Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension

BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to evaluate the incremental prognostic value of echocardiography of the RV and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred-thirty treatment-naïve IPAH patients were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-minute walk distance plus an increase in functional class, or non elective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (Model-1). With addition of echocardiographic and CPET variables (Model-2), peak O2 pulse (peak VO2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (AUC: 0.81 vs 0.66, respectively; p=0.005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC+low O2 pulse showed 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk -RR- of 41.1 and 25.3, respectively), compared with high RVFAC+high O2 pulse (p=0.0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration

Audio-Vestibular Alterations During the Phases of the Menstrual Cycle in Patients with Cochlear Implant

Background: The female hormones fluctuations in woman’s life play a dominant role in homeostasis of the body and can influence the psycho-neurological processes in different body systems. In particular, in the auditory system seems that hormonal alterations during the menstrual cycle can compromise the homeostasis of the labyrinthine fluids altering balance and/or hearing. Aims/Objectives: Our study aims to verify if hormonal changes during different menstrual phases may have an influence, in females with cochlear implants, on the trend of auditory and vestibular performances. Materials and methods: Tonal, speech audiometry, vestibular examination and a measure of cochlear implants electrodes impedances were realized in the follicular and luteal phases on a group of eight women who are at a fertile age, affected by profound sensorineural form of hearing loss and carrying a monolateral cochlear implant. Results: Audio-vestibular alterations, as well as, an increase of impedance electrodes are reported in the luteal phase. Conclusions: Our work suggests that audio-vestibular alterations are related to the different phases of the menstrual cycle with consequent variation also of the performances of the implant. It is very important to keep in mind this aspect to avoid negative results during rehabilitation

Identification and Characterization of a Novel Plasmid-Encoded Laccase-Like Multicopper Oxidase from Ochrobactrum sp. BF15 Isolated from an On-Farm Bio-Purification System

Research background. In recent decades, laccases (p-diphenol-dioxygen oxidoreductases; EC 1.10.3.2) have attracted the attention of researchers due to their wide range of biotechnological and industrial applications. Laccases can oxidize a variety of organic and inorganic compounds, making them suitable as biocatalysts in biotechnological processes. Even though the most traditionally used laccases in the industry are of fungal origin, bacterial laccases have shown an enormous potential given their ability to act on several substrates and in multiple conditions. The present study aims to characterize a plasmid-encoded laccase-like multicopper oxidase (LMCO) from Ochrobactrum sp. BF15, a bacterial strain previously isolated from polluted soil. Experimental approach. We used in silico profile hidden Markov models to identify novel laccase-like genes in Ochrobactrum sp. BF15. For laccase characterization, we performed heterologous expression in Escherichia coli, purification and activity measurement on typical laccase substrates. Results and conclusions. Profile hidden Markov models allowed us to identify a novel LMCO, named Lac80. In silico analysis of Lac80 revealed the presence of three conserved copper oxidase domains characteristic of three-domain laccases. We successfully expressed Lac80 heterologously in E. coli, allowing us to purify the protein for further activity evaluation. Of thirteen typical laccase substrates tested, Lac80 showed lower activity on 2,2\u2019-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), pyrocatechol, pyrogallol and vanillic acid, and higher activity on 2,6-dimethoxyphenol. Novelty and scientific contribution. Our results show Lac80 as a promising laccase for use in industrial applications. The present work shows the relevance of bacterial laccases and highlights the importance of environmental plasmids as valuable sources of new genes encoding enzymes with potential use in biotechnological processes

Galdieria sulphuraria ACUF427 Freeze-Dried Biomass as Novel Biosorbent for Rare Earth Elements

Rare earth elements (REEs) are essential components of modern technologies and are often challenging to acquire from natural resources. The demand for REEs is so high that there is a clear need to develop efficient and environmentally-friendly recycling methods. In the present study, freeze-dried cells of the extremophile Galdieria sulphuraria were employed to recover yttrium, cerium, europium, and terbium from quaternary-metal aqueous solutions. The biosorption capacity of G. sulphuraria freeze-dried algal biomass was tested at different pHs, contact times, and biosorbent dosages. All rare earths were biosorbed in a more efficient way by the lowest dose of biosorbent, at pH 4.5, within 30 min; the highest removal rate of cerium was recorded at acidic pH (2.5) and after a longer contact time, i.e., 360 min. This study confirms the potential of freeze-dried cells of G. sulphuraria as innovative ecological biosorbents in technological applications for sustainable recycling of metals from e-waste and wastewater

Echocardiographic evaluation of right ventricular diastolic function in pulmonary hypertension

Background: Right ventricular (RV) diastolic dysfunction may be prognostic in pulmonary hypertension (PH). However, its assessment is complex and relies on conductance catheterisation. We aimed to evaluate echocardiography-based parameters as surrogates of RV diastolic function, provide validation against the gold standard, end-diastolic elastance (Eed), and define the prognostic impact of echocardiography-derived RV diastolic dysfunction. Methods: Patients with suspected PH who underwent right heart catheterisation including conductance catheterisation were prospectively recruited. In this study population, an echocardiography-based RV diastolic function surrogate was derived. Survival analyses were performed in patients with precapillary PH in the Giessen PH Registry, with external validation in patients with pulmonary arterial hypertension at Sapienza University (Rome). Results: In the derivation cohort (n=61), the early/late diastolic tricuspid inflow velocity ratio (E/A) and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (E/e') did not correlate with Eed (p>0.05). Receiver operating characteristic analysis revealed a large area under the curve (AUC) for the peak lateral tricuspid annulus systolic velocity/right atrial area index ratio (S'/RAAi) to detect elevated Eed (AUC 0.913, 95% confidence interval (CI) 0.839-0.986) and elevated end-diastolic pressure (AUC 0.848, 95% CI 0.699-0.998) with an optimal threshold of 0.81 m2·s-1·cm-1. Subgroup analyses demonstrated a large AUC in patients with preserved RV systolic function (AUC 0.963, 95% CI 0.882-1.000). Survival analyses confirmed the prognostic relevance of S'/RAAi in the Giessen PH Registry (n=225) and the external validation cohort (n=106). Conclusions: Our study demonstrates the usefulness of echocardiography-derived S'/RAAi for noninvasive assessment of RV diastolic function and prognosis in PH

Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases.

Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. A large part of these effects are related to its antioxidant properties. Here we review: a) the sources, the metabolism, and the bioavailability of resveratrol; b) the ability of resveratrol to modulate redox signalling and to interact with multiple molecular targets of diverse intracellular pathways; c) its protective effects against oxidative damage in cardio-cerebro-vascular districts and metabolic disorders such as diabetes; and d) the evidence for its efficacy and toxicity in humans. The overall aim of this review is to discuss the frontiers in the field of resveratrol's mechanisms, bioactivity, biology, and health-related use

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

Effect of dual-chamber minimal ventricular pacing on paroxysmal atrial fibrillation incidence in myotonic dystrophy type 1 patients: A prospective, randomized, single-blind, crossover study

Background: Atrial fibrillation (AF) is a common finding in the myotonic dystrophy type 1 (DM1) population. Pacemakers (PMs) may facilitate the diagnosis and management of frequent subclinical asymptomatic AF episodes. Objective: The purpose of this study was to evaluate the effect of minimal ventricular pacing on paroxysmal AF incidence in DM1 patients during a 24-month follow-up period. Methods: We enrolled 70 DM1 patients (age 43.4 ± 13.8 years; 39 women) who underwent dual-chamber PM implantation. Patients were randomized to minimizing ventricular pacing features (ON) or not (OFF). Patients crossed over to the opposite pacing programming 12 months later. We counted the number of DM1 patients with at least 1 episode of AF, the AF total duration, and the burden recorded by PM diagnostics during the MVP ON and OFF phases. Results: Twenty-five DM1 patients (41.7%) showed at least 1 AF episode. Seven patients (11.7%) demonstrated AF episodes during MVP ON phase and 25 patients (41.7%) during MVP OFF phase (P <.001). Thirty-five patients had no AF during MVP ON or OFF phase, 3 patients had AF episodes only during MVP ON phase, 21 patients had AF episodes only during MVP OFF phase, and 4 patients had AF episodes during MVP ON and OFF phases. Activation of the MVP algorithm was associated with a 44% reduction in relative risk of developing AF. Furthermore, during the MVP ON phases, the study population showed a shorter total AF duration and a lower AF burden. Conclusion: MVP is an efficacy strategy for reducing the risk of AF in DM1 patients who have undergone PM implantation