Worsening of early DME after cataract surgery. The DICAT II Study report #2.

PURPOSE: To analyse the long anatomical and functional outcome of a subgroup of the DICAT II study cohort, consisting of 26 patients undergoing cataract surgery and withdrawn from the study for a clinically significant worsening of early diabetic macular edema (DME). MATERIALS: Patients who underwent cataract surgery and withdrawn from the DICAT II study for a clinically significant worsening of early DME with at least 12 months follow-up after the dropout. The study population was divided into two groups according to the clinical evaluation at one-year follow-up: ongoing treatment patients for DME (Treatment group, TG) and patients no longer treated (Non Treatment group, NTG). RESULTS: Central foveal thickness (CFT) at baseline and dropout time were higher in TG than in the NTG, with a statistically significant difference (p < 0.05). In addition, TG patients reported a higher levels of glycated hemoglobin at time baseline compared to NTG patients (7.81 ± 1.15 vs 7.02 ± 0.56; p = 0.048). The linear regression analysis demonstrated a statistically significant relationship between the visual acuity and the ongoing treatment group at one-year follow-up (p = 0.042). CONCLUSION: The study provides parameters to be considered when assessing the risk of developing persistent DME after cataract surgery in diabetic patients. In particular, CFT at baseline and dropout time have been reported to be an effective and predictable OCT biomarkers when evaluating DME progression. During the evaluation of the systemic disease, similar results were found for the glycated hemoglobin at baseline.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Chemo- and optogenetic activation of hypothalamic Foxb1-expressing neurons and their terminal endings in the rostral-dorsolateral PAG leads to tachypnea, bradycardia, and immobility.

Foxb1 -expressing neurons occur in the dorsal premammillary nucleus (PMd) and further rostrally in the parvafox nucleus, a longitudinal cluster of neurons in the lateral hypothalamus of rodents. The descending projection of these Foxb1+ neurons end in the dorsolateral part of the periaqueductal gray (dlPAG). The functional role of the Foxb1+ neuronal subpopulation in the PMd and the parvafox nucleus remains elusive. In this study, the activity of the Foxb1+ neurons and of their terminal endings in the dlPAG in mice was selectively altered by employing chemo- and optogenetic tools. Our results show that in whole-body barometric plethysmography, hM3Dq-mediated, global Foxb1+ neuron excitation activates respiration. Time-resolved optogenetic gain-of-function manipulation of the terminal endings of Foxb1+ neurons in the rostral third of the dlPAG leads to abrupt immobility and bradycardia. Chemogenetic activation of Foxb1+ cell bodies and ChR2-mediated excitation of their axonal endings in the dlPAG led to a phenotypical presentation congruent with a 'freezing-like' situation during innate defensive behavior.

A Mechanistic Understanding of the Modes of Ca2+ Ion Binding to the SARS-CoV-1 Fusion Peptide and Their Role in the Dynamics of Host Membrane Penetration.

The SARS-CoV-1 spike glycoprotein contains a fusion peptide (FP) segment that mediates the fusion of the viral and host cell membranes. Calcium ions are thought to position the FP optimally for membrane insertion by interacting with negatively charged residues in this segment (E801, D802, D812, E821, D825, and D830); however, which residues bind to calcium and in what combinations supportive of membrane insertion are unknown. Using biological assays and molecular dynamics studies, we have determined the functional configurations of FP-Ca2+ binding that likely promote membrane insertion. We first individually mutated the negatively charged residues in the SARS CoV-1 FP to assay their roles in cell entry and syncytia formation, finding that charge loss in the D802A or D830A mutants greatly reduced syncytia formation and pseudoparticle transduction of VeroE6 cells. Interestingly, one mutation (D812A) led to a modest increase in cell transduction, further indicating that FP function likely depends on calcium binding at specific residues and in specific combinations. To interpret these results mechanistically and identify specific modes of FP-Ca2+ binding that modulate membrane insertion, we performed molecular dynamics simulations of the SARS-CoV-1 FP and Ca2+ions. The preferred residue pairs for Ca2+ binding we identified (E801/D802, E801/D830, and D812/E821) include the two residues found to be essential for S function in our biological studies (D802 and D830). The three preferred Ca2+ binding pairs were also predicted to promote FP membrane insertion. We also identified a Ca2+ binding pair (E821/D825) predicted to inhibit FP membrane insertion. We then carried out simulations in the presence of membranes and found that binding of Ca2+ to SARS-CoV-1 FP residue pairs E801/D802 and D812/E821 facilitates membrane insertion by enabling the peptide to adopt conformations that shield the negative charges of the FP to reduce repulsion by the membrane phospholipid headgroups. This calcium binding mode also optimally positions the hydrophobic LLF region of the FP for membrane penetration. Conversely, Ca2+ binding to the FP E801/D802 and D821/D825 pairs eliminates the negative charge screening and instead creates a repulsive negative charge that hinders membrane penetration of the LLF motif. These computational results, taken together with our biological studies, provide an improved and nuanced mechanistic understanding of the dymanics of SARS-CoV-1 calcium binding and their potential effects on host cell entry.

Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication.

Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates ("hibernation"). However, a newly isolated Pseudomonas aeruginosa phage, named Paride, can directly replicate and induce the lysis of deep-dormant hosts. While non-growing bacteria are notoriously tolerant to antibiotic drugs, the combination with Paride enables the carbapenem meropenem to eradicate deep-dormant cultures in vitro and to reduce a resilient bacterial infection of a tissue cage implant in mice. Our work might inspire new treatments for persistent bacterial infections and, more broadly, highlights two viral strategies to infect dormant bacteria (hibernation and direct replication) that will guide future studies on phage-host interactions.

Impaired intestinal immunity and microbial diversity in common carp exposed to cadmium.

Waterborne cadmium (Cd) accumulates in the fish intestine and causes irreversible toxicity by disrupting intestinal immunity and microbial diversity. To explore the toxicity of environmentally available high Cd concentration on intestinal immunity and microbial diversity of fish, we selected the widely used bioindicator model species, Common carp (Cyprinus carpio). Literature review and Cd pollution data supported sequential doses of 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/L Cd for 30 days. Based on intestinal tissue Cd accumulation, previous studies, and environmentally available Cd data, 0.4 and 1.6 mg/L Cd were selected for further studies. Intestinal Cd bioaccumulation increased significantly to ~100 times in fish exposed to 1.6 mg/L Cd. We observed villous atrophy, increased goblet cells with mucus production, muscularis erosion, and thickened lamina propria due to intense inflammatory cell infiltration in the intestine at this Cd concentration. Cd-induced immunosuppression occurred with increased lysozyme, alkaline phosphate (AKP), and acid phosphate (ACP). High levels of catalase (CAT), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and hydrogen peroxide (H2O2) suggested induced oxidative stress and poor metabolism by α-amylase and lipase suppression for Cd toxicity. Proteobacteria (41.2 %), Firmicutes (21.8 %), and Bacteroidetes (17.5 %) were the dominant bacterial phyla in the common carp intestine. Additionally, potential pathogenic Cyanobacteria increased in Cd-treated fish. The decrease of beneficiary bacteria like Aeromonas, and Cetobacterium indicated Cd toxicity. Overall, these findings indicate harmful consequences of high Cd concentration in the intestinal homeostasis and health status of fish.

Aortic Arch Plaques and the Long-Term Risk of Stroke and Cardiovascular Events in the Statin Era.

BACKGROUND: Aortic arch plaques are associated with an increased risk of ischemic stroke in patients with cryptogenic stroke or prior embolic events. However, this relationship is unclear in the community. We investigated (1) the long-term risk of stroke and cardiovascular events associated with arch plaques and (2) whether statin therapy prescribed for any indication modified the association. METHODS: A total of 934 stroke-free participants (72±9 years; 37% men) from the CABL study (Cardiovascular Abnormalities and Brain Lesion) were evaluated. Arch plaques were assessed by suprasternal transthoracic echocardiography; plaques ≥4 mm in thickness were classified as large plaques. The primary outcome was ischemic stroke; the secondary outcome was combined cardiovascular events (ischemic stroke, myocardial infarction, and cardiovascular death). The plaque-related risk of outcomes was also analyzed according to the presence of statin treatment. No plaque was used as a reference. RESULTS: Aortic arch plaques were present in 645 participants (69.1%), with large plaques in 114 (12.2%). During a mean follow-up of 11.3±3.6 years, 236 (25.3%) cardiovascular events occurred (76 ischemic strokes, 27 myocardial infarctions, and 133 cardiovascular deaths). Large arch plaques were independently associated with combined events (adjusted hazard ratio, 2.19 [95% CI, 1.40-3.43]) but not stroke alone (adjusted hazard ratio, 1.09 [95% CI, 0.50-2.38]). The association between large plaques and cardiovascular events was significant in participants receiving statins (adjusted hazard ratio, 2.57 [95% CI, 1.52-4.37]) but not in others; however, participants on statin treatment also had a worse risk profile (higher body mass index, greater frequencies of hypertension, diabetes, and coronary artery disease). CONCLUSIONS: Aortic arch plaques may be a marker of cardiovascular risk rather than a direct embolic stroke source in older adults without prior stroke. The efficacy of broader cardiovascular risk factors control, beyond cholesterol levels alone, for primary prevention of cardiovascular events in individuals with aortic arch plaques may require further investigation.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Association between non-alcoholic fatty liver disease and subclinical left ventricular dysfunction in the general population.

Aims: Emerging evidence suggests an association between non-alcoholic fatty liver disease (NAFLD) and heart failure (HF). We investigated the relationship between NAFLD and left ventricular (LV) functional remodelling in a general population sample without overt cardiac and liver disease. Methods and results: We included 481 individuals without significant alcohol consumption who voluntarily underwent an extensive cardiovascular health check. The fatty liver index (FLI) was calculated for each participant, and NAFLD was defined as FLI ≥ 60. All participants underwent 2D transthoracic echocardiography; LV global longitudinal strain (LVGLS) was assessed with speckle-tracking analysis. Univariable and multivariable linear regression models were constructed to investigate the possible association between NAFLD and LVGLS. Seventy-one (14.8%) participants were diagnosed with NAFLD. Individuals with NAFLD exhibited larger LV size and LV mass index than those without NAFLD, although left atrial size and E/e' ratio did not differ between groups. Left ventricular global longitudinal strain was significantly reduced in participants with vs. without NAFLD (17.1% ± 2.4% vs. 19.5% ± 3.1%, respectively; P < 0.001). The NAFLD group had a significantly higher frequency of abnormal LVGLS (<16%) than the non-NAFLD group (31.0% vs. 10.7%, respectively; P < 0.001). Multivariable linear regression analysis demonstrated that higher FLI score was significantly associated with impaired LVGLS independent of age, sex, conventional cardiovascular risk factors, and echocardiographic parameters (standardized ß -0.11, P = 0.031). Conclusion: In the general population without overt cardiac and liver disease, the presence of NAFLD was significantly associated with subclinical LV dysfunction, which may partly explain the elevated risk of HF in individuals with NAFLD.

Entomological Survey and Leishmania (Leishmania) mexicana Prevalence in Sand Fly Species during an Outbreak of Cutaneous Leishmaniasis in Quintana Roo State, Mexico.

(1) Background: Localized cutaneous leishmaniasis is a neglected vector-borne disease that has become a serious public health problem in the Yucatan Peninsula. Although more than 60% of cases originate from the state of Quintana Roo, it is one of the least explored areas in terms of incriminating vectors of the Leishmania parasite. Additionally, cases of leishmaniasis have increased substantially in that region in recent years. For this reason, we explored and provided primary evidence of Leishmania DNA in sand fly species from four localities during outbreaks of leishmaniasis in Quintana Roo. We also contributed information on the regional genetic diversity of Leishmania parasites. (2) Methods: Sand flies were collected during several periods from November 2022 to April 2023 using Mosquito Light Circle and Shannon traps, as well as an active entomological search in refuges. For Leishmania detection, we amplified a fragment of 300-350 bp of the internal transcribed spacer subunit 1 (ITS-1). (3) Results: Of the 242 females collected, we detected Leishmania DNA in 25 specimens represented by Bichromomyia olmeca (1), Psathyromyia shannoni (17), Lutzomyia cruciata (4), Psathyromyia undulata (2), and Dampfomyia deleoni (1). The detection of Leishmania in these last two species represents new records for the Yucatan Peninsula and for Mexico. Leishmania (Leishmania) mexicana was the only species detected in the Phlebotominae species, with prevalence values that ranked between 7.41% and 33.33% from specimens collected in the sylvatic areas of Cozumel Island and Petcacab. (4) Conclusions: This study provides the first evidence of infection of Da. deleoni and Pa. undulata by L. (L.) Mexicana. In addition, the presence of three dominant haplotypes in all the evaluated localities was evidenced using the analysis of genetic diversity, and the locality of Petcacab was the one with the circulation of two new haplotypes not previously described in Mexico or neighboring countries. These results highlight the importance of intensive epidemiological surveillance due to the dynamics of transmission of Leishmania between different species.

3D assessment after maxillary sinus grafting with a porcine, a bovine and a synthetical bone substitute material. A randomized controlled clinical trial.

AIM: This randomized controlled clinical study focused on graft volume alterations after sinus floor augmentation with a deproteinized bovine bone mineral (DBBM, Geistlich Bio-Oss®), deproteinized porcine bone mineral (DPBM, THE GRAFT®) or a biphasic calcium phosphate (BCP, OSOPIA®). MATERIAL AND METHODS: 28 patients with edentulous situations in the posterior maxilla with less or equal to 5 mm of residual bone height received a two- staged external sinus grafting procedure with DBBM, DPBM or BCP. CBCT scans were performed prior surgery (CBCT1), directly after surgery (CBCT2) and after a healing period of 4-6 months prior implant placement (CBCT3). CBCT scans were used to analyze volumetric alterations of the sinus grafts by virtual 3D model matching of CBCT1- CBCT2 (situation after sinus grafting) and CBCT1 and CBCT2 (situation prior implant placement). RESULTS: The volume of the bone graft in the maxillary sinus (volume (VOL%) directly after grafting rated as 100%) was stable after the healing period in the DBBM (VOL%: 103±4%) and the PBBM groups (VOL%: 112± 23) with no statistically significant differences concerning 3D measurements. In the BCP group, the grafted volume declined to 66± 25% (VOL%), statistically inferior to the DBBM and DPBM groups. CONCLUSION: Concerning bone graft stability/ 25 volume DBBM and DPBM show comparable outcomes. Due to resorption, BCP showed inferior bone graft volume after healing (statistically significant) compared to DBBM and DPBM.

Alien plant fitness is limited by functional trade-offs rather than a long-term increase in competitive effects of native communities.

Alien plants experience novel abiotic conditions and interactions with native communities in the introduced area. Intra- and interspecific selection on functional traits in the new environment may lead to increased population growth with time since introduction (residence time). However, selection regimes might differ depending on the invaded habitat. Additionally, in high-competition habitats, a build-up of biotic resistance of native species due to accumulation of eco-evolutionary experience to aliens over time may limit invasion success. We tested if the effect of functional traits and the population dynamics of aliens depends on interspecific competition with native plant communities. We conducted a multi-species experiment with 40 annual Asteraceae that differ in residence time in Germany. We followed their population growth in monocultures and in interspecific competition with an experienced native community (varying co-existence times between focals and community). To more robustly test our findings, we used a naïve community that never co-existed with the focals. We found that high seed mass decreased population growth in monocultures but tended to increase population growth under high interspecific competition. We found no evidence for a build-up of competition-mediated biotic resistance by the experienced community over time. Instead, population growth of the focal species was similarly inhibited by the experienced and naïve community. By comparing the effect of experienced and naïve communities on population dynamics over 2 years across a large set of species with a high variation in functional traits and residence time, this study advances the understanding of the long-term dynamics of plant invasions. In our study system, population growth of alien species was not limited by an increase of competitive effects by native communities (one aspect of biotic resistance) over time. Instead, invasion success of alien plants may be limited because initial spread in low-competition habitats requires different traits than establishment in high-competition habitats.

Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.

Despite enabling Streptococcus pneumoniae to acquire antibiotic resistance and evade vaccine-induced immunity, transformation occurs at variable rates across pneumococci. Phase variants of isolate RMV7, distinguished by altered methylation patterns driven by the translocating variable restriction-modification (tvr) locus, differed significantly in their transformation efficiencies and biofilm thicknesses. These differences were replicated when the corresponding tvr alleles were introduced into an RMV7 derivative lacking the locus. RNA-seq identified differential expression of the type 1 pilus, causing the variation in biofilm formation, and inhibition of competence induction in the less transformable variant, RMV7domi. This was partly attributable to RMV7domi's lower expression of ManLMN, which promoted competence induction through importing N-acetylglucosamine. This effect was potentiated by analogues of some proteobacterial competence regulatory machinery. Additionally, one of RMV7domi's phage-related chromosomal island was relatively active, which inhibited transformation by increasing expression of the stress response proteins ClpP and HrcA. However, HrcA increased competence induction in the other variant, with its effects depending on Ca2+ supplementation and heat shock. Hence the heterogeneity in transformation efficiency likely reflects the diverse signalling pathways by which it is affected. This regulatory complexity will modulate population-wide responses to synchronising quorum sensing signals to produce co-ordinated yet stochastic bet hedging behaviour.

Treatment Outcomes for Carbapenem-Resistant and Cephalosporin-Susceptible Pseudomonas aeruginosa Pneumonia.

BACKGROUND: Carbapenem-resistant (Car-R) Pseudomonas aeruginosa is an urgent threat. These isolates may remain susceptible to traditional noncarbapenem antipseudomonal ß-lactams, but it is unclear if carbapenem resistance impacts the effectiveness of these agents. OBJECTIVE: The purpose of this study was to compare clinical outcomes in Car-R and cephalosporin-susceptible (Ceph-S) P. aeruginosa pneumonia treated with cefepime versus other susceptible agents. METHODS: This retrospective cohort study evaluated patients diagnosed with hospital-acquired or ventilator-associated pneumonia who had a respiratory isolate of Car-R Ceph-S P. aeruginosa. Patients were excluded if they had polymicrobial respiratory cultures, other concomitant infections, empyema, death within 3 days of index culture, or received less than 3 days of susceptible therapy. Patients treated with cefepime were compared to other susceptible therapies. The primary endpoint was 30-day in-hospital mortality. RESULTS: Eighty-seven patients were included: cefepime, n = 61; other susceptible therapies, n = 26. There were no differences in 30-day in-hospital mortality between cefepime and other susceptible therapies (19.6% vs. 19.2%, p value = 0.719). In addition, there were no differences between clinical cure rates (cefepime 65.6% vs. other therapies 72 %, p value = 0.47). In multivariate logistic regression, treatment with cefepime (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.11-2.52) was not independently associated with 30-day in-hospital mortality. CONCLUSION AND RELEVANCE: For the treatment of Car-R Ceph-S P. aeruginosa pneumonia, cefepime showed similar rates of 30-day in-hospital mortality and clinical outcomes when compared to other susceptible therapies. Cefepime may be utilized to conserve novel ß-lactam and ß-lactamase inhibitors.

Left Atrial Strain and Incident Atrial Fibrillation in Older Adults.

Atrial fibrillation (AF) is frequent in older adults and associated with left atrial (LA) dysfunction. LA strain (LAε) and LA strain rate (LASR) may detect subclinical LA disease. We investigated whether reduced LAε and LASR predict new-onset AF in older adults without history of AF or stroke. LAε and LASR were assessed by speckle-tracking echocardiography in 824 participants from the community-based Cardiovascular Abnormalities and Brain Lesions study. Positive longitudinal LAε and LASR during ventricular systole, LASR during early ventricular diastole, and LASR during LA contraction were measured. Cause-specific hazards regression model evaluated the association of LAε and LASR with incident AF, adjusting for pertinent covariates. The mean age was 71.1 ± 9.2 years (313 men, 511 women). During a mean follow-up of 10.9 years, new-onset AF occurred in 105 participants (12.7%). Lower LAε and LASR at baseline were observed in patients with new-onset AF (all p <0.01). In multivariable analysis, positive longitudinal LAε (adjusted hazard ratio [HR] per SD decrease 2.05, confidence interval [CI] 1.24 to 3.36) and LASR during LA contraction (HR per SD increase 2.24, CI 1.37 to 3.65) remained associated with new-onset AF, independently of LA volumes and left ventricular function. Along with positive longitudinal LAε, reduced LASR during ventricular systole predicted AF in participants with LA volume below the median value (HR 2.54, CI 1.10 to 6.09), whereas reduced LASR during LA contraction predicted AF in participants with larger LA (HR 2.35, CI 1.31 to 4.23). In conclusion, reduced positive longitudinal LAε and LASR predict new-onset AF in older adults regardless of LA size and may improve AF risk stratification.

Subclinical Left Ventricular Dysfunction and Ventricular Arrhythmias in Older Adults With Normal Ejection Fraction.

Background Premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) are known to be associated with reduced left ventricular (LV) ejection fraction and adverse outcomes in patients with structural heart disease. The relationship between subclinical LV dysfunction and ventricular arrhythmias in the general population is not established. Methods and Results Participants in the SAFARIS (Subclinical Atrial Fibrillation and Risk of Ischemic Stroke) study with normal left ventricular ejection fraction (n=503; mean age 77 years, 63% women) underwent 14-day electrocardiographic monitoring and 2-dimensional echocardiography. Frequent PVCs were defined as PVCs >500 per 24 hours and NSVT as ≥4 consecutive ventricular ectopic beats. Reduced LV global longitudinal strain (GLS) was used as an indicator of subclinical LV dysfunction. Seventy-six participants (15.1%) had PVCs >500/d, 117 (23.3%) had NSVT episodes. LV GLS was significantly reduced in both frequent PVCs and NSVT groups (P<0.01). In multivariable analyses, lower LV GLS was associated with frequent PVCs (adjusted odds ratio [aOR], 1.19 [95% CI, 1.09-1.30 per unit reduction]; P<0.001) and NSVT (aOR, 1.09 [95% CI, 1.01-1.17]; P=0.036) independently of established risk factors and other echocardiographic parameters. Abnormal LV GLS (>-15.8%) carried a 2-fold increase in risk of ventricular arrhythmias (aOR, 2.18, P=0.029 for PVCs; aOR, 2.09, P=0.026 for NSVT). Conclusions PVCs and NSVT episodes were frequent in this community-based elderly cohort with normal left ventricular ejection fraction and were independently associated with lower LV GLS. The association between LV dysfunction and ventricular arrhythmias is present at an early, subclinical stage, an observation that carries possible preventative implications.

Introverted and yet effective? A faceted approach to the relationship between leadership and extraversion.

Introduction: Extraversion and its facets of assertiveness and sociability were identified as stable predictors for leader emergence and effectiveness. However, recent research suggested that extraversion may lie in the eyes of the beholder; it might not be the leader's possession but their followers' attribution of the trait that shapes these criteria of leader success. Methods: In our study, we reverse-engineered this relationship and assessed the effects of effective leadership behaviors on personality perceptions. More specifically, we created scenarios of a leader responding to coordination challenges with passive-avoidant, transactional, or transformational leadership behaviors. We presented 204 participants with these scenarios and assessed how extraverted, assertive, and sociable they perceived the leader to be. Results: Interestingly, and not fully meeting our expectations, ascriptions of extraversion and its facets of assertiveness and sociability did not directly relate to the effectiveness of the behaviors, as the moderately effective transactional leadership style garnered the highest ascriptions of extraversion and its facets. Further, ascriptions of extraversion to the transformational behavior of intellectual stimulation were remarkably low, matched only by the laissez-faire dimension of the passive-avoidant leadership style. Discussion: We integrate and contrast these unexpected but explainable findings with current research, discuss potential associations between introversion and empowering leadership practices and provide suggestions for future discourse, illustrating the potential of investigating the presence of an introverted leadership advantage in the workplace of tomorrow.

The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in-depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.

Diagnóstico diferencial de las reacciones inflamatorias tras uso de medicación intravítrea en degeneración macular asociada a la edad: estéril vs. infeccioso / Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: Sterile vs. infectious

El interés por las complicaciones inflamatorias tras la inyección intravítrea de fármacos antiangiogénicos ha aumentado tras la comercialización de brolucizumab y el desarrollo de nuevas moléculas como el abicipar pegol. Dichos fármacos se asocian a una tasa de complicaciones inflamatorias mayor a los antiangiogénicos clásicos. En este contexto resulta clave el diferenciar procesos infecciosos y estériles para realizar un tratamiento efectivo y precoz. El solapamiento del cuadro clínico entre procesos infecciosos y estériles, la baja tasa de positividad en los cultivos y la heterogeneidad en la terminología son barreras para el correcto diagnóstico y reporte de las complicaciones inflamatorias tras la inyección de medicación antiangiogénica intravítrea. Los cuadros estériles comienzan de forma precoz tras la inyección, dentro de las primeras 48 h, o alrededor de 20 días después en los casos de vasculitis asociada a brolucizumab. Los procesos infecciosos comienzan como promedio en el tercer día tras la inyección, y hasta una semana después de la misma. La disminución grave de la agudeza visual, el dolor severo, la hiperemia severa, el hipopion y un mayor grado de inflamación intraocular deben orientar hacia procesos infecciosos. En los casos en que exista duda sobre la etiología de la inflamación, debe procederse a un control muy estrecho del paciente o al tratamiento antimicrobiano empírico junto con la toma de muestra para evitar complicaciones derivadas de una endoftalmitis infecciosa. Por el contrario, los fenómenos estériles deben ser tratados con observación en los casos más leves o corticoterapia adaptada a la gravedad de inflamación en los casos más graves (AU)

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or “tap and inject” antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation (AU)

Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: sterile vs. infectious.

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48 h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or "tap and inject" antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation.