Natural Products for Neurocognitive Disorders

ABSTRACT Neurocognitive disorders are devastating. In 2016, 43.8 million people were estimated to have Alzheimer's disease worldwide. By 2050, this figure is expected to rise by 56%. Despite the extreme importance of the disease, the weapons available to us to combat it are very scarce. Natural substances may be a worthwhile option for the treatment and management of neurocognitive disorders. Some of these natural products have been shown to be capable of positively impacting memory, behavior, and functions of patients with Alzheimer's disease. These substances act on the disease mainly through antioxidant properties, the ability to eliminate oxygen radicals, the capacity to influence cell survival and programmed cell death, and the potential to condition amyloidogenesis. This chapter provides an overview of our current knowledge on the potential of natural products to be effective neuroprotective agents for Alzheimer's disease. Current evidence on Ginkgo biloba, bacopia, resveratol, curcumin, quercetin, kaempferol, capsaicin, and berberine, along with their adverse effects and drug interactions are discussed

New frontiers of cognitive rehabilitation in geriatric age: the Mozart effect (ME)

The ME was described for the first time in 1993. Subsequently other studies with similar designs were performed. The present study, therefore, proposes: (i) to verify the existence of the benefits of exposure to music in elderly subjects with mild cognitive impairment (MCI), (ii) to explore whether it is possible to find any lasting improvement after training, conducted for a long period of time, with such musical pieces, in the measurable cognitive performances. The study we conducted showed that the ME is present in geriatric patients with MCI; the influence on spatial–temporal abilities remains constant in time if the stimulation is maintained. The continuation of our study will consist of increasing the number of individuals examined and in having them listen to music during the study of ECG rhythms and during the acquisition of cerebral functional magnetic resonance imaging (fMRI), and, at the same time, testing them by neuropsychometric methods

PCSK9 regulates Nox2-mediated platelet activation via CD36 receptor in patients with atrial fibrillation

Background: High levels of proprotein convertase subtilisin/kexin 9 (PCSK9) is predictive of cardiovascular events (CVEs) in atrial fibrillation (AF). We hypothesized that PCSK9 may directly induce platelet activation (PA). Methods: We measured platelet aggregation, recruitment, Thromboxane B2 (TxB2) formation and soluble P-selectin levels as markers of PA and soluble Nox2-derived peptide (sNox2-dp), H2O2, isoprostanes and oxidized Low-Density-Lipoprotein (oxLDL) to analyze oxidative stress (OS) in 88 patients having PCSK9 values < (n = 44) or > (n = 44) 1.2 ng/mL, balanced for age, sex and cardiovascular risk factors. Furthermore, we investigated if normal (n = 5) platelets incubated with PCSK9 (1.0–2.0 ng/mL) alone or with LDL (50 µg/mL) displayed changes of PA, OS and down-stream signaling. Results: PA and OS markers were significantly higher in patients with PCSK9 levels > 1.2 ng/mL compared to those with values < 1.2 ng/mL (p < 0.001). Levels of PCSK9 significantly correlated with markers of PA and OS. Platelets incubation with PCSK9 increased PA, OS and p38, p47 and Phospholipase A2 (PLA2) phosphorylation. These changes were amplified by adding LDL and blunted by CD36 or Nox2 inhibitors. Co-immunoprecipitation analysis revealed an immune complex of PCSK9 with CD36. Conclusions: We provide the first evidence that PCSK9, at concentration found in the circulation of AF patients, directly interacts with platelets via CD36 receptor and activating Nox2: this effect is amplified in presence of LDL

Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%). CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

A&A Architettura e Ambiente 24 Strutture residenziali per la terza età. Discipline mediche

L'invecchiamento è un processo che interessa tutti gli organismi viventi e che comporta modificazioni biologiche. Nell'uomo si assiste a tali modificazioni del corpo e delle sue funzioni, seguite da un processo di adattamento psicofisico, già dopo i 30 anni; il fenomeno è graduale e progressivo, anche se variabile per ogni individuo. Tuttavia la vecchiaia può assumere un significato positivo e può essere vissuta nel modo giusto ...non è soltanto il momento della saggezza, ma può essere anche quello della creatività

Epidemiologia della Longevità

La sopravvivenza di un organismo è in relazione a numerosi fattori, ma la nozione che le varie specie dei mammiferi presentano un ciclo vitale caratteristico per ciascuna specie suggerisce l'ipotesi che alla base della durata della vita ci siano dei meccanismi genetici. I biologi generalmente ritengono che la durata massima della vita di ogni singola specie corrisponde al quintuplo del periodo di accrescimento. Poiché nella specie umana il periodo di accrescimento si conclude con la saldatura degli ultimi anelli di ossificazione, e cioè nella donna a 21 anni e nell'uomo a 25, la durata massima della vita dovrebbe essere di 105-125 anni. È evidente, tuttavia, che tutti i metodi per stabilire il limite teorico della vita umana hanno un valore esclusivamente orientativo. Nonostante gli studi sulla longevità umana siano influenzati dalla presenza di numerose varianti (modificazioni dell'alimentazione, dell'attività lavorativa, ecc.), si ritiene che anche nell'uomo la longevità abbia un carattere in gran parte ereditario. In questo senso, per esempio, depone la maggiore durata di vita dei soggetti con genitori longevi rispetto a gruppi di controllo. Gli studi sugli aspetti genetici della longevità si ricollegano spesso a quelli dell'invecchiamento. Le numerose teorie proposte fino ad oggi possono essere schematicamente ricondotte a due modelli generali. Il primo modello (teoria dell’orologio biologico) suggerisce che l'invecchiamento non è altro che una parte del normale processo di sviluppo e che quindi esso è geneticamente determinato. Nel nostro patrimonio genetico sarebbero presenti i cosiddetti geni della longevità di Sacher e Cutler, che determinerebbero uno sviluppo programmato ed il raggiungimento potenziale di un determinato numero di anni. Il secondo modello (teoria stocastica) suggerisce che l'invecchiamento è il risultato di un processo casuale di deterioramento che si produce nel corso dei processi fisico-chimici propri dell'essere vivente. Per quanto riguarda più specificamente i meccanismi genetici della longevità, secondo numerosi studiosi esistono dei geni anti-invecchiamento, cioè alcuni geni che regolano vari processi biologici ostacolando l'invecchiamento: la longevità sarebbe fondamentalmente assicurata da quegli stessi geni che controllano i vari meccanismi di difesa delle cellule contro i danni prodotti da agenti esterni ed interni