Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy.

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early DR and that targeting CD200R can attenuate high glucose-induced inflammation and phagocytosis in cultured microglia. Last, we demonstrate that targeting CD200R in vivo can prevent visual dysfunction, microglia activation, and retinal inflammation in the diabetic mouse. These studies provide a molecular framework for the pivotal role that microglia play in early DR pathogenesis and identify a potential immunotherapeutic target for treating DR in patients.

High-Pressure Synthesis and Recovery of Single Crystals of the Metastable Manganese Carbide, MnCx.

Transition metal carbides find widespread use throughout industry due to their high strength and resilience under extreme conditions. However, they remain largely limited to compounds formed from the early d-block elements, since the mid-to-late transition metals do not form thermodynamically stable carbides. We report here the high-pressure bulk synthesis of large single crystals of a novel metastable manganese carbide compound,MnCxP63/mmc, which adopts the anti-NiAs-type structure with significant substoichiometry at the carbon sites. We demonstrate how synthesis pressure modulates the carbon loading, with~40% occupancy being achieved at 9.9 GPa.

High-Pressure Polymorphism in Silver Ferrite Delafossite, AgFeO2.

The delafossites are a class of layered metal oxides that are notable for being able to exhibit optical transparency alongside an in-plane electrical conductivity, making them promising platforms for the development of transparent conductive oxides. Pressure-induced polymorphism offers a direct method for altering the electrical and optical properties in this class, and although the copper delafossites have been studied extensively under pressure, the silver delafossites remain only partially studied. We report two new high-pressure polymorphs of silver ferrite delafossite, AgFeO2, that are stabilized above ∼6 and ∼14 GPa. In situ X-ray diffraction and vibrational spectroscopy measurements are used to examine the structural changes across the two phase transitions. The high-pressure structure between 6 and 14 GPa is assigned as a monoclinic C2/c structure that is analogous to the high-pressure phase reported for AgGaO2. Nuclear resonant forward scattering reveals no change in the spin state or valence state at the Fe3+ site up to 15.3(5) GPa.

Risk factors for Cryptosporidium contamination in Minnesota public supply wells.

In a recent monitoring study of Minnesota's public supply wells, Cryptosporidium was commonly detected with 40% of the wells having at least one detection. Risk factors for Cryptosporidium occurrence in drinking water supply wells, beyond surface water influence, remain poorly understood. To address this gap, physical and chemical factors were assessed as potential predictors of Cryptosporidium occurrence in 135 public supply wells in Minnesota. Univariable analysis, regression techniques, and classification trees were used to analyze the data. Many variables were identified as significant risk factors in univariable analysis and several remained significant throughout the succeeding analysis techniques. These factors fell into general categories of well use and construction, aquifer characteristics, and connectedness to the land surface, well capture zones, and land use therein, existence of potential contaminant sources within 200-feet of the well, and variability in the chemical and isotopic parameters measured during the study. These risk categories, and the specific variables and threshold values we have identified, can help guide future research on factors influencing Cryptosporidium contamination of wells and can be used by environmental health programs to develop risk-based sampling plans and design interventions that reduce associated health risks.

Stable Clinical and Radiological Outcomes at Medium and over 5 Year Follow Up of Calcaneus Fracture Open Reduction Internal Fixation Using a Sinus Tarsi Approach.

The sinus tarsi approach is increasingly growing in popularity for open reduction internal fixation of calcaneus fractures. Multiple studies have demonstrated favorable short-term results compared to the traditional extensile L incision, however long-term data over 5 years is currently limited to a single retrospective case series. Following local ethical approval, all patients who had completed a minimum 5 years from time of operation were contacted with a Standardized Telephone Questionnaire completed. This followed a previous retrospective chart review, with follow up telephone or clinic consultation performed by Davey et al. of this cohort at mean 35 months. Thirty-four fractures (31 patients) completed minimum 5 year follow up from the eligible group of 54 fractures (49 patients). Regarding functional outcomes, a significant improvement in mean Maryland Foot Score was observed between short- (mean 35.8 months) and medium-term (mean 81.9 months) of 77.6 (SD 15.0) to 86 (SD 7.9) (p = .0082). There was no significant difference in postoperative and long term radiographic Bohler's angle (p = .9683). Eleven feet (32%) proceeded to require reoperation, with removal of metal performed in 10 (29%), fusion in 2 (6%), and skin grafting following wound breakdown for 1 (3%). Four feet (12.9%) experienced post operative wound complications, including 3 (9.68%) cases of infection and 2 (6.45%) of delayed wound healing. This study demonstrated stable clinical and radiographic outcomes over 5 years following Calcaneus Fracture Open Reduction Internal Fixation using a sinus tarsi approach, supporting its continued usage when treating intraarticular calcaneus fractures for which operative intervention is indicated.

Vitamin D: determinants of status, indications for testing and knowledge in a convenience sample of Irish adults.

Vitamin D deficiency is common in Irish adults, though there is limited research on its determinants, knowledge of vitamin D or indications for testing. We aimed to explore the determinants of vitamin D status in adults and examine knowledge and reasons for testing. The study population comprised adults who had serum 25-hydroxyvitamin D tested by general practitioners request at a Dublin Hospital in 2020. Questionnaires detailing dietary intake, sun exposure, ethnicity, biophysical factors and vitamin D knowledge were sent to a sample stratified by age, sex and vitamin D status. In total, there were 383 participants, mean age 56·0 (sd 16·6) years. Wintertime deficiency disproportionally affected non-white v. white (60 % v. 24 %, P < 0·001). The greatest predictors of deficiency were low vitamin D intake (< 10 µg/d) (P < 0·001) and non-white ethnicity (P = 0·006), followed by sun avoidance (P = 0·022). It was also more prevalent in those with lower body exposure when outdoors. The majority (86 %) identified vitamin D as important for bone health. However, 40 % were tested for non-clinical indications and half were not aware of the recommended daily allowance (RDA). Low vitamin D intake was the most important determinant of deficiency, but ethnicity and sun exposure habits were also significant predictors. The majority had no clear indication for testing and were not aware of the RDA. Public health policies to improve knowledge and vitamin D intake, especially for those of non-white ethnicity and with reduced sun exposure, should be considered.

In Situ Pulmonary Arterial Thrombosis: Literature Review and Clinical Significance of a Distinct Entity.

Filling defects identified in the pulmonary arterial tree are commonly presumed to represent an embolic phenomenon originating from thrombi formed in remote veins, particularly lower-extremity deep venous thrombosis (DVT). However, accumulating evidence supports an underappreciated cause for pulmonary arterial thrombosis (PAT), namely, de novo thrombogenesis-whereby thrombosis arises within the pulmonary arteries in the absence of DVT. Although historically underrecognized, in situ PAT has become of heightened importance with the emergence of SARS-CoV-2 infection. In situ PAT is attributed to endothelial dysfunction, systemic inflammation, and acute lung injury and has been described in a range of conditions including COVID-19, trauma, acute chest syndrome in sickle cell disease, pulmonary infections, and severe pulmonary arterial hypertension. The distinction between pulmonary embolism and in situ PAT may have important implications regarding management decisions and clinical outcomes. In this review, we summarize the pathophysiology, imaging appearances, and management of in situ PAT in various clinical situations. This understanding will promote optimal tailored treatment strategies for this increasingly recognized entity.

Susceptibility and transcriptomic response to plasma-activated water of Listeria monocytogenes planktonic and sessile cells.

Plasma-Activated Water (PAW) was generated from tap water using a surface dielectric barrier discharge at different discharge power (26 and 36 W) and activation time (5 and 30 min). The inactivation of a three-strain Listeria monocytogenes cocktail in planktonic and biofilm state was evaluated. PAW generated at 36 W-30 min showed the lowest pH and the highest hydrogen peroxide, nitrates, nitrites contents and effectiveness against cells on planktonic state, resulting in 4.6 log reductions after a 15-min treatment. Although the antimicrobial activity in biofilms formed on stainless steel and on polystyrene was lower, increasing the exposure time to 30 min allowed an inactivation >4.5 log cycles. The mechanisms of action of PAW were investigated using chemical solutions that mimic its physico-chemical characteristics and also RNA-seq analysis. The main transcriptomic changes affected carbon metabolism, virulence and general stress response genes, with several overexpressed genes belonging to the cobalamin-dependent gene cluster.

Cholesterol-dependent cytolysins: The outstanding questions.

The cholesterol-dependent cytolysins (CDCs) are a major family of bacterial pore-forming proteins secreted as virulence factors by Gram-positive bacterial species. CDCs are produced as soluble, monomeric proteins that bind specifically to cholesterol-rich membranes, where they oligomerize into ring-shaped pores of more than 30 monomers. Understanding the details of the steps the toxin undergoes in converting from monomer to a membrane-spanning pore is a continuing challenge. In this review we summarize what we know about CDCs and highlight the remaining outstanding questions that require answers to obtain a complete picture of how these toxins kill cells.

Cadaveric Classification of the Genicular Arteries, with Implications for the Interventional Radiologist.

PURPOSE: To document and assess the genicular arterial variation in a large multicenter cadaveric sample and to generate an anatomical classification with implications for genicular artery embolization (GAE). MATERIALS AND METHODS: A total of 212 dissected donor body lower limbs from 3 medical school institutions were included. The descending genicular artery (DGA), superior lateral genicular artery, superior medial genicular artery, middle genicular artery, inferior lateral genicular artery, inferior medial genicular artery, and anterior tibial recurrent artery were identified for gross anatomical appearance, location of origin, diameter of vessels, and variation in branching patterns. RESULTS: A total of 198 DGAs, 204 popliteal-origin genicular arteries, and 183 anterior tibial recurrent arteries were adequately preserved and reviewed. Three types (A: 26%, B: 71%, and C: 5%) of DGA branching patterns were proposed along with 6 types (I: 28%, II: 22%, III: 15%, IV: 15%, V: 10%, and VI: 6%) of popliteal-origin genicular artery branching variants. Right versus left comparisons did not reveal clinically significant differences in the vessel distance (P = .30 to .82). CONCLUSIONS: Despite the large number of possible anatomical variations of the genicular arteries, 6 main patterns corresponded to >96% of the cases. The description and classification of the genicular arterial anatomy may provide useful information to the interventional radiologist and add to the technical nuances of GAE.

Statewide Quantitative Microbial Risk Assessment for Waterborne Viruses, Bacteria, and Protozoa in Public Water Supply Wells in Minnesota.

Infection risk from waterborne pathogens can be estimated via quantitative microbial risk assessment (QMRA) and forms an important consideration in the management of public groundwater systems. However, few groundwater QMRAs use site-specific hazard identification and exposure assessment, so prevailing risks in these systems remain poorly defined. We estimated the infection risk for 9 waterborne pathogens based on a 2-year pathogen occurrence study in which 964 water samples were collected from 145 public wells throughout Minnesota, USA. Annual risk across all nine pathogens combined was 3.3 × 10-1 (95% CI: 2.3 × 10-1 to 4.2 × 10-1), 3.9 × 10-2 (2.3 × 10-2 to 5.4 × 10-2), and 1.2 × 10-1 (2.6 × 10-2 to 2.7 × 10-1) infections person-1 year-1 for noncommunity, nondisinfecting community, and disinfecting community wells, respectively. Risk estimates exceeded the U.S. benchmark of 10-4 infections person-1 year-1 in 59% of well-years, indicating that the risk was widespread. While the annual risk for all pathogens combined was relatively high, the average daily doses for individual pathogens were low, indicating that significant risk results from sporadic pathogen exposure. Cryptosporidium dominated annual risk, so improved identification of wells susceptible to Cryptosporidium contamination may be important for risk mitigation.

Statistical predictions on the encapsulation of single molecule binding pairs into sized-dispersed nanocontainers.

Single molecule experiments have recently attracted enormous interest. Many of these studies involve the encapsulation of a single molecule into nanoscale containers (such as vesicles, droplets and nanowells). In such cases, the single molecule encapsulation efficiency is a key parameter to consider in order to get a statistically significant quantitative information. It has been shown that such encapsulation typically follows a Poisson distribution and such theory of encapsulation has only been applied to the encapsulation of single molecules into perfectly sized monodispersed containers. However, experimentally nanocontainers are usually characterized by a size distribution, and often just a single binding pair (rather than a single molecule) is required to be encapsulated. Here the use of Poisson distribution is extended to predict the encapsulation efficiency of two different molecules in an association equilibrium. The Poisson distribution is coupled with a log-normal distribution in order to consider the effect of the container size distribution, and the effect of adsorption to the container is also considered. This theory will allow experimentalists to determine what single molecule encapsulation efficiency can be expected as a function of the experimental conditions. Two case studies, based on experimental data, are given to support the theoretical predictions.

Cold plasma for the disinfection of industrial food-contact surfaces: An overview of current status and opportunities.

Food safety is the primary goal for food and drink manufacturers. Cleaning and disinfection practices applied to the processing environment are vital to maintain this safety; yet, current approaches can incur costly downtime and the potential for microorganisms to grow and establish, if not effectively removed. For that reason, manufacturers are seeking nonthermal, online, and continuous disinfection processes to control the microbial levels within the processing environment. One such emerging technique, with great potential, is cold atmospheric pressure plasma (CAP). This review presents the latest advances and challenges associated with CAP-based technologies for the decontamination of surfaces and equipment found within the food-processing environment. It provides a detailed overview of the technology and a comprehensive analysis of the many CAP-based antimicrobial studies on food-contact surfaces and materials. As CAP is considered an emerging technique, many of the recent studies are still in the preliminary stages, with results obtained under widely different conditions. This lack of cohesive information and an inability to directly compare CAP systems has greatly impeded technological development. The review further explores the challenge of scaling CAP technology to meet industry needs, considering aspects such as regulatory constraints, environmental credentials, and cost of use. Finally, a discussion is presented on the future outlook for CAP technology in this area, identifying key challenges that must be addressed to promote industry uptake.

A newly identified prophage-encoded gene, ymfM, causes SOS-inducible filamentation in Escherichia coli.

Rod-shaped bacteria such as Escherichia coli can regulate cell division in response to stress, leading to filamentation, a process where cell growth and DNA replication continues in the absence of division, resulting in elongated cells. The classic example of stress is DNA damage which results in the activation of the SOS response. While the inhibition of cell division during SOS has traditionally been attributed to SulA in E. coli, a previous report suggests that the e14 prophage may also encode an SOS-inducible cell division inhibitor, previously named SfiC. However, the exact gene responsible for this division inhibition has remained unknown for over 35 years. A recent high-throughput over-expression screen in E. coli identified the e14 prophage gene, ymfM, as a potential cell division inhibitor. In this study, we show that the inducible expression of ymfM from a plasmid causes filamentation. We show that this expression of ymfM results in the inhibition of Z ring formation and is independent of the well characterised inhibitors of FtsZ ring assembly in E. coli, SulA, SlmA and MinC. We confirm that ymfM is the gene responsible for the SfiC phenotype as it contributes to the filamentation observed during the SOS response. This function is independent of SulA, highlighting that multiple alternative division inhibition pathways exist during the SOS response. Our data also highlight that our current understanding of cell division regulation during the SOS response is incomplete and raises many questions regarding how many inhibitors there actually are and their purpose for the survival of the organism.Importance:Filamentation is an important biological mechanism which aids in the survival, pathogenesis and antibiotic resistance of bacteria within different environments, including pathogenic bacteria such as uropathogenic Escherichia coli Here we have identified a bacteriophage-encoded cell division inhibitor which contributes to the filamentation that occurs during the SOS response. Our work highlights that there are multiple pathways that inhibit cell division during stress. Identifying and characterising these pathways is a critical step in understanding survival tactics of bacteria which become important when combating the development of bacterial resistance to antibiotics and their pathogenicity.

Computationally Directed Discovery of MoBi2.

Incorporating bismuth, the heaviest element stable to radioactive decay, into new materials enables the creation of emergent properties such as permanent magnetism, superconductivity, and nontrivial topology. Understanding the factors that drive Bi reactivity is critical for the realization of these properties. Using pressure as a tunable synthetic vector, we can access unexplored regions of phase space to foster reactivity between elements that do not react under ambient conditions. Furthermore, combining computational and experimental methods for materials discovery at high-pressures provides broader insight into the thermodynamic landscape than can be achieved through experiment alone, informing our understanding of the dominant chemical factors governing structure formation. Herein, we report our combined computational and experimental exploration of the Mo-Bi system, for which no binary intermetallic structures were previously known. Using the ab initio random structure searching (AIRSS) approach, we identified multiple synthetic targets between 0-50 GPa. High-pressure in situ powder X-ray diffraction experiments performed in diamond anvil cells confirmed that Mo-Bi mixtures exhibit rich chemistry upon the application of pressure, including experimental realization of the computationally predicted CuAl2-type MoBi2 structure at 35.8(5) GPa. Electronic structure and phonon dispersion calculations on MoBi2 revealed a correlation between valence electron count and bonding in high-pressure transition metal-Bi structures as well as identified two dynamically stable ambient pressure polymorphs. Our study demonstrates the power of the combined computational-experimental approach in capturing high-pressure reactivity for efficient materials discovery.

Rapid HIV-1 Capsid Interaction Screening Using Fluorescence Fluctuation Spectroscopy.

The HIV capsid is a multifunctional protein capsule that mediates the delivery of the viral genetic material into the nucleus of the target cell. Host cell proteins bind to a number of repeating binding sites on the capsid to regulate steps in the replication cycle. Here, we develop a fluorescence fluctuation spectroscopy method using self-assembled capsid particles as the bait to screen for fluorescence-labeled capsid-binding analytes ("prey" molecules) in solution. The assay capitalizes on the property of the HIV capsid as a multivalent interaction platform, facilitating high sensitivity detection of multiple prey molecules that have accumulated onto capsids as spikes in fluorescence intensity traces. By using a scanning stage, we reduced the measurement time to 10 s without compromising on sensitivity, providing a rapid binding assay for screening libraries of potential capsid interactors. The assay can also identify interfaces for host molecule binding by using capsids with defects in known interaction interfaces. Two-color coincidence detection using the fluorescent capsid as the bait further allows the quantification of binding levels and determination of binding affinities. Overall, the assay provides new tools for the discovery and characterization of molecules used by the HIV capsid to orchestrate infection. The measurement principle can be extended for the development of sensitive interaction assays, utilizing natural or synthetic multivalent scaffolds as analyte-binding platforms.

Objective adherence to dental device versus positive airway pressure treatment in adults with obstructive sleep apnea.

Although mandibular advancement device (MAD) treatment of adults with obstructive sleep apnea (OSA) is generally less efficacious than positive airway pressure (PAP), the two treatments are associated, with similar clinical outcomes. As a sub-analysis of a randomized trial comparing the effect of MAD versus PAP on blood pressure, this study compared objectively measured adherence to MAD versus PAP treatment in adults with OSA. Adults with OSA (age 54.1 ± 11.2 [standard deviation] years, 71.1% male, apnea-hypopnea index 31.6 ± 22.7 events/h) were randomized to MAD (n = 89) or PAP (n = 91) treatment for 3-6 months. Objective adherence was assessed with a thermal sensor embedded in the MAD and a pressure sensor in the PAP unit. In a per protocol analysis, no difference was observed in average daily hours of use over all days in participants on MAD (n = 35, 4.4 ± 2.9 h) versus PAP (n = 51, 4.7 ± 1.6 h, p = .597) treatment when days with missing adherence data were included as no use. MAD was used on a lower percentage of days (62.5 ± 36.4% versus 79.9 ± 19.8%, p = .047), but with greater average daily hours of use on days used (6.4 ± 1.9 h versus 5.7 ± 1.2 h, p = .013). Average daily hours of use in the first week were associated with long-term adherence to MAD (p < .0001) and PAP (p = .0009) treatment. Similar results were obtained when excluding days with missing adherence data. In conclusion, no significant difference was observed in objectively measured average daily hours of MAD and PAP adherence in adults with OSA, despite differences in the patterns of use. MAD adherence in the first week predicted long-term use.

Vitamin D retesting by general practitioners: a factor and cost analysis.

OBJECTIVES: Vitamin D testing by Primary Care doctors is increasing, placing greater workloads on healthcare systems. There is little data though on vitamin D retesting in Ireland. This study aims to investigate the factors associated with vitamin D retesting by Irish General Practitioners (GPs) and examine the resulting costs. METHODS: This is a retrospective analysis over 5 years (2014-2018) of GP requested 25-hydroxyvitamin D (25(OH)D) results in 36,458 patients at a major city hospital in Dublin, Ireland. Those with one test were compared with individuals who were retested and samples categorised to determine changes in status between tests. RESULTS: Nearly one in four patients (n=8,305) were retested. Positive predictors of retesting were female (p<0.001), age (60-69 years, p<0.001), location (Co. Kildare, p<0.001) and initial deficiency (<30 nmol/L, p<0.001) or insufficiency (30-49.9 nmol/L, p<0.001). Vitamin D status improved on retesting, with deficiency halving on first retest (9 vs. 18%, p<0.001) and dropping to 6% on further retests. About 12.2% of retests were done within 3 months and 29% had ≥2 retests within 1 year. 57% of retests were in those initially vitamin D replete (>50 nmol/L). The annual cost of inappropriate testing was €61,976. CONCLUSIONS: One in four patients were retested and this varied by age, gender and patient location. Over 10% of retests were inappropriately early (<3 months), a third too frequent and over half were in replete individuals incurring significant costs. Clear guidance for GPs on minimum retesting intervals is needed, as well as laboratory ordering systems to limit requests using pre-defined criteria.

CetZ tubulin-like proteins control archaeal cell shape.

Tubulin is a major component of the eukaryotic cytoskeleton, controlling cell shape, structure and dynamics, whereas its bacterial homologue FtsZ establishes the cytokinetic ring that constricts during cell division. How such different roles of tubulin and FtsZ evolved is unknown. Studying Archaea may provide clues as these organisms share characteristics with Eukarya and Bacteria. Here we report the structure and function of proteins from a distinct family related to tubulin and FtsZ, named CetZ, which co-exists with FtsZ in many archaea. CetZ X-ray crystal structures showed the FtsZ/tubulin superfamily fold, and one crystal form contained sheets of protofilaments, suggesting a structural role. However, inactivation of CetZ proteins in Haloferax volcanii did not affect cell division. Instead, CetZ1 was required for differentiation of the irregular plate-shaped cells into a rod-shaped cell type that was essential for normal swimming motility. CetZ1 formed dynamic cytoskeletal structures in vivo, relating to its capacity to remodel the cell envelope and direct rod formation. CetZ2 was also implicated in H. volcanii cell shape control. Our findings expand the known roles of the FtsZ/tubulin superfamily to include archaeal cell shape dynamics, suggesting that a cytoskeletal role might predate eukaryotic cell evolution, and they support the premise that a major function of the microbial rod shape is to facilitate swimming.

High intensity interval training versus moderate intensity continuous training for people with interstitial lung disease: protocol for a randomised controlled trial.

BACKGROUND: Interstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease. METHODS: Eligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program. Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George's Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation. DISCUSSION: The standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease. Trial registration ClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019, https://clinicaltrials.gov/ct2/show/NCT03800914 Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true.