Anticooperative Supramolecular Oligomerization Mediated by V-Shaped Monomer Design and Unconventional Hydrogen Bonds.

After more than three decades of extensive investigations on supramolecular polymers, strategies for self-limiting growth still remain challenging. Herein, we exploit a new V-shaped monomer design to achieve anticooperatively formed oligomers with superior robustness and high luminescence. In toluene, the monomer-oligomer equilibrium is shifted to the monomer side, enabling the elucidation of the molecular packing modes and the resulting (weak) anticooperativity. Steric effects associated with an antiparallel staircase organization of the dyes are proposed to outcompete aromatic and unconventional B-F⋅⋅⋅H-N/C interactions, restricting the growth at the stage of oligomers. In methylcyclohexane (MCH), the packing modes and the anticooperativity are preserved; however, pronounced solvophobic and chain-enwrapping effects lead to thermally ultrastable oligomers. Our results shed light on understanding anticooperative effects and restricted growth in self-assembly.

Reduction in new cardiac electronic device implantations in Catalonia during COVID-19.

AIMS: During the COVID-19 pandemic, concern regarding its effect on the management of non-communicable diseases has been raised. However, there are no data on the impact on cardiac implantable electronic devices (CIED) implantation rates. We aimed to determine the impact of SARS-CoV2 on the monthly incidence rates and type of pacemaker (PM) and implantable cardiac defibrillator (ICD) implantations in Catalonia before and after the declaration of the state of alarm in Spain on 14 March 2020. METHODS AND RESULTS: Data on new CIED implantations for 2017-20 were prospectively collected by nine hospitals in Catalonia. A mixed model with random intercepts corrected for time was used to estimate the change in monthly CIED implantations. Compared to the pre-COVID-19 period, an absolute decrease of 56.5% was observed (54.7% in PM and 63.7% in ICD) in CIED implantation rates. Total CIED implantations for 2017-19 and January and February 2020 was 250/month (>195 PM and >55 ICD), decreasing to 207 (161 PM and 46 ICD) in March and 131 (108 PM and 23 ICD) in April 2020. In April 2020, there was a significant fall of 185.25 CIED implantations compared to 2018 [95% confidence interval (CI) 129.6-240.9; P < 0.001] and of 188 CIED compared to 2019 (95% CI 132.3-243.7; P < 0.001). No significant differences in the type of PM or ICD were observed, nor in the indication for primary or secondary prevention. CONCLUSIONS: During the first wave of the COVID-19 pandemic, a substantial decrease in CIED implantations was observed in Catalonia. Our findings call for measures to avoid long-term social impact.

Mapping potentials adjacent to the cavo-tricuspid isthmus ablation line during incremental pacing: A feasible and highly accurate maneuver to confirm complete CTI conduction block.

BACKGROUND: The diagnostic accuracy of incremental atrial pacing (IP) to determine complete cavo-tricuspid isthmus (CTI) block during typical atrial flutter (AFL) ablation is limited by both an extensive/nonlinear ablation and/or the presence of intra-atrial conduction delay elsewhere in the right atrium. We examined the diagnostic performance of an IP variant based on the assessment of the atrial potentials adjacent to the ablation line which aims at overcoming both limitations. METHODS: From a prospective population of 108 consecutive patients, 15 were excluded due to observation of inconclusive CTI ablation potentials precluding for a straight comparison between the IP maneuver and its variant. In the remaining 93, IP was performed from the low lateral right atrium and the coronary sinus ostium, with the ablation catheter positioned both at the CTI line and adjacent (<5 mm) to its septal and lateral aspect. The IP variant consisted of measuring the interval between the two atrial electrograms situated on the same side of the ablation line, opposite to the pacing site, a ≤10 ms increase indicating complete CTI block. RESULTS: The IP maneuver and its variant were consistent with complete CTI block in 82/93 (88%) and 87/93 (93%) patients, respectively. Four patients had AFL recurrence during follow-up: 2/4 and 4/4 had been adequately classified as incomplete block by the IP maneuver and its variant, respectively. Twenty-three patients (24%) had significant intra-atrial conduction delay elsewhere in the right atrium. The IP maneuver and its variant were suggestive of an incomplete CTI block in 11/23 and 4/23 in this setting (P = .028), with the later best predicting subsequent AFL relapses (2/12 vs 2/4, P = .01). CONCLUSIONS: The IP variant, which was designed to overcome the limitations of the conventional IP maneuver, accurately distinguishes complete from incomplete CTI block and helps to predict AFL recurrences after ablation.

Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3).

Matrix metalloprotease 13 (MMP13) deficiency in pulmonary fibrosis has described contradictory phenotypes on inflammatory and fibrotic responses after lung injury, and its role during lung fibrosis resolution is still undefined. MMP13 has been considered the main collagenase in rodents, and the remodeling of fibrillar collagen is widely attributed to the action of this enzyme. In this study we aimed to explore the role of MMP13 during lung fibrosis progression and resolution. Lung fibrosis was induced by intratracheal instillation, and inflammatory, fibrotic, and resolution stages were evaluated in Mmp13-null and wild-type (WT) mice. Bronchoalveolar lavage fluid was taken for cytokine array analysis and activity of gelatinases. Our results showed that MMP13 is upregulated mainly during two stages after lung injury, inflammation and resolution of fibrosis, and it is mainly expressed by alveolar and interstitial macrophages. Mmp13-null mice exhibited more extensive inflammation at 7 days after bleomycin treatment, and it was characterized by increased macrophage infiltration and significant alterations in proinflammatory cytokines. We also documented that Mmp13-deficient mice experienced more severe and prolonged lung fibrosis compared with WT mice. Delayed resolution in Mmp13-deficient lungs was characterized by a decreased overall collagenolytic activity and persistent fibrotic foci associated with emphysema-like areas. Together, our findings indicate that MMP13 plays an antifibrotic role and its activity is crucial in lung repair and restoration of tissue integrity during fibrosis resolution.

Impact of an Online Training Program in Smoking Cessation Interventions in Hospitals.

PURPOSE: To assess changes in the self-reported performance of smoking cessation interventions according to the 5A's model (Ask; Advise; Assess; Assist; and Arrange follow-up) among clinicians; and to identify the main barriers and facilitators in smoking cessation implementation before and after an online smoking cessation training program. DESIGN: Pre-post evaluation. METHODS: We assessed self-reported smoking cessation interventions in the implementation of the 5A's model among clinicians working in Catalan hospitals (Spain). In addition, we assessed individual-, behavioral-, and organizational-level factors that act as barriers and facilitators in the implementation of the 5A's model. We used a questionnaire of 63 items reflecting each of the 5A's performance (scored from 0 = none to 10 = most possible). The questionnaire was completed both immediately before and 6 months after the training. We analyzed the data of those participants who had a clinical role and answered pre- and post-questionnaires. We used the nonparametric test for paired data (Wilcoxon) to examine changes in scores. FINDINGS: A total of 127 clinicians completed the pre-post questionnaire; 63.0% were registered nurses, 17.3% were nursing assistants, 7.9% were physicians, and 11.8% were other professionals (p < .001). Overall, there were significant increases in the implementation of the assist component (from a score of 4.5 to 5.2; p < .003) and arrange a follow-up component (from 3.6 to 4.5; p < .001) of the intervention. Scores in the perception of the level of overall preparation, preparedness in using smoking cessation drugs, level of competence, and organizational recognition improved (p < .001) at the follow-up; however, the score in the perception that implementing smoking cessation is part of their job decreased (from 6.3 to 4.4; p < .001). CONCLUSIONS: The online training had a positive impact on the implementation of assist and arrange follow-up components. Although self-preparedness in the management of smokers increased, the motivation and involvement of key professionals decreased. Organizational factors related to the incorporation of resources (such as protocols, records, etc.) should be improved for the correct progression of smoking cessation interventions within the institutions. CLINICAL RELEVANCE: Smoking cessation training programs should incorporate some motivational content to increase the engagement of health professionals in smoking cessation interventions in their clinical practice.

Upregulation and Nuclear Location of MMP28 in Alveolar Epithelium of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive aging-associated disease of unknown etiology. A growing body of evidence indicates that aberrant activated alveolar epithelial cells induce the expansion and activation of the fibroblast population, leading to the destruction of the lung architecture. Some matrix metalloproteinases (MMPs) are upregulated in IPF, indicating that they may be important in the pathogenesis and/or progression of IPF. In the present study, we examined the expression of MMP28 in this disease and evaluated its functional effects in two alveolar epithelial cell lines and in human primary bronchial epithelial cells. We found that the enzyme is expressed in bronchial (apical and cytoplasmic localization) and alveolar (cytoplasmic and nuclear localization) epithelial cells in two different groups of patients with IPF. In vitro MMP28 epithelial silencing decreased the proliferation rate and delayed wound closing, whereas overexpression showed opposite effects, protecting from apoptosis and enhanced epithelial-mesenchymal transition. Our findings demonstrate that MMP28 is upregulated in epithelial cells from IPF lungs, where it may play a role in increasing the proliferative and migratory phenotype in a catalysis-dependent manner.

Hierarchy of Asymmetry at Work: Chain-Dependent Helix-to-Helix Interactions in Supramolecular Polymers.

A detailed investigation of the hierarchy of asymmetry operating in the self-assembly of achiral (1) and chiral ((S)-2 and (R)-3) 1,3,5-triphenylbenzenetricarboxamides (TPBAs) is reported. The aggregation of these TPBAs is conditioned by the point chirality at the peripheral side chains for (S)-2 and (R)-3. An efficient helix-to-helix interaction that goes further in the organization of fibrillar bundles is experimentally detected and theoretically supported only for the achiral TPBA 1. The effective interdigitation of the achiral aliphatic side chains produces a social self-sorting to form preferentially heterochiral macromolecular aggregates.

Burning the Gap: Electrical and Anatomical Basis of the Incremental Pacing Maneuver for Cavotricuspid Isthmus Block Assessment.

INTRODUCTION: The incremental pacing (IP) maneuver is a highly specific technique that improves the ability to confirm complete CTI conduction block during typical atrial flutter (AFL) ablation, and reduces long-term AFL recurrences. The purpose of this study is to assess the performance of new catheters equipped with additional high precision bipoles (AHPB) to allow the visualization of the cavotricuspid isthmus (CTI) conduction gap and to compare them with the IP maneuver. METHODS AND RESULTS: Twenty consecutive patients undergoing catheter ablation of the CTI for AFL were included. The IP maneuver confirmed functional versus complete CTI block. Local electrogram analysis using AHPB was then used to assess the presence or absence of gaps across the CTI line. Mean age was 67 years and 80% were male. At the end of the procedure CTI block was achieved in all patients. A transient stage of functional CTI block was observed in 40%. In all cases a continuous fragmented electrogram was present between the double potentials in the CTI in the AHPB channels. In contrast, no electrogram was observed between the CTI double potentials in any of the 20 patients once complete block was confirmed by the IP maneuver. When both techniques were compared a significant association and correlation were observed (chi-square <0.01, Spearman's rho = 1, P < 0.01). CONCLUSION: Catheters equipped with AHPB can aid in the assessment of complete CTI block during AFL ablation procedures by detecting conduction gaps that correlate with incomplete functional block diagnosed by the IP maneuver.

Role of matrix metalloproteinases in the pathogenesis of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating lung disorder of unknown origin, with very poor prognosis and no effective treatment. The disease is characterized by abnormal activation of alveolar epithelial cells, which secrete numerous mediators involved in the expansion of the fibroblast population, its differentiation to myofibroblasts, and in the exaggerated accumulation of extracellular matrix provoking the loss of lung architecture. Among the excessively produced mediators are several matrix metalloproteases (MMPs) which may contribute to modify the lung microenvironment by various mechanisms. Thus, these enzymes can not only degrade all the components of the extracellular matrix, but they are also able to release, cleave and activate a wide range of growth factors, cytokines, chemokines and cell surface receptors affecting numerous cell functions including adhesion, proliferation, differentiation, recruiting and transmigration, and apoptosis. Therefore, dysregulated expression of MMPs may have profound impact on the biopathological mechanisms implicated in the development of IPF. This review focuses on the current and emerging evidence regarding the role of MMPs on the fibrotic processes in IPF as well as in mouse models of lung fibrosis.

Increased ER Stress and Unfolded Protein Response Activation in Epithelial and Inflammatory Cells in Hypersensitivity Pneumonitis.

Several types of cytotoxic insults disrupt endoplasmic reticulum (ER) homeostasis, cause ER stress, and activate the unfolded protein response (UPR). The role of ER stress and UPR activation in hypersensitivity pneumonitis (HP) has not been described. HP is an immune-mediated interstitial lung disease that develops following repeated inhalation of various antigens in susceptible and sensitized individuals. The aim of this study was to investigate the lung expression and localization of the key effectors of the UPR, BiP/GRP78, CHOP, and sXBP1 in HP patients compared with control subjects. Furthermore, we developed a mouse model of HP to determine whether ER stress and UPR pathway are induced during this pathogenesis. In human control lungs, we observed weak positive staining for BiP in some epithelial cells and macrophages, while sXBP1 and CHOP were negative. Conversely, strong BiP, sXBP1- and CHOP-positive alveolar and bronchial epithelial, and inflammatory cells were identified in HP lungs. We also found apoptosis and autophagy markers colocalization with UPR proteins in HP lungs. Similar results were obtained in lungs from an HP mouse model. Our findings suggest that the UPR pathway is associated with the pathogenesis of HP.

Gene expression profiles reveal molecular mechanisms involved in the progression and resolution of bleomycin-induced lung fibrosis.

Lung fibrosis is the final result of a large number of disorders and is usually considered an irreversible process. However, some evidence suggests that fibrosis could eventually be reversible. In this study we aimed to document the time-related reversibility of bleomycin-induced lung fibrosis and to examine the gene expression profile associated with its initial progression and subsequent resolution. C57BL/6 mice were instilled with a single dose of bleomycin and euthanized at 1, 4, 8, 12, and 16 wk. Control animals received an equal volume of saline. Lung fibrosis was examined by morphology and hydroxyproline content and the transcriptional signature by gene microarray analysis. Our results showed that bleomycin-injured mice developed prominent inflammation at 1 wk, followed by fibrosis that peaked at 2 mo. Then fibrosis resolved until lungs displayed almost normal architecture at 4 mo. Genomewide transcriptional profiling revealed 533 significantly changed genes. Self-organizing maps analysis of these genes identified four clusters based on the temporal pattern of gene expression. Clusters 1 and 2 contained genes upregulated during the inflammatory and fibrotic response and were enriched for extracellular matrix-related genes including several collagens, matrix metalloproteinases, and TIMP-1. Cluster 3 identified upregulated genes during the fibrotic response, and cluster 4 contained genes decreased during inflammation and fibrosis that increased during resolution. Most enriched pathways included genes involved in cell cycle and in regulation of transcription. Our findings corroborate the reversibility of bleomycin-induced lung fibrosis and reveal transcriptional signatures that characterize the progression and resolution.

Matrix metalloproteinase-19 is a key regulator of lung fibrosis in mice and humans.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by epithelial phenotypic changes and fibroblast activation. Based on the temporal heterogeneity of IPF, we hypothesized that hyperplastic alveolar epithelial cells regulate the fibrotic response. OBJECTIVES: To identify novel mediators of fibrosis comparing the transcriptional signature of hyperplastic epithelial cells and conserved epithelial cells in the same lung. METHODS: Laser capture microscope and microarrays analysis were used to identify differentially expressed genes in IPF lungs. Bleomycin-induced lung fibrosis was evaluated in Mmp19-deficient and wild-type (WT) mice. The role of matrix metalloproteinase (MMP)-19 was additionally studied by transfecting the human MMP19 in alveolar epithelial cells. MEASUREMENTS AND MAIN RESULTS: Laser capture microscope followed by microarray analysis revealed a novel mediator, MMP-19, in hyperplastic epithelial cells adjacent to fibrotic regions. Mmp19(-/-) mice showed a significantly increased lung fibrotic response to bleomycin compared with WT mice. A549 epithelial cells transfected with human MMP19 stimulated wound healing and cell migration, whereas silencing MMP19 had the opposite effect. Gene expression microarray of transfected A549 cells showed that PTGS2 (prostaglandin-endoperoxide synthase 2) was one of the highly induced genes. PTGS2 was overexpressed in IPF lungs and colocalized with MMP-19 in hyperplastic epithelial cells. In WT mice, PTGS2 was significantly increased in bronchoalveolar lavage and lung tissues after bleomycin-induced fibrosis, but not in Mmp19(-/-) mice. Inhibition of Mmp-19 by siRNA resulted in inhibition of Ptgs2 at mRNA and protein levels. CONCLUSIONS: Up-regulation of MMP19 induced by lung injury may play a protective role in the development of fibrosis through the induction of PTGS2.

Remnant Blood Quantification: Informing the Definition of Minimal Risk in Clinical Research.

Guidelines from the Office for Human Research Protections regarding categories of research that institutional review boards (IRBs) may review through expedited procedures limit the volume of blood that can be obtained from research participants for minimal risk research purposes. As defined by the Common Rule, minimal risk research is research in which the probability and magnitude of harm or discomfort anticipated are not greater than the probability and magnitude of harm or discomfort encountered from routine clinical tests. For this study, we considered the volume of remnant blood following routine clinical tests in light of the current definition of minimal risk in research. Conducted at a single institution, this was a prospective cross-sectional study that evaluated blood draws from 122 patients. The median daily remnant blood volume was 11.6 (interquartile range [IQR]: 12.3, 15.2) ml for all patients and 12.9 (IQR: 13.1, 16.9) ml for patients admitted to the intensive care unit. Our findings regarding daily remnant blood volume suggest that the currently allowable blood-volume limits to qualify for expedited review or to qualify as not more than minimal risk research involving blood draws from nonhealthy adults are less than what patients experience in routine medical testing. These findings support permitting an increase in the allowable blood-volume limits to meet the regulatory definition of minimal risk research for obtaining expedited IRB review of studies in which blood samples will be collected.

Performance evaluation of an industrial ceramic nanofiltration unit for wastewater treatment in oil production.

An industrial ceramic nanofiltration membrane (pore size 0.9 nm) was tested in a Canadian oil field for more than 12,500 h to treat wastewater directly from daily operations, without any type of pre-treatment. This wastewater contained a high content of total suspended solids (13 to 510 mg/kg), and total organic carbon (31 to 134 mg/kg). The membrane unit was operated at different transmembrane pressure (TMP) set points (4-16 bar) and recovery set points (40-80%). The data show that ion and compound rejection depend strongly on a combination of both TMP and recovery, with the largest rejection occurring at low recovery values and high TMP values. Two mechanisms were responsible for rejection: sieving, which mostly impacted compound rejection, and electrostatic phenomena that impacted ion rejection. It is shown that ion rejection depends linearly on charge density of the ion. Ion rejection was measured as high as 85% and compounds (such as TSS) were rejected as high as 100%. The specific flux varied between 1-10 L/(m2.h.bar). Results from this field testing indicate the possibility of using these types of ceramic membranes for oil field wastewater treatment.

Influence of PACE score and conduction disturbances in the incidence of early new onset atrial fibrillation after typical atrial flutter ablation.

PURPOSE: Patients undergoing cavotricuspid isthmus (CTI) ablation for typical flutter (AFL) have a high incidence of new onset atrial fibrillation (AF). We aimed to analyze the influence of PACE score to predict new onset AF in this subset of patients to stratify thromboembolic risk. METHODS: Between 2017 and 2019, patients undergoing CTI ablation for AFL and without history of AF were prospectively included. All patients were monitored continuously by implantable loop recorder and followed by remote monitoring. RESULTS: Overall 48 patients were included. New onset AF rate at 12 months was 56.3%. We observed two very strong independent predictors for new onset AF: a PACE score ≥ 30 (HR:6.9; 95% CI:1.71-27.91; p = 0.007) and an HV interval ≥ 55 (HR:11.86; 95% CI:2.57-54.8; p = 0.002). CONCLUSIONS: The incidence of newly diagnosed AF is high in patients with AFL after CTI ablation, and can occur early. A high PACE score and/or long HV interval predict even higher risk, and may be useful in the decision for empiric long-term anticoagulation.

COVID-19 among workers of a comprehensive cancer centre between first and second epidemic waves (2020): a seroprevalence study in Catalonia, Spain.

OBJECTIVES: Patients with cancer are at higher risk for severe COVID-19 infection. COVID-19 surveillance of workers in oncological centres is crucial to assess infection burden and prevent transmission. We estimate the SARS-CoV-2 seroprevalence among healthcare workers (HCWs) of a comprehensive cancer centre in Catalonia, Spain, and analyse its association with sociodemographic characteristics, exposure factors and behaviours. DESIGN: Cross-sectional study (21 May 2020-26 June 2020). SETTING: A comprehensive cancer centre (Institut Català d'Oncologia) in Catalonia, Spain. PARTICIPANTS: All HCWs (N=1969) were invited to complete an online self-administered epidemiological survey and provide a blood sample for SARS-CoV-2 antibodies detection. PRIMARY OUTCOME MEASURE: Prevalence (%) and 95% CIs of seropositivity together with adjusted prevalence ratios (aPR) and 95% CI were estimated. RESULTS: A total of 1266 HCWs filled the survey (participation rate: 64.0%) and 1238 underwent serological testing (97.8%). The median age was 43.7 years (p25-p75: 34.8-51.0 years), 76.0% were female, 52.0% were nursing or medical staff and 79.0% worked on-site during the pandemic period. SARS-CoV-2 seroprevalence was 8.9% (95% CI 7.44% to 10.63%), with no differences by age and sex. No significant differences in terms of seroprevalence were observed between onsite workers and teleworkers. Seropositivity was associated with living with a person with COVID-19 (aPR 3.86, 95% CI 2.49 to 5.98). Among on-site workers, seropositive participants were twofold more likely to be nursing or medical staff. Nursing and medical staff working in a COVID-19 area showed a higher seroprevalence than other staff (aPR 2.45, 95% CI 1.08 to 5.52). CONCLUSIONS: At the end of the first wave of the pandemic in Spain, SARS-CoV-2 seroprevalence among Institut Català d'Oncologia HCW was lower than the reported in other Spanish hospitals. The main risk factors were sharing household with infected people and contact with COVID-19 patients and colleagues. Strengthening preventive measures and health education among HCW is fundamental.

Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models.

Matrix metalloproteinases (MMPs) are a large family of zinc-endopeptidases which play important roles in multiple physiological and pathological processes. These enzymes are widely distributed in all kingdoms of life and have likely evolved from a single-domain protein which underwent successive rounds of duplication, gene fusion and exon shuffling events to generate the multidomain architecture and functional diversity currently exhibited by MMPs. Proper regulation of these enzymes is required to prevent their unwanted activity in a variety of disorders, including cancer, arthritis and cardiovascular diseases. Multiple hormones, cytokines and growth factors are able to induce MMP expression, although the tissue specificity of the diverse family members is mainly achieved by the combination of different transcriptional control mechanisms. The integration of multiple signaling pathways, coupled with the cooperation between several cis-regulatory elements found at the MMP promoters facilitates the strict spatiotemporal control of MMP transcriptional activity. Additionally, epigenetic mechanisms, such as DNA methylation or histone acetylation, may also contribute to MMP regulation. Likewise, post-transcriptional regulatory processes including mRNA stability, protein translational efficiency, and microRNA-based mechanisms have been recently described as modulators of MMP gene expression. Parallel studies have led to the identification of MMP polymorphisms and mutations causally implicated in the development of different genetic diseases. These genomic analyses have been further extended through the generation of animal models of gain- or loss-of-function for MMPs which have allowed the identification of novel functions for these enzymes and the establishment of causal relationships between MMP dysregulation and development of different human diseases. Further genomic studies of MMPs, including functional analysis of gene regulation and generation of novel animal models will help to answer the multiple questions still open in relation to a family of enzymes which strongly influence multiple events in life and disease.

Pacemaker clinic: an opportunity to detect silent atrial fibrillation and improve antithrombotic treatment.

AIMS: The prevalence of atrial fibrillation (AF) in patients with pacemakers is high, and often passes unnoticed. Our aim was to assess the use of antithrombotic treatment in this group of patients. METHODS AND RESULTS: All patients who came to our institution to have their pacemakers checked during the year 2008 were included in this study. The atrial activity was assessed by slowing down the paced frequency if necessary, and by the analysis of atrial electrograms in atrial-based pacemakers. The appropriateness of the antithrombotic treatment was evaluated by a cardiologist. Out of 585 patients, 216 (36.9%) displayed AF at some point during the 5.5-year monitoring period (1.5-11), although only 58 (9.9%) displayed it at the time of the implant. Of these 216, 58% were men, with an average age of 80 years (76-86 years). The pacemaker was implanted in response to an atrioventricular block (AVB) in 46.3% of the cases, sinoatrial node disorder in 24.1% of the cases, and slow AF in 25.9% of the cases. The CHADS2 score was 0 points in 4.2% (9) of the cases, 1 point in 19% (41) of the cases, and ≥ 2 points in 77% (173) of the cases. Despite this, only 58.3% of the cases received anticoagulant treatment. The existence of arrhythmia at the time of implantation [odds ratio (OR) = 4.25; 95% confidence interval (95% CI), 1.72-10.51; P = 0.002] and the implantation of a pacemaker with atrioventricular synchronization (OR = 13.23; 95% CI, 2.89-60.56; P = 0.001) were associated with the use of anticoagulant treatment in those cases with CHADS2>2. CONCLUSION: Atrial fibrillation is common in patients fitted with pacemakers. Despite the high risk of embolism, an underuse of anticoagulant treatment was observed.

Absence or inhibition of matrix metalloproteinase-8 decreases ventilator-induced lung injury.

Mechanical ventilation is a life-saving therapy that can also damage the lungs. Ventilator-induced lung injury (VILI) promotes inflammation and up-regulates matrix metalloproteinases (MMPs). Among these enzymes, MMP-8 is involved in the onset of inflammation by processing different immune mediators. To clarify the role of MMP-8 in a model of VILI and their relevance as a therapeutic target, we ventilated wild-type and MMP-8-deficient mice with low or high pressures for 2 hours. There were no significant differences after low-pressure ventilation between wild-type and knockout animals. However, lack of MMP-8 results in better gas exchange, decreased lung edema and permeability, and diminished histological injury after high-pressure ventilation. Mmp8(-/-) mice had a different immune response to injurious ventilation, with decreased neutrophilic infiltration, lower levels of IFN-γ and chemokines (LPS-induced CXC chemokine, macrophage inflammatory protein-2), and significant increases in anti-inflammatory cytokines (IL-4, IL-10) in lung tissue and bronchoalveolar lavage fluid. There were no differences in MMP-2, MMP-9, or tissue inhibitor of metalloproteinase-1 between wild-type and knockout mice. These results were confirmed by showing a similar protective effect in wild-type mice treated with a selective MMP-8 inhibitor. We conclude that MMP-8 promotes acute inflammation after ventilation with high pressures, and its short-term inhibition could be a therapeutic goal to limit VILI.