Identification of Cannabidiolic and Cannabigerolic Acids as MTDL AChE, BuChE, and BACE-1 Inhibitors Against Alzheimer's Disease by In Silico, In Vitro, and In Vivo Studies.

Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model.

Cross-linking impacts the physical properties of mycelium leather alternatives by targeting hydroxyl groups of polysaccharides and amino groups of proteins.

Cross-linking, also called tanning, improves mechanical properties of leather and also increases its enzymatic and thermal stability. As a final product, leather has an ultimate tensile strength (σ) of 8-25 MPa and an elongation at break (ε) of >30 %. Mycelium-based materials are a sustainable alternative to leather.

Socioeconomic position during pregnancy and pre-school exposome in children from eight European birth cohort studies.

Distribution of environmental hazards and vulnerability to their effects vary across socioeconomic groups. Our objective was to analyse the relationship between child socioeconomic position (SEP) at birth and the external exposome at pre-school age (0-4 years). This study included more than 60,000 children from eight cohorts in eleven European cities (Oslo, Copenhagen, Bristol, Bradford, Rotterdam, Nancy, Poitiers, Gipuzkoa, Sabadell, Valencia and Turin).

Dietary Protein and Physical Exercise for the Treatment of Sarcopenia.

Sarcopenia is a multifactorial age-related disorder that causes a decrease in muscle mass, strength, and function, leading to alteration of movement, risk of falls, and hospitalization. This article aims to review recent findings on the factors underlying sarcopenia and the strategies required to delay and counteract its symptoms. We focus on molecular factors linked to ageing, on the role of low-grade chronic and acute inflammatory conditions such as cancer, which contributes to the onset of sarcopenia, and on the clinical criteria for its diagnosis.

Evaluation of Blood Lactate among Different Player Roles: A Pilot Study on Competitive Young Male Soccer Players.

Background: Soccer match requires anaerobic and aerobic energetic metabolism. The aim of this pilot study was to investigate the changes in blood lactate concentration in young male soccer players in different playing roles at different time points after the soccer match.

Methods: Following an initial screening of 134 young soccer athletes, 8 male athletes (average age of 15.

Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage.

Monoamine oxidase and xanthine oxidase inhibitors represent useful multi-target drugs for the prevention, attenuation, and treatment of oxidative damage and neurodegenerative disorders. Chimeric molecules, constituted by naturally derived compounds linked to drugs, represent lead compounds to be explored for the discovery of new synthetic drugs acting as enzyme inhibitors. We have previously reported that seven hydroxytyrosol-donepezil hybrid compounds play a protective role in an in vitro neuronal cell model of Alzheimer's disease.

Identification and Characterization of Neuroprotective Properties of Thaumatin-like Protein 1a from Apple Flesh Polyphenol Extract.

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are multifactorial neurodegenerative disorders that are mostly treated with drugs inhibiting key enzymes of cholinergic and aminergic neurotransmission, such as acetyl and butyryl cholinesterase (AChE, BuChE) or monoamine oxidases (MAO)-A/B, and of A aggregation. Diet plant components with multitarget functions are promising compounds in the prevention of AD and PD. Our aim was to identify neuroprotective compounds from apple polyphenol extract (AFPE).

Sub-THz wireless transmission based on graphene-integrated optoelectronic mixer.

Optoelectronics is a valuable solution to scale up wireless links frequency to sub-THz in the next generation antenna systems and networks. Here, we propose a low-power consumption, small footprint building block for 6 G and 5 G new radio wireless transmission allowing broadband capacity (e.g.

Inhibition of Enzymes Involved in Neurodegenerative Disorders and A Aggregation by Peel Polyphenol Extract.

Alzheimer's (AD) and Parkinson's diseases (PD) are multifactorial neurogenerative disorders of the Central Nervous System causing severe cognitive and motor deficits in elderly people. Because treatment of AD and PD by synthetic drugs alleviates the symptoms often inducing side effects, many studies have aimed to find neuroprotective properties of diet polyphenols, compounds known to act on different cell signaling pathways. In this article, we analyzed the effect of polyphenols obtained from the agro-food industry waste of peel (LPE) on key enzymes of cholinergic and aminergic neurotransmission, such as butyryl cholinesterase (BuChE) and monoamine oxidases (MAO)-A/B, on A aggregation and on superoxide dismutase (SOD) 1/2 that affect oxidative stress.

Hydroxytyrosol-Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer's Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells.

Alzheimer's disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. Under normal conditions, beta-amyloid peptides exert important trophic and antioxidant roles, while their massive presence leads to a cascade of events culminating in the onset of AD. The fibrils of beta-amyloid proteins are formed by the process of fibrillogenesis that, starting from individual monomers of beta-amyloid, can generate polymers of this protein, constituting the hypothesis of the "amyloid cascade".

Inhibition of Interleukin-6 Dependent Metalloproteinases-9/2 Expression in Cancer Cells by Diet Polyphenols.

Among inflammatory cytokines, Interleukin-6 (IL-6) is one of the major activators of acute phase response and is also involved in immune response and cancer progression. IL-6 is involved in the up-regulation of enzymes and growth factors acting on the extracellular matrix (ECM) remodelling components in physio-pathological processes. IL-6 enhances the expression of metalloproteases (MMP-)2/9, enzymes that play a key role in ECM degradation and therefore contribute to the process of tumor metastasis.

Heart transplantation and anti-HLA antibodY: myocardial dysfunction and prognosis - HeartLAy study.

Aims: The presence of anti-human leucocyte antigen (HLA) antibodies has been implicated in a higher incidence of complications as well as mortality rate in heart transplantation. The aim of the study was to identify through non-invasive parameters early signs of myocardial dysfunction in the presence of anti-HLA antibodies but without evidence of antibody-mediated rejection (AMR) and its possible prognostic impact.

Methods And Results: A total of 113 heart-transplanted patients without acute cellular rejection (ACR) and AMR or cardiac allograft vasculopathy (CAV) were prospectively enrolled and divided into two groups ['HLA+' (50 patients) and 'HLA-' (63 patients)], based on the presence of anti-HLA antibodies.

[Exposome: from definition to future challenges.].

The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure.

Modelling socioeconomic position as a driver of the exposome in the first 18 months of life of the NINFEA birth cohort children.

Background: The exposome drivers are less studied than its consequences but may be crucial in identifying population subgroups with unfavourable exposures.

Objectives: We used three approaches to study the socioeconomic position (SEP) as a driver of the early-life exposome in Turin children of the NINFEA cohort (Italy).

Methods: Forty-two environmental exposures, collected at 18 months of age (N = 1989), were classified in 5 groups (lifestyle, diet, meteoclimatic, traffic-related, built environment).

Phase noise mitigation in photonics-based radio frequency multiplication.

Two photonics-based radio frequency multiplication schemes for the generation of high-frequency carriers with low phase noise are proposed and experimentally demonstrated. With respect to conventional frequency multiplication schemes, the first scheme induces a selective cancelation of phase noise at periodic frequency-offset values, whereas the second scheme provides a uniform 3-dB mitigation of phase noise. The two schemes are experimentally demonstrated for the generation of a 110-GHz carrier by sixfold multiplication of an 18.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

Background: Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.

Maternal pesticides exposure in pregnancy and the risk of wheezing in infancy: A prospective cohort study.

Introduction: Pesticide exposure in pregnancy may have health effects in the offspring. We studied whether maternal pesticides exposure during pregnancy is associated with infant wheezing.

Methods: The study involved 5997 children from the Italian NINFEA birth cohort, whose mothers were recruited during pregnancy between 2005 and 2016.

Transient Hypogonadism Is Associated With Heart Rate-Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men.

Background Systemic inflammation and male hypogonadism are 2 increasingly recognized "nonconventional" risk factors for long-QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate-corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men.

Inhibition of Interleukin-6-Induced Matrix Metalloproteinase-2 Expression and Invasive Ability of Lemon Peel Polyphenol Extract in Human Primary Colon Cancer Cells.

Among matrix metalloproteinases (MMPs), MMP-9/2 are key enzymes involved in the proteolysis of extracellular matrices in the inflammatory process and in cancer. Since MMP-9/2 expression levels, activity, and secretion is up-regulated during inflammation in response to pro-inflammatory cytokines, such as interleukin-6 (IL-6), many efforts have been devoted to identifying factors that could inhibit the IL-6-induced MMP-9/2 expression. Up to now, several reports indicated that polyphenols from fruits and vegetables are among the major components of health promotion for their antioxidant properties and also for their anti-inflammatory and anti-cancer agents.

Is the New EN689 a Better Standard to Test Compliance With Occupational Exposure Limits in the Workplace?

Objective: To evaluate the performance of three measurement strategies to test compliance with occupational exposure limits of similarly exposed groups (SEGs): the old and new versions of EN689, and the BOHS-NVvA guidance on measuring compliance.

Methods: Respirable dust exposures concentrations (n = 1383) measured within the member companies of IMA-Europe were used to compare compliance decisions between the three measurement strategies. A total of 210 SEGs of which 158 with repeated measurements were analysed.

Unravelling Atrioventricular Block Risk in Inflammatory Diseases: Systemic Inflammation Acutely Delays Atrioventricular Conduction via a Cytokine-Mediated Inhibition of Connexin43 Expression.

Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap-junctions containing connexin43 coupling cardiomyocytes and inflammation-related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms.

Survival in acute heart failure in intensive cardiac care unit: a prospective study.

The aim of this study is to identify the best predictors of mortality among clinical, biochemical and advanced echocardiographic parameters in acute heart failure (AHF) patients admitted to coronary care unit (CCU). AHF is a clinical condition characterized by high mortality and morbidity. Several studies have investigated the potential prognostic factors that could help the risk assessment of cardiovascular events in HF patients, but at the moment it has not been found a complete prognostic score (including clinical, laboratory and echocardiographic parameters), univocally used for AHF patients.

Cardiac Arrest Risk During Acute Infections: Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-Mediated Effects on Potassium Channel Expression.

Background: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K channel expression.

Androgen Deprivation Therapy for Prostatic Cancer in Patients With Torsades de Pointes.

Background: Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases.

Expressive writing. A tool to help health workers. Research project on the benefits of expressive writing.

Background And Aims: Numerous studies in the international literature hold that expressive writing is a useful tool to take care of the person as a whole. It gives voice to emotions, moods and intimate thoughts of patients, as well as caregivers and family members. The reference model is based on Pennebaker's theory (2004), which posits that expressing our deeper thoughts and feelings can result in significant health benefits in the short and long term.