Novel Insights into the Molecular Mechanisms Underlying Robustness and Stability in Probiotic Bifidobacteria.

Some probiotic bifidobacteria are highly robust and shelf-stable, whereas others are difficult to produce, due to their sensitivity to stressors. This limits their potential use as probiotics. Here, we investigate the molecular mechanisms underlying the variability in stress physiologies of Bifidobacterium animalis subsp. lactis BB-12 and Bifidobacterium longum subsp. longum BB-46, by applying a combination of classical physiological characterization and transcriptome profiling. The growth behavior, metabolite production, and global gene expression profiles differed considerably between the strains. BB-12 consistently showed higher expression levels of multiple stress-associated genes, compared to BB-46. This difference, besides higher cell surface hydrophobicity and a lower ratio of unsaturated to saturated fatty acids in the cell membrane of BB-12, should contribute to its higher robustness and stability. In BB-46, the expression of genes related to DNA repair and fatty acid biosynthesis was higher in the stationary than in the exponential phase, which was associated with enhanced stability of BB-46 cells harvested in the stationary phase. The results presented herein highlight important genomic and physiological features contributing to the stability and robustness of the studied Bifidobacterium strains. IMPORTANCE Probiotics are industrially and clinically important microorganisms. To exert their health-promoting effects, probiotic microorganisms must be administered at high counts, while maintaining their viability at the time of consumption. In addition, intestinal survival and bioactivity are important criteria for probiotics. Although bifidobacteria are among the most well-documented probiotics, the industrial-scale production and commercialization of some Bifidobacterium strains is challenged by their high sensitivity to environmental stressors encountered during manufacturing and storage. Through a comprehensive comparison of the metabolic and physiological characteristics of 2 Bifidobacterium strains, we identify key biological markers that can serve as indicators for robustness and stability in bifidobacteria.

Bioactive natural products from orchids native to the Americas - A review.

The purpose of this review is to provide information on the traditional uses, phytochemical and pharmacological studies performed with species of orchids native to the Americas and the Caribbean Islands. The treatment of inflammation is the most traditional use for plants of this family, specially in Central America, while anti-inflammatory and anticancer assays are oftenly reported in pharmacological investigations. From the chemical point of view, they are sources of phenanthrenoids and stilbenes, rare secondary metabolites not commonly found in other families of plants, as well as cycloartane triterpenes, pyrrolizidine alkaloids and flavonoids. Since just few species were chemically and pharmacologically studied, in comparison to the large number of native species (less than 0.5% of the total), the orchids of the New World may be an interesting niche for the discovery of new, bioactive natural products.

Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: How to guide the diagnostic strategy?

BACKGROUND: Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM. METHODS: Multicenter study including 780 patients with the ESC definition of HCM. FD screening was performed by enzymatic assay in males and genetic testing in females. Multivariate regression analysis identified independent predictors of FD in HCM. A discriminant function analysis defined a score based on the weighted combination of these predictors. RESULTS: FD was found in 37 of 780 patients with HCM (4.7%): 31 with p.F113L mutation due to a founder effect; and 6 with other variants (p.C94S; p.M96V; p.G183V; p.E203X; p.M290I; p.R356Q/p.G360R). FD prevalence in HCM adjusted for the founder effect was 0.9%. Symmetric HCM (OR 3.464, CI95% 1.151-10.430), basal inferolateral late gadolinium enhancement (LGE) (OR 10.677, CI95% 3.633-31.380), bifascicular block (OR 10.909, CI95% 2.377-50.059) and ST-segment depression (OR 4.401, CI95% 1.431-13.533) were independent predictors of FD in HCM. The score ID FABRY-HCM [-0.729 + (2.781xBifascicular block) + (0.590xST depression) + (0.831xSymmetric HCM) + (2.130xbasal inferolateral LGE)] had a negative predictive value of 95.8% for FD, with a cut-off of 1.0, meaning that, in the absence of both bifascicular block and basal inferolateral LGE, FD is a less probable cause of HCM, being more appropriate to perform HCM gene panel than targeted FD screening. CONCLUSION: FD prevalence in HCM was 0.9%. Bifascicular block and basal inferolateral LGE were the most powerful predictors of FD in HCM. In their absence, HCM gene panel is the most appropriate step in etiological study of HCM.

Estimation of (co)variance components for birth weight in Nellore cattle using alternative data editing criteria.

The aim of this study was to estimate the (co)variance components and breeding values for birthweight (BW) in Nellore cattle by considering or not identical weights that exhibit a high frequency within the contemporary group (CG). A total of 175,258 BW records of Nellore cattle born between 2002 and 2018 were used. The CG was formed by farm, year of birth, sex and feeding regime at birth. CGs with more than 16% of identical BW values were eliminated, generating a data file called BWd. Another file was created without removing these animals (BWt). A mixed linear model was used for statistical analysis, which included fixed and random effects. In both data files analysed, single-trait analysis was performed by Bayesian inference. The mean direct and maternal heritability for BW and the correlation between direct and maternal effects were 0.27, 0.07 and -0.07 for BWt, respectively, and 0.30, 0.093 and -0.07 for BWd. This method should affect the estimation of genetic merits of animals for BW, providing greater safety in the choice of sires.

Genome-wide identification of runs of homozygosity islands in the Gyr breed (Bos indicus).

Runs of homozygosity (ROH) are contiguous homozygous regions of the genome. These regions can be used to identify genes associated with traits of economic interest, as well as inbreeding levels. The aim of the present study was to analyse the length and distribution of ROH islands in Gyr cattle and to identify genes within these regions. A population of 173 animals selected for beef production and a population of 291 animals selected for dairy production were used. Differences in the number of short ROH (ROH1-2 Mb ) were observed between the two populations, while the number of long ROH (ROH>16 Mb ) was similar. ROH islands with the highest incidences (>0.50) overlapped in several segments of the genome in the two populations. The genes identified were associated with milk production, growth, reproduction, immune response and resistance traits. Our results contribute to the understanding of how selection can shape the distribution of ROH and ROH islands within the same breed when animals are selected for different purposes such as dairy or beef production.

Non-Enzymatic Impedimetric Sensor Based on 3-Aminophenylboronic Acid Functionalized Screen-Printed Carbon Electrode for Highly Sensitive Glucose Detection.

A highly sensitive glucose sensor was prepared by a one-step method using 3-aminophenyl boronic acid as a unit of recognition and a screen-printed carbon electrode (SPCE) as an electrochemical transducer. Scanning Electron Microscopy confirmed the success of the functionalization of the SPCE due to the presence of clusters of boronic acid distributed on the carbon surface. In agreement with the Electrochemical Impedance Spectroscopy (EIS) tests performed before and after the functionalization, Cyclic Voltammetry results indicated that the electroactivity of the electrode decreased 37.9% owing to the presence of the poly phenylboronic acid on the electrode surface. EIS revealed that the sensor was capable to selectively detect glucose at a broad range of concentrations (limit of detection of 8.53 × 10-9 M), not recognizing fructose and sucrose. The device presented a stable impedimetric response when immediately prepared but suffered the influence of the storage time and some interfering species (dopamine, NaCl and animal serum). The response time at optimized conditions was estimated to be equal to 4.0 ± 0.6 s.

Population genetics of IFITM3 in Portugal and Central Africa reveals a potential modifier of influenza severity.

Influenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified. SNP distributions in the Portuguese appeared at an intermediate level between the Africans and other Europeans. According to HapMap, rs34481144 belongs to the same linkage disequilibrium (LD) block as rs12252 and is in strong LD with rs6421983. A negative association with severe relative to mild disease was observed for allele rs34481144-A, indicating a protective effect under the dominant model. Moreover, haplotype Hap4 with rs34481144-A, not including rs12252-C, was significantly associated to mild influenza. Conversely, although with borderline significance, haplotype Hap1 with rs34481144-G, not including rs12252-C, was associated to severe disease. Moreover, in comparison to the general Portuguese population, statistical significant differences in the frequencies of the protective allele rs34481144-A in the severe disease group, the deleterious Hap1 in the mild disease group, and the protective Hap4 in the severe disease group were observed. The population attributable risk (PAR) for the targeted rs34481144 allele or genotype was of 55.91 and 64.44% in the general population and the mildly infected individuals, respectively. Implication of these variants in disease phenotype needs further validation, namely through functional analysis as is discussed.

Comparing the Effect of Throughput and Output Factors on Emergency Department Crowding: A Retrospective Observational Cohort Study.

STUDY OBJECTIVE: This study compares how throughput and output factors affect emergency department (ED) median waiting room time. METHODS: Administrative health care use records were used to identify all daytime (8 am to 8 pm) visits made to adult EDs in Winnipeg, Canada, between April 1, 2012, and March 31, 2013. First, we measured the waiting room time (from patient registration until transfer into the ED) of each index visit (incoming patient). We then linked each index visit to a group of existing patients surrounding it and counted the number of existing patients engaged in throughput processes (radiographs, computed tomography [CT] scans, advanced diagnostic tests) and one output process (waiting to be hospitalized). Regression analysis was used to measure how strongly each factor uniquely affected incoming patient median waiting room time, stratified by the acuity level. RESULTS: Analyses were performed on 143,172 index visits. On average, 153.4 radiographs and 48.5 CT scans were conducted daily, whereas 45.3 patients were admitted daily to hospital. Median waiting room time was shortest (8.0 minutes) for the highest-acuity index visits and was not influenced by these throughput or output factors. For all other index visits, median waiting room time was associated strongly with the number of existing patients receiving radiographs, and, to a lesser extent, with the number of existing patients receiving CT scans and waiting for hospital admission. CONCLUSION: Both throughput and output factors affect how long newly arriving ED patients remain in the waiting room. This suggests that a range of strategies may help to reduce ED wait time, each requiring stronger ED and hospital partnerships.

Depression in medical students: insights from a longitudinal study.

BACKGROUND: Factors associated with depression of medical students are poorly understood. The purpose of this study is to determine the prevalence of depression in medical students, its change during the course, if depression persists for affected students, what are the factors associated with depression and how these factors change over time. METHODS: A prospective, longitudinal observational study was conducted at the Medical School of the University of Minho, Portugal, between academic years 2009-2010 to 2012-2013. We included students who maintained their participation by annually completing a questionnaire including Beck Depression Inventory (BDI). Anxiety and burnout were assessed using the State Trait Anxiety Inventory and Maslach Burnout Inventory. Surveys on socio-demographic variables were applied to evaluate potential predictors, personal and academic characteristics and perceived difficulties. ANOVA with multiple comparisons were used to compare means of BDI score. The medical students were organized into subgroups by K-means cluster analyses. ANOVA mixed-design repeated measurement was performed to assess a possible interaction between variables associated with depression. RESULTS: The response rate was 84, 92, 88 and 81% for academic years 2009-2010, 2010-2011,2011-2012 and 2012/2013, respectively. Two hundred thirty-eight medical students were evaluated longitudinally. For depression the prevalence ranged from 21.5 to 12.7% (academic years 2009/2010 and 2012/2013). BDI scores decreased during medical school. 19.7% of students recorded sustained high BDI over time. These students had high levels of trait-anxiety and choose medicine for anticipated income and prestige, reported more relationship issues, cynicism, and decreased satisfaction with social activities. Students with high BDI scores at initial evaluation with low levels of trait-anxiety and a primary interest in medicine as a career tended to improve their mood and reported reduced burnout, low perceived learning problems and increased satisfaction with social activities at last evaluation. No difference was detected between men and women in the median BDI score over time. CONCLUSIONS: Our findings suggest that personal factors (anxiety traits, medicine choice factors, relationship patterns and academic burnout) are relevant for persistence of high levels of BDI during medical training. Medical schools need to identity students who experience depression and support then, as early as possible, particularly when depression has been present over time.

An ED paradox: patients who arrive by ambulance and then leave without consulting an ED provider.

BACKGROUND: Scientists have called for strategies to identify ED patients with unmet needs. We identify the unique profile of ED patients who arrive by ambulance and subsequently leave without consulting a provider (ie, a paradoxical visit, PV). METHODS: Using a retrospective cohort design, administrative data from Winnipeg, Manitoba were interrogated to identify all ED patients 17+ years old as having zero, single or multiple PVs in 2012/2013. Analyses compare the sociodemographic, physical (eg, arthritis), mental (eg, substance abuse) and concurrent healthcare use profile of non-PV, single and multiple PV patients. RESULTS: The study cohort consisted of 122 639 patients with 250 754 ED visits. Across all ED sites, 2.3% of patients (N=2815) made 3387 PVs, comprising 1.4% of all ED visits. Descriptively, more single versus non-PV patients lived in urban core and lowest-income areas, were frequent ED users generally, were substance abusers and had seven plus primary care physician visits. Multiple PV patients had a similar but more extreme profile versus their single PV counterparts (eg, 54.7% of multiple vs 27.4% of single PV patients had substance abuse challenges). From multivariate statistics, single versus non-PV patients are defined uniquely by their frequent ED use, by their substance abuse, as living in a core and low income area, and as having multiple visits with primary care physicians. CONCLUSIONS: PV patients have needs that do not align with the acute model of ED care. These patients may benefit from a more integrated care approach likely involving allied health professionals.

Next-generation sequencing of hereditary hemochromatosis-related genes: Novel likely pathogenic variants found in the Portuguese population.

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1G>C)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c.-25G>A). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.

Bioguided identification of antifungal and antiproliferative compounds from the Brazilian orchid Miltonia flavescens Lindl.

The Orchidaceae family is appreciated worldwide for the beauty of its flowers, and hundreds of species of this family occur in Brazil. Yet little is known about the potential of orchids for therapeutic application. We have investigated bioactive compounds produced by the South Brazilian orchid Miltonia flavescens Lindl. Bioguided studies with the fungus Cladosporium herbarum allowed the identification of hydrocinnamic acid as the active antifungal compound. In addition, the chloroform fraction exhibited an interesting activity against human cancer cells, and 5,7-dihydroxy-6,4'-dimethoxyflavone isolated from this fraction was found to be active against seven human cancer cell lines, including NCI/ADR-RES ovary sarcoma, with an IC50 value of 2.6 microg/mL. This is the first report on the cytostatic activity of this flavone against human ovary sarcoma.

Racing Performance of the Quarter Horse: Genetic Parameters, Trends and Correlation for Earnings, Best Time and Time Class.

The aim of this study was to evaluate the sprint racing performance of Quarter Horses in Brazil. Estimating genetic parameters, trends and correlations were obtained by single- and two-trait analyses using Bayesian inference (earnings to 2 years of equestrian age, best time and time class at distances of 301 m and 402 m). The data comprised a period of 38 equestrian years (1978 to 2015) with 23,482 sprint race records from 5861 animals. The heritability estimates were of low to moderate magnitude, ranging from 0.10 to 0.37 (single-trait) and from 0.15 to 0.41 (two-traits), and the repeatability was 0.31 to 0.46. The additive, residual and phenotypic correlations between earnings to 2 years of equestrian age and the other traits (best time and time class in distances 301 m and 402 m) were high (-0.95, -0.96, 0.69 and 0.92), low (-0.29, -0.37, 0.26 and 0.27) and moderate (-0.41, -0.47, 0.37 and 0.47), respectively. There is a positive genetic trend for all traits considered. However, evaluation of the last 10 equestrian years (2006 to 2015) showed negative trends (genetic loss) and trends close to zero (genetic stagnation). The design of breeding programs using the earnings trait in conjunction with other racing performance traits can enhance changes in the genetic gains as a whole in speed-racing Quarter Horses. These findings suggest that the traits studied should be included in breeding selection programs for racing Quarter Horses.

Genotype-environment interaction for milk production of Gyr cattle in Brazil and Colombia.

BACKGROUND: Genotype by environment interactions (G × E) can play an important role in cattle populations and should be included in breeding programs in order to select the best animals for different environments. OBJECTIVE: The aim of this study was to investigate the G × E for milk production of Gyr cattle in Brazil and Colombia by applying a reaction norm model used genomics information, and to identify genomic regions associated with milk production in the two countries. METHODS: The Brazilian and Colombian database included 464 animals (273 cows and 33 sires from Brazil and 158 cows from Colombia) and 27,505 SNPs. A two-trait animal model was used for milk yield adjusted to 305 days in Brazil and Colombia as a function of country of origin, which included genomic information obtained with a single-step genomic reaction norm model. The GIBBS3F90 and POSTGSf90 programs were used. RESULTS: The results obtained indicate G × E based on the reranking of bulls between Brazil and Colombia, demonstrating environmental differences between the two countries. The findings highlight the importance of considering the environment when choosing breeding animals in order to ensure the adequate performance of their progeny. Within this context, the reranking of bulls and the different SNPs associated with milk production in the two countries suggest that G × E is an important effect that should be included in the genetic evaluation of Dairy Gyr cattle in Brazil and Colombia. CONCLUSION: The Gyr breeding program can be optimized by choosing a selection environment that will allow maximum genetic progress in milk production in different environments within and between countries.

Nutritional status in perianal Crohn's disease: are we underestimating the impact?

Symptomatic perianal disease is common in patients with Crohn's disease (CD), and perianal fistulas represent the primary form of anal involvement. This type of involvement is associated with a poor prognosis and a disabling course. The treatment is challenging and involves both surgical and medical approaches. Despite combined therapy, a significant portion of patients may still require proctectomy to control the symptoms. Consequently, investigating factors that may influence the outcome of perianal disease remains a priority area of research in CD. Nutritional deficiencies are well documented among CD patients with luminal forms of involvement and are closely related to poor clinical outcomes, therapy response, and postoperative complications. As a result, leading guidelines recommend regular nutritional assessment and correction of nutritional deficiencies in patients requiring a surgical approach. Despite these recommendations and the high rate of surgeries among CD patients with perianal disease, there is a shortage of studies addressing the real impact of nutritional status on the course and outcomes of perianal disease. This knowledge gap underscores the importance of further research to understand better and improve the management of perianal CD. This narrative review aims to provide an overview of nutritional status assessment and the influence of nutritional status on the outcomes of patients with perianal CD.

[The impact of direct access to primary angioplasty on reducing the mortality associated with anterior ST-segment elevation myocardial infarction: the experience of the Algarve region of Portugal]. / Impacto da via verde coronária e da angioplastia primária na redução da mortalidade associada ao enfarte com elevação do segmento ST anterior. A experiência algarvia.

INTRODUCTION: There are few published data on mortality in anterior ST-segment elevation myocardial infarction (STEMI) in Portugal, particularly in centers with direct access to primary angioplasty. We present the experience of a center with direct access to primary angioplasty in the management of patients admitted with anterior STEMI. METHODS: We performed a retrospective study of 120 patients admitted with anterior STEMI in 2008 to Faro Hospital (Algarve region, Portugal). RESULTS: Significant coronary artery stenosis was found in 99 patients (82.5%). These patients were predominantly male (79%), and had a mean age of 63 years. Primary angioplasty was performed in the majority of patients within 6 hours of symptom onset and median ECG-to-balloon time was 89 minutes. Primary angioplasty was successful in 98% of patients and complete revascularization was achieved in 83%. Radial access was used in 82% of cases. In-hospital and 30-day mortality was 3%. CONCLUSION: Direct access to primary angioplasty was associated with low mortality in patients admitted with anterior STEMI.

[Loeffler's endocarditis--a case report]. / Endomiocardite de Löffler--a propósito de um caso clínico.

Loeffler's endocarditis is an acute form of primary restrictive cardiomyopathy. We report the case of a young woman with pleuritic chest pain associated with fever and hypereosinophilia. She was hospitalized with suspected acute myopericarditis and was treated with aspirin, leading to clinical improvement. Ten days after discharge, she was rehospitalized due to recurrence of chest pain. The echocardiogram showed what appeared to be a mass filling the apex of the right ventricle (RV). She was referred for magnetic resonance imaging, which revealed marked myocardial thickening in the apex of the RV. The patient underwent an endomyocardial biopsy, resulting in a diagnosis of eosinophilic endocarditis. After treatment with prednisolone, all symptoms and the eosinophilia disappeared, and there was complete remission of the RV abnormalities. After three years of follow-up, the patient remains asymptomatic. This case shows that, even without an etiologic diagnosis of eosinophilia, the prognosis for Loeffler's endocarditis can be favorable if treatment is initiated early.

[Fulminant myocarditis]. / Miocardite fulminante - a propósito de um caso clínico.

A 46-year-old woman was admitted due to diplopia because of ophthalmoplegia, which improved with corticosteroid therapy. Eight days later, she was admitted with fulminant myocarditis in cardiogenic shock, with severe left ventricular dysfunction and frequent episodes of nonsustained ventricular tachycardia. As there was no clinical improvement, an endomyocardial biopsy was performed that revealed inflammatory infiltrate, vasculitis, and PCR positive for cytomegalovirus, Epstein-Barr virus, parvovirus B19 and enterovirus. Left ventricular function recovered with heart failure treatment and corticosteroids. Three months later, after progressive withdrawal of prednisolone, there was recurrence of myocarditis and left ventricular dysfunction, which was successfully treated by restarting corticosteroid therapy. One month later she was readmitted with fulminant myocarditis which again responded to steroids. She intermittently presented cutaneous purpura lesions. At this time the provisional diagnosis was vasculitis and she started monthly cycles of cyclophosphamide. Before the second cycle she was admitted with pneumonia and ventricular dysfunction and died.

Immunoglobulin G4-Associated Cholangitis: Two Case Reports and Clinical Use of Classic and Emerging International Diagnostic Criteria.

Immunoglobulin G4-related disease is a multisystem disorder with unique gastrointestinal tract manifestations, often simulating neoplasms and other inflammatory conditions. Appropriate clinical suspicion and application of internationally validated criteria can assist in making the proper diagnosis. This article describes two cases of patients presenting with biliary tract manifestations simulating lymphoproliferative disease and adenocarcinoma, respectively. Clinical, radiological, and histopathological findings ultimately led to the correct diagnosis, and revealed useful nuances for detection of future cases. Application of specific criteria, such as the classic Japan Biliary Association clinical diagnostic criteria published in 2012 and revised in 2020 as well as the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria, has limitations but provides important warnings to be considered in the diagnostic journey of these challenging cases.

Left ventricular noncompaction associated with a pathogenic mutation in the MYH7 gene: Known mutation, different phenotype.

Left ventricular noncompaction (LVNC) is a genetically heterogeneous cardiomyopathy, with familial and sporadic forms, but genetic testing only identifies a pathogenic mutation in a minority of cases. The main complications are heart failure, embolism and dysrhythmias. Herein we report a familial case of LVNC associated with a mutation in the MYH7 gene and review the literature regarding controversies in LVNC. A 50-year-old woman was referred to the cardiology clinic for palpitations. She underwent echocardiography and cardiac magnetic resonance imaging that revealed mild left ventricular systolic dysfunction and LVNC criteria. She had several episodes of non-sustained ventricular tachycardia and received an implantable cardioverter-defibrillator (ICD). Genetic testing revealed the c.1003G>C (p.Ala335Pro) mutation in the MYH7 gene. Familial screening showed clear genotype-phenotype cosegregation, which provided strong evidence for the pathogenic role of this mutation. To the best of our knowledge, this is the first report of LVNC associated with the p.Ala335Pro mutation in the MYH7 gene. This mutation has been described in hypertrophic cardiomyopathy, suggesting that the same pathogenic sarcomere mutation may be associated with different cardiomyopathies. This case also highlights the current difficulties regarding decisions on ICD implantation for primary prevention of sudden cardiac death in LVNC.