Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aβ 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.     

Biosignal pattern recognition and interpretation systems. 3.Methods of classification

The following topics are discussed: Bayes/minimum distance classifiers; maximum likelihood classification estimation; k-nearest neighbor classification; entropy criteria; syntactic techniques; string matching; the Cocke-Younger-Kasami parsing algorithm; syntactic learning; finite-state automata; neural network classification techniques; learning vector quantization; cluster swapping; hierarchial clustering procedures     

Biosignal pattern recognition and interpretation systems

A general framework is given to describe pattern recognition and interpretation. Pattern analysis stages are described, with consideration of difficulties in implementation and uncertainties present at each level. The main forms of pattern analysis-statistical, syntactic, and artificial intelligence (connectionist and symbolic) methods-have different strengths and weaknesses, depending on the stage of pattern analysis at which they are used. In general, statistical, syntactic, and connectionist techniques are used for pattern recognition, and statistical and symbolic techniques are used for pattern interpretation. Largely, pattern interpretation involves reasoning with uncertainty. Multichannel recordings increase the information available about specific physiologic events, at the expense of processing complexity     

Novel Therapeutical Approaches to Managing Atherosclerotic Risk

Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals that promise improvement in the atheromatous plaque from a molecular point of view, because have actions on the exposure of the LDL-Receptor (LDL-R), on endothelial dysfunction, activation of macrophages, on lipid oxidation, formations on foam cells, and deposition extracellular lipids. Atheroma plaque reduction both as a result of LDL-Cholesterol (LDL-C) intensive lowering and reducing inflammation and other residual risk factors is an integral part of the management of atherosclerotic disease, and the use of valid therapeutic alternatives appear to be appealing avenues to solving the problem.     

Mycobacterial and Human Ferrous Nitrobindins: Spectroscopic and Reactivity Properties

Structural and functional properties of ferrous Mycobacterium tuberculosis (Mt-Nb) and human (Hs-Nb) nitrobindins (Nbs) were investigated. At pH 7.0 and 25.0 °C, the unliganded Fe(II) species is penta-coordinated and unlike most other hemoproteins no pH-dependence of its coordination was detected over the pH range between 2.2 and 7.0. Further, despite a very open distal side of the heme pocket (as also indicated by the vanishingly small geminate recombination of CO for both Nbs), which exposes the heme pocket to the bulk solvent, their reactivity toward ligands, such as CO and NO, is significantly slower than in most hemoproteins, envisaging either a proximal barrier for ligand binding and/or crowding of H₂O molecules in the distal side of the heme pocket which impairs ligand binding to the heme Fe-atom. On the other hand, liganded species display already at pH 7.0 and 25 °C a severe weakening (in the case of CO) and a cleavage (in the case of NO) of the proximal Fe-His bond, suggesting that the ligand-linked movement of the Fe(II) atom onto the heme plane brings about a marked lengthening of the proximal Fe-imidazole bond, eventually leading to its rupture. This structural evidence is accompanied by a marked enhancement of both ligands dissociation rate constants. As a whole, these data clearly indicate that structural–functional relationships in Nbs strongly differ from what observed in mammalian and truncated hemoproteins, suggesting that Nbs play a functional role clearly distinct from other eukaryotic and prokaryotic hemoproteins.     

Prelordotic behavior in the hamster: A hormonally modulated transition from aggression to sexual receptivity.

Analyzed the behavioral responses of 60 female golden hamsters to sexually experienced males as a function of the stage of the female's estrous cycle. Exogenous estradiol or estradiol followed by progesterone was given to ovariectomized Ss to determine the role of these hormones in regulation of cyclic changes in the female's response to the male. Ss were paired daily with sexually active males for 10 min, and behavioral interactions were recorded. Significantly more fighting occurred during early diestrus than later in the cycle. By 8 hrs prior to the onset of sexual receptivity, 86% of Ss exhibited a behavior resembling the onset of lordosis without immobilization. Following ovariectomy, fighting was at a high level. Estradiol replacement over 28 days resulted in a significant decrease in aggression and increase in display of the prelordotic response. Initially, treatment with progesterone following 7 days of estradiol caused lordosis display. After 24 hrs a significant increase in aggression, which continued as long as progesterone was present, was observed. Thus, estradiol causes the female to become tolerant of the male's approach, the female exhibiting prelordosis in response to the male's investigation. Estradiol and progesterone are necessary for normal sexual receptivity; however, after 24 hrs, estrogen/progesterone-treated females become agonistic to the male. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)