The purpose of this work is to study the gap between the research evidence and the clinical practice in the physical rehabilitation of people with cerebral palsy. A review process was performed to (1) identify physical therapies to improve postural control in children with cerebral palsy and (2) determine the scientific evidence supporting the effectiveness of those therapies. A Likert-based survey addressing a total of 43 healthcare professionals involved in pediatric physical therapy departments in Spain was carried out. The discussion was mainly supported by studies of level I or II evidence . The search process yielded 50 studies reporting 16 therapies. A strong positive correlation between the most used treatments and elevated levels of satisfaction was found. Some well-known but not often used techniques, such as hippotherapy, were identified. The treatment with the highest degree of use and satisfaction—neurodevelopment therapy (Bobath)—and some emerging techniques, such as virtual reality, were also identified. The fact that there is a meaningful gap between clinical practice and the scientific evidence was confirmed. The identified gap brings a certain degree of controversy. While some classic and well-known therapies had poor levels of supporting evidence, other relatively new approaches showed promising results. Cerebral palsy (CP) is a well-known neurodevelopmental condition beginning in early childhood and persisting throughout the lifespan. It is defined as a “a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain” . CP has According to the World Health Organization’s (WHO) International Classification of Functioning, Disability and Health (ICF)—a framework for measuring health and disability at both the individual and population levels, which was officially endorsed by all 191 Member States in 2001 (resolution WHA 54.21) as the international standard to describe and measure health and disability—clinicians should focus the intervention on the person’s ‘functioning’ and autonomy in daily living.The Gross Motor Function Classification System (GMFCS) was developed to classify functional mobility in children diagnosed with CP by the level of motor function in lower limbs. It describes five levels ranging from level I, indicating children with minimal or no mobility dysfunction compared to the general population, to level V, covering children who are dependent and need technical aids to move . RegardiIn addition to several well-known consequences of brain damage, including learning disability, speech and language disorders, orthopedic complications, and epilepsy, people with CP usually develop postural and motor abnormalities, which give rise to different degrees of postural control dysfunction . FurtherPostural control can be defined as the ability to control the body’s position in space for purposes of stability and orientation ,8,9 and These limitations clearly influence and restrict a wide range of daily activities such as self-care or education. However, although there is currently a broad spectrum of physical interventions designed to treat this core deficit, and children with CP usually receive or participate in many passive or active interventions aimed to improve movement and posture, often the real impact on postural control is not well-measured or documented, and some of them have even been proven to be ineffectual or unnecessary ,13,14,15Previous studies ,17 confiThe vast volume of research published makes it difficult to distinguish the most effective interventions. However, several works have studied the level of evidence of these interventions, and they should be useful tools for clinical practice. Novak et al.  conducteAll in all, the question  that motivates this study is: what are the differences between the most-used interventions in pediatric physical therapy in children with CP in Spain and the actual scientific evidence regarding their effectiveness? To answer this question, the purpose of this work (in line with the objectives of the SEFIP) is to study and discuss the gap between the research evidence and clinical practice in the physical rehabilitation of people with CP in Spain, in three main steps. The first step consisted of identifying those physiotherapy techniques, therapies and interventions currently used to improve postural control in children with CP. The second step consisted of analyzing those previously identified methods according to the experience-based opinions and ideas obtained from a survey using the Likert scale addressed to clinical professionals involved in the rehabilitation of people with CP. The survey, performed in Spain, included general information about the participants, questions about the knowledge, the degree of use and the satisfaction of those techniques, therapies and interventions, and an open-ended question to identify alternative treatments and emerging research lines in the rehabilitation of CP. The last step consisted of discussing the differences between the clinical practice preferences and the scientific evidence of effectiveness, defined as the ability of an intervention to provide benefits during usual conditions of clinical care , regardihttps://eu-rd-platform.jrc.ec.europa.eu/scpe_en (accessed on 2 November 2022)), the Cerebral Palsy Foundation (https://cpresource.org/ (accessed on 2 November 2022)), the Cerebral Palsy Alliance ), and the Sociedad Española de Fisioterapia en Pediatría (www.sepif.org (accessed on 2 November 2022)); and (3) the top 25 hits in Google using the search term ‘cerebral palsy’, to target the population of interest, and terms such as ‘postural control’, ‘techniques’, ‘treatments’ ‘methods’, ‘interventions’ or ‘rehabilitation’, to target the postural control rehabilitation processes.A review of techniques, therapies, and interventions for improving postural control in children with CP was performed. The review process was focused on works published between 2010 and 2021 to have access to the latest advances, considering the work of Novak et al.  as the fIn order to identify those physiotherapy techniques, therapies and interventions currently used to improve postural control in children with CP, articles were included if (1) they were full articles published in English, (2) they exclusively included participants aged between 0 to 18 years old (children) with CP regardless of the type and level of dysfunction, (3) the performed therapies and interventions in the target population involved land-based exercises and physiotherapy techniques, and (4) the outcome measures were focusing on assessing postural control of either postural stability or postural orientation. Works were excluded if they were (1) opinion articles, (2) if they reported water-based interventions, or (3) medical or surgical interventions.The level of evidence was not an exclusion criterion for this first step, including from systematic reviews of randomized trials (level I according to The Oxford 2011 Levels of evidence) to case studies or mechanism-based reasoning (levels IV and V). This decision was taken because we did not want to dismiss methods that could be popular in clinical practice regardless of their levels of evidence.On the other hand, the discussion is mainly supported by studies of level I or II evidence. Levels III to IV were included only if the highest level of evidence did not exist on the topic.This project was conducted with the collaboration of the “Hospital Infantil Universitario Niño Jesús”, which is a national reference centre in the rehabilitation of children with cerebral palsy. The research group of this hospital in turn sought collaborators from other centres also specialized in cerebral palsy with which the hospital works regularly, with the aim of sending the survey to physiotherapists/pediatric physiotherapists (1) and occupational/neuro-psychomotricity therapists (2) with fully demonstrated experience  in the treatment of children with CP at all levels of the disease involvement, covering the entire spectrum of motor impairment described in the GMFCS. These profiles were included because, even though the first (1) specialize in working with the function and the second (2) in working with the activity and the participation of the users, they both collaborate and coordinate their performance in multidisciplinary clinical teams. A total of 43 people participated in the survey.General information about the participants, including age, education or professional career, number of years of experience and working institution.Knowledge of the different treatments. Participants answered if they knew (Yes) or not (No) about each one of the listed techniques, therapies, and interventions.Degree of use of the treatments using a Likert scale. Participants had to choose among six different options depending on how often they had used each one of the listed techniques, therapies, and interventions throughout their careers, according to the following scale: always, very often, sometimes, almost never, never, N/A.Degree of satisfaction of the treatments using a Likert scale. Participants had to choose among six different options based on their degree of satisfaction with each one of the listed techniques, therapies, and interventions after its use on children with cerebral palsy throughout their careers, according to the following scale: very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, very dissatisfied, N/A.The last part of the survey was an open-ended question asking participants to state which treatments, both from the listed ones or from other sources according to their professional experience, they thought had more future in the rehabilitation of this type of patients. Participants had a comment box with no specific pre-set to answer the previous question, and an extra comment box to add extra observations if considered.The survey see  consisteThis structure, as well as the questions of the survey, were validated by the research group of the “Hospital Infantil Universitario Niño Jesús”. All their recommendations about the clarity of the questions and their relevance were considered and included in the final version of the survey that was subsequently sent to the collaborating institutions.Once the survey data were recollected, a series of description tables and histograms were made so that the data could be more clearly interpreted. In addition, to compare extensively used treatments and treatments with a high level of satisfaction, both the bivariate correlation (Pearson correlation coefficient) and their corresponding scatter plot and regression line were obtained.Using the search strategy, 153 citations were identified, of which 50 met the inclusion criteria, highlighting the systematic reviews of Novak , where aThe survey, based on the previously identified sixteen treatments, firstly showed the demographic characteristics of the participants as seen in The results on the knowledge of each one of the listed treatments are shown in The results on the degree of use of each one of the listed treatments are shown in On the other hand, a relatively high percentage of treatments were never used (more than 50% of the participants never had used them): trunk targeted-training interventions, the Doman-Delacato method, the Padovan method, hippotherapy stimulators and hippotherapy. Moreover, there were a couple of treatments that were rarely used : reflex locomotion: Vojta therapy  and functional electrical stimulation .It is important to consider that the options ‘Never’ and ‘N/A’ regarding the degree of use of each one of the listed techniques, therapies, and interventions, were not only selected by the participants who did not know them, but also by some of the participants who knew them. That is why the lower limit for the percentage of participants who knew each one of the listed treatments but did not use them was obtained.The results shown in The results on the level of satisfaction of each one of the listed treatments are shown in According to the previous data, the bivariate correlation  and the corresponding scatter plot and regression line were obtained to compare regularly used treatments  and treatments with a high level of satisfaction (sum of ‘very satisfied’ and ‘satisfied’ percentages for each one of the listed treatments). According to these results, there was a strong positive correlation (ρ = 0.92) between the most used treatments and elevated levels of satisfaction, which could be corroborated by the corresponding regression line see .The results concerning the opinion of the participants (expressed in an open-ended question) about the treatments with a more promising future in the rehabilitation of patients with CP show, on the one hand, that many of them opted for the Bobath approach in combination with some other techniques such as reflex locomotion: Vojta therapy, the Perfetti method, virtual reality or biofeedback. On the other hand, a few participants named other techniques which were not considered in this study, such as Therasuit, myofascial structural integration, kinesio-taping, and proprioceptive neuromuscular facilitations.In addition, a series of points from the final observations and comments of the participants should be highlighted: the need for a multidisciplinary approach in the rehabilitation processes of children with CP, the lack of facilities and equipment in many health centers to carry out the more innovative rehabilitation techniques, the need for new methods based on sports, games or dance to improve postural control, and the proposal of using classic techniques with new and technologically advanced approaches.This discussion analyses the previous results and aims to determine if there is a correspondence between clinical practice preferences and the scientific evidence supporting the effectiveness of each treatment.To begin with, it is important to highlight that some of the best-known treatments  are also the most well-established methods in clinical practice, not only in the field of CP rehabilitation but also in other rehabilitation areas . In fact, there is an abundance of publications in recent years describing them, as well as their applications, pros and cons, effects, improvements, evolution, and associated results ,33,34,35On the other hand, the lesser-known methods  deserve individual analysis.Regarding biofeedback , it is important to highlight that even though there are several studies that have researched biofeedback-based interventions for people with CP and other neuromotor diseases, there is still no consensus regarding the correct implementation of biofeedback mechanisms . This laTM SD (three times per week for 12 weeks) improved the limits of stability and standing balance and reduced fall risk in children with diplegic CP [The reactive balance training methods were traditionally used by fitness instructors, but since these kinds of exercises may improve the control of reactions and have the potential to prevent falls after losing balance in daily life, the technique is being tested in children with CP. According to our results, those clinicians who use these methods in children with CP are mostly satisfied with them. Regarding the evidence for its effectiveness, while one recent level II evidence study concluded that although postural control is modifiable, and does improve in response to intense balance training, more research is necessary to determine the type and frequency of intervention needed to impact postural control in these patients . Other slegic CP ,39. Fromlegic CP , and theThe Doman–Delacato method  is a classic procedure claiming that passively repeating steps in normal development can overcome brain injuries. However, the absence of a neuroscientific basis, the inconsistent results of uncontrolled studies over the years, and the lack of controlled trials resulted in the method not being recommended for many years ,42,43,44The Padovan method, also known as the neurofunctional reorganization method, and supported on the plasticity of the nervous system, is based on the passive repetition of a sequence of neuroevolutionary movements until the patient has the autonomy to perform them actively. Although there are a few studies claiming the effectiveness of the method in premature and term infants who suffered perinatal hypoxia ,46 thereHippotherapy is a well-known and well-established technique, but its degree of use is not as high as expected. One possible reason is that, despite its benefits, it is restricted by availability, high cost and safety factors . These rRegarding the degree of use of the different techniques, therapies, and interventions, it is remarkable that there are several methods which are not commonly used among those who know them. The possible reasons behind this for some of the methods  have already been discussed, but others  need a deeper insight.Trunk-targeted training involves exercises aimed at improving trunk muscle strength and control and, in recent years, some studies suggest that although the technique should be further investigated, it could be a potentially effective treatment for children with poor trunk control ,50. AccoVotja therapy is a dynamic neuromuscular treatment method based on the developmental kinesiology and principles of reflex locomotion but, although quite a few recent case studies , controlFunctional electrical stimulation (FES), also known as neuromuscular electrical stimulation (NES), is a therapy utilizing advanced computer technology to deliver electrical stimulation to paralyzed or weak muscles. FES was originally developed to help people with paralysis but is now being used to treat quite a few medical conditions. However, according to recent scientific publications, there is no high level of evidence of the effectiveness of this therapy on its own , but theOn the other hand, as presented previously, the techniques, therapies and interventions that were used always or used very often with a higher percentage were neurodevelopment therapy: Bobath approach, upper limb interventions, reactive balance training, progressive resistance exercises and gross motor training.Among these, neurodevelopment therapy: Bobath approach was, by far, the therapy which was said to be always used by a higher percentage of the respondents. The Bobath concept, which emphasizes both the integration of postural control and task performance, and the selective movement control to produce coordinated sequences of movements, is, as mentioned before, one of the most well-established problem-solving approaches in the field of rehabilitation of neuro-motor dysfunctions ,59,60. IUpper limb interventions , which are focused on helping children with hemiplegic CP mainly learn to use both hands together to complete everyday activities, also showed relatively high percentages regarding frequency of use. The fact that of those children with cerebral palsy, 80–90% present hemiplegic cerebral palsy , and theRegarding the reactive balance methods, it is important to highlight that although some participants did not know them, those who knew and used them were mostly satisfied with the obtained results as discussed before, which can explain why these methods are among those with higher frequency  of use.With regard to progressive resistance exercises, there is a certain degree of controversy: although the method is commonly used in clinical practice , which aIn addition, it is remarkable that the analysis for gross motor task training also shows a gap, because although the kind of interventions proposed by this method are commonly used in children with CP , there aNext, after discussing the results regarding the degree of knowledge and frequency of use of the techniques, therapies and interventions identified for this study, it is important to analyze the results regarding the associated degree of satisfaction.On the one hand, as previously shown in the results, there was a strong positive correlation (0.92) between the most used treatments, already discussed, and elevated levels of satisfaction as expected: it is reasonable that health professionals use in their daily clinical practice those solutions they are most satisfied with according to their previous experience and perception. This could explain why neurodevelopment therapy: Bobath approach, reactive balance training, or even progressive resistance exercises and gross motor task training, despite the controversy regarding their level of evidence commented on above, are the options that, along with upper limb interventions, are associated with a higher level of satisfaction.On the other hand, there are other solutions whose levels of satisfaction are also remarkable but, on the contrary, are not as commonly used in clinical practice as the previous ones. The following methods are included within this group: the Perfetti method, virtual reality and visual biofeedback.The Perfetti method, also known as cognitive sensory motor training, is a motor learning model that emphasizes high-level cognitive function thanks to the integration of perception–cognition–activity processes . Even thIn fact, in recent years, several solutions based on both biofeedback, that is the technique of providing biological information to patients in real-time, and on virtual reality were developed not only as a novelty associated with the Perfetti method or as a complementary option for other therapies, but as a real and complete alternative of rehabilitation in children with CP . CliniciOn the other hand, only a moderate uphill relationship was found between the percentage of participants who knew but never used each one of the studied treatments and elevated levels of dissatisfaction. In this case, two extreme cases deserve a detailed analysis: hippotherapy and the Doman-Delacato method.Although both solutions were known but not used in more than 60% of the cases, the first one showed no dissatisfaction results while the second one showed the highest level of dissatisfaction (18.7%) registered among the participants. Regarding hippotherapy, despite those who tested the technique being satisfied with the results, its restricted availability, high cost and other logistical and safety factors can explain its lack of use as commented before . In contAfter the previous analysis, there is still one technique among those considered for the study which has not been analyzed yet: treadmill training. A typical form of gait training has been performed traditionally with assistive devices or parallel bars. The treadmill has recently gained more attention as an instrument for gait training and assessment, and it is used for children with CP to help them to improve balance and build the strength of their lower limbs . In factTo round up this discussion, we also considered other techniques, such as Therasuit, myofascial structural integration, kinesio-taping, and proprioceptive neuromuscular facilitations that, while not considered for the study, were brought up by the participants.®) that aligns the body as close to normal as possible. The creators of the method described it as the “new standard treatment for cerebral palsy” [The Therasuit method is based on an intensive and specific exercise program aimed at eliminating pathological reflexes and establishing new and functional patterns of movements. This solution uses, among other tools, a soft dynamic proprioceptive orthosis  combined with conventional rehabilitation can be effective in reducing spasticity and improving range of motion, strength, and function of the upper limb in children with CP, compared to conventional rehabilitation by itself ,97,98. HKinesio-taping is a relatively new therapeutic tool used in rehabilitation programs of children with CP, although it has been in use for a long time in the sport and orthopedic fields. Kinesio tape is a specialized elastic-like tape designed to mimic the elastic properties of the muscle, skin, and fascia, leading to enhancing proprioception, diminishing pain and edema, reducing muscle spasms, and strengthening the muscles ,101. SomProprioceptive neuromuscular facilitation (PNF) training  is a motor learning approach that targets the improvement of proprioceptive function, focusing on the use of somatosensory signals to improve or restore the sensorimotor function. According to recent research, there is converging evidence that PNF training, not only based on its classical approach but also on more innovative approaches, could yield meaningful improvements in somatosensory and sensorimotor function. Such approaches include the use of virtual reality systems as proprioception methods  or simulTo summarize this discussion, it is important to highlight its main ideas as well as describe its possible implications in education, clinical practice, and research, derived from the previous analysis:On the one hand, it is remarkable that some well-known methods, such as Votja therapy, the Doman–Delacato method, or the Bobath approach, that have been used for years in clinical practice, do not have a solid level of scientific evidence to support their use. According to our preliminary results, the level of satisfaction for the first two methods is relatively low , but, surprisingly, the levels of satisfaction registered for the Bobath approach are the highest among all the proposed techniques. These results suggest that the education of clinical professionals in this context could lack the scientific rigor that should be expected, transmitting knowledge about techniques that have traditionally been used without prioritizing those that are effective, based on scientific evidence, or those emerging techniques whose level of evidence needs to be demonstrated with further research. This fact calls into question the rigor of some interventions carried out in clinical practice and opens the door to the need to introduce new protocols in the training of professionals with scientific evidence and objectivity as the fundamental pillars. In fact, awakening the scientific interest of students, as well as the motivation to stay updated, could lead to breaking the current gap, which, on the other hand, would help to classify and determine the level of evidence of those emerging techniques, mainly supported by the use of new technologies , that, according to preliminary studies, show promising results in the rehabilitation of children with CP.In short, the application of any method in clinical practice should always be supported by solid scientific evidence. The scientific community already offers relevant studies such as ,15,22, aThe existing gap between the scientific evidence and the clinical practice in physical therapies for cerebral palsy presented in this paper is a first step in the objective of constructing an evidence-based physical therapy practice for children with CP. Despite the limitations of having a small sample, this work contributes to identifying the importance of being aware of the need to use scientific methodology to measure the effectiveness of the treatments that centers use in their daily routines. By following the therapeutic approaches supported by the literature, the clinical practice could become less reliant on the individual therapist’s skill and more robust. All in all, it is important to highlight that there is a pressing need for functionally based research in the clinical practice that uses objective protocols and outcome measurements to evaluate the interventions on children with neuromotor disorders.


Science literacy, which is literacy relevant to the processes and products of science, related to the content of science taught in classrooms (literacy about issues within science); and Scientific literacy, which is literacy relevant to questions that students may encounter as citizens and to the socio-ethical implications of scientific knowledge (literacy about the implications of science for society). Based on this, we can in turn distinguish between two types of literacy related to evolution: Evolution literacy, which is literacy relevant to the evolution content taught in classrooms; and Evolutionary literacy, which is literacy relevant to questions that students may encounter as citizens and to the socio-ethical implications of scientific knowledge. In this article I argue that whereas a lot of attention has been given to evolution literacy as a learning goal, there has been less reflection and discussion about evolutionary literacy—and it is exactly the distinction between these two types of literacy that helps one realize this. Teaching for evolutionary literacy requires specific skills from teachers, which go beyond their ability to teach concepts and explanations. My aim is to initiate a discussion about how to set evolutionary literacy as a learning objective at schools along evolution literacy. A key issue in such a case is how we could prepare teachers who would be capable, and confident, to address issues going beyond the typical science content, and which are often related to worldviews, in the classroom.In this paper, I argue that for both theoretical and practical purposes, it is useful for science education to clearly distinguish between science content knowledge and skills on the one hand, and the competencies related to their application in everyday life. This can be based on a distinction made by Douglas Roberts between two visions of literacy, and it can be effectively reconceptualized as the distinction between two types of literacy relevant to science:  Whereas there is a general agreement among scientists and educators that teaching evolution ought to have a prominent place in school science curricula and that learning evolution should be a main goal of science education, it should not be taken for granted that such learning makes significant contributions to literacy about science. Rather, it is necessary to clearly define what learning about evolution contributes to this kind of literacy. To achieve this, teachers need to set specific learning goals as well as to be given guidelines about how to attain those. To figure these out, it is necessary to begin reconsidering what literacy with respect to science actually consists of.In its fundamental sense, literacy was defined by UNESCO in 1958 as “the ability to read and write, with understanding, a short, simple sentence about one’s everyday life”. In 1978, the definition was revised as “A person is functionally literate who can engage in all those activities in which literacy is required for effective functioning of his group and community and also for enabling him to continue to use reading, writing and calculation for his own and the community’s development.” Oxenham . TherefoVision I: literacy relevant to “… the products and processes of science itself … literacy within science”Vision II: literacy relevant to “… situations with a scientific component, situations that students are likely to encounter as citizens … literacy about science-related situations in which considerations other than science have an important place at the table.”In 2007, Douglas Roberts made a crucial distinction between two visions of scientific/science literacy, which represent the extremes of a continuum:Vision I literacy: “literacy, in this view, is within science—general familiarity and fluency within the discipline, based on mastering a sampling of the language, products, processes, and traditions of science itself.”Vision II literacy: “begins by looking outside science… what counts as scientific literacy is learning how science fits appropriately with such personal and societal perspectives for a more complete grasp of the issues”.This view was further elaborated a few years later by Roberts and Bybee  to two tScience literacy: literacy relevant to processes and products of science (literacy about issues within science).Scientific literacy: literacy relevant to questions that students may encounter as citizens and to the socio-ethical implications of scientific knowledge (literacy about the implications of science for society).Roberts and Bybee considered that Vision I should be used as default because historically, it has been the dominant model for curriculum, its measures are less complex than those of Vision II, which in turn might seem as too broad to be taught in schools and require that teachers master new content, as well as teaching and discourse styles. Eventually they suggested that “…there is more need than ever to develop ways to balance science literacy (Vision I) and scientific literacy (Vision II) in science education programs that can successfully meet the needs of all students”. This is where they make explicit and clear the distinction between science literacy and scientific literacy, which is the focus of the present article. This distinction can be represented as follows:Table Evolution literacy: literacy relevant to processes and products of evolutionary biology.Evolutionary literacy: literacy relevant to questions that students may encounter as citizens and to the philosophical implications of scientific knowledge for one’s worldviews.Whereas Table It is the last element, the philosophical implications of scientific knowledge for one’s worldviews, which we do not find in most other disciplines (and when we do it is not as strong as in evolutionary theory) that makes this distinction necessary to be made clear. When it comes to teaching, evolution is a topic that requires careful additional consideration compared to other science topics . Therefore, in these cases the aim is not to explain a pattern but a unique event or a sequence of events that took place in the past. One important component of evolutionary explanations are the antecedent conditions. These are the conditions due to which a particular outcome, and not something else took place. For example, in explaining adaptations, we should not only consider the role of natural selection, but also the antecedent conditions that made the process of natural selection possible in the first place. For instance, in a population that has no variation, there will be no selection because there is nothing to be “naturally selected.” The existence of variation in a particular environment is one of the antecedent conditions that cause natural selection, and, perhaps, adaptations. Another important component is contingency. Evolutionary outcomes are contingent per se, that is unpredictable, and contingent upon what has previously happened. Whether natural selection will take place at all, or which direction it will take is contingent in this sense, and antecedent conditions are again important here as, for instance, the outcomes depend what kind of variation was available in a population, or what kind of environment this population was living in , in order to deal with or make decisions about issues one might encounter as a citizen in their everyday life. The reason I emphasize this is that it should not be taken for granted that if one develops evolution literacy, one would also be able to apply this understanding to socio-scientific questions. Rather, additional skills are required for this purpose, and this is why developing those skills is part of evolutionary literacy. One such additional skill is about constructing arguments, which in their simplest form are claims warranted on particular grounds: a claim is an assertion that is based on particular evidence (grounds), under a specific assumption (warrant) that links the grounds to the claim  Particular categories distinguish between fundamentally different kinds of people; (ii) The boundaries that separate these categories are strict and absolute, making the groups discrete, or non-overlapping; (iii) The individuals within the categories are physically and behaviorally homogenous; (iv) Variation within and between groups is due to internal factors (essences) that are shared within a group and which differ categorically across the groups .ii.The boundaries that separate these categories are strict and absolute, so that a person who belongs to a particular category cannot belong to another (A person can be either Black or White).iii.These categories are homogeneous, that is, their members share fundamental similarities with one another and have fundamental differences from members of other groups (White people are more similar to other White people in terms of their skin color than to Black people).iv.All this is due to internal factors that make the members of each category what they are, which is the category essence (Black and White people have different DNA sequences related to their skin color)  would look like this:Both the premises and the implications of the above scheme are entirely mistaken. There are no fundamentally different kinds of people, no strict boundaries between social categories, no homogeneous social categories and no racial essences. Still, people intuitively believe that this is the case. For instance, in one study that involved 5269 self-reported African Americans, 8663 Latinos, and 148,789 European Americans living across the USA and drawn from the customer base of the test company 23andMe, most participants self-reported a single ancestry/ethnicity category. Yet, the analysis of their DNA showed a more complicated picture, and many had multiple ancestries (assuming that the respective ancestry categories exist), as shown in Table Analysis of genomes from around the world establishes that there is indeed a biological reality to race, despite the official statements to the contrary of leading social science organizations. … an illustration of the point is the fact that with mixed-race populations, such as African Americans, geneticists can now track along an individual’s genome and assign each segment to an African or European ancestor, an exercise that would be impossible if race did not have some basis in biological reality Wade .However, people are prone to interpret research results in terms of the existence of racial essences. For instance, a widely discussed study of human DNA variation arrived at the conclusion that there exist distinct genetic clusters of humans, which differed in the frequencies of particular variable DNA markers. As the researchers noted: “Genetic clusters often corresponded closely to predefined regional or population groups or to collections of geographically and linguistically similar populations.” (Rosenberg et al. Wade’s view has received a lot of criticism Fuentes , and hasBut why should biology teachers worry about these issues? Because empirical research has shown that teaching students about human DNA variation and can reduce the prevalence of essentialist views about races (Donovan et al. In this article, I have argued that if we want to teach for literacy in evolution, then we need to clearly distinguish between evolution literacy and evolutionary literacy. There is no way that students could deal with socio-scientific questions without the necessary understanding and knowledge of concepts and explanations. However, as I have argued in the present paper, there are important reasons for going beyond that. Evolution literacy is already something difficult to achieve, given students’ preconceptions and teachers’ difficulties. Nevertheless, the difficulties are well documented and suggestions for what to do are available (e.g., Branch et al. But how should we deal with evolutionary literacy? For instance, in order to deal with the issue of biological racism that I described, biology teachers should be able to master a variety of topics: identity and belonging, race as a social construction, population genetics studies, and more. Can we educate teachers to deal with these issues? I definitely believe that we do, but how exactly is far from clear and straightforward. I hope that the present article will mark the beginning of a fruitful dialogue on this topic. Otherwise, we will continue teaching science content knowledge to students that will not be as useful as it ought to be for their lives. This, however, might require a total reconceptualization of science curricula that should become more trans- and inter-disciplinary, and less focused on content knowledge and exams. I think it is time to make science teaching in schools more interesting, more relevant to everyday life and more useful to our students as future citizens.


There are increasing calls for mental health treatments to be adapted for different groups to maximize their acceptability and benefit to patients. However, adaptations can be costly to develop and evaluate, difficult to implement in routine clinical practice and may reduce service capacity at a time when there is unprecedented unmet need. An alternative method is personalization on an individual level. This review provides an overview of the issues related to personalization and adaptation of mental health interventions.Several terms have been used to describe changes to existing therapies, these reflect different extents to which existing treatments have been changed. Evidence-based practice and modular therapies allow a level of flexibility within intervention delivery without formal changes and not all changes to therapy should be considered as a new/adapted treatment but instead regarded as ‘metacompetence’. Implementing existing interventions in new contexts is preferable to developing new interventions in many instances. New guidance outlines how researchers can adapt and transfer interventions to varied contexts.The review provides proposed definitions of different changes to therapy. Modified and personalized treatments may improve acceptability to patients whilst maximizing implementation of evidence-based practice within clinical services. Estimates suggest that in 2019, one in eight people around the world were living with a mental health disorder ,4. At thindividual client, whereas adaptation suggests that treatments are changed to suit groups of clients. ‘Tailoring’ (‘make or adapt for a particular purpose or person’), can refer to both groups or individuals. Table There are a number of overlapping terms in the literature associated with changes to evidence-based interventions. The overlapping terminology may make it difficult to assess the extent to which treatments are ‘standard’ evidence-based interventions, and therefore, how confident services are to implement them without further training or specialist staff. Dictionary definitions of personalization (‘to make something suitable for the needs of a particular person’) and adaptation  demonstrate that these concepts are related, yet different. Personalization suggests that an individual treatment can be changed to suit an ▪▪]. Content adaptations included cognitive restructuring of illness-related thoughts, behavioural activation balancing illness-related and enjoyable activities, and psychoeducation of the link between chronic illness and mental health. Adaptations to the delivery included being flexible through the use of the telephone and including parents in the intervention. A systematic review and conceptual typology of adapted psychological interventions for people from ethnic minority groups [▪▪] categorized adaptations that were therapist-related, content-related and organization-specific . There was evidence for greater efficacy for adapted interventions compared with nonadapted treatments, with suggestion that organization-specific adaptations may have the greatest benefits.Treatments can be adapted or personalized in different ways. A recent review of adaptations to cognitive behavioural therapy (CBT) for adolescents with comorbid depression and chronic illness found that adaptations included those to both content and delivery ▪▪. Contey groups ▪▪ categoet al. have developed the ‘ADAPT guidance’, recognizing that ‘Implementing interventions with a previous evidence base in new contexts might be more efficient than developing new interventions for each context’ but that ‘although some interventions transfer well, effectiveness and implementation often depend on the context’. The guidance outlines methods to adapt existing interventions for new contexts, including new settings and healthcare systems or new populations or population subgroups. They suggest that this may support efforts to reduce inequalities through ensuring interventions are appropriate for the needs of disadvantaged groups. Their approach emphasizes the importance of implementation science rather than creation of new interventions. Implementation Science is: ‘the scientific study of methods and strategies that facilitate the uptake of evidence-based practice and research into regular use by practitioners and policymakers’ and implementation-focused trials that centre on such factors are likely to be of value.Moore et al. ▪▪ have dThere are two key points to be kept in mind when adapting interventions to maximize implementation:The new Medical Research Council (MRC) and National Institute for Health Research (NIHR) complex intervention research framework provides a structure for developing and evaluating complex interventions . It statet al.[et al. have described how therapists are prone to cognitive processing errors, assuming that the specific circumstances of the client or client groups we work with make them different to the empirical findings of trials, and therefore, discount standard evidence-based interventions. In reality, ‘actuarial prediction is superior to clinical prediction’ (p. 2), and therefore, it is likely to be more beneficial to use the evidence-based treatment. Kendall et al. suggest that rather than using a nonevidence-based treatment, therapists should ‘take the client's specifics into account and apply the known-to-be-effective treatment with flexibility’ (p. 2).This concept has also been described by Kendall et al.▪ as ‘fleThis recommended flexibility is fundamental to CBT, which is recommended by guidelines as a first-line treatment for many common mental health problems globally. Competence frameworks for CBT therapists, which describe the skills, competent CBT therapists should possess , state a(1)Capacity to implement treatment models in a flexible but coherent manner.(2)Capacity to adapt interventions in response to client feedback.(3)Capacity to use and respond to humour.(4)Capacity to implement CBT in a manner consonant with its underlying philosophy.(5)Capacity to formulate and to apply CBT models to the individual client.(6)Capacity to select and skilfully to apply the most appropriate CBT intervention method.(7)Capacity to structure sessions and maintain appropriate pacing.(8)Capacity to manage obstacles to carrying out CBT.Evidence-based interventions such as CBT are inherently flexible, should be personalized to meet the needs of individual clients and therapists who do not modify the treatment are not competent therapists delivering good therapy. This is consistent with evidence-based practice within medicine more broadly. The definition of evidence-based practice constitutes three components: research evidence, clinical expertise and patient values, preferences and characteristics , that isWhilst a multitude of specific, adapted interventions tested in randomized controlled trials may not be a feasible way to meet the current mental health needs of the population, personalized interventions may be a helpful way forward. Changing the individual treatment to suit individual clients in this way allows for one standardized intervention to be applied flexibly across a range of populations or presenting difficulties. There is some evidence that patients prefer personalized interventions, and that personalization may enhance adherence and engagement .One method by which personalization can be achieved is modular treatments. Modular treatments, in which therapists and/or clients can select the elements of protocols most suited to their presentation and needs allow protocolized, standard interventions to be delivered flexibly, allowing for patient variation. Decisions regarding which modules or elements are used may be based on clinical judgement, patient choice, data from outcome measurement or a combination . For exaOther ways in which interventions may be personalized include maximizing the use of technology, for example, using apps to collect measures of mental health symptoms and providing different strategies according to the results of those measures (see ). It is A number of terms have been used to describe changes to existing therapies, including adaptation, personalization, modification, tailoring and expansion. These reflect different extents to which existing treatments have been changed. It is recommended that that these terms are used consistently, and that the flexibility inherent in evidence-based practice means that standard protocols can be used across a variety of mental health patients and settings without the need for extensive revision. When needed, ADAPT guidance outlines how researchers can adapt and transfer interventions to new contexts. Modified and personalized treatments may balance the need for personalization with the implementation of standardized interventions, hence improving relevance and acceptability to patients whilst maximizing implementation within clinical services.We would like to thank Professor Isobel Heyman for insightful discussions regarding adapting therapies for children and young people with additional complexities, such as those with chronic physical illnesses.All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.None.There are no conflicts of interest.


Dirofilaria immitis is a parasitic nematode and causes dirofilariosis, a potentially fatal pulmonary infection which primarily infects canids. Dirofilariosis infections are controlled via prophylactic macrocyclic lactone (ML) regimens. Recent evidence has confirmed the development of ML-resistant isolates in the USA, which are genetically distinct from wildtype populations. Single nucleotide polymorphisms (SNP) associated with ML-resistant phenotypes were clinically validated in USA populations. In this study, 3 USA laboratory-maintained isolates  and 11 randomly selected European clinical samples from 7 hosts were analyzed. The samples tested were fresh microfilaria (mf) in blood or adult worms preserved in ethanol. The samples underwent MiSeq sequencing of the top 9 SNP associated with ML resistance. The results provide the first genotypic analysis of the three USA laboratory-maintained isolates and any European samples. The European clinical samples show no genomic evidence of ML resistance based on the 9 SNP. The early adoption of genotyping of clinical D. immitis samples could provide an early indication of the potential development of ML resistance and aid to distinguish clinical cases of heartworm infection due to ML resistance from those due to a lack compliance with the recommended treatments, as has been seen in North America. Dirofilaria immitis is a veterinary parasitic filarial nematode and the cause of dirofilariosis, a potentially fatal pulmonary infection which primarily affects canids, with humans occasionally acting as an incidental host. Macrocyclic lactones (MLs) were first approved as a monthly prophylactic treatment for dirofilariosis in 1987 and remain the standard of care ..9].The Berkeley isolate displayed some allele alteration in comparison to the reference genome at SNPs 5, 6, and 8 ranging from 8–17% at these three sites . The GeoD. immitis infections in the USA . Th. Th11]. The regions encompassing the 9 SNPs of interest were sequenced on an Illumina MiSeq Platform, at a coverage of 2000×. The Fluidigm Access Array system performed target enrichment using array-based PCR amplification of the genomic target regions. The 3 USA samples and the 11 European samples underwent parallel amplification using custom primers with added CS1 and CS2 tails, as described in Ballesteros et al. [D. immitis reference genome nDi.2.2 (http://www.nematodes.org/genomes/dirofilaria_immitis (accessed on 1 September 2019)) using BWA-mem (http://bio-bwa.sourceforge.net/ (accessed on 1 September 2019)) resulting in binary alignment map files (BAM) [https://broadinstitute.github.io/picard (accessed on 1 September 2019)) for the realignment of indels, mate fixing, and marking of duplicate reads. BVATools (https://bitbucket.org/mugqic/bvatools/src (accessed on 1 September 2019)) was used to extract base frequencies at each of the 9 SNP positions and the read frequencies were assimilated to the allele frequencies (Dataset S1). Alternate alleles frequencies for the 9 SNP molecular markers were compared as half the samples were individual adult worms, for which population fixation indexes (FST) could not be calculated.Trimmomatic was used to trim for minimal trailing quality (30 PHRED score) and filter for minimum read length by removing the Illumina sequencing adapters from read and adapter clippings . The reses (BAM) . The aliD. immitis appear to be migrating from the Mediterranean and Iberian Peninsula, moving further into Central and Northern Europe, likely a result of the movement of dogs around Europe, and possibly a result of increasing mosquito populations. To date, no case of ML-resistant D. immitis infection has been documented in Europe. As the number of D. immitis infections continues to rise and spread throughout Europe, the early adoption of genotyping of clinical D. immitis samples could provide an early indication of the potential development of ML resistance and aid to distinguish clinical cases of heartworm infection due to ML resistance from those due to a lack of prevention or inadequate compliance, as has been seen in North America. Epidemiological surveys of D. immitis samples collected across Europe with diverse chemoprophylactic treatment histories from historically endemic regions of the Mediterranean, newly endemic regions such as the Balkans and Austria, and previously non-endemic regions of Northern Europe can provide insight into the genetic makeup and genetic diversity of European clinical samples.Autochthonous transmission of canine


Similia similibus curentur, or ‘Let like be cured by like’), classical  homeopathic therapy is based on the individual and not on the indication. Based on the following three facts, the discussion of the evidence in human and veterinary homeopathy lays the foundations for a comprehensive presentation of the evidence on homeopathy: (a) homeopathic medicinal products without indication are 100% identical with regard to production, quality, safety, and principles of application, regardless of whether they are used in animals or humans; (b) if the simile principle is adhered to that classical  homeopathic therapy is based on the individual and not on the indication; and (c) if the proof of effectiveness of individualized homeopathy in one or more indications is available, the logical consequence seems to be that it can be concluded that it is effective in other indications. When criteria for evidence-based medicine for design, conduction, documentation, and rating of studies in homeopathy are considered, effects on all quality levels according to Cochrane criteria are recognizable, especially for individualized homeopathy, even in methodologically high-quality studies. In view of One Health and of the demands of the European Green Deal (Farm2Fork Strategy) and the EU Organic Regulation 2018/848, the application of homeopathy in the sense of integrative veterinary medicine  and the integration of complementary medicine including homeopathy at the universities seems a necessary consequence and requirement in the interests of the patient.According to the simile principle  is adhered to that classical  homeopathic therapy is based on the individual and not on the indication; and (c) if the proof of effectiveness of individualized homeopathy in one or more indications is available, the logical consequence seems to be that it can be concluded that it is effective in other indications. In view of One Health and of the demands of the European Green Deal (Farm2Fork Strategy) and the EU Organic Regulation 2018/848, the application of homeopathy in the sense of integrative veterinary medicine and the integration of complementary medicine including homeopathy at universities seems a necessary consequence and requirement in the interests of the patient, which is already expressed in the American consensus guidelines for an integrative veterinary medicine curriculum and is legally anchored in Switzerland by the Medical Professions Act for university teaching and research.(1) Background: Classical  homeopathic therapy is based on the individual and not on the indication. (2) Methods: The prerequisite for conducting methodologically high-quality studies on indvidualized homeopathy is that the principles of homeopathy are considered, since the selection of the simile  is decisive for the effectiveness of the homeopathic treatment, because only an application lege artis can be effective for the respective patient. Apart from this, criteria for evidence-based medicine must be considered for design, conduction, documentation, and rating of studies in homeopathy. (3) Results: When criteria for evidence-based medicine for design, conduction, documentation, and rating of studies in homeopathy are considered, effects on all quality levels according to Cochrane criteria are recognizable, especially for individualized homeopathy, even in the methodologically high-quality studies. (4) Conclusions: Based on the following three facts, the discussion of the evidence in human and veterinary homeopathy lays the foundations for a comprehensive presentation of the evidence on homeopathy: (a) homeopathic medicinal products without indication are 100% identical with regard to production, quality, safety, and principles of application, regardless of whether they are used in animals or humans; (b) if the simile principle ( A Systematic Review of Complementary and Alternative Veterinary Medicine: “Miscellaneous Therapies”’, a systematic review on published papers [The way homeopathy has been represented over the past years as well as in the article ‘d papers , clearlyd papers ,3,4.Similia similibus curentur, or ‘Let like be cured by like’. The patient’s individual symptoms lead to the simile, i.e., the homeopathic medicinal product, the symptoms of which, generated in healthy individuals, best reflect the patient’s symptoms [The German physician Dr. Samuel Hahnemann 1755–1843) developed the medical system of individualized, so-called classical homeopathy or single-substance homeopathy. The treatment is based on the law of similars—5–1843 desymptoms ,7.Since the selection of the simile is decisive for the effectiveness of the homeopathic treatment, for conducting methodologically high-quality studies on individualized homeopathy it is the prerequisite that the principles of homeopathy are considered. Only an application lege artis can be effective for the respective patient. It is unlikely that the desired effectiveness will follow, if the individually appropriate homeopathic medicinal product, the simile, is not selected by appropriately trained and experienced homeopathic doctors/veterinarians according to the basic homeopathic principles . A studyp < 0.001), i.e., a statistical significance for the effectiveness of homeopathy compared with placebo. Such ‘effect size’ seems comparable with, for example, sumatriptan for migraine, fluoxetine for major depressive disorder, and cholinesterase inhibitors for dementia [A Systematic Review of Complementary and Alternative Veterinary Medicine: “Miscellaneous Therapies”’ exclude farm animals from the systematic review, they exclude 16 out of 18 RCTs on veterinary homeopathy which were analyzed by the meta-analysis of 2015 [p = 0.01 for n = 15, pooled OR = 1.69 (CI = 1.12–2.56), p = 0.02 for n = 2, pooled OR = 2.62 (CI = 1.13–6.05)) [Up to 2014, five of the six meta-analyses on various indications concluded that the effectiveness of homeopathic therapy differs from that of placebo ,12,13,14dementia ,20,21,22 of 2015 . However3–6.05)) ,24. In aA 2007 Cochrane review of systematic reviews of predominantly conventional therapies revealed that 96% of all systematic reviews call for more methodologically high-quality research . Forty-nA Systematic Review of Complementary and Alternative Veterinary Medicine: “Miscellaneous Therapies”’, which describes the different results and outcome variables, that for an intervention to be considered as being effective it needs to be able to be ‘explainable’. In other words, ‘scientific’ can only be associated with explanations of the mode of action of treatments based on the current anatomopathological approach to medicine and that only medical techniques based on these models deserve attention from the research community. However, knowing how a medicine works has never been intended to be a prerequisite for its use according to the founder of modern evidence-based medicine, David Sackett [By definition, modern evidence-based medicine (EBM) is based on three pillars: the current state of scientific research, the clinical experience of doctors and veterinarians, and the values and wishes of clients and patients . Homeopa Sackett . Aspirin Sackett . Science Sackett .(1)to reduce the use of antibiotics by 50% throughout the EU by 2030(2)to increase the number of organic farms in the EU from 8% to 25% by 2030(3)to give preference to homeopathy and phytotherapy in organic farms before conventional medicines are used, including antibiotics, the application of these complementary medical disciplines in the sense of integrative veterinary medicine, i.e., to combine best practices of conventional and complementary medical therapy procedures, seems proactive and innovative ,31. HencIn view of One Health and of the demands of the European Green Deal (Farm2Fork Strategy) and the EU Organic Regulation 2018/848:A Systematic Review of Complementary and Alternative Veterinary Medicine: “Miscellaneous Therapies”’ [Similia similibus curentur, or ‘Let like be cured by like’) is adhered to that classical  homeopathic therapy is based on the individual and not on the indication; and (c) if the proof of effectiveness of individualized homeopathy in one or more indications is available, the logical consequence seems to be that it can be concluded that it is effective in other indications [Evidence for the effectiveness of human and veterinary homeopathy in general, and in particular in the treatment of infections, has been sufficiently proven to justify further research in homeopathy . Hence, rapies”’ . Based oications . Especiaications . In viewications ,3,30,31.


The purpose of this study was to collect and analyse the available scientific evidence on the clinical practice variability and effectiveness of shock wave therapy as a treatment for spasticity.the systematic search was performed in the following databases: PubMed, PEDro, Cochrane, Embase, and the Virtual Health Library. All publications from November 2009 to November 2019 were selected that included a sample of patients with spasticity and prior suspension of botulinum toxin, to whom shock wave therapy was applied. The methodological quality of the articles was evaluated using the Jadad scale and the pyramid of quality of scientific evidence.25 studies involving 866 participants with spasticity were selected. The results obtained suggest that shock wave therapy appears to be effective in reducing spasticity levels irrespective of the age of the participants, the type of injury, and the tool used to measure the effect.shock wave therapy reports evidence of improvement in motor function, motor impairment, pain, and functional independence, applied independently of botulinum toxin. However, due to the heterogeneity of the protocols, there is no optimum protocol for its application, and it would be appropriate to gain more high-quality scientific evidence through primary studies.• Shock wave therapy reports evidence of improvement in motor function, motor impairment, pain, and functional independence, applied independently of botulinum toxin.• Due to the heterogeneity of the protocols, there is no optimum protocol for its application, and it would be appropriate to gain more high-quality scientific evidence through primary studies.


Choanal atresia is the most common congenital anatomical abnormality of the nasal cavities, manifested with a clinical picture of neonatal respiratory distress. The treatment requires interdisciplinary management based mainly on tertiary referral centre experiences. However, there is a lack of high-quality evidence in the available literature. Recommendations were prepared based on a systematic review of the supporting literature: on a website survey addressed to the participating authors consisting of 28 questions and on five live meetings. The initial response to the recommendations was determined at their presentation at the sectional meeting of the section for otorhinolaryngology of the Slovenian Medical Association. Then, reactions from the professional public were accepted until the recommendations were presented at the Expert Council for Otorhinolaryngology of the Slovenian Medical Association. A systematic literature review identified eight systematic reviews or meta-analyses and four randomized controlled clinical trials. Thirty-four recommendations for diagnosis, treatment and postoperative management were consolidated. The paper presents the proposal and first Slovenian recommendations for treating patients with choanal atresia. They are based on foreign medical institutions’ published literature and our clinical experience. They represent the basic requirements of diagnostics and may represent an essential guide in treatment. Normal nasal patency is essential for the breathing of a baby, who, in the first months of life, breathes mainly through the nose . HoweverChoanae are paired anatomical structures that are superiorly delimited by the inferior surface of the sphenoid body, medially by vomer, laterally by the medial plate of the pterygoid process and inferiorly by horizontal part of the palatine bone.CA is the most common congenital anatomical abnormality of the nasal cavities . It occuCA results from disturbed embryogenesis in the fourth week of gestational age . From thThe clinical picture of a patient with CA depends on the side and degree of impairment, associated craniofacial anomalies and systemic disease.The position of the epiglottis above the soft palate and the tongue’s contact with the soft palate along its entire length a few months after birth prevents normal breathing through the mouth. The infant begins to learn to breathe through the mouth between the fourth and sixth week of age, allowing for normal feeding through the mouth . At six The clinical picture of nasal obstruction consists of cyanosis during feeding and improvement of breathing during crying , episodes of apnea, snoring, nasal flutter, nasal congestion, nasal discharge, stertor, snoring, intercostal and jugulum retractions, hyponasal cry, aerophagia with abdominal tension, sleep disturbances and growth retardation . In addiBilateral CA is associated in 34% with other upper respiratory tract abnormalities, which lead to respiratory distress. These include subglottic stenosis, laryngomalacia and tracheomalacia. In addition, in 21%, bilateral CA is accompanied by other congenital craniofacial abnormalities  5]..5].Unilateral CA rarely causes neonatal respiratory distress syndrome. It is most commonly expressed later than bilateral CA, with a clinical picture of chronic unilateral nasal discharge and unilateral obstruction, which may resemble chronic rhinosinusitis or a foreign body in the nasal cavity. As a result, unilateral CA is often diagnosed later in adulthood .When preparing the recommendations, we followed the procedure of Rosenfeld et al. (2013) for the preparation of clinical guidelines and recommendations in otorhinolaryngology—head and neck surgery  and geneInstead of conference calls, five live meetings were held. Recommendations were written , which wFor each recommendation, we determined the level of evidence and the evidence grade using the OCEBM Levels of Evidence  29]. In. In29]. ∙ Strongly recommended means that the physician should follow the recommendation unless there is a clear and compelling argument against the recommendation.∙ Recommended means that the physician should follow the recommendation but pay attention to new information and patient peculiarities.∙ Optional means that the physician must be flexible in making decisions and accepting the recommendation. He must consider the possibility of taking different measures and measures adapted to the patient .First, the evidence grade was determined for the included studies according to OCEBM , and theThe preliminary response to the recommendations was determined at their presentation at the sectional meeting of the section for otorhinolaryngology of the Slovenian Medical Association on 19th December 2020. We accepted responses from the professional public until the recommendations were presented at the Expert Council for Otorhinolaryngology of the Slovenian Medical Association. This is the umbrella regulatory body for the field of otorhinolaryngology in Slovenia. It reviewed recommendations, suggested corrections and approved them on 10th May 2021.Thirty-four recommendations were written  and coorAt birth or in the early postpartum period, the clinical picture of respiratory obstruction should be checked for nasal patency to rule out bilateral CA  and otheRecommendation 1:In the case of respiratory distress in a neonate, we recommend that the physician perform a test with a saline solution to confirm or rule out nasal obstruction—level of Evidence IIa, evidence grade C  Figure .A few drops of saline solution are instilled into both nostrils. If the saline solution pours forward from the nostrils, the test is positive on the side (or both) where the spill is observed. This makes CA likely. If the saline solution passes into the throat, the test is negative. Therefore, CA is not possible, but respiratory distress can be caused by other causes of nasal obstruction .Recommendation 2:We recommend a positive saline test followed by a Fr 6-8 aspiration catheter test—level of Evidence IIa, evidence grade C  Figure .An aspiration catheter is used to assess the patency of the nasal cavities and the nasopharynx and, in some cases, eliminates the reversible cause of nasal obstruction . If it is not possible to insert the aspiration catheter 1–2 cm beyond the nostril, the obstruction is most likely due to deviation of the nasal septum or thickening of the inferior nasal turbinate, and in the case of the obstruction 3–3.5 cm deep, it is most likely CA or choanal stenosis. In addition to the test with an aspiration catheter, there is also a test with the instillation of methylene blue in the nostril with the examination of the pharynx, a test with a cotton swab or a mirror to observe the airflow through the nostrils  and the After establishing a free airway and the initial clinical examination, an extended diagnostic workup is required in the early postpartum period, which depends on the clinical presentation and risk factors for associated abnormalities.Recommendation 3:We strongly recommend that the otorhinolaryngological examination include examining the nose and face to rule out associated abnormalities . This shRecommendation 4:Although CA is a clinical diagnosis, we strongly recommend that a 2–5 mm slice thickness CT scan of the facial structures, nose, paranasal sinuses and skull base be performed in every patient to confirm the diagnosis and plan treatment—level of evidence I, evidence grade A  4,13].,13.4,13]A CT can also identify other causes of nasal obstruction  4]. Bef. Bef4]. Recommendation 5:We strongly recommend that a head ultrasound be performed to rule out central nervous system involvement, which is common, especially in preterm newborns—level of Evidence I, evidence grade C  26]..26].An MRI of the head should only be performed in CA in selected cases .Recommendation 6:Bilateral CA often occurs in the context of other congenital syndromes, so clinical geneticist consultation is strongly recommended—level of Evidence I, evidence grade B .Recommendation 7:From the point of view of the need for surgical care of a child with bilateral CA, we strongly recommend excluding congenital abnormalities that would put the child at risk during the procedure, especially heart disease, so we recommend an evaluation by a cardiologist—level of Evidence I, evidence grade B .Recommendation 8:Even within otorhinolaryngology and in the postoperative period, we strongly recommend an audiovestibulological examination for a hearing evaluation and evaluation by a phoniatrician for additional swallowing problems—level of evidence I, evidence grade D  2,4,5,7,75,7,8,9A neurologist, urologist or ophthalmologist is included in the treatment if necessary  13]..13].In the case of unilateral CA, the diagnosis is usually established later, as the clinical picture of unilateral CA is rarely manifested as respiratory distress. Therefore, diagnostics can be performed on an outpatient basis. The otorhinolaryngologist determines the patency of the nose using an aspiration catheter (appropriate size for the patient’s age), anterior rhinoscopy and nasal endoscopy. Despite everything, he must also pay special attention to possible associated diseases and refer the patient for further treatment.Recommendation 9:In the case of unilateral CA, we recommend a CT of the facial structures, nose, paranasal cavities and skull base be performed. With an unmistakable clinical picture and endoscopic status, this is indicated only before surgical treatment to avoid the unnecessary exposure of the child to ionizing radiation—level of Evidence IIa, evidence grade D .Recommendation 10:In all cases of unilateral CA, we strongly recommend audiovestibulological evaluation, and for additional swallowing problems, treatment by a phoniatrician—level of evidence I, evidence grade D .Before a thorough diagnosis and therapy, it is necessary to immediately ensure a free airway through the mouth by inserting a McGovern nipple in case of bilateral CA . Then, aRecommendation 11:We strongly recommend that bilateral CA be surgically treated between the 10th and 13th day of the neonate’s age, even in the case of prematurity—level of evidence I, evidence grade A  16,27].,27.16,27Before surgical treatment, it is first necessary to carry out urgent diagnostic procedures to determine associated diseases and risk factors, especially cardiological treatment  13]. Th. Th13]. Even though the first description of surgical treatment of CA dates back to the mid-19th century, there is still no clear consensus on surgical techniques to date . There aSurgical treatment can be divided into transnasal perforation, transpalatal resection, transnasal endoscopically assisted perforation and transnasal endoscopic choanoplasty . A stent2 laser .,13.4,13]The procedure is identical to the described blind perforation with additional endoscopic control. This reduces the possibility of unwanted damage to adjacent tissues C.In the case of prematurity, endoscopic transparency and the use of endoscopic instruments are limited, so transnasal endoscopic choanoplasty is often not possible. Then, transnasal endoscopically assisted perforation is the method of choice for treating bilateral CA. This procedure will most likely require a later  transnasal endoscopic choanoplasty when the child has grown, and the anatomical conditions allow this surgical treatment method.There is no mucosal flap elevation and posterior nasal septum resection in transnasal perforation techniques .In transpalatal resection, the mucous membrane of the hard palate is raised in a local flap, and the entire thickness of the bone in the area of bony atresia is drilled away . DespiteRecommendation 17:In the primary treatment of CA, we recommend against transpalatal resection of CA—level of evidence III, evidence grade A  4,13].,13.4,13]The age at which unilateral CA is treated depends on the patient’s age at the time of the unequivocal diagnosis, which is based on the results of a systematic review by Murray et al. (2019).Recommendation 18:Surgical treatment of unilateral CA is recommended after the infant is six months old—level of evidence IIa, evidence grade A  Table 2Table 2 .Even with the start of treatment after the third year of age, we expect the same results as before .Recommendation 19:Transnasal endoscopic choanoplasty is strongly recommended for unilateral CA due to the mostly good endoscopic visualization in older patients with unilateral CA. The extent of the resection should be large enough so that it is not necessary to use a stent—level of evidence I, evidence grade A  13]..13].Postoperative management depends on the CA’s location, the patient’s general health and the patient’s setting .Postoperative treatment after surgical treatment of bilateral CA depends mainly on associated diseases, the gestational age of the neonate and the related need for treatment of other conditions. Children with CHARGE syndrome have a higher risk of postoperative complications and prolonged hospitalization . The samRecommendation 20:In the case of bilateral CA where a stent was used to ensure nasal patency, it is recommended that the stent be changed several times a week endoscopically during the first and second postoperative week—level of evidence IIa, evidence grade D  Table 2Table 2.During this period, it is reasonable to increase the outer diameter of the stent so that the lumen of the neochoana increases significantly, such as twice the outer diameter of the endotracheal tube, as long as the anatomical conditions allow this increase (we did not reach the maximum possible dimensions). This is especially necessary after transnasal endoscopically guided perforation and transnasal perforation. After transnasal endoscopic choanoplasty, the insertion of stents is often not needed.Recommendation 21:We recommend that discharge from the hospital be planned for the second postoperative week or as soon as possible when the general state of health allows it and the patency of the stents is satisfactory with appropriate care—level of Evidence IIa, evidence grade D .We monitor the child’s breathing patterns until discharge. In addition to normal breathing, the main goal of treatment for bilateral CA is independent feeding without breaks as soon as possible after surgical treatment.Recommendation 22:Stent replacement on an outpatient basis in the second week is optional—level of evidence IIb, evidence grade D .Recommendation 23:In the third week, it is optional to replace the stent twice, and from the fourth week onwards, only once more—level of evidence IIb, evidence grade D .Recommendation 24:We strongly recommend removing the stent in the coming weeks and rechecking the patency the week after—level of Evidence I, evidence grade D .The replacement of stents in the postoperative period can be postponed as long as their patency is satisfactory. Instead of changing stents, we can perform regular dilations, especially after transnasal endoscopically controlled perforation and transnasal perforation, for example, with a balloon dilator, which has already been used in the treatment of bilateral CA .Recommendation 25:Photo documentation of the lumen is recommended—level of evidence IIa, evidence grade D .The intervals between check-ups are gradually being prolonged. Otherwise, restenosis after one year is rare .Recommendation 26:Follow-up is strongly recommended for at least two years after the procedure or until the end of growth to detect restenosis—level of evidence I, evidence grade C  Table 2Table 2.Upon discharge from the hospital, it is necessary to include the child’s parents in the treatment process. They should be taught how to clean the nose effectively and reinsert the stent, and clear instructions should be given in the event of the infant’s respiratory distress. In the case of breathing problems, poor nasal patency or discharge, a repeat examination by an otorhinolaryngologist is necessary to assess choanal patency accurately. In the postoperative period, we plan as few examinations as possible in the hospital.Recommendation 27:Revision transnasal endoscopic surgery is recommended in case of breathing problems, poor nasal patency or discharge and more than 50% reduction of the choanal lumen—level of evidence IIa, evidence grade A .CT or other radiological examinations are not routinely indicated in postoperative management, even in restenosis .Recommendation 28:During the postoperative treatment of the infant, the daily use of proton pump inhibitors is recommended for the first two months —level of evidence IIa, evidence grade C .Recommendation 29:During the postoperative management of the infant, the instillation of saline solution  and nasal glucocorticoid drops with low systemic absorption  are strongly recommended for the first two months—level of evidence I, evidence grade C ,28.The drops should be instilled next to the stent and not into it.Recommendation 30:During the first two months of postoperative treatment of the infant, antibiotic drops are recommended exceptionally in the first postoperative week or later when noticeable purulent discharge appears—level of Evidence IIa, evidence grade D .In the case of systemic signs of infection, identification of the source of infection and systemic treatment are indicated.In the postoperative treatment of patients after transnasal endoscopic choanoplasty of bilateral CA without inserted stents, the infant can already start eating food by mouth on the first day, as soon as the effects of general anaesthesia (anaesthetics and narcotics) wear off after a few hours. We monitor the child’s breathing patterns, which must be appropriate in all life circumstances (sleeping and feeding). Otherwise, it is necessary to determine the cause of breathing problems, which may be local or an associated, unrecognized pathology.Recommendation 31:The first postoperative examination with the assessment of nasal breathing with the mouth closed and feeding by mouth without pauses for breathing is recommended the day after surgery (first postoperative day)—level of evidence Iia, evidence grade D.Recommendation 32:We allow the possibility of discharge from the hospital on the second postoperative day—level of evidence Iib, evidence grade D.Recommendation 33:We recommend nasal endoscopy one week after surgery, two weeks after surgery and four weeks after surgery—level of evidence IIa, evidence grade D  Table 2Table 2.Photo documentation enables comparison between inspections. Instructions to parents and recommendations regarding the use of drops and revision surgery are the same as for patients with inserted stents .Recommendation 34:With unilateral CA, the risk of respiratory distress is very low, so we recommend discharge on the first postoperative day—level of evidence IIa, evidence grade D .We perform the first examination on this day, especially the nasal cavity toilet. We are planning the subsequent outpatient check-up in one week. In the following weeks, the otorhinolaryngologist decides on the frequency of check-ups. Parental instructions and recommendations regarding the use of drops, follow-up and revision surgery are the same as for patients with stents.The paper presents the first Slovenian recommendations for treating patients with choanal atresia. They are based on foreign medical institutions’ published literature and our clinical experience. They represent the basic requirements of diagnostics and are a possible essential guide in treatment, which, however, must be adapted according to the current situation. Therefore, a thorough review of each recommendation is necessary before implementation.However, these recommendations focus on the otorhinolaryngological management of choanal atresia, which should be considered. Moreover, only a small number of systematic reviews and meta-analyses are included in this study.In further decades of experience and technology development, recommendations can be expected to improve due to changes in treatment, especially transnasal endoscopic surgical techniques, the use of stents and other methods of preventing restenosis. Therefore, it makes sense to create a register of patients with choanal atresia and other congenital anomalies of the craniofacial area, upper respiratory tract and gastrointestinal tract for prospective data collection.


Intrinsically disordered proteins (IDPs) lack a stable three-dimensional structure under physiological conditions but play crucial roles in many biological processes. Intrinsically disordered proteins perform various biological functions by interacting with other ligands.http://www.s-bioinformatics.cn/idpsbind/home/.Here, we present a database, IDPsBind, which displays interacting sites between IDPs and interacting ligands by using the distance threshold method in known 3D structure IDPs complexes from the PDB database. IDPsBind contains 9626 IDPs complexes and 880 intrinsically disordered proteins verified by experiments. The current release of the IDPsBind database is defined as version 1.0. IDPsBind is freely accessible at IDPsBind provides more comprehensive interaction sites for IDPs complexes of known 3D structures. It can not only help the subsequent studies of the interaction mechanism of intrinsically disordered proteins but also provides a suitable background for developing the algorithms for predicting the interaction sites of intrinsically disordered proteins. Still, they participate in many important biological processes such as cell signal transduction, DNA metabolism, mRNA alternative splicing, protein–protein interaction, and so on –3. Recenroteomes , in whicroteomes  providesroteomes  is a datroteomes .These IDPs perform critical biological functions by interacting with other proteins or ligands. Currently, there are some databases about binding sites –15, suchhttp://www.Disprot.org/, release: 2020_12) [The following is the procedure for IDPsBind construction. (a) The intrinsically disordered proteins (IDPs) are derived from the Disprot (2020_12) ; (b) EliAs in previous studies, an amino acid residue within a protein sequence is designated as a binding site if it contains at least one atom that falls within a cutoff distance from any atoms of the ligand molecule in the complex –19. BindHome’ page describes the introduction of the IDPsBind database provides links to the three primary associated databases. The ‘Browse’ page displays the summary of all entries in the IDPsBind database. This interface lists six components: IDPsBind ID, Disprot ID, UniProt ID, Protein name, Source, and Disordered content. All items collected in IDPsBind numbered from IDP0001 to IDP0880 can be retrieved by clicking the ‘Browse’ option. Clicking any IDPsBind ID will return a display of the detailed information on the target chain. The data stored for each ID has three parts. The first part shows the basic information about the protein. The second part provides the sequence of IDPs in the Disprot database and color-codes the disordered regions. The third part shows the labeled binding sites of the PDB chains (resolution better than 3.5 angstroms) when the protein interacts with ligands. Moreover, the interface displays the abbreviation of the ligand, click the ‘?’ label will show the full name of the ligand. Users can also check specific ligand information clicking the abbreviated ligand jump link to a new interface. And clicking the ‘load’ option, the corresponding structure of the complex is visualized on the right side of the page. The IDPsBind database is freely available for download. Users can download them as a whole on the ‘Download’ page. On the Search interface, users enter any keyword or IDPsBind /Disprot / Uniprot ID and then click the ‘search’, then the page shows the results similar to the “Browse the entry” page. The ‘Statistics’ interface shows some basic data and information about the IDPsBind database. The ‘Help’ interface answers some questions on the IDPsBind database. The current release of IDPsBind is 1.0, which will be updated in the future during the PDB release update.IDPsBind provides six basic interfaces: Home, Browse, Download, Search, Statistics, and Help. The ‘We have developed a comprehensive IDPs-ligand interaction database, IDPsBind, in which IDPs are taken from the DisProt database (2020_12), and corresponding IDPs complexes are from the PDB database. Although there are already a handful of ligand-binding databases in the literature, IDPsBind is distinguished from other databases in the following aspects. (a) IDPsBind contains many interactions of IDPs, 3203 binding ligands including proteins, DNA, RNA, et al. (b) The interaction includes not only the disordered regions with the ligand, but also that of the ordered regions in IDPsBind. (c) The IDPs-ligand binding information is based on the PDB file, and all the PDB chains (resolution better than 3.5 angstroms) for IDPs were analyzed. In this way, ligand-binding sites of the target chain cannot be missing in IDPsBind. (d) All data in IDPsBind database are freely available for download. We hope that the IDPsBind can provide helpful information required for specific IDPs-relevant studies.


Mobile-linked point-of-care diagnostics forms an integral part of diagnostic health services for efficient communication between patients and healthcare professionals despite geographical location and time of diagnosis. The efficiency of this technology lies in the user experience which means that the interaction of the user with the implemented technology needs to be simple, convenient, and consistent. Having a well-structured user experience of these devices in community-based healthcare will aid in sustainable implementation. Herein, we propose to conduct a literature search to systematically map out evidence based on mobile-linked POC diagnostics user experience at a community level in resource-limited settings.et al. A comprehensive search will be conducted to find relevant published literature from the following electronic databases: Scopus, Web of Science, EBSCOhost . Grey literature will also be searched, including reports from government and international organizations such as World Health Organization (WHO), Foundation for Innovative New Diagnostics (FIND), and the Food and Drug Administration (FDA). Two independent reviewers will screen the relevant studies and the degree of the agreement will be determined by calculating Cohen’s kappa statistic. The quality of eligible data will also be appraised using the mixed method appraisal tool version 2018.The proposed scoping review will be guided by the advanced Arksey and O’Malley methodological framework and further advanced by Levac We anticipate that the planned scoping review will present useful evidence to inform stakeholders on the integration of mobile-linked diagnostic devices in community-based healthcare which will guide further research on the subject. Mobile health  refers to the use of mobile devices with medical-based software to make healthcare more accessible to patients and potentially improve the manner in which patient medical information is managed . mHealthIn order to address this shortfall, the Joint United Nations Programme on HIV/AIDS (UNAIDs) and World Health Organization (WHO) developed a strategic plan that entailed the linking of wireless mobile communication to POC diagnostics and the implementation of this strategy in health policies and programs, which was aimed at addressing the advanced technology improvements and their contribution to healthcare systems . The estIn community-based healthcare, the integration of mobile-linked POC diagnostics needs to be carried out in a manner that will be useful and accessible in resource-limited settings . Reportshttps://archive.org/details/osf-registrations-zs3pb-v1The methodological framework that was proposed by Arksey and O’Malley  and furtTable 1). The research question is: What is the level of user experience of mobile-linked (m-linked) POC diagnostics in community-based healthcare? The identified population was m-linked POC diagnostics which we define as technology that allows for the screening and diagnostics of communicable and non-communicable diseases in remote settings by healthcare professionals and patients [We employed the PCC  nomenclature to determine the eligibility of the research question for a scoping review . The principal investigator (PI), subject specialist, and university librarian will develop a comprehensive search strategy to ensure the correct use of indexing terminology and Medical Subject Headings (MeSH) terms. Grey literature including dissertations/theses, conference proceedings, websites of international organizations such as WHO, and government reports, will also be explored. Additional relevant studies will be identified by manually searching all references cited in the included studies to identify studies not indexed in electronic databases. There will be no language restrictions applied, to minimize the risk of excluding relevant studies. The following keywords will be used (and refined to suit each database): 1- “User experience” or “user experience in health technologies” or “UX” or “UX in health technologies” 2- “point of care” or “point of care testing” or “point of care diagnostics” or “point of care diagnostic services” or “mobile-linked point-of-care diagnostics” and 3- “community-based health” or “community-based healthcare” or “primary healthcare”. Each search will be documented in detail, showing the keywords date of search, electronic database, and the number of retrieved studies, and the results of the search will be tabulated. The search strategy will be optimized by adopting the search summary table (SST) outlined by Bethel et al.,  as a guiA pilot search in various electronic databases was conducted to demonstrate the feasibility of addressing our research question using a scoping review. The results of our pilot search are indicated in This scoping review will be guided using inclusion and exclusion criteria to ensure that relevant studies are selected:The included articles should meet the following criteria:Articles reporting on mobile-linked POC diagnostics in a community-based healthcare settingArticles reporting on technology that allows for the screening and diagnostics of communicable and non-communicable diseases in remote settingsArticles reporting on the user experience (UX) in health technologiesArticles reporting on the evidence of community-based healthcare on a local, personalized levelAll reviews providing evidence of mobile-linked point-of-care diagnostic systemsArticles were excluded from the scoping review if they fall under the following description:Articles that lacked evidence on point-of-care diagnostics in community-based healthcareArticles that lacked evidence on the user experience (UX) of health technologies at the primary healthcare levelAll reviews not providing evidence of integrated mobile-linked point-of-care diagnostic systemsFig 1.The articles will be screened in three stages: title, abstract and full article. Reviewers will use a screening tool developed by the PI and pilot tested by the reviewers. The eligible articles will be exported to an Endnote 20 library, and the duplicates will be removed. The PI will screen abstracts in parallel with the co-reviewer. After screening the abstracts, the reviewers will discuss any discrepancies in the selected articles until a consensus is reached. Two reviewers will then screen the full texts of articles selected during the first stage. A third screener will resolve any discrepancies in the selected articles after the full-text screening. Both abstract and full-article screening will be guided by the screening tool that factored in all aspects of the inclusion/exclusion criteria and the PCC elements. The level of agreement between screeners’ results after screening the abstracts and full articles will be determined by calculating Cohen’s kappa statistics. The kappa statistics were interpreted as follows: values <0.1 indicate no agreement and 0.10–0.20 indicate none to slight, 0.21–0.40 as fair, 0.41–0.60 as moderate, 0.61–0.80 as substantial, and 0.81–1.00 as almost perfect agreement. Database search and screening results will be presented using the PRISMA chart which is shown in A data charting form will be used to capture all relevant data from the articles reviewed. Two independent reviewers will pilot the data charting form and recommend modifications that will be implemented. The following data will be extracted from the included articles: author and year of publication, the title of study, aim of the study, study design, study setting, study population, type of point-of-care test investigated, the level of user experience of the identified POC diagnostic tests and other significant findings.The quantitative data extracted from the included articles will be presented in a table and graphic format. Qualitative data will be summarised according to emerging themes.The quality of the included articles will be evaluated using the mixed method appraisal tool  version This scoping review will be developed and compiled using existing literature. No primary data will be collected to answer the research question.According to the Foundation for Innovative New Diagnostics (FIND) 2021 strategy report, no diagnostic tests exist for 60% of the pathogens already identified by the World Health Organization (WHO) to have the potential of developing into another pandemic. In addition, half of the known top 20 diseases which are responsible for the highest mortality rate have no reliable diagnostic test kits . To solvIn order to gather relevant evidence to answer our research question, this scoping review will exclude articles that lack evidence on point-of-care diagnostics in community-based healthcare. Articles that lack evidence on the user experience (UX) of health technologies in community-based healthcare and all reviews that do not provide evidence of integrated mobile-linked point-of-care diagnostic systems will also be excluded. The third sustainable development goal (SDG3) is to ensure healthy lives and promote well-being for all. More specifically, SDG 3.4 aims to reduce premature mortality by a third, from non-communicable diseases through prevention and treatment . This woS1 Checklist(DOCX)Click here for additional data file.