The main aim of this study is to test the validity of the Motivation, Engagement, and Thriving in User Experience (METUX) model  in higher education. We propose a process model in which we investigate how the need-satisfaction of digital learning tools within the interface sphere and task sphere accounts for engagement, learning, and well-being. A total of 426 higher education students drawn from two subsamples participated in this cross-sectional study. A structural equation model shows that interface autonomy and competence satisfaction positively predict task autonomy and competence. Task competence, in turn, negatively predicts focused attention and positively predicts perceived usability and well-being. Task autonomy positively predicts perceived usability and reward. Based on our results, we provide some initial support for the METUX model in higher education. However, more validation work is needed to improve the scale that measures need-satisfaction in the interface and task spheres. Moreover, we find no support for the effect of task sphere on learning. Further investigations are needed into how METUX can be used in domain- and situation-specific contexts to account for increases in engagement, learning, and well-being. Finally, future studies need to include all aspects of the METUX model in order to fully test its validity. Technological devices  have become ubiquitous for higher education students in everyday life and for learning purposes. Recent reports suggest that 97% of the student population in Norway owns some form of technological device  app may result in the adoption of this digital learning tool in order to support the learning task. According to the METUX model, the extent to which the technology is adopted and used over time depends on the motivation of the student for acquiring it. This motivation may be either autonomous (behaviors enacted out of volition and choice) or controlled (behaviors enacted out of pressure or contingent on self-worth).The interface sphere consists of interacting with the technology's interface during use, for instance, a student's experience of controls and navigation, display, and aesthetic within Coursera or LMS app when using it for a learning task. When students interact with a digital learning tool, the satisfaction of the basic psychological needs, via the user interface, predict usability, engagement with technology, and user satisfaction.The task sphere consists of engaging in a technology-specific task. An example of this is the extent to which students experience that Coursera or an LMS app support their learning by means of features and functionalities in these digital tools. When students engage with tasks, the satisfaction of basic psychological needs, via engagement with technology-specific tasks, predicts engagement with the task and user satisfaction.The behavior, which consists of engaging in a behavior that the technology is intended to support. For example, students experience that the Coursera or LMS app increases learning, which is what it is intended to do. When students engage in a behavior that the digital learning tool is intended to increase, the extent to which students actually learn as a result of using the digital learning tool depends on the need-satisfaction when learning.The fourth sphere is experience of life sphere lies beyond the technology. For example, students may learn skills such as mindfulness, mental health awareness, and sleep improvement within a Coursera course that increases their well-being beyond the behavior sphere, that is, learning about mindfulness and doing mindfulness may increase learning of the practice and theory (behavior sphere), plus practicing mindfulness may increase life satisfaction and positive affect (life sphere) because the student becomes more aware and attentive of moment-to-moment situations, which may in itself be need-satisfying.The user's overall society sphere consists of the experience of all members of society, beyond the technology. An example of this is a well-designed instructional video in Coursera on environmental conservation. After interacting and learning the content of the video, the viewer may display more environment-friendly behaviors, thus reducing pollution of the sea, land, and air.The As previously mentioned, the METUX model has yet to be validated, and there is no empirical support for its effectiveness in a higher education context. However, Peters et al.  providedIn particular, research has shown that interaction with digital tools in learning is related to the quality of user experience  , which may lead to overuse  higher education students in natural sciences (n = 147), social sciences (n = 109), economics (n = 94), health (n = 30), humanities (n = 24), law (n = 5), and arts (n = 14). Students who participated in this study were both bachelor's degree and master's degree students, and the average student had 3.44 years of higher education. The participants were drawn from two sub-samples. Sample 1 consisted of 224  Norwegian higher education students. The students from sample 1 were recruited when participating in different campus courses. Sample 2 consisted of 201  higher education students recruited through TurkPrime crowding source , software (n = 105), online resource (n = 235), and others (n = 14).Following the research on passion , and we followed the ethical guidelines from NSD. The students in both samples were informed that they could withdraw at any time and that participation was voluntary and anonymous. The students in the Norwegian sample were given the possibility to win one of 10 gift cards if they provided their mobile number on a different questionnaire. This was done in order to ensure that the participants' mobile numbers were not linked to their responses. Students from the TurkPrime sample were paid 1 USD for participation. Answering the questionnaire took around 5–7 min to complete.To measure the students' interface satisfaction of the need for autonomy and competence, we used the 10-item Technology-Based Experience of Need Satisfaction scale  approach. The FIML approach is, according to Byrne , Tucker–Lewis Index (TLI), and Incremental Fit Index (IFI) above or equal to 0.90, and root mean square error of approximation (RMSEA) and standardized root mean square residual (SRMR) within 0.00–0.05 is recommended, whereas 0.05–0.10 is acceptable , CFI = 0.81, TLI = 0.62, RMSEA = 0.28, and SRMR = 0.10. Modification indices suggest covarying items 1 and 2 (both reverse-worded). We re-specified the model, and the model fit improved substantially. Results from the chi-square difference test indicate that the new model is significantly better: χ2-diff = 156(1), p < 0.001. For interface autonomy, CFA shows a poor model fit: χ2 = 68.73(5), CFI = 0.90, TLI = 0.80, RMSEA = 0.17, and SRMR = 0.09. The model evaluation shows that two items, both negatively worded, have weak factor loadings (<0.30), and these items are therefore omitted. Finally, the CFA for task competence also shows a poor model fit: χ2 = 88.35(2), CFI = 0.85, TLI = 0.55, RMSEA = 0.31, and SRMR = 0.09. The modification indices suggest that the covariation between items 1 and 2 (both reverse-worded) would improve the model fit. Re-specification of the model with covariation between items 1 and 2 improved the model fit significantly: χ2-diff = 81.6(1), p < 0.001. The model fit for the remaining latent variables is within the acceptable range and as expected. We find that the standardized factor loadings for each scale are within the acceptable range for most scales. One item has a standardized factor loading of 0.47 and 0.58 for interface competence and perceived learning, respectively, which is below the recommended range. Furthermore, AVE for interface autonomy, task competence, and task autonomy are below the recommended threshold, indicating that more error remains than can be explained by the latent factors of the items. The final results of the CFA for each latent variable are presented in 2 = 1,014.76(333), CFI = 0.90, TLI = 0.89, RMSEA = 0.06 , and SRMR = 0.07.In order to test the factor structure for each latent variable, we performed separate CFAs for each of the study variables. The results from the CFA for interface competence reveal a poor model fit: χ2 = 1,719.83(705), p < 0.001, CFI = 0.91, TLI = 0.90, IFI = 0.90, RMSEA = 0.05 , and SRMR = 0.07. The model shows that interface competence and interface autonomy positively predict task competence. Task autonomy is positively predicted by both interface competence and interface autonomy. Task competence is negatively related to focused attention, whereas task autonomy is unrelated. Perceived usability is predicted by task competence but is unrelated to task autonomy. Task competence is unrelated to aesthetic appeal, whereas task autonomy is positively related. Task competence is unrelated to reward, whereas task autonomy is positively related. Perceived learning is unrelated to both task competence and task autonomy. Finally, task competence is positively related to well-being, whereas task autonomy is unrelated.A full latent structural equation model was specified according to theoretical assumptions described in the introduction section. The overall results of the structural model  show an via task competence as mediator. Furthermore, the effect of interface competence increases perceived usability indirectly and positively via task competence. Interface competence positively enhances well-being through the effect of task competence. Interface competence indirectly and positively predicts perceived usability via task autonomy.The indirect effect analyses  show thaInterface autonomy predicted both focused attention negatively and perceived usability positively through the effect of task competence as mediator. Interface autonomy is indirectly and positively related to perceived usability, mediated through task autonomy. Lastly, the effect of interface autonomy on reward is mediated by task autonomy.The main aim of this study is to investigate the extent to which the design of digital learning tools in the interface and task spheres predict engagement, learning, and well-being among students in higher education. We tested these relations on the basis of the METUX model which is derived from SDT. In general, the results from our analyses partly support our hypotheses.As expected, we find support for the assumption that need-satisfaction in the interface sphere predicts need-satisfaction in the task sphere. This is found both at the correlational level and in our structural equation model. Importantly, the shared variance between need-satisfaction in the interface and task spheres is not substantially high, indicating that we are measuring two distinct constructs . The strongest coefficient in our model is the effect from interface competence to task competence which shares ~66% of the variance. These findings are in line with the preliminary results of Peters et al.  and hintWe find only partial support for our predictors of engagement, learning, and well-being. Specifically, we find that task competence is a negative predictor of focused attention, while interface competence is a negative and indirect predictor, which is unexpected. However, task autonomy has no effect on engagement, learning, and well-being. This latter finding is also unexpected, given that need-satisfaction within technology should enhance feelings of immersion as suggested by the METUX model . In contrast, some students may use Coursera because they feel pressured by teachers or because they want to show that they are intelligent compared to other peers (controlled motivation). These different underlying reasons for using digital learning tools may have an impact on behavioral engagement, persistence on task, and learning. Hence, we recommend future studies to measure the adoption sphere. Similarly, if measuring relevant digital learning tools, future studies would have to include the social sphere in order to further test the validity of the METUX model. Furthermore, we did not measure relatedness. This could be important given that relatedness satisfaction may be crucial when students are collaborating through social media, for instance. Future studies would need to replicate our study and include relatedness in their model. In order to remove the confounding effect of relatedness found in different digital learning tools, future studies should include only social media platforms in order to test the effect of relatedness on engagement, learning, and well-being.Third, we only measured perceived learning as opposed to actual achievement. It may be argued that actual academic achievement scores are more reliable than perceived learning , future studies need to investigate these relations in multiple countries  and contexts . This will further test the validity of the METUX model.Several implications can be drawn from our results. First, our confirmatory factor analyses show that some of the items on specific scales need improvement. Specifically, we find that negatively worded items are the items that were removed or needed residual covariation, both of which are recommended with caution . The METUX model can potentially be used to inform different digital learning tools, learning management systems, and design of motivational mechanisms to facilitate engagement, learning, and well-being. However, there is a need for more empirical research to further test the validity of the METUX model in different contexts by using a different research design before implementing this as a framework for designing digital learning tools in educational contexts.https://osf.io/ds2pu/]. R-codes for the analyses are available in the GitHub repository [https://github.com/lujeno/METUX/blob/main/METUX2018.R].The dataset generated for this study is available in the Open Science Framework repository [The studies involving human participants were reviewed and approved by Norwegian Centre for Research Data. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.LJ and J-AG designed the study. LJ and ÅD prepared the study materials. LJ collected and analyzed the data and wrote the first draft of the manuscript. All the authors have read, commented, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Thanks to the rapid advances of technology, we are currently experiencing the fourth industrial revolution, which is introducing several changes in how organizations operate and how people learn and do their work. Many questions arise within this framework about how these transformations may affect workers’ wellbeing, and the Work and Organizational Psychology is called upon to address these open issues. This study aims to investigate personal and organizational antecedents  and one consequence (work engagement) of technology acceptance within factories, comparing white- and blue-collar workers. The study involved a sample of 598 workers  employed at an Italian company who filled in a self-report questionnaire. In both samples, the multi-group structural equation model showed a positive relationship between resilience, opportunities for information and training, and technology acceptance, which in turn showed a positive association with work engagement. All indirect effects were significant. This study investigated the motivational dynamics related to the introduction of new technologies within factories involving the little-studied population of blue-collar workers. Results highlighted the importance of providing information and opportunities for training to all employees, in order to support Industry 4.0 transformations without impacting on workers’ motivation. The fourth industrial revolution, also called Industry 4.0, especially in Europe, is already underway. Rapid advances in technology, digitalization, smart technologies, automation and the industrial internet have enabled and characterized its progression. As with any previous industrial revolution, this one, too, has important economic, political and social implications, and deeply modifies how organizations function and how people work . AccordiIn general, Industry 4.0 refers to a series of transformations related to the use of several new technologies that will lead to more flexible, automated and interconnected manufacturing processes. What defines this revolution is the presence of Cyber Physical Systems (CPSs), the combination of enabling technologies which can facilitate the interconnection between different subjects, hardware, software and humans . More spMany benefits of Industry 4.0 may be acknowledged ,6.On the other side, some risks emerge. New technology implementation often fails because of employee resistance  and becaIn light of this premise, the aim of this study was to analyse technology acceptance among white- and blue-collar workers employed in an Italian manufacturing company that was introducing innovative systems. More specifically, the study intended to analyse the antecedents of technology acceptance, considering personal  and organizational (opportunities for information and training) dimensions, and their relationship with work engagement. In doing so, the study highlighted the role of organizations in the promotion of public health. Work engagement, indeed, which is a state of motivation, enthusiasm and energy caused by work, is considered one of the work-related wellbeing dimensions  and, morTechnology acceptance literature is aimed at studying how individuals’ perceptions affect their intentions to use technology as well as its actual usage. Understanding the dynamics that can influence people’s acceptance of new technologies has become an increasingly central issue given the massive spread of new tools and devices. Several authors have tried to explain technology acceptance and many models are available in the psychological and sociological literature today . The Technology Acceptance Model (TAM)  is the oA third belief construct has been proposed for the TAM by Mathieson and colleagues . They inAnother prominent theory in the study and application of technology acceptance is the Unified Theory of Acceptance and Use of Technology (UTAUT) , which wMore recently, Kaasinen and colleagues  proposedThe framework of Kaasinen and colleagues  aims to In this study, we used part of the Worker-Centric Design and Evaluation Framework for Operator 4.0 to investigate the antecedents and impacts of technology acceptance. As a wellbeing outcome, we considered work engagement, defined by Schaufeli and colleagues  as “a poIn the literature, positive associations between work engagement and performance outcomes have been found, such as in-role and extra-role performance, team performance, customer loyalty, quality of service and care ; thus, wThe Industry 4.0 revolution entails several changes for industries and societies and is contributing to the current perception of the world being a place characterized by Vulnerability, Uncertainty, Complexity and Ambiguity (VUCA) . In ordeThe second personal resource considered in this study is goal orientation, originally defined as a situated orientation for action or a disposition toward developing and demonstrating abilities in the accomplishment of a task . In applAmong organizational antecedents, opportunities for information and training have been considered. The lack of technical and digital skills and the subsequent need for training is one of the most significant hindrances to the implementation of new innovative technologies . At the In order to introduce and implement new systems in an effective way, organizations should develop interventions that can encourage acceptance and compliance among workers ,42. A coGiven these premises, this study intended to investigate how resilience and goal orientation (as user characteristics) and opportunities for information and training received  are related to technology acceptance, and how the latter is associated with work engagement. Hypothesis 1 (H1).(a) resilience and (b) goal orientation have a positive relationship with technology acceptance in white- and blue-collar workers.Hypothesis 2 (H2).Opportunities for information and training have a positive relationship with technology acceptance in white- and blue-collar workers.Hypothesis 3 (H3).Technology acceptance has a positive relationship with work engagement in white- and blue-collar workers.Hypothesis 4 (H4).(a) resilience and (b) goal orientation have a positive relationship with work engagement in white- and blue-collar workers.Hypothesis 5 (H5).Opportunities for information and training have a positive relationship with work engagement in white- and blue-collar workers.The study was carried out in an Italian manufacturing company and involved two production plants, with similar processes, located in the North of Italy. The company was investing in Industry 4.0 and had recently introduced innovations such as new technologies, automation systems, exoskeletons and robots within the plants. The project was approved by the company Board of Directors and was designed in collaboration with the Health, Safety & Environment Department. Moreover, the project’s aims, methods and tools were shared with the trade unions. The study was carried out in line with the Helsinki Declaration  and the At the two plants, all white-collar workers (257) were invited to fill-in the questionnaire; the participants (220 employees) represented 86% of the whole population of white-collar workers. As for blue-collar employees, a representative sample of the whole population was involved in the research; the final sample (378 participants) included 17% of the whole population (2287 employees). In this study, we have considered only participants whose work activity was recently modified by the introduction of new technologies. The participants received a paper questionnaire and an informed consent form, which described the study’s aims, the measures taken to guarantee anonymity, participants’ rights in terms of data protection and their voluntary participation in the study. Questionnaires were administered to the participants on site in small groups during working hours and in the presence of a researcher. Respondents returned their questionnaire in drop-boxes provided by the researcher. A total of 598 employees participated in the research. The group of white-collar workers was made up of 220 employees. Among them, 83% were male and 16% were female; the mean age was 43.97 years (SD = 8.67). A total of 68% had a high school diploma; 24% a bachelor’s or master’s degree; and 8% had a lower educational level. The mean level of seniority on the job was 21.33 years (SD = 10.43). The group of blue-collar workers was made up of 378 participants. Among them, 85% were male and 15% were female; the mean age was 42.16 years (SD = 9.60). A total of 50% had a high school diploma; 3% a Bachelor’s or Master’s degree, and 47% had a lower educational level. The mean level of job seniority was 21.33 years (SD = 10.35). Work engagement was measured using eight items of the Oldenburg Burnout Inventory ; an examTechnology acceptance was detected through four items taken from the Subjective Acceptance Questionnaire ; an examResilience was measured with five items of the Connor and Davidson’s resilience scale ; an examGoal orientation was measured through five items of the Italian Motivational Orientation Test ; an exam2 (4) = 9.50; p < 0.05; Root Mean Square Error of Approximation (RMSEA) = 0.05 ; Comparative Fit Index (CFI) = 0.99; Tucker–Lewis Index (TLI) = 0.99; Standardized Root Mean Square Residual (SRMR) = 0.02. Factor loadings were significant and ranged between 0.50 and 0.84. The covariance between the residuals of item 1 and item 2 (both related to the opportunity to find information) was calculated.Opportunities for information and training was detected using five ad-hoc items, which investigated how much respondents felt they received adequate opportunities to be informed about their work and to be trained. t-test for independent samples, was considered to investigate differences in the variables’ means between white-collar and blue-collar samples. The above-mentioned analyses were performed through the support of statistics software SPSS 25 . Descriptive data analysis was performed in the two samples (white-collar and blue-collar) separately. Pearson correlations were calculated to investigate the relationships among variables in each sample. Cronbach’s alpha coefficients were tested to examine the reliability of each measure. The analysis of variance, through 2  = 3230.17, p < 0.001, RMSEA = 0.12 , CFI = 0.52, TLI = 0.48, SRMR = 0.10); thus, the common method variance problem was rejected in this study.Harman’s single-factor test  was usedThe hypothesized model, which compared the two samples, was tested using a multi-group full structural equation model (SEM), performed with the aid of Mplus 7 . The method of estimation was Maximum Likelihood (ML). Age and professional seniority were considered in the model as control variables. The item parcelling technique  was adop2 goodness-of-fit statistic ; the RMSEA ; the CFI and the TLI ; the SRMR ; and AIC . The significance of the indirect effects was tested through a bootstrapping procedure which extracted 2000 new samples from the original one in order to calculate the direct and indirect parameters of the model [The model was assessed by the following goodness-of-fit criteria : the χ2 he model .Means, standard deviations, and correlations between the study variables are presented in M = 3.95) compared with blue-collar (M = 3.81) (t (562) = 6.45, p < 0.001) workers. Moreover, goal orientation was significantly higher for white-collar (M = 4.21) than for blue-collar (M = 4.09) (t (536) = 2.24, p = 0.026) workers.The analysis of variance between the white-collar and blue-collar groups showed a significant difference in the technology acceptance variable, with a higher level for white-collar  = 255.99, p < 0.001, CFI = 0.93, TLI = 0.91, RMSEA = 0.07 , SRMR = 0.07. M2, an alternative model without the mediation of technology acceptance, showed a significantly worse fit to the data than M1. After examination of the modification indices of M1, it appeared that, when releasing the equality constraint of the relationship between opportunities for information and training and work engagement, the fit model significantly improved. The final model (M3) with the mediation of technology acceptance and one free structural parameter had the best fit to the data: χ2 (102) = 250.67, p < 0.001, CFI = 0.93, TLI = 0.91, RMSEA = 0.07 , SRMR = 0.07. In the final model, which is shown in The study contributes to the literature on technology acceptance in different ways: (1) it investigated its antecedents considering personal and organizational resources; (2) it is one of the first that considered the relationship of technology acceptance with a dimension of workers’ wellbeing, namely work engagement; and (3) it is one of the few studies in work and organizational psychology literature that involved blue-collar workers and compared them with white-collar colleagues. Moreover, findings supported the use of the Worker-Centric Design and Evaluation Framework for Operator 4.0  in orderAmong the personal resources, only resilience showed a positive relationship with technology acceptance in both groups; therefore, Hypothesis 1a was confirmed, while Hypothesis 1b was rejected. The implementation of new technologies and/or new tools means an important change for workers and, in some cases, entails difficulties, especially at the beginning. Thus, the capability to face adverse situations and overcome them in an adaptive way, typical of resilient people , is one Opportunities for information and training—the organizational resource considered in this study—showed a positive association with technology acceptance in both groups, confirming Hypothesis 2. This result reinforces the importance of considering the implementation of new tools and systems in organizations as a change process, which requires adequate communication and training to involve workers in a positive and effective way . Having The positive relationship between technology acceptance and work engagement was also confirmed in white- and blue-collar groups (Hypothesis 3). As far as we know, few studies have considered workers’ wellbeing as a consequence of technology acceptance, despite the great attention paid to the concept of human-centricity in the factories of the future . As we aWith regards to the relationship between personal resources and work engagement, only goal orientation showed a positive association, confirming Hypothesis 4b. This result is supported by the job demands–resources model , which aFinally, the positive relationship between opportunities for information and training and work engagement (Hypothesis 5) was confirmed in both groups. This result is in line with previous studies that suggested opportunities for development and information as two of the core job resources involved in the motivational process described by the job demands–resources model ,59. In oA first limitation of this study is its cross-sectional design, as longitudinal or diary studies would be necessary to test causal relationships across time. In addition, this kind of method would be useful to monitor the effects of training and other interventions over time. A second limitation is that only self-reported data has been considered, supporting the risk of common method-bias . DespiteAs for the model that the study investigated, a limited set of variables has been considered, while other personal resources, such as self-efficacy and flexibility, may play an important role. Moreover, it would be notably important to investigate the role of supervisors and their leadership style with multilevel studies. Finally, the study involved employees who use different tools in their work activities; therefore, the acceptance construct was not related to a common technology. Nevertheless, the study permitted us to consider a large representative sample of white- and blue-collar workers employed in the same company, providing useful suggestions, especially for HR practice, which are discussed below.In summary, this study contributed to the literature showing the role of certain personal and organizational resources as antecedents of technology acceptance. Moreover, it highlighted the connection between technology acceptance and work engagement, clarifying how important acceptance is not only in fostering effective usage of the new technology by workers, but also in preventing and encouraging their wellbeing. From a practical point of view, these findings suggest useful and primary implications for organizations, HR managers and supervisors. First of all, in accordance with change management models, when a new technology is introduced, adequate opportunities for information and training should be offered to all workers. These strategic interventions should encompass three levels. The first level includes a communication and information program for the company population at large, in order to anticipate and prepare for the change and promote collective awareness and involvement. The second level regards training for all workers to improve their knowledge, technical and soft skills and to embrace their doubts and fears; this type of training should not be directly relevant to workers’ jobs, but is useful for increasing the variety of skills . FinallyWhen introducing new interventions or changes, blue-collar workers require particular attention by management. Their profession is characterized by repetition, highly standardized processes and poor communication. Nevertheless, an adequate level of autonomy and a supportive climate should be guaranteed through commensurate opportunities to be informed and trained . MoreoveIn conclusion, the ongoing transformations imply a progressive and continuous change of processes and technologies, which in turn requires new skills and new working assignments. In this scenario, employees play a fundamental role; involving them in the development and implementation of new systems is crucial, for example, by asking them to propose suggestions to make improvements to their working environment . Finall


Diabetes mellitus (DM) is a global health care problem that can impose a substantial economic burden. Diabetic peripheral neuropathy (DPN) is a common microvascular complication of DM that increases the potential for morbidity and disability due to ulceration and amputation. Though there is a significant amount of variation in the primary studies on DM regarding the prevalence of DPN in Africa. Hence, this study was aimed to estimate the overall prevalence of DPN in DM patients in Africa.2). Publication bias was examined by funnel plot and Egger’s regression test. The random-effect model was fitted to estimate the pooled prevalence of diabetic peripheral neuropathy among patients in Africa. The meta-analysis was performed using the STATA™ Version 14 software.PubMed, Scopus, Google Scholar, African Journals OnLine, WHO African Library, and the Cochrane Review were systematically searched online to retrieve related articles. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines was followed. Heterogeneity across the included studies was evaluated by the inconsistency index . Based on the subgroup analysis, the highest prevalence of diabetic peripheral neuropathy in DM patients was reported in West Africa at 49.4% .This study revealed that the overall prevalence of diabetic peripheral neuropathy is relatively high in Africa. Hence, DPN needs situation-based interventions and preventive strategies, which are specific to the country. Further meta-analysis is needed to identify associated factors for the occurrence of diabetic peripheral neuropathy. Diabetes melllitus (DM) is a significant health concern for many countries in the world. According to the International Diabetic Federation’s (IDF) latest estimated data, about 425 million adults in 2017 were living with diabetes globally; by 2045, this number is projected to rise to 629 million. In Africa, by 2017, 39 million people were living with diabetes and by 2045, this number is projected to rise to 82 million [Morbidity and mortality in patients with DM is mainly attributed to microvascular and macrovascular complications . DiabetiThe prevalence of DPN varies widely in the literature. This is due to differences in the diagnostic criteria employed, types of diabetes, the different methods of patient selection, and the sample size , 9. HowePeripheral nerve damage in diabetic patients is mostly irreversible. This has led health care professionals to focus on prevention as well as the identification of modifiable risk factors . StudiesPatients with DPN often suffer from the loss or absence of a protective sensation in the lower extremities leading to balance problems , risk ofTo extract all relevant literature, electronic databases such as PubMed, Google Scholar, African Journals of OnLine, Scopus, Web of Science, WHO African Library, and the Cochrane Review were searched. In addition, a hand search of grey literature and other related articles were conducted to retrieve additional relevant articles. All electronic sources of information were searched for the period of January 1st, 2000 to August 22nd, 2019. The search was deployed using the following MeSH and free-text terms: “peripheral neuropathy”, “diabetic neuropathy”, “diabetic polyneuropathy”, “diabetes mellitus”, and “Africa”. Boolean operators like “AND” and “OR” were used to combine search terms.Studies were included if they met the following criteria: (1) studies reported their outcome variable as prevalence of DPN, (2) articles were published in peer-reviewed journals or grey literature, (3) articles were published in English between 2000 to 2019, and (4) studies were conducted using an African population. Studies were excluded on any one of the following conditions: (1) the article was not fully accessible  at the time of our search, (2) it was a duplicate citation, (3) the article had a sub-standard quality score per stated criteria, (4) the study was not relevant to DPN, (5) the study involved peripheral neuropathy not related to DM, and (6) the patients in the study had comorbidities of human immunodeficiency virus (HIV), tuberculosis, and/or chemotherapy.Data were extracted using a pre-piloted data extraction format prepared in Microsoft™ Excel. The extracted information from the literature included author names, year of publication, study area, study design, sample size, data collection year, data collection method, reported prevalence, and its 95% confidence interval. The data were extracted by three independent authors. The methodological and overall quality of each article was assessed by both authors based on the modified version of the Newcastle-Ottawa Scale (NOS) for cross-sectional studies . Studies2 statistical test were conducted to assess the random variations between primary studies [p ≤ 0.05 was considered statistically significant for the presence of publication bias [™ version 14 statistical software for Windows™.To estimate the pooled prevalence of DPN, a meta-analysis using the random effect DerSimonian and Laird model was deployed. Cochran’s Q chi-square statistics and I studies . To miniion bias , 35. TheTo estimate the pooled prevalence of DPN in patients with DM, this systematic review and meta-analysis was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , and PRIIn total, 1278 studies were retrieved, of which, 1261 were found from six international databases and the remaining 17 were found through manual searches. The articles retrieved from the databases were as follows: PubMed (161), Scopus (53), Google Scholar (507), WHO African Library (3), Cochrane Reviews (7), and the African Journals OnLine (530). Of these papers, 659 duplicate records were identified and removed. From the remaining 619 articles, 492 articles were excluded after reading of titles and abstracts based on the pre-defined eligibility criteria. Finally, 127 full-text articles were read and assessed. After applying the pre-defined criteria and quality assessment, 23 articles were eligible for review and included in the final analysis .The result of this meta-analysis using a random effects model showed that the pooled prevalence of DPN was 46% (95% CI: 36.21–55.78)  as the variable of interest. From this we found that the highest prevalence of DPN was observed in a study conducted in West Africa 49.4%   of variation across the included studies, we performed meta-regression analysis using publication year and sample size as covariates of interest. However, the result of this meta-regression analysis showed that both covariates were not significantly associated with the presence of heterogeneity, Table .Table 2p = 0.024).To identify the presence of publication bias, both a funnel plot and Egger’s test were performed. Visual inspection of the funnel plot showed an asymmetrical distribution, which indicated the presence of publication bias Fig. . The finWe conducted a sensitivity analysis to assess the effect of any individual study on the pooled effect size. Our analyses using a random effects model revealed that no single study affected the overall prevalence of DPN Fig. .Fig. 5SIn this systematic review and meta-analysis, the overall prevalence of DPN was 46% . This finding was in line with a systematic review and meta-analysis conducted in Iran which yielded a prevalence of 53% . In contDPN prevalence varied greatly in the included studies, ranging from 7.5%  to 83.4%This systematic review and meta-analysis was conducted based on PRISMA guidelines for literature reviews. In addition, publication bias was quantified using Egger’s regression statistical test, and NOS was used to assess the quality of the included studies. To the best of our knowledge this is the first study on the prevalence of DPN in DM patients from Africa which may be helpful for future researchers, public health practitioners, and health care policymakers.This study was conducted with the use of a comprehensive search strategy to incorporate the studies involving African patients. All of the included studies were observational studies with high methodological quality based on NOS assessment. In addition, the inclusion of previously published studies that met our inclusion criteria further strengthened our meta-analysis. There are several limitations to this review which must be acknowledged and may inform future research. First, we only used English language articles although our target was the African content which could be in several other languages such as Spanish, French, or Portuguese. Also, our study was exclusively driven by hospital-based data, which reduced the community-based capture on this topic. Finally, we did not explore the predictors of DPN in DM patients.This study revealed that the overall prevalence of DPN was relatively high in Africa. Hence, African nations need to implement situation-based interventions and preventive strategies in order to try to curb this debilitating disease. In addition, policymakers and other concerned bodies need to give special attention to improve healthcare delivery for patients with DM to reduce the risk of DPN. Furthermore, further research is needed to identify associated factors for the development of DPN in patients with DM.Additional file 1: Supplementary file 1. Methodological quality assessment of cross-sectional studies using the modified Newcastle-Ottawa Scale (NOS).


Campylobacter control on poultry farms. A longitudinal molecular epidemiological study was performed during two production cycles, in which the broilers, the poultry house, and the environment of 10 (mixed) broiler farms were monitored weekly. Cecal droppings from the second production cycle were also used for 16S metabarcoding to study the differences in the microbiota of colonized and uncolonized flocks. Results showed that 3 out of 10 farms were positive for Campylobacter in the first production cycle, and 4 out of 10 were positive in the second. Broilers became colonized at the earliest when they were four weeks old. The majority of the flocks (57%) became colonized after partial depopulation. Before colonization of the flocks, Campylobacter was rarely detected in the environment, but it was frequently isolated from cattle and swine. Although these animals appeared to be consistent carriers of Campylobacter, molecular typing revealed that they were not the source of flock colonization. In accordance with previous reports, this study suggests that partial depopulation appears to be an important risk factor for Campylobacter introduction into the broiler house. Metabarcoding indicated that two Campylobacter-free flocks carried high relative abundances of Megamonas in their ceca, suggesting potential competition with Campylobacter.Biosecurity seems to be the most promising tool for  Campylobacter species appear to be the main cause of human gastroenteritis. Within Europe, 246,541 cases are diagnosed each year, making Campylobacter the most commonly reported bacterial food pathogen [Campylobacter cases originate from the poultry reservoir [Campylobacter infections. Intervention at the level of primary production may potentially reduce the number of human infections. Calculations of Messens and co-authors [Campylobacter counts in the chicken ceca may lead to a 55% reduction in the human campylobacteriosis cases.Both globally and nationally, campylobacteriosis is a recognized health risk. In the industrialized world, eservoir . Based oCampylobacter introduction in the poultry house are the presence of other animals on the farm such as rodents, insects, wild birds, pets, and other animals. Other risk factors are the slaughter age, flock size, age and number of poultry houses, farm personnel, insufficient biosecurity including partial depopulation, farm equipment, and transport vehicles [Campylobacter, other farm animals such as cattle and swine are also seen to be carriers of Campylobacter [Campylobacter spread to the broiler house [Identified risk factors for vehicles . Even thlobacter ,7. Thereer house . In BelgCampylobacter reduction [Campylobacter seems to be strict biosecurity management [Campylobacter prevalence by 30% [Campylobacter introduction are presumably similar between various countries, climate conditions can have a major impact on the survival and occurrence of Campylobacter in the environment, because it is a thermotolerant bacterium. Therefore, regional differences in the presence and spread of this pathogen may be present.Interventions such as vaccination and immunization, phage therapy, and feeding strategies such as adding prebiotics to the feed or additives to the drinking water have only shown limited success in eduction . Currentnagement ,11. In De by 30% ,13. AlthCampylobacter development in the broiler’s gastrointestinal tract [Besides differences in biosecurity approaches and hygiene practices, biological variation between flocks may be an important factor. An important cause of biological variation is the composition of the gut microbiota. Competitive exclusion of bacteria present in the gut can influence al tract , and conCampylobacter-colonized and Campylobacter-free flocks. This knowledge may be useful for the implementation of biosecurity measures and may provide insights into individual flock susceptibility.The aim of this study was to reveal the possible contamination sources and transmission routes on both mixed and exclusive broiler farms, as well as identifying cecal microbial composition of both Campylobacter could be isolated from the broiler house immediately after cleaning and disinfection. At that time, Campylobacter was only isolated outside the broiler house in the wider environment, such as in puddles, carcass containers, and in the stables for the other livestock animals (if present). During rearing of the broilers, Campylobacter was only detected in the broiler house or in the anteroom if the broilers were colonized themselves. This means that contamination of the direct environment in the broiler house and colonization of the broiler flock was detected simultaneously.No Campylobacter, and farm A was affected twice (with two different C. jejuni strains). During the first cycle, three flocks were found to be positive . During the second cycle, four flocks were Campylobacter-colonized . Additionally, 4 of the 10 farms managed to keep the flocks Campylobacter-free during both production cycles .In total (production cycle 1 + 2), 7 out of 20 flocks became colonized with Campylobacter was detected on farms: where the broilers were Campylobacter-positive for at least one cycle  or in the anteroom  were in most cases identical to the strain isolated from the colonized birds. Campylobacter was isolated twice from the buckets. In four cases, Campylobacter strains identical to those colonizing the broilers were isolated from boots, and in three cases they were also detected on the internal side of the hygiene barrier (inside HB), where those boots are stored and exchanged. The external side of the hygiene barrier (outside HB) tested positive in one anteroom belonging to farm H. At that farm, the outdoor door handle of the anteroom was also found to be contaminated with Campylobacter.ne cycle  and wherlobacter . An overCampylobacter status of the flock. C. jejuni was once isolated from a puddle on farm A, but this was before the birds became colonized, and was also a different strain than the one found in the colonized broilers. C. jejuni was also isolated twice from puddles on farm J, where the broilers did not become colonized. C. jejuni was isolated from wild bird droppings on farm B. Again, this was a different strain from the strain isolated from the colonized flock. Campylobacter was detected three times on the carcass containers . C. lari was isolated from the carcass container present at farm B.In contrast to the inside of the broiler house and anteroom, contamination of the outside environment often occurred independently from the C. jejuni and C. coli, respectively. However, strains could not be matched with the strains isolated from the broilers. Campylobacter was not constantly detected in dairy herds. Dairy cows present on farm G were consistently shedding C. jejuni during the first cycle. However, during the second cycle, Campylobacter could not be demonstrated in samples originating from the same herd. On this farm, broilers were only found to be Campylobacter-positive during this second cycle. Moreover, the Campylobacter strain isolated from the broilers did not match the strains found in the dairy herd during the first production cycle. On farm F, the dairy cows were shedding campylobacters during both production rounds, but the broilers remained Campylobacter-free. On the three broiler–pig farms, pigs were colonized with C. coli during both production cycles, whereas the broilers were colonized with C. jejuni (farm A) or remained Campylobacter-free (farms E and J). Cattle (farms F and G) and swine  were colonized with Campylobacter in cecal samples. Some (culture confirmed) Campylobacter-positive samples remained undetected using 16S metabarcoding, regardless of the Campylobacter counts. In the second production cycle, four flocks were found to be positive by classic culture: flocks from farms A, D and H at the age of six weeks, and a flock from farm G at four weeks. Each time, all pooled samples were positive by classical culture. With metabarcoding, the same flocks were identified as being Campylobacter-colonized, but only one to four out of the five samples appeared positive.When comparing results of 16S metabarcoding (only production cycle 2) and cultivation, cultivation appeared to be a more accurate technique to detect p < 0.001) than the microbiome of older broilers (Campylobacter colonization (p = 0.894) based on the culture status (Campylobacter-positive versus Campylobacter-negative samples). Nevertheless, even though there were no differences in bacterial richness between colonized and non-colonized flocks, results showed that both the farm of origin (p = 0.001) and the age of the broilers (p = 0.001) did have a significant influence on the composition of the microbial community and the abundance of some taxonomic groups in the broilers’ ceca , as indicated by the negative log2-fold changes (p < 0.05) at an age of four weeks compared to an age of three weeks. In contrast, the positive log2-fold change values showed that the genera of Streptococcus, Fusicatenibacter, and Subdoligranulum had a significantly increased relative abundance in four-week-old broilers compared to three-week-old broilers. However, values for the latter two groups were very low, indicating only a small difference.However, the results of the metabarcoding analysis were relevant regarding the richness and composition of the microbiome. In each flock, bacterial richness (the number of various taxonomic groups present) was dependent on age, because the diversity of the gut microbiome of three-week-old broilers was significantly smaller . These bacteria occurred within this group in an abundance >8% of the total microflora and appeared to be absent in Campylobacter-positive flocks. Remarkably, the presence of this genus was seen to increase with age, and rose strongly from five weeks of age onwards. Furthermore, Sutterella, Helicobacter, and Barnesiella were also significantly more present in Campylobacter-negative flocks, but the mean percentage of occurrence was relatively low compared to Megamonas spp.Similar statistical analyses also showed some significant differences between microbial genera of non-colonized versus colonized flocks . We consCampylobacter. According to data from the European Food Safety Authority (EFSA) [Campylobacter. This is in accordance with our findings. In earlier Belgian studies, the prevalence of Campylobacter in flocks was between 65 and 80% at slaughter age [Campylobacter is known to be susceptible to dry conditions [Campylobacter prevalence as a consequence.In this Belgian study, 35% of the flocks became colonized with y (EFSA) , 26% of hter age ,16,17. Anditions . In addiCampylobacter throughout the poultry house, as reported before [Campylobacter is spread via the air, litter, and water, and leads to the contamination of boots, buckets, the anteroom, and the exterior of the poultry house, such as the carcass container. These findings are in agreement with the results of previous studies [Campylobacter colonization. This hypothesis could not be confirmed in the present study.Although the sampling was specifically designed to identify the initial contamination sources for flock colonization, we were unable to unambiguously identify them in the present study. Contamination of the environment and colonization of the broilers were detected at the same sampling point; therefore, it was impossible to distinguish the direction of contamination. However, the observations indicate the direction of a rapid spread of d before ,20. Both studies ,23,24,25 studies , air samCampylobacter contamination of the floor ended at the hygiene barrier, with the exception of farm H where the barrier consisted of a single line drawn on the floor instead of a physical barrier. At this farm, the “clean” side of the hygiene barrier was also contaminated with Campylobacter. This indicates the advantages of this small biosecurity measure when properly applied. Moreover, it is seen that buckets, boots and the carcass container may be contaminated with Campylobacter and can potentially operate as a transmission vehicle in and outside the broiler house.In all cases, Campylobacter introduction in broiler houses compared to farms that only held poultry at their site. In our study, farm animals were not a risk factor for Campylobacter introduction. Mixed and single poultry farms seemed to show an equal level of Campylobacter prevalence, although this is based on a low number of flocks. This could either be due to applying strict biosecurity, or to a lower susceptibility of the broilers to Campylobacter strains that colonize pigs or cows. Broilers seemed to become colonized with C. jejuni more frequently compared to C. coli in this current study; no C. coli was found in the flocks. This is in accordance with findings of other studies, as reviewed by Hermans et al. [C. coli colonization in poultry flocks that are exposed to pigs on their site. On the other hand, transmission of C. jejuni genotypes from herds of cattle to broiler meat was already demonstrated by Ragimbeau and co-workers [Campylobacter shedders, demonstrated both in the present study and in previous studies [One of the aims of this study was to investigate whether mixed farms would be at higher risk for s et al. . Accordis et al.  there do-workers . Althoug-workers  consider studies . ContrarCampylobacter introduction in half of the cases—this was shown in a previous study by our group when monitoring the same farms [Campylobacter [Even though we were unable to indicate the source of contamination, we hypothesize that partial depopulation may have been the source of me farms . The majlobacter , and forlobacter . Campylobacter species, as described previously [Campylobacter thrives under non-optimal environmental conditions, it can be present in a state in which it is not detectable by culturing but is still able to cause colonization. One hypothesis may be that Campylobacter in environmental samples, taken in this current study, was present in a VBNC state, and therefore was not detected via cultivation. Once the broiler flock became colonized, there was a constant flow of Campylobacter to the environment, making the bacteria more detectable in environmental swab samples after enrichment.The lack of evidence for the source of earlier colonizations could potentially be explained by a viable-but-non-culturable state (VBNC) of the eviously . When CaCampylobacter-colonized and Campylobacter-negative flocks. Although we did find a significant difference between both groups, these results should be interpreted with care. Firstly, antimicrobials  were used in all flocks during the second production round, with the exception of farm C. Clearly, this influenced the composition of the microbiota. Secondly, the farm effect was significant, suggesting that each farm flock had its own microbiome composition, making it more difficult to draw overall conclusions. Additionally, we found that the microbiome richness and composition of three-week-old broilers was significantly different from older age groups. The increase in bacterial richness with broiler age has been described by Gong et al. [Campylobacter-positive and Campylobacter-negative flocks. The genus Bacteroides, for example, was shown to be more present in non-colonized flocks. However, this was mainly a consequence of only one flock that carried high numbers of Bacteroides plebeius in their ceca. More interesting is the increased abundance of Megamonas in two Campylobacter-negative flocks, which was undetected in all colonized flocks. In addition, this genus was seen to increase with age, and was highly abundant at an age of five weeks, which corresponded to the most common period that Campylobacter colonized the ceca. Megamonas hypermegas (formerly known as Bacteroides hypermegas) was previously described as being competitive with Salmonella in vitro [Salmonella  that could suppress the growth of these bacteria within the broiler intestinal tract. Out of all SCFAs, Megamonas is seen to mainly produce propionic acid [C. jejuni on contaminated broiler skin samples [Megamonas hypermegale strains to suppress C. jejuni strains in turkeys [Megamonas representatives as a probiotic against Campylobacter in broilers under field conditions.This study also aimed to determine the differences in microbiota of g et al. . Neverthin vitro , which min vitro ,37,38. Tnic acid . Additio samples , and a s turkeys . More inCampylobacter colonizations occurred in the last week of the rearing period, and initial contamination sources could not be identified. Thinning may be responsible for Campylobacter introduction in the broiler house in many cases, because this practice was performed before Campylobacter appeared. Outcomes of this current study suggest the need for further research in this area. Furthermore, mixed farms were not considered as a risk factor for Campylobacter colonization of the broilers. Finally, Megamonas could act as a probiotic strain to reduce Campylobacter colonization.In conclusion, results of this current study indicate that half of the Campylobacter introduction in broiler houses [The choice of places to sample on the farms was based on results of studies conducted in the European Union regarding the potential risk factors for r houses ,45,46,47Campylobacter status and/or voluntary registration. The first production cycle was sampled from April to August 2018. During this period, the mean temperature was considered as exceptional. The mean monthly temperatures increased from 13 °C (April) to 22.1 °C (July) which was a few degrees higher than normal. This period was also dryer than normal. The second production cycle took place from the end of July 2018 until January 2019. The mean monthly temperatures decreased from 22.1 °C (July) to 3 °C (January), and the monthly mean temperatures were considered as normal during this period [This current study was performed from April 2018 to January 2019 on 10 Belgian broiler farms (A–J), selected either based on their prior s period . Flock sCampylobacter agar medium (RCA) . Dry sponge sticks were used for sampling of puddles, both inside and outside of the broiler house. Cattle and swine were screened for the presence of Campylobacter by using one pair of overshoes per animal species. The (empty) carcass container was also sampled for Campylobacter using a pre-moistened sponge stick.The first sampling cycle took place during the down period after cleaning and disinfection of the broiler house. At that time, sampling included the anteroom and the broiler house with all fomites, flies, and beetles if present, wet spots on the floor, cracks in the floor and walls, the drinking system, and the air. Outside the broiler house, puddles, wild bird droppings, and the carcass container were all sampled. In addition, manure from cattle or swine was collected . The floCampylobacter , and 0.1 mL of each dilution was plated on rapid Campylobacter agar  plates with rapid Campylobacter supplement , while for detection 90 mL Bolton Broth supplemented with Modified Bolton Broth Selective Supplement (Oxoid) and 5% of defibrinated horse blood  was added to 10 g cecal droppings. Overshoes worn in the barn of the other farm animals present were directly plated on RCA, as well as enriched in 225 mL Bolton Broth. Environmental samples were only enriched. In total, 90 mL of Bolton Broth was added to the sponge sticks, 10 mL to the cotton swabs, and 225 mL to the overshoes. All sponge samples and overshoes were homogenized using a stomacher .For culturing, 3 pools of cecal droppings were used. They were used both for enumeration, as shown in the Campylobacter colonies. In the case of enumeration, the number of suspect colonies were counted. The mean value of all countable plates (<300 cfu/plate) was calculated, and expressed in number of cfu/g. Three suspect colonies were purified by streaking onto modified charcoal cefoperazone deoxycholate agar (mCCDA) . All incubations occurred under microaerophilic conditions  at a temperature of 41.5 °C. Presumptive Campylobacter isolates were suspended in 1 mL lysed horse blood and stored at −80 °C for later molecular analyses. A maximum of either 2 (enrichment at 24 h and 48 h) or 3 (direct plating and enrichment) isolates per sample were stored.One loopful of each enrichment broth was transferred after 24 h and 48 h of incubation onto RCA. After incubation of the RCA media for both 24 h and 48 h, plates were examined for the presence of suspected Campylobacter colonies were cultured on mCCDA plates, and lysates were made by resuspending a few of the colonies in 100 µL of sterile water and heating it at a temperature of 95 °C for 10 min. These lysates were screened with Campylobacter-specific PCRs [C. jejuni isolates were further typed by means of Flagellin gene A PCR/restriction fragment length polymorphism  and pulsed field gel electrophoresis (PFGE) according to the harmonized protocol from PulseNet [Campylobacter isolates for both FlaA analysis and PFGE (SmaI and/or KpnI if tested).Presumptive fic PCRs ,50. All PulseNet ,52. SmaIn = 178) using the PowerSoil Pro extraction kit . DNA yield was measured by use of nanodrop spectrophotometry  and Quantus fluorometry . Samples were diluted according to their total DNA yield, as measured by the Quantus double-stranded DNA assay. If >100 ng/µL: 1:5 dilution, if <100 ng/µL: 1:2 dilution, if <10 ng/µL: no dilution. Subsequently, amplicon sequencing of the bacterial V3–V4 region of the 16S rRNA gene was performed as described by the Illumina protocol and the primers of Klindworth et al. [All five pools of cecal droppings originating from the second production cycle were used for DNA extraction  were considered significant. The models included Age and Farm as co-variables to correct for confounding. This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.The entire processing pipeline, from reads to count table to statistical analyses, was performed in R v3.6.1 , run in


Unilateral vocal fold paralysis (UVFP) is a common disorder that may cause glottal closure insufficiency and then hoarseness of voice and aspiration during swallowing. We conducted a systematic review and meta-analysis to evaluate whether hyaluronic acid (HA) injection laryngoplasty (IL) is an effective treatment for patients with UVFP. Comprehensive systematic searches were undertaken using PubMed, EBSCO Medline, and Cochrane Library databases. We appraised the quality of studies according to preset inclusion and exclusion criteria. The lengths of follow-up were divided into “short-term” (3 months or shorter), “medium-term” (6 months), and “long-term” (12 months or longer). We performed random-effect meta-analysis to estimate the changes in voice-related quality of life, perceptual evaluation by grading systems, voice lab analysis of maximal phonation time, and normalized glottal gap area, before and after HA IL. Fourteen studies were eligible for the final analysis. The results showed that patients’ glottal closure insufficiency could be improved; maximal phonation time could be prolonged; perceptual evaluations of the voice and quality of life were better after HA IL, but the duration of treatment effect varied among different studies. In conclusion, HA IL is an effective treatment for UVFP, which may achieve a long-term effect and therefore reduce the likelihood of requiring permanent medialization thyroplasty. Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common disorder that may cause incomplete vocal fold adduction with glottal closure insufficiency, leading to hoarseness of the voice and aspiration during swallowing. This causes severe impairment of the patient’s quality of life. Apart from the use of voice therapy as a conservative form of management, surgical treatments are usually applied to improve glottal closure and to synchronize the vocal fold vibration during phonation. Although laryngeal reinnervation may increase the muscle tone of laryngeal muscles and the long-term maintenance of the vocal fold resistance necessary for glottis vibration during phonation, the effect of axonal growth occurs between months 4 and 6 after the reinnervation procedure and the beneficial effect on voice outcome takes a while to manifest. Therefore, it is recommended as a salvage option in UVFP . Other sOpen laryngeal framework surgery is a transcutaneous invasive surgery involving the creation of a window in the thyroid cartilage and the insertion of an implant to push the paralyzed vocal fold medially  and/or adjust the position of arytenoid cartilage (arytenoid adduction) to improve glottal closure. Because RLN function may recover to some degree over the next several months after UVFP, many surgeons defer invasive open laryngeal framework surgery in the early stage of UVFP . Compared to open laryngeal framework surgery, IL is relatively noninvasive without a cervical open approach and is usually done early after the onset of UVFP at a very low risk to the patient . This prThe aim of this systematic review was to synthesize evidence on the use of IL with HA for the treatment of UVFP. Meta-analyses of clinical outcomes were also undertaken to estimate the treatment effects of IL with different HA materials and injection techniques. Evidence on the safety of IL is also reviewed herein, and the results may be of value in clinical practice.https://www.crd.york.ac.uk/prospero/) [Prior to undertaking the systematic review, we developed a protocol which was registered in the international prospective register of systematic reviews PROSPERO (ospero/) , registrospero/) . We included original research studies that investigated the effect of HA IL for UVFP. We excluded case reports, review articles, and correspondence. The detailed inclusion and exclusion criteria are listed in We conducted a comprehensive search of three databases, PubMed, EBSCO Medline, and Cochrane Library, without language restriction, from December 2002  to 5 ApWe developed a data extraction form to record the following key information: first author’s name, year of publication, country, study designs , number of analyzed patients, anesthesia for injection, technique of injection, brand name of hyaluronic acid, injected volume, gauge of injection needle, pre- and post-injection evaluation, longest follow-up time after injection. Data extraction was independently performed by 2 authors (Wang C.C. and Lin W.J.), and any discrepancy was resolved by consensus-based discussion with a third reviewer (Liu S.A.). The clinical outcomes in our meta-analyses were the quantitative evaluation of glottal function undertaken before and after the injection, including quality of life assessment by questionnaires, perceptual evaluation by grading systems, voice lab analysis of various acoustic and aerodynamic parameters, and image or video evaluation of glottal closure. As the included studies reported outcomes measured at different time points after treatments, we therefore divided the follow-up lengths into “short-term” (3 months or shorter), “medium-term” (6 months), and “long-term” (12 months or longer) to determine the trends of treatment effects. As the number of studies within each group of follow-up lengths was small, we did not, therefore, undertake an assessment of publication bias.B and sF are the standard deviations of the baseline and follow-up values, respectively. Because the included studies used different questionnaires for the assessment of quality of life, we therefore calculated the standardized mean gain and its standard error [The effect size measure is the difference in the outcome between the baseline and follow-up. For studies that only reported the baseline and the follow-up values, we assumed their correlation, r, to be 0.5 when calculating the standard deviation for the difference  was used in seven (50%) studies; Restylane Perlane  was used in four (30.8%) studies; the effect of Restylane and Restylane Perlane injection was compared in a study. Hyaluronic acid-dextranomer was used in one (7.1%) study. The effect of Restylane Perlane and collagen was compared in another study. In two studies, it is unclear which type of HA was used. For the volume of injected HA: less than 1cc or 1cc of HA was injected in seven (50%) studies, 2cc was used in one (7.1%) study, while no detailed information was reported in the other six studies. The needle gauge ranged from 21 to 27. The follow-up evaluation was undertaken as early as 3 days and up to 17.4 months after injection. For our meta-analyses, the longest follow-up length was divided into short-term (≤3 months) in four (28.5%) studies, medium-term (6 months) in four (28.5%) studies; and long-term (≥12 months) in six (42.9%) studies.The evaluation tools used in different studies are summarized in Voice handicap index (VHI)  was used2 = 18.7%) to large (I2 = 98%) in different subgroups.The perceptual evaluation grading system of GRBAS, developed by the Japanese Society of Logopedics and Phoniatrics, was used in five (26.3%) studies . GRBAS cNumerous acoustic analyses can be conducted, including the collection of aerodynamic data, in a voice laboratory to objectively evaluate the quality of voice from different perspectives. In our systematic review, we noted that various parameters, such as pitch, fundamental frequency (F0), intensity, jitter (perturbation of frequency), shimmer (perturbation of intensity), pitch range, intensity range, mean air flow rate (MAFR), phonation quotient, ratio of phonation time in speaking S and Z (S/Z), harmonic to noise ratio (H/N), voice range profile (VRP), maximal phonation time (MPT) have been reported in different studies. The normal range of these parameters may vary among patients of different genders, ages, and races ,34,35,362 (pixels × pixels) × 100. Only one study, conducted by Lau et al., employed other measurements, such as glottic closed phase and glottis open fraction [UVFP may cause incomplete vocal fold adduction with glottal closure insufficiency. Therefore, the glottal gap during phonation is commonly measured to evaluate the severity of glottal closure insufficiency. In this systematic review, the normalized glottal gap area (NGGA), based on the definition by Omori et al. , was usefraction . We therIn addition to the aforementioned evaluations that were used to measure the change before and after IL with HA, other evaluations were done in some of the studies included in this systematic analysis. For example, in the study by Ng , a subtlIn another study by Pei , the HA p = 0.746). The mean age in studies was negatively associated with the mean MPT . The proportion of males in a study was not correlated with the mean QOL (p = 0.469), nor was the mean age across studies (0.807). The proportion of males in a study was not correlated with the mean NGGA in a study (p = 0.598), nor was the mean age in studies (0.481). The mean MPT in studies with local anesthesia/no anesthesia was 0.69 s  shorter than that in studies with general anesthesia, but the difference was not significant. The mean MPT in studies of the transcervical approach was 1.07 s  shorter than that in studies of the transoral approach, but the difference was still not significant. However, as the number of studies was small, the statistical power of the meta-regression was low. The relationships between outcomes and other clinical variables, such as sex, age, type of anesthesia, transcervical versus transoral approaches, and so on, were analyzed. The results showed that the proportion of males in any given study was not correlated with the mean MPT in that study , which is commonly used for treating pediatric vesicoureteral reflux has also been used for IL. [HA is a polysaccharide and is a universal component of the extracellular matrix. It is not species specific and does not elicit any humoral or cell-mediated immune response. There are two commercially available products: Hylan B gel  and Restylane  commonly used for IL ,25,26,27 for IL. ,40,42. G for IL.  and one  for IL.  and Domi for IL.  describe for IL. . According to ®) is mainly used for vesicoureteral reflux. The detranomer microspheres have an average size of 130 microns. The stabilized HA acts mainly as a carrier, leaving the detranomeres at the implant site. Hylaform is a nonpyrogenic, clear, colorless gel implant created through the reaction of divinyl sulfone with hyaluronan hydroxyl groups (from rooster combs). Restylane is a non-animal, stabilized hyaluronic acid (NASHA), which is biotechnologically generated by Streptococcus species of bacteria and chemically cross-linked with diepoxide 1, 4-butanediol diglycidyl ether. Both were developed as dermal filler, but a study by Caton [As mentioned above, three HA-based materials are available for IL. Hyaluronan dextranomer (Defluxby Caton  showed tby Caton  show thaby Caton  used 2 mby Caton . Theoretically, any management that could reduce the glottal gap of UVFP could potentially improve the patient’s voice and quality of life. Normalized glottal gap area or NGGA is a standardized method that directly evaluates the glottal gap of UVFP. The pooled estimates of mean differences were statistically significant in all three lengths of follow-up in our reviews . The resA wide range of studies have been published on the topic of UVFP, but only a small number of studies investigated the use of HA IL. In real-world practice, there is no standard procedure of injection laryngoplasty for UVFP. We have observed substantial differences in the injection techniques between institutions and Sulica et al. have commented that the choice of technique is usually based on the surgeon’s preference . In addiHA IL has been used for treating UVFP for more than 10 years. It can be done in a clinic using flexible laryngoscopy or LEMG guidance. Under local anesthesia, about 1 mL of commercially available HA can be delivered by a thin needle up to 27 G. The most common approach is trans-cervical trans-cutaneous puncture via the cricothyroid membrane to deliver HA into the submucosa region of the vocal fold. After treatment, patients’ glottal closure insufficiency can be improved and their maximal phonation time can be prolonged with increased voice range performance. Perceptual evaluations of the voice and patients’ quality of life can also be enhanced. The duration of treatment effect varied in different studies, and the long-term effects were observed in some patients. Early injection after symptom onset could reduce the rate of permanent medialization thyroplasty. A combination of LEMG guidance, diagnosis, treatment, and prognosis prediction can be obtained in one procedure.


Background: Anaphylaxis is an allergic disease that requires special handling due to its potential fatality. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. However, actual data on the prevalence or causes of anaphylaxis in Korea are limited. Methods: The emergency room attendees diagnosed with anaphylaxis between 2011 and 2015 in five university hospitals were included. Medical records were reviewed retrospectively. Results: During the 5 years, a total of 505 subjects were diagnosed with anaphylaxis. Respiratory presentations were more common in children than in adults, while adults presented more frequently with cardiovascular symptoms. Intraoral angioedema was more often observed in the countryside than in the city. Insect stings/bites were more common in the countryside than in the city. Drugs were much more common in adults than in children. In the countryside, the frequency of anaphylaxis was higher in summer and autumn than in spring and winter. The use of corticosteroids was less common in children than in adults, while children more frequently got treatment with inhaled beta 2 agonist. Conclusions: The principal causes of anaphylaxis in Korean patients were food, drugs, and stings/bites. The cause, clinical features and management of anaphylaxis were significantly different depending on age and region. These real-world data on anaphylaxis could be helpful to deepen that understanding of this condition for physicians and patients. Anaphylactic reactions include systemic allergic reactions such as urticaria, dyspnea, hypotension, and loss of consciousness. These are explained by an IgE-mediated reaction that activates mast cells or basophils that secrete chemical media ,2,3. HowIn domestic research, six years of data on 138 anaphylaxis patients from a university hospital in Seoul showed that the causes of anaphylaxis were drugs (34.8%), food (21.0%), unknown (13.0%), exercise (13.0%), and insect bites 11.6%) [% [6]. AtIn this study, we examined the clinical characteristics of anaphylaxis in target patients visiting five university hospitals in Seoul, Anyang, Dongtan (Gyeonggi-do) and Chuncheon (Gangwon-do) over five years. In particular, we aimed to distinguish the differences between anaphylaxis in children and adults, as well as regional differences between urban and rural areas.Data were collected retrospectively on patients who were diagnosed with anaphylaxis between January 2011 and December 2015 in five university hospitals including Hallym University, Kangnam, Kangdong, Dongtan and Chuncheon Sacred Heart Hospital located in Seoul, Anyang, Dongtan (Gyeonggi-do) and in Chuncheon (Gangwon-do) in Korea.The present study protocol was reviewed and approved by the Institutional Review Board of Kangnam Sacred Heart Hospital . Informed consent was submitted by all subjects when they were enrolled.The diagnosis of anaphylaxis was defined according to the three criteria below, one of which was based on definitions reported by Simons et al. . AnaphylIn accordance with the International Statistical Classification of Diseases, 10th Revision (ICD-10), patients diagnosed with anaphylaxis were targeted . The ICDFrom January 2011 to December 2015, we analyzed the selected patients’ demographic characteristics and clinical modalities: (1) age of onset, (2) onset place , (3) duration of symptoms, (4) personal/family history of atopy, (5) history of drug eruption, (6) history of other chronic systemic diseases, such as cardiovascular disease, diabetes, respiratory diseases, and other ailments, and (7) personal/family history of anaphylaxis.Based on the respective medical records, first, the types of symptoms were categorized. Clinical manifestations of anaphylaxis were classified into four groups: cutaneous, respiratory, cardiovascular, and gastrointestinal symptoms. The medical records of the selected patients and the laboratory results were analyzed. The treatments used, including the drug administration history and management of symptom control for each patient, were investigated.t-test (Student’s t-test). The Mann–Whitney U-test was used to establish difference between the two groups with no normal distribution. Statistical significance for all analyses was defined as p < 0.05. All statistical analyses were performed using Predictive Analysis SoftWare package version 18 .Results were expressed using mean and standard deviation (means ± standard deviation). A comparison was made between the two subgroups using a chi-square test. The statistical significance of continuous variables was confirmed by using an independent sample p = 0.002). The presence of a personal history of allergic diseases was significantly higher in children than adults, especially asthma (p < 0.001).The number of anaphylaxis episodes included during the 5-year study period was 505 at the emergency rooms of five university hospitals in Korea . The chap = 0.685), allergic rhinitis , and asthma  were higher in children with anaphylaxis than in adults with anaphylaxis. Among atopic dermatitis, allergic rhinitis, and asthma, only asthma showed statistical significance.We found that manifestations of atopic dermatitis , while adults presented more frequently with cardiovascular symptoms . The incidence of cardiovascular and respiratory presentations by age was statistically significant.The clinical manifestations of subjects are listed on The causative agents are listed in p < 0.001). Drugs were much more common in adults than in children . All the patients with anaphylaxis due to sting/bites were adults (p = 0.002). The above results were statistically significant.In the present study, food was the most common cause in adults and children. Moreover, the causative foods were different between the two age groups. Sea food accounted for 14.7% of anaphylaxis in children and 3% in adults  (p < 0.001). Among 38 subjects who had a personal history of atopy, 17 subjects conducted total IgE level. Since most of them  showed a total IgE level above 100 IU/mL, IgE-mediated atopy was a possible cause of anaphylaxis.Although there was no statistical significance, the total eosinophil count was higher in children than in adults  . The abnp < 0.001), intravenous fluid , and epinephrine  were less common in children than in adults, while children received treatment with inhaled beta 2 agonist more frequently .The majority of the patients received histamine antagonist (95.4%) or corticosteroids (95.4%) as the mainstay treatment . EpinephAnaphylaxis is a condition that can manifest itself in various ways, including such as dizziness, upper respiratory tract closure, low blood pressure, and cardiac arrhythmia ,19. In EFrom the perspective of the leading causes of anaphylaxis, one coincidence found in previous studies and with the present study is that food is the major cause of anaphylaxis . There hThe most common symptoms and signs in the present study involved the cutaneous system, then the respiratory, cardiovascular, and gastrointestinal systems, and finally, the oral area. This order has also been confirmed by other studies ,16,18. IThe number of anaphylaxis events during all four seasons appeared to be similar in the urban area, but in the case of the rural area, the frequency was higher in summer and autumn. In the rural area, there are many outdoor activities, such as recreation and farming, that occur mainly in summer and autumn, and it seems that patterns of sightseeing in places such as Chuncheon (Gangwon-do) might also be pertinent.p = 0.012), but fewer cardiovascular symptoms (p < 0.001). As in this study, the cause and clinical features in children in other studies also differed from those of adult patients [There have been a few studies investigating clinical characteristics of anaphylaxis in children or adolescents. In our results, children had more respiratory symptoms  for approaches to anaphylaxis and treatment were modified and amended in 2012 ,16. In tBy retrospectively investigating the clinical features, causes, and management, we better understand the major causal factors of Korean anaphylactic patients. In particular, we were able to identify the causes, clinical features and laboratory findings of anaphylaxis for “adults and children” and “urban and rural” patients in Korea, which had not been investigated previously. This study is expected to provide more accurate information about anaphylaxis to patients or physicians. In the future, large-scale prospective epidemiologic studies will be needed to show the overall condition of anaphylaxis in Korea.Although this study was conducted at five university hospitals in the urban area and the rural area in the past five years, there are limits to how well these results show the overall present state of anaphylaxis in Korea. The rural group is much smaller than the city group to draw complete conclusions by statistical analysis. Moreover, we could not avoid underestimation. This was a retrospective study, which means that it is likely that some patients may not have been included and that some data items could be missing. Due to the way patients were recruited for this study, the true incidence of anaphylaxis could not be determined. Furthermore, when patients report that they have taken certain foods or taken any of a variety of medicines, it is not certain that the reported items are actually responsible for the anaphylactic reactions.In conclusion, analysis of anaphylaxis over five years using data from five emergency hospitals in Korea showed that 505 cases of anaphylaxis in the study patients were mainly caused by food, drugs, stings/bites, and exercise. Common clinical symptoms involved the cutaneous, respiratory, circulatory, and gastrointestinal systems, and the oral area. The clinical characteristics and management of anaphylaxis were significantly different depending on age and region.


We also found WHtR to be positively associated with the volume of the central nucleus (CEN) region of the amygdala (p = 0.006), after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity.A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex  and the amygdala (a key brain region for reward-related processing) are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8–22 years  participated in this study; each participant completed a computer-based food choice task and a T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index (BMIz) and waist-to-height ratio (WHtR). The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant’s self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary “self-control” was calculated as the proportion of trials where the individual chose the healthier food item (vs. the tastier food item) over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions ( Obesity is a common and serious public health problem, with a prevalence of 18.5% in youth between 2 and 19 years old in the United States  and middle frontal gyrus (MFG) were among the regions that showed reduced activation during self-control as a function of body mass index (BMI) in healthy adults , and BMI percentile and BMI z-score for youth were determined based on the U.S. Center for Disease Control normative data  and weight (kg) were measured using a stadiometer and calibrated digital scale respectively. BMI was calculated . The T1 sequence lasted 6 min and 38 s, and the T2 sequence lasted 5 min and 57 s. All scans were reviewed by a radiologist for incidental findings of abnormalities and all images underwent visual quality control to assess for motion and were rated on a 3-point scale of Pass, Check, Fail . The task was modified for youth from a food choice task previously employed in adults  in this task is defined as the time between the initial presentation of a food cue and the subject’s keyboard response.Participants rated each of the 60 food cues for tastiness, healthiness, and overall desire (liking) to eat the food. Block and stimulus orders were randomized across participants. Ratings were made on the computer keyboard, using a 5-point scale with emoticons and words. Response time . These challenge trials were deemed to present a self-control challenge to the participant.Participants were counseled to keep the health of foods in mind, with the instructions for the task including a reminder slide to “try to keep it healthy,” to increase the frequency at which they exhibited dietary self-control in the task .Each trial was presented as follows: (1) a display box labeled “START” appeared at the bottom center of a black screen; (2) participants were required to click this box to begin the trial; (3) a blank screen of variable duration  then appeared; (4) the cursor would reappear in the bottom center of the screen and two food pictures were pseudo-randomized to appear with one at the left and one at the right upper corner; and (5) participants selected the food they preferred by moving the cursor continuously to the box that contained their preferred food. A participant’s RT was recorded as the time between food cue presentation and choice. Fluid cursor movements were promoted by the food cues not being displayed until the mouse movement was detected. To further encourage smooth and direct mouse movements, if the participant took longer than 4 s to make a choice, a message prompting faster decisions was displayed. Trials were separated by a fixation cross of random duration . During choice, the At the end of the task, a computer algorithm selected a food item (out of six different items in stock) that corresponded to one of the food items selected by the participant during the Food Choices task. The chosen food item was displayed on the screen and then offered to the participant at the end of the computer task.Dietary self-control was considered successful when the healthier food cue in the challenge trial was chosen. An individual measure of overall dietary self-control, the “self-control success ratio (SCSR)” was computed as the proportion of challenge trials per participant in which dietary self-control was successful.p < 0.05 . Linear regression, as well as the linear mixed-effects model (LME) analyses, were conducted using the R package “nlme.”Whole-brain vertex-wise cortical analyses were performed using Freesurfer’s Query, Design, Estimate, Contrast (Qdec) interface including the main predictor of WHtR while also accounting for age and sex, and results were corrected for multiple comparisons by the method of Monte Carlo simulation with In all analyses, a model reduction strategy was applied to first examine a potential WHtR by age interaction. However, in all analyses, the interaction term was found not to be significant. Thus, the interaction was removed, and the final model included the main effects of WHtR while adjusting for age.For the behavioral task, LME analyses included examining how WHtR related to ratings of the food stimuli and RT during food choices with the repeated measures including food attributes  and calorie content of the food , with subject as a random factor. A separate model was performed to examine how WHtR and age related to liking ratings.a priori subregions of interest , while including age, sex, hemisphere , and ICV as covariates, and subject as a random factor. Post hoc tests were completed using the package “reghelper” to calculate the simple slopes of interaction at the mean level of any continuous covariates.For amygdala volumes, separate LME analyses examined how WHtR related to volumes of the total amygdala or a priori analyses, we aimed to also examine the link between obesity-related brain correlates with behavior, we examined if identified cortical and amygdala correlates and their potential interactions predicted SCSR on the food task while adjusting for WHtR, age, sex, and ICV. Last, we implemented a stepwise regression using both forward and backward selection to examine the best brain predictors in a single model to determine the best predictors of the SCSR on the food choice task. For completeness, we also explored models using BMIz in place of WHtR  = 435.51, p < 0.001; F = 1.20, p = 0.27) or age  = 1.55, p = 0.22) and rating outcomes. Post hoc comparisons showed participants rated high-calorie food stimuli less healthy than low-calorie food stimuli (p < 0.001). However, participants rated the high and low-calorie food stimuli similar for tastiness (p = 0.83). The marginal effects of the LME models for RT showed trend level associations with WHtR  = 3.90, p = 0.05), and age  = 3.67, p = 0.06), with faster RTs seen for both higher WHtR and age. Also, the marginal effect of food attribute was significant  = 24.20, p < 0.001) with faster RT seen for the taste vs. health conditions. In terms of rating how much they would like to eat each food item, no association was found between WHtR or age  and ratings, but significantly faster RT was seen with age  = 4.68, p < 0.034) as well as a significant interaction was seen between WHtR and image calorie type for RT  = 4.61, p < 0.035). Post hoc analyses showed that those at 1 SD below the mean in WHtR had significantly faster RTs for rating how much they would like to eat the low-calorie vs. high-calorie items (p = 0.01), whereas those with a higher WHtR did not show differences in RT between high- and low-calorie food items when rating them on how much they would like to eat each item . SCSR had an average of 0.32 and ranged from 0.01 to 0.97. In terms of the decision-making portion of the task, no association was seen between SCSR and age  or SCSR and WHtR .Descriptive data for ratings and RT are included in R2 = 11.30, Model p = 0.09).Linear regression models examining WHtR related brain structures of cortical thickness, CEN amygdala volumes, and/or their interactions on SCSR showed a significant left CEN amygdala-by-right superior frontal thickness interaction . A larger = 0.71, p < 0.0001). Brain and behavior analyses utilizing BMIz were found to be relatively similar, yet less robust as compared to WHtR. Specifically, we found that BMIz was negatively associated with thickness in the superior frontal left PFC while controlling for age and sex , BMIz , or an age-by-BMIz interaction . However, a significant interaction of left superior frontal PFC thickness and CEN amygdala volume was found across all participants in predicting dietary self-control, controlling for BMIz, hemisphere, age, sex, and ICV . Although we did not find significant BMI or WHtR-by-age interaction on brain structures and dietary self-control, larger studies with additional participants per age group  are needed to more fully examine interactions of obesity and age on brain structure and dietary self-control. There might also be other important regions relevant to dietary decisions and obesity, such as the ventral striatum, which we did not investigate here. Last, given the prominent role of the amygdala in emotion processing, it is possible that the amygdala may be important for the emotional aspects of eating behaviors, which we did not have measures to probe here. Future studies are merited to study the relationships between the amygdala morphology and emotional eating.In conclusion, the differential development of the PFC and amygdala relate to both obesity and dietary self-control. Adolescents have the largest differential development of PFC and limbic regions. As such, this age group may be particularly susceptible to making poor dietary choices, as seen by studies that report adolescents eat more fast food and refined sugars than any other age group . Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.MH, SL, and MK take responsibility for the integrity of the data in the study and the accuracy of the data analysis and concept and design. MK, SL, AA, CC, KF, and MH: drafting of the manuscript. SL and MH: statistical analysis. MK and MH: obtained funding and supervision. AA, CC, KF, and RK: administrative, technical, or material support. All authors: acquisition, analysis, or interpretation of data and critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.