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1.
3D Print Med ; 10(1): 10, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38564090

ABSTRACT

BACKGROUND: Femoral head avascular necrosis (AVN), or death of femoral head tissue due to a lack of blood supply, is a leading cause of total hip replacement for non-geriatric patients. Core decompression (CD) is an effective treatment to re-establish blood flow for patients with AVN. Techniques aimed at improving its efficacy are an area of active research. We propose the use of 3D printed drill guides to accurately guide therapeutic devices for CD. METHODS: Using femur sawbones, image processing software, and 3D modeling software, we created a custom-built device with pre-determined drill trajectories and tested the feasibility of the 3D printed drill guides for CD. A fellowship trained orthopedic surgeon used the drill guide to position an 8 ga, 230 mm long decompression device in the three synthetic femurs. CT scans were taken of the sawbones with the drill guide and decompression device. CT scans were processed in the 3D modeling software. Descriptive statistics measuring the angular and needle-tip deviation were compared to the original virtually planned model. RESULTS: Compared to the original 3D model, the trials had a mean displacement of 1.440 ± 1.03 mm and a mean angle deviation of 1.093 ± 0.749º. CONCLUSIONS: The drill guides were demonstrated to accurately guide the decompression device along its predetermined drill trajectory. Accuracy was assessed by comparing values to literature-reported values and considered AVN lesion size. This study demonstrates the potential use of 3D printing technology to improve the efficacy of CD techniques.

2.
Arthroplast Today ; 26: 101337, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38497084

ABSTRACT

Avascular necrosis of the femoral head is a debilitating condition that can lead to femoral head collapse. Core decompression with adjuvant cellular therapies, such as bone marrow aspirate concentrate, delays disease progression and improves outcomes. However, inconsistent results in the literature may be due to limitations in surgical technique and difficulty in targeting the necrotic lesions. Here, we present a surgical technique utilizing computed tomography-based three-dimensional modeling and instrument tracking to guide the therapy to the center of the lesion. This method minimizes the number of attempts to reach the lesion and confirms the three-dimensional positioning of the instrumentation within the lesion. Our technique may improve the outcomes of core decompression and adjuvant therapy and prevent or delay hip collapse in patients with femoral head avascular necrosis.

3.
Res Sq ; 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38106183

ABSTRACT

Background: Femoral head avascular necrosis (AVN), or death of femoral head tissue due to a lack of blood supply, is a leading cause of total hip replacement for non-geriatric patients. Core decompression (CD) is an effective treatment to re-establish blood flow for patients with AVN. Techniques aimed at improving its efficacy are an area of active research. We propose the use of 3D printed drill guides to accurately guide therapeutic devices for CD. Methods: Using femur sawbones, image processing software, and 3D modeling software, we created a custom-built device with pre-determined drill trajectories and tested the feasibility of the 3D printed drill guides for CD. A fellowship trained orthopedic surgeon used the drill guide to position an 8 ga, 230 mm long decompression device in the three synthetic femurs. CT scans were taken of the sawbones with the drill guide and decompression device. CT scans were processed in the 3D modeling software. Descriptive statistics measuring the angular and needle-tip deviation were compared to the original virtually planned model. Results: Compared to the original 3D model, the trials had a mean displacement of 1.440±1.03 mm and a mean angle deviation of 1.093±0.749°. Conclusions: The drill guides were demonstrated to accurately guide the decompression device along its predetermined drill trajectory. Accuracy was assessed by comparing values to literature-reported values and considered AVN lesion size. This study demonstrates the potential use of 3D printing technology to improve the efficacy of CD techniques.

4.
JMIR Public Health Surveill ; 9: e39700, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37155240

ABSTRACT

BACKGROUND: Vaccine safety surveillance is a core component of vaccine pharmacovigilance. In Canada, active, participant-centered vaccine surveillance is available for influenza vaccines and has been used for COVID-19 vaccines. OBJECTIVE: The objective of this study is to evaluate the effectiveness and feasibility of using a mobile app for reporting participant-centered seasonal influenza adverse events following immunization (AEFIs) compared to a web-based notification system. METHODS: Participants were randomized to influenza vaccine safety reporting via a mobile app or a web-based notification platform. All participants were invited to complete a user experience survey. RESULTS: Among the 2408 randomized participants, 1319 (54%) completed their safety survey 1 week after vaccination, with a higher completion rate among the web-based notification platform users (767/1196, 64%) than among mobile app users (552/1212, 45%; P<.001). Ease-of-use ratings were high for the web-based notification platform users (99% strongly agree or agree) and 88.8% of them strongly agreed or agreed that the system made reporting AEFIs easier. Web-based notification platform users supported the statement that a web-based notification-only approach would make it easier for public health professionals to detect vaccine safety signals (91.4%, agreed or strongly agreed). CONCLUSIONS: Participants in this study were significantly more likely to respond to a web-based safety survey rather than within a mobile app. These results suggest that mobile apps present an additional barrier for use compared to the web-based notification-only approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT05794113; https://clinicaltrials.gov/show/NCT05794113.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Mobile Applications , Humans , Influenza, Human/prevention & control , COVID-19 Vaccines , Vaccination/adverse effects , Influenza Vaccines/adverse effects , Internet
5.
J Microsc ; 288(3): 169-184, 2022 12.
Article in English | MEDLINE | ID: mdl-35502816

ABSTRACT

We present a trainable segmentation method implemented within the python package ParticleSpy. The method takes user labelled pixels, which are used to train a classifier and segment images of inorganic nanoparticles from transmission electron microscope images. This implementation is based on the trainable Waikato Environment for Knowledge Analysis (WEKA) segmentation, but is written in python, allowing a large degree of flexibility and meaning it can be easily expanded using other python packages. We find that trainable segmentation offers better accuracy than global or local thresholding methods and requires as few as 100 user-labelled pixels to produce an accurate segmentation. Trainable segmentation presents a balance of accuracy and training time between global/local thresholding and neural networks, when used on transmission electron microscope images of nanoparticles. We also quantitatively investigate the effectiveness of the components of trainable segmentation, its filter kernels and classifiers, in order to demonstrate the use cases for the different filter kernels in ParticleSpy and the most accurate classifiers for different data types. A set of filter kernels is identified that are effective in distinguishing particles from background but that retain dissimilar features. In terms of classifiers, we find that different classifiers perform optimally for different image contrast; specifically, a random forest classifier performs best for high-contrast ADF images, but that QDA and Gaussian Naïve Bayes classifiers perform better for low-contrast TEM images.


Measurement of the size, shape and composition of nanoparticles is routinely performed using transmission electron microscopy and related techniques. Typically, distinguishing particles from the background in an image is performed using the intensity of each pixel, creating two sets of pixels to separate particles from background. However, this separation of intensity can be difficult if the contrast in an image is low, or if the intensity of the background varies significantly. In this study, an approach that takes into account additional image features (such as boundaries and texture) was investigated to study electron microscope images of metallic nanoparticles. In this 'trainable segmentation' approach, the user labels examples of particle and background pixels in order to train a machine learning algorithm to distinguish between particles and background. The performance of different machine learning algorithms was investigated, in addition to the effect of using different features to aid the segmentation. Overall, a trainable segmentation approach was found to perform better than use of an intensity threshold to distinguish between particles and background in electron microscope images.


Subject(s)
Image Processing, Computer-Assisted , Nanoparticles , Image Processing, Computer-Assisted/methods , Bayes Theorem , Neural Networks, Computer , Microscopy, Electron, Transmission
6.
JMIR Form Res ; 6(1): e32273, 2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35023840

ABSTRACT

BACKGROUND: Vaccine-preventable infections result in significant morbidity, mortality, and costs in pediatric transplant recipients. However, at the time of transplant, less than 20% of children are up-to-date for age-appropriate immunizations that could prevent these diseases. Smartphone apps have the potential to increase immunization rates through their ability to provide vaccine education, send vaccine reminders, and facilitate communication between parents and a multidisciplinary medical group. OBJECTIVE: The aim of this study was to describe the development of a smartphone app, Immunize PediatricTransplant, to promote pretransplant immunization and to report on app functionality and usability when applied to the target population. METHODS: We used a mixed methods study design guided by the Mobile Health Agile Development and Evaluation Lifecycle. We first completed a formative research including semistructured interviews with transplant stakeholders (12 primary care physicians, 40 parents or guardians of transplant recipients, 11 transplant nurse coordinators, and 19 transplant subspecialists) to explore the acceptability of an immunization app to be used in the pretransplant period. Based on these findings, CANImmunize Inc developed the Immunize PediatricTransplant app. We next held 2 focus group discussions with 5-6 transplant stakeholders/group (n=11; 5 parents of transplant recipients, 2 primary care physicians, 2 transplant nurse coordinators, and 2 transplant subspecialists) to receive feedback on the app. After the app modifications were made, alpha testing was conducted on the functional prototype. We then implemented beta testing with 12 stakeholders (6 parents of transplant recipients, 2 primary care doctors, 2 transplant nurse coordinators, and 2 transplant subspecialists) to refine the app through an iterative process. Finally, the stakeholders completed the user version of the Mobile Application Rating Scale (uMARS) to assess the functionality and quality of the app. RESULTS: A new Android- and Apple-compatible app, Immunize PediatricTransplant, was developed to improve immunization delivery in the pretransplant period. The app contains information about vaccine use in the pretransplant period, houses a complete immunization record for each child, includes a communication tool for parents and care providers, and sends automated reminders to parents and care providers when immunizations are due. During usability testing, the stakeholders were able to enter a mock vaccine record containing 16 vaccines in an average of 8.1 minutes (SD 1.8) with 87% accuracy. The stakeholders rated engagement, functionality, aesthetics, and information quality of the app as 4.2/5, 4.5/5, 4.6/5, and 4.8/5, respectively. All participants reported that they would recommend this app to families and care teams with a child awaiting solid organ transplant. CONCLUSIONS: Through a systematic, user-centered, agile, iterative approach, the Immunize PediatricTransplant app was developed to improve immunization delivery in the pretransplant period. The app tested well with end users. Further testing and agile development among patients awaiting transplant are needed to understand real-world acceptability and effectiveness in improving immunization rates in children awaiting transplant.

7.
Front Physiol ; 12: 625762, 2021.
Article in English | MEDLINE | ID: mdl-34335284

ABSTRACT

Podocyte loss plays a pivotal role in the pathogenesis of glomerular disease. However, the mechanisms underlying podocyte damage and loss remain poorly understood. Although detachment of viable cells has been documented in experimental Diabetic Nephropathy, correlations between reduced podocyte density and disease severity have not yet been established. YAP, a mechanosensing protein, has recently been shown to correlate with glomerular disease progression, however, the underlying mechanism has yet to be fully elucidated. In this study, we sought to document podocyte density in Diabetic Nephropathy using an amended podometric methodology, and to investigate the interplay between YAP and cytoskeletal integrity during podocyte injury. Podocyte density was quantified using TLE4 and GLEPP1 multiplexed immunofluorescence. Fourteen Diabetic Nephropathy cases were analyzed for both podocyte density and cytoplasmic translocation of YAP via automated image analysis. We demonstrate a significant decrease in podocyte density in Grade III/IV cases (124.5 per 106 µm3) relative to Grade I/II cases (226 per 106 µm3) (Student's t-test, p < 0.001), and further show that YAP translocation precedes cytoskeletal rearrangement following injury. Based on these findings we hypothesize that a significant decrease in podocyte density in late grade Diabetic Nephropathy may be explained by early cytoplasmic translocation of YAP.

8.
Nat Commun ; 12(1): 3636, 2021 06 17.
Article in English | MEDLINE | ID: mdl-34140467

ABSTRACT

To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ART558. ART558 inhibits the major Polθ-mediated DNA repair process, Theta-Mediated End Joining, without targeting Non-Homologous End Joining. In addition, ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor. Genetic perturbation screening revealed that defects in the 53BP1/Shieldin complex, which cause PARP inhibitor resistance, result in in vitro and in vivo sensitivity to small molecule Polθ polymerase inhibitors. Mechanistically, ART558 increases biomarkers of single-stranded DNA and synthetic lethality in 53BP1-defective cells whilst the inhibition of DNA nucleases that promote end-resection reversed these effects, implicating these in the synthetic lethal mechanism-of-action. Taken together, these observations describe a drug class that elicits BRCA-gene synthetic lethality and PARP inhibitor synergy, as well as targeting a biomarker-defined mechanism of PARPi-resistance.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , DNA Repair/drug effects , DNA-Directed DNA Polymerase/genetics , Nucleic Acid Synthesis Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Synthetic Lethal Mutations/drug effects , Allosteric Regulation , Animals , Apoptosis/drug effects , Apoptosis/genetics , BRCA1 Protein/metabolism , BRCA2 Protein/metabolism , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cell Survival/drug effects , Cell Survival/radiation effects , DNA Damage/drug effects , DNA-Binding Proteins/metabolism , DNA-Directed DNA Polymerase/metabolism , Deoxyribonucleases/antagonists & inhibitors , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Female , Homologous Recombination/drug effects , Humans , Inhibitory Concentration 50 , Mice , Organoids/drug effects , Ovarian Neoplasms/genetics , Rats , Synthetic Lethal Mutations/genetics , Tumor Suppressor p53-Binding Protein 1/deficiency , Tumor Suppressor p53-Binding Protein 1/metabolism , DNA Polymerase theta
9.
Sci Total Environ ; 774: 144795, 2021 Jun 20.
Article in English | MEDLINE | ID: mdl-33609849

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are synthetic, organic chemicals that resist environmental breakdown. The properties that made PFAS into an industrial success also led to their persistence and bioaccumulation. As PFAS were widely used for many decades their presence is evident globally, and their persistence and potential for toxicity create concern for human, animal and environmental health. Following the precautionary principle, a reduction in human exposure is generally recommended. The most significant source of human exposure to PFAS is dietary intake (food and water) with additional exposure via dust. As PFAS concentrations have been more frequently studied in aquatic food sources, there is less understanding of exposure via terrestrial animals. To further define human exposure via animal products, it is necessary to determine PFAS concentrations and persistence in terrestrial livestock and game species. Studies assessing ambient concentrations of PFAS have noted that, aside from point sources of contamination, there is generally low input of PFAS into terrestrial agricultural food chains. However, livestock and game species may be exposed to PFAS via contaminated water, soil, substrate, air or food, and the contribution of these exposures to PFAS concentrations in food products is less well studied. This review focuses on perfluoroalkyl substances (PFAAs) and compiles information from terrestrial livestock and game species as a source of dietary exposure in humans, and discusses toxicokinetics and health effects in animals, while identifying future focus areas. Publications describing the transfer of PFAAs to farmed and hunted animals are scarce, and demonstrate large variability in distribution and elimination. We outline several relatively small, short-term studies in cattle, sheep, pigs and poultry. While negative effects have not been noted, the poultry investigations were the only studies to explicitly assess health effects. Comparative information is presented on PFAA concentrations in livestock products and edible tissues of game animals.


Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Animals , Cattle , Dietary Exposure , Fluorocarbons/analysis , Livestock , Sheep , Swine , Water Pollution
10.
Nucleic Acids Res ; 49(1): 458-478, 2021 01 11.
Article in English | MEDLINE | ID: mdl-33332560

ABSTRACT

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1.


Subject(s)
Autoantigens/physiology , Poly(A)-Binding Protein I/physiology , Polyribosomes/metabolism , Protein Biosynthesis/physiology , RNA, Messenger/metabolism , Ribonucleoproteins/physiology , TOR Serine-Threonine Kinases/physiology , 5' Untranslated Regions/genetics , Autoantigens/genetics , Gene Expression Regulation , Genes, Reporter , HeLa Cells , Humans , Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors , Mechanistic Target of Rapamycin Complex 2/antagonists & inhibitors , Mutagenesis, Site-Directed , Mutation, Missense , Naphthyridines/pharmacology , Point Mutation , Protein Biosynthesis/genetics , RNA Interference , RNA, Messenger/genetics , RNA-Binding Proteins/isolation & purification , RNA-Binding Proteins/metabolism , Recombinant Fusion Proteins/metabolism , Ribonucleoproteins/genetics , SS-B Antigen
11.
Can J Anaesth ; 67(12): 1749-1760, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32929659

ABSTRACT

PURPOSE: Patients want personalized information before surgery; most do not receive personalized risk estimates. Inadequate information contributes to poor experience and medicolegal complaints. We hypothesized that exposure to the Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment (PREDICT) app, a personalized risk communication tool, would improve patient knowledge and satisfaction after anesthesiology consultations compared with standard care. METHODS: We conducted a prospective clinical study (before-after design) and used patient-reported data to calculate personalized risks of morbidity, mortality, and expected length of stay using a locally calibrated National Surgical Quality Improvement Program risk calculator embedded in the PREDICT app. In the standard care (before) phase, the application's materials and output were not available to participants; in the PREDICT app (after) phase, personalized risks were communicated. Our primary outcome was knowledge score after the anesthesiology consultation. Secondary outcomes included patient satisfaction, anxiety, feasibility, and acceptability. RESULTS: We included 183 participants (90 before; 93 after). Compared with standard care phase, the PREDICT app phase had higher post-consultation: knowledge of risks (14.3% higher; 95% confidence interval [CI], 6.5 to 22.0; P < 0.001) and satisfaction (0.8 points; 95% CI, 0.1 to 1.4; P = 0.03). Anxiety was unchanged (- 1.9%; 95% CI, - 4.2 to 0.5; P = 0.13). Acceptability was high for patients and anesthesiologists. CONCLUSION: Exposure to a patient-facing, personalized risk communication app improved knowledge of personalized risk and increased satisfaction for adults before elective inpatient surgery. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03422133); registered 5 February 2018.


RéSUMé: OBJECTIF: Les patients veulent disposer d'informations personnalisées avant leur chirurgie, mais la plupart d'entre eux ne reçoivent pas d'estimations de leur risque personnalisées. Des informations inadéquates contribuent à une mauvaise expérience et à des plaintes médicolégales. Nous avons émis l'hypothèse qu'une exposition à l'application PREDICT (Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment), un outil de communication du risque personnalisé, améliorerait les connaissances et la satisfaction des patients après leurs consultations en anesthésiologie comparativement à des soins standard. MéTHODE: Nous avons réalisé une étude clinique prospective (de type avant-après) et utilisé les données rapportées par les patients afin de calculer leur risque personnalisé de morbidité et de mortalité, ainsi que la durée de séjour anticipée à l'aide d'un calculateur de risque tiré du Programme national d'amélioration de la qualité chirurgicale que nous avons calibré localement et intégré à l'application PREDICT. Dans la phase de soins standard (avant), le contenu et les résultats de l'application n'étaient pas divulgués aux participants; dans la phase comportant l'application PREDICT (après), les risques personnalisés étaient communiqués. Notre critère d'évaluation principal était le score des connaissances des patients après la consultation en anesthésiologie. Les critères d'évaluation secondaires comprenaient la satisfaction des patients et leur niveau d'anxiété ainsi que la faisabilité et l'acceptabilité d'une telle approche. RéSULTATS: Nous avons inclus 183 participants (90 avant; 93 après). Comparativement à la phase de soins standard, la phase avec l'application PREDICT a démontré un niveau plus élevé de connaissances des risques post consultation (14,3 % plus élevé; intervalle de confiance [IC] 95 %, 6,5 à 22,0; P < 0,001) et de satisfaction (0,8 point; IC 95 %, 0,1 à 1,4; P = 0,03). L'anxiété est demeurée inchangée (− 1,9 %; IC 95 %, − 4,2 à 0,5; P = 0,13). L'acceptabilité était élevée, tant chez les patients que chez les anesthésiologistes. CONCLUSION: L'exposition des patients à une application de communication du risque personnalisé a amélioré leurs connaissances de leur risque personnalisé et augmenté la satisfaction des adultes avant une chirurgie non urgente et non ambulatoire. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03422133); enregistrée le 5 février 2018.


Subject(s)
Communication , Patient Satisfaction , Adult , Elective Surgical Procedures , Humans , Prospective Studies , Quality Improvement
12.
Ther Adv Vaccines Immunother ; 8: 2515135520967203, 2020.
Article in English | MEDLINE | ID: mdl-33681700

ABSTRACT

To ensure the effectiveness of increasingly complex immunization programs in upper-middle and high-income settings, comprehensive information systems are needed to track immunization uptake at individual and population levels. The maturity of cloud systems and mobile technologies has created new possibilities for immunization information systems. In this paper, we describe a vision for the next generation of digital immunization information systems for upper-middle and high-income settings based on our experience in Canada. These systems center on the premise that the public is engaged and informed about the immunization process beyond their interaction with primary care, and that they will be a contributor and auditor of immunization data. The digital immunization system of the future will facilitate reporting of adverse events following immunization, issue digital immunization receipts, permit identification of areas of need and allow for delivery of interventions targeting these areas. Through features like immunization reminders and targeted immunization promotion campaigns, the system will reduce many of the known barriers that influence immunization rates. In light of the global COVID-19 pandemic, adaptive digital public health information systems will be required to guide the rollout and post-market surveillance of the SARS-CoV-2 vaccine.

13.
Am J Med ; 132(5): 567-571, 2019 05.
Article in English | MEDLINE | ID: mdl-30550756

ABSTRACT

The maternal cardiovascular system undergoes profound changes to support the increasing demands of fetal growth during pregnancy. An accumulating body of evidence has shown that common pregnancy complications, including gestational diabetes mellitus, preeclampsia, low birth weight, and preterm delivery, can be associated with future cardiovascular adverse events in mothers. Factors such as glucose metabolism, hyperlipidemia, inflammatory markers, and large- and small-vessel stiffness/functionality have been linked with these pregnancy conditions. Critically, there are no established guidelines to account for these maternal factors when considering future cardiovascular disease risk, one of the leading causes of female mortality. This article reviews the study of cardiovascular disease and pregnancy, and proposes possible connections that should spur future investigation in an area of medicine that requires significant research.


Subject(s)
Cardiovascular Diseases , Pregnancy Complications , Reproductive History , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Female , Humans , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications/metabolism , Pregnancy Complications/physiopathology , Risk Assessment , Risk Factors
14.
Sci Adv ; 4(6): eaap8030, 2018 06.
Article in English | MEDLINE | ID: mdl-29963620

ABSTRACT

In the healthy kidney, specialized cells called podocytes form a sophisticated blood filtration apparatus that allows excretion of wastes and excess fluid from the blood while preventing loss of proteins such as albumin. To operate effectively, this filter is under substantial hydrostatic mechanical pressure. Given their function, it is expected that the ability to apply mechanical force is crucial to the survival of podocytes. However, to date, podocyte mechanobiology remains poorly understood, largely because of a lack of experimental data on the forces involved. We perform quantitative, continuous, nondisruptive, and high-resolution measurements of the forces exerted by differentiated podocytes in real time using a recently introduced functional imaging modality for continuous force mapping. Using an accepted model for podocyte injury, we find that injured podocytes experience near-complete loss of cellular force transmission but that this loss of force is reversible under certain conditions. The observed changes in force correlate with F-actin rearrangement and reduced expression of podocyte-specific proteins. By introducing robust and high-throughput mechanical phenotyping and by demonstrating the significance of mechanical forces in podocyte injury, this research paves the way to a new level of understanding of the kidney. In addition, in an advance over established force mapping techniques, we integrate cellular force measurements with immunofluorescence and perform continuous long-term force measurements of a cell population. Hence, our approach has general applicability to a wide range of biomedical questions involving mechanical forces.


Subject(s)
Biomarkers , Biomechanical Phenomena , Mechanotransduction, Cellular , Podocytes/metabolism , Animals , Cell Differentiation , Cytoskeleton/metabolism , Fluorescent Antibody Technique , Humans , Mice , Phenotype , Podocytes/cytology , Stress, Physiological
15.
J Burn Care Res ; 39(1): 141-147, 2018 01 01.
Article in English | MEDLINE | ID: mdl-28368918

ABSTRACT

Daily burn wound care for nonintubated patients involves administration of intravenous analgesic and sedation agents. Vital signs and oxygen saturation monitoring alone can result in late signs of oversedation and ineffective breathing. End-tidal carbon dioxide (EtCo2) monitoring provides immediate feedback of effective breathing during procedural sedation. The purpose of this study was to describe the nurse's sedation and analgesic therapy management of nonintubated patients during burn wound care when EtCo2 was used. This IRB approved study involved observing 22 burn nurses and 4 burn technicians during burn wound care of nonintubated patients. This descriptive, observational study compared adverse breathing/airway events, pain measurements, and sedation effectiveness, before and after introducing EtCo2 monitoring. Patients observed in this study were similar in age, type and size of burn, and use of recreational substances. Nurses and technicians also had similar burn experience. No statistically significant findings were found in this study; however, nurses in practice longer were found to apply oxygen sooner, which prevented decreased oxygen saturation events. When EtCo2 was used, less analgesia and sedation were required to maintain patient comfort. Time required for burn wound care was reduced by 22%, and 30% less overall analgesic and sedation agent dosages were administered after the introduction of EtCo2 monitoring. EtCo2 was found to enhance nurses' assessment of patients' response to intravenous analgesia and sedation effectiveness during burn wound care for nonintubated patients. Nurses with greater experience used oxygen sooner in the procedure, and patients had fewer decreases in SpO2.


Subject(s)
Burns/therapy , Capnography , Carbon Dioxide/metabolism , Respiratory Insufficiency/diagnosis , Adult , Aged , Analgesics/therapeutic use , Burns/complications , Female , Humans , Hypnotics and Sedatives/therapeutic use , Male , Middle Aged , Monitoring, Physiologic , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Tidal Volume , Young Adult
16.
NPJ Digit Med ; 1: 46, 2018.
Article in English | MEDLINE | ID: mdl-31304326

ABSTRACT

Mobile health (mHealth) technology is increasingly being used, but academic evaluations supporting its use are not keeping pace. This is partly due to the disconnect between the traditional pharmaceutical approach to product evaluation, with its incremental approach, and the flexible way in which mHealth products are developed. An important step to addressing these problems lies in establishing agile research methods that complement the agile development methodologies used to create modern digital health applications. We describe an mHealth research model that mirrors traditional clinical research methods in its attention to safety and efficacy, while also accommodating the rapid and iterative development and evaluation required to produce effective, evidence-based, and sustainable digital products. This approach consists of a project identification stage followed by four phases of clinical evaluation: Phase 1: User Experience Design, Development, & Alpha Testing; Phase 2: Beta testing; Phase 3: Clinical Trial Evaluation; and Phase 4: Post-Market Surveillance. These phases include sample gating questions and are adapted to accommodate the unique nature of digital product development.

17.
Healthc Q ; 20(3): 41-46, 2017.
Article in English | MEDLINE | ID: mdl-29132449

ABSTRACT

Medicine is experiencing a paradigm shift, where patients are increasingly involved in the management of their health data. We created a mobile app which permitted parental reporting of immunization status to public health authorities. We describe app use as a proxy for feasibility and acceptability as well as data utility for public health surveillance. The evaluation period ran from April 27, 2015, to April 18, 2017, during which time 2,653 unique children's records were transmitted, containing 36,105 vaccinations. Our findings suggest that mobile immunization reporting is feasible and may be an acceptable complement to existing reporting methods. Measures of data utility suggest that mobile reporting could enable more accurate assessments of vaccine coverage.


Subject(s)
Electronic Health Records/organization & administration , Mobile Applications/statistics & numerical data , Vaccines/administration & dosage , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Local Government , Male , Ontario , Parents , Quality Assurance, Health Care , Registries , Vaccination
18.
Int J Circumpolar Health ; 76(1): 1358566, 2017.
Article in English | MEDLINE | ID: mdl-28782441

ABSTRACT

Despite the best efforts of local healthcare workers and health officials, Nunavut, a large geographical region in Northern Canada, has struggled with outbreaks of vaccine-preventable diseases (VPD). We contend that the implementation of an immunisation information system (IIS) could strengthen prevention and response efforts to this and future outbreaks of vaccine-preventable diseases. Developing an IIS in Nunavut that builds on the existing CANImmunize infrastructure would reduce the cost and complexity of developing a new IIS, and allow Nunavut to benefit from the ongoing efforts to secure data on the CANImmunize platform. Such a system would enable the identification of individuals and subpopulations at highest risk of infection based on vaccine series completion and permit the exploration of the underlying causes of outbreaks in the territory through consideration of demographic and temporal factors. Confirmed high rates of vaccination in the context of an outbreak would indicate potential issues with vaccine efficacy while low rates of vaccination would suggest that efforts should be devoted to increasing vaccine coverage. This approach could also lay the foundation for infrastructure expansion to other remote and/or Indigenous communities where geographical and accessibility issues complicate health care utilisation and monitoring, both in Canada and internationally.


Subject(s)
Information Systems/organization & administration , Mobile Applications , Public Health Surveillance/methods , Vaccination Coverage , Arctic Regions , Canada , Computer Security , Confidentiality , Cultural Competency , Humans , Information Systems/standards , Nunavut , Time Factors
19.
J Med Syst ; 41(4): 57, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28247303

ABSTRACT

Collection of timely and accurate immunization information is essential for effective immunization programs. Current immunization information systems have important limitations that impact the ability to collect this data. Based on our experience releasing a national immunization app we describe a cloud-based platform that would allow individuals to store their records digitally and exchange these records with public health information systems thus improving the quality of immunization information held by individuals and public health officials.


Subject(s)
Cloud Computing , Electronic Health Records , Mobile Applications , Vaccination , Computer Security , Health Information Exchange , Humans , Information Systems/organization & administration
20.
Stapp Car Crash J ; 61: 175-209, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29394439

ABSTRACT

Improving injury prediction accuracy and fidelity for mounted Warfighters has become an area of focus for the U.S. military in response to improvised explosive device (IED) use in both Iraq and Afghanistan. Although the Hybrid III anthropomorphic test device (ATD) has historically been used for crew injury analysis, it is only capable of predicting a few select skeletal injuries. The Computational Anthropomorphic Virtual Experiment Man (CAVEMAN) human body model is being developed to expand the injury analysis capability to both skeletal and soft tissues. The CAVEMAN model is built upon the Zygote 50th percentile male human CAD model and uses a finite element modeling approach developed for high performance computing (HPC). The lower extremity subset of the CAVEMAN human body model presented herein includes: 28 bones, 26 muscles, 40 ligaments, fascia, cartilage and skin. Sensitivity studies have been conducted with the CAVEMAN lower extremity model to determine the structures critical for load transmission through the leg in the underbody blast (UBB) environment. An evaluation of the CAVEMAN lower extremity biofidelity was also carried out using 14 unique data sets derived by the Warrior Injury Assessment Manikin (WIAMan) program cadaveric lower leg testing. Extension of the CAVEMAN lower extremity model into anatomical tissue failure will provide additional injury prediction capabilities, beyond what is currently achievable using ATDs, to improve occupant survivability analyses within military vehicles.


Subject(s)
Blast Injuries , Computer Simulation , Explosions , Leg Injuries , War-Related Injuries , Acceleration , Biomechanical Phenomena , Cadaver , Finite Element Analysis , Humans , Lower Extremity , Male , Manikins , Military Personnel , Models, Biological , Weight-Bearing
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