-aged drivers usually experience more severe crashes and this group of drivers influence the probability of accident size positively . It indicates that pedestrians usually experience higher accident sizes while colliding with old-aged at-fault drivers, the reason of which can be some weaknesses in the eyesight and also longer perception-reaction time of drivers.Considering the vehicle and driver characteristics, it is represented that heavy vehicles are associated with higher accident sizes . The study of Kim et al. (2008) shows that with a larger mass and a longer stopping distance, sport-utility vehicles and, in particular, trucks have greater momentum, which leads to greater impacts and more serious injuries. Besides, the driver’s gender also affects the accident significantly and female drivers are related to higher accident sizes. Finally, as it is investigated in some studies,1 Critical ratio2 Average variance extractedMost of the prior studies in the field of pedestrian safety have focused on one feature of the accident such as injury severity or crash severity. For filling this gap, the objective of this study was to investigate the effective factors on the accident size of pedestrian’s traffic crashes. In this regard, 3718 accident data for the pedestrian crashes was used. The considered accidents occurred on urban roads of Isfahan province between 2011-2018. The results showed the characteristics related to road, driver and pedestrian influence the accident size positively. According to the results, highways and heavy vehicles are related to higher accident sizes which shows the importance of constructing safe pathways for pedestrians while crossing the high speed roads. Furthermore, older pedestrians are involved in more severe crashes indicating that this group of people should be taken into account while designing and constructing various infrastructures. Finally, it is better to inform the people with the importance of having a proper clothing in relation to the daytime. The findings highlight some information about the relationships between accident size and different factors influencing the traffic accident size. This study was limited to data set related to the accidents in Iran over a 5-year period. Therefore, there are important factors such as driver’s error, driving experience and pedestrian’s behavior that are not included in this study due to the lack of information and it can be considered as a possible limitation of this investigation. For the future studies, considering driver’s reactions and behaviors, land use type, accident type, the condition of the road lights can be done for improving the model.