Specialized Mechanosensory Epithelial Cells in Mouse Gut Intrinsic Tactile Sensitivity.

BACKGROUND AND AIMS: The gastrointestinal (GI) tract extracts nutrients from ingested meals while protecting the organism from infectious agents frequently present in meals. Consequently, most animals conduct the entire digestive process within the GI tract while keeping the luminal contents entirely outside the body, separated by the tightly sealed GI epithelium. Therefore, like the skin and oral cavity, the GI tract must sense the chemical and physical properties of the its external interface to optimize its function. Specialized sensory enteroendocrine cells (EECs) in GI epithelium interact intimately with luminal contents. A subpopulation of EECs express the mechanically gated ion channel Piezo2 and are developmentally and functionally like the skin's touch sensor- the Merkel cell. We hypothesized that Piezo2+ EECs endow the gut with intrinsic tactile sensitivity. METHODS: We generated transgenic mouse models with optogenetic activators in EECs and Piezo2 conditional knockouts. We used a range of reference standard and novel techniques from single cells to living animals, including single-cell RNA sequencing and opto-electrophysiology, opto-organ baths with luminal shear forces, and in vivo studies that assayed GI transit while manipulating the physical properties of luminal contents. RESULTS: Piezo2+ EECs have transcriptomic features of synaptically connected, mechanosensory epithelial cells. EEC activation by optogenetics and forces led to Piezo2-dependent alterations in colonic propagating contractions driven by intrinsic circuitry, with Piezo2+ EECs detecting the small luminal forces and physical properties of the luminal contents to regulate transit times in the small and large bowel. CONCLUSIONS: The GI tract has intrinsic tactile sensitivity that depends on Piezo2+ EECs and allows it to detect luminal forces and physical properties of luminal contents to modulate physiology.

Interferometric Imaging Using Shared Quantum Entanglement.

Quantum entanglement-based imaging promises significantly increased resolution by extending the spatial separation of optical collection apertures used in very-long-baseline interferometry for astronomy and geodesy. We report a tabletop entanglement-based interferometric imaging technique that utilizes two entangled field modes serving as a phase reference between two apertures. The spatial distribution of a simulated thermal light source is determined by interfering light collected at each aperture with one of the entangled fields and performing joint measurements. This experiment demonstrates the ability of entanglement to implement interferometric imaging.

Using Machine Learning to Predict Remission in Patients With Major Depressive Disorder Treated With Desvenlafaxine.

BACKGROUND: Major depressive disorder (MDD) is a common and burdensome condition that has low rates of treatment success for each individual treatment. This means that many patients require several medication switches to achieve remission; selecting an effective antidepressant is typically a sequential trial-and-error process. Machine learning techniques may be able to learn models that can predict whether a specific patient will respond to a given treatment, before it is administered. This study uses baseline clinical data to create a machine-learned model that accurately predicts remission status for a patient after desvenlafaxine (DVS) treatment. METHODS: We applied machine learning algorithms to data from 3,399 MDD patients (90% of the 3,776 subjects in 11 phase-III/IV clinical trials, each described using 92 features), to produce a model that uses 26 of these features to predict symptom remission, defined as an 8-week Hamilton Depression Rating Scale score of 7 or below. We evaluated that learned model on the remaining held-out 10% of the data (n = 377). RESULTS: Our resulting classifier, a trained linear support vector machine, had a holdout set accuracy of 69.0%, significantly greater than the probability of classifying a patient correctly by chance. We demonstrate that this learning process is stable by repeatedly sampling part of the training dataset and running the learner on this sample, then evaluating the learned model on the held-out instances of the training set; these runs had an average accuracy of 67.0% ± 1.8%. CONCLUSIONS: Our model, based on 26 clinical features, proved sufficient to predict DVS remission significantly better than chance. This may allow more accurate use of DVS without waiting 8 weeks to determine treatment outcome, and may serve as a first step toward changing psychiatric care by incorporating clinical assistive technologies using machine-learned models.

Cl- and H+ coupling properties and subcellular localizations of wildtype and disease-associated variants of the voltage-gated Cl-/H+ exchanger ClC-5.

Dent disease 1 (DD1) is caused by mutations in the CLCN5 gene encoding a voltage-gated electrogenic nCl-/H+ exchanger ClC-5. Using ion-selective microelectrodes and Xenopus oocytes, here we studied Cl-/H+ coupling properties of WT ClC-5 and four DD1-associated variants (S244L, R345W, Q629*, and T657S), along with trafficking and localization of ClC-5. WT ClC-5 had a 2Cl-/H+ exchange ratio at a Vh of +40 mV with a [Cl-]out of 104 mm, but the transport direction did not reverse with a [Cl-]out of 5 mm, indicating that ClC-5-mediated exchange of two Cl- out for one H+ in is not permissible. We hypothesized that ClC-5 and H+-ATPase are functionally coupled during H+-ATPase-mediated endosomal acidification, crucial for ClC-5 activation by depolarizing endosomes. ClC-5 transport that provides three net negative charges appeared self-inhibitory because of ClC-5's voltage-gated properties, but shunt conductance facilitated further H+-ATPase-mediated endosomal acidification. Thus, an on-and-off "burst" of ClC-5 activity was crucial for preventing Cl- exit from endosomes. The subcellular distribution of the ClC-5:S244L variant was comparable with that of WT ClC-5, but the variant had a much slower Cl- and H+ transport and displayed an altered stoichiometry of 1.6:1. The ClC-5:R345W variant exhibited slightly higher Cl-/H+ transport than ClC-5:S244L, but co-localized with early endosomes, suggesting decreased ClC-5:R345W membrane trafficking is perhaps in a fully functional form. The truncated ClC-5:Q629* variant displayed the lowest Cl-/H+ exchange and was retained in the endoplasmic reticulum and cis-Golgi, but not in early endosomes, suggesting the nonsense mutation affects ClC-5 maturation and trafficking.

Utilizing bacteriophage to define the minimum residence time within a plug flow reactor.

As part of a viral mitigating strategy for continuous bioprocessing, that utilizes a plug flow reactor (PFR) for continuous viral inactivation (CVI), understanding the minimum residence time as a function of reactor scale and operational conditions is critical. An empirical-based model was utilized to calculate the minimum duration a virus particle experiences within a plug flow reactor as a function of reactor design and operational conditions. This empirical model's calculations were challenged by pulse injecting the bacteriophage ΦX-174 in non-inactivating conditions and monitoring the discharge of the PFR with infectivity assays. The initial proposed empirical model, with the constraint of requiring an operational Dean number of >100, proved to be effective at calculating first breakthrough of ΦX-174 but only for the appropriate Dean number conditions. With the knowledge gained from the first empirical model, a second was generated to eliminate the Dean number constraint. This second modified empirical model proved to be successful at calculating the first breakthrough at all Dean number's tested, however CVI operation at the lower Dean's number will lead to an increased asymmetry (i.e., increased tailing) in the residence time distribution.

Pain in the Cancer Survivor.

Recent decades have demonstrated significant strides in cancer screening, diagnostics and therapeutics. As such there have been dramatic changes in survival following a diagnosis of cancer.

Feasibility of palliating recurrent gynecological tumors with MRGHIFU: comparison of symptom, quality-of-life, and imaging response in intra and extra-pelvic disease.

OBJECTIVE: To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra- versus extra-pelvic lesions. METHODS: Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra- and extra-pelvic tumors. RESULTS: Two of five patients with intra-pelvic and three of six patients with extra-pelvic tumors were classified as responders (>2 point reduction in NRS pain score without analgesia increase or a > 25% reduction in analgesic use). Cohort reductions in worst pain scores were not significant for either group. Emotional functioning for the whole cohort improved, although physical functioning did not. Ablative thermal temperatures were achieved in three patients with extra-pelvic tumors, but in none whose tumors were intra-pelvic. Pain response did not correlate with thermal dose. Tumor volume increased by 18% immediately post-treatment in the extra-pelvic but not in the intra-pelvic group. Ratio of perfused to whole lesion volume decreased by >20% by day 30 in extra-pelvic, but not intra-pelvic tumors although at day 30 both extra-pelvic and intra-pelvic tumors increased in volume. CONCLUSION: MRgHIFU treatments can be delivered safely to patients with recurrent gynecological tumors. Extra-pelvic tumors responded better than intra-pelvic tumors and showed immediate swelling and reduction in perfused volume by day 30.

Dietary carbohydrates modulate metabolic and ß-cell adaptation to high-fat diet-induced obesity.

Obesity is associated with several chronic comorbidities, one of which is type 2 diabetes mellitus (T2DM). The pathogenesis of obesity and T2DM is influenced by alterations in diet macronutrient composition, which regulate energy expenditure, metabolic function, glucose homeostasis, and pancreatic islet cell biology. Recent studies suggest that increased intake of dietary carbohydrates plays a previously underappreciated role in the promotion of obesity and consequent metabolic dysfunction. Thus, in this study, we utilized mouse models to test the hypothesis that dietary carbohydrates modulate energetic, metabolic, and islet adaptions to high-fat diets. To address this, we exposed C57BL/6J mice to 12 wk of 3 eucaloric high-fat diets (>60% calories from fat) with varying total carbohydrate (1-20%) and sucrose (0-20%) content. Our results show that severe restriction of dietary carbohydrates characteristic of ketogenic diets reduces body fat accumulation, enhances energy expenditure, and reduces prevailing glycemia and insulin resistance compared with carbohydrate-rich, high-fat diets. Moreover, severe restriction of dietary carbohydrates also results in functional, morphological, and molecular changes in pancreatic islets highlighted by restricted capacity for ß-cell mass expansion and alterations in insulin secretory response. These studies support the hypothesis that low-carbohydrate/high-fat diets provide antiobesogenic benefits and suggest further evaluation of the effects of these diets on ß-cell biology in humans.

Leveraging flow mechanics to determine critical process and scaling parameters in a continuous viral inactivation reactor.

A continuous viral inactivation (CVI) chamber has been designed to operate with acceptable residence time distribution (RTD) characteristics. However, altering the CVI's geometry and operation to accommodate the scale was not obvious. In this work, we elucidate the influence of Dean vortices and leverage the transition into the weak turbulent regime to establish relationships between input variables and process outputs. This study was targeted to understand and quantify the impact of viscosity, Dean number, internal diameter, and path length on the RTD. When the Dean number exceeds 70, radial mixing generated by the Dean vortices began to consistently alter the axial dispersive effects experienced by the pulse injection. Increasing to a Dean number of >100, the axial dispersive effects were dominated by the Dean vortices which allowed the calculation of the minimum and maximum residence time to be generated. This work provides a method to calculate operational solutions for a tubular incubation reactor in terms of path length, internal diameter, flow rate, and target minimum and maximum residence time specifications that assures both viral residence times while also establishing criteria to maximize product quality during continuous operation.

Comparison of Imaging Changes and Pain Responses in Patients with Intra- or Extraosseous Bone Metastases Treated Palliatively with Magnetic Resonance-Guided High-Intensity-Focused Ultrasound.

PURPOSE: This study compared changes in imaging and in pain relief between patients with intraosseous, as opposed to extraosseous bone metastases. Both groups were treated palliatively with magnetic resonance-guided high-intensity-focused ultrasound (MRgHIFU). MATERIALS AND METHODS: A total of 21 patients were treated prospectively with MRgHIFU at 3 centers. Intraprocedural thermal changes measured using proton resonance frequency shift (PRFS) thermometry and gadolinium-enhanced T1-weighted (Gd-T1W) image appearances after treatment were compared for intra- and extraosseous metastases. Pain scores and use of analgesic therapy documented before and up to 90 days after treatment were used to classify responses and were compared between the intra- and extraosseous groups. Gd-T1W changes were compared between responders and nonresponders in each group. RESULTS: Thermal dose volumes were significantly larger in the extraosseous group (P = 0.039). Tumor diameter did not change after treatment in either group. At day 30, Gd-T1W images showed focal nonenhancement in 7 of 9 patients with intraosseous tumors; in patients with extraosseous tumors, changes were heterogeneous. Cohort reductions in worst-pain scores were seen for both groups, but differences from baseline at days 14, 30, 60, and 90 were only significant for the intraosseous group (P = 0.027, P = 0.013, P = 0.012, and P = 0.027, respectively). By day 30, 67% of patients (6 of 9) with intraosseous tumors were classified as responders, and the rate was 33% (4 of 12) for patients with extraosseous tumors. In neither group was pain response indicated by nonenhancement on Gd-T1W. CONCLUSIONS: Intraosseous tumors showed focal nonenhancement by day 30, and patients had better pain response to MRgHIFU than those with extraosseous tumors. In this small cohort, post-treatment imaging was not informative of treatment efficacy.

Correction to: After the Fort McMurray wildfire there are significant increases in mental health symptoms in grade 7-12 students compared to controls.

.

After the Fort McMurray wildfire there are significant increases in mental health symptoms in grade 7-12 students compared to controls.

BACKGROUND: In order to examine the impact of disasters on adolescent mental health, this study compared population mental health survey data from two communities in Alberta, Canada: Fort McMurray, which experienced a major natural disaster, and Red Deer, which did not. METHODS: Data from 3070 grade 7-12 students from Fort McMurray, Alberta, Canada (collected in 2017, 18 months after the 2016 wildfire) was compared with data from 2796 grade 7-12 students from Red Deer, Alberta, Canada (collected in 2014). The same measurement scales were used for both surveys. Both of these cities have populations of approximately 100,000, and both cities are located in Alberta, Canada. For this reason, Red Deer is an appropriate non-disaster impacted community to compare to the disaster impacted community of Fort McMurray. RESULTS: The results of this comparison demonstrate that mental health symptoms were statistically significantly elevated in the Fort McMurray population when compared to the control population in Red Deer. This occurred for scores consistent with a diagnosis of depression (31% vs. 17%), moderately severe depression (17% vs. 9%), suicidal thinking (16% vs. 4%), and tobacco use (13% vs. 10%). Consistent with there being major mental health impacts from the 2016 Fort McMurray wildfire, self-esteem scores and quality of life scores were also statistically significantly lower in Fort McMurray. While the rates of anxiety disorder were similar (15% vs. 16%), the mean scores on the anxiety scale were slightly higher, with this difference reaching statistical significance. There were no statistical differences in the rates or scores for alcohol or substance use. CONCLUSIONS: Our results are consistent with previous findings showing a significant negative impact of disasters on many aspects of adolescent mental, with a particular increase in symptoms related to depression and suicidal thinking. These findings highlight first, the need to identify adolescents most at risk of developing psychiatric symptoms after experiencing the trauma of disaster and second, the importance and necessity of implementing short and long term mental health intervention programs specifically aimed at adolescents, in order to help mitigate the negative effects of disasters on their mental health.

Deep grey matter iron accumulation in alcohol use disorder.

PURPOSE: Evaluate brain iron accumulation in alcohol use disorder (AUD) patients compared to controls using quantitative susceptibility mapping (QSM). METHODS: QSM was performed retrospectively by using phase images from resting state functional magnetic resonance imaging (fMRI). 20 male AUD patients and 15 matched healthy controls were examined. Susceptibility values were manually traced in deep grey matter regions including caudate nucleus, combined putamen and globus pallidus, combined substantia nigra and red nucleus, dentate nucleus, and a reference white matter region in the internal capsule. Average susceptibility values from each region were compared between the patients and controls. The relationship between age and susceptibility was also explored. RESULTS: The AUD group exhibited increased susceptibility in caudate nucleus (+8.5%, p=0.034), combined putamen and globus pallidus (+10.8%, p=0.006), and dentate nucleus (+14.9%, p=0.022). Susceptibility increased with age in two of the four measured regions - combined putamen and globus pallidus (p=0.013) and combined substantia nigra and red nucleus (p=0.041). AUD did not significantly modulate the rate of susceptibility increase with age in our data. CONCLUSION: Retrospective QSM computed from standard fMRI datasets provides new opportunities for brain iron studies in psychiatry. Substantially elevated brain iron was found in AUD subjects in the basal ganglia and dentate nucleus. This was the first human AUD brain iron study and the first retrospective clinical fMRI QSM study.

Adapting viral safety assurance strategies to continuous processing of biological products.

There has been a recent drive in commercial large-scale production of biotechnology products to convert current batch mode processing to continuous processing manufacturing. There have been reports of model systems capable of adapting and linking upstream and downstream technologies into a continuous manufacturing pipeline. However, in many of these proposed continuous processing model systems, viral safety has not been comprehensively addressed. Viral safety and detection is a highly important and often expensive regulatory requirement for any new biological product. To ensure success in the adaption of continuous processing to large-scale production, there is a need to consider the development of approaches that allow for seamless incorporation of viral testing and clearance/inactivation methods. In this review, we outline potential strategies to apply current viral testing and clearance/inactivation technologies to continuous processing, as well as modifications of existing unit operations to ensure the successful integration of viral clearance into the continuous processing of biological products. Biotechnol. Bioeng. 2017;114: 21-32. © 2016 Wiley Periodicals, Inc.

A step-wise approach to define binding mechanisms of surrogate viral particles to multi-modal anion exchange resin in a single solute system.

Multi-modal anion exchange resins combine properties of both anion exchange and hydrophobic interaction chromatography for commercial protein polishing and may provide some viral clearance as well. From a regulatory viral clearance claim standpoint, it is unclear if multi-modal resins are truly orthogonal to either single-mode anion exchange or hydrophobic interaction columns. To answer this, a strategy of solute surface assays and High Throughput Screening of resin in concert with a scale-down model of large scale chromatography purification was employed to determine the predominant binding mechanisms of a panel of bacteriophage (i.e., PR772, PP7, and ϕX174) to multi-modal and single mode resins under various buffer conditions. The buffer conditions were restricted to buffer environments suggested by the manufacturer for the multi-modal resin. Each phage was examined for estimated net charge expression and relative hydrophobicity using chromatographic based methods. Overall, PP7 and PR772 bound to the multimodal resin via both anionic and hydrophobic moieties, while ϕX174 bound predominantly by the anionic moiety. Biotechnol. Bioeng. 2017;114: 1487-1494. © 2017 Wiley Periodicals, Inc.

Conjugation to Poly(amidoamine) Dendrimers and Pulmonary Delivery Reduce Cardiac Accumulation and Enhance Antitumor Activity of Doxorubicin in Lung Metastasis.

Lung is one of the most common sites to which almost all other primary tumors metastasize. The major challenges in the chemotherapy of lung metastases include the low drug concentration found in the tumors and high systemic toxicity upon systemic administration. In this study, we combine local lung delivery and the use of nanocarrier-based systems for improving pharmacokinetics and biodistribution of the therapeutics to fight lung metastases. We investigate the impact of the conjugation of doxorubicin (DOX) to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) through a bond that allows for intracellular-triggered release, and the effect of pulmonary delivery of the dendrimer-DOX conjugate in decreasing tumor burden in a lung metastasis model. The results show a dramatic increase in efficacy of DOX treatment of the melanoma (B16-F10) lung metastasis mouse model upon pulmonary administration of the drug, as indicated by decreased tumor burden (lung weight) and increased survival rates of the animals (male C57BL/6) when compared to iv delivery. Conjugation of DOX further increased the therapeutic efficacy upon lung delivery as indicated by the smaller number of nodules observed in the lungs when compared to free DOX. These results are in agreement with the biodistribution characteristics of the DOX upon pulmonary delivery, which showed a longer lung accumulation/retention compared to iv administration. The distribution of DOX to the heart tissue is also significantly decreased upon pulmonary administration, and further decreased upon conjugation. The results show, therefore, that pulmonary administration of DOX combined to conjugation to PAMAM dendrimer through an intracellular labile bond is a potential strategy to enhance the therapeutic efficacy and decrease systemic toxicity of DOX.

NHS-Reimbursed Cannabis Flowers for Cancer Palliative Care and the Management of Chemotherapy-Induced Nausea and Vomiting: An Autobiographical Case Report.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of cancer treatment, affecting many patients. Cannabinoid agonists, such as nabilone and Δ9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis sativa L., have shown efficacy as antiemetics. Here, we report the case of Michael Roberts (MR), who we believe is the first British patient reimbursed by the National Health Service (NHS) England for the cost of medicinal cannabis flowers to manage CINV. Medical data were obtained from NHS records and individual funding request (IFR) forms. Patient-reported outcome measures (PROMs) were collected using validated questionnaires as part of the standard of care at the specialized private clinics where the prescription of medicinal cannabis was initiated. The patient presented with rectosigmoid adenocarcinoma with lung metastases. He received FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy and underwent an emergency Hartmann's procedure with subsequent second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy and lung ablation. MR reported severe nausea and vomiting associated with the initial FOLFIRI treatment. Antiemetics metoclopramide and aprepitant demonstrated moderated efficacy. Antiemetics ondansetron, levomepromazine, and nabilone were associated with intolerable side effects. Inhalation of THC-predominant cannabis flowers in association with standard medication improved CINV, anxiety, sleep quality, appetite, overall mood, and quality of life. Our results add to the available evidence suggesting that medicinal cannabis flowers may offer valuable support in cancer palliative care integrated with standard-of-care oncology treatment. The successful individual funding request in this case demonstrates a pathway for other patients to gain access to these treatments, advocating for broader awareness and integration of cannabis-based medicinal products in national healthcare services.

Multidimensional digital biomarker phenotypes for mild cognitive impairment: considerations for early identification, diagnosis and monitoring.

Mild Cognitive Impairment (MCI) poses a challenge for a growing population worldwide. Early identification of risk for and diagnosis of MCI is critical to providing the right interventions at the right time. The paucity of reliable, valid, and scalable methods for predicting, diagnosing, and monitoring MCI with traditional biomarkers is noteworthy. Digital biomarkers hold new promise in understanding MCI. Identifying digital biomarkers specifically for MCI, however, is complex. The biomarker profile for MCI is expected to be multidimensional with multiple phenotypes based on different etiologies. Advanced methodological approaches, such as high-dimensional statistics and deep machine learning, will be needed to build these multidimensional digital biomarker profiles for MCI. Comparing patients to these MCI phenotypes in clinical practice can assist clinicians in better determining etiologies, some of which may be reversible, and developing more precise care plans. Key considerations in developing reliable multidimensional digital biomarker profiles specific to an MCI population are also explored.

Body Mindsets are Associated With Pain and Threat-Related Risk Factors for Pain in Survivors of Childhood Cancer.

Pain is a common consequence of childhood cancer. While most research has examined biomedical predictors of post-cancer pain, biopsychosocial conceptualisations such as the cancer threat interpretation (CTI) model hold promise for guiding comprehensive pain management strategies. Guided by the CTI model, this cross-sectional study evaluated correlates of post-cancer pain in childhood cancer survivors including threat-related risk factors (bodily threat monitoring, fear of cancer recurrence, help-seeking) and mindsets about the body. In the preceding three months, 21.8% of the survivors reported chronic pain (>3 months), and 14.3% experienced pain most days. Greater bodily threat monitoring, more fear of cancer recurrence, and more help-seeking were associated with more pain. There was heterogeneity in the mindsets that survivors of childhood cancer hold about their bodies. Holding the mindset that the 'body is an adversary' was associated with more pain, greater bodily threat monitoring, and more fear of cancer recurrence. Holding the mindset that the 'body is responsive' was associated with less bodily threat monitoring, while the mindset that the 'body is capable' was associated with greater help-seeking. A path model demonstrated a significant combined indirect effect of the 'body is an adversary' mindset on pain through bodily threat monitoring and fear of cancer recurrence. Overall, this study supported that a sub-group of childhood cancer survivors experience persistent and interfering pain and provided cross-sectional support for threat-related correlates for pain aligning with the CTI model. Body mindsets were associated with pain and threat-related correlates and may represent a novel target to support survivors with pain. PERSPECTIVE: This article presents associations of body mindsets, threat-related risk factors, and pain in survivors of childhood cancer (aged 11-25), guided by the Cancer Threat Interpretation model. The study indicates that body mindsets may be novel targets to embed in comprehensive post-cancer pain management approaches to support young survivors with pain.

Digital outpatient health solutions as a vehicle to improve healthcare sustainability-a United Kingdom focused policy and practice perspective.

Introduction: In the midst of a global climate emergency and with health care systems across the world facing extreme pressure, interest in digital approaches as a potential part-solution to these challenges has increased rapidly. The evidence base to support the role that digitalization can play in moving towards more sustainable models of healthcare is growing, as is the awareness of this key area of healthcare reform amongst policy makers, clinicians and the public. Method and Results: In this policy and practice review we explore four domains of healthcare sustainability-environmental, economic, and patient and clinician, delineating the potential impact that digitally enabled healthcare can have on each area. Real-world examples are provided to illustrate the impact individual digital interventions can have on each pillar of sustainability and demonstrate the scale of the potential benefits which can be achieved. Discussion: Digitally enabled healthcare solutions present an approach which offer numerous benefits, including environmental sustainability, economic benefits, and improved patient experience. There are also potential drawbacks such as the risk of digital exclusion and the need for integration with existing technology platforms. Overall, it is essential to strike a balance between the benefits and potential drawbacks of digital healthcare solutions to ensure that they are equitable, effective, and sustainable.