Direct identification of A-to-I editing sites with nanopore native RNA sequencing.

Inosine is a prevalent RNA modification in animals and is formed when an adenosine is deaminated by the ADAR family of enzymes. Traditionally, inosines are identified indirectly as variants from Illumina RNA-sequencing data because they are interpreted as guanosines by cellular machineries. However, this indirect method performs poorly in protein-coding regions where exons are typically short, in non-model organisms with sparsely annotated single-nucleotide polymorphisms, or in disease contexts where unknown DNA mutations are pervasive. Here, we show that Oxford Nanopore direct RNA sequencing can be used to identify inosine-containing sites in native transcriptomes with high accuracy. We trained convolutional neural network models to distinguish inosine from adenosine and guanosine, and to estimate the modification rate at each editing site. Furthermore, we demonstrated their utility on the transcriptomes of human, mouse and Xenopus. Our approach expands the toolkit for studying adenosine-to-inosine editing and can be further extended to investigate other RNA modifications.

Regulation of tissue architecture and stem cell dynamics to sustain homeostasis and repair in the skin epidermis.

Stratified epithelia are made up of several layers of cells, which act as a protective barrier for the organ they cover. To ensure their shielding effect, epithelia are naturally able to cope with constant environmental insults. This ability is enabled by their morphology and architecture, as well as the continuous turnover of stem and progenitor cells that constitute their building blocks. Stem cell fate decisions and dynamics are fundamental key biological processes that allow epithelia to exert their functions. By focusing on the skin epidermis, this review discusses how tissue architecture is generated during development, maintained through adult life, and re-established during regeneration.

Transient infantile lingual leukoplakia: An underrecognized cause of white tongues in infancy.

We have observed a distinct phenomenon of transient oral lingual leukoplakia in infancy and report 22 healthy infants with gray-white plaques on the dorsal tongue with sparing of the tip from four medical centers in three countries. The onset of the eruption ranged from 1 week to 7 months of life and resolved in 19 patients (86%, with 3 patients lost to follow-up). None of the eight patients examined at 1 year of age had residual findings. We believe this is a common entity that can be distinguished from oral candidiasis on clinical and/or laboratory examination and name this entity "transient infantile lingual leukoplakia."

Benzofuran sulfonates and small self-lipid antigens activate type II NKT cells via CD1d.

Natural killer T (NKT) cells detect lipids presented by CD1d. Most studies focus on type I NKT cells that express semi-invariant αß T cell receptors (TCR) and recognize α-galactosylceramides. However, CD1d also presents structurally distinct lipids to NKT cells expressing diverse TCRs (type II NKT cells), but our knowledge of the antigens for type II NKT cells is limited. An early study identified a nonlipidic NKT cell agonist, phenyl pentamethyldihydrobenzofuransulfonate (PPBF), which is notable for its similarity to common sulfa drugs, but its mechanism of NKT cell activation remained unknown. Here, we demonstrate that a range of pentamethylbenzofuransulfonates (PBFs), including PPBF, activate polyclonal type II NKT cells from human donors. Whereas these sulfa drug-like molecules might have acted pharmacologically on cells, here we demonstrate direct contact between TCRs and PBF-treated CD1d complexes. Further, PBF-treated CD1d tetramers identified type II NKT cell populations expressing αßTCRs and γδTCRs, including those with variable and joining region gene usage (TRAV12-1-TRAJ6) that was conserved across donors. By trapping a CD1d-type II NKT TCR complex for direct mass-spectrometric analysis, we detected molecules that allow the binding of CD1d to TCRs, finding that both selected PBF family members and short-chain sphingomyelin lipids are present in these complexes. Furthermore, the combination of PPBF and short-chain sphingomyelin enhances CD1d tetramer staining of PPBF-reactive T cell lines over either molecule alone. This study demonstrates that nonlipidic small molecules, which resemble sulfa drugs implicated in systemic hypersensitivity and drug allergy reactions, are targeted by a polyclonal population of type II NKT cells in a CD1d-restricted manner.

Deep transcriptome profiling reveals limited conservation of A-to-I RNA editing in Xenopus.

BACKGROUND: Xenopus has served as a valuable model system for biomedical research over the past decades. Notably, ADAR was first detected in frog oocytes and embryos as an activity that unwinds RNA duplexes. However, the scope of A-to-I RNA editing by the ADAR enzymes in Xenopus remains underexplored. RESULTS: Here, we identify millions of editing events in Xenopus with high accuracy and systematically map the editome across developmental stages, adult organs, and species. We report diverse spatiotemporal patterns of editing with deamination activity highest in early embryogenesis before zygotic genome activation and in the ovary. Strikingly, editing events are poorly conserved across different Xenopus species. Even sites that are detected in both X. laevis and X. tropicalis show largely divergent editing levels or developmental profiles. In protein-coding regions, only a small subset of sites that are found mostly in the brain are well conserved between frogs and mammals. CONCLUSIONS: Collectively, our work provides fresh insights into ADAR activity in vertebrates and suggest that species-specific editing may play a role in each animal's unique physiology or environmental adaptation.

Features, measurements, determinants, treatments, and outcomes of musculoskeletal symptoms in postmenopausal women: A scoping review.

BACKGROUND: The literature lacks a consistent review of musculoskeletal symptoms in postmenopausal women. AIM: To identify features, measurements, determinants, treatments, and outcomes of musculoskeletal symptoms in postmenopausal women. METHOD: A scoping review was completed using six databases: Embase, Medline, Cochrane, CINAHL, Web of Science, and Scopus up to December 2022. Sixty-three articles were identified. RESULTS: Musculoskeletal symptoms in postmenopausal women include somatic symptoms of non-specific origin, upper and lower limb symptoms, spinal pain, and decline in physical performance. Measurements were categorized into four groups: musculoskeletal symptoms for menopause, general musculoskeletal symptoms, menopause-specific quality of life, and general quality of life questionnaires. The determinants were grouped into four themes: demographics, physical determinants, psychosocial determinants, and lifestyle. Pharmacological interventions, supplementation options, and exercise regimens exist for postmenopausal women with musculoskeletal symptoms. CONCLUSION: A comprehensive policy is needed to address musculoskeletal symptoms in postmenopausal women, promoting diverse treatments for improved quality of life.

Hexavalent Chromium Inhibited Zebrafish Embryo Development by Altering Apoptosis- and Antioxidant-Related Genes.

This study aimed to assess the effects of hexavalent chromium on zebrafish (Danio rerio) embryo development. The zebrafish embryos were treated with solutions containing chromium at different concentrations (0.1, 1, 3.125, 6.25, 12.5, 50, and 100 µg/mL). The development of zebrafish embryos was estimated by the determination of survival rate, heart rate, and the measurement of larvae body length. Real time RT-PCR and Western blot were performed to assess the expression of apoptosis- and antioxidant-related genes. The results showed that the reduced survival rate of zebrafish embryos and larvae was associated with an increase in chromium concentration. The exposure of higher concentrations resulted in a decrease in body length of zebrafish larvae. In addition, a marked increase in heart rate was observed in the zebrafish larvae under chromium treatment, especially at high concentrations. The real-time RT-PCR analysis showed that the transcript expressions for cell-cycle-related genes (cdk4 and cdk6) and antioxidant-related genes (sod1 and sod2) were downregulated in the zebrafish embryos treated with chromium. Western blot analysis revealed the upregulation of Caspase 3 and Bax, while a downregulation was observed in Bcl2. These results indicated that hexavalent chromium induced changes in zebrafish embryo development by altering apoptosis- and antioxidant-related genes.

Effects of Transcription Elongation Rate and Xrn2 Exonuclease Activity on RNA Polymerase II Termination Suggest Widespread Kinetic Competition.

The torpedo model of transcription termination asserts that the exonuclease Xrn2 attacks the 5'PO4-end exposed by nascent RNA cleavage and chases down the RNA polymerase. We tested this mechanism using a dominant-negative human Xrn2 mutant and found that it delayed termination genome-wide. Xrn2 nuclease inactivation caused strong termination defects downstream of most poly(A) sites and modest delays at some histone and U snRNA genes, suggesting that the torpedo mechanism is not limited to poly(A) site-dependent termination. A central untested feature of the torpedo model is that there is kinetic competition between the exonuclease and the pol II elongation complex. Using pol II rate mutants, we found that slow transcription robustly shifts termination upstream, and fast elongation extends the zone of termination further downstream. These results suggest that kinetic competition between elongating pol II and the Xrn2 exonuclease is integral to termination of transcription on most human genes.

Rapidly developed, optimized, and applied wastewater surveillance system for real-time monitoring of low-incidence, high-impact MPOX outbreak.

Recent MPOX viral resurgences have mobilized public health agencies around the world. Recognizing the significant risk of MPOX outbreaks, large-scale human testing, and immunization campaigns have been initiated by local, national, and global public health authorities. Recently, traditional clinical surveillance campaigns for MPOX have been complemented with wastewater surveillance (WWS), building on the effectiveness of existing wastewater programs that were built to monitor SARS-CoV-2 and recently expanded to include influenza and respiratory syncytial virus surveillance in wastewaters. In the present study, we demonstrate and further support the finding that MPOX viral fragments agglomerate in the wastewater solids fraction. Furthermore, this study demonstrates that the current, most commonly used MPOX assays are equally effective at detecting low titers of MPOX viral signal in wastewaters. Finally, MPOX WWS is shown to be more effective at passively tracking outbreaks and/or resurgences of the disease than clinical testing alone in smaller communities with low human clinical case counts of MPOX.

Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling.

The extracellular matrix (ECM) initiates mechanical cues that activate intracellular signaling through matrix-cell interactions. In blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from the ECM and their interaction with the mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood. Here, we identified the matricellular protein thrombospondin-1 (Thbs1) as an extracellular mediator of matrix mechanotransduction that acts via integrin αvß1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to high strain of cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin ß1/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload and inhibition of neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall. We thus propose a mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.

Caregivers' experiences of having a child with cerebral palsy. A meta-synthesis.

AIM: To synthesize qualitative research findings of caregiver experiences and challenges in caring for and raising a child with cerebral palsy. DESIGN: A systematic review and meta-synthesis. METHODS: Four electronic databases: CINAHL, Embase, OVID Medline, and Cochrane, were systematically searched for qualitative research papers published before December 2022. Two independent reviewers assessed eligibility and further appraised the quality of methodology using the Critical Appraisal Skills Program (CASP) tool for qualitative research. A content thematic analysis approach was used to synthesize the qualitative research findings, construct core subthemes, and synthesize themes. RESULTS: Sixty-seven findings were extracted from the 12 included studies. The findings were grouped into eleven sub-themes and then into five synthesized themes. The synthesized themes are 1. Need for convenient healthcare facilities, therapeutic services, and accessible public places, 2. Need for healthcare information and financial aid, 3. Psychological, and physical constraints, 4. Societal rejection and stigma, and 5. Overwhelming caring burden. CONCLUSION: Caregivers face many challenges in adjusting their lifestyles to meet the needs of the child with cerebral palsy. Some adjustments reported included giving up full-time jobs and businesses to be full-time caregivers, giving up leisure activities, and confinement to one place.

Multi-Level Influences of Smoke-Free Policies in Subsidized Housing: Applying the COM-B Model and Neighborhood Assessments to Inform Smoke-Free Policies.

Smoke-free policies in multi-unit housing are associated with reduced exposure to secondhand smoke (SHS); however, attitudes toward comprehensive smoke-free policies among residents in subsidized multi-unit housing are unknown. In this mixed-methods study, we explored the socio-ecological context for tobacco and cannabis use and attitudes toward policies restricting indoor use of these products through interviews with residents (N = 134) and staff (N = 22) in 15 federally subsidized multi-unit housing in San Francisco, California. We conducted a geo-spatial and ethnographic environmental assessment by mapping alcohol, cannabis, and tobacco retail density using ArcGIS, and conducted systematic social observations of the neighborhood around each site for environmental cues to tobacco use. We used the Capability, Opportunity, and Motivation behavior (COM-B) model to identify factors that might influence implementation of smoke-free policies in multi-unit housing. Knowledge and attitudes toward tobacco and cannabis use, social norms around smoking, neighborhood violence, and cannabis legalization were some of the social-ecological factors that influenced tobacco use. There was spatial variation in the availability of alcohol, cannabis, and tobacco stores around sites, which may have influenced residents' ability to maintain smoke-free homes. Lack of skill on how to moderate indoor smoking (psychological capability), lack of safe neighborhoods (physical opportunity), and the stigma of smoking outdoors in multi-unit housing (motivation) were some of the barriers to adopting a smoke-free home. Interventions to increase adoption of smoke-free policies in multi-unit housing need to address the co-use of tobacco and cannabis and commercial and environmental determinants of tobacco use to facilitate smoke-free living.

Clenbuterol attenuates immune reaction to lipopolysaccharide and its relationship to anhedonia in adolescents.

While inflammation has been implicated in psychopathology, relationships between immune-suppressing processes and psychiatric constructs remain elusive. This study sought to assess whether ß2-agonist clenbuterol (CBL) would attenuate immune activation in adolescents with mood and anxiety symptoms following ex vivo exposure of whole blood to lipopolysaccharide (LPS). Our focus on adolescents aimed to target a critical developmental period when psychiatric conditions often emerge and prior to chronicity effects. To capture a diverse range of immunologic and symptomatologic phenotypes, we included 97 psychotropic-medication free adolescents with mood and anxiety symptoms and 33 healthy controls. All participants had comprehensive evaluations and dimensional assessments of psychiatric symptoms. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, then analyzed for 41 cytokines, chemokines, and hematopoietic growth factors. Comparison analyses used Bonferroni-corrected nonparametric tests. Levels of nine immune biomarkers-including IL-1RA, IL-1ß, IL-6, IP-10, MCP-1, MIP-1α, MIP-1ß, TGF-α, and TNF-α-were significantly reduced by CBL treatment compared to LPS alone. Exploratory factor analysis reduced 41 analytes into 5 immune factors in each experimental condition, and their relationships with psychiatric symptoms were examined as a secondary aim. CBL + LPS Factor 4-comprising EGF, PDGF-AA, PDGF-AB/BB, sCD40L, and GRO-significantly correlated with anticipatory and consummatory anhedonia, even after controlling for depression severity. This study supports the possible inhibitory effect of CBL on immune activation. Using a data-driven method, distinctive relationships between CBL-affected immune biomarkers and dimensional anhedonia were reported, further elucidating the role of ß2-agonism in adolescent affective symptomatology.

Building capacity for integrated knowledge translation: a description of what we can learn from trainees' experiences during the COVID-19 pandemic.

The use of collaborative health research approaches, such as integrated knowledge translation (IKT), was challenged during the COVID-19 pandemic due to physical distancing measures and transition to virtual platforms. As IKT trainees (i.e. graduate students, postdoctoral scholars) within the Integrated Knowledge Translation Research Network (IKTRN), we experienced several changes and adaptations to our daily routine, work and research environments due to the rapid transition to virtual platforms. While there was an increased capacity to communicate at local, national and international levels, gaps in equitable access to training and partnership opportunities at universities and organizations have emerged. This essay explores the experiences and reflections of 16 IKTRN trainees during the first 2 years of the COVID-19 pandemic at the micro (individual), meso (organizational) and macro (system) levels. The micro level, or individual experiences, focuses on topics of self-care (taking care of oneself for physical and mental well-being), maintaining research activities and productivity, and leisure (social engagement and taking time for oneself), while conducting IKT research during the pandemic. At the meso level, the role of programmes and organizations explores whether and how institutions were able to adapt and continue research and/or partnerships during the pandemic. At the macro level, we discuss implications for policies to support IKT trainees and research, during and beyond emergency situations. Themes were identified that intersected across all levels, which included (i) equitable access to training and partnerships; (ii) capacity for reflexivity; (iii) embracing changing opportunities; and (iv) strengthening collaborative relationships. These intersecting themes represent ways of encouraging sustainable and equitable improvements towards establishing and maintaining collaborative health research approaches. This essay is a summary of our collective experiences and aims to provide suggestions on how organizations and universities can support future trainees conducting collaborative research. Thus, we hope to inform more equitable and sustainable collaborative health research approaches and training in the post-pandemic era.

Low-Complexity Multi-Size Circular-Shift Network for 5G New Radio LDPC Decoders.

This paper presents a low-complexity multi-size circular-shift network (MCSN) structure for 5th-generation (5G) New Radio (NR) quasi-cyclic low-density parity-check (QC-LDPC) decoders. In particular, a fine-coarse approach-based multi-size cyclic shift network, which decomposes the cyclic shift size into fine part and coarse part, is introduced. The proposed MCSN structure is composed of a pre-rotator performing the fine part of the cyclic shift, and a main rotator executing the coarse part of the cyclic shift. In addition, a forward routing circular-shift (FRCS) network, which is based on the barrel shifter and the forward routing process is presented. The proposed switch network is able to support all 51 different submatrix sizes as defined in the 5G NR standard through an efficient forward routing switch network and help reduce the hardware complexity using a cyclic shift size decomposition method. The proposed MCSN is analyzed, and indicates a substantial reduction in the hardware complexity. The experimental results on TSMC 65-nm CMOS technology show that the proposed MCSN structure for 5G NR LDPC decoder offers an area saving up to 56.75% compared to related works in the literature.

The Use of a Production Function to Evaluate Caribbean Ocean Health Conflicts and Economic Development: Policy Implications.

Central American and Caribbean (CAC) countries enjoy diverse marine environments. The oceans that enclose these coastlines contribute significantly to their economic growth. Industrial expansion and tourism place pressure on the marine ecosystems causing a decline in ocean health. To evaluate the cause of ocean health changes we investigated the factors influencing CAC ocean health using a health production function. Using Rank-Based Regression and the set of extractive, cultural and human well-being and services goals measuring Ocean Health Index (OHI), data from the World Bank, and the Human Development Index we developed a production function for CAC countries ocean health. Results show that all regional OHI scores, but Tourism and Recreation, the main income earning industry for most of the CAC countries, are less than the global score with four of the goals less than 40. The production function shows that all the goals, but the biodiversity sub-goal species, positively influencing OHI. Two climatic related variables, Nitrous Oxide and Carbon Dioxide negatively influenced OHI. The results are important to policy makers as they decide on the need to make greater effort towards improving sustainable contribution of CAC ocean resources to the blue economy.

Pharmacists' Perspectives on the Use of Telepharmacy in Response to COVID-19 Pandemic in Ho Chi Minh City, Vietnam.

Introduction: Telepharmacy, the application of information and communication technologies in healthcare services, has been adopted in many countries to provide patients with pharmaceutical care. However, it has yet to be widely used in Vietnam. This study was conducted to assess the current status of use and the factors associated with the willingness to use telepharmacy of pharmacists in Vietnam. Methods: A descriptive cross-sectional study was conducted from February to July 2021; 414 pharmacists were recruited to fill in an online survey. Results: Overall, 86.7% of participants have used telepharmacy application and 87.2% of them were willing to apply telepharmacy in pharmacy practice. According to our multivariate analysis, the level of readiness was associated with positive attitude (odds ratio [OR] = 4.67; 95% confidence interval [CI]: 2.26-9.66), and a good behavior (OR = 11.34; 95% CI: 3.84-33.45). Discussion: Developing a telepharmacy system with appropriate features is essential to meet the requirements of pharmacy practice amid the spread of the COVID-19 pandemic.

Stretch increases alveolar type 1 cell number in fetal lungs through ROCK-Yap/Taz pathway.

Accurate fluid pressure in the fetal lung is critical for its development, especially at the beginning of the saccular stage when alveolar epithelial type 1 (AT1) and type 2 (AT2) cells differentiate from the epithelial progenitors. Despite our growing understanding of the role of physical forces in lung development, the molecular mechanisms that regulate the transduction of mechanical stretch to alveolar differentiation remain elusive. To simulate lung distension, we optimized both an ex vivo model with precision cut lung slices and an in vivo model of fetal tracheal occlusion. Increased mechanical tension showed to improve alveolar maturation and differentiation toward AT1. By manipulating ROCK pathway, we demonstrate that stretch-induced Yap/Taz activation promotes alveolar differentiation toward AT1 phenotype via ROCK activity. Our findings show that balanced ROCK-Yap/Taz signaling is essential to regulate AT1 differentiation in response to mechanical stretching of the fetal lung, which might be helpful in improving lung development and regeneration.

Cortactin Interacts with Hepatitis C Virus Core and NS5A Proteins: Implications for Virion Assembly.

Hepatitis C virus (HCV) exploits cellular proteins to facilitate viral propagation. To identify the cellular factors involved in the HCV life cycle, we previously performed protein microarray assays using either HCV nonstructural 5A (NS5A) protein or core protein as a probe. Interestingly, cellular cortactin strongly interacted with both NS5A and core. Cortactin is an actin-binding protein critically involved in tumor progression by regulating the migration and invasion of cancerous cells. Protein interaction between cortactin and NS5A or core was confirmed by coimmunoprecipitation and immunofluorescence assays. We showed that cortactin interacted with NS5A and core via the N-terminal acidic domain of cortactin. Cortactin expression levels were not altered by HCV infection. Small interfering RNA (siRNA)-mediated knockdown of cortactin dramatically decreased HCV protein expression and infectivity levels, whereas overexpression of cortactin increased viral propagation. Ectopic expression of the siRNA-resistant cortactin recovered the viral infectivity, suggesting that cortactin was specifically required for HCV propagation. We further showed that cortactin was involved in the assembly step without affecting viral entry, HCV internal ribosome entry site (IRES)-mediated translation, and the replication steps of the HCV life cycle. Of note, silencing of cortactin markedly reduced both NS5A and core protein levels on the lipid droplets (LDs), and this effect was reversed by the overexpression of cortactin. Importantly, NS5A and core promoted cell migration by activating the phosphorylation of cortactin at tyrosine residues 421 and 466. Taken together, these data suggest that cortactin is not only involved in HCV assembly but also plays an important role in the cell migration.IMPORTANCE Cortactin is a cytoskeletal protein that regulates cell migration in response to a number of extracellular stimuli. The functional involvement of cortactin in the virus life cycle is not yet fully understood. The most significant finding is that cortactin strongly interacted with both hepatitis C virus (HCV) core and NS5A. Cortactin is involved in HCV assembly by tethering core and NS5A on the lipid droplets (LDs) with no effect on LD biogenesis. It was noteworthy that HCV NS5A and core activated cortactin by phosphorylation at tyrosines 421 and 466 to regulate cell migration. Collectively, our study shows that cortactin is a novel host factor involved in viral production and HCV-associated pathogenesis.

Trainee-led research using an integrated knowledge translation or other research partnership approaches: a scoping reviews.

BACKGROUND: There are increasing expectations for researchers and knowledge users in the health system to use a research partnership approach, such as integrated knowledge translation, to increase the relevance and use of research findings in health practice, programmes and policies. However, little is known about how health research trainees engage in research partnership approaches such as IKT. In response, the purpose of this scoping review was to map and characterize the evidence related to using an IKT or other research partnership approach from the perspective of health research trainees in thesis and/or postdoctoral work. METHODS: We conducted this scoping review following the Joanna Briggs Institute methodology and Arksey and O'Malley's framework. We searched the following databases in June 2020: MEDLINE, Embase, CINAHL and PsycINFO. We also searched sources of unpublished studies and grey literature. We reported our findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. RESULTS: We included 74 records that described trainees' experiences using an IKT or other research partnership approach to health research. The majority of studies involved collaboration with knowledge users in the research question development, recruitment and data collection stages of the research process. Intersecting barriers to IKT or other research partnerships at the individual, interpersonal and organizational levels were reported, including lack of skills in partnership research, competing priorities and trainees' "outsider" status. We also identified studies that evaluated their IKT approach and reported impacts on partnership formation, such as valuing different perspectives, and enhanced relevance of research. CONCLUSION: Our review provides insights for trainees interested in IKT or other research partnership approaches and offers guidance on how to apply an IKT approach to their research. The review findings can serve as a basis for future reviews and primary research focused on IKT principles, strategies and evaluation. The findings can also inform IKT training efforts such as guideline development and academic programme development.