LONG-TERM PROGNOSIS AND MODES OF DEATH IN HEART FAILURE PATIENTS WITH REDUCED VERSUS PRESERVED LEFT VENTRICULAR SYSTOLIC FUNCTION

Background: There are conflicting reports regarding the prognosis of heart failure patients with preserved (HFPSF) comparative to reduced systolic left ventricular function (HFRSF). We evaluated the clinical characteristics, mortality rates and modes of death in 309 consecutive symptomatic heart failure patients. In 133(56%) patients LVEF was <50% (HFRSF), and in 133 (44%), LVEF was ≥50% (HFPSF). Methods: Three hundred nine consecutive patients hospitalized between January 1, 2009 and January 1, 2010 (176 men and 133 women, mean age 64.3 years) were followed up for a mean period of 23±14 months. The severity of symptoms at admission was assessed by NYHA classification. 196 patients were in NYHA class I-II, and 113 in III–IV. All patients underwent chest X-ray, echocardiogram, and a 6-minute walking test. We compared the clinical profiles, mortality rates and modes of death. Results: More than a third (44%) of the patients had preserved systolic LVEF based on echocardiography. Compared to the HFPSF group, HFRSF patients were predominantly younger males with ischemic aetiology and less cardiovascular comorbidities such as obesity, hypertension, diabetes mellitus and atrial fibrillation. During a mean follow-up period of 1.9 years, 22 (7.1%) patients died: 14 of cardiac causes and 8 of non-cardiac causes (4 of respiratory causes, 2 of stroke, 1 of major bleeding and 1 of cancer). Overall mortality was similar between the two groups: 8 (6%) in HFPSF patients and 14 (7.9%) in HFRSF patients (p=0.67). HFRSF patients had higher death rates due to pump failure compared to the HFPSF group [ 5/14(36%) vs. 1/8(12%) patients, p=0.5]. Non-cardiac deaths were more frequent in HFPSF group [4/8 (50%) patients vs. 4/14(28%) patients, respectively, p=0.5]. The prevalence of arrhythmic death was similar in the two groups [5/14(36%) vs.3/8(37%) patients, p=0.6]. With Cox stepwise regression analysis for survival, the independent predictors for mortality were age, gender, ischemic etiology of heart failure and renal impairment. Conclusions: Although the characteristics of HFPSF and SHF patients are different, the mortality rates were similar in our study. The mode of death was different among the two groups of patients, as pump failure death rate was higher in patients with LVEF <50%, while non-cardiac death was higher in heart failure patients with preserved systolic function. The differences were not statistically significant. A high NYHA class at admission, age over 65, male gender and renal impairment were related to a worse prognosis

Complex Networks of Prion-Like Proteins Reveal Cross Talk Between Stress and Memory Pathways in Plants.

Prions are often considered as molecular memory devices, generating reproducible memory of a conformational change. Prion-like proteins (PrLPs) have been widely demonstrated to be present in plants, but their role in plant stress and memory remains unexplored. In this work, we report the widespread presence of PrLPs in plants through a comprehensive meta-analysis of 39 genomes representing major taxonomic groups. We find diverse functional roles associated with these proteins in various species and term the full complement of PrLPs in a genome as its "prionome." In particular, we found the rice prionome being significantly enriched in transposons/retrotransposons (Ts/RTRs) and identified over 60 rice PrLPs that were differentially regulated in stress and developmental responses. This prompted us to explore whether and to what extent PrLPs may build stress memory. By integrating the available rice interactome, transcriptome, and regulome data sets, we could find links between stress and memory pathways that would not have otherwise been discernible. Regulatory inferences derived from the superimposition of these data sets revealed a complex network and cross talk between PrLPs, transcription factors (TFs), and the genes involved in stress priming. This integrative meta-analysis connects transient and transgenerational memory mechanisms in plants with PrLPs, suggesting that plant memory may rely upon protein-based signals in addition to chromatin-based epigenetic signals. Taken together, our work provides important insights into the anticipated role of prion-like candidates in stress and memory, paving the way for more focused studies for validating the role of the identified PrLPs in memory acclimation

METALLOME OF ORIGANUM VULGARE: THE UNKNOWN SIDE OF A MEDICINAL AND AROMATIC PLANT USED WORLDWIDE

Abstract Potential health benefits of aromatic and medicinal plants connected to their content in minerals are usually not evoked by the relevant literature. However, they may be significant for persons using regularly phytotherapy, as well as for those adopting diets which are rich in herbal spices. In this context, we performed an extensive investigation of metal and metalloid elements present in different populations of wild-growing Origanum vulgare samples from Romania. Forty-nine elements were identified and quantified through inductively coupled plasma -mass spectrometry (ICP-MS). Results were discussed as to their significance for human health. The present study provides, for the first time, a complete set of reference data on the mineral content of Origanum vulgare from South-Western Romania. Rezumat Aportul elementelor minerale din plantele medicinale şi aromatice la menţinerea stării de sănătate este rareori abordată în literatura de specialitate. Totuși, această contribuţie ar putea fi semnificativă la persoanele care recurg în mod regulat la fitoterapie, precum şi la cele care adoptă o alimentaţie bogată în condimente vegetale. În acest context a fost realizată o analiză extensivă a elementelor metalice şi metaloizilor prezenţi în diferite populaţii de şovârf (Origanum vulgare) din flora spontană a României. Patruzeci şi nouă de elemente au fost identificate şi cuantificate prin inductively coupled plasma -mass spectrometry (ICP-MS). Rezultatele au fost analizate sub aspectul semnificaţiei lor pentru sănătatea umană. Prezentul studiu oferă, pentru prima dată, un set complet de date de referinţă pentru conţinutul în elemente minerale ale speciei Origanum vulgare din sud-vestul României

IN SILICO IDENTIFICATION OF NOVEL DRUG TARGETS IN ACINETOBACTER BAUMANNII BY SUBTRACTIVE GENOMIC APPROACH

 Objective: Multiple drug resistance (MDR) in bacteria, particularly Gram-negative bacilli, has significantly hindered the treatment of infections caused by these bacteria. This results in the need for identifying new drugs and drug targets for these bacteria. The objective of this study was to identify novel drug targets in Acinetobacter baumannii which has emerged as a medically important pathogen due to an increasing number of infections caused by it and its MDR property.Methods: In our study, we implemented in silico subtractive genomics approach to identify novel drug targets in A. baumannii American type culture collection 17978. Various databases and online software were used to build a systematic workflow involving comparative genomics, metabolic pathways analysis, and drug target prioritization to identify pathogen-specific novel drug targets.Results: First, 458 essential proteins were retrieved from a database of essential genes, and by performing BLASTp against Homo sapiens, 246 human non-homologous essential proteins were selected of 458 proteins. Metabolic pathway analysis performed by Kyoto Encyclopedia of Genes and Genomes–Kyoto Automatic Annotation Server revealed that these 246 essential non-homologous proteins were involved in 66 metabolic pathways. Among these metabolic pathways, 12 pathways were found to be unique to Acinetobacter that involved 37 non-homologous essential proteins. Of these essential non-homologous proteins, 19 proteins were found in common as well as unique metabolic pathways and only 18 proteins were unique to Acinetobacter. Finally, these target proteins were filtered to 9 potential targets, based on subcellular localization and assessment of druggability using Drug bank, ChEMBL, and literature.Conclusion: Our study identified nine potential drug targets which are novel targets in A. baumannii and can be used for designing drugs against these proteins. These drugs will be pathogen specific with no side effects on human host, as the potential drug targets are human non-homologous

The Predictive Role of NLR, d-NLR, MLR, and SIRI in COVID-19 Mortality

(1) Background: Since its discovery, COVID-19 has caused more than 256 million cases, with a cumulative death toll of more than 5.1 million, worldwide. Early identification of patients at high risk of mortality is of great importance in saving the lives of COVID-19 patients. The study aims to assess the utility of various inflammatory markers in predicting mortality among hospitalized patients with COVID-19. (2) Methods: A retrospective observational study was conducted among 108 patients with laboratory-confirmed COVID-19 hospitalized between 1 May 2021 and 31 October 2021 at Municipal Emergency Clinical Hospital of Timisoara, Romania. Blood cell counts at admission were used to obtain NLR, dNLR, MLR, PLR, SII, and SIRI. The association of inflammatory index and mortality was assessed via Kaplan–Maier curves univariate Cox regression and binominal logistic regression. (3) Results: The median age was 63.31 ± 14.83, the rate of in-hospital death being 15.7%. The optimal cutoff for NLR, dNLR, MLR, and SIRI was 9.1, 9.6, 0.69, and 2.2. AUC for PLR and SII had no statistically significant discriminatory value. The binary logistic regression identified elevated NLR (aOR = 4.14), dNLR (aOR = 14.09), and MLR (aOR = 3.29), as independent factors for poor clinical outcome of COVID-19. (4) Conclusions: NLR, dNLR, MLR have significant predictive value in COVID-19 mortality

A two-phase, two-component bubbly flow model.

This thesis is focused attention on one-dimensional models for fast transient flows in a kinematic non-equilibrium. Besides the thermodynamic non-equilibrium, there is another type of non-equilibrium: the kinematic non-equilibrium, or drift between the phases. Such flow models include bubbly gas/liquid flows which are characterized by strong coupling between the phases, due to the rapid interphase transfers of mass, momentum and energy. As a consequence the assumptions that the phase pressures and the phase temperatures are equal at any cross-section appear consistent with experimental observations. The set of equations includes a momentum equation which has the form of a relaxation law of the drift velocity. This equation is based on a simplified version of the so-called Voinov - Berne equation for the momentum of the gas in a bubbly flow. The ability of the model to predict steady state critical flows is tested first. This is done by means of an analysis of the sensitivity to variations of the main parameters, and also by comparing the results with two sets of original experimental data on air-water critical flows. Finally, the model is tested in transient conditions, modelling the water hammer phenomena.(FSA 3)--UCL, 200

Calcium, Magnesium, and Zinc Supplementation during Pregnancy: The Additive Value of Micronutrients on Maternal Immune Response after SARS-CoV-2 Infection

Magnesium may contribute to the immune response during and after SARS-CoV-2 infection by acting as a cofactor for immunoglobulin production and other processes required for T and B cell activity. Considering magnesium as a recommended dietary supplement during pregnancy and the possible role of magnesium deficiency in COVID-19 and its complications, the current study sought to determine the effect of magnesium and magnesium-containing nutritional supplements on the immune response following SARS-CoV-2 infection in pregnant women, as well as to observe differences in pregnancy outcomes based on the supplements taken during pregnancy. The study followed a cross-sectional design, where patients with a history of SARS-CoV-2 infection during their pregnancy were surveyed for their preferences in nutritional supplementation and their profile compared with existing records from the institutional database. A cohort of 448 pregnant women with COVID-19 during 22 months of the pandemic was assembled, out of which 13.6% took a magnesium-only supplement, and 16.5% supplemented their diet with a combination of calcium, magnesium, and zinc. Around 60% of patients in the no-supplementation group had the SARS-CoV-2 anti-RBD lower than 500 U/mL, compared with 50% in those who took magnesium-based supplements. A quantity of magnesium >450 mg in the taken supplements determined higher levels of antibody titers after COVID-19. Low magnesium dosage (<450 mg) was an independent risk factor for a weak immune response (OR-1.25, p-value = 0.003). The observed findings suggest supplementing the nutritional intake of pregnant women with magnesium-based supplements to determine higher levels of SARS-CoV-2 anti-RBD antibodies, although causality remains unclear

The Risk of Spontaneous Abortion Does Not Increase Following First Trimester mRNA COVID-19 Vaccination

Clinical trials for COVID-19 vaccines initially excluded pregnant women due to safety concerns, and when the vaccines were authorized for emergency use, they were not recommended for this population. However, observational studies discovered that pregnant women infected with COVID-19 have higher risks of negative pregnancy and delivery outcomes compared to non-pregnant women, raising the question of the risks–benefits of administering COVID-19 vaccines to pregnant women. By mid-2021, there was general consensus on the relative safety of COVID-19 vaccination during pregnancy; therefore, it is critical to investigate the safety issues related to these vaccines, considering the increasing acceptance among pregnant women. To address these concerns, we developed a research project to study the short-term effects and outcomes of COVID-19 vaccination during the first trimester of pregnancy. Our research followed an observational retrospective design for 12 months from the beginning of the vaccination campaign, and included 124 cases of spontaneous abortions and 927 ongoing pregnancies. The odds of spontaneous abortion were non-significant for both versions of the mRNA vaccine (Pfizer BNT162b2 AOR = 1.04, CI = 0.91–1.12; Moderna mRNA-1273 AOR = 1.02, CI = 0.89–1.08). Overall, our data indicated that the risk of spontaneous abortion after mRNA COVID-19 immunization during the first trimester of pregnancy is commensurate with the predicted risk in non-vaccinated pregnant women. These findings contribute to the growing body of information regarding the safety of mRNA COVID-19 vaccination during pregnancy