Percutaneous suture-mediated patent foramen ovale closure: two-year clinical follow-up.

BACKGROUND: Percutaneous suture-mediated patent foramen ovale (PFO) closure has been recently introduced in clinical practice showing a favorable efficacy and safety profile in most PFO cases. The aim of this study was to assess the long-term outcomes of PFO closure by direct suture in a large consecutive series of patients. METHODS: We extracted all consecutive patients who underwent percutaneous closure of the PFO by suture technique (HeartStitch, Fountain Valley, CA, USA) from June 2016 with a follow-up of at least 2 years. After PFO closure, patients were followed-up clinically at 1, 6 and up to 12 months and microbubble transthoracic echocardiography (TTE) scheduled between 3 and 6 months, and at 12-month follow-up. After 12 months, patients were clinically checked every 6 months. RESULTS: As of September 1, 2020, 187 patients had undergone PFO closure with suture for at least two years and, of these, 181 (121 women and 60 men, mean age 45±13 years, range 15-75 years) had complete clinical and instrumental follow-up (97%). There were no peri-procedural complications. Mean follow-up was 1076±251 days (range 727-1574). At 12-month TTE, a significant residual atrial shunt was found in 39 patients (21%). At follow-up no recurrent thromboembolic or cerebral event occurred, no instrumental evidence of suture dehiscence detected and, 18 months after the procedure, one patient had an episode of transient atrial fibrillation lasting less than 24 hours and resolved spontaneously. CONCLUSIONS: Long-term follow-up data indicate that PFO closure by direct suturing is safe and effective. Two years after the procedure, there were no significant complications, no permanent arrhythmic complications and evidence of suture dehiscence.

Multi-omics data integration provides insights into the post-harvest biology of a long shelf-life tomato landrace.

In this study we investigated the transcriptome and epigenome dynamics of the tomato fruit during post-harvest in a landrace belonging to a group of tomatoes (Solanum lycopersicum L.) collectively known as "Piennolo del Vesuvio", all characterized by a long shelf-life. Expression of protein-coding genes and microRNAs as well as DNA methylation patterns and histone modifications were analysed in distinct post-harvest phases. Multi-omics data integration contributed to the elucidation of the molecular mechanisms underlying processes leading to long shelf-life. We unveiled global changes in transcriptome and epigenome. DNA methylation increased and the repressive histone mark H3K27me3 was lost as the fruit progressed from red ripe to 150 days post-harvest. Thousands of genes were differentially expressed, about half of which were potentially epi-regulated as they were engaged in at least one epi-mark change in addition to being microRNA targets in ~5% of cases. Down-regulation of the ripening regulator MADS-RIN and of genes involved in ethylene response and cell wall degradation was consistent with the delayed fruit softening. Large-scale epigenome reprogramming that occurred in the fruit during post-harvest likely contributed to delayed fruit senescence.

Tomato genomic prediction for good performance under high-temperature and identification of loci involved in thermotolerance response.

Many studies showed that few degrees above tomato optimum growth temperature threshold can lead to serious loss in production. Therefore, the development of innovative strategies to obtain tomato cultivars with improved yield under high temperature conditions is a main goal both for basic genetic studies and breeding activities. In this paper, a F4 segregating population was phenotypically evaluated for quantitative and qualitative traits under heat stress conditions. Moreover, a genotyping by sequencing (GBS) approach has been employed for building up genomic selection (GS) models both for yield and soluble solid content (SCC). Several parameters, including training population size, composition and marker quality were tested to predict genotype performance under heat stress conditions. A good prediction accuracy for the two analyzed traits (0.729 for yield production and 0.715 for SCC) was obtained. The predicted models improved the genetic gain of selection in the next breeding cycles, suggesting that GS approach is a promising strategy to accelerate breeding for heat tolerance in tomato. Finally, the annotation of SNPs located in gene body regions combined with QTL analysis allowed the identification of five candidates putatively involved in high temperatures response, and the building up of a GS model based on calibrated panel of SNP markers.

Perclose Proglide™ for vascular closure.

In the past 20 years, numerous percutaneous vascular closure devices have been tested and compared with manual compression and to surgical cut-down. The suture-mediated closure device Perclose ProGlide™ system (Abbott Vascular, CA, USA) emerged as a safe and effective alternative for many procedures requiring either small or large bore vascular accesses. In this review, we will discuss the characteristics of this vascular closure device and the main studies that proved its potential to reduce vascular complications, time to deambulation, time to discharge and patient discomfort.

Accelerating Tomato Breeding by Exploiting Genomic Selection Approaches.

Genomic selection (GS) is a predictive approach that was built up to increase the rate of genetic gain per unit of time and reduce the generation interval by utilizing genome-wide markers in breeding programs. It has emerged as a valuable method for improving complex traits that are controlled by many genes with small effects. GS enables the prediction of the breeding value of candidate genotypes for selection. In this work, we address important issues related to GS and its implementation in the plant context with special emphasis on tomato breeding. Genomic constraints and critical parameters affecting the accuracy of prediction such as the number of markers, statistical model, phenotyping and complexity of trait, training population size and composition should be carefully evaluated. The comparison of GS approaches for facilitating the selection of tomato superior genotypes during breeding programs is also discussed. GS applied to tomato breeding has already been shown to be feasible. We illustrated how GS can improve the rate of gain in elite line selection, and descendent and backcross schemes. The GS schemes have begun to be delineated and computer science can provide support for future selection strategies. A new promising breeding framework is beginning to emerge for optimizing tomato improvement procedures.

Accumulation of Ascorbic Acid in Tomato Cell Culture: Influence of the Genotype, Source Explant and Time of In Vitro Cultivation.

The production and commercialization of natural antioxidants is gaining increasing importance due to their wide range of biological effects and applications. In vitro cell culture is a valuable source of plant bioactive compounds, especially those highly dependent on environmental factors. Nonetheless, research on the accumulation in plant cultured cells of water-soluble antioxidant vitamins, such as the ascorbic acid (AsA), is very limited. Tomato fruits are a main dietary source of vitamin C and in this work, we explored the potential of in vitro cultured cells for AsA accumulation. Specifically, using a full factorial design, we examined the effect of the source explant, the time in tissue culture and the genetic difference present in two Introgression Line (IL7-3 and IL12-4) that harbor Quantitative Trait Loci (QTLs) for ascorbic acid in fruits. Moreover, we performed an expression analysis of genes involved in AsA metabolism to highlight the molecular mechanisms that can account for the difference between fruit explants and calli. Our work indicated that cultured tomato cells accumulate AsA well beyond the amount present in fruits and that the three factors under investigation and their interaction significantly influence AsA accumulation. The time in tissue culture is the main single factor and, different from the expectations for secondary metabolites, explants from unripe, mature green fruits provided the highest increase in AsA. Moreover, in controlled conditions the genetic differences between the ILs and the control genotype are less relevant for calli cultivated for longer time. Our work showed the potential of tomato cell culture to produce AsA and prompt further refinements towards its possible large-scale exploitation.

Variations of peel essential oils during fruit ripening in four lemon (Citrus limon (L.) Burm. F.) cultivars.

BACKGROUND: Lemon processing procedures yield a significant amount of waste as peels, which are 57% of processed lemons and represent a possible source of bioactive compounds (essential oils, EOs). EOs were extracted from lemon fruits belonging to four cultivars harvested at four different sampling times (25 October, 23 November, 20 December, 1 February), characterized, and quantified through gas chromatography-mass spectrometry. RESULTS: The chemical composition of EOs highlighted that 26 compounds of the four lemon cultivars at the different ripening stages were clearly identified. The compounds analysed belonged to four chemical classes: monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpenes, and fatty alcohol esters. Among the monoterpene hydrocarbons, d-limonene, ß-pinene, and γ-terpinene were the most abundant; and among the oxygenated monoterpenes, α-terpineol, nerol, and geraniol were the most abundant. Quantitative gas chromatography-mass spectrometry analysis of the most abundant monoterpene hydrocarbons (α-pinene, ß-pinene, myrcene, d-limonene, and γ-terpinene) highlighted that the amount of EOs decreased during ripening stages. 'Ovale di Sorrento' and 'Sfusato Amalfitano' showed the highest level of EOs in December, whereas in 'Femminello Cerza' and 'Femminello Adamo' this occurred in November. EOs, as well as the phenolic compounds, were positively correlated with the antioxidant activity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid). CONCLUSIONS: EOs reached the highest level in the four lemon cultivars at different ripening stages. Campanian cultivars ('Ovale di Sorrento' and 'Sfusato Amalfitano') showed the greatest EO content in November, whereas in Sicilian cultivars ('Femminello Cerza' and 'Femminello Adamo') this occurred in December. Besides phenolic compounds, measured in lemon peel extracts, EOs can contribute to antioxidant activity, as demonstrated by the positive correlation. © 2019 Society of Chemical Industry.

Characterisation of ground motion recording stations in the Groningen gas field.

The seismic hazard and risk analysis for the onshore Groningen gas field requires information about local soil properties, in particular shear-wave velocity (VS). A fieldwork campaign was conducted at 18 surface accelerograph stations of the monitoring network. The subsurface in the region consists of unconsolidated sediments and is heterogeneous in composition and properties. A range of different methods was applied to acquire in situ VS values to a target depth of at least 30 m. The techniques include seismic cone penetration tests (SCPT) with varying source offsets, multichannel analysis of surface waves (MASW) on Rayleigh waves with different processing approaches, microtremor array, cross-hole tomography and suspension P-S logging. The offset SCPT, cross-hole tomography and common midpoint cross-correlation (CMPcc) processing of MASW data all revealed lateral variations on length scales of several to tens of metres in this geological setting. SCPTs resulted in very detailed VS profiles with depth, but represent point measurements in a heterogeneous environment. The MASW results represent VS information on a larger spatial scale and smooth some of the heterogeneity encountered at the sites. The combination of MASW and SCPT proved to be a powerful and cost-effective approach in determining representative VS profiles at the accelerograph station sites. The measured VS profiles correspond well with the modelled profiles and they significantly enhance the ground motion model derivation. The similarity between the theoretical transfer function from the VS profile and the observed amplification from vertical array stations is also excellent.

Whole-genome re-sequencing of two Italian tomato landraces reveals sequence variations in genes associated with stress tolerance, fruit quality and long shelf-life traits.

Tomato is a high value crop and the primary model for fleshy fruit development and ripening. Breeding priorities include increased fruit quality, shelf life and tolerance to stresses. To contribute towards this goal, we re-sequenced the genomes of Corbarino (COR) and Lucariello (LUC) landraces, which both possess the traits of plant adaptation to water deficit, prolonged fruit shelf-life and good fruit quality. Through the newly developed pipeline Reconstructor, we generated the genome sequences of COR and LUC using datasets of 65.8 M and 56.4 M of 30-150 bp paired-end reads, respectively. New contigs including reads that could not be mapped to the tomato reference genome were assembled, and a total of 43, 054 and 44, 579 gene loci were annotated in COR and LUC. Both genomes showed novel regions with similarity to Solanum pimpinellifolium and Solanum pennellii. In addition to small deletions and insertions, 2, 000 and 1, 700 single nucleotide polymorphisms (SNPs) could exert potentially disruptive effects on 1, 371 and 1, 201 genes in COR and LUC, respectively. A detailed survey of the SNPs occurring in fruit quality, shelf life and stress tolerance related-genes identified several candidates of potential relevance. Variations in ethylene response components may concur in determining peculiar phenotypes of COR and LUC.

Characterization of autochthonous sweet cherry cultivars (Prunus avium L.) of southern Italy for fruit quality, bioactive compounds and antioxidant activity.

BACKGROUND: Characterizing germplasm collections of autochthonous cultivars for fruit quality traits could be a successful approach for selection, improvement of organoleptic quality and levels of antioxidants of crop produce, and development of new market opportunities and coherent strategies for conservation and valorization. The aim of the study was the evaluation of fruit physicochemical traits as well as the content of bioactive compounds and the antioxidant capacity in 25 sweet cherry autochthonous cultivars. RESULTS: Cultivars were a source of statistically significant variation for all evaluated traits. Notably, average fruit ascorbate levels ranged from 34.45 to 244.68 µg g-1 fresh weight (FW) , total flavonoids from 1396.40 to 4694.75 µg quercetin equiv. g-1 FW, monomeric anthocyanins from 4.80 to 360.90 µg g-1 FW, and total antioxidant capacity from 1.53 to 2.58 nmol Trolox equiv. mg-1 FW. Fruit profiling of eight cultivars by high-resolution mass spectrometry identified a total of eight different anthocyanins and twenty-five non-anthocyanin polyphenolic compounds - mostly coumaroylquinic acid and neochlorogenic acid. CONCLUSION: Among the better-performing cultivars for fruit quality traits, Mulegnana Nera and Pagliarella shared high fruit levels of phenolics, flavonoids and antioxidant capacity. This is a forerunner work on the characterization of genetic resources, which is critical to researchers and breeders for exploitation of the genetic potential of cultivars and for their conservation. © 2016 Society of Chemical Industry.

Epistatic interaction between MyD88 and TIRAP against Helicobacter pylori.

The genes MyD88 and TIRAP encode the adaptor proteins MyD88 and TIRAP. TIRAP plays the crucial role of activating the MyD88-dependent pathway, which in turn controls the immune response (innate and adaptive) to Helicobacter pylori. We looked for an association of MyD88 and TIRAP with H. pylori infection. Cases and controls were genotyped at the polymorphic sites MyD88 rs6853 and TIRAP rs8177374 by real-time PCR. When the genes were analyzed separately, only TIRAP was associated with infection. When the genes were analyzed concurrently, certain combinations of MyD88 and TIRAP protected the host against H. pylori colonization more efficiently than could be done by TIRAP alone.

Transcriptome and metabolome of synthetic Solanum autotetraploids reveal key genomic stress events following polyploidization.

Polyploids are generally classified as autopolyploids, derived from a single species, and allopolyploids, arising from interspecific hybridization. The former represent ideal materials with which to study the consequences of genome doubling and ascertain whether there are molecular and functional rules operating following polyploidization events. To investigate whether the effects of autopolyploidization are common to different species, or if species-specific or stochastic events are prevalent, we performed a comprehensive transcriptomic and metabolomic characterization of diploids and autotetraploids of Solanum commersonii and Solanum bulbocastanum. Autopolyploidization remodelled the transcriptome and the metabolome of both species. In S. commersonii, differentially expressed genes (DEGs) were highly enriched in pericentromeric regions. Most changes were stochastic, suggesting a strong genotypic response. However, a set of robustly regulated transcripts and metabolites was also detected, including purine bases and nucleosides, which are likely to underlie a common response to polyploidization. We hypothesize that autopolyploidization results in nucleotide pool imbalance, which in turn triggers a genomic shock responsible for the stochastic events observed. The more extensive genomic stress and the higher number of stochastic events observed in S. commersonii with respect to S. bulbocastanum could be the result of the higher nucleoside depletion observed in this species.

Evaluation of fruit quality, bioactive compounds and total antioxidant activity of flat peach cultivars.

BACKGROUND: Fruit quality traits (fresh weight, dry weight, soluble solids content, titratable acidity and firmness) as well as the content of bioactive compounds (phenolic compounds) and total antioxidant activity were evaluated in four commercial cultivars of peach (Greta, Ufo 4, Rome Star and Ufo 6) and four of nectarine (Neve, Planet 1, Maria Carla and Mesembrina) differing in fruit shape (standard or flat) and flesh colour (white or yellow), important cultivars of the Italian and foreign market. The higher fruit organoleptic quality and nutritional profile of flat peach and nectarine cultivars make them candidates for exploiting new market opportunities and the chance to improve profits of farmers. RESULTS: The results showed that assayed quality parameters differed greatly among cultivars. In particular, flesh color and fruit shape accounted for most of the variation in traits underlying organoleptic and nutritional quality. CONCLUSION: Overall data suggested that the flat white-fleshed nectarine Planet 1, the yellow-fleshed nectarine Mesembrina and the yellow-fleshed peach Ufo 6, because of their profiles in terms of soluble solids content, titratable acidity and bioactive compounds, have the greatest potential to meet current consumer requirements.

Heterozygosity at the A625C polymorphic site of the MyD88 gene is associated with Mycobacterium bovis infection in cattle.

The study demonstrates that in cattle, animals heterozygous at the MyD88 A625C polymorphic marker have a 5-fold reduced risk for active pulmonary tuberculosis (odds ratio [OR] = 0.19; P = 6 × 10(-12)). The reduced risk, however, does not extend to animals with latent pulmonary tuberculosis (OR = 0.83; P = 0.40). Heterozygosity at the A625C single nucleotide polymorphism is associated with intermediate levels of tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase (NOS). Accordingly, deficiency as well as overexpression of proinflammatory cytokines or NOS favor tuberculosis, while heterozygosity provides the animals with the optimal level of inflammation.

Identification of candidate genes for phenolics accumulation in tomato fruit.

Phenolics are antioxidants present in tomato fruit that confer healthy benefits and exhibit crucial roles for plant metabolism and response to environmental stimuli. An approach based on two genomics platforms was undertaken to identify candidate genes associated to higher phenolics content in tomato fruit. A comparative transcriptomic analysis between the S. pennellii Introgression Line 7-3, which produced an average higher level of fruit phenolics, and the cultivated variety M82, revealed that their differences are attributed to genes involved in phenolics accumulation into the vacuole. The up-regulation of genes coding for one MATE-transporter, one vacuolar sorting protein and three GSTs supported this hypothesis. The observed balancing effect between two ethylene responsive factors (ERF1 and ERF4) was also hypothesized to drive the transcriptional regulation of these transport genes. In order to confirm such model a TILLING platform was explored. A mutant was isolated harbouring a point mutation in the ERF1 cds that affects the protein sequence and its expected function. Fruits of the mutant exhibited a significant reduced level of phenolics than the control variety. Changes in the expression of genes involved in sequestration of phenolics in vacuole also supported the hypothesized key-role of ERF1 in orchestrating these genes.

Quantitative trait loci pyramiding for fruit quality traits in tomato.

Fruit quality is a major focus for most conventional and innovative tomato breeding strategies, with particular attention being paid to fruit antioxidant compounds. Tomatoes represent a major contribution to dietary nutrition worldwide and a reservoir of diverse antioxidant molecules. In a previous study, we identified two Solanum pennellii introgression lines (IL7-3 and IL12-4) harbouring quantitative trait loci (QTL) that increase the content of ascorbic acid (AsA), phenols and soluble solids (degrees Brix; °Bx) in tomato fruit. The purpose of the present work was to pyramid into cultivated varieties the selected QTL for enhanced antioxidant and °Bx content. To better understand the genetic architecture of each QTL, the two ILs were crossed to the recurrent parent M82 (ILH7-3 and ILH12-4) and between them (ILH7-3+12-4). F1 hybrids (ILH7-3+12-4) were then selfed up to obtain F3 progenies in order to stabilize the favourable traits at the homozygous condition. Species-specific molecular markers were identified for each introgressed region and allowed us to select four F2 genotypes carrying both introgressions at the homozygous condition. The F3 double homozygous plants displayed AsA, total phenols and °Bx content significantly higher than M82. Therefore, they may represent suitable genetic material for breeding schemes aiming to increase antioxidant content in tomato fruit.

Comparative transcriptomic profiling of two tomato lines with different ascorbate content in the fruit.

In recent years, interest in tomato breeding for enhanced antioxidant content has increased as medical research has pointed to human health benefits from antioxidant dietary intake. Ascorbate is one of the major antioxidants present in tomato, and little is known about mechanisms governing ascorbate pool size in this fruit. In order to provide further insights into genetic mechanisms controlling ascorbate biosynthesis and accumulation in tomato, we investigated the fruit transcriptome profile of the Solanum pennellii introgression line 10-1 that exhibits a lower fruit ascorbate level than its cultivated parental genotype. Our results showed that this reduced ascorbate level is associated with an increased antioxidant demand arising from an accelerated oxidative metabolism mainly involving mitochondria, peroxisomes, and cytoplasm. Candidate genes for controlling ascorbate level in tomato fruit were identified, highlighting the role of glycolysis, glyoxylate metabolism, and purine breakdown in modulating the ascorbate pool size.

The ascorbic acid content of tomato fruits is associated with the expression of genes involved in pectin degradation.

BACKGROUND: High levels of ascorbic acid (AsA) in tomato fruits provide health benefits for humans and also play an important role in several aspects of plant life. Although AsA metabolism has been characterized in detail, the genetic mechanisms controlling AsA accumulation in tomatoes are poorly understood. The transcriptional control of AsA levels in fruits can be investigated by combining the advanced genetic and genomic resources currently available for tomato. A comparative transcriptomic analysis of fruit tissues was carried out on an introgression line containing a QTL promoting AsA accumulation in the fruit, using a parental cultivar with lower AsA levels as a reference. RESULTS: Introgression line IL 12-4 (S. pennellii in a S. lycopersicum background) was selected for transcriptomic analysis because it maintained differences in AsA levels compared to the parental genotypes M82 and S. pennellii over three consecutive trials. Comparative microarray analysis of IL 12-4 and M82 fruits over a 2-year period allowed 253 differentially-expressed genes to be identified, suggesting that AsA accumulation in IL 12-4 may be caused by a combination of increased metabolic flux and reduced utilization of AsA. In particular, the upregulation of a pectinesterase and two polygalacturonases suggests that AsA accumulation in IL12-4 fruit is mainly achieved by increasing flux through the L-galactonic acid pathway, which is driven by pectin degradation and may be triggered by ethylene. CONCLUSIONS: Based on functional annotation, gene ontology classification and hierarchical clustering, a subset of the 253 differentially-expressed transcripts was used to develop a model to explain the higher AsA content in IL 12-4 fruits in terms of metabolic flux, precursor availability, demand for antioxidants, abundance of reactive oxygen species and ethylene signaling.

Management of nonvalvular atrial fibrillation: a comprehensive approach.

Atrial fibrillation is the most common arrhythmia in clinical practice, may coexist with conditions common to both cardiovascular and noncardiovascular diseases and is associated with considerable morbidity and mortality. Atrial fibrillation is often asymptomatic and diagnosed only when it has caused a potentially serious complication, such as an ischemic stroke. When atrial fibrillation has been identified, 2 objectives have to be addressed--the antiarrhythmic therapy based on rate control or rhythm control, and prevention of thromboembolism. A rhythm or rate control strategy can be chosen indifferently because they have comparable efficacy for the outcome measure of mortality, but the antithrombotic therapy is ever mandatory. The risk of stroke increases cumulatively with increasing age, previous transient ischemic attack or stroke, hypertension, diabetes mellitus, impaired left ventricular function and heart failure. Warfarin reduces the risk of stroke by about two thirds; and aspirin, by about one fifth, but its use must be weighted with the risk of bleeding. The risk of anticoagulant-associated hemorrhage increases with age, the presence of serious concomitant diseases, with poorly controlled hypertension and poorly controlled anticoagulation.