As teachers are central to digitalizing education, we summarize 40 years of research on their role in that process within a systematic umbrella review that includes 23 systematic reviews with a total of 1062 primary studies focusing technology integration and aspects of digital literacy. Our findings highlight the international acceptance of the TPACK framework as well as the need for a clear concept of digital literacy. It is unique that we identify and discuss parallels in developing teachers’ digital literacy and integrating digital technologies in the teaching profession as well as barriers to those goals. We conclude by suggesting future directions for research and describing the implications for schools, teacher education, and institutions providing professional development to in-service teachers.Kindly check and confirm whether the corresponding author is correctly identified.Olivia Wohlfart is correctly identified as corresponding author. A variety of stakeholders must be mutually committed to creating digitally competent schools  digital literacy or on their willingness and ability to integrate technology  research focus of previous reviews concerning teachers’ role in the digitalization of school education?RQ2What is the current state of research on the digital literacy of teachers?RQ3What is the current state of research on the role of teachers in technology integration?RQ4What are the future directions for research focusing on the role of teachers in the digitalization of school education?Due to global trends of digitalization, the literature on digitalization in education has flourished in recent decades, occasioning a number of literature reviews in this crowded field. As the number of publications per year relentlessly increases, it has become difficult to stay abreast of current findings, but literature reviews have the advantage of systematically structuring and summarizing the previous literature on a specific topic ) AND teacher* AND . A total of 9,080 results were identified in the search . To further reduce the number of articles to a manageable amount, we adapted our search string to consider only studies including “review,” “synthesis,” or “meta-analysis” in the title, which yielded a total of 683 results across the three databases. After duplicates were removed, 542 studies were submitted for further title and abstract screening. Figure All the identified articles were examined by two researchers through an initial screening of titles and abstracts based on the inclusion and exclusion criteria. This resulted in the exclusion of 498 publications. We excluded articles that did not conduct a systematic review or meta-study as well as those lacking an educational, digital, or teacher-centered focus. Articles focusing on studies of early childhood or higher education were also excluded from further analysis.Of the selected 44 articles, we were not able to access one paper and received no positive response after reaching out to the authors via email. Furthermore, we conducted hand searches of pertinent academic journals in the field and of the reference lists of the identified articles and extracted two additional papers: Rokenes and Krumsvik  and WangContext the study examined digitization in the context of teaching and learning.Teacher sample the study targeted pre- or in-service teachers in primary or secondary education.Methodological quality the study was a systematic review or meta-study.The decision to exclude full-text articles was made by the first author in discussion with the second author. Upon reading the full texts, 11 articles were excluded due to the context or sample of the study.Next, the methodological quality of the remaining 34 articles was assessed with an appraisal checklist based on the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses /questions). This was followed by a content-based thematic analysis of the 23 articles to identify latent patterns, themes, and subthemes through an iterative reading and coding process ,Role of Teachers,Institutional Environment,Technology Integration, and.Technology as Tools.The most prominent theme, which was included in over half of the reviews, concerned teachers’ digital literacy n = 14). Within these reviews, methods and instruments which assessed and discussed digital literacy of teachers were analyzed . In 11 reviews, no specific theoretical framework was applied , TPACK (4.2.2), approaches to developing teachers’ digital literacy (4.2.3), and prevalent requirements (4.2.4).The reviews offer a variety of definitions of digital literacy from policy papers and scientific studies alike. Rokenes and Krumsvik , p. 252 Eight reviews specifically focus on the TPACK framework and examine various aspects of previous research, including publication development, the distinction between TPACK knowledge domains, the measurement of TPACK, the interplay between context and TPACK, and model development and TPACK development Table .The reviews report (in broad agreement) on the emergence and publication development of the TPACK model based on the original contribution of Shulman  and the Concerning the distinction of knowledge domains, four reviews specifically acknowledge that a clear definition and delineation of individual knowledge domains is rare and nearly impossible. They also concur that clear definitions and operationalization of knowledge domains would be helpful in (further) developing both the theoretical model and individual survey instruments. The reviews often report TPACK as an overarching knowledge domain. Nevertheless, individual reviews refer to specific knowledge domains, with technical knowledge (TK) taking a special role, as it strongly correlates with the development of TPACK  modelling (in 7 reviews). Rokenes and Krumsvik  describeIn addition to modelling, collaboration is considered to be important in developing teachers’ digital literacy and enhancing it in various formats; this was examined among preservice teachers, preservice teachers and teacher educators, in-service teachers, and in-service teachers and their students. In this context, the social dimensions of knowledge creation are repeatedly highlighted as important elements in increasing digital literacy.Authentic learning situations are also highlighted as fruitful elements in developing teachers’ digital literacy (in 5 reviews). In discussing TPACK, Willermark  argues tFurther strategies to develop teachers’ digital literacy include metacognition as reflection on action, bridging the theory/practice gap, learning by doing, implementing diverse assessment strategies, and blended learning. While the reviews present a variety of strategies, the success or effectiveness of these measures in developing teachers’ digital literacy is seldom reported.Several reviews critically reflect on the requirements for developing teachers’ digital literacy, highlighting the importance of teacher preparation, the institutional environment, and the role of teachers. The reviews strongly agree on the need to integrate approaches to develope digital literacy in both teacher education (n = 6) and teacher professional development (n = 6) to prepare teachers for digitalized schools. In light of this, digitally literate teacher educators are indispensable in teacher preparation. Tondeur et al.  recommenFurthermore, the reviews report that institutional environment significantly affects success in developing digital literacy in various arenas, including leadership (n = 5), the policy debate (n = 4), and school culture (n = 2). Pettersson  concludeA final identified factor in developing digital literacy is the teachers’ role in the process. In the reviews, we identified four areas that directly impact digital literacy and its development: pedagogical beliefs (n = 11), personal characteristics (n = 7), interaction with students (n = 6), and experience with technology (n = 3). While not all these items can be directly influenced, the results highlight two main findings: (1) the evidence shows no differences in developing digital literacy between in-service and pre-service teachers ; (2) introducing and promoting a student-centered, constructivist pedagogical approach in teacher education positively influences the development of digital literacy.To answer the third research question, we examined whether and how the reviews discussed the integration and application of technology from the teachers’ perspective. We identified seven reviews which focus aspects of technology integration. The qualitative analysis highlights the relevance of specific strategies, requirements, and barriers to technology integration (4.3.1) as well as various facets of technology acceptance (4.3.2).knowledge as key to a better integration of technology and highlight the relevance of specific teacher education courses for technology integration. In this sense, Spiteri and Chang Rundgren  contexts, future research should go beyond the mere identification of contextual factors and critically examine how and why these factors (may) influence teachers’ digital literacy and/or willingness to integrate digital tools  diversity in the methodological approaches to examining teachers’ digital literacy. More specifically, the results highlight the need for more case studies, interventional or experimental designs . This is discussed in conjunction with a call for improvement and agreement within the scientific community in future research . Although previous research has shown that digital literacy correlates positively with the integration of technology in teaching  approaches and requirements for developing digital literacy as well as integrating technology into classes. The reviews identify and present an abundance of strategies for “developing” digital literacy and “supporting” technology integration (see Chaps. 4.2.3 & 4.3.1) but provide no evidence of the actual impact of these strategies. Based on the findings of our umbrella review, we recommend a critical discussion, application, and evaluation of these strategies in practice as a holistic approach involving the scientific community, schools, and policy representatives. In this sense, several reviews often lacked a clear theoretical background which could support their respective research focus.This appears to be the case for the successful integration of technology in teaching. While an abundance of moderator variables for technology acceptance are mentioned in the reviews (Chap. 4.3.2), the reviews lack a discussion of the results and associated implications. In addition, as the findings show that multiple concepts are used to define digital literacy and that the TPACK model lacks clear definitions of the individual knowledge domains (Chaps. 4.2.1 & 4.2.2), we believe it is essential to more clearly define the concepts applied in the analysis of digitalization in education. The (further) development of the TPACK framework as proposed by Willermark  represenBecause education relies on a large, complex network of involved stakeholders , future research should consider multiple perspectives. For example, Tondeur et al.  suggest Our review’s findings have practical implications for schools, teacher education, and institutions offering professional development services to in-service teachers. In addition, we highlight implications for the research community in critically reflecting independent research on digital literacy and technology integration. First, the findings concerning schools highlight the pivotal role (and responsibility) of school leaders in translating the potential of digitalization into specific goals (Chap. 4.2.4). In line with McKnight et al. , we encoA second key implication is that institutions of teacher education must act to adequately prepare preservice teachers for the 21st -century classroom. Responsible persons in teacher education programs need to embrace their status as role models, as our findings underline the importance of leading by example (Chap. 4.2.3). Integrating digital technologies into preservice teachers’ instruction both increases their digital literacy and prospectively motivates them to integrate technology into their future teaching.Third, teacher professional development should be seen as an important resource for developing in-service teachers’ digital literacy (Chap. 4.2.4) as well as showcasing and teaching best practices for the integration of digital technology into classes (Chap. 4.3.1). According to the findings, both general formats for developing TK and subject-specific (TCK) and pedagogical formats (TPK) need to be addressed. Finally, we encourage dedicated sessions for school leaders to support them in the individual and complex process of digitalizing their schools.Finally, we strengthen the need for the research community to critically reflect the current status of as well as the approach towards research on the teachers’ role in digitalizing education. While the reviews did a good job in synthesizing the abundance of specific studies, the current findings offer little practical support for schools, teacher education programs and institutions offering professional development measures. Rather than repeatedly examining the status of digital literacy or technology integration of a specific cohort of teachers, this review implies the critical role of the research community in actively supporting and shaping digital transformation processes. The identified areas for future research (Chap. 4.4) mark a starting point for the next phase of research.Applying an umbrella review allowed us to synthesize the current state of research in an efficient and pragmatic manner. With this method, we can assess whether reviews aligning in topic independently reflect similar results and arrive at comparable conclusions  reflecting on processes and outcomes, variety in methodological approaches, diversity of perspectives, and clarifying concepts.


The recovery experiment also showed that overexpression of TGF-β could reverse the inhibitory effect of NORAD knockdown on VSMCs in terms of proliferation, migration, and glycolysis. Collectively, these results indicated that the NORAD/LIN28B/TGF-β axis promoted cell proliferation and migration through regulating aerobic glycolysis in VSMCs. Therefore, NORAD may regulate the occurrence of AD by affecting the reprogramming of glucose metabolism, and NORAD can be recognized as a good target for VSMC phenotypic intervention and AD treatment.Glucose metabolism reprogramming is an important reason for the functional remodeling, growth, and migration of vascular smooth muscle cells (VSMCs). It is also an important basis for the occurrence and development of aortic dissection (AD), but the specific regulatory factors are not clear. Noncoding RNA activated by DNA damage (NORAD) is dysfunctional in many diseases, but the role of NORAD in AD etiology is unclear. We first established a vascular remodeling cell model of AD, and the expression of NORAD in VSMCs was significantly increased. Functional experiments showed that inhibition of NORAD could downregulate the proliferation and migration of VSMCs. Meanwhile, silencing NORAD could also inhibit the flux of glycolysis, suggesting that NORAD may aggravate AD by promoting glycolysis. In addition, mechanism studies have shown that NORAD can exert VSMCs-regulating function by recruiting LIN28B to bind to TGF- Aortic dissection (AD) is a kind of cardiovascular disease, which is fatal and seriously affects the prognosis of patients. AD can often show symptoms of chest pain. When the arterial membrane is torn or bleeding due to atherosclerosis or trauma, it can lead to partial separation of the arterial wall, resulting in AD . AD is cβ1) is an important cytokine, which can promote the migration of immune cytokines and vascular remodeling in AD [VSMC remodeling, including increased growth and accelerated migration, is still a clear sign of bronchial remodeling in AD. TGF-1  is a RNA molecule with a length of more than 200 bp but does not have the ability to encode a protein. There is growing evidence that lncRNA plays a role in the origin and progression of many cancers, especially AD. It has also been shown to play an important role in VSMC, thus affecting the AD curriculum. For example, lncRNA BCYRN1 increases the growth and metastasis of rat VSMC by overexpressing transient receptor potentials . GAS5 enWe speculate that the level of noncoding RNA activated by DNA damage (NORAD) in the noncoding region activated by DNA damage in VSMC is increased, NORAD gene knockout can inhibit the proliferation and migration of VSMC, and NORAD may regulate the occurrence of AD through reprogramming that affects glucose metabolism, so we carried out this study.As has been publicly confirmed, VSMC in the AD rat model has been identified and standardized. After the rats were killed under anesthesia, the trachea was removed, and the epithelial fibrous tissue was removed. The remaining tissue was stored in PBS and degraded by various enzymes at 37°C. After digestion, the free VSMC was centrifuged and incubated with RPMI-1640 and 10% fetal bovine serum (FBS).β was introduced into the pcDNA3.1 template . Following incubation for 24 h, VSMC was transduced by sh-NORAD or sh-NC solely or in combination with pcDNA3.1/TGF-β or pcDNA3.1 vector as needed. The cells were transfected with Lipofectamine 3000  for two days based on the production's instructions.shRNA of lnc-NORAD and control (sh-NC) was bought from Novoprotein Technology . The entire cDNA of TGF-Following extraction from cells by the RNAiso Plus Kit  according to the production's guidelines, RNA was totally synthesized utilizing the GoScript Reverse Transcription System . The SYBR Green PCR Kit  was applied to the amplification in the RT-PCR assay. GAPDH was employed as an internal reference.3 into the 96-well plate. Then, cell viability was tested utilizing the MTT Assay Kit . The cellular proliferation was performed by the BrdU Cell Proliferation ELISA Kit  according to the protocols.Cell growth was examined via VSMC viability and proliferation, respectively. Cells were planted at a density of 1.5 × 105) resuspended in 100 ml of DMEM were introduced to the upper chamber, while 600 ml of DMEM with 10% FBS was given to the bottom chamber. VSMCs that had moved into the bottom chamber were fixed with 4% formalin solution, dyed with 0.5 percent crystal violet, and quantified using optical microscopy .Matrigel was applied to detect the capacity of cells to migrate . VSMCs (1 × 10The RNA Immunoprecipitation (RIP) Kit (Bersin Bio) was used in the RIP assays. RIP lysate was used to obtain cell extracts, which were then combined to magnetic beads and antibody against EIF4A3 (Sigma-Aldrich). The secondary antibody was Anti-IgG (Sigma-Aldrich). The isolated coprecipitation RNA was submitted to the qRT-PCR assay.After transfection, 2 mg/ml Actinomycin D  was put into the medium to stop the transcriptional process. The residual mRNA was measured utilizing qRT-PCR following administration with Actinomycin D for various time points.To isolate RNA in the nucleoplasm, the PARIS Kit  was used. In a word, samples were extracted, digested on freezing, and then centrifuged at 12,000g for 3 minutes. U6 and GAPDH were used as nuclei reference and cytoplasmic reference, respectively. The precipitate was tested for cytoplasmic RNA, and the nuclei pellet was applied to identify nuclei RNA.t-test was used to analyze the statistical differences between the two groups. One-way ANOVA was used to examine comparisons between three or more groups. In order to have statistical significance, the P value cut-off selection is 0.05.All data collection was carried out with SPSS 23.0, and all experimental findings were presented as the mean ± SD. All the data conform to the normal distribution, and the P < 0.05) (P < 0.05) (P < 0.05) (P < 0.05)  . Thus, i < 0.05) . The CCK < 0.05) . In addi < 0.05) . TherefoP < 0.05). In addition, NORAD knockdown in VSMCs resulted in a lower extracellular acidification rate (ECAR), which is a measure of cellular total glycolysis flux, and there was a significant difference between the groups (P < 0.05) (P < 0.05)  . Moreove < 0.05) . CollectP < 0.05)    . In orde Figures . In addi < 0.05) . All theβ impacted the growth and metastasis of VSMCs. While TGF-β was abundantly expressed, cell viability was suppressed by suppression of NORAD, as seen in P < 0.05). It was claimed that ectopic TGF-β expression prevented the NORAD knockdown-induced decrease in migration, and there was a significant difference between the groups (P < 0.05)    . To summ Figures . In addi Figures . In summβ mRNA. These results indicated that the NORAD/LIN28B/TGF-β axis promoted cell proliferation and migration through regulating aerobic glycolysis in VSMCs. Therefore, NORAD may regulate the occurrence of AD through reprogramming that affects glucose metabolism, and NORAD can be used as a good target for VSMC phenotypic intervention and AD therapy.This study identified that the noncoding RNA activated by DNA damage (NORAD) level in VSMC was obviously increased, and NORAD knockdown could impede the proliferation and migration of VSMCs; meanwhile, the silence of NORAD could also inhibit glycolysis. In addition, mechanism studies have shown that NORAD can exert VSMCs-regulating function by recruiting LIN28B to bind to TGF-That being said, VSMC performed important parts in the pathogenesis and development of AD, according to mounting evidence , 16. Bloβ mRNA degradation and modulate the transcription at the genomic and epigenetic levels among many other things. This research investigates and identifies the epigenetic regulation of NORAD on the VSMC via the RNA-binding protein regulation mechanism. This pathway of RNA-binding protein provides an excellent regulating manner for the lncRNA. Via this pathway, NORAD could promote the proliferation and migration of VSMC in the AD. Then, we carried out a chain of measurements and observed that the inhibitory effect of NORAD knockdown on VSMC growth and migration was greatly changed via TGF-β high expression. This finding implies that the NORAD knockdown-induced reduction of VSMC growth and invasion needs TGF-β activity. According to existing research, a variety of biosynthetic processes may play a key role in the innate immune system of AD [β axis promoted cell proliferation and migration through regulating aerobic glycolysis in VSMCs. There are some limitations to this study. First, the sample size of this study is not large, and it is a single-center study, so bias is inevitable. In future research, we will carry out multicenter, large-sample prospective studies, or more valuable conclusions can be drawn.Previous research has shown that lncRNA can engage RBPs to modulate the mRNA stabilization of their target genes . The RBPem of AD . Solvingem of AD . Gluconeem of AD . What isβ. All the results are helpful to reveal the biochemical pathways associated with VSMC-related vascular remodeling, thus providing new potential biomarkers for diagnosis or treatment.Ultimately, this study identified potential biological pathways for vascular remodeling controlled by VSMC. The upregulation of NORAD promotes the proliferation and migration of VSMC through posttranscriptional regulation of TGF-


Prevotella to Bacaeroides ratios, possibly related to fiber consumption. Frugivorous primates are colonized predominantly by Prevotella and Bacteroides, pointing to an increased adaptation to high-sugar and simple carbohydrate diets. Likewise, BA profiles differ according to diet in a manner predictable from the known effects of BAs on metabolism. Folivorous primates have high conjugated bile acid levels and low unconjugated to conjugated BA ratios, consistent with their fiber-rich leaf-eating diet. Much of the differentiation in secondary and unconjugated BAs is associated with microbiome composition shifts and individual bile acid concentrations are correlated with the abundance of distinct bacterial taxonomic groups. Omnivores have higher concentrations of secondary BAs, mainly lithocholic acid (LCA). These levels are significantly positively correlated with the presence of Clostrida species, showing that the digestion requirements of omnivores are different from plant-eating primates. In conclusion, gut microbiome and BAs can respond to changes in diet and are associated with nutrient component consumption in each diet primate group. Our study is the first to demonstrate BA profile differentiation among primates preferring diverse diets. BAs thus appear to work with gut microbiome to help primates adapt to their diet.Primates have evolved a variety of feeding habits and intestinal physiological structure. Gut microbiome act as metabolic organs in many biological processes and play a vital role in adaptation to dietary niches. Gut microbiome also convert primary bile acids (BAs) to secondary. BAs profile and gut microbiome are together influenced by diets and play a significant role in nutrient absorption. The regulation between gut microbiome and BAs metabolism is bidirectional although the relationship in primates consuming diverse diets is still unclear. Here, we investigated gut microbiome structures, fecal BAs profile, and their relationship in primates preferring three distinct diets. We found that gut microbiome communities are well differentiated among dietary groups. Folivorous primates had higher Firmicutes abundance and lower  Over the long course of evolution primates have adapted to diverse diets and display a diverse array of anatomical specializations in their stomachs, caeca, and colons . In addiHost hepatocytes synthesize primary BAs from cholesterol . These pRhinopithecus roxellana) are representative colobidae species (Macaca mulatta) are omnivores and representative species of the Cercopithecinae subfamily (Hylobates syndactylus), commonly known as lesser apes, are representative primate frugivores that inhabit tropical and subtropical rainforests , the omnivorous Macaca mulatta , and the frugivorous Hylobates pileatus, Nomascus annamensis, and Nomascus leucogenys . Additional sample information is in the We collected 30 fecal samples from three primate species with different dietary preferences: the folivorous R. roxellana: assembly ASM756505v1; Homo sapiens: assembly GRCh38.p13; M. mulatta: assembly Mmul_10; N. leucogenys assembly Asia_NLE_v1; and Hylobates moloch: assembly HMol_V2) using bowtie2 . DNA quality and quantity DNA were determined using a nanodrop (ND-1000) spectrophotometer  and agarose gel electrophoresis. Shotgun sequencing was performed using Illumina NovaSeq 6000, with at least 10 Gb per sample . Adaptor v2.3.5;  with theTaxonomic profiles were generated with the mOTUs profiler (v2.0.0) 52  using thMOTUs profiles and K-numbers were first converted to relative abundance to account for library size, then were analyzed using a nonparametric test and correlation S5. SpecA UHPLC–MS/MS system was used to quantify BAs at Novogene Co., Ltd . We analyzed 33 kinds of BAs along with six stable isotope-labeled internal standards obtained from ZZ Standards Co., LTD . Ammonium acetate was of analytical grade and obtained from Sigma-Aldrich . Methanol (Optima LC–MS), acetonitrile (Optima LC–MS), and formic acid (Optima LC–MS) were purchased from Thermo-Fisher Scientific . Standard operating procedures were followed to prepare standard solutions and extract BAs from fecal samples.Separation was performed on an Agela Venusil MP C18 column  maintained at 50°C. The mobile phase, consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B), was delivered at a flow rate of 0.50 ml/min. The solvent gradient was set as follows: initial 20% B, 0.5 min; 20–35% B, 1 min; 35–37% B, 2.5 min; 37–38% B, 4.1 min; 38–39% B, 6 min; 39–40% B, 6.5 min; 40–44% B, 8.5 min; 44–45% B, 9 min; 45–52% B, 9.5 min; 52–55% B, 11.5 min; 55–100% B, 12.5 min; 100–20% B, 15.1 min; and 20% B, 17.1 min. The mass spectrometer was operated in negative multiple reaction mode (MRM). Parameters were as follows: IonSpray Voltage , Curtain Gas (30 psi), Ion Source Temp (550°C), and Ion Source Gas of 1 and 2 65 psi; .Quality control (QC) was used to evaluate the stability of methods and machines –1. Data post hoc tests  used the adjusted p-value. Spearman correlations were used to explore the relationship between fecal concentrations of individual BAs metabolites and the relative abundance of bacterial taxonomic groups obtained by the LEfSe analysis, performed using OmicStudio tools. Value of p < 0.05 was considered statistically significant.Statistical analyses were performed using GraphPad Prism version 5.0 (GraphPad Software). Differences in characteristics between groups were analyzed using the Kruskal–Wallis test with Dunn pFF = 0.0034, pOF = 0.0412; ACE index: pFF < 0.0001, pFO = 0.0045; R = 0.8333, p = 0.001; We identified 473 species from fecal samples of three dietary groups of primates. These species belong to 14 phyla, 24 classes, 38 orders, 59 families, and 110 genera . We founpFF < 0.0001, pOF = 0.0049) and the lowest log P/B .We next compared BAs profiles among groups of non-human primates consuming different diets. We observed obvious differences in BAs composition among diet groups, when viewed directly  or throupFO = 0.0026, pFF = 0.0105), TCA (pFF = 0.0168), GDCA , TDCA , HCA (pFF = 0.0228), and NorCA  are highest in folivores, while individuals in this group are relatively deficient in alloLCA , isoLCA (pOF = 0.0063), and 3_DHCA (pFO = 0.0002), but relatively little CDCA (pOF = 0.0002), β-MCA (pFO = 0.0248), and DCA  and TUDCA (pOF < 0.0003), but relatively little TLCA  associations. HCA, NorCA, and most conjugated BAs  are positively correlated with Enterobacterales (Proteobacteria) and Coraliomargarita (Verrucomicrobia) in folivores  in omnivores, while CDCA and TUDCA are negatively correlated with Intestinibacter (Clostridia) and Helicobacter , K15870 (pFO = 0.0183), K15872 (pFO = 0.0065), and K07007 . K15871, K15873, and K15874 are no significantly different among dietary groups (pFF = 0.0021), K22604 (pFO = 0.0436), and K22607 (pFO = 0.0203) are also overrepresented in folivores (pFF = 0.0021) is underrepresented among frugivores  and 7-dehydroxylation . We also identified genes coding for the HSD class of enzymes that catalyze the reversible oxidation of hydroxyl groups on the C-3  and C-7  carbon positions of the BAs steroid core. Furthermore, we found genes whose products belong to 13 KEGG ontologies involved in secondary BAs synthesis. Products of these genes cover all the major metabolic steps, except for K15869 and K23231. These were not found possibly due to detection and processing problems. Of the genes, we did identify, only three  were detected across all samples, and one (K22607) was absent in omnivores . The BSHy groups . Furtherolivores . In contugivores .Using microbiome shotgun sequencing and metabolite mass spectrometry, we examined gut microbiome and BAs metabolite profiles of non-human primates consuming a variety of diets. We found significant differences in both gut microbiome composition and BAs profiles among three major dietary groups . Furthermore, correlations between bacterial taxon abundance and metabolite concentration vary among three groups. We further focused on the abundance of individual bacterial genes coding for BA metabolizing enzymes and found that some were associated bile acid profile differences among dietary groups. This suggests that the microbiome plays a direct role in diet-driven differentiation in BAs prevalence among primate species.Prevotella to Bacaeroides ratio. This combination is thought to promote dietary fiber digestion  and Bacteroides (Bacteroidetes) are enriched in frugivores. These bacteria help to degrade simple sugars and carbohydrates  abundance among dietary groups  can help degrade simple sugars and carbohydrates, alleviating the adverse effects of fruit-derived sugars (Phascolarctobacterium (Negativicutes) in frugivores. CDCA is beneficial to the host because it can prevent the growth of Clostridioides difficile , increased abundance of a secondary BAs producer (Clostridium hiranonis), and increased levels of secondary BAs, LCA, and DCA , and The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: NCBI, BioProject ID PRJNA799478 .ML and HP designed the study. XL, MZ, and SW collected samples in the field. XL and XW performed the experiments. XL, XW, and ZW analyzed the data. XL, XW, ZW, HP, and ML wrote the manuscript. ZX provided constructive comments. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China and the Strategic Priority Research Program of Chinese Academy of Sciences .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The presence of middle-latency evoked auditory potentials allows for integrity evaluation of both peripheral and the central auditory systems, and also, that of the nucleus and auditory pathways of sub-cortical region. They have also been used to study alterations of these structures in different neurological diseases.the aim of this study is to verify the latency of the middle-latency evoked auditory potentials and detect the presence of any deflections in subjects with neurological diseases.In a clinical and prospective trial, 20 patients having central neurological diseases of various etiologies were evaluated and, positive and negative deflections produced by the middle-latency evoked auditory potentials in these patients were analyzed.Data was statistically analyzed and showed significant modifications in middle-latency evoked auditory potentials.The authors concluded that patients with neurological disorders have either wave suppression or enlarged latency periods in relation to normal subjects. Obtaining middle latency auditory evoked potentials is highly important in an attempt to improve the objectiveness of assessing patients with hearing loss, both in regards of determining their thresholds, as well as in locating the lesion. Today, they have also been used to study the alterations that happen in different neurological disorders.These potentials represent a series of deflections that happen between 10 and 80 milliseconds (ms) after the auditory stimulus, and are located beyond brainstem evoked potentials, preceding later responses, which are related to cortical and cognitive functions.These responses were firstly recorded at the “Massachusetts Institute of Technology” by Geisler et al.Nonetheless, in 1963, Bickford et al., stated that these responses were purely generated by muscle potentialsStarting in 1967, studiesIn 1974, many waves were described, such as N18 (Na), P30 (Pa) and P50 (Pb), trying to separate these responses from the pure myogenic responses, such as the ones that occur by contraction of the post-auricular and temporal musclesLater studiesFrom then on, many authors carried out studies on the sites that generate deflections with latencies between 10 and 80ms. It was so demonstrated that wave Pa suffers a clear reduction in patients with temporal lobe lesion, when compared to the normal hemisphereThe many deflections are described in details in relation to their sites of generation, using surface electrodes in patients undergoing neurosurgeriesDespite these evidences, more systematized studies about these responses were made to assess afferent auditory pathways, studies that only started to gain some ground at the late 80’s.In 1990, these middle latency potentials are characterized between 20 and 70ms, both with monoauricular and binauricular stimulation, with the following distribution: Pa, the best established middle latency response, at 29ms; Pb at 53ms and Tp at 41ms. Intracranial pharmacological and topographical evaluation, and those by induced lesions indicate that these three positive deflections are of neural origin. It is still unclear if Pa and/or Pb are produced in the Heschl gyrus, in the primary cortex; while Tp is probably generated by the auditory cortex, on the lateral surface of the temporal lobeIn studies carried out with lab animals, it was shown that responses obtained at the ventral and caudal-medial subdivisions of the medial geniculate body are functionally different. The inhibitory effect on recordings obtained from the ventral subdivision is similar to the one seen in middle latency components recorded on the temporal cortex, while the recording obtained from the caudal-medial subdivision is similar to the ones in the middle line. Moreover, these imply that binauricular patterns seen in the primary and non-primary auditory cortex may be processed and coded in the thalamusOther studies showed that the generators of the components obtained at 30, 50, 60 and 75ms are distributed medio-lateraly along the Heschl gyrusIt is believed that the generation of middle latency auditory potentials may reflect an interface of primary and non-primary areas of the thalamic-cortical auditory pathways. Primary and non-primary components may be differentiated in numerous ways: by lesion, by stimuli variations and topographically. Non-primary components develop early on and are likely to be dependent on sleep status, while primary components develop later on and are detectable during sleepThus, it is characterized that middle latency auditory responses, are a sequence of evoked potentials, which occur within a given time span, with latencies of 10 to 60ms. These potentials would have a relatively long development time, which extends through a person’s first decade of life. We then describe the characteristics of development alterations for each one of these deflections, not only related to their formats, but also to the potential reproducibility, alert status dependence and stimuli rates. Studies both in humans and animals indicate that these complex changes may be the result of multiple generator systems that have different development stagesObtaining middle latency auditory potentials start having major clinical applications in different situations, such as in the electrophysiological determination of auditory thresholds in low frequencies, in assessing cochlear implant functioning, assessing the functioning of the auditory pathways, in locating lesions in the auditory pathways and in intra-operative applicationsThese evoked potentials may be used to assess information processing. When we analyze somatosensory and auditory middle latency auditory potentials concurrentlyIn an attempt to explore other aspects of information processing, there are some researchers studying the habituation of auditory evoked responses (P50) with the use of repetitive stimuliStill in 2001, based on middle latency evoked auditory responses seen in patients with Obstructive Sleep Apnea Syndrome, before and after treatment, it is suggested that the ascending reticular activity may be involved in these patientsIn this same year, a study was carried out in which they obtained brain stem auditory responses and also middle latency auditory responses in three groups: one from patients with tinnitus, another one from normal individuals and, the third, from elderly patientsAs they researched using two comparative methods, obtaining middle latency evoked auditory responses by electroencephalographic recordings or by means of magnetoencephalographics, multiple supratemporal bypasses were suggested for the different deflections observed. Therefore, Pa (28ms) is correlated to the medial portion of the Heschl gyrus; Nb (40ms)/ Pb1(52ms) to the lateral face of the supratemporal gyrus; and Pb2 (74ms) to the antero-lateral portion of the Heschl gyrusLater on, carrying out a simultaneous capture of intracranial auditory evoked potentials directly from the auditory cortex and the medial geniculate bodyIn our country, in 2003, a study considered critical the need to understand the maturation of the auditory system when one wants to check the integrity of central auditory pathways. When we studied middle latency potentials in 155 normal individuals from 07 to 16 years of age, we noticed that it was possible to observe a Pa wave in all individuals tested; however, it was not possible to check central nervous system maturity through its latency and amplitudeWhen middle latency potentials were analyzed in patients with myotonic dystrophy and central nervous system involvement, one notices that Na and Pa amplitudes are significantly higher when compared to the ones recorded from normal individuals It has been shown the importance of recording different accessible potentials in order to monitor the functional status of the central nervous system when assessing cortical dysfunctions resulting from hemorrhagic, ischemic or hypoxic strokesBrainstem evoked auditory potentials are altered in pregnant diabetic women when compared to normal pregnant women. In the former, latencies were observed in deflections I to V and interpeak latencies I-III and I-V were significantly higher, while wave V amplitude was reduced. Nonetheless, we did not find any significant alteration in the latencies of medium potentialsThese potentials represent an important tool to assess cerebral function, not only from the auditory standpoint, but also in patients with neurological disorders, as it has been shown in many studies with comatose patients or patients who suffered a head injury. Prognostic values of the somatosensorial and auditory cortex evoked responses are evaluated in comatose patients.In a population of 27 patients with schizophrenia, when compared to the normal population, alterations were detected in the form of middle latency deflections, and also increased latencies. It is suggested that the morphological abnormalities of middle latencies in schizophrenia are significant and must be examined in this populationInvestigating the P50 deflection in patients with post-traumatic disorders secondary to urban violenceIn recent years, many scientific investigations have been carried out, showing that these potentials are related to the auditory nuclei and pathways located on the subcortical and primary cortical regions, especially in the thalamic-cortical tract.1.Assess the presence of the many deflections originated from medium latency auditory potentials.2.Compare the values of their latencies, as well as that from the Na-Pa interval, with the values found in a normal, standardized, previously studied population.Our study of middle latency evoked auditory potentials in a sample of individuals with neurological disorders, with central involvement , had the following goals:Our series counted on 20 individuals, from both genders, without a pre-determined age, who had neurological disorders, of different etiologies of a central level, who were neurologically, otologically and audiologically assessed. These evaluations were not invasive and, usually, do not cause any harm to the individual.All the individuals participating in this study were duly informed about the procedures to which they would be submitted, as well as the study’s goal, and they signed an informed consent.This study was quantitative and the sampling was non-probabilistic. The study subjects were chosen by convenience and the data collected were assessed taking into account inter-individual relations. We used a cohorte approach, with contemporary evaluation.We applied descriptive and inference statistical studies. In them, data were analyzed having in mind the “T student”, bi-caudal, test, with equal sample variance, considering a significance level (p) below or equal to 0.05.The study that involved human beings followed strict ethical rules that were established and was submitted to the Ethics Committee of the institution under protocol # 201/04.The selection process counted on anamnesis, neurological assessment, clinical otological inspection, acoustic immittance measures, stapedial reflexes study, conventional tonal audiometry and logoaudiometry. When necessary, it was complemented with other tests, such as electroencephalography and image evaluations .With that we would only have left the interferences belonging to the individuals that were tested or the examiner. We also tried to avoid them by means of additional care. The electrodes, as well as the ear phones were positioned always by the same examiner, after proper individual education. Booth environmental conditions  were the most adequate ones to keep the subject calm and relaxed, without letting him/her sleep. The electrodes were attached after careful skin cleaning, with proper electrolytic paste, so as to better capture the potentials of interest. The test only started when the baseline electroencephalogram was stable and without interferences.The equipment used was the CE - EP 25 operational system. The CE brand indicates that “Interacoustics” fulfills the demands required in attachment VI of medical guideline 93/42/EEC and was approved by TÜV, with identification # 0123.-Stimulus: “Click”, lasting for 100ms, with alternate polarity, without masking, at the frequency of 7.0 stimuli per second, in a total of 1000 stimuli.-Stimulus intensity: 70 dB SPL, introduced through TDH 39 ear phones.-Electrodes: Two “Live” electrodes, placed on the upper region of the scalp, at half the distance between the cranial vault vertex and the mastoid region, in each side; two “reference” electrodes, were placed in the mastoid region, on each side, and a “ground” electrode was placed on the glabella.-Impedance: electrodes impedance was around 2W, and a maximum of 3W is accepted.-Recording time span: from 0 to 80ms.-Recording time span: from 0 to 80ms.Filters: 10 Hz high pass and 1200 Hz low pass.-Recording time span: from 0 to 80ms.Reproducibility index: 95%.-Recording time span: from 0 to 80ms.We used mono-auricular stimulation.-1.Stimulus: Right Ear Capture: Right Hemisphere (RERH)2.Stimulus: Left Ear Capture: Right Hemisphere (LERH)3.Stimulus: Right Ear Capture: Left Hemisphere (RELH)4.Stimulus: Left Ear Capture: Left Hemisphere (LELH)Recording time span: from 0 to 80ms.Stimuli and response capture sequence:The exam protocol used in our research for the capture of middle latency potentials is the following:The patients evaluated, in a total of 20, in relation to their respective neurological disorders, are detailed on After submitting these patients to the predicted exams, the records obtained were analyzed and plotted on the following tables.The statistical comparison between the results obtained from the group with neurological disorders and the normal group, previously standardized can be seen on The capture of middle latency evoked auditory potentials, described approximately five decades ago, was the topic of much controversy during a long time in regards of its origin Many authors have performed research with normal individuals using surface electrodes or placed inside the cranial cavity during a surgical procedure in human beings,Some authors, by means of electroencephalographic records and magnetoencephalographic data suggest multiple supratemporal sources for the many deflections observed. They then correlate Pa (28ms) to the medial portion of the Heschl’s gyrus; Nb (40ms)/ Pb1(52ms) to the lateral face of the supratemporal region; and Pb2 (74ms) to the antero-lateral portion of the Heschl’s gyrusIt is then believed that these responses originate from the auditory and non-auditory primary cortical area, especially from the thalamic-cortical bundlesThe clinical applicability of these potentials are found in many situations, such as, in the electrophysiological determination of auditory thresholds in the range of low frequenciesIn this study we noticed that these potentials make up an important tool for cerebral function evaluation, not only from the auditory standpoint, but also in patients with neurological disorders, as it has been shown in many studies with comatose patients or those who suffered head injuries, including prognosis,It is paramount to understand auditory system maturation when one wishes to check the integrity of the central auditory pathwaysIn this study we grouped neurological disorders of different etiologies and we compared the results attained from the normal group previously assessed in our serviceThrough statistical comparison among the results found  in the groups of neurological disorders and the normal group, previously standardized, it was established that the mean values are significantly higher in the first group. The most significant statistical differences were mainly related to the Pa, Nb and Pb deflections.By crossing the values obtained from the recordings of each cerebral hemisphere, with auditory stimulation in each ear, respectively, we did not find statistically significant differences as to the site of response capture, and this allows the exam to be carried out without the concern of where the electrodes will be placed.We can see that the recording of these potentials provide a reliable basis for the assessment of dysfunctions or even lesions in the central nervous system. In this study we did not sequentially follow up the patients, therefore there are no grounds in order to assess prognosis.During the exams, we concurrently captured the middle latency auditory evoked responses and also the short latency auditory evoked responses. At this time, we did no analyze these results comparatively. Notwithstanding, this facility makes this exam an extraordinary tool of great importance in daily clinical practice.There was no concern in specifically analyzing the characteristics of each disorder separately. The goal of the study was to analyze the results obtained and the alterations seen in the whole set of diseases present in the patients examined. This is important, considering the different diseases that may cause diffuse alterations in the structure and functioning of the cerebral tissue.The investigation of these middle latency potentials presents a great study possibility from the auditory and neurological standpoint. It allows us to perform an electrophysiological assessment of the subjects hearing level, and also provides for the identification of the possible lesion side, in the case of neurological disorders.1.Almost all the recordings were captures, there was suppression in only a few of them.2.The maximum and middle values of their latency periods, as well as the Na-Pa intervals, were significantly increased when compared to the ones obtained from a normal standardized population in our settings.In our sample of patients with neurological disorders, in relation to the deflections generated by the middle latency auditory potentials, we concluded that:


The fast pace of innovations in medicine and technology as well as the abundance of information available to doctors and patients is continually reshaping the notion of what constitutes an excellent doctor.write a prescription that can help doctors achieve that goal, with the following ingredients:-Current best evidence;-Critical thinking;-Continued education;-Collaboration, communication and collegiality;-De-centralized learning;-Compassion.A hundred years ago physicians acquired most of their medical knowledge during their medical school training years. A doctor's professional excellence mainly stemmed from their availability and the degree of attention and care dispensed to the immediate community. Today the stakes have progressively become much higher and a doctor needs to continuously seek new knowledge and rethink old practices. But what exactly do physicians need to do to be considered excellent nowadays? In the next paragraphs we shall attempt to Current Evidence-Based Medicine, in which physicians are encouraged to use the most current evidence found in the literature to make clinical decisions for an individual patient.levels of evidence, where research is arranged in a ranking system to describe the strength of the results measured in the study. Meta analyses and randomized controlled trials are ranked at level 1, the highest level, while case series or expert opinions at the lowest. By using such a scale, the reader can quickly weigh the level evidence of a certain paper in the literature.We now live in an era of every level 1 evidence – or that only level 1 evidence – is always the best choice for the research question. In otolaryngology, as a surgical specialty, there are many important papers that may have a lower level of evidence . Another great tool available for physicians are the Clinical Practice Guidelines (CPG), which are created by a group of experts that assess the evidence about important clinical questions or conditions based on systematic reviews. This evidence is then translated into a recommendation within a clinical practice guideline.It is essential to keep in mind that the designated level of evidence does not always guarantee the quality of the research. One should not assume that critical thinking comes into play: a doctor needs to understand patients as a whole  when using the current literature and CPGs to make clinical decisions.All this information is to be used judiciously when treating individual patients with their own specific conditions. This is where continued education. Participation in local, national, and society meetings are a fantastic way of keeping current with the latest knowledge and advances and to exchange ideas with peers. Online courses and forums are very helpful as well and can eliminate financial and geographical barriers that can be encountered when traveling to meetings.Another effective way of staying up-to-date with novel information is to engage in events that offer opportunities for collaboration, communication and collegiality. These come hand in hand, and are crucial for patient care. Collaboration in health care is defined as health care professionals assuming complementary roles and cooperatively working together, sharing responsibility for problem-solving and making decisions to formulate and carry out plans for each patient.Other ingredients included in this excellent doctor's prescription are correct answer, so learning something in different ways  can allow an individual to determine what works best in a physician's practice and for a specific patient. In the United States it is very common for physicians to go to college, medical school, residency and fellowship in different institutions. By doing so future doctors are exposed to more teachers and different “medical cultures”, which can enhance their education as physicians. In places where most trainees continue in their own institution there might be a bias in the selection of future candidates and less exchange of information. This is another reason why a decentralized learning process is important in the medical education. But one doesn’t necessarily need to travel far or spend a long time in a different institution to accomplish that. Visiting other centers, even if in the same town or state (and even for a short period of time), can be very beneficial.In regards to our medical education, great part of it comes in the form of lessons received from teachers during medical school, residency and beyond. Besides the technical aspects of medicine, each teacher and mentor influences us with their different ways of relating to patients, subtle cultural nuances, and distinctive thought processes. In the surgical field we also relate to the particular ways of someone performing surgical procedures. For many disease processes there is no single compassion. In spite of all the knowledge and technology available today, being able to respect and listen to our patients and to treat them with the dignity and care that they deserve continues to be, as it did a hundred years ago, a crucial part of what constitutes being an outstanding doctor.Even the most knowledgeable and up-to-date physician with the best technical skills will not become excellent without prescription for physician excellence should be taken daily. Long-term side effects include a rewarding professional life and a host of grateful patients, families and co-workers.We have chosen a challenging but much rewarding profession. Being an excellent doctor requires continued balance between the knowledge and the art of medicine. This The author declares no conflicts of interest.


Children with foetal alcohol spectrum disorder (FASD) can experience neurodevelopmental, physical, psychological and behavioural impairments that can result in a disrupted school experience. However, educators often have limited knowledge or experience in the identification and support of students with FASD, and there is a critical need for effective tools and resources to ensure students with FASD are supported in their ongoing learning and development. This scoping review aimed to identify and evaluate publicly available educator resources that aid in the identification, and support of students with FASD in primary/elementary school. In addition, educators and FASD experts were consulted to obtain feedback on currently available resources, and key issues and priorities for FASD resources. In total, 124 resources were identified by searching peer‐reviewed and grey literature databases, app stores, podcast services and contacting FASD experts. Information was found on identification (23 resources) and support of students with FASD (119 resources). No resources provided information on the referral. Most resources were average (40%) to good (33%) quality, as measured by a composite tool based on adaptions of the NHMRC FORM Framework and iCAHE Guideline Quality Checklist. A minority of resources had been formally evaluated (7%). Review findings and consultations with experts and educators indicate a critical need for referral guides, evidence‐based short‐format resources and centralised access for school communities to high‐quality resources. Taken together, this study has identified key areas for future resource development and research to better support primary school students with FASD. The review aimed to identify and evaluate publicly available resources for educators that aid in identifying and providing learning support for primary school‐aged students with FASD. The review focused specifically on resources for primary school educators because early identification and intervention are associated with reduced risk of long‐term adverse outcomes.2Ethical approval was provided by the University of XXX Human Research Ethics Committee (2020/825). The pre‐registered review protocol2.1The primary research question was “what resources and/or guidelines are available for educators that (a) enhance identification, assessment, and referral of students with developmental, learning, social and behavioural problems consistent with FASD and (b) aid support or accommodation of FASD‐related symptoms and behaviours in a school setting?”. Secondary research questions included “what is the quality of existing resources?” and “what are the effective components of resources designed to improve the support or accommodation of developmental, learning, social and behavioural problems associated with FASD?”.2.2Resources were identified by searching nine peer‐reviewed databases; 11 grey literature websites; two app stores; two podcast streaming services; contacting 15 FASD and education sector experts. The search terms and strategies are provided in Table 2.3A three‐phase screening and selection process was undertaken. First, the titles/abstracts/ descriptions of resources were screened for eligibility by one co‐author, with 20% of retrieved resources additionally screened by a second co‐author. Inter‐rater reliability was high . Second, full‐text versions and data sources of potentially relevant resources were assessed by two co‐authors to determine whether the resource would be included in the review . Finally, reference lists of identified materials were screened to identify other relevant resources.2.4Resource characteristics were tabulated to summarise relevant data Table . The qua2.5FASD experts, identified via team networks and online searches, completed online surveys to provide feedback on high‐quality resources from each resource type and identified gaps in currently available resources for educators. Additionally, Australian educators, recruited on social media, were consulted via online surveys and asked to provide feedback on FASD resources they have previously accessed barriers to obtaining information about FASD, and resources that they require to support students with FASD. Due to word constraints, these results are provided in the Supplement. The surveys took approximately one hour and included a combination of quantitative and qualitative open‐ended responses. Experts and educators were offered $40 as reimbursement for their time.33.1Searches were conducted up to February 2021. Of 3010 resources identified through the search strategy and screened, 124 met the criteria and were included in this review Figure .Resources were developed in the United States , Canada , Australia , the United Kingdom , New Zealand  and the Netherlands . Development dates ranged from 1969 to 2021, with 50% developed in the previous eight years (2013‐2021).Most resources focused on support of FASD‐related symptoms and behaviours (n = 119). A minority focused on identification of FASD indicators (n = 23). Most resources were text‐based  and a smaller portion were videos , podcast episodes , screening tools , student‐focused games , interventions  and professional development resources . Notably, 89% of resources identified were free for educators.3.2The overall quality of resources is summarised in Table There was considerable variation in the quality of the evidence base, currency, and the impact and utility of resources Figure . In term3.3Of the 23 included resources which provide information to aid identification of students with FASD indicators, 16 were text‐based (70%), 5 were screening tools (22%), 1 was a video (4%) and 1 was a professional development resource (4%)  included text‐based resources (n = 75), videos (n = 26), podcast episodes (n = 10), games (n = 2) and interventions for students (n = 2), and professional development modules (n = 4) Table . No rele3.4.1Seventy‐five resources were identified, including 38 longer guides and books (32% peer‐reviewed), 22 short factsheets and booklets, eight peer‐reviewed literature reviews, three classroom planning tools and worksheets (one peer‐reviewed), two peer‐reviewed primary research studies, and two peer‐reviewed theses. Nine of 75 text‐based resources were current and had undergone peer review. These resources describe evidence‐based practices to support students with FASD in the school setting Figures . Short f3.4.2Of the 26 videos identified, 22 were short videos or cartoons  and four were longer webinars or lectures. Webinars and lectures (n = 4) provided support strategies for behavioural management and academic success. Short videos and cartoons (n = 22) often focused on case studies and described strategies for a single domain, such as memory difficulties or sensory processing pace. No reference to evaluation or evidence for the effectiveness was provided for any of these resources.3.4.3Ten podcast episodes from four podcast shows were identified. Episodes focused on classroom adjustments , establishing the educator‐student connection, tips from tutors and school interventions. No reference to scientific evidence or evaluation of support strategies was described in podcasts.3.4.4PAX Good Behaviour Game introduces a positive classroom discipline system and is typically delivered across the first three years of primary school. A meta‐analysis of randomised controlled trials found the game has a small effect on improving classroom management and reducing behavioural problems.Two games for students were identified and one was of good quality. The 3.4.5Math Interactive Learning Experience program is a 6‐week intervention shown to significantly improve mathematics and handwriting skills and behavioural problems that interfere with learning readiness in children with FASD  were from Australia (n = 17) and the United Kingdom (n = 1) and worked as academics (n = 5), health professionals (n = 5), paediatricians (n = 3), in the not‐for‐profit sector (n = 1), social worker (n = 1), psychologist (n = 2) or as a school principal (n = 1). Years of experience in the field of FASD ranged from 3 to 30 years .Fourteen high‐quality resources were reviewed by experts and five (38%) were recommended for educators by all experts who reviewed them Table . These iFour key gap themes were identified from the expert survey: (1) low awareness about FASD, (2) low accessibility of current high‐quality resources, (3) need for evidence‐based referral resources and (4) need for evidence‐based resources providing classroom support strategies (see Supplement for further details).44.1The aim of this scoping review was to identify resources that are publicly available to the primary/elementary education sector and provide staff with skills and strategies to improve the identification and support of students with indicators of FASD. In total, 124 relevant resources were identified and reviewed, 23 included information on identification, 119 included information to support students with FASD, but no resources provided information to facilitate referral. Resources were typically of average to good quality; however, less than 10% of resources had been formally evaluated. Most resources were developed in North America and made available to the education sector in the past eight years. Text‐based resources and videos were the most common type of resource identified, text‐based resources generally being higher quality than videos. Notably, many short format resources —which are arguably more accessible and usable for time‐poor educators—were of very poor to average quality. Consulted experts and educators noted high‐quality resources are hard to access due to both challenges in locating resources online and a lack of evidence‐based resources. Some experts called for a centralised Australian repository (website) of FASD resources for school communities including evidence‐based identification and support resources, available in short and accessible formats.4.2This review identified only two evaluated screening tools available for use by educators4.3Thirty good to excellent quality support resources were current, including 17 guides and books, three booklets and factsheets, three professional development resources, two student interventions, two podcast episodes, one webinar, one short video and one game for students. Although there are a variety of high‐quality resources available to educators, experts note it is difficult for educators to locate these resources given they are spread across multiple websites and suggest the need for a centralised repository of high‐quality resources, such as FASD Hub or a dedicated platform for educators. Furthermore, many text‐based FASD resources identified are over 50 pages long and educators noted that time constraints are a key barrier to accessing resources. Development of short format resources, such as fact sheets or explainer videos that provide classroom strategies to support students with FASD Figure  and skilIn alignment with findings from previous reviews of FASD interventions,Finally, there is generally a lack of formal evaluation of resources and support strategies. The evidence base is often unclear, as reflected in the quality ratings. It is recommended that developers of future FASD support resources: (1) only include evidence‐based strategies, (2) test the utility and effectiveness of the resource with target users and (3) clearly state the evidence base of the resource. Adoption of these recommendations will improve the quality and utility of FASD support resources for educators.4.4This scoping review and consultation with experts and educators have identified five priority areas for future resource development and research: (1) development and evaluation of guides that facilitate discussions between educators and caregivers about referral pathways for clinical assessment, (2) development of short‐format resources that outline evidence‐based FASD support and accommodation strategies in an accessible format for educators, (3) development of strengths‐focused, school‐based FASD interventions and evaluation of such interventions by randomised trial, (4) evaluation of resources for feasibility and effectiveness and (5) improved access to high‐quality resources for the school community via online platforms, including professional development and training. Addressing these priorities will ensure that educators are better equipped with a suite of resources that allow them to effectively recognise and respond to students with or suspected of having FASD.4.5First, the search strategy focused on websites and databases in Australia, New Zealand, Canada, the US and the UK. This strategy was employed as previous reviews show this is where most resources have been developed.4.6This scoping review identified 124 publicly available resources for educators that provide information on the identification and support of primary/elementary school‐aged students with FASD. Most resources were of average to good quality but few were formally evaluated. Generally, short‐format, easy‐to‐access resources were of poor to average quality and less accessible guides and books were of higher quality. Following the review and consultation with experts and educators, priority areas for future resource development were identified, including development and evaluation of referral guides and evidence‐based short‐format resources and evaluation of interventions targeting primary and secondary consequences of FASD in students. Experts called for increased access to high‐quality resources for school communities including evidence‐based resources for the identification and support of students with FASD. Addressing these priority areas will better equip educators with resources that allow them to effectively identify and support students with FASD.None to declare.Supplementary MaterialClick here for additional data file.


Healthcare in the third millennium is largely delivered through systems involving the use of the technological devices and services, foremost among them telemedicine. For the adequate delivery of digital medicine services, however, it is necessary for users to be digitally literate, that is, able to consciously make use of technology. In order to understand how relevant digital literacy is in determining the effectiveness of e-Health services, we performed a traditional literature review on 3 major databases by combining the terms “Digital Literacy” and “Computer Literacy” with the terms “Telemedicine” and “Telehealth”. Starting from an initial library of 1,077 papers, we selected 38 articles. At the outcome of the search, we found that digital literacy is a pivotal element in conditioning the effectiveness of telemedicine and digital medicine services in general, however, with some limitations. A major driving force behind the amplification of the primary role played by technology in the delivery of health care services was undoubtedly the COVID-19 pandemic, which by imposing a restriction on interhuman contact forced the adoption of health care measures that could be delivered remotely, by means of technological tools , but one of the cornerstones of an evolved society is equity in healthcare provision, and today, in the third millennium, it seems really difficult to think that this goal can be pursued apart from a serious and structured digital literacy policy.Since health is a basic human right, the delivery of health services must be done equitably, that is, by ensuring that all individuals could reach their full potential for health and wellbeing. The digital divide brought about by the increasingly pervasive diffusion of technology in health care necessitates the implementation of increasingly efficient education programs in the use of new digital tools, as it has become clear that education is a primary tool for ensuring health equity, no less important than scientific progress , 11.any healthcare development that doesn't rapidly become available to all individuals has the unintended consequence of fuelling health inequality” . The search was performed entering the following base string:  AND , limiting the results to English-language articles published in the above time frame. The basic string was, of course, modified according to the individual peculiarities of the various databases on which the search was carried out. We voluntarily omitted to include the databases for the gray literature search to avoid contaminating the review with papers with uncertified scientific validity.We performed a preliminary skimming independently. Each author read the abstracts of the articles and identified those they considered useful for the review. At the end of the preliminary evaluation phase, the authors discussed the selected articles, debating the suitability of the individual papers. At the end of the selection procedure, the authors read all the articles in order to collect the data for the review.n = 453) and articles for which the full text was not available (n = 7). We then read the titles and abstracts of the remaining 617 articles in order to identify papers suitable for reading the full text. A total of 94 articles were discarded just by reading the titles, which were clearly not in line with the purpose of the review. After reading the abstracts of the remaining 523 papers, we excluded an additional 293 papers: 107 because they illustrated particular telemedicine services without a clear discussion of the link to digital literacy, 112 because they delved into the topic of digital literacy without particular reference to its impact on access of telemedicine services, and an additional 74 because, although they dealt with the impact of digital literacy on access to telemedicine, they did not provide useful insights to answer the review questions.The research initially provided 1,077 results. Specifically, 223 papers were found in PubMed, 682 in Scopus, and 172 in Web of Science. The types of study objects of interest were original researches, review articles, and perspective papers. We made an initial pre-selection by removing duplicate papers   was emplThe search identified 37 articles suitable for inclusion in this review. The 37 papers were published between 2013 and 2022. Specifically, 1 article was published in 2013, 1 in 2016, 4 in 2018, 3 in 2019, 1 in 2020, 11 in 2021, and 16 in 2022. A total of 14 papers are literature reviews or papers in which the authors express their views on the topic , and 23 are papers in which actual research was conducted (mainly retrospective and survey studies). Given the large number of articles included in the review and the objective difficulty in discursively describing the results of all 37 papers, we briefly illustrated the main characteristics of the selected papers within The insights provided by the analysis of the reviewed articles are numerous. A first fundamental point seems to be the importance that is universally recognized to digital literacy as the key to ensuring an equitable distribution of health services in the society of the third millennium, permeated by digitization and technologization , 47, 50.Intimately associated with this concept is the principle that ensuring equity of access to digital health through the enhancement and development of digital literacy must be a priority felt by multiple stakeholders: consumers (patient and carers), consumer advocacy groups, health service staff , health services (providers), policy-makers/funders, researchers, and industries . This isIt is very important to note, however, that like any ambitious project, that of adapting digital literacy to the levels of technology that characterize our society today must come to terms with realism. This means that providing for an extension and capillarization of digital skills would risk further exacerbating technological evolution, thus risking leading to a widening of the “digital divide” secondary to the gap that could arise from the speed of growth of digital skills (fast) and the speed of growth of technology (very fast). In other words, there would be a risk of favoring technology that evolves too fast compared to how fast digital skills evolve .It is therefore essential to pursue the goal of supporting increasing digital literacy in a prudent and reasoned manner, also in view of the fact that e-Health services are often, paradoxically, particularly effective in low digitally literate individuals . This paAnother interesting food for thought that emerged from the review is how to identify individuals who may benefit from digital literacy programs. Despite the fact that very often the category of people unable to independently use digital tools in the service of health coincides with the elderly population, this correspondence is not always true, depending, as the review clearly demonstrated, on numerous other factors. Even the parameter of socioeconomic status is not accurate in defining who is reliably digitally competent and who is not. In fact, not always those with high incomes  possess a sufficient degree of digital literacy to make beneficial use of e-Health services . It is tIt is also interesting to note that, based on the review conducted, it can be concluded that underlying the need to ensure uniform digital literacy should not only be the desire to ensure “equitable” healthcare, but also to prevent the development of “unfair” healthcare. Indeed, those who are poorly digitally literate not only have fewer options in terms of access to care, but are also more vulnerable to the negative and detrimental effects that can result from finding unreliable online information or the product of fraudulent scientific research . From thIn summary, then, we can conclude how digital literacy is an essential element in the development of equitable digital medicine. However, this is a complex road ahead, given the complexity of the underlying socioeconomic and cultural scenarios, the critical issues in identifying the target population, and the need for a multidisciplinary and multiple stakeholder approach.As a final consideration, we can note how it is not only important to implement digital education programs that can bridge as much of the “digital divide” as possible, but how it is equally important to plan for evaluation studies of the effectiveness of such programs in the immediate future.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.LC: conceptualization and writing original draft. FG, PB, and GN: writing, reviewing, and editing. AS and GR: supervision and coordination. All authors contributed to the article and approved the submitted version.


Nature  creating the capacities, opportunities and motivation to use evidence to address societal challenge, and putting in place the structures and processes to sustain them”. The commission explored the levels, sectors and complexity of societal challenges needing evidence; decision-making processes and who decision-makers are; forms of evidence encountered in decision-making; how forms of evidence can be mapped to decisions; the need for high-quality local and global evidence; the critical role of system infrastructure for evidence-based decision-making; and the role of evidence intermediaries, public goods and distributed capacity. The report presents recommendations that encompass the framing/approach, structures and processes, accountabilities and funding, together with actions that emerge from these foundations. The document includes 8 main and 24 total recommendations clearly presented in short-form in the executive summary of the report  to supporting the use of evidence in everyday life” [The COVID-19 Evidence Network to support Decision-making (COVID-END)  is a glooducers” . The titay life” .Table 2RFinally, Cochrane  publisheEvidence-based medicine (EBM) and evidence-based practice in health are only a few decades old and combine the 3 components of research-based evidence: the clinician's expertise and the patient's values and preferences . An esseEBM in rehabilitation has not always been accepted as the best way forward . RehabilThe documents highlighted in this paper call for evidence as the main tool to make decisions about the treatment of health conditions in individuals and populations. This approach to decision-making is becoming clearer to policymakers, too. The documents call us to action or provide the resources to support action for evidence-based decision making in health and in societal challenges that face us locally and globally. We are stakeholders in health and human systems and in the evidence-ecology that have the opportunity to feed into decision-making systems that affect us all. We have to enhance evidence-informed decision-making in our own practice and in the systems in which we live and work. We can be decision-makers or decision intermediaries, adopting or advocating for the specific strategies outlined in sources presented here in practice, policy and education. We can be evidence-producers, advancing the strength and quality of research by asking questions suited to answers that use well-designed randomised controlled designs, primarily because these provide the greatest opportunity for synthesis and uptake in clinical guidelines. When other questions are asked and other research designs are used, we can build capacity to ensure the appropriate interpretation and application of less rigorous findings. Beyond intervention research, rehabilitation systems and services need high-quality evidence to inform the managerial and administrative decision-makers who ultimately control access to and provision of human and infrastructure resources.The world of rehabilitation cannot afford to do without evidence, nor to remain diffident and passive on this issue. Our campaign to improve evidence in rehabilitation is fundamental to the future of the field, and we need to identify the optimal approach to the generation and utilization of evidence appropriate for rehabilitation. First, wherever appropriate and possible, we need to conduct well-designed RCTs. When RCTs are not appropriate or possible, other types of study designs such as rigorous quasi-experimental and n-of-1 designs can be used depending on the nature of the research question. Second, the 3 documents summarized in this editorial repeatedly stress the need for collaboration. To implement the many strategies and work toward achievement of the many recommendations, we need to champion rehabilitation as an essential, multidisciplinary, collaborative field. In rehabilitation, collaboration is particularly required, and divisions of any type  interfere with efforts to generate the best evidence and strengthen the field. This emphasis on collaboration includes other fields of inquiry because it facilitates a supportive environment, with evidence guiding discussions and decisions beyond healthcare systems to health policy and other areas important to society.Rehabilitation as a field and the community of rehabilitation journals are not new to collaborations. Rehabilitation journals have co-published several important papers during the last decade on various topics, including implementation of reporting guidelines  and triaAnnals of Physical and Rehabilitation Medicine – Dominic PérennouAmerican Journal of Physical Medicine & Rehabilitation – Walter FronteraDevelopmental Neurorehabilitation – Wendy MachalicekEuropean Journal of Physical and Rehabilitation Medicine – Stefano Negrini and Giorgio FerrieroJournal of Occupational Rehabilitation – Douglas GrossJournal of Rehabilitation Medicine – Kristian Borg and Henk StamMusculoskeletal Science & Practice – Ann MooreNeurorehabilitation and Neural Repair – Randolph NudoThis paper is supported and co-published by the following journals, and their Editors in Chief:


Caregiving is a strong source of stress and leads the family caregiver to experience the burden of being responsible for the care of a severely mentally ill family member. The Burden Assessment Scale (BAS) assesses burden in family caregivers. This study aimed to analyze the psychometric properties of the BAS in a sample of family caregivers of people diagnosed with Borderline Personality Disorder (BPD).M = 54.44, SD = 10.09) of people diagnosed with BPD. The BAS, the Multicultural Quality of Life Index, and the Depression Anxiety Stress Scale-21 were used.Participants were 233 Spanish family caregivers  = 56.873, p = 1.000, CFI = 1.000, TLI = 1.000, RMSEA = .000, SRMR = .060), good internal consistency (ω = .93), a negative correlation with quality of life, and a positive correlation with anxiety, depression, and stress.An exploratory analysis resulted in a three-factor 16-item model  with an excellent fit (χThe model obtained for the BAS is a valid, reliable, and useful tool for assessing burden in family caregivers of relatives diagnosed with BPD. Caring for people diagnosed with a severe mental disorder (SMD) usually falls on their relatives, for whom such responsibility is a strong source of stress and leads them to experience burden (e.g. ). BurdenBailey and Grenyer , in a reKay et al.  found thJørgensen et al.  found thReinhard et al.  stated tSeveral studies have analyzed the psychometric properties of the BAS, obtaining different results for both the number of factors and the items included in each factor Table . Horwitzr = .86, p < .001. Likewise, in Aydemir et al. .We used the Spanish adaptation . The MQLWe used the Spanish adaptation . The DASn = 233). In addition to McDonald’s ω, the Average Interitem Correlation (AIC) of the BAS was analyzed  . The AIC = .399, 95% CI  suggested that the items of the BAS were reasonably homogenous and contained enough unique variance to avoid being isomorphic with each other .All the MSAs for the BAS items were > .800, and the MSA for the whole BAS was 0.900. The solution showed a three-factor model for the BAS: Factor 1 contained 7 items (2–8), Factor 2 contained 6 items (9–11 and 14–16), and Factor 3 contained 3 items  (Table (F1-F2) = .531, ρ(F1-F3) = .460, and ρ(F2-F3) = .458. The effect sizes of these correlations were between intermediate and strong , SRMR = .060. All the parameters were significant at the .01 level  using exploratory procedures, as in Ivarsson et al.  (ActivitIt is worthy to note that (1) the mean for item 10 (Friction with others) was the lowest, and this item was included in Factor 2 ; (2) the mean score on item 1  was low; (3) the highest mean score was on item 18 (Worry about the future), close to the maximum of the scale; and (4) the mean for item 19 (Stigma upsetting) was comparable to that of other BAS items that were included in any factor (e.g. items 16 (Upset about relative’s change) and 17 (Worry about making illness worse), among others). With regard to item 1 , its non-inclusion could be due to the fact that financial problems, even if they exist, are not significantly related to caring for a relative with an SMD . Regarding items 18 (Worry about future) and 19 (Stigma upsetting), it is possible that in the past 6 months the family caregivers have not felt a significant amount of worry about the future or upset due to the stigma of having a relative diagnosed with an SMD . It would be interesting to investigate how family caregivers interpret worrying about the future: is it concern about possible economic hardship, the evolution of their relative diagnosed with BPD, or the future understood in a vague and diffuse way? Likewise, it would be interesting to find out whether family caregivers are aware of the meaning of the term “stigma” and, therefore, respond appropriately to that item. It must be noted that, in the present study, the sample was exclusively composed of family caregivers of people diagnosed with BPD, unlike previous studies that used samples composed of people with different diagnoses of SMD. The different composition of the samples used in these studies may have led to the differences in the results of the BAS structural analyses.Previous studies that analyzed the structure of the BAS used Principal Component Analysis (PCA) with Varimax rotation, with the exception of Hunger et al. , who useWe tested the model obtained for the BAS using confirmatory procedures in Subsample 2. Results showed the goodness of this model. Only Hunger et al.  tested tIn conclusion, the present study offers a cross-analysis, both exploratory and confirmatory, of the BAS, and it proposes a reduced three-factor model with 16 items that shows good structural properties.The model for the BAS obtained in this study showed good internal consistency, with estimations between .85 and 0.91 for the factors and .92 for the whole scale, which are similar to those obtained in previous studies that found Cronbach’s alphas between .89 , 36 and As expected, the factors in the model for the BAS obtained in this study correlated negatively with quality of life and positively with anxiety, depression, and stress. These results are comparable to those obtained in the study by Kwak et al. , and supSome limitations of the present study should be mentioned. Regarding the sample, it would be desirable to confirm the structure obtained for the BAS in a larger sample than the one we used. It would also be interesting to analyze the invariance of this scale with regard to sex and other variables of clinical interest. For example, in our study, most of family caregivers of people diagnosed with BPD were biological mothers, and as previous studies have found, this population could be more vulnerable to feelings of burden than other caregivers and, therefore, need more support . It woulIt would be interesting to have repeated measurements in a longitudinal design, in order to analyze the test–retest reliability of the model obtained for the BAS, and to confirm the construct validity of this scale using scales other than the ones used in our study.It would be useful to take into account the psychological health of family caregivers of people diagnosed with SMD (e.g. ), and toFuture studies should consider the socio-economic status of the family caregivers, in order to identify factors that might facilitate or hinder the care of a relative diagnosed with an SMD, and assess the possibility of drafting statements that are more in line with the content of each item on the BAS.It would be interesting to analyze the psychometric properties of the BAS model obtained in our study in family caregivers of people diagnosed with an SMD other than BPD, chronic disabilities or degenerative diseases, among others.The BAS can be a useful instrument for clinicians, who can assess burden in family caregivers of people diagnosed with BPD (or another SMD) and improve the efficiency of programs designed to provide resources and develop skills to manage the symptoms of the burden of caring, such as Family Connections e.g. , 11, 20), 2011, 2