Effect of sacubitril/valsartan in heart failure with preserved ejection fraction across the age spectrum in PARAGON-HF.

Aims: To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial.

Methods And Results: A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65-74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory.

Two still unanswered questions about uric acid and cardiovascular prevention: Is a specific uric acid cut-off needed? Is hypouricemic treatment able to reduce cardiovascular risk?

Aims: The most frequent consequence of elevated uric acid (UA) levels is the development of gout and urate kidney disease. Besides these effects, several studies have investigated the association between hyperuricemia and cardiovascular (CV) disease. High serum UA has been identified as an important determinant of all-cause and CV mortality and CV events (acute and chronic coronary syndrome, stroke and peripheral artery disease).

Acute kappa opioid receptor blocking disrupts the pro-cognitive effect of cannabidiol in neuropathic rats.

Cannabidiol has been shown to ameliorate neuropathic pain and its affective components. Previous studies highlighted the pharmacological interaction between the CBD and opioid system, particularly the MOR, but the understanding of the interaction between CBD and kappa opioid receptor (KOR), physiologically stimulated by the endogenous opioid dynorphin, remains elusive. We assessed the pharmacological interactions between CBD and nor-BNI, a selective KOR antagonist in a rat neuropathic pain model.

Advances in molecular genetics have increased knowledge of Tuber species' life cycle and population genetic structure, indicating ways to improve yield.

Truffles are possibly the only high-value cultivated organisms for which some aspects of the habit and life cycle have only recently been elucidated or remain unknown. Molecular techniques have helped explain the biological basis for some traditional empirical management techniques, such as inoculating soil with ascospores to improve yield, and have enhanced the detection of competitive or pathogenic soil microorganisms. Improved precision of assessment of the quality of inoculated seedlings is now possible.

Structure-based targeting of the lipid A-modifying enzyme PmrC to contrast colistin resistance in .

Introduction: Antimicrobial-resistant pathogens are an ongoing threat to human and animal health. According to the World Health Organization (WHO), colistin is considered the last resort antibiotic against human infections due to multidrug-resistant Gram-negative organisms-including , a priority-1 pathogen. Despite colistin being considered a last resort antibiotic, transferable bacterial resistance to this drug has been reported in humans and animals.

-related disorder in 87 adults: Natural history and self-sustainability.

Purpose: is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with -related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with -related disorder were collected through an online questionnaire completed by clinicians and parents.

Io's tidal response precludes a shallow magma ocean.

Io experiences tidal deformation due to its eccentric orbit around Jupiter, which provides a primary energy source for Io's ongoing volcanic activity and infrared emission. The amount of tidal energy dissipated within Io is enormous and has been hypothesized to support the large-scale melting of Io's interior and the formation of a global subsurface magma ocean. If Io has a shallow global magma ocean, its tidal deformation would be much larger than in the case of a more rigid, mostly solid interior.

A preliminary study on the effects of rainfall-related conditions on chromium increase in ultramafic-hosted springs: A possible climate change concern?

This study investigates the impact of intense rainfall on chromium concentrations in five springs discharging from ultramafic rocks in the Northern Apennines (Italy), which are used for drinking water supply through integration into the local water network. Total chromium concentration increased significantly in response to heavy rain, exceeding the WHO drinking water guideline value (up to 80 μg/L) in one spring and the forthcoming 2036 EU target of 25 μg/L in all the springs. This increase could be attributed to a synergistic combination of factors: i) the reduction of Cr(VI) to Cr(III) by natural organic matter (NOM) in soil and transport as NOM-Cr(III) colloids and/or during the oxidation of magnetite to ferrihydrite in the aquifer; ii) the abundance of detrital ultramafic material in the study area, which may store Cr(III)-bearing colloids too; iii) a triggering effect of first intense rainfall after a 20 dry consecutive days period (wet-dry cycle).

Csp-Csp Coupling of Isonitriles and (Hetero)arenes through a Photoredox-Catalyzed Double Decyanation Process.

Herein, we demonstrate the ability of isonitriles to be used as alkyl radical precursors in a photoredox-catalyzed transformation involving selective C-N cleavage and Csp-Csp bond formation. This protocol allows for the preparation of functionalized heteroarenes from readily available isonitriles through a decyanation process. The reaction is general for primary, secondary, and tertiary substrates, including amino acid derivatives and druglike molecules.

The reporting of disproportionality analysis in pharmacovigilance: spotlight on the READUS-PV guideline.

Disproportionality analyses are the most-commonly used study design used in the post-marketing phase to detect suspected adverse drug reactions in individual case safety reports. Recent years have witnessed an exponential increase in published articles on disproportionality analyses, thanks to publicly accessible databases. Unfortunately, this trend was accompanied by concerns on lack of transparency and misinterpretation of results, both generating unjustified alarm and diluting true signals into overwhelming noise.

Predictors of VILI risk: driving pressure, 4DPRR and mechanical power ratio-an experimental study.

Background: Ventilator-induced lung injury (VILI) is one of the side effects of mechanical ventilation during ARDS; a prerequisite for averting it is the quantification of its risk factors associated with a given ventilatory setting. Many clinical variables have been proposed as predictors of VILI, of which driving pressure is the most widely used. In this study, we compared the performance of driving pressure, four times the driving pressure added to respiratory rate (4DPRR) and mechanical power ratio.

Rethinking ARDS classification: oxygenation impairment fails to predict VILI risk.

Purpose: The selection and intensity of respiratory support for ARDS are guided by PaO/FiO. However, ventilator-induced lung injury (VILI) is linked to respiratory mechanics and ventilator settings. We explored whether the VILI risk is related to ARDS severity based on oxygenation.

Perspectives, perceptions, and expectations of subjects with frozen shoulder: a web-based Italian survey.

Introduction: Frozen shoulder (FS) is a musculoskeletal disorder affecting the glenohumeral joint. This condition leads to disability and a worsening in quality of life. Despite its considerable impact on patients and its economic burden, research on the psychological and social implications of FS-as well as patients' perspectives and needs-is limited.

Trichoscopy of Frontal Fibrosing Alopecia in Caucasians: A Review.

Background: Frontal fibrosing alopecia (FFA) is a scarring hair loss condition primarily affecting the frontotemporal hairline and often leading to partial or complete loss of eyebrows in a significant number of cases. It is characterized by slow progression and typically shows poor response to available treatments. Diagnosis relies on clinical, trichoscopic, and histopathological assessments, with specific criteria proposed by Vañó-Galván et al.

Chemoradiation of locally advanced biliary cancer: A PRISMA-compliant systematic review.

Introduction: Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option.

Polygenic and Polyenvironment Interplay in Schizophrenia-Spectrum Disorder and Affective Psychosis; the EUGEI First Episode Study.

Background: Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified.

Methods: We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry.

Infrared spectroscopy and chemometrics for predicting commercial categories of virgin olive oils and supporting the panel test.

The aim of this study was to create rapid and sustainable instrumental methods for screening virgin olive oils (VOOs) to support the Panel test. The Panel test is the official sensory method used in EU regulations to determine the commercial category of VOOs. The Panel test is based on a time-consuming and expensive approach, so reducing the number of samples to be analysed is crucial.

Impact of concomitant aortic valve replacement in patients with mild-to-moderate aortic valve regurgitation undergoing left ventricular assist device implantation: EUROMACS analysis.

Introduction: Left ventricular assist device (LVAD) therapy may lead to an aortic regurgitation, limiting left ventricular unloading and causing adverse events. Whether concomitant aortic valve replacement may improve outcomes in patients with preoperative mild-to-moderate aortic regurgitation remains unclear.

Methods: A retrospective propensity score-matched analysis of adult patients with preoperative mild-to-moderate aortic regurgitation undergoing durable LVAD implantation between 01/01/2011 and 30/11/2021 was performed.

Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.

Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment.

Pyoderma Gangrenosum: A Retrospective Case Series of 44 Patients.

Introduction: Pyoderma gangrenosum (PG) poses a significant dermatological challenge due to its rapidly evolving painful necrotic ulcerations. Understanding its multifaceted pathogenesis and diverse clinical presentation is crucial for effective management.

Objectives: We aimed to analyze demographic characteristics, clinical manifestations, lesion distributions, systemic disease associations, therapeutic interventions, and patient outcomes in PG cases.