Dysregulated homeostasis of acetylcholine levels in immune cells of RR-multiple sclerosis patients

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNF alpha, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNF alpha, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis

DAPT plus anticoagulant therapy: The difficult coexistence post-ACS in older patients with atrial fibrillation

Atrial fibrillation (AF) and coronary artery disease requiring percutaneous coronary intervention (PCI) and stenting often coexist in older patients. This poses the difficult problem of concurrent anticoagulant and double antiplatelet therapy (triple therapy). Current treatment guidelines do recommend triple therapy, especially in the course of acute coronary syndrome (ACS), with limitations due to an excessive risk of bleeding associated with this therapeutic regimen. This review summarizes randomized clinical trials and observational studies that compared triple therapy with a variety of different therapeutic options. Although the available evidence is not completely satisfactory and other studies are urgently needed, alternative regimens to triple therapy in AF patients undergoing PCI and stenting are promising, at least in terms of safety

Estimating Prognosis and Frailty in Persons Aged ≥75 Years in the Emergency Department: Further Validation of Dynamic Silver Code.

OBJECTIVES To assess concurrent validity of the Dynamic Silver Code (DSC), a tool based on administrative data that predicts prognosis in older adults accessing the emergency department (ED), in terms of association with markers of poor functional and cognitive status. DESIGN Cross-sectional. SETTING AND PARTICIPANTS Data were obtained in the AIDEA study, which enrolled a cohort of ≥75-year-old patients, accessing the ED of 2 hospitals in Florence, Italy. METHODS The DSC score and classes (I to IV, corresponding to an increasing risk of death) were obtained from administrative data. Information on health and functional status prior to ED access were collected from face-to-face, direct, or proxy interviews. The 4AT test was administered to screen for possible delirium. Bivariate comparisons of the prevalence of each functional and cognitive marker across 4 DSC classes were performed. Multinomial logistic regression was used to assess the multivariable risk of being in II, III, or IV DSC class vs I. RESULTS Among 3358 participants (mean age 83 years, men 44%), 32.9%, 30.3%, 19.5%, and 17.2% were in DSC class I, II, III, and IV. Preadmission abnormal functional and cognitive conditions, and delirium in the ED, were increasingly more common from DSC class I through IV (P < .001). In particular, the prevalence of total inability to walk increased from 2.9% (class I) to 23.4% (class IV). In multivariable analyses, this was the strongest predictor of being in progressively worse DSC classes, whereas feeling of exhaustion, reporting of serious falls, weight loss, and severe memory loss or diagnosis of dementia gave some contribution. CONCLUSIONS AND IMPLICATIONS The ability of the DSC to predict survival in older persons appears to rely on its prevailing association with markers of functional impairment. These results may support clinical use of the tool

Caratterizzazione del profilo istolesivo ed immunolocalizzazione della PrP_sc in casi naturali di scrapie ovina

Gli autori descrivono i quadri istopatologici e l’immunolocalizzazione della GFAP e della PrPsc in 25 aree del SNC di 8 ovini con scrapie naturale, provenienti da due allevamenti della Sardegna. Il quadro clinico e lesivo sostanzialmente omogeneo portano a supporre una identità del ceppo, o dei ceppi conoivoli nei due focolai di malattia

Gerstmann-Sträussler-Scheinker disease subtypes efficiently transmit in bank voles as genuine prion diseases.

Gerstmann-Sträussler-Scheinker disease (GSS) is an inherited neurodegenerative disorder associated with mutations in the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrPres) of 6–8 kDa