The soybean Rpp3 gene encodes a TIR-NBS-LRR protein that confers resistance to Phakopsora pachyrhizi.

Soybean rust is an economically significant disease caused by the fungus Phakopsora pachyrhizi that negatively impacts soybean (Glycine max (L.) Merr.) production throughout the world. Susceptible plants infected by P. pachyrhizi develop tan-colored lesions on the leaf surface that give rise to funnel-shaped uredinia as the disease progresses. While most soybean germplasm is susceptible, seven genetic loci (Rpp1 to Rpp7) that provide race-specific resistance to P. pachyrhizi (Rpp) have been identified. Rpp3 was first discovered and characterized in the soybean accession PI 462312 (Ankur), and it was also determined to be one of two Rpp genes present in PI 506764 (Hyuuga). Genetic crosses with PI 506764 were later used to fine-map the Rpp3 locus to a 371 kb region on chromosome 6. The corresponding region in the susceptible Williams 82 (Wm82) reference genome contains several homologous nucleotide binding site-leucine rich repeat (NBS-LRR) genes. To identify Rpp3, we designed oligonucleotide primers to amplify Rpp3 candidate (Rpp3C) NBS-LRR genes at this locus from PI 462312, PI 506764, and Wm82 using polymerase chain reaction (PCR). Five Rpp3C genes were identified in both Rpp3-resistant soybean lines, and co-silencing these genes compromised resistance to P. pachyrhizi. Gene expression analysis and sequence comparisons of the Rpp3C genes in PI 462312 and PI 506764 suggest that a single candidate gene, Rpp3C3, is responsible for Rpp3-mediated resistance.

GmGLU1 and GmRR4 contribute to iron deficiency tolerance in soybean.

Iron deficiency chlorosis (IDC) is a form of abiotic stress that negatively impacts soybean yield. In a previous study, we demonstrated that the historical IDC quantitative trait locus (QTL) on soybean chromosome Gm03 was composed of four distinct linkage blocks, each containing candidate genes for IDC tolerance. Here, we take advantage of virus-induced gene silencing (VIGS) to validate the function of three high-priority candidate genes, each corresponding to a different linkage block in the Gm03 IDC QTL. We built three single-gene constructs to target GmGLU1 (GLUTAMATE SYNTHASE 1, Glyma.03G128300), GmRR4 (RESPONSE REGULATOR 4, Glyma.03G130000), and GmbHLH38 (beta Helix Loop Helix 38, Glyma.03G130400 and Glyma.03G130600). Given the polygenic nature of the iron stress tolerance trait, we also silenced the genes in combination. We built two constructs targeting GmRR4+GmGLU1 and GmbHLH38+GmGLU1. All constructs were tested on the iron-efficient soybean genotype Clark grown in iron-sufficient conditions. We observed significant decreases in soil plant analysis development (SPAD) measurements using the GmGLU1 construct and both double constructs, with potential additive effects in the GmRR4+GmGLU1 construct. Whole genome expression analyses (RNA-seq) revealed a wide range of affected processes including known iron stress responses, defense and hormone signaling, photosynthesis, and cell wall structure. These findings highlight the importance of GmGLU1 in soybean iron stress responses and provide evidence that IDC is truly a polygenic trait, with multiple genes within the QTL contributing to IDC tolerance. Finally, we conducted BLAST analyses to demonstrate that the Gm03 IDC QTL is syntenic across a broad range of plant species.

Women's Heart Health and the Menopausal Transition: Two Faces of the Same Coin.

The impact of the presence or absence of sex hormones on women's health is woefully underresearched. Fundamentally, women's bodies are now understood to spend considerable time under widely fluctuating hormonal influences, including puberty, pregnancy, peripartum, and menopause, and a woman's vessels are therefore preset for functional and physiological alterations based on levels of sex hormones. However, our understanding of the influences of sex hormones on the regulation of a multitude of biological and physiological processes has not translated into the development and/or collection or analyses of data on therapeutic treatments and/or outcomes in the context of women's disease management.

Les effets sur la santé des femmes associés à la présence ou à l'absence d'hormones sexuelles ont fait l'objet de trop peu d'études. On sait essentiellement que les taux d'hormones fluctuent considérablement tout au long des étapes de la vie des femmes, qu'il s'agisse de la puberté, de la grossesse, de la période périnatale et de la ménopause, et que leurs vaisseaux sont en fait préréglés pour permettre diverses modifications fonctionnelles et physiologiques en fonction du taux d'hormones sexuelles. Cependant, notre compréhension de l'influence des hormones sexuelles sur la régulation d'une multitude de processus biologiques et physiologiques ne s'est pas traduite par la collecte et/ou l'analyse de données sur les traitements ou les résultats thérapeutiques dans le contexte de la prise en charge de diverses maladies chez les femmes.

The epidemic of immobility in hospitalized patients: How to get your patient up and moving.

The global population is ageing and with cardiovascular disease (CVD) prevalence also increasing, the face of the prototypical cardiology inpatient is changing, from a middle-aged man with cardiovascular risk factors, to an older adult with multimorbidity and frailty. Hospital care is inherently harmful, with immobilization and reliance on others causing functional decline to be the leading complication of hospitalization in older adults. It is imperative to reinvent hospital care, employing age-friendly health systems to maintain health and function in older adults, improving not only CVD outcomes, but patient-centered outcomes such as function and independence and preventing avoidable harms.

Pharmacist-Led Follow-Up Program for Rural Patients with Acute Coronary Syndrome: The PLURAL-ACS Pilot Program.

Background: Patients living in rural settings have poorer access to care and more frequent readmissions after treatment for acute coronary syndrome (ACS) than patients in urban settings. It is unclear what types of medication-related issues are encountered by this cohort and whether pharmacist-led care could resolve them. Objectives: To describe the issues related to cardiac medications encountered by rural patients after treatment for ACS and the impact of a pharmacist-led virtual follow-up pilot program in this population. Methods: A quality improvement initiative was developed whereby a cardiology pharmacist provided follow-up to post-ACS rural patients in Alberta, Canada, between March and May 2022. For each patient, the pharmacist identified and resolved cardiac medication-related issues through regular telephone visits over a 30-day period following hospital discharge. The primary outcome was the number of cardiac medication-related issues identified. Secondary outcomes included the types of medication-related issues identified and actions taken by the pharmacist to resolve them. Results: During the 15-week program, 40 patients received care, and 139 virtual visits were completed. The median time spent per visit was 60 (interquartile range [IQR] 50-80) minutes. In total, 255 cardiac medication-related issues (6 per patient, IQR 3.75-8.25) were identified, of which 233 (91%) were resolved by the pharmacist. Prescription errors, adverse effects, and drug therapy optimization were the most common issues identified on days 1, 10, and 30, respectively. The pharmacist commonly undertook patient counselling (n = 126, 54%) and medication prescribing (n = 63, 27%) to address medication-related issues. Conclusions: A substantial number of cardiac medication-related issues were identified and resolved through a pharmacist-led virtual follow-up program in rural post-ACS patients. These findings could assist in the development of future follow-up programs to improve care for this high-risk population.

Contexte: L'accès des patients vivant en milieu rural aux soins est plus difficile et leur réadmission plus fréquente après un traitement pour le syndrome coronarien aigu (SCA) que les patients vivant en milieu urbain. On ne sait pas exactement quels types de problèmes liés aux médicaments rencontre cette cohorte et si les soins dispensés par les pharmaciens pourraient les résoudre. Objectifs: Décrire les problèmes liés aux médicaments cardiaques que rencontrent les patients vivant en milieu rural après un traitement pour le SCA et les effets d'un programme pilote de suivi virtuel dirigé par un pharmacien dans cette population. Méthodes: Une initiative d'amélioration de la qualité a été développée dans le cadre de laquelle un pharmacien en cardiologie a assuré le suivi des patients vivant en milieu rural après un SCA en Alberta, au Canada, entre mars et mai 2022. Pour chaque patient, le pharmacien a identifié et résolu les problèmes liés aux médicaments cardiaques grâce à des visites téléphoniques régulières sur une période de 30 jours après le congé de l'hôpital. Le critère de jugement principal était le nombre de problèmes identifiés liés aux médicaments cardiaques. Les critères de jugement secondaires comprenaient les types de problèmes liés aux médicaments identifiés et les mesures prises par le pharmacien pour les résoudre. Résultats: Au cours du programme de 15 semaines, 40 patients ont reçu des soins et 139 visites virtuelles ont été réalisées. La durée médiane de chaque visite était de 60 minutes (intervalle interquartile [IQR] 50­80). Au total, 255 problèmes liés aux médicaments cardiaques (6 par patient, IQR 3,75­8,25) ont été identifiés, dont 233 (91 %) ont été résolus par le pharmacien. Les erreurs de prescription, les événements indésirables et l'optimisation du traitement médicamenteux étaient les problèmes les plus fréquents les jours 1, 10 et 30, respectivement. Le pharmacien offrait généralement du counseling aux patients (n = 126, 54 %) et prescrivait des médicaments (n = 63, 27 %) pour résoudre les problèmes liés aux médicaments. Conclusions: Un nombre important de problèmes liés aux médicaments cardiaques ont été identifiés et résolus grâce à un programme de suivi virtuel dirigé par un pharmacien chez les patients vivant en milieu rural après un SCA. Ces résultats pourraient aider à élaborer de futurs programmes de suivi pour améliorer les soins dans cette population à haut risque.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology 2023 Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Sex differences in post-operative outcomes following non-cardiac surgery.

It is uncertain whether sex is an independent risk factor for poor outcomes after non-cardiac surgery. We examined sex differences in short- and long-term mortality and morbidity in patients undergoing non-cardiac surgery in Alberta, Canada. Using linked administrative databases, we identified patients undergoing one of 45 different non-cardiac surgeries who were hospitalized between 2008 and 2019. Adjusted odds ratios (95% CI) were reported for mortality at 30-days, 6-months, and 1-year stratified by sex. Secondary outcomes including all-cause hospitalization, hospitalization for heart failure (HF), hospitalization for acute coronary syndrome (ACS), hospitalization for infection, hospitalization for stroke, and hospitalization for bleeding were also analyzed. Multivariate logistic regression was adjusted for age, sex, surgery type, the components of the Charlson Comorbidity Index, and the Revised Cardiac Risk Index. We identified 552,224 unique patients who underwent non-cardiac surgery of which 304,408 (55.1%) were female. Male sex was a predictor of mortality at 30-days (aOR 1.25 (1.14, 1.38), p<0.0001), 6-months (aOR 1.26 (1.20, 1.33), p<0.0001), and 1-year (aOR 1.25 (1.20, 1.31), p<0.0001). Similarly, male sex was a predictor of hospital readmission at 30-days (1.12 (1.09, 1.14), p<0.0001), 6-months (aOR 1.11 (1.10, 1.13), p<0.0001), and 1-year (aOR 1.06 (1.04, 1.07), p<0.0001). When the results were stratified by age, the effect of male sex on clinical outcome diminished for age ≥ 65years compared to younger patients. In conclusion, male patients undergoing non-cardiac surgery have higher risks of all-cause mortality and readmission after adjustment for baseline risk factor differences, particularly in those under 65-years-old. The overall incidence of readmission for stroke, bleeding, HF and ACS after non-cardiac surgery was low. The impact of male sex on clinical outcomes decreases with increasing age, suggesting the importance of considering the effect of both sex and age on clinical outcomes after non-cardiac surgery.

Change Management Accompanying Implementation of Decision Support for Prevention of Acute Kidney Injury in Cardiac Catheterization Units: Program Report.

Purpose of program: Different models exist to guide successful implementation of electronic health tools into clinical practice. The Contrast Reducing Injury Sustained by Kidneys (Contrast RISK) initiative introduced an electronic decision support tool with physician audit and feedback into all of the cardiac catheterization facilities in Alberta, Canada, with the goal of preventing contrast-associated acute kidney injury (CA-AKI) following coronary angiography and intervention. This report describes the change management approaches used by the initiative and end-user's feedback on these processes. Sources of information and methods: The Canada Health Infoway Change Management model was used to address 6 activities relevant to project implementation: governance and leadership, stakeholder engagement, communications, workflow analysis and integration, training and education, and monitoring and evaluation. Health care providers and invasive cardiologists from all sites completed preimplementation, usability, and postimplementation surveys to assess integration and change success. Key findings: Prior to implementation, 67% of health providers were less than satisfied with processes to determine appropriate contrast dye volumes, 47% were less than satisfied with processes for administering adequate intravenous fluids, and 68% were less than satisfied with processes to ensure follow-up of high-risk patients. 48% of invasive cardiologists were less than satisfied with preprocedural identification of patients at risk of acute kidney injury (AKI). Following implementation, there were significant increases among health providers in the odds of satisfaction with processes for identifying those at high risk of AKI (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.36-6.66, P = .007), quantifying the appropriate level of contrast dye for each patient (OR 6.98, 95% CI 3.06-15.91, P < .001), determining the optimal amount of IV fluid for each patient (OR 1.86, 95% CI 0.88-3.91, P = .102), and following up of kidney function of high risk patients (OR 5.49, 95%CI 2.45-12.30, P < .001). There were also significant increases among physicians in the odds of satisfaction with processes for identifying those at high risk of AKI (OR 19.53, 95% CI 3.21-118.76, P = .001), quantifying the appropriate level of contrast dye for each patient (OR 26.35, 95% CI 4.28-162.27, P < .001), and for following-up kidney function of high-risk patients (OR 7.72, 95% CI 1.62-36.84.30, P = .010). Eighty-nine percent of staff perceived the initiative as being successful in changing clinical practices to reduce the risk of CA-AKI. Physicians uniformly agreed that the system was well-integrated into existing workflows, while 42% of health providers also agreed. Implications: The Canada Health Infoway Change Management model was an effective framework for guiding implementation of an electronic decision support tool and audit and feedback intervention to improve processes for AKI prevention within cardiac catheterization units.

Objectif du program: Il existe différents modèles pour guider la mise en œuvre efficace d'outils électroniques dans la pratique clinique. L'initiative Contrast RISK (Contrast Reducing Injury Sustained by Kidneys) a permis d'introduire un outil électronique d'aide à la décision avec surveillance par le médecin et rétroaction dans tous les établissements de l'Alberta (Canada) pratiquant le cathétérisme cardiaque, dans le but de prévenir les insuffisances rénales aiguës associées aux produits de contraste (IRA-PC) après une coronarographie et une intervention. Le présent rapport décrit les approches de gestion du changement utilisées dans le cadre de l'initiative, ainsi que les commentaires des utilisateurs sur ces processus. Sources de l'information et méthodologie: Le modèle de gestion du changement d'Inforoute Santé du Canada a été employé pour aborder six activités pertinentes pour la mise en œuvre de projets: gouvernance et leadership, engagement des intervenants, communications, analyze du flux de travail et intégration, formation et éducation, surveillance et évaluation. Les prestataires de soins et les cardiologues spécialisés en interventions invasives de tous les sites ont répondu à un sondage avant, pendant et après la mise en œuvre afin d'évaluer le succès de l'intégration et du changement. Principaux résultats: Avant la mise en œuvre, 67% des prestataires de soins étaient insatisfaits des processus pour déterminer les volumes appropriés des produits de contraste, 47% étaient insatisfaits des processus pour administrer l'hydratation intraveineuse et 68% étaient insatisfaits des processus de surveillance des patients présentant un risque élevé. Près de la moitié (48%) des cardiologues spécialisés en interventions invasives étaient insatisfaits du processus d'identification préalable des patients présentant un risque élevé d'IRA. Après la mise en œuvre, on a observé une augmentation significative de la satisfaction des prestataires de soins à l'égard des processus pour identifier les patients présentant un risque élevé d'IRA (rapport de cote [RC]: 3,01; IC 95%: 1,36-6,66; P = .007), quantifier le niveau approprié de produit de contraste pour chaque patient (RC: 6,98; IC 95%: 3,06-15,91; P < .001), déterminer le volume optimal d'hydratation IV pour chaque patient (RC: 1,86, IC 95%: 0,88-3,91; P = .102) et surveiller la fonction rénale chez les patients présentant un risque élevé (RC: 5,49 IC 95%: 2,45-12,30; P < .001). On a également observé une augmentation significative de la satisfaction des médecins à l'égard des processus pour identifier les patients présentant un risque élevé d'IRA (RC: 19,53; IC 95%: 3,21-118,76; P = .001), quantifier le niveau approprié de produit de contraste pour chaque patient (RC: 26,35; IC 95%: 4,28-162,27; P < .001) et surveiller la fonction rénale des patients présentant un risque élevé (RC: 7,72; IC 95%: 1,62-36,84,30; P = .010). Une grande majorité du personnel (89%) était d'avis que l'initiative avait permis de changer les pratiques cliniques visant à réduire le risque d'IRA-PC. L'ensemble des médecins s'entendait pour dire que le système était bien intégré dans les flux de travail existants; 42% des prestataires de soins étaient également de cet avis. Conclusion: Le modèle de gestion du changement d'Inforoute Santé du Canada s'est avéré un cadre efficace pour guider la mise en œuvre d'un outil électronique d'aide à la décision et d'une intervention de surveillance et de rétroaction visant à améliorer les processus de prévention de l'IRA dans les unités de cathétérisme cardiaque.

Sex-Specific Differences in Potent P2Y12 Inhibitor Use in British Cardiovascular Intervention Society Registry STEMI Patients.

BACKGROUND: Sex-based outcome differences for women with ST-segment-elevation myocardial infarction (STEMI) have not been adequately addressed, and the role played by differences in prescription of potent P2Y12 inhibitors (P-P2Y12) is not well defined. This study explores the hypothesis that disparities in P-P2Y12 (prasugrel or ticagrelor) use may play a role in outcome disparities for women with STEMI. METHODS: Data from British Cardiovascular Intervention Society national percutaneous coronary intervention database were analyzed, and 168 818 STEMI patients treated with primary percutaneous coronary intervention from 2010 to 2020 were included. RESULTS: Among the included women (43 131; 25.54%) and men (125 687; 74.45%), P-P2Y12 inhibitors were prescribed less often to women (51.71%) than men (55.18%; P<0.001). Women were more likely to die in hospital than men (adjusted odds ratio, 1.213 [95% CI, 1.141-1.290]). Unadjusted mortality was higher among women treated with clopidogrel (7.57%), than P-P2Y12-treated women (5.39%), men treated with clopidogrel (4.60%), and P-P2Y12-treated men (3.61%; P<0.001). The strongest independent predictor of P-P2Y12 prescription was radial access (adjusted odds ratio, 2.368 [95% CI, 2.312-2.425]), used in 67.93% of women and 74.38% of men (P<0.001). Two risk adjustment models were used. Women were less likely to receive a P-P2Y12 (adjusted odds ratio, 0.957 [95% CI, 0.935-0.979]) with risk adjustment for baseline characteristics alone, when procedural factors including radial access were included in the model differences were not significant (adjusted odds ratio, 1.015 [95% CI, 0.991-1.039]). CONCLUSIONS: Women were less likely to be prescribed prasugrel or ticagrelor, were less likely to have radial access, and had a higher mortality when being treated for STEMI. Improving rates of P-P2Y12 use and radial access may decrease outcome disparities for women with STEMI.

Optical absorption spectra and corresponding in vivo photoacoustic visualization of exposed peripheral nerves.

Significance: Multispectral photoacoustic imaging has the potential to identify lipid-rich, myelinated nerve tissue in an interventional or surgical setting (e.g., to guide intraoperative decisions when exposing a nerve during reconstructive surgery by limiting operations to nerves needing repair, with no impact to healthy or regenerating nerves). Lipids have two optical absorption peaks within the NIR-II and NIR-III windows (i.e., 1000 to 1350 nm and 1550 to 1870 nm wavelength ranges, respectively) which can be exploited to obtain photoacoustic images. However, nerve visualization within the NIR-III window is more desirable due to higher lipid absorption peaks and a corresponding valley in the optical absorption of water. Aim: We present the first known optical absorption characterizations, photoacoustic spectral demonstrations, and histological validations to support in vivo photoacoustic nerve imaging in the NIR-III window. Approach: Four in vivo swine peripheral nerves were excised, and the optical absorption spectra of these fresh ex vivo nerves were characterized at wavelengths spanning 800 to 1880 nm, to provide the first known nerve optical absorbance spectra and to enable photoacoustic amplitude spectra characterization with the most optimal wavelength range. Prior to excision, the latter two of the four nerves were surrounded by aqueous, lipid-free, agarose blocks (i.e., 3% w/v agarose) to enhance acoustic coupling during in vivo multispectral photoacoustic imaging using the optimal NIR-III wavelengths (i.e., 1630 to 1850 nm) identified in the ex vivo studies. Results: There was a verified characteristic lipid absorption peak at 1725 nm for each ex vivo nerve. Results additionally suggest that the 1630 to 1850 nm wavelength range can successfully visualize and differentiate lipid-rich nerves from surrounding water-containing and lipid-deficient tissues and materials. Conclusions: Photoacoustic imaging using the optimal wavelengths identified and demonstrated for nerves holds promise for detection of myelination in exposed and isolated nerve tissue during a nerve repair surgery, with possible future implications for other surgeries and other optics-based technologies.

Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients a Prospective Observational Cohort Study.

OBJECTIVE: The objective of this study was to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described. METHODS: This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first 3 postoperative days. MINS was defined as a hsTnT of 20-65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (1) whether MINS is prognostically important in major general surgical patients, (2) the clinical characteristics of major general surgical patients with and without MINS, (3) the 30-day outcomes for major general surgical patients with and without MINS, and (4) the proportion of MINS that would have gone undetected without routine postoperative monitoring. RESULTS: The incidence of MINS in the major general surgical patients was 16.3% (95% CI, 15.3-17.4%). Thirty-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI, 5.1%-8.9%) in patients with MINS compared with 1.2% (95% CI, 0.9%-1.6%) in patients without MINS ( P <0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI, 3.0-7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (ie, no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI, 3.7%-7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI, 6.7%-15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI, 87.5-92.0). CONCLUSIONS: Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly 5-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Anticoagulation in type 2 myocardial infarctions: Lessons learned from the rivaroxaban in type 2 myocardial infarctions feasibility trial.

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment.

Preferences of Patients With Chronic Kidney Disease for Invasive Versus Conservative Treatment of Acute Coronary Syndrome: A Discrete Choice Experiment.

Background Patients with chronic kidney disease (CKD) can experience acute coronary syndromes (ACS) with high morbidity and mortality. Early invasive management of ACS is recommended for most high-risk patients; however, choosing between an early invasive versus conservative management approach may be influenced by the unique risk of kidney failure for patients with CKD. Methods and Results This discrete choice experiment measured the preferences of patients with CKD for future cardiovascular events versus acute kidney injury and kidney failure following invasive heart procedures for ACS. The discrete choice experiment, consisting of 8 choice tasks, was administered to adult patients attending 2 CKD clinics in Calgary, Alberta. The part-worth utilities of each attribute were determined using multinomial logit models, and preference heterogeneity was explored using latent class analysis. A total of 140 patients completed the discrete choice experiment. The mean age of patients was 64 years, 52% were male, and mean estimated glomerular filtration rate was 37 mL/min per 1.73 m2. Across the range of levels, risk of mortality was the most important attribute, followed by risk of end-stage kidney disease and risk of recurrent myocardial infarction. Latent class analysis identified 2 distinct preference groups. The largest group included 115 (83%) patients, who placed the greatest value on treatment benefits and expressed the strongest preference for reducing mortality. A second group of 25 (17%) patients was identified who were procedure averse and had a strong preference toward conservative management of ACS and avoiding acute kidney injury requiring dialysis. Conclusions The preferences of most patients with CKD for management of ACS were most influenced by lowering mortality. However, a distinct subgroup of patients was strongly averse to invasive management. This highlights the importance of clarifying patient preferences to ensure treatment decisions are aligned with patient values.

Virus induced gene silencing confirms oligogenic inheritance of brown stem rot resistance in soybean.

Brown Stem Rot (BSR), caused by the soil borne fungal pathogen Phialophora gregata, can reduce soybean yields by as much as 38%. Previous allelism studies identified three Resistant to brown stem Rot genes (Rbs1, Rbs2, and Rbs3), all mapping to large, overlapping regions on soybean chromosome 16. However, recent fine-mapping and genome wide association studies (GWAS) suggest Rbs1, Rbs2, and Rbs3 are alleles of a single Rbs locus. To address this conflict, we characterized the Rbs locus using the Williams82 reference genome (Wm82.a4.v1). We identified 120 Receptor-Like Proteins (RLPs), with hallmarks of disease resistance receptor-like proteins (RLPs), which formed five distinct clusters. We developed virus induced gene silencing (VIGS) constructs to target each of the clusters, hypothesizing that silencing the correct RLP cluster would result in a loss of resistance phenotype. The VIGS constructs were tested against P. gregata resistant genotypes L78-4094 (Rbs1), PI 437833 (Rbs2), or PI 437970 (Rbs3), infected with P. gregata or mock infected. No loss of resistance phenotype was observed. We then developed VIGS constructs targeting two RLP clusters with a single construct. Construct B1a/B2 silenced P. gregata resistance in L78-4094, confirming at least two genes confer Rbs1-mediated resistance to P. gregata. Failure of B1a/B2 to silence resistance in PI 437833 and PI 437970 suggests additional genes confer BSR resistance in these lines. To identify differentially expressed genes (DEGs) responding to silencing, we conducted RNA-seq of leaf, stem and root samples from B1a/B2 and empty vector control plants infected with P. gregata or mock infected. B1a/B2 silencing induced DEGs associated with cell wall biogenesis, lipid oxidation, the unfolded protein response and iron homeostasis and repressed numerous DEGs involved in defense and defense signaling. These findings will improve integration of Rbs resistance into elite germplasm and provide novel insights into fungal disease resistance.