Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present ...angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term “coronary microvascular dysfunction” (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD (“primary” microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.
With approximately 450 species, spiny Solanum species constitute the largest monophyletic group in the Solanaceae family, but a high-quality genome assembly from this group is presently missing. We ...obtained a chromosome-anchored genome assembly of eggplant (Solanum melongena), containing 34,916 genes, confirming that the diploid gene number in the Solanaceae is around 35,000. Comparative genomic studies with tomato (S. lycopersicum), potato (S. tuberosum) and pepper (Capsicum annuum) highlighted the rapid evolution of miRNA:mRNA regulatory pairs and R-type defense genes in the Solanaceae, and provided a genomic basis for the lack of steroidal glycoalkaloid compounds in the Capsicum genus. Using parsimony methods, we reconstructed the putative chromosomal complements of the key founders of the main Solanaceae clades and the rearrangements that led to the karyotypes of extant species and their ancestors. From 10% to 15% of the genes present in the four genomes were syntenic paralogs (ohnologs) generated by the pre-γ, γ and T paleopolyploidy events, and were enriched in transcription factors. Our data suggest that the basic gene network controlling fruit ripening is conserved in different Solanaceae clades, and that climacteric fruit ripening involves a differential regulation of relatively few components of this network, including CNR and ethylene biosynthetic genes.
It is known from previous literature that type II Spinal Muscular Atrophy (SMA) patients generally, after the age of 5 years, presents a steep deterioration until puberty followed by a relative ...stability, as most abilities have been lost. Although it is possible to identify points of slope indicating early improvement, steep decline and relative stabilizations, there is still a lot of variability within each age group and it's not always possible to predict individual trajectories of progression from age only. The aim of the study was to develop a predictive model based on machine learning using an XGBoost algorithm for regression and report, explore and quantify, in a single centre longitudinal natural history study, the influence of clinical variables on the 6/12-months Hammersmith Motor Functional Scale Expanded score prediction (HFMSE). This study represents the first approach to artificial intelligence and trained models for the prediction of individualized trajectories of HFMSE disease progression using individual characteristics of the patient. The application of this method to larger cohorts may allow to identify different classes of progression, a crucial information at the time of the new commercially available therapies.
There is a growing interest in photoplethysmography (PPG) for the continuous monitoring of cardio-respiratory signals by portable instrumentation aimed at the early diagnosis of cardiovascular ...diseases. In this context, it is conceivable that PPG sensors working at different wavelengths simultaneously can optimize the identification of apneas and the quantification of the associated heart-rate changes or other parameters that depend on the PPG shape (e.g., systematic vascular resistance and pressure), when evaluating the severity of breathing disorders during sleep and in general for health monitoring. Therefore, the objective of this work is to present a novel pulse oximeter that provides synchronous data logging related to three light wavelengths (green, red, and infrared) in transmission mode to optimize both heart rate measurements and a reliable and continuous assessment of oxygen saturation. The transmission mode is considered more robust over motion artifacts than reflection mode, but current pulse oximeters cannot employ green light in transmission mode due to the high absorbance of body tissues at this wavelength. For this reason, our device is based on a Single-Photon Avalanche Diode (SPAD) with very short deadtime (less than 1 ns) to have, at the same time, the single photon sensitivity and high-count rate that allows acquiring all the wavelengths of interest on the same site and in transmission mode. Previous studies have shown that SPAD cameras can be used for measuring the heart rate through remote PPG, but oxygen saturation and heart-rate measures through contact SPAD-based PPG sensors have never been addressed so far. The results of the preliminary validation on six healthy volunteers reflect the expected physiological phenomena, providing rms errors in the Inter Beat Interval estimation smaller than 70 ms (with green light) and a maximum error in the oxygen saturation smaller than 1% during the apneas. Our prototype demonstrates the reliability of SPAD-based devices for continuous long-term monitoring of cardio-respiratory variables as an alternative to photodiodes especially when minimal area and optical power are required.
Abstract
Background
Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in ...determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis.
Methods
We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up.
Results
We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 73.1% men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 53.75%) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 63.4% vs. 68 45.9%, p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 14.5% vs. 12 8.1%, p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months).
Conclusions
The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.
Human papillomavirus 16 (HPV-16) L1 protein has the capacity to self-assemble into capsomers or virus-like particles (VLPs) that are highly immunogenic, allowing their use in vaccine production. ...Successful expression of HPV-16 L1 protein has been reported in plants, and plant-produced VLPs have been shown to be immunogenic after administration to animals.
We investigated the potential of HPV-16 L1 to act as a carrier of two foreign epitopes from Influenza A virus: (i) M2e2-24, ectodomain of the M2 protein (M2e), that is highly conserved among all influenza A isolates, or (ii) M2e2-9, a shorter version of M2e containing the N-terminal highly conserved epitope, that is common for both M1 and M2 influenza proteins. A synthetic HPV-16 L1 gene optimized with human codon usage was used as a backbone gene to design four chimeric sequences containing either the M2e2-24 or the M2e2-9 epitope in two predicted surface-exposed L1 positions. All chimeric constructs were transiently expressed in plants using the Cowpea mosaic virus-derived expression vector, pEAQ-HT. Chimeras were recognized by a panel of linear and conformation-specific anti HPV-16 L1 MAbs, and two of them also reacted with the anti-influenza MAb. Electron microscopy showed that chimeric proteins made in plants spontaneously assembled in higher order structures, such as VLPs of T = 1 or T = 7 symmetry, or capsomers.
In this study, we report for the first time the transient expression and the self-assembly of a chimeric HPV-16 L1 bearing the M2e influenza epitope in plants, representing also the first record of a successful expression of chimeric HPV-16 L1 carrying an epitope of a heterologous virus in plants. This study further confirms the usefulness of human papillomavirus particles as carriers of exogenous epitopes and their potential relevance for the production in plants of monovalent or multivalent vaccines.
Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary ...circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.
The aim of the study was to build a machine learning-based predictive model to discriminate between hospitalized patients at low risk and high risk of bloodstream infection (BSI). A Data Mart ...including all patients hospitalized between January 2016 and December 2019 with suspected BSI was built. Multivariate logistic regression was applied to develop a clinically interpretable machine learning predictive model. The model was trained on 2016-2018 data and tested on 2019 data. A feature selection based on a univariate logistic regression first selected candidate predictors of BSI. A multivariate logistic regression with stepwise feature selection in five-fold cross-validation was applied to express the risk of BSI. A total of 5660 hospitalizations (4026 and 1634 in the training and the validation subsets, respectively) were included. Eleven predictors of BSI were identified. The performance of the model in terms of AUROC was 0.74. Based on the interquartile predicted risk score, 508 (31.1%) patients were defined as being at low risk, 776 (47.5%) at medium risk, and 350 (21.4%) at high risk of BSI. Of them, 14.2% (72/508), 30.8% (239/776), and 64% (224/350) had a BSI, respectively. The performance of the predictive model of BSI is promising. Computational infrastructure and machine learning models can help clinicians identify people at low risk for BSI, ultimately supporting an antibiotic stewardship approach.
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•A 2D heterogeneous transient model for multi-tubular methanol reactor is developed.•The model is used to simulate the operations of a biogas-to-methanol process.•The flexibility of a ...multi-tubular reactor is shown in the presence of load changes.•A sensitivity analysis is conducted on reactor inlet flowrate and composition.•The effects of tube length and gas hourly space velocity are assessed.
The present modelling work studies the steady state and transient performances of a multi–tubular fixed bed reactor for methanol production from biogas. The modelled system comprises a methanol synthesis reactor, a flash unit, and accounts for the unconverted gas recycle. The novel concept herein proposed and assessed is the possibility to run a multi–tubular methanol synthesis reactor flexibly, i.e., using the carbon dioxide present in biogas, together with renewable H2, to increase methanol productivity, only when this is economically convenient. Accordingly, the methanol synthesis multi–tubular reactor under study is run in two operating conditions: when the cost of green hydrogen is high, the excess of CO2 present in biogas is vented and the reactor is fed with CO2-lean syngas only; conversely, in the presence of affordable renewable H2, CO2 and green H2 are cofed to the reactor. This study focuses in particular on the impacts of the two working conditions on the methanol productivity, as well as on temperature profiles and transient behaviour of the reactor. The effects of tube length and number are also simulated. The study shows that the multi–tubular reactor design well manages both operating conditions and that the steady-state conditions can be reached in a few hours after the switch from one condition to the other. In view of a small scale process, simulations show that it is better to reduce the tube number rather than their length, as the latter choice would lead to unacceptable temperature hotspots, due to a worsening of convective heat transfer.
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