Diversifying the menu for crop powdery mildew resistance.

Powdery mildew, a potentially severe crop disease, can be controlled by mlo mutations, which suppress fungal proliferation but typically also reduce yield. Li et al. (2022) demonstrate that productivity can be restored by overexpressing a host sugar transporter, thus offering a new option for economically and environmentally benign disease control.

Harnessing landrace diversity empowers wheat breeding.

Harnessing genetic diversity in major staple crops through the development of new breeding capabilities is essential to ensure food security1. Here we examined the genetic and phenotypic diversity of the A. E. Watkins landrace collection2 of bread wheat (Triticum aestivum), a major global cereal, by whole-genome re-sequencing of 827 Watkins landraces and 208 modern cultivars and in-depth field evaluation spanning a decade. We found that modern cultivars are derived from two of the seven ancestral groups of wheat and maintain very long-range haplotype integrity. The remaining five groups represent untapped genetic sources, providing access to landrace-specific alleles and haplotypes for breeding. Linkage disequilibrium-based haplotypes and association genetics analyses link Watkins genomes to the thousands of identified high-resolution quantitative trait loci and significant marker-trait associations. Using these structured germplasm, genotyping and informatics resources, we revealed many Watkins-unique beneficial haplotypes that can confer superior traits in modern wheat. Furthermore, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritized quantitative trait loci in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilizing genetic diversity in crop improvement to achieve sustainable food security.

The genotype of barley cultivars influences multiple aspects of their associated microbiota via differential root exudate secretion.

Plant-associated microbes play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley (Hordeum vulgare) cultivars. Distinct differences were observed between the plant-associated microbiomes of the 2 cultivars, with the plant-growth promoting rhizobacterial genus Pseudomonas substantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruited Pseudomonas populations, alongside distinct genotypic clustering by cultivar. Cultivar-driven Pseudomonas selection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and Chevallier Pseudomonas isolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assays.

Centrosome amplification promotes cell invasion via cell-cell contact disruption and Rap-1 activation.

Centrosome amplification (CA) is a prominent feature of human cancers linked to tumorigenesis in vivo. Here, we report mechanistic contributions of CA induction alone to tumour architecture and extracellular matrix (ECM) remodelling. CA induction in non-tumorigenic breast cells MCF10A causes cell migration and invasion, with underlying disruption of epithelial cell-cell junction integrity and dysregulation of expression and subcellular localisation of cell junction proteins. CA also elevates expression of integrin ß-3, its binding partner fibronectin-1 and matrix metalloproteinase enzymes, promoting cell-ECM attachment, ECM degradation, and a migratory and invasive cell phenotype. Using a chicken embryo xenograft model for in vivo validation, we show that CA-induced (+CA) MCF10A cells invade into the chick mesodermal layer, with inflammatory cell infiltration and marked focal reactions between chorioallantoic membrane and cell graft. We also demonstrate a key role of small GTPase Rap-1 signalling through inhibition using GGTI-298, which blocked various CA-induced effects. These insights reveal that in normal cells, CA induction alone (without additional oncogenic alterations) is sufficient to confer early pro-tumorigenic changes within days, acting through Rap-1-dependent signalling to alter cell-cell contacts and ECM disruption.

Pathogen-induced biosynthetic pathways encode defense-related molecules in bread wheat.

Wheat is a widely grown food crop that suffers major yield losses due to attack by pests and pathogens. A better understanding of biotic stress responses in wheat is thus of major importance. The recently assembled bread wheat genome coupled with extensive transcriptomic resources provides unprecedented new opportunities to investigate responses to pathogen challenge. Here, we analyze gene coexpression networks to identify modules showing consistent induction in response to pathogen exposure. Within the top pathogen-induced modules, we identify multiple clusters of physically adjacent genes that correspond to six pathogen-induced biosynthetic pathways that share a common regulatory network. Functional analysis reveals that these pathways, all of which are encoded by biosynthetic gene clusters, produce various different classes of compounds­namely, flavonoids, diterpenes, and triterpenes, including the defense-related compound ellarinacin. Through comparative genomics, we also identify associations with the known rice phytoalexins momilactones, as well as with a defense-related gene cluster in the grass model plant Brachypodium distachyon. Our results significantly advance the understanding of chemical defenses in wheat and open up avenues for enhancing disease resistance in this agriculturally important crop. They also exemplify the power of transcriptional networks to discover the biosynthesis of chemical defenses in plants with large, complex genomes.

LAMA: automated image analysis for the developmental phenotyping of mouse embryos.

Advanced 3D imaging modalities, such as micro-computed tomography (micro-CT), have been incorporated into the high-throughput embryo pipeline of the International Mouse Phenotyping Consortium (IMPC). This project generates large volumes of raw data that cannot be immediately exploited without significant resources of personnel and expertise. Thus, rapid automated annotation is crucial to ensure that 3D imaging data can be integrated with other multi-dimensional phenotyping data. We present an automated computational mouse embryo phenotyping pipeline that harnesses the large amount of wild-type control data available in the IMPC embryo pipeline in order to address issues of low mutant sample number as well as incomplete penetrance and variable expressivity. We also investigate the effect of developmental substage on automated phenotyping results. Designed primarily for developmental biologists, our software performs image pre-processing, registration, statistical analysis and segmentation of embryo images. We also present a novel anatomical E14.5 embryo atlas average and, using it with LAMA, show that we can uncover known and novel dysmorphology from two IMPC knockout lines.

Safety, Pharmacokinetics, and Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-Associated Hepatitis.

INTRODUCTION: This study is to evaluate the safety and pharmacokinetics (PK) of larsucosterol (DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating acute illness without US Food and Drug Administration-approved therapies. METHODS: This phase 2a, multicenter, open-label, dose escalation study evaluated the safety, PK, and efficacy signals of larsucosterol in 19 clinically diagnosed subjects with AH. Based on the model for end-stage liver disease (MELD) score, 7 subjects were considered to have moderate AH and 12 to have severe AH. All subjects received 1 or 2 intravenous infusions (72 hours apart) of larsucosterol at a dose of 30, 90, or 150 mg and were followed up for 28 days. Efficacy signals from a subgroup of subjects with severe AH were compared with those from 2 matched arms of those with severe AH treated with standard of care (SOC), including corticosteroids, from a contemporaneous study. RESULTS: All 19 larsucosterol-treated subjects survived the 28-day study. Fourteen (74%) of all subjects including 8 (67%) of the subjects with severe AH were discharged ≤72 hours after receiving a single infusion. There were no drug-related serious adverse events nor early terminations due to the treatment. PK profiles were not affected by disease severity. Biochemical parameters improved in most subjects. Serum bilirubin levels declined notably from baseline to day 7 and day 28, and MELD scores were reduced at day 28. The efficacy signals compared favorably with those from 2 matched groups treated with SOC. Lille scores at day 7 were <0.45 in 16 of the 18 (89%) subjects with day 7 samples. Lille scores from 8 subjects with severe AH who received 30 or 90 mg larsucosterol (doses used in phase 2b trial) were statistically significantly lower ( P < 0.01) than those from subjects with severe AH treated with SOC from the contemporaneous study. DISCUSSION: Larsucosterol was well tolerated at all 3 doses in subjects with AH without safety concerns. Data from this pilot study showed promising efficacy signals in subjects with AH. Larsucosterol is being evaluated in a phase 2b multicenter, randomized, double-blinded, placebo-controlled (AHFIRM) trial.

Radial artery vs right internal mammary artery as a second conduit during coronary artery bypass grafting.

OBJECTIVE: To compare the clinical outcomes of radial artery (RA) grafts during CABG to those of right internal mammary artery (RIMA) grafts. METHODS: This was a retrospective, single-institution cohort study of isolated CABG with multiple grafts between 2010-2022. To balance graft cohorts, propensity score matching (PSM) was performed using a 1:1 match ratio. Long-term postoperative survival was compared among RA and RIMA groups. Similarly, major adverse cardiac and cerebrovascular events (MACCE) were compared among both cohorts, with MACCE comprising death, myocardial infarction (MI), coronary revascularization, and stroke. Kaplan-Meier estimation was performed for mortality, while cumulative incidence estimation was utilized for MACCE. RESULTS: A total of 8,774 patients underwent CABG. Of those, 1,674 (19.1%) patients who underwent multiarterial CABG were included in this analysis. 326 (19.5%) patients received RA grafts and 1,348 (80.5%) received RIMA grafts. PSM yielded a cohort of 323 RA patients and 323 RIMA patients. After matching, groups were well-balanced across all baseline variables. No significant differences were observed in immediate postoperative complications or long-term survival, with 5-year survival estimates of 89.5% for the RA group vs 90.1% for the RIMA group. There was a nonsignificant trend toward a higher incidence of MACCE at 5 years in the RA group compared to the RIMA group (31.3% in the RA group vs 24.1% in the RIMA group), especially after 1-year follow-up (21.6% in the RA group vs 15.1% in the RIMA group). Specifically, for RA patients, there were higher rates of repeat revascularization in the 5-year postoperative period (14.7% in the RA group vs 5.3% in the RIMA group), particularly in the territory revascularized by the RA during the index operation (45.7% in the RA group vs 10.3% in the RIMA group). CONCLUSION: Overall, RA and RIMA secondary conduits for CABG were associated with comparable immediate postoperative complications, 5-year MACCE, and 5-year survival after PSM. RA grafting was associated with significantly higher rates of repeat coronary revascularization at 5 years, specifically in the territory revascularized by the RA during the index operation.

Native myocardial T1 and right ventricular size by CMR predict outcome in systemic sclerosis-associated pulmonary hypertension.

OBJECTIVES: Measures of right heart size and function are prognostic in systemic sclerosis-associated pulmonary hypertension (SSc-PH), but the importance of myocardial tissue characterisation remains unclear. We aimed to investigate the predictive potential and interaction of cardiovascular magnetic resonance (CMR) myocardial tissue characterisation and right heart size and function in SSc-PH. METHODS: A retrospective, single-centre, observational study of 148 SSc-PH patients confirmed by right heart catheterization who underwent clinically-indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2023 was performed. RESULTS: Sixty-six (45%) patients died during follow-up (median 3.5 years, range 0.1-7.3). Patients who died were older (65 vs 60 years, p= 0.035) with more dilated (RVEDVi and RVESVi, p< 0.001), hypertrophied (RVMi, p= 0.013) and impaired (RVEF, p< 0.001) right ventricles, more dilated right atria (RAi, p= 0.043) and higher native myocardial T1 (p< 0.001).After adjustment for age, RVESVi (p = 0.0023) and native T1 (p = 0.0024) were independent predictors of all-cause mortality. Both RVESVi and native T1 remained independently predictive after adjusting for age and PH subtype (RVESVi p < 0.001, T1 p = 0.0056). Optimal prognostic thresholds for RVESVi and native T1 were ≤38 mL/m2 and ≤1119 ms, respectively (p < 0.001). Patients with RVESVi ≤ 38 mL/m2 and native T1 ≤ 1119 ms had significantly better outcomes than all other combinations (p < 0.001). Furthermore, patients with RVESVi > 38mL/m2 and native T1 ≤ 1119 ms had significantly better survival than patients with RVESVi > 38mL/m2 and native T1 > 1119ms (p = 0.017). CONCLUSION: We identified prognostically relevant CMR metrics and thresholds for patients with SSc-PH. Assessing myocardial tissue characterisation alongside RV function confers added value in SSc-PH and may represent an additional treatment target.

Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study.

OBJECTIVE: Functional and morphologic changes in extracranial organs can occur after acute brain injury. The neuroanatomic correlates of such changes are not fully known. Herein, we tested the hypothesis that brain infarcts are associated with cardiac and systemic abnormalities (CSAs) in a regionally specific manner. METHODS: We generated voxelwise p value maps of brain infarcts for poststroke plasma cardiac troponin T (cTnT) elevation, QTc prolongation, in-hospital infection, and acute stress hyperglycemia (ASH) in 1,208 acute ischemic stroke patients prospectively recruited into the Heart-Brain Interactions Study. We examined the relationship between infarct location and CSAs using a permutation-based approach and identified clusters of contiguous voxels associated with p < 0.05. RESULTS: cTnT elevation not attributable to a known cardiac reason was detected in 5.5%, QTc prolongation in the absence of a known provoker in 21.2%, ASH in 33.9%, and poststroke infection in 13.6%. We identified significant, spatially segregated voxel clusters for each CSA. The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were 3 clusters for ASH, the largest of which was in the left hemisphere. We found 2 clusters for poststroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSAs persisted after adjusting for infarct volume. INTERPRETATION: Our results show that there are discrete regions of brain infarcts associated with CSAs. This information could be used to bootstrap toward new markers for better differentiation between neurogenic and non-neurogenic mechanisms of poststroke CSAs. ANN NEUROL 2023;94:1155-1163.

Six-Year Outcomes of Total Arch Replacement vs Debranching With TEVAR for Aortic Arch Pathologies: Meta-Analysis of Kaplan-Meier-Derived Data From Propensity Score-Matched Studies.

BACKGROUND: Total arch replacement (TAR) and debranching plus thoracic endovascular aortic repair (TEVAR) serve as significant therapeutic options for aortic arch pathologies. It remains unclear whether one of these approaches should be considered preferable. Our study aimed to compare the long-term outcomes of these 2 approaches. METHODS: We carried out a pooled meta-analysis of time-to-event data extracted from studies published by December 2023. Eligibility criteria included populations with any aortic arch pathology who underwent debranching plus TEVAR or TAR, propensity score-matched (PSM) studies (prospective/retrospective; single-center/multicentric), and the outcomes included follow-up for overall survival/mortality and/or reinterventions. RESULTS: Eleven PSM studies met our eligibility criteria, including a total of 1142 patients (571 matched pairs). We did not observe any statistically significant difference in the risk of all-cause death between the groups (hazard ratio [HR]=1.20, 95% confidence interval [CI]=0.91-1.56, p=0.202), but patients who underwent TAR had a significantly lower risk of late aortic reinterventions compared with patients who underwent debranching plus TEVAR (HR=0.38, 95% CI=0.23-0.64, p<0.001). Our meta-regression analyses for all-cause mortality identified statistically significant coefficients for age (coefficient=-0.047; p=0.012) and type A aortic dissections (coefficient=0.012; p=0.010). CONCLUSIONS: Debranching plus TEVAR and TAR demonstrate no statistically significant differences in terms of survival in patients with aortic arch pathologies, but TAR is associated with lower risk of late aortic reinterventions over time. Although older patients may benefit more from debranching plus TEVAR rather than from TAR, patients with dissections may benefit more from TAR. CLINICAL IMPACT: Although the 2 strategies seem to be equally valuable in terms of survival, total aortic arch replacement (when compared with debranching plus TEVAR to treat patients with aortic arch pathologies) is associated with reduction of late aortic reinterventions over time in patients with and without aortic dissections. However, we should consider debranching plus TEVAR in older patients as it is associated with lower risk of death in this population. The novelty of our study lies in the fact that, instead of comparing study-level effect estimates, we analyzed the outcomes with reconstructed time-to-event data. This offered us the opportunity of performing our analyses with a mathematically appropriate model which consider events and time; however, these findings might be under the influence of treatment allocation bias.

HIV-related Legal Needs, Demographic Change, and Trends in Australia since 1992: A Review of Legal Administrative Data.

An enabling legal environment is essential for an effective HIV response. Using legal administrative data from the HIV/AIDS Legal Centre (HALC), Australia's specialist HIV community legal service, this article characterizes the nature and trends in the legal issues and needs of those with HIV-related legal issues in New South Wales, Australia since 1992. At present, approximately 40% of all PLHIV living in NSW receive a legal service from HALC during the most recent five-year period. Clients received legal services relating to immigration law at a greatly increased rate (2010: 36%; 2019: 53%), discrimination matters decreased (2010: 17%; 2019: 5.9%), wills and estates remained steady (2010: 9%; 2019: 8.3%). Most clients identify as male (76.9%), homosexual (55%) and are aged between 35 and 49 years of age (34.6%). This demographic profile of clients changed over time, becoming younger and more likely to have been born overseas, and increasingly identifying as heterosexual.

Outcomes of laparoscopic subtotal cholecystectomy: a comparative analysis of fenestrating and reconstituting approaches in 170 cases.

BACKGROUND: Laparoscopic subtotal cholecystectomy (LSC) is a recognised alternative to laparoscopic cholecystectomy (LC) when it is unsafe to achieve the "critical view of safety". Although LSC reduces the risk of bile duct injury, it is associated with increased morbidity, primarily due to bile leak. LSC can be classified as fenestrating (F-LSC) or reconstituting (R-LSC), with the latter being more complex. The objective of this study was to evaluate the two LSC techniques, their complications, and overall outcomes. METHODS: We conducted a retrospective analysis of all adult patients who underwent LSC between January 2015 and December 2021 using our electronic database. Data collected included patient demographics, prior acute biliary presentations, operative details/techniques, length of stay (LOS), 30-day complications, 30-day mortality, readmissions, and follow-up investigations/procedures. Descriptive statistics, Chi-squared tests, and relative risk were employed for data analysis. RESULTS: In the study period, LSC was performed on 170 patients, showing an increasing trend over time. Most procedures (76%) were performed in the acute setting, and 37.1% of patients had a history of previous acute biliary presentations. Fenestrating LSC was the most performed technique (115 [67.6%] vs. 55 [32.4%]). Complications occurred in 80 (47.1%) patients; 60 patients (35.3%) had a bile leak. 16 patients (9.4%) required reoperation, and readmission was observed in 14 patients (8.2%). F-LSC was associated with more complications [p = 0.03 RR 2.46 (95% CI 1.5-4)], more bile leaks [p < 0.01, RR 2.1 (95% CI 1.2-3.7)], greater need for rescue postoperative endoscopic retrograde cholangiopancreatography (ERCP) [p < 0.01, RR 3.8 (95% CI 1.4-10.2)], and longer LOS (6 vs. 4 days p < 0.01). CONCLUSION: Although LSC is seen as a safe alternative to open conversion, our findings demonstrate a high morbidity, including reoperation/reintervention, readmissions, and complications, associated with LSC especially with F-LSC. We suggest that if LSC is performed, the reconstituted technique should be chosen, if feasible.

Feedback, learning and becoming: Narratives of feedback in complex performance challenges.

INTRODUCTION: Becoming a general practitioner (or family medicine specialist) is challenging, as trainees learn to manage complex and ambiguous situations. Feedback is a key component of this learning. Although research has tended to focus on feedback's momentary processes and impacts, there is value in seeking to understand the work it does over time and how trainees position themselves across multiple feedback encounters. We ask: how do newly qualified GPs narrate themselves and their experiences with complex performance challenges? Within these narratives, what is the role of feedback? METHODS: The research adopts a holistic and sequential narrative analysis approach, with in-depth narrative interviews of 16 general practice trainees who had just completed their training requirements. The analysis involved restorying the participant narratives chronologically. Each narrative formed a unit of analysis where narrative commonalities across plots, characters, emotions and the role of feedback were interpreted. RESULTS: Four plotlines within GP trainees' stories of complex performance challenges were identified: Journeyperson, Hero's Quest, Solo Journeyer and Endless Struggle. Trainees, supervisors and feedback are positioned differently within these plotlines. Narratives were saturated with emotions. DISCUSSION: The plotlines bring together an alternative way of understanding how feedback, learning and becoming are woven together. They illustrate how multiple interactions with patients, supervisors, peers and systems thread together into an overall trajectory. How a trainee positions themselves as protagonists and who they characterise as their antagonists can help direct the focus of supervisors' feedback conversations.

Non-reporting of sport-related concussion symptoms: a cross-sectional study of community rugby league players in the UK.

Recognising and removing players with suspected sport-related concussions is crucial for community sports. OBJECTIVES: Quantify rates and factors associated with non-reporting of concussion symptoms in community rugby league. METHODS: Overall, 484 community rugby league players aged ≥18 years and 965 parents of rugby league players aged <18 years completed an online survey, regarding concussion history, knowledge, prevalence and reasons for non-reporting of concussion, long-term implications and perceptions of concussion. RESULTS: Thirty-five percent of players aged ≥18 years and 22% of parents of players aged <18 years reported at least one concussion in the last two seasons. Forty-three percent of players aged ≥18 years and 5% of parents of players aged<18 years surveyed stated they did not report concussion-related symptoms sustained during 2020 and 2021 seasons. The two most common reasons for non-reporting of concussion symptoms were 'didn't want to be ruled out of a match' and 'didn't want to let down the team'. Players aged ≥18 years who received external coaching pressures around concussion were more likely to not report concussion symptoms. Over 40% of parents and players were concerned about the potential long-term implications. Ten percent of players aged ≥18 years and 7% of parents of players aged <18 years would encourage their family members/children to not play rugby league. CONCLUSIONS: Non-reporting rates of suspected concussion symptoms in adult community players were twice as high as in professional rugby league, with similar reasons (wanting to play and not letting the team down). Engaging coaches to prioritise brain health and providing broader and appropriate education on concussion should be focused on, given the concerns reported by community players and parents.

Exploring watercolor illusion spreading between dissected stimulus parts.

The watercolor illusion (WCI) occurs when an achromatic region is surrounded by an outer contour and inner chromatic fringe, resulting in an apparent pale tint of the same hue as the fringe. The WCI both fills in and spreads out, with the previous literature suggesting it always spreads out in the absence of an enclosing border. We examined how global stimulus configuration affects this illusion by dissecting various WCI-inducing stimuli into parts. Specifically, would color spread out of the unenclosed ends of the disconnected parts? Participants provided WCI illusion magnitude ratings and shading data indicating perceived locations of color spreading for a variety of stimulus configurations. Instead of the WCI spreading modally into the spaces between the disconnected parts, we found a global reorganization of the stimuli occurred. The dissected WCI stimuli were perceived as either amodally completed behind a white illusory surface perceptually different than the physically identical background or, as empty space between separate objects depending in part on the distance between dissected parts. This study demonstrates the WCI does not always spread outside of unenclosed borders when the global interpretation interferes with spreading. These findings highlight the importance of global configuration and perceptual organization in the WCI.

Carbapenemase gene blaOXA-48 detected at six freshwater sites in Northern Ireland discharging onto identified bathing locations.

Faecal contamination of surface waters has the potential to spread not only pathogenic organisms but also antimicrobial resistant organisms. During the bathing season of 2021, weekly water samples, from six selected coastal bathing locations (n = 93) and their freshwater tributaries (n = 93), in Northern Ireland (UK), were examined for concentrations of faecal indicator bacteria Escherichia coli and intestinal enterococci. Microbial source tracking involved detection of genetic markers from the genus Bacteroides using PCR assays for the general AllBac marker, the human HF8 marker and the ruminant BacR marker for the detection of human, and ruminant sources of faecal contamination. The presence of beta-lactamase genes blaOXA-48, blaKPC, and blaNDM-1 was determined using PCR assays for the investigation of antimicrobial resistance genes that are responsible for lack of efficacy in major broad-spectrum antibiotics. The beta-lactamase gene blaOXA-48 was found in freshwater tributary samples at all six locations. blaOXA-48 was detected in 83% of samples that tested positive for the human marker and 69% of samples that tested positive for the ruminant marker over all six locations. This study suggests a risk of human exposure to antimicrobial resistant bacteria where bathing waters receive at least episodically substantial transfers from such tributaries.

The Clinical Significance of Unplanned Coronary Artery Bypass Grafting in Aortic Root Replacement.

OBJECTIVES: Unexpected coronary artery bypass grafting (CABG) is occasionally required during aortic root replacement (ARR). However, the impact of unplanned CABG remains unknown. DESIGN: A single-center, retrospective observational study. SETTING: At university-affiliated tertiary hospital. PARTICIPANTS: All patients who underwent ARR from 2011 through 2022. INTERVENTIONS: Aortic root replacement with or without unplanned CABG. MEASUREMENTS AND MAIN RESULTS: A total of 795 patients underwent ARR. Among them, 131 (16.5%) underwent planned concomitant CABG, and 34 (4.3%) required unplanned CABG. The most common indication of unplanned CABG was ventricular dysfunction (33.3%), followed by disease pathology (25.6%), anatomy (15.4%), and surgical complications (10.3%). A vein graft to the right coronary artery was the most commonly performed bypass. Infective endocarditis and aortic dissection were observed in 27.8% and 12.8%, respectively. Prior cardiac surgery was seen in 40.3%. The median follow-up period was 4.3 years. Unplanned CABG was not associated with operative mortality (odds ratio [OR] 1.54, 95% CI 0.33-7.16, p = 0.58) or long-term mortality (hazard ratio 0.91, 95% CI 0.44-1.89, p = 0.81). Body surface area smaller than 1.7 was independently associated with an increased risk of unplanned CABG (OR 4.51, 95% CI 1.85-11.0, p < 0.001). CONCLUSIONS: Unplanned CABG occurred in 4.3% of patients during ARR, but was not associated with operative mortality or long-term mortality. A small body surface area was a factor associated with unplanned CABG.

Outcomes of Aortomitral Continuity Reconstruction During Concomitant Aortic and Mitral Valve Replacement.

OBJECTIVES: To describe outcomes of reconstruction of the aortomitral continuity (AMC) during concomitant aortic and mitral valve replacement (ie, the "Commando" procedure). DESIGN: A retrospective study of consecutive cardiac surgeries from 2010 to 2022. SETTING: At a single institution. PARTICIPANTS: All patients undergoing double aortic and mitral valve replacement. INTERVENTIONS: Patients were dichotomized by the performance (or not) of AMC reconstruction. MEASUREMENTS AND MAIN RESULTS: A total of 331 patients underwent double-valve replacement, of whom 21 patients (6.3%) had a Commando procedure. The Commando group was more likely to have had a previous aortic valve replacement (AVR) or mitral valve replacement (MVR) (66.7% v 27.4%, p < 0.001), redo cardiac surgery (71.4% v 31.3%, p < 0.001), and emergent/salvage surgery (14.3% v 1.61%, p = 0.001), whereas surgery was more often performed for endocarditis in the Commando group (52.4% v 22.9%, p = 0.003). The Commando group had higher operative mortality (28.6% v 10.7%, p = 0.014), more prolonged ventilation (61.9% v 31.9%, p = 0.005), longer cardiopulmonary bypass time (312 ± 118 v 218 ± 85 minutes, p < 0.001), and longer ischemic time (252 ± 90 v 176 ± 66 minutes, p < 0.001). Despite increased short-term morbidity in the Commando group, Kaplan-Meier survival estimation showed no difference in long-term survival between each group (p = 0.386, log-rank). On multivariate Cox analysis, the Commando procedure was not associated with an increased hazard of death, compared to MVR + AVR (hazard ratio 1.29, 95% CI: 0.65-2.59, p = 0.496). CONCLUSIONS: Although short-term postoperative morbidity and mortality were found to be higher for patients undergoing the Commando procedure, AMC reconstruction may be equally durable in the long term.

Trehalose and α-glucan mediate distinct abiotic stress responses in Pseudomonas aeruginosa.

An important prelude to bacterial infection is the ability of a pathogen to survive independently of the host and to withstand environmental stress. The compatible solute trehalose has previously been connected with diverse abiotic stress tolerances, particularly osmotic shock. In this study, we combine molecular biology and biochemistry to dissect the trehalose metabolic network in the opportunistic human pathogen Pseudomonas aeruginosa PAO1 and define its role in abiotic stress protection. We show that trehalose metabolism in PAO1 is integrated with the biosynthesis of branched α-glucan (glycogen), with mutants in either biosynthetic pathway significantly compromised for survival on abiotic surfaces. While both trehalose and α-glucan are important for abiotic stress tolerance, we show they counter distinct stresses. Trehalose is important for the PAO1 osmotic stress response, with trehalose synthesis mutants displaying severely compromised growth in elevated salt conditions. However, trehalose does not contribute directly to the PAO1 desiccation response. Rather, desiccation tolerance is mediated directly by GlgE-derived α-glucan, with deletion of the glgE synthase gene compromising PAO1 survival in low humidity but having little effect on osmotic sensitivity. Desiccation tolerance is independent of trehalose concentration, marking a clear distinction between the roles of these two molecules in mediating responses to abiotic stress.