Bacterial biofilm is ubiquitous in nature. However, it is not clear how this crowded habitat would impact the evolution of bacteriophage (phage) life history traits. In this study, we constructed ...isogenic lambda phage strains that only differed in their adsorption rates, because of the presence/absence of extra side tail fibers or improved tail fiber J, and maker states. The high cell density and viscosity of the biofilm environment was approximated by the standard double-layer agar plate. The phage infection cycle in the biofilm environment was decomposed into three stages: settlement on to the biofilm surface, production of phage progeny inside the biofilm, and emigration of phage progeny out of the current focus of infection.
We found that in all cases high adsorption rate is beneficial for phage settlement, but detrimental to phage production (in terms of plaque size and productivity) and emigration out of the current plaque. Overall, the advantage of high adsorption accrued during settlement is more than offset by the disadvantages experienced during the production and emigration stages. The advantage of low adsorption rate was further demonstrated by the rapid emergence of low-adsorption mutant from a high-adsorption phage strain with the side tail fibers. DNA sequencing showed that 19 out of the 21 independent mutant clones have mutations in the stf gene, with the majority of them being single-nucleotide insertion/deletion mutations occurring in regions with homonucleotide runs.
We conclude that high mutation rate of the stf gene would ensure the existence of side tail fiber polymorphism, thus contributing to rapid adaptation of the phage population between diametrically different habitats of benthic biofilm and planktonic liquid culture. Such adaptability would also help to explain the maintenance of the stf gene in phage lambda's genome.
Summary The pathogenesis of heart failure with a preserved ejection fraction (HFpEF) is unclear. Myocardial fibrosis, inflammation, and cardiac hypertrophy have been suggested to contribute to the ...pathogenesis of HFpEF. Cardiosphere-derived cells (CDCs) are heart-derived cell products with antifibrotic and anti-inflammatory properties. This study tested whether rat CDCs were sufficient to decrease manifestations of HFpEF in hypertensive rats. Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6 to 7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. High-salt rats developed hypertension, left ventricular (LV) hypertrophy, and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion, and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed that CDCs reversed changes in numerous transcripts associated with HFpEF, including many involved in inflammation and/or fibrosis. These studies suggest that CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF.
Fetuin-A is a ubiquitous anti-inflammatory glycoprotein that counteracts proinflammatory cytokine production. Previous studies have shown that low fetuin-A concentration is associated with ...cardiovascular death and may play an important role in the prognosis of patients with acute coronary syndromes (ACS). The purpose of this study was to assess in large cohort of patients admitted for ACS the prognostic value of fetuin-A adjusted for C-reactive protein value (CRP) and Global Registry of Acute Coronary Events (GRACE) risk score. Plasma fetuin-A and CRP concentrations were measured on day 3 in 754 consecutive patients with ACS (mean age 66 ± 14 years, 404 with ST-segment elevation and 350 without ST-segment elevation) included in the French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction (FAST-MI), and these data were correlated to 1-year mortality. Plasma fetuin-A and CRP concentrations at admission averaged 95 ± 27 and 12 ± 16 mg/L, respectively. Overall, 1-year cardiovascular mortality was 10% (28 in-hospital deaths and 51 deaths after discharge), 17% in patients with low fetuin-A (less than the first tertile), 18% with high CRP (higher than the third tertile), and 23% in patients with low fetuin associated with high CRP (p <0.01). In contrast, patients with neither low fetuin-A nor high CRP had a low mortality rate (5%). Multivariate analysis adjusted for GRACE risk score showed that low fetuin-A and high CRP concentration remained associated with outcomes (odds ratio 2.28, 95% confidence interval 1.20 to 4.33). In conclusion, fetuin-A combined with CRP level is associated with cardiovascular death in patients with ACS.
Decrease in blood platelet count has been described after percutaneous coronary intervention and surgical valve replacement, although no study has been performed in the setting of transcatheter ...aortic valve implantation (TAVI). The aim of this study was to address the incidence, mechanism, and impact of blood platelet count decrease after TAVI. One hundred forty-four consecutive patients (mean age 84 ± 7 years, 64 men) with severe symptomatic aortic stenosis who underwent TAVI from December 2007 to July 2011 were enrolled. Blood platelet count was recorded before and after aortic valve implantation. Decrease in blood platelet count was compared with in-hospital major adverse cardiovascular events (death, stroke, and major or life-threatening bleeding). Blood platelet count decreases occurred in all but 1 patient. The percentage of platelet count decrease averaged 34 ± 15% and was 24% greater than blood protein decrease. Decrease in platelet count was associated with a higher rate of prosthesis migration, longer x-ray and procedural times, and larger contrast amounts (230 ± 128 ml for the third tertile vs 170 ± 77 ml for the second and first tertiles, p = 0.0006), but no association was observed with regard to changes in bilirubin. In-hospital major adverse cardiovascular events (n = 50 35%) were observed more frequently in patients with severe platelet count decreases (21% for the first tertile, 35% for the second tertile, and 48% for the third tertile, p = 0.02). Finally, the percentage of blood platelet count decrease was the only predictor of in-hospital major adverse cardiovascular events (odds ratio 1.67, 95% confidence interval 1.05 to 2.67, p = 0.03). In conclusion, a decrease in platelet count is a common phenomenon after TAVI, and its severity is associated with poor outcomes.
Turnip mosaic virus (TuMV, family Potyviridae) and cauliflower mosaic virus (CaMV, family Caulimoviridae) are transmitted by aphid vectors. They are the only viruses shown so far to undergo ...transmission activation (TA) immediately preceding plant-to-plant propagation. TA is a recently described phenomenon where viruses respond to the presence of vectors on the host by rapidly and transiently forming transmissible complexes that are efficiently acquired and transmitted. Very little is known about the mechanisms of TA and on whether such mechanisms are alike or distinct in different viral species. We use here a pharmacological approach to initiate the comparison of TA of TuMV and CaMV. Our results show that both viruses rely on calcium signaling and reactive oxygen species (ROS) for TA. However, whereas application of the thiol-reactive compound N-ethylmaleimide (NEM) inhibited, as previously shown, TuMV transmission it did not alter CaMV transmission. On the other hand, sodium azide, which boosts CaMV transmission, strongly inhibited TuMV transmission. Finally, wounding stress inhibited CaMV transmission and increased TuMV transmission. Taken together, the results suggest that transmission activation of TuMV and CaMV depends on initial calcium and ROS signaling that are generated during the plant's immediate responses to aphid manifestation. Interestingly, downstream events in TA of each virus appear to diverge, as shown by the differential effects of NEM, azide and wounding on TuMV and CaMV transmission, suggesting that these two viruses have evolved analogous TA mechanisms.
Transcatheter aortic valve implantation (TAVI) using a transfemoral approach under local anesthesia with conscious sedation (LACS) is becoming an increasingly common TAVI strategy. However, patients ...who are awake during the TAVI procedure can experience stress, anxiety, and pain, even when LACS is used. Clinical hypnotherapy is an anxiolytic intervention that can be beneficial for patients undergoing invasive surgery. This study aimed to assess the perioperative outcomes of adjunctive hypnotherapy undergoing transfemoral TAVI with LACS.Consecutive patients (n = 143) with symptomatic severe aortic stenosis who underwent transfemoral TAVI with LACS only (n = 107) or with LACS and hypnotherapy (n = 36) between January 2015 and April 2016 were retrospectively included in the study. The clinical outcomes were compared between the two groups. The LACS with hypnotherapy group had a significantly shorter length of stay in the intensive care unit (ICU; LACS only versus LACS with hypnotherapy: 4.0 (4.0-5.5) days versus 3.0 (3.0-5.0) days, P < 0.01). Moreover, the use of anesthetics (propofol and remifentanil) and norepinephrine was significantly lower in the LACS with hypnotherapy group (e.g., for propofol, LACS only versus LACS with hypnotherapy: 96.4 ± 104.7 mg versus 15.0 ± 31.8 mg, P < 0.001). The multiple regression analysis showed that being male, hypnotherapy, and the composite complication score were independently associated with the length of stay in the ICU.The adjunctive hypnotherapy on LACS among transfemoral TAVI patients may facilitate perioperative management. However, a prospective randomized study is necessary to confirm the efficacy of hypnotherapy among TAVI patients.
Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more ...coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients.
Abstract
Background
The influence of microbiota in ecological interactions, and in particular competition, is poorly known. We studied competition between two insect species, the invasive pest
...Drosophila suzukii
and the model
Drosophila melanogaster
, whose larval ecological niches overlap in ripe, but not rotten, fruit.
Results
We discovered
D. suzukii
females prevent costly interspecific larval competition by avoiding oviposition on substrates previously visited by
D. melanogaster
. More precisely,
D. melanogaster
association with gut bacteria of the genus
Lactobacillus
triggered
D. suzukii
avoidance. However,
D. suzukii
avoidance behavior is condition-dependent, and
D. suzukii
females that themselves carry
D. melanogaster
bacteria stop avoiding sites visited by
D. melanogaster
. The adaptive significance of avoiding cues from the competitor’s microbiota was revealed by experimentally reproducing in-fruit larval competition: reduced survival of
D. suzukii
larvae only occurred if the competitor had its normal microbiota.
Conclusions
This study establishes microbiotas as potent mediators of interspecific competition and reveals a central role for context-dependent behaviors under bacterial influence.
Background
Patients with severe symptomatic tricuspid regurgitation (TR) are often deemed ineligible for surgical valve repair due to comorbidities. In this setting, transcatheter tricuspid valve ...replacement (TTVR) is undergoing development, but delivery technique and prosthesis design have yet to be optimized. We sought to assess the challenges of TTVR and the determinants of venous route using computed tomography (CT) analysis.
Methods and results
A total of 195 end-diastolic cardiac CT performed prior to surgical correction of a severe TR (
n
= 38), transcatheter aortic valve replacement (
n
= 89), or left atrial appendage closure (
n
= 68) were analyzed. Patients with TR (
n
= 68; 19 primary and 49 secondary) were compared with patients without (
n
= 127). Continuous variables with normal and non-normal distributions were compared using Student
t
test or Mann–Whitney test respectively. The angle from the tricuspid annulus (TA) to the inferior vena cava was tighter (mean = 101 ± 18°) with a broader range of value (44° to 164°) than to the superior vena cava (mean = 143 ± 9°). Patients with TR had rounder TA (eccentricity index of 0.88 ± 0.08,
p
< 0.001), with a larger area (
p
< 0.0001), and septolateral (45.3 ± 8.0 mm,
p
< 0.0001) and anteroposterior (44.4 ± 7.4 mm,
p
< 0.0001) diameters than patients without. The distances from the TA to the coronary sinus, the right ventricular outflow tract, and the moderator band were respectively 11.4 ± 3.8 mm, 17.2 ± 3.4 mm, and 31.0 ± 6.7 mm, without differences between groups.
Conclusion
The transjugular access for TTVR is straighter and more reproducible than the transfemoral access. Prosthesis development may be challenged by the close position of the coronary sinus, the presence of a moderator band, and the large TA size of patients with severe TR.
Key Points
• The tricuspid annulus is larger in patients with severe tricuspid regurgitation, confirming existing data.
• The coronary sinus ostium is close to the tricuspid annulus, requiring a prosthesis with a short atrial length.
• The transjugular venous route may be the preferred access to the tricuspid annulus, straighter with less inter-individual variations than the transfemoral route.
Background Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the ...prevalence and prognostic impact of AS among patients with CA. Methods and Results We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) 1.09–3.64; ATTRv: SRR, 3.41; 95%CI 1.64–4.60; ATTRwt: SRR, 10.8; 95%CI 5.25–14.53). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI 0.56–1.14; ATTRv: SRR, 1.27; 95%CI 0.85–1.44; ATTRwt: SRR, 4.01; 95%CI 2.71–4.54). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI 0.42–1.19; P =0.19). Conclusions Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
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