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1.
Can Pharm J (Ott) ; 157(4): 190-199, 2024.
Article in English | MEDLINE | ID: mdl-39092087

ABSTRACT

Importance: We designed an online educational program for primary care health care providers, the Hypertension Canada Professional Certification Program (HC-PCP), based upon its 2020 guidelines. Objective: The objective was to determine the effect of the HC-PCP, taken by pharmacists, on systolic blood pressure (BP) in patients with poorly controlled hypertension. Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy). Participants: Patients with poorly controlled hypertension (BP >140/90 mmHg or >130/80 mmHg [diabetes]) in community pharmacies in Alberta, Canada, were recruited by their pharmacist. Intervention: Pharmacists completed the HC-PCP program, then provided care to their patients with poorly controlled hypertension according to what they learned in the course. Control: Pharmacists were given a copy of the Hypertension Canada guidelines and provided their usual care to their patients prior to undertaking the HC-PCP later. Main outcome and measure: The primary outcome was a difference in change in systolic BP at 3 months between groups, while the secondary outcome was patient satisfaction with using the Consultation Satisfaction Questionnaire. Results: We enrolled 890 patients from 59 pharmacies (including 104 pharmacists). Using a linear mixed-effect model with BP reduction as the dependent variable and independent variables of treatment allocation, baseline BP, site effect and patient effect, the intervention was associated with a 4.76 mmHg (95% confidence interval, 2.02-7.50, p < 0.0001) systolic BP reduction at 3 months. Patient satisfaction with using the Consultation Satisfaction Questionnaire was high at 75.9 (/90). Conclusion and relevance: Most educational programs are not evaluated at the patient care level. The HC-PCP taken by pharmacists resulted in a 4.76 mmHg systolic BP reduction in their patients over 3 months. This would have major implications for public health, reducing heart disease, stroke and kidney failure.

2.
Front Cardiovasc Med ; 11: 1365798, 2024.
Article in English | MEDLINE | ID: mdl-39011493

ABSTRACT

Right ventricle (RV) failure is a common complication of many cardiopulmonary diseases. Since it has a significant adverse impact on prognosis, precise determination of RV function is crucial to guide clinical management. However, accurate assessment of RV function remains challenging owing to the difficulties in acquiring its intricate pathophysiology and imaging its complex anatomical structure. In addition, there is historical attention focused exclusively on the left ventricle assessment, which has led to overshadowing and delayed development of RV evaluation. Echocardiography is the first-line and non-invasive bedside clinical tool for assessing RV function. Tricuspid annular plane systolic excursion (TAPSE), RV systolic tissue Doppler velocity of the tricuspid annulus (RV S'), and RV fractional area change (RV FAC) are conventional standard indices routinely used for RV function assessment, but accuracy has been subject to several limitations, such as load-dependency, angle-dependency, and localized regional assessment. Particularly, load dependency is a vexing issue, as the failing RV is always in a complex loading condition, which alters the values of echocardiographic parameters and confuses clinicians. Recently, novel echocardiographic methods for improved RV assessment have been developed. Specifically, "strain", "RV-pulmonary arterial (PA) coupling", and "RV myocardial work" are newly applied methods for RV function assessment, a few of which are designed to surmount the load dependency by taking into account the afterload on RV. In this narrative review, we summarize the latest data on these novel RV echocardiographic parameters and highlight their strengths and limitations. Since load independency is one of the primary advantages of these, we particularly emphasize this aspect.

3.
J Extracell Vesicles ; 13(7): e12469, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965984

ABSTRACT

Extracellular vesicles (EVs) play key roles in diverse biological processes, transport biomolecules between cells and have been engineered for therapeutic applications. A useful EV bioengineering strategy is to express engineered proteins on the EV surface to confer targeting, bioactivity and other properties. Measuring how incorporation varies across a population of EVs is important for characterising such materials and understanding their function, yet it remains challenging to quantitatively characterise the absolute number of engineered proteins incorporated at single-EV resolution. To address these needs, we developed a HaloTag-based characterisation platform in which dyes or other synthetic species can be covalently and stoichiometrically attached to engineered proteins on the EV surface. To evaluate this system, we employed several orthogonal quantification methods, including flow cytometry and fluorescence microscopy, and found that HaloTag-mediated quantification is generally robust across EV analysis methods. We compared HaloTag-labelling to antibody-labelling of EVs using single vesicle flow cytometry, enabling us to measure the substantial degree to which antibody labelling can underestimate proteins present on an EV. Finally, we demonstrate the use of HaloTag to compare between protein designs for EV bioengineering. Overall, the HaloTag system is a useful EV characterisation tool which complements and expands existing methods.


Subject(s)
Extracellular Vesicles , Flow Cytometry , Extracellular Vesicles/metabolism , Humans , Flow Cytometry/methods , Protein Engineering/methods , Microscopy, Fluorescence/methods , Bioengineering/methods
4.
Int J Cardiol ; 413: 132371, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39047795

ABSTRACT

BACKGROUND: The LATE score (LATE: Left Atrial reservoir strain (LASr), Tricuspid regurgitation maximum velocity (TR Vmax), and E/e' average) is a novel framework for echocardiographic assessment of left ventricular filling pressure (LVFP). LATE = 0 indicates normal LVFP. LATE = 1 indicates resting LVFP is borderline elevated, and the patient may be at risk of pathological elevation of LVFP during exertion. LATE ≥2 indicates LVFP is severely elevated. METHODS: The LATE score was derived from reported thresholds of LASr and conventional echocardiographic parameters for predicting LVFP. The LATE score was prospectively evaluated in a cross-sectional study of 63 patients undergoing transthoracic echocardiography immediately prior to cardiac catheterization with invasive assessment of LVFP. Accuracy of the LATE score was compared to 2016 ASE diastology algorithms. RESULTS: Mean patient age was 62.9 ± 13.6 years with 22% female. LATE = 0 in 29 patients, of which 24 (83%) had normal LVFP (mean LVFP 9 mmHg, SD ±3 mmHg). LATE = 1 in 23 patients, of which 11 (48%) had elevated LVFP (mean LVFP 12 mmHg, SD ± 4 mmHg). LATE was ≥2 in 11 patients, all of which had elevated LVFP (100%) (mean LVFP 16 mmHg, SD ±3 mmHg). The LATE score showed greater agreement with invasive assessment than the 2016 algorithms (LATE kappa = 0.73, 2016 kappa = 0.37). CONCLUSIONS: The LATE score is a simple and effective tool for evaluation of LVFP that is more accurate than the 2016 algorithms. The LATE score provides insight beyond binary classification of normal versus elevated LVFP.

6.
Eur J Clin Invest ; : e14259, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845111

ABSTRACT

BACKGROUND: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload-independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non-invasive echocardiographic parameter, Pressure-Strain Product (PSP), as a potential surrogate of catheter-based LVSWI. This study aimed to investigate if PSP could correlate with catheter-based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post-transplant hearts was also evaluated. METHODS: Thirty-one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter-based LVSWI were simultaneously measured at 8-timepoints during 24-h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6-h observation after heart transplantation. RESULTS: In BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut-off point; mean value of complex 1,2 O2 Flux) in post-transplant hearts, which was greater than other echocardiographic parameters. CONCLUSIONS: PSPcirc could be used as a surrogate of catheter-based LVSWI reflecting mitochondrial function.

7.
Eur J Clin Invest ; : e14263, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849326

ABSTRACT

BACKGROUND: Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non-invasively measuring these parameters during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure-Strain Product (PSP), a novel speckle-tracking echocardiography parameter, (1) can correlate with pressure-volume catheter-based LVSWI and CPI, and (2) can be load-independent during the flow modification of V-A ECMO. METHODS: Nine Dorset-cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V-A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24-h observation, echocardiographic parameters as well as pressure-volume catheter-based LVSWI and CPI were simultaneously measured with X and following X-1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively. RESULTS: PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure-volume catheter-based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558). CONCLUSIONS: A novel echocardiographic parameter, PSP, may non-invasively predict pressure-volume catheter-based LVSWI and CPI in a load-independent manner in a cardiogenic shock supported by V-A ECMO.

9.
Eur J Cell Biol ; 103(2): 151414, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38640594

ABSTRACT

The RAS isoforms (KRAS, HRAS and NRAS) have distinct cancer type-specific profiles. NRAS mutations are the second most prevalent RAS mutations in skin and hematological malignancies. Although RAS proteins were considered undruggable for decades, isoform and mutation-specific investigations have produced successful RAS inhibitors that are either specific to certain mutants, isoforms (pan-KRAS) or target all RAS proteins (pan-RAS). While extensive structural and biochemical investigations have focused mainly on K- and H-RAS mutations, NRAS mutations have received less attention, and the most prevalent NRAS mutations in human cancers, Q61K and Q61R, are rare in K- and H-RAS. This manuscript presents a crystal structure of the NRAS Q61K mutant in the GTP-bound form. Our structure reveals a previously unseen pocket near switch II induced by the binding of a ligand to the active form of the protein. This observation reveals a binding site that can potentially be exploited for development of inhibitors against mutant NRAS. Furthermore, the well-resolved catalytic site of this GTPase bound to native GTP provides insight into the stalled GTP hydrolysis observed for NRAS-Q61K.


Subject(s)
GTP Phosphohydrolases , Guanosine Triphosphate , Membrane Proteins , GTP Phosphohydrolases/metabolism , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/chemistry , Membrane Proteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/chemistry , Humans , Guanosine Triphosphate/metabolism , Crystallography, X-Ray , Ligands , Mutation , Models, Molecular
11.
Jpn J Ophthalmol ; 68(3): 174-182, 2024 May.
Article in English | MEDLINE | ID: mdl-38658452

ABSTRACT

PURPOSE: To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex. STUDY DESIGN: A cross-sectional study. METHODS: A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group. RESULTS: The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (ß = -0.37, p = 0.002; ß = -1.22, p = 0.03) and deep retinal vessel density, respectively (ß = -0.66, p < 0.001; ß = -1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (ß = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (ß = -0.50, p = 0.003). CONCLUSIONS: This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences.


Subject(s)
Fluorescein Angiography , Macula Lutea , Retinal Vessels , Tomography, Optical Coherence , Humans , Male , Cross-Sectional Studies , Female , Tomography, Optical Coherence/methods , Retinal Vessels/diagnostic imaging , Middle Aged , Fluorescein Angiography/methods , Sex Factors , Macula Lutea/blood supply , Macula Lutea/diagnostic imaging , Fundus Oculi , Aged , Adult , Risk Factors , Body Mass Index , Microvascular Density , Population Surveillance , Retrospective Studies
12.
Rheumatol Ther ; 11(3): 563-582, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38467912

ABSTRACT

INTRODUCTION: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA. METHODS: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events. RESULTS: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports. CONCLUSION: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile. TRIAL REGISTRATION: NCT04574492.

13.
J Rheumatol ; 51(5): 479-487, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38359937

ABSTRACT

OBJECTIVE: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA. METHODS: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies. RESULTS: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East. CONCLUSION: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment.


Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , Registries , Severity of Illness Index , Humans , Arthritis, Psoriatic/drug therapy , Male , Female , Middle Aged , Canada , Retrospective Studies , Adult , Antirheumatic Agents/therapeutic use , Aged , Treatment Outcome , Cost of Illness
14.
CJC Open ; 6(1): 54-56, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38313341

ABSTRACT

Background: Measurement of home blood pressure is an important tool for the management of hypertension. However, the validity of home devices is of concern. The Recommended Blood Pressure Devices Program of Hypertension Canada reviews and recommends blood pressure devices using international validation standards. We sought to determine the proportion of Hypertension Canada-recommended devices available for purchase in pharmacies and online. Methods: We visited 16 community pharmacies in the Edmonton area to record the blood pressure devices they sold. We also reviewed the 50 most popular devices from online retailers (Amazon, Walmart, Best Buy, and Canadian Tire). All devices were referenced against the Recommended Blood Pressure Device Program of Hypertension Canada (www.hypertension.ca/bpdevices) to determine if the models were recommended. Results: We reviewed 170 devices. Of those sold in pharmacies, 61 of 68 (89.7%) were Hypertension Canada-recommended devices, whereas online retailers had only 46 of 102 (45.1%) recommended devices; P < 0.001. Conclusions: Most blood pressure devices sold in pharmacies are Hypertension Canada recommended, in contrast to less than one-half from online retailers. The lack of validation of many home blood pressure devices could have important clinical implications, leading to over- or undertreatment of hypertension. Clinicians should advise patients on the importance of home blood pressure device validation and direct them to resources such as Hypertension Canada (https://hypertension.ca/public/recommended-devices) for guidance.


Contexte: La mesure de la pression artérielle au domicile est un outil important dans la prise en charge de l'hypertension. Or, il semble que les appareils utilisés à la maison à cette fin ne soient pas toujours des dispositifs validés. Dans le cadre de son Programme de recommandation d'appareils de mesure de la pression artérielle, Hypertension Canada analyse et recommande des tensiomètres selon des normes de validation internationales. Nous avons donc cherché à déterminer la proportion des tensiomètres recommandés par Hypertension Canada qu'il est possible d'acheter dans les pharmacies et en ligne. Méthodologie: Nous avons rendu visite à 16 pharmacies communautaires dans la région d'Edmonton pour recenser les tensiomètres qui y étaient vendus. Nous avons également analysé les 50 tensiomètres les plus vendus par des détaillants en ligne (Amazon, Walmart, Best Buy et Canadian Tire). Nous avons vérifié si chacun des modèles faisait partie de la liste des appareils recommandés par Hypertension Canada (www.hypertension.ca/bpdevices). Résultats: Nous avons passé en revue 170 appareils. Dans les pharmacies, 61 appareils sur 68 (89,7 %) étaient recommandés par Hypertension Canada, alors qu'en ligne, cette proportion n'était que de 46 sur 102 (45,1 %); p < 0,001. Conclusions: La plupart des tensiomètres vendus dans les pharmacies sont recommandés par Hypertension Canada, contrairement à moins de la moitié de ceux qui sont vendus en ligne. L'absence de validation pour de nombreux tensiomètres pourrait avoir d'importantes conséquences cliniques, menant à un traitement excessif ou insuffisant de l'hypertension. Les cliniciens doivent informer les patients de l'importance d'utiliser un tensiomètre validé à la maison et les orienter vers des ressources comme Hypertension Canada (https://hypertension.ca/public/recommended-devices) pour guider leur choix.

15.
Curr Cardiol Rev ; 20(2): 29-38, 2024.
Article in English | MEDLINE | ID: mdl-38284706

ABSTRACT

BACKGROUND: Heart failure is a clinical condition with high mortality and morbidity that occurs when the heart is unable to pump enough blood to meet the metabolic demands of the body. The pharmacological management of heart failure has been revolutionized over the past decade with novel treatments. OBJECTIVE: The aim of the review is to highlight the recent pharmacological advances in the management of heart failure. RESULTS: Sodium-glucose cotransporter-2 inhibitor (SGLT2i), iron carboxymaltose, finerenone, omecamtiv mecarbil, and vericiguat have been shown to reduce hospitalization for heart failure. However, only SGLT2i, vericiguat, and omecamtiv mecarbil have been shown to reduce cardiovascular death. Finerenone has been shown to reduce cardiovascular events and renal adverse outcomes in patients with diabetes and kidney disease. Currently, only SGLT2i has been studied in patients beyond the heart failure with reduced ejection fraction population. CONCLUSION: The current quadruple therapy in the treatment of heart failure has demonstrated a reduction in the hospitalization of patients and a decrease in mortality associated with the condition. Individualized heart failure therapy research have shown some benefit in select heart failure patients. Further research on novel therapies will help improve heart failure patient outcomes.


Subject(s)
Heart Failure , Humans , Glucosides/therapeutic use , Heart Failure/drug therapy , Heterocyclic Compounds, 2-Ring , Naphthyridines , Pyrimidines , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Spironolactone/therapeutic use , Urea/therapeutic use , Urea/analogs & derivatives
16.
Nanoscale ; 16(5): 2409-2418, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38230506

ABSTRACT

The single-chain physics of bottlebrush polymers plays a key role in their macroscopic properties. Although efforts have been made to understand the behavior of single isolated bottlebrushes, studies on their behavior in crowded, application-relevant environments have been insufficient due to limitations in characterization techniques. Here, we use single-molecule localization microscopy (SMLM) to study the conformations of individual bottlebrush polymers by direct imaging. Our previous work focused on bottlebrushes in a matrix of linear polymers, where our observations suggested that their behavior was largely influenced by an entropic incompatibility between the bottlebrush side chains and the linear matrix. Instead, here we focus on systems where this effect is reduced: in solvent-swollen polymer materials and in systems entirely composed of bottlebrushes. We measure chain conformations and rigidity using persistence length (lp) as side chain molecular weight (Msc) is varied. Compared to a system of linear polymers, we observe greater flexibility of the backbone in both systems. For bottlebrushes in bottlebrush matrices, we additionally observed a scaling relationship between lp and Msc that more closely follows theoretical predictions. For the more flexible chains in both systems, we reach the edge of our resolution limit and cannot visualize the entire contour of every chain. We bypass this limitation by discussing the aspect ratios of the features within the super-resolution images.

17.
Eur J Clin Invest ; 54(2): e14106, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37822060

ABSTRACT

BACKGROUND: Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. METHODS: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). RESULTS: PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. CONCLUSIONS: A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.


Subject(s)
Cardiomyopathies , Respiratory Distress Syndrome , Sepsis , Stroke , Ventricular Dysfunction, Left , Animals , Sheep , Echocardiography , Stroke Volume , Ventricular Function, Left , Lactates , Ventricular Dysfunction, Left/diagnostic imaging
18.
bioRxiv ; 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37808729

ABSTRACT

Extracellular vesicles (EVs) play key roles in diverse biological processes, transport biomolecules between cells, and have been engineered for therapeutic applications. A useful EV bioengineering strategy is to express engineered proteins on the EV surface to confer targeting, bioactivity, and other properties. Measuring how incorporation varies across a population of EVs is important for characterizing such materials and understanding their function, yet it remains challenging to quantitatively characterize the absolute number of engineered proteins incorporated at single-EV resolution. To address these needs, we developed a HaloTag-based characterization platform in which dyes or other synthetic species can be covalently and stoichiometrically attached to engineered proteins on the EV surface. To evaluate this system, we employed several orthogonal quantification methods, including flow cytometry and fluorescence microscopy, and found that HaloTag-mediated quantification is generally robust across EV analysis methods. We compared HaloTag-labeling to antibody-labeling of EVs using single vesicle flow cytometry, enabling us to quantify the substantial degree to which antibody labeling can underestimate the absolute number of proteins present on an EV. Finally, we demonstrate use of HaloTag to compare between protein designs for EV bioengineering. Overall, the HaloTag system is a useful EV characterization tool which complements and expands existing methods.

19.
Echocardiography ; 40(11): 1251-1258, 2023 11.
Article in English | MEDLINE | ID: mdl-37855213

ABSTRACT

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Coronary Artery Disease/diagnostic imaging , Computed Tomography Angiography , Echocardiography/methods , Tomography, X-Ray Computed/methods , Predictive Value of Tests , Coronary Angiography/methods
20.
Data Brief ; 51: 109653, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37869625

ABSTRACT

This article presents a dataset comprising signal data collected from Inertial Measurement Unit (IMU) sensors during the administration of the Time Up and Go (TUG) test for assessing fall risk in older adults. The dataset is divided into two main sections. The first section contains personal, behavioral, and health-related data from 34 participants. The second section contains signal data from tri-axial acceleration and tri-axial gyroscope sensors embedded in an IMU sensor, which was affixed to the participants' waist area to capture signal data while they walked. The chosen assessment method for fall risk analysis is the TUG test, requiring participants to walk a 3-meter distance back and forth. To prepare the dataset for subsequent analysis, the raw signal data underwent processing to extract only the walking periods during the TUG test. Additionally, a low-pass filter technique was employed to reduce noise interference. This dataset holds the potential for the development of effective models for fall risk detection based on insights garnered from questionnaires administered to specialists who observed the experiments. The dataset also contains anonymized participant information that can be explored to investigate fall risk, along with other health-related conditions or behaviors that could influence the risk of falling. This information is invaluable for devising tailored treatment or rehabilitation plans for individual older adults. The complete dataset is accessible through the Mendeley repository."

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