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Background and Objectives: An elevated heart rate is an independent risk factor for cardiovascular disease; however, the relationship between heart rate control and the long-term outcomes of patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. This study explored the long-term prognostic importance of heart rate control in patients hospitalized with HFrEF. Materials and Methods: We retrieved the records of patients admitted for decompensated heart failure with a left ventricular ejection fraction (LVEF) of ≤40%, from 1 January 2005 to 31 December 2019. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure (HHF) during follow-up. We analyzed the outcomes using Cox proportional hazard ratios calculated using the patients' heart rates, as measured at baseline and approximately 3 months later. The mean follow-up duration was 49.0 ± 38.1 months. Results: We identified 5236 eligible patients, and divided them into five groups on the basis of changes in their heart rates. The mean LVEFs of the groups ranged from 29.1% to 30.6%. After adjustment for all covariates, the results demonstrated that lesser heart rate reductions at the 3-month screening period were associated with long-term cardiovascular death, HHF, and all-cause mortality (p for linear trend = 0.033, 0.042, and 0.003, respectively). The restricted cubic spline model revealed a linear relationship between reduction in heart rate and risk of outcomes (p for nonlinearity > 0.2). Conclusions: Greater reductions in heart rate were associated with a lower risk of long-term cardiovascular death, HHF, and all-cause mortality among patients discharged after hospitalization for decompensated HFrEF. [ABSTRACT FROM AUTHOR]

Dicer is the key component in the miRNA pathway. Degradation of Dicer protein is facilitated during vaccinia virus (VV) infection. A C-terminal cleaved product of Dicer protein was detected in the presence of MG132 during VV infection. Thus, it is possible that Dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product. There is a potential I7 protease cleavage site in the C-terminus of Dicer protein. Indeed, reduction of Dicer protein was detected when Dicer was co-expressed with I7 protease but not with an I7 protease mutant protein lack of the protease activity. Mutation of the potential I7 cleavage site in the C-terminus of Dicer protein resisted its degradation during VV infection. Furthermore, Dicer protein was reduced dramatically by recombinant VV vI7Li after the induction of I7 protease. If VV could facilitate the degradation of Dicer protein, the process of miRNA should be affected by VV infection. Indeed, accumulation of precursor miR122 was detected after VV infection or I7 protease expression. Reduction of miR122 would result in the suppression of HCV sub-genomic RNA replication, and, in turn, the amount of viral proteins. As expected, significant reduction of HCVNS5A protein was detected after VV infection and I7 protease expression. Therefore, our results suggest that VV could cleave Dicer protein through I7 protease to facilitate Dicer degradation, and in turn, suppress the processing of miRNAs. Effect of Dicer protein on VV replication was also studied. Exogenous expression of Dicer protein suppresses VV replication slightly while knockdown of Dicer protein does not affect VV replication significantly. [ABSTRACT FROM AUTHOR]

Plants acquire phosphorus in the form of phosphate (Pi), the concentration of which is often limited for plant uptake. Plants have developed diverse responses to conserve and remobilize internal Pi and to enhance Pi acquisition to secure them against Pi deficiency. These responses are achieved by the coordination of an elaborate signaling network comprising local and systemic machineries. Recent advances have revealed several important components involved in this network. Pi functions as a signal to report its own availability. miR399 and sugars act as systemic signals to regulate responses occurring in roots. Hormones also play crucial roles in modulating gene expression and in altering root system architecture. Transcription factors function as a hub to perceive the signals and to elicit steady outputs. In this review, we outline the current knowledge on this subject and present hypotheses pertaining to other potential signals and to the organization and coordination of signaling. [ABSTRACT FROM AUTHOR]

Climate change might potentially cause extreme weather events to become more frequent and intense. It could also enhance water scarcity and reduce food security. More efficient water management techniques are thus required to ensure a stable food supply and quality. Maintaining proper soil water content and soil temperature is necessary for efficient water management in agricultural practices. The usage of water and fertilizers can be significantly improved with a precise water content prediction tool. In this study, we proposed a new framework that combines weather forecast data, numerical models, and machine learning methods to simulate and predict the soil temperature and volumetric water content in a greenhouse. To test the framework, we performed greenhouse experiments with cherry tomatoes. The numerical models and machine learning methods we selected were Newton's law of cooling, HYDRUS-1D, the random forest model, and the ICON (inferring connections of networks) model. The measured air temperature, soil temperature, and volumetric water content during the cultivation period were used for model calibration and validation. We compared the performances of the models for soil temperature and volumetric water content predictions. The results showed that the random forest model performed a more accurate prediction than other methods under the limited information provided from greenhouse experiments. This approach provides a framework that can potentially learn best water management practices from experienced farmers and provide intelligent information for smart greenhouse management. [ABSTRACT FROM AUTHOR]

Summary: Although microRNAs (miRNAs) have been documented to regulate development in plants and animals , the function of miRNAs in physiology is unclear. miR399 has multiple target sites in the 5′ untranslated region (UTR) of a gene encoding a putative ubiquitin-conjugating enzyme (UBC) in Arabidopsis thaliana. We report here that miR399 was highly induced, whereas the target UBC mRNA was reduced by low-phosphate (Pi) stress. In transgenic plants with constitutive expression of miR399, UBC mRNA accumulation was suppressed even under high Pi. The expression of transgene UBC mRNA with 5′ UTR miR399 target sites, but not the one without 5′ UTR, was reduced under low-Pi condition. Furthermore, transgenic Arabidopsis plants with constitutive expression of miR399 accumulated more Pi than the wild-type, and transgenic plants expressing the UBC mRNA without 5′ UTR (miRNA-deregulated) showed less inhibition of primary root growth and less induction of a Pi transporter gene by low-Pi stress than those of wild-type plants. We conclude that miR399 downregulates UBC mRNA accumulation by targeting the 5′ UTR, and this regulation is important for plant responses to Pi starvation. The results suggest that miRNAs have functional roles for plants to cope with fluctuations in mineral-nutrient availability in the soil. [Copyright &y& Elsevier]

Background: Current guidelines recommend that all infected cardiac implantable electronic devices (CIEDs) should be removed. However, financial or anatomical concerns can lead to management of infection with simple debridement, as opposed to complete removal. In this observational study, we report the outcomes of our modified procedure for this real-world dilemma., Methods and Results: The Quarantine (RESQ) method is characterized as follows: the removal (R) of all non-essential foreign materials, including old sutures and leads; the excision (E) of all non-viable, chronically inflamed, granulation, or scar tissue; the sterilization (S) of the remaining generator; and the quarantine (Q) of a new pocket in the sub-muscular layer for reimplantation. From a review of electronic medical records, 30 patients were selected and divided into three groups according to the intervention used: RESQ (n = 9) in group A, simple debridement (n = 16) in group B, and guideline-recommended replacement (n = 5) in group C. Patient baseline characteristics were similar between the groups. After analyzing the proportion of patients that were free from infection one year following their respective interventions, we found that group A performed better than group B (100% and 31.2% infection-free, respectively, p = 0.001), and was comparable to group C (both 100% infection-free, p = not applicable)., Conclusions: The RESQ method is a feasible and beneficial alternative for selected patients with CIED infections who are unable to receive a generator replacement according to the recommended guideline.

Wild tomatoes (Solanum peruvianum) are important genomic resources for tomato research and breeding. Development of a foreign DNA-free clustered regularly interspaced short palindromic repeat (CRISPR)-Cas delivery system has potential to mitigate public concern about genetically modified organisms. Here, we established a DNA-free CRISPR-Cas9 genome editing system based on an optimized protoplast regeneration protocol of S. peruvianum, an important resource for tomato introgression breeding. We generated mutants for genes involved in small interfering RNAs biogenesis, RNA-DEPENDENT RNA POLYMERASE 6 (SpRDR6), and SUPPRESSOR OF GENE SILENCING 3 (SpSGS3); pathogen-related peptide precursors, PATHOGENESIS-RELATED PROTEIN-1 (SpPR-1) and PROSYSTEMIN (SpProSys); and fungal resistance (MILDEW RESISTANT LOCUS O, SpMlo1) using diploid or tetraploid protoplasts derived from in vitro-grown shoots. The ploidy level of these regenerants was not affected by PEG-Ca2+-mediated transfection, CRISPR reagents, or the target genes. By karyotyping and whole genome sequencing analysis, we confirmed that CRISPR-Cas9 editing did not introduce chromosomal changes or unintended genome editing sites. All mutated genes in both diploid and tetraploid regenerants were heritable in the next generation. spsgs3 null T0 regenerants and sprdr6 null T1 progeny had wiry, sterile phenotypes in both diploid and tetraploid lines. The sterility of the spsgs3 null mutant was partially rescued, and fruits were obtained by grafting to wild-type (WT) stock and pollination with WT pollen. The resulting seeds contained the mutated alleles. Tomato yellow leaf curl virus proliferated at higher levels in spsgs3 and sprdr6 mutants than in the WT. Therefore, this protoplast regeneration technique should greatly facilitate tomato polyploidization and enable the use of CRISPR-Cas for S. peruvianum domestication and tomato breeding., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: Renal denervation (RDN) is effective to lower systolic blood pressure (SBP) in essential hypertension. However, patient selection under medications remains an important unmet clinical need., Methods: This multicenter study aimed at observing whether preprocedural features associated with increased renin-angiotensin-aldosterone activity influence RDN response. This study enrolled the patients who underwent RDN for uncontrolled hypertension. Medical records were reviewd and patients were divided into 2 groups depending by meeting any of the following conditions prior to RDN: (1) >10 mmHg of office SBP reduction after aldosterone inhibition, (2) aldosterone-renin ratio >30 or (3) slow flow on the renal angiogram. RDN responders were defined by a reduction in 24-hour mean ≥6 mmHg or by ≥1 class of antihypertensive drug withdraw., Results: A total of 46 patients were enrolled, of which 27 (59%) were in control group A and 19 (41%) in group B. The baseline age, gender, office and 24-hour SBP (mean 140.0 ± 12.8 mmHg vs. 144.0 ± 16.5 mmHg, p = 0.577) were comparable, while the number of prescribed drug classes was fewer in group A (4.0 ± 1.3 vs. 4.9 ± 0.9, p = 0.014). The proportion patients with prescribed aldosterone antagonist or high aldosterone-renin ratios were higher in group B. At 12 months post RDN, the results were significantly better in group B in terms of mean change in office SBP (12.4 ± 23.5 mmHg vs. 29.9 ± 25.5 mmHg, p = 0.046) and the proportion of RDN responders (51.9% vs. 89.5%, p < 0.001)., Conclusion: RDN was more effective in patients with any of 3 clinical indices., Competing Interests: The authors declare no conflict of interest. Tzung-Dau Wang is serving as one of the Editorial Board members of this journal. We declare that Tzung-Dau Wang had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Stefano Omboni, Brian Tomlinson and Takatoshi Kasai., (© 2022 The Author(s). Published by IMR Press.)

In this illustrative case, a transesophageal echocardiographic examination in a 69-year-old woman revealed normally functioning mechanical mitral prosthesis and a 4 cm left atrial heterogenous thrombus moving around her left atrium like a ping pong ball. Also visible was a thrombus within the left atrial appendage; the left atrial thrombus moved toward the mitral orifice and was bounced away by the mitral regurgitant jet.

In the current era of transcatheter edge-to-edge repair, deciding clip size in each case is still a challenge. We demonstrate that the XTR clip can achieve a better outcome than the NTR clip in a calcified leaflet.

Despite significant improvements in transcatheter aortic valve implantation (TAVI) outcomes, periprocedural conduction disturbances, such as new-onset left bundle branch block (LBBB) and new pacemaker implantation (PMI), remain relatively frequent concerns. The development of periprocedural conduction disturbances can be explained by the proximity between the aortic valve and the conduction system. Although prior studies reported heterogeneity in PMI rates after TAVI, current evidence supports the potentially deleterious consequence of LBBB and PMI, and several predisposing factors have been reported. Therefore, new strategies to avoid conduction disturbances and to improve their management are required, particularly with the current trend to expand TAVI to a low-risk population., Competing Interests: Disclosure: MM has been a consultant for Japan Lifeline. APT is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (Finance Code 001). RP has received consulting fees from Medtronic and has minor equity in Centerline Biomedical. FM has received grant and/or research support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific Corporation, NVT and Terumo; receives consulting fees and honoraria from Abbott, Medtronic, Edwards Lifesciences, SwissVortex, Perifect, Xeltis, Transseptal Solutions, Cardiovalve and Magenta; has royalty income or intellectual property rights from Edwards Lifesciences; and is a shareholder of Cardiovalve, Cardiogard, Magenta, SwissVortex, Transseptal Solutions, 4Tech and Perifect. MT is a consultant for Abbott Vascular, Boston Scientific, 4tech and CoreMedic; and has received speaker honoraria from Edwards Lifesciences. All other authors have no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Until recently, tricuspid valve (TV) disease has been relatively neglected for a long time, but recently tricuspid regurgitation (TR) has attracted attention. Although the prognosis of patients with these disorders is poor, the high mortality and morbidity associated with TV surgery have resulted in many patients not receiving surgical therapy. Current guidelines recommend that TV surgery should be considered in patients with severe TR who are symptomatic or have progressive right ventricle (RV) dilatation or dysfunction. In the absence of severe RV or left ventricle dysfunction, surgery should be considered in cases of severe pulmonary vascular disease or hypertension; however, it is difficult to assess RV dysfunction. Symptoms of right heart failure are more nonspecific and difficult to diagnose than those of left heart failure. Furthermore, the severity of TR is easily influenced by the use of diuretics. These factors lead to difficulties in patient selection and in determination of optimal timing for surgery. Transcatheter therapies for TR have begun to emerge as an alternative for patients with severe symptomatic TR who are at high-risk for standard surgery. Although initial results from a recent international multicenter registry have demonstrated that transcatheter TV therapy is feasible and safe, its clinical experience is still under development. In the present review, we describe the currently available techniques of transcatheter TV intervention and preliminary clinical results.

The Portico™ transcatheter aortic valve implantation (TAVI) system (Abbott Vascular, Santa Clara, CA, USA) was specifically designed to reduce some of the limitations associated with first-generation TAVI devices. Most of the currently available clinical evidence was obtained from randomized studies that compared TAVI to aortic valve replacement using first-generation transcatheter heart valve devices. The aim of this review is to describe the characteristics of the repositionable and retrievable Portico™ system and the technique of implantation, as well as to provide an overview of the most recent outcomes in the literature, along with our institutional experience.

Background: Catheter-based renal denervation (RDN) has emerged as a promising treatment option for hypertension. However, randomized controlled trials (RCTs) have reported conflicting results on blood pressure (BP) reduction. Patient- and procedure-related confounders have been implied as the potential sources of inconsistent BP responses. We aimed to investigated whether unplanned and frequent medication changes in RDN studies affected the BP response to RDN by conducting sensitivity and subgroup analyses, according to antihypertensive medication change rates in a meta-analysis of RCTs., Methods: We searched the PUBMED, EMBASE, and COCHRANE databases up to May 2018. RCTs that studied the effects of RDN on hypertensive patients were included. A meta-analysis was carried out using RevMan 5.3., Results: A total of 12 studies were included, of which four fulfilled the inclusion criteria of < 10% medication change rate in our review. Subgroup meta-analyses of the four RCTs with < 10% medication change rates showed statistically significant reductions of 6.07 mmHg and 7.12 mmHg in 24-hour and office systolic BP, respectively. The 24-hour and office diastolic BP were also reduced (mean difference = -3.89 mmHg and -4.27 mmHg, respectively). These subgroup analyses had no heterogeneity (I 2 = 0%). In contrast, the pooled analysis of the 12 studies and the subgroup analysis of eight studies with > 10% medication change rates both had a high level of heterogeneity and no significant BP reduction., Conclusions: The effectiveness of RDN was demonstrated across a broad range of antihypertensive medications used at baseline after removing the confounder of unplanned medication changes.

In this paper, we present quantitative data on how the social network and sex of infants influence allomothering behaviour among wild Formosan macaques, Macaca cyclopis. Using long-term field data collected from the Mount Longevity study site in Kaohsiung (Taiwan), we have tested relevant hypotheses incorporating data on age, rank and reproductive state of infant handlers, and the relationship between handlers and infants. The results support 2 major hypotheses, i.e. those of reciprocity and alliance formation. Nevertheless, neither could account for the observed occurrences of unrelated infant handling by dominant females., (© 2016 S. Karger AG, Basel.)

Several research advances have indicated an important role of transfer RNA (tRNA)-derived small RNAs in modulating developmental processes or stress responses. Recently, from the deep sequencing of small RNAs in Arabidopsis (Arabidopsis thaliana), we identified a new class of 19-nucleotide (nt) small RNAs corresponding to the 5' end of tRNA accumulated at high levels in phosphate-starved roots. In two very recent studies, 19-nt tRNA fragments were also observed in human cells, suggesting their widespread nature. In our study, tRNA halves cleaved at the anticodon loop, the most common tRNA fragments found, were predominant in roots. These results showed a spatial and temporal expression pattern of small RNAs derived from specific cleavage of tRNA molecules. Although the function of these tRNA-derived small RNAs under phosphate deficiency remains unknown, their diversity, biogenesis and potential function are henceforth summarized and discussed. Certainly, they will emerge as a novel class of regulatory small RNAs.

We have previously demonstrated that miR399s control phosphate (Pi) homeostasis by regulating the expression of a ubiquitin-conjugating E2 enzyme (UBC24/PHO2) in Arabidopsis. Changes in miR399-dependent PHO2 gene expression modulate Pi uptake, allocation and remobilization. More recently, we provided evidence that miR399s are able to move in the phloem stream and across grafting junctions from the scions overexpressing miR399 to the wild-type rootstocks. Movement of miR399s serves as a long-distance signal to report and balance the Pi status between shoots and roots. Of note, results from grafting experiments indicate that miR399b is less efficient in cleaving the PHO2 mRNA than is miR399f, despite the similar mobility of the two miR399s. We propose that nucleotide 13 of miR399s, which gives rise to the sequence variation among different miR399 species, could be involved in regulating the abundance of PHO2 mRNA through sequence complementarity to the target sequences of PHO2 mRNA and mimicking target sequence of At4/IPS1 noncoding RNAs.

The development of a highly efficient and stereoselective methodology for the preparation of alpha-amino acids is described. The chiral template, tricyclic iminolactone 7, was synthesized from (1R)-(+)-camphor in five steps in 50% overall yield. Alkylation of iminolactone 7 afforded the alpha-monosubstituted products in good yields (74-96%) and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired alpha-amino acids in good yields and enantioselectivities with nearly quantitative recovery of the chiral auxiliary 4.