Exploring xylose metabolism in non-conventional yeasts: kinetic characterization and product accumulation under different aeration conditions.

d-Xylose is a metabolizable carbon source for several non-Saccharomyces species, but not for native strains of S. cerevisiae. For the potential application of xylose-assimilating yeasts in biotechnological processes, a deeper understanding of pentose catabolism is needed. This work aimed to investigate the traits behind xylose utilization in diverse yeast species. The performance of 9 selected xylose-metabolizing yeast strains was evaluated and compared across 3 oxygenation conditions. Oxygenation diversely impacted growth, xylose consumption, and product accumulation. Xylose utilization by ethanol-producing species such as Spathaspora passalidarum and Scheffersomyces stipitis was less affected by oxygen restriction compared with other xylitol-accumulating species such as Meyerozyma guilliermondii, Naganishia liquefaciens, and Yamadazyma sp., for which increased aeration stimulated xylose assimilation considerably. Spathaspora passalidarum exhibited superior conversion of xylose to ethanol and showed the fastest growth and xylose consumption in all 3 conditions. By performing assays under identical conditions for all selected yeasts, we minimize bias in comparisons, providing valuable insight into xylose metabolism and facilitating the development of robust bioprocesses. ONE-SENTENCE SUMMARY: This work aims to expand the knowledge of xylose utilization in different yeast species, with a focus on how oxygenation impacts xylose assimilation.

Evaluating the American Heart Association/American College of Cardiology Guideline-Recommended and Contemporary Pretest Probability Models in a Mixed Asian Cohort: The Contribution of Coronary Artery Calcium.

BACKGROUND: Most pretest probability (PTP) tools for obstructive coronary artery disease (CAD) were Western -developed. The most appropriate PTP models and the contribution of coronary artery calcium score (CACS) in Asian populations remain unknown. In a mixed Asian cohort, we compare 5 PTP models: local assessment of the heart (LAH), CAD Consortium (CAD2), risk factor-weighted clinical likelihood, the American Heart Association/American College of Cardiology and the European Society of Cardiology PTP and 3 extended versions of these models that incorporated CACS: LAH(CACS), CAD2(CACS), and the CACS-clinical likelihood. METHODS AND RESULTS: The study cohort included 771 patients referred for stable chest pain. Obstructive CAD prevalence was 27.5%. Calibration, area under the receiver-operating characteristic curves (AUC) and net reclassification index were evaluated. LAH clinical had the best calibration (χ2 5.8; P=0.12). For CACS models, LAH(CACS) showed least deviation between observed and expected cases (χ2 37.5; P<0.001). There was no difference in AUCs between the LAH clinical (AUC, 0.73 [95% CI, 0.69-0.77]), CAD2 clinical (AUC, 0.72 [95% CI, 0.68-0.76]), risk factor-weighted clinical likelihood (AUC, 0.73 [95% CI: 0.69-0.76) and European Society of Cardiology PTP (AUC, 0.71 [95% CI, 0.67-0.75]). CACS improved discrimination and reclassification of the LAH(CACS) (AUC, 0.88; net reclassification index, 0.46), CAD2(CACS) (AUC, 0.87; net reclassification index, 0.29) and CACS-CL (AUC, 0.87; net reclassification index, 0.25). CONCLUSIONS: In a mixed Asian cohort, Asian-derived LAH models had similar discriminatory performance but better calibration and risk categorization for clinically relevant PTP cutoffs. Incorporating CACS improved discrimination and reclassification. These results support the use of population-matched, CACS-inclusive PTP tools for the prediction of obstructive CAD.

Acute Coronary Syndrome at Altitude: Diagnostic Dilemma on Aconcagua Using Point-of-Care Ultrasound.

At the Plaza de Mulas medical tent, located at 4300 m (14,100 ft) along the Normal Route to the 6960 m (22,837 ft) summit of Aconcagua in Argentina, a Korean male in his 50s with no known medical conditions presented with lightheadedness and shortness of breath. He had taken sildenafil and acetazolamide that morning without improvement. Vital signs on arrival were notable for oxygen saturations in the high 60s with basilar crackles on lung auscultation, concerning for high altitude pulmonary edema. The patient was started on oxygen via nasal cannula and given dexamethasone. History was limited secondary to language barriers, but on review of systems the patient noted mild chest pressure. Bedside cardiac echocardiogram was performed, which revealed a septal wall motion abnormality. The patient was therefore given aspirin and clopidogrel and was flown to a lower trailhead, where he was met by local Emergency Medical Services. A 12-lead electrocardiogram revealed an anterior ST-elevation myocardial infarction, and the patient was taken emergently to the catheterization lab in Mendoza and underwent stent placement with a full recovery.

Temporal trends in the contribution of modifiable cardiovascular risk factors to cardiovascular and all-cause mortality in patients undergoing myocardial perfusion imaging in a large city in Brazil.

BACKGROUND: Most cardiovascular (CV) events stem from modifiable risk factors, but it remains uncertain whether their impact on mortality has decreased in recent years as a result of treatment, particularly in low- and middle-income countries. We evaluated the temporal trends in the population attributable fraction (PAF) of modifiable risk factors to CV mortality in patients undergoing myocardial perfusion imaging (MPI) for suspected coronary artery disease in a large city in Brazil. METHODS: The cohort comprised 25,127 patients without established CV disease undergoing MPI in a referral center in Curitiba, Brazil, from 2010 to 2018. Baseline demographic, clinical and risk factors were prospectively collected. Modifiable risk factors encompassed hypertension, dyslipidemia, diabetes mellitus, sedentary lifestyle, obesity, and smoking. The primary outcome was CV death occurring up to 4 years of follow-up. The PAF of each risk factor was calculated for each triennium using multivariable Cox proportional regression models, adjusting for age, sex and family history of premature coronary disease. RESULTS: Over 9 years, there were 1438 deaths, 444 due to CV causes. In the first triennium, sedentary lifestyle exhibited the highest PAF (49%) for CV death, followed by hypertension (17%), diabetes mellitus (8%) and smoking habit (6%). The PAF for all risk factors combined remained relatively stable thorough the triennia (2010-2012: 57% vs 2013-2015: 64% vs 2016-2018: 47%, p = NS). CONCLUSION: In this large cohort of patients referred to MPI, the PAF of modifiable CV risk factors did not diminish in the last decade, with sedentary lifestyle having the largest contribution for CV mortality. CONDENSED ABSTRACT: This study examinated temporal trends in the impact of modifiable cardiovascular (CV) risk factors on CV and overall mortality in a cohort of 25,127 patients undergoing myocardial perfusion imaging from 2010 to 2018. Sedentary behavior consistently had the greatest impact on both CV and overall mortality, followed by hypertension and diabetes. Smoking had a lesser effect, while obesity showed no independent association with the outcomes. The contributions of these modifiable CV risk factors remained stable over the study period, suggesting that interventions promoting physical activity may be essential in mitigating the burden of CV disease.

A plasma protein-based risk score to predict hip fractures.

As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined.

Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC.

Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of ERα. In vitro studies with this PROTAC demonstrate excellent ERα degradation and ER antagonism in ER+ breast cancer cell lines. However, upon dosing the compound in vivo we observe an in vitro-in vivo disconnect. ERα degradation is lower in vivo than expected based on the in vitro data. Investigation into potential causes for the reduced maximal degradation reveals that metabolic instability of the PROTAC linker generates metabolites that compete for binding to ERα with the full PROTAC, limiting degradation. This observation highlights the requirement for metabolically stable PROTACs to ensure maximal efficacy and thus optimisation of the linker should be a key consideration when designing PROTACs.

Hotspots of biogeochemical activity linked to aridity and plant traits across global drylands.

Perennial plants create productive and biodiverse hotspots, known as fertile islands, beneath their canopies. These hotspots largely determine the structure and functioning of drylands worldwide. Despite their ubiquity, the factors controlling fertile islands under conditions of contrasting grazing by livestock, the most prevalent land use in drylands, remain virtually unknown. Here we evaluated the relative importance of grazing pressure and herbivore type, climate and plant functional traits on 24 soil physical and chemical attributes that represent proxies of key ecosystem services related to decomposition, soil fertility, and soil and water conservation. To do this, we conducted a standardized global survey of 288 plots at 88 sites in 25 countries worldwide. We show that aridity and plant traits are the major factors associated with the magnitude of plant effects on fertile islands in grazed drylands worldwide. Grazing pressure had little influence on the capacity of plants to support fertile islands. Taller and wider shrubs and grasses supported stronger island effects. Stable and functional soils tended to be linked to species-rich sites with taller plants. Together, our findings dispel the notion that grazing pressure or herbivore type are linked to the formation or intensification of fertile islands in drylands. Rather, our study suggests that changes in aridity, and processes that alter island identity and therefore plant traits, will have marked effects on how perennial plants support and maintain the functioning of drylands in a more arid and grazed world.

Simulation in pediatric anesthesiology: current state and visions for the future.

PURPOSE OF REVIEW: Simulation is a well established practice in medicine. This review reflects upon the role of simulation in pediatric anesthesiology in three parts: training anesthesiologists to care for pediatric patients safely and effectively; evaluating and improving systems of care for children; and visions for the future. RECENT FINDINGS: Simulation continues to prove a useful modality to educate both novice and experienced clinicians in the perioperative care of infants and children. It is also a powerful tool to help analyze and improve upon how care is provided to infants and children. Advances in technology and computational power now allow for a greater than ever degree of innovation, accessibility, and focused reflection and debriefing, with an exciting outlook for promising advances in the near future. SUMMARY: Simulation plays a key role in developing and achieving peak performance in the perioperative care of infants and children. Although simulation already has a great impact, its full potential is yet to be harnessed.

Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures.

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5 K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 × 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. To increase the understanding of the underlying mechanisms, we performed a meta-analysis of the associations between 4860 circulating proteins and risk of fractures using two large cohorts, including 6430 participants with 643 incident hip fractures. We identified 23 proteins/aptamers associated with incident hip fractures. Two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR were most strongly associated with hip fracture risk. High levels of several inflammation-related proteins were also associated with increased hip fracture risk. Pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. Future mechanistic studies should investigate the underlying biology of these novel protein biomarkers which may be potential drug targets.

Effects of Ivabradine on Myocardial Perfusion in Chronic Angina: A Prospective, Preliminary, Open-Label, Single-Arm Study.

INTRODUCTION: Ivabradine reduces heart rate (HR), episodes of angina, and nitrate consumption, and increases exercise capacity in patients with chronic angina (CA). In this exploratory study, myocardial perfusion scintigraphy (MPS) was used to evaluate changes in the percentage of myocardial ischemia after ivabradine therapy in patients with CA. METHODS: This prospective, open-label, single-arm study included patients with CA receiving maximum tolerated doses of beta blockers, who had a resting HR ≥ 70 bpm and had experienced ischemia according to MPS during an exercise test at baseline. Participants received ivabradine 5 mg twice daily (titrated according to HR) concomitant with beta blockers. A second MPS was performed after 3 months, without interruption of treatment with beta blockers or ivabradine. The primary outcome was change in the percentage of myocardial ischemia from baseline to 3 months. Time to ischemia during the exercise test, the proportion of patients presenting angina during the exercise test, and health status, assessed using the seven-item Seattle Angina Questionnaire-7 (SAQ-7), were also evaluated. RESULTS: Twenty patients (3 females) with a mean (± standard deviation [SD]) age of 62.2 ± 6.5 years were included in the study, of whom 55% had diabetes, 70% had previous myocardial revascularization, and 45% had previous myocardial infarction. The percentage of patients with myocardial ischemia significantly decreased from baseline to 3 months after initiation of treatment with ivabradine (- 2.9%; 95% confidence interval [CI] - 0.3 to - 5.5; p = 0.031). Mean time to appearance of ischemia increased from 403 ± 176 s at baseline to 466 ± 136 s at 3 months after initiation of ivabradine (Δ62 s; 95% CI 18-106 s; p = 0.008), and the proportion of patients experiencing angina during the exercise test decreased from 40% at baseline to 5% also at 3 months (p = 0.016). Mean resting HR decreased from 76 ± 7 bpm at baseline to 55 ± 8 bpm at 3 months (p < 0.001). The mean SAQ-7 summary score improved from 69 ± 21 at baseline to 83 ± 12 at 3 months (p = 0.001). No serious adverse effects were reported. CONCLUSION: Ivabradine added to beta blockers was associated with a reduction in detectable myocardial ischemia by MPS in patients with CA. Infographic available for this article. TRIAL REGISTRATION: The trial has been retrospectively registered with the Brazilian Registry of Clinical Trials (REBEC) under the following number RBR-5fysqrh (date of registration: 30 November 2023).

Terminology of e-Oral Health: Consensus Report of the IADR's e-Oral Health Network Terminology Task Force.

OBJECTIVE: Authors reported multiple definitions of e-oral health and related terms, and used several definitions interchangeably, like mhealth, teledentistry, teleoral medicine and telehealth. The International Association of Dental Research e-Oral Health Network (e-OHN) aimed to establish a consensus on terminology related to digital technologies used in oral healthcare. METHOD: The Crowdsourcing Delphi method used in this study comprised of four main stages. In the first stage, the task force created a list of terms and definitions around digital health technologies based on the literature and established a panel of experts. Inclusion criteria for the panellists were: to be actively involved in either research and/or working in e-oral health fields; and willing to participate in the consensus process. In the second stage, an email-based consultation was organized with the panel of experts to confirm an initial set of terms. In the third stage, consisted of: a) an online meeting where the list of terms was presented and refined; and b) a presentation at the 2022-IADR annual meeting. The fourth stage consisted of two rounds of feedback to solicit experts' opinion about the terminology and group discussion to reach consensus. A Delphi-questionnaire was sent online to all experts to independently assess a) the appropriateness of the terms, and b) the accompanying definitions, and vote on whether they agreed with them. In a second round, each expert received an individualised questionnaire, which presented the expert's own responses from the first round and the panellists' overall response (% agreement/disagreement) to each term. It was decided that 70% or higher agreement among experts on the terms and definitions would represent consensus. RESULTS: The study led to the identification of an initial set of 43 terms. The list of initial terms was refined to a core set of 37 terms. Initially, 34 experts took part in the consensus process about terms and definitions. From them, 27 experts completed the first rounds of consultations, and 15 the final round of consultations. All terms and definitions were confirmed via online voting (i.e., achieving above the agreed 70% threshold), which indicate their agreed recommendation for use in e-oral health research, dental public health, and clinical practice. CONCLUSION: This is the first study in oral health organised to achieve consensus in e-oral health terminology. This terminology is presented as a resource for interested parties. These terms were also conceptualised to suit with the new healthcare ecosystem and the place of e-oral health within it. The universal use of this terminology to label interventions in future research will increase the homogeneity of future studies including systematic reviews.

Bone microarchitectural alterations associated with spinal cord injury: Relation to sex hormones, metabolic factors, and loading.

CONTEXT: People living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. OBJECTIVE: To determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DESIGN: Cross-sectional analyses of bone properties in people with SCI. PARTICIPANTS: Twenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). OUTCOME MEASURES: Distal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (µFEA); sex hormones; metabolic and inflammatory markers. RESULTS: The mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score - 3.3), trabecular (-2.93), and cortical vBMD (-1.87), and Failure Load by µFEA (-2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (ß = 0.77, p = 0.02), thickness (ß = 0.52, p = 0.04) and number (ß = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (ß = 0.59, p = 0.01), trabecular thickness (ß = 0.43, p = 0.04), cortical thickness (ß = 0.63, p = 0.01) and cortical porosity (ß = 0.74 p = 0.04). CONCLUSIONS: Radius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading. CLINICALTRIALS: gov registration #: (NCT03576001).

Bridge: A New Algorithm for Rooting Orthologous Genes in Large-Scale Evolutionary Analyses.

Orthology information has been used for searching patterns in high-dimensional data, allowing transferring functional information between species. The key concept behind this strategy is that orthologous genes share ancestry to some extent. While reconstructing the history of a single gene is feasible with the existing computational resources, the reconstruction of entire biological systems remains challenging. In this study, we present Bridge, a new algorithm designed to infer the evolutionary root of orthologous genes in large-scale evolutionary analyses. The Bridge algorithm infers the evolutionary root of a given gene based on the distribution of its orthologs in a species tree. The Bridge algorithm is implemented in R and can be used either to assess genetic changes across the evolutionary history of orthologous groups or to infer the onset of specific traits in a biological system.

Microneedle array delivery of Yersinia pestis recapitulates bubonic plague.

Fleas transmit Yersinia pestis directly within the dermis of mammals to cause bubonic plague. Syringe-mediated inoculation is widely used to recapitulate bubonic plague and study Y. pestis pathogenesis. However, intradermal needle inoculation is tedious, error prone, and poses a significant safety risk for laboratorians. Microneedle arrays (MNAs) are micron-scale polymeric structures that deliver materials to the dermis, while minimizing the risk of needle sticks. We demonstrated that MNA inoculation is a viable strategy to recapitulate bubonic plague and study bacterial virulence by defining the parameters needed to establish a lethal infection in the mouse model and characterizing the course of infection using live-animal optical imaging. Using MNAs, we also demonstrated that Y. pestis must overcome calprotectin-mediated zinc restriction within the dermis and dermal delivery of an attenuated mutant has vaccine potential. Together, these data demonstrate that MNAs are a safe alternative to study Y. pestis pathogenesis in the laboratory.

Disparities in Noninvasive Traditional and Advanced Testing for Coronary Artery Disease: Findings from the INCAPS-COVID 2 Study.

The COVID-19 pandemic disrupted the delivery of cardiovascular care, including noninvasive testing protocols and test selection for the evaluation of coronary artery disease (CAD). Trends in test selection in traditional versus advanced noninvasive tests for CAD during the pandemic and in countries of varying income status have not been well studied. The International Atomic Energy Agency conducted a global survey to assess the pandemic-related changes in the practice of cardiovascular diagnostic testing. Site procedural volumes for noninvasive tests to evaluate CAD from March 2019 (prepandemic), April 2020 (onset), and April 2021 (initial recovery) were collected. We considered traditional testing modalities, such as exercise electrocardiography, stress echocardiography, and stress single-photon emission computed tomography, and advanced testing modalities, such as stress cardiac magnetic resonance, coronary computed tomography angiography, and stress positron emission tomography. Survey data were obtained from 669 centers in 107 countries, reporting the performance of 367,933 studies for CAD during the study period. Compared with 2019, traditional tests were performed 14% less frequently (recovery rate 82%) in 2021 versus advanced tests, which were performed 15% more frequently (128% recovery rate). Coronary computed tomography angiography, stress cardiac magnetic resonance, and stress positron emission tomography showed 14%, 25%, and 25% increases in volumes from 2019 to 2021, respectively. The increase in advanced testing was isolated to high- and upper middle-income countries, with 132% recovery in advanced tests by 2021 compared with 55% in lower income nations. The COVID-19 pandemic exacerbated economic disparities in CAD testing practice between wealthy and poorer countries. Greater recovery rates and even new growth were observed for advanced imaging modalities; however, this growth was restricted to wealthy countries. Efforts to reduce practice variations in CAD testing because of economic status are warranted.

Synthesis of polysubstituted azepanes by dearomative ring expansion of nitroarenes.

The synthesis of functionalized nitrogen heterocycles is integral to discovering, manufacturing and evolving high-value materials. The availability of effective strategies for heterocycle synthesis often biases the frequency of specific ring systems over others in the core structures of bioactive leads. For example, while the six- and five-membered piperidine and pyrrolidine are widespread in medicinal chemistry libraries, the seven-membered azepane is essentially absent and this leaves open a substantial area of three-dimensional chemical space. Here we report a strategy to prepare complex azepanes from simple nitroarenes by photochemical dearomative ring expansion centred on the conversion of the nitro group into a singlet nitrene. This process is mediated by blue light, occurs at room temperature and transforms the six-membered benzenoid framework into a seven-membered ring system. A following hydrogenolysis provides the azepanes in just two steps. We have demonstrated the utility of the strategy with the synthesis of several azepane analogues of piperidine drugs.

Legal issues in digital oral health: a scoping review.

BACKGROUND: This scoping review aims to systematically and critically describe the numerous legal challenges brought about by the utilization of digital oral health in the delivery of oral healthcare. METHODS: A systematic search was conducted. The following electronic databases were reviewed from inception up to March 2023: MEDLINE, Embase, Scopus, and LILACS. The search included any scientific document and paper in English, Spanish, or Portuguese on legal issues raised using digital health in oral healthcare delivery. Two reviewers conducted the selection process and data extraction. Legal issues raised concerning the adoption of digital health technology were analysed using the modified Mars' framework. RESULTS: Seventeen studies were included. Most of the documents identified and covered generic aspects of delivering digital oral healthcare (n = 11) without explicitly referring to any dental specialty. The most mentioned legal issues were data security (n = 15); liability and malpractice (n = 14); consent (n = 12); and confidentiality (n = 12). To a lower extent, patient-practitioner relationship (n = 11); and license and jurisdiction (n = 11) were also covered. These were followed by privacy of information (n = 10); adequacy of records (n = 9); and e-referrals (n = 8). On the other hand, fewer studies commented on social media use (n = 3), authentication (n = 2); or e-prescriptions (n = 2). Before implementing any digital health solution, practitioners need to be aware of the many legal issues that the introduction of these technologies involves, be clear where the responsibility lies, and apply extreme caution in following national guidelines. Current literature concentrates on a few well-known legal issues. Issues around authentication, use of social media, and e-prescriptions received less attention.