Peak left atrial longitudinal strain is associated with all-cause mortality in patients with ventricular functional mitral regurgitation.

PURPOSE: Chronic mitral regurgitation promotes left atrial (LA) remodeling. However, the significance of LA dysfunction in the setting of ventricular functional mitral regurgitation (FMR) has not been fully investigated. Our aim was to assess the prognostic impact of peak atrial longitudinal strain (PALS), a surrogate of LA function, in patients with FMR and reduced left ventricular ejection fraction (LVEF). METHODS: Patients with at least mild ventricular FMR and LVEF < 50% under optimized medical therapy who underwent transthoracic echocardiography at a single center were retrospectively identified in the laboratory database. PALS was assessed by 2D speckle tracking in the apical 4-chamber view and the study population was divided in two groups according to the best cut-off value of PALS, using receiver operating characteristics (ROC) curve analysis. The primary endpoint-point was all-cause mortality. RESULTS: A total of 307 patients (median age 70 years, 77% male) were included. Median LVEF was 35% (IQR: 27 - 40%) and median effective regurgitant orifice area (EROA) was 15mm2 (IQR: 9 - 22mm2). According to current European guidelines, 32 patients had severe FMR (10%). During a median follow-up of 3.5 years (IQR 1.4 - 6.6), 148 patients died. The unadjusted mortality incidence per 100 persons-years increased with progressively lower values of PALS. On multivariable analysis, PALS remained independently associated with all-cause mortality (adjusted hazard ratio 1.052 per % decrease; 95% CI: 1.010 - 1.095; P = 0.016), even after adjustment for several (n = 14) clinical and echocardiographic confounders. CONCLUSION: PALS is independently associated with all-cause mortality in patients with reduced LVEF and ventricular FMR.

The role of local inflammation in complications associated with intubation in pediatric patients: A narrative review.

Although the most important primary local inflammatory response factor to intubation is not yet clear, it is known that it may be directly attributed to the presence of trauma during intubation or the response of oral bacterial flora present in the trachea. It is known that prolonged intubation is associated with worse outcomes, but other underlying systemic issues, such as sepsis and trauma, are also associated with this result. Likewise, patients who require advanced airway management and excessive manipulation are more likely to experience complications. There are various inflammatory mediators that are generated during orotracheal intubation, many of which can be considered targets for therapies to help reduce inflammation caused by intubation. However, there is little evidence on the management of the inflammatory response induced by orotracheal intubation in pediatric patients. Therefore, the aim of this narrative review is to highlight the intubation associated complications that can arise from poorly controlled inflammation in intubated pediatric patients, review the proposed pathophysiology behind this, and discuss the current treatments that exist. Finally, taking into account the discussion on pathophysiology, we describe the current therapies being developed and future directions that can be taken in order to create more treatment options within this patient population.

Proteomics as a New-Generation Tool for Studying Moulds Related to Food Safety and Quality.

Mould development in foodstuffs is linked to both spoilage and the production of mycotoxins, provoking food quality and food safety concerns, respectively. The high-throughput technology proteomics applied to foodborne moulds is of great interest to address such issues. This review presents proteomics approaches useful for boosting strategies to minimise the mould spoilage and the hazard related to mycotoxins in food. Metaproteomics seems to be the most effective method for mould identification despite the current problems related to the bioinformatics tool. More interestingly, different high resolution mass spectrometry tools are suitable for evaluating the proteome of foodborne moulds able to unveil the mould's response under certain environmental conditions and the presence of biocontrol agents or antifungals, being sometimes combined with a method with limited ability to separate proteins, the two-dimensional gel electrophoresis. However, the matrix complexity, the high ranges of protein concentrations needed and the performing of multiple steps are some of the proteomics limitations for the application to foodborne moulds. To overcome some of these limitations, model systems have been developed and proteomics applied to other scientific fields, such as library-free data independent acquisition analyses, the implementation of ion mobility, and the evaluation of post-translational modifications, are expected to be gradually implemented in this field for avoiding undesirable moulds in foodstuffs.

An in vitro assay of the effect of lysine oxidation end-product, α-aminoadipic acid, on the redox status and gene expression in probiotic Lactobacillus reuteri PL503.

This study was designed to gain information about the underlying mechanisms of the effects of a food-occurring free oxidized amino acid, α-aminoadipic acid (AAA), on the probiotic Lactobacillus reuteri PL503. This bacterium was incubated in colonic-simulated conditions (37 °C for 24 h in microaerophilic conditions) and exposed to three food-compatible AAA concentrations, namely, 1 mM, 5 mM, and 10 mM. A control group with no AAA exposure was also considered. Each of the four experimental conditions was replicated three times and samplings were collected at 12, 16, 20, and 24 h. The downregulation of the uspA gene by AAA (0.5-fold decrease as compared to control) suggests that AAA is identified as a potential chemical threat. The dhaT gene, implicated in the antioxidant defense, was found to be upregulated in bacteria treated with 1 and 5 mM AAA (up to twofold increase, as compared to control), which suggest the ability of the oxidized amino acid to impair the redox status of the bacterium. In fact, AAA caused an increased production of reactive oxygen species (ROS) and the accretion of post-translational changes (protein carbonylation) in L. reuteri (up to 13 nmol allysine/mg protein vs 1.8 nmol allysine/mg protein in control). These results suggest that probiotic bacteria identify oxidized amino acids as harmful species and activate mechanisms that may protect themselves and the host against their noxious effects.

Pectoralis major muscle quantification by cardiac MRI is a strong predictor of major events in HF.

Clinical overt cardiac cachexia is a late ominous sign in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The main goal of this study was to assess the feasibility and prognostic significance of muscle mass quantification by cardiac magnetic resonance (CMR) in HF with reduced LVEF. HF patients with LVEF < 40% (HFrEF) referred for CMR were retrospectively identified in a single center. Key exclusion criteria were primary muscle disease, known infiltrative myocardial disease and intracardiac devices. Pectoralis major muscles were measured on standard axial images at the level of the 3rd rib anteriorly. Time to all-cause death or HF hospitalization was the primary endpoint. A total of 298 HF patients were included (mean age 64 ± 12 years; 76% male; mean LVEF 30 ± 8%). During a median follow-up of 22 months (IQR: 12-33), 67 (22.5%) patients met the primary endpoint (33 died and 45 had at least 1 HF hospitalization). In multivariate analysis, LVEF [Hazard Ratio (HR): 0.950; 95% Confidence Interval (CI): 0.917-0.983; p = 0.003), NYHA class I-II vs III-IV (HR: 0.480; CI: 0.272-0.842; p = 0.010), creatinine (HR: 2.653; CI: 1.548-4.545; p < 0.001) and pectoralis major area (HR: 0.873; 95% CI: 0.821-0.929; p < 0.001) were independent predictors of the primary endpoint, when adjusted for gender and NT-pro-BNP levels. Pectoralis major size measured by CMR in HFrEF was independently associated with a higher risk of death or HF hospitalization. Further studies to establish appropriate age and gender-adjusted cut-offs of muscle areas are needed to identify high-risk subgroups.

Effect of Debaryomyces hansenii and the antifungal PgAFP protein on Alternaria spp. growth, toxin production, and RHO1 gene expression in a tomato-based medium.

Tomato fruit is susceptible to Alternaria spp. spoilage, which poses a health risk due to their mycotoxin production. Biopreservation relies on the use of whole microorganisms or their metabolites to manage spoilage microorganisms including filamentous fungi. However, the use of treatments at fungistatic level might activate intracellular pathways, which can cause an increment in mycotoxin accumulation. The objective of this work was to evaluate the effect of two strains of Debaryomyces hansenii and the antifungal protein PgAFP at 10 and 40 µg/mL. Both growth and production of two of the most common mycotoxins (tenuazonic acid and alternariol monomethyl ether) by Alternaria tenuissima sp.-grp. and Alternaria arborescens sp.-grp. on a tomato-based matrix, were analysed at 12 °C. Additionally, the impact of these biocontrol agents on the stress-related RHO1 gene expression was assessed. All treatments reduced mycotoxin accumulation (from 27 to 92% of inhibition). Their mode of action against Alternaria spp. in tomato seems unrelated to damages to fungal cell wall integrity at the genomic level. Therefore, the two D. hansenii strains (CECT 10352 and CECT 10353) and the antifungal protein PgAFP at 10 µg/mL are suggested as biocontrol strategies in tomato fruit at postharvest stage.

Development of a multiplex real-time PCR to differentiate the four major Listeria monocytogenes serotypes in isolates from meat processing plants.

Listeria monocytogenes is an important foodborne pathogen, causative agent of listeriosis. The epidemiology and persistence of this bacterium in meat processing plants may be related to its serotype, so it is of utmost importance to carry out a correct differentiation of L. monocytogenes serotypes. The objective of this study was to develop a unique quadruplex real-time quantitative PCR (qPCR) method able to differentiate the four most predominant and worrying L. monocytogenes serotypes (1/2a, 1/2b, 1/2c and 4b) in isolates from meat processing plants and ready-to-eat (RTE) dry-cured meat products. The design of specific primers and probes was based on the lmo0737, lmo0308, ORFC (locus genomically equivalent to gltA-gltB) and ORF2110 genes. A qPCR based on a fragment of the 16S rRNA gene was used to ensure the amplification of Listeria spp. genomic DNA. The standard curves showed efficiency values ranging between 92.3% and 105.8% and, R2 values > 0.98. The specificity of the method was also confirmed by the comparison of the results with those obtained by a previously reported conventional multiplex PCR. In addition, none of the strains which were not ascribed to L. monocytogenes amplified any of the target genes related to the four major serotypes of this pathogenic species. The qPCR, therefore, provides a sensitive, specific and rapid tool for identifying the L. monocytogenes serotypes 1/2a, 1/2b, 1/2c and 4b. This method could be very useful for identifying sources of L. monocytogenes contamination in the meat industry or for epidemiological monitoring of persistent strains throughout the processing of RTE meat products.

Biocontrol of aflatoxigenic Aspergillus parasiticus by native Debaryomyces hansenii in dry-cured meat products.

Dry-cured meat products, such as dry-cured ham or dry-fermented sausages, are characterized by their particular ripening process, where a mould population grows on their surface. Some of these moulds are hazardous to the consumers because of their ability to produce mycotoxins including aflatoxins (AFs). The use of native yeasts could be considered a potential strategy for controlling the presence of AFs in dry-cured meat products. The aim of this work was to evaluate the antagonistic activity of two native Debaryomyces hansenii strains on the relative growth rate and the AFs production in Aspergillus parasiticus. Both D. hansenii strains significantly reduced the growth rates of A. parasiticus when grown in a meat-model system at different water activity (aw) conditions. The presence of D. hansenii strains caused a stimulation of AFs production by A. parasiticus at 0.99 aw. However, at 0.92 aw the yeasts significantly reduced the AFs concentration in the meat-model system. The relative expression levels of the aflR and aflS genes involved in the AFs biosynthetic pathway were also repressed at 0.92 aw in the presence of both D. hansenii strains. These satisfactory results were confirmed in dry-cured ham and dry-fermented sausage slices inoculated with A. parasiticus, since both D. hansenii strains significantly reduced AFs amounts in these matrices. Therefore, both tested D. hansenii strains could be proposed as biocontrol agents within a HACCP framework to minimize the hazard associated with the presence of AFs in dry-cured meat products.

Gene expression as a good indicator of aflatoxin contamination in dry-cured ham.

Aspergillus flavus and Aspergillus parasiticus are mould species producers of aflatoxins (AFs) and may grow on dry-cured ham during the ripening process. In this study, the influence of different water activity (aw) and temperatures on the temporal relative expression of three genes involved in AFs biosynthesis and their relationship with AFs production on dry-cured ham-based medium were evaluated. In general, the regulatory aflR and aflS genes showed similar expression patterns, and the expression of the structural aflP gene was much higher than that obtained for aflR and aflS genes. Regarding A. flavus, a decrease of aw regardless of temperature caused an increase of the expression of the regulatory aflR and aflS genes. Concerning A. parasiticus, the highest and lowest expression values of the regulatory aflR and aflS genes were found at 0.95 aw and 0.85 aw, respectively. The expression of the structural aflP gene of both species was stimulated at low temperature and aw. The PCA analysis indicated that both toxigenic species showed a strong correlation between the relative expression of the aflR and aflS genes and the concentration of AFs under conditions which simulate dry-cured ham ripening. This suggests that an early detection of the expression of regulatory genes can be a good indicator of possible AFs contamination of dry-cured ham through ripening.

Selection of reference genes to quantify relative expression of ochratoxin A-related genes by Penicillium nordicum in dry-cured ham.

Penicillium nordicum is an important and consistent producer of ochratoxin A (OTA) in NaCl-rich foods such as dry-cured ham. OTA is a toxic secondary metabolite which provokes negative effects on consumer health. Once OTA is produced in ham, this mycotoxin is difficult to remove. Since gene expression always precedes OTA production, analysis of expression of OTA-related genes by reverse transcription real-time PCR (RT-qPCR) could be a valuable tool to predict OTA contamination in ham. However scarce RT-qPCR protocols are properly validated leading to inconsistent data analyses. The objective of this study was to examine reference genes suitable for normalisation in designing and developing new RT-qPCR methods for quantifying the relative expression of genes involved in OTA biosynthesis (otapks and otanps) by P. nordicum on a dry-cured ham model system after 7 days of incubation. Firstly, primers based on three housekeeping genes commonly found in moulds, ß-tubulin, COI and ITS, and on the otapks gene were designed. The primer pair F/R-npstr previously developed on the otanps gene was also used. Although most of the designed primers met the requirements needed to be used in qPCR assays, the primer pairs ß-tubF1/R1, COI-F1/R1, ITSF2/R2 and otapksF3/R3 for the ß-tubulin, COI, ITS and otapks genes, respectively, were selected due to their lowest Cq value. Next, the two assumptions of the 2-ΔΔCT method to evaluate the relative expression of the otapks and otanps genes were fulfilled for two of the three endogenous genes tested, ß-tubulin and COI. However, ß-tubulin was considered more proper as reference gene than COI under the environmental conditions assayed since its expression values by day 7 were more related to OTA production. Therefore, the two RT-qPCR methods for the analysis of the relative expression of the otapks and otanps genes have been properly validated and can be used as control tools to avoid or minimise the presence of OTA in ham.

Selection and evaluation of Debaryomyces hansenii isolates as potential bioprotective agents against toxigenic penicillia in dry-fermented sausages.

Biocontrol using autochthonous Debaryomyces hansenii isolates is a potentially suitable strategy for inhibiting toxigenic moulds in dry-cured meat products. The antifungal activity of 280 D. hansenii isolated from dry-cured meat products as well as the mode of action of the most active isolates against toxigenic penicillia were evaluated in this work. A 13.9% of the D. hansenii isolates showed inhibitory activity in a radial inhibition assay. The effects on penicillia growth of both the cell-free culture filtrate and volatile compounds from active yeast isolates were analysed. Penicillia growth inhibition by D. hansenii was probably based on additive or synergistic effects of several inhibiting factors such as competition for nutrient and space, and production of soluble or volatile compounds. When four D. hansenii isolates were tested on dry-fermented sausage, two of them produced a significantly growth reduction of the ochratoxigenic Penicillium verrucosum, keeping its counts under the level considered as hazardous for the mycotoxin presence. Therefore, the use of these two D. hansenii isolates during the processing of dry-fermented meat product could be a promising tool to control toxigenic moulds in the meat industry.

Deciphering the antiochratoxigenic activity of plant extracts and Debaryomyces hansenii against Penicillium nordicum in a "chorizo"-based medium by proteomic analysis.

Penicillium nordicum is the main ochratoxin A (OTA)-producing species on the surface of dry-fermented sausages, such as the "chorizo". New antifungal strategies are being developed using biocontrol agents (BCAs), such as plant extracts and native microorganisms. This work aimed to evaluate the antiochratoxigenic capacity and the causative modes of action of BCAs (rosemary essential oil (REO), acorn shell extract and the yeast Debaryomyces hansenii (Dh)) in a "chorizo"-based medium (Ch-DS). BCAs were inoculated on Ch-DS together with P. nordicum and incubated at 12 °C for 15 days to collect mycelia for OTA analyses and comparative proteomics. Both REO and Dh alone decreased OTA accumulation up to 99% and affected the abundance of P. nordicum proteins linked to cell wall organisation, synthesis of OTA-related metabolites and ergosterol synthesis. It is worth highlighting the increased abundance of an amidase by REO, matching with the decrease in OTA. The use of REO and Dh as BCAs could be an effective strategy to reduce the OTA hazard in the meat industry. Based on their not fully coincident modes of action, their combined application could be of interest in "chorizo" to maximise their potential against ochratoxigenic strains.

Perspectives on the Probiotic Potential of Indigenous Moulds and Yeasts in Dry-Fermented Sausages.

The role of indigenous fungi in the appropriate development of sensory properties and the safety of dry-fermented sausages has been widely established. Nonetheless, their applications as probiotic agents have not been elucidated in such products yet, despite their promising functional features. Thus, it should be interesting to evaluate the probiotic potential of native Debaryomyces hansenii isolates from dry-fermented sausages and their application in the meat industry, because it is the most frequently isolated yeast species from these foodstuffs and its probiotic effects for animals as well as its possible probiotic activity for human beings have been demonstrated. Within the functional ability of foodborne yeasts, anti-inflammatory, antioxidant, antimicrobial, antigenotoxic, and immunomodulatory properties have been reported. Similarly, the use of dry-fermented sausages as vehicles for probiotic moulds remains a challenge because the survival and development of moulds in the gastrointestinal tract are still unknown. Nevertheless, some moulds have been isolated from faeces possibly from their spores as a form of resistance. Additionally, their beneficial effects on animals and humans, such as the decrease in lipid content and the anti-inflammatory activity, have been reported, although they seem to be more related to their postbiotic capacity due to the generated bioactive compounds with profunctional attributes than to their role as probiotics. Therefore, further studies providing knowledge useful for generating dry-fermented sausages with improved functionality are fully necessary.

Cardiovascular effects of hyoscine butylbromide in patients under general anaesthesia.

BACKGROUND: Cardiovascular effects for drugs such as hyoscine butylbromide are poorly documented in the literature, unlike atropine, which is considered the antimuscarinic of choice in the presence of intraoperative bradycardia. AIM: The aim of the study was to describe the dose-related cardiovascular effect of hyoscine butylbromide in patients between 18 and 65 years of age, with low perioperative risk undergoing elective surgery under general anaesthesia on an outpatient basis or hospitalised at our institution between 1 January and 31 May 2019. METHODS: Descriptive, cross-sectional, retrospective study; 28 patients with low perioperative risk who underwent general anaesthesia were selected. Changes in heart rate and blood pressure were analysed during the first 6 minutes after the administration of hyoscine butylbromide. The data obtained was recorded in a Microsoft Excel database and analysed using the Excel analysis tool and IBM SPSS. RESULTS: The average dose of 0.15mg/kg of hyoscine butylbromide achieved an increase in heart rate and mean arterial pressure in 96% and 92.8%, respectively, in the first 6 minutes after the administration. Significant changes in heart rate and blood pressure were obtained during the first 6 minutes at doses between 0.05mg/kg and 0.15mg/kg. CONCLUSION: Hyoscine butylbromide generates positive effects on the heart rate and blood pressure of patients under general anaesthesia, representing a possible alternative in the management of intraoperative bradycardia.

External validation of the unifying concept for the quantitative assessment of functional mitral regurgitation.

PURPOSE: A novel conceptual framework was introduced to enhance the quantitative assessment of functional mitral regurgitation (FMR) and improve risk stratification. However, the data was derived from a single-center cohort and lack external validation. We aimed to validate the proposed algorithm using a different patient population. METHODS: Patients with at least mild FMR and reduced left ventricular ejection fraction (< 50%) were retrospectively identified at a single-center. The cohort was stratified in low, intermediate and high-risk according to the proposed framework, on the basis of effective regurgitant orifice area (EROA) and regurgitant volume (RegVol). Patients within the intermediate-risk group were subsequently reclassified into either the low-risk category (Regurgitant Fraction, RegFrac < 50%) or the high-risk category (RegFrac ≥ 50%) based on their regurgitant fraction. The primary endpoint was all-cause mortality. RESULTS: A total of 572 patients were included. During a median follow-up of 3.8 years there were 254 deaths (44%). On multivariable analysis, the proposed thresholds for FMR severity remained independently associated with all-cause mortality (adjusted hazard ratio: 1.488; 95% confidence interval [CI]: 1.110-2.013; p-value = 0.010). This algorithm demonstrated superior discriminative ability (C-statistic: 0.664) compared to contemporary guidelines (C-statistic: 0.522; p-value for comparison < 0.001). Additionally, it resulted in a significant improvement in the net reclassification index (0.162; p-value < 0.001). CONCLUSIONS: Within our cohort, the application of the proposed concept demonstrated a significant association with a higher risk of all-cause mortality. Moreover, this conceptual framework showcased the potential to improve the accuracy of risk prediction beyond current guidelines.

Beyond exercise oscillatory ventilations: the prognostic impact of loop gain in heart failure.

Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) ≤ 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016-2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared to patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF ≤ 50%, outperforming the classification of EOV.

Loop gain is an objective parameter that quantifies ventilatory instability and demonstrated strong prognostic value in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤ 50%. Loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of exercise oscillatory ventilation was not prognostically significant when added to loop gain measurement.

Proteomic evaluation of the effect of antifungal agents on Aspergillus westerdijkiae ochratoxin A production in a dry-cured fermented sausage-based medium.

Aspergillus westerdijkiae may produce large amounts of ochratoxin A (OTA) in dry-cured meat products. Natural strategies to control ochratoxigenic moulds using biocontrol agents (BCAs) are currently in the spotlight. The aim of this study was to test the effects of Debaryomyces hansenii and its combination with rosemary derivatives and with a commercial antifungal preparation composed by natamycin and potassium sorbate (AP) against A. westerdijkiae in a dry-cured fermented sausage based-medium. The yeast and rosemary leaves were added to the medium, and rosemary essential oil and AP were added on the casings put on the medium surface to simulate the real product. The growth rate, OTA production and comparative proteomics were analysed. The mould growth in the presence of each treatment was not indicative of their efficiency on OTA repression. The treatment with AP did not affect to the OTA concentration, maybe as consequence of the stressful stimulation of the subinhibitory doses used. D. hansenii added alone or with rosemary showed the best results, decreasing the OTA production >80 %, suggesting that it can be useful as preservative agent during industrial processing. Attending to the proteomic results, its antifungal activity seems to be based on the reduction in abundance of proteins involved in OTA biosynthesis and in the cell wall integrity pathway.

A case report of arrhythmogenic mitral valve disease: still a long way to go.

Background: Mitral valve prolapse (MVP) is a common valvular heart disease and has often been associated with an increased risk of sudden cardiac death (SCD). This underlines the pressing need for the establishment of consistent tools for arrhythmic risk prediction. Case summary: A 73-year-old man with previous diagnosis of MVP was referred to the cardiology outpatient consult for a 1-month history of near-syncope and light-headedness. He had no family history of SCD. Physical examination was unremarkable. Holter monitoring recorded frequent and multiple long episodes of non-sustained ventricular tachycardia (VT) and paroxysmal atrial fibrillation with controlled ventricular response. Echocardiogram revealed mitral bileaflet billowing, systolic curling, and annular disjunction, as well as increased peak systolic strain dispersion with two-dimensional speckle tracking. Cardiac magnetic resonance disclosed additional tricuspid annular dilatation and disjunction, as non-ischaemic late gadolinium enhancement on the left ventricular basal inferolateral wall. The Heart Team decided to implant a defibrillator as primary prevention for SCD due to arrhythmogenic mitral valve disease (AMVD) with high-risk features. The patient remained asymptomatic over the next 2 years, when he suffered an appropriate shock due to VT at 200 b.p.m. Discussion: Here, we present a case of a patient with AMVD with classic features of high arrhythmic risk but also with some unusual characteristics such as older age, male gender, and only little pronounced mitral valve billowing, emphasizing the wide heterogeneity and lack of knowledge surrounding this entity.

Molecular mechanisms of the disturbance caused by malondialdehyde on probiotic Lactobacillus reuteri PL503.

This study aimed to provide insight into the molecular and genetic mechanisms implicated in the responses of Lactobacillus reuteri against the oxidative stress induced by malondialdehyde (MDA) by analysing protein oxidation and assessing the uspA and the dhaT genes. Four experimental groups were evaluated depending on the concentration of MDA added in Man, Rogosa and Sharpe (MRS) broth: Control (L. reuteri), 5 µM (L. reuteri + 5 µM MDA), 25 µM (L. reuteri + 25 µM MDA) and 100 µM (L. reuteri + 100 µM MDA). Three replicates were incubated at 37 °C for 24 h in microaerophilic conditions and sampled at 12, 16, 20 and 24 h. The upregulation of the uspA gene by L. reuteri indicates the recognition of MDA as a potential DNA-damaging agent. The dhaT gene, encoding a NADH-dependent-oxidoreductase, was also upregulated at the highest MDA concentrations. This gene was proposed to play a role in the antioxidant response of L. reuteri. The incubation of L. reuteri with MDA increased the production of ROS and caused thiol depletion and protein carbonylation. L. reuteri is proposed to detoxify pro-oxidative species while the underlying mechanism requires further elucidation.

Assessing proportionate and disproportionate functional mitral regurgitation with individualized thresholds.

AIMS: The concept of proportionate/disproportionate functional mitral regurgitation (FMR) has been limited by the lack of a simple way to assess it and by the paucity of data showing its prognostic superiority. The aim of this study was to evaluate the prognostic value of an individualized method of assessing FMR proportionality. METHODS AND RESULTS: We retrospectively identified 572 patients with at least mild FMR and reduced left ventricular ejection fraction (<50%) under medical therapy. To determine FMR proportionality status, we used an approach where a simple equation determined the individualized theoretical regurgitant volume (or effective regurgitant orifice area) threshold associated with haemodynamically significant FMR. Then, we compared the measured with the theoretical value to categorize the population into non-severe, proportionate, and disproportionate FMR. The primary endpoint was all-cause mortality. During a median follow-up of 3.8 years (interquartile range: 1.8-6.2), 254 patients died. The unadjusted mortality incidence per 100 persons-year rose as the degree of FMR disproportionality worsened. On multivariable analysis, disproportionate FMR remained independently associated with all-cause mortality [adjusted hazard ratio: 1.785; 95% confidence interval (CI): 1.249-2.550; P = 0.001]. The FMR proportionality concept showed greater discriminative power (C-statistic 0.639; 95% CI: 0.597-0.680) than the American (C-statistic 0.583; 95% CI: 0.546-0.621; P for comparison <0.001) and European guidelines (C-statistic 0.584; 95% CI: 0.547-0.620; P for comparison <0.001). When added to any of the before-mentioned guidelines, FMR proportionality also improved risk stratification by reclassifying patients into lower and higher risk subsets. CONCLUSION: Disproportionate FMR is independently associated with all-cause mortality and improves the risk stratification of current guidelines.