Early detection of memory impairments in older adults: standardization of a short version of the verbal and nonverbal Recognition Memory Test.

In several neurological conditions, in elderly and cognitively impaired subjects, memory functioning must be evaluated to early detect the cognitive deterioration processes. In particular, recognition memory assessment is an essential step in the clinical and neuropsychological evaluation of early memory impairments. The Recognition Memory Test (RMT) developed by Smirni et al. (G Ital Psicol XXXVII(1):325-343, 2010) is an effective instrument to assess verbal and nonverbal recognition memory in the Italian population. The current study provides a new, brief, and reliable RMT format to evaluate recognition memory on elderly subjects and it reports normative data in an older adult Italian population sample (including 100 participants well distributed across sex, education, and age categories). The shortened version of RMT keeps the administration procedures and materials of the original Italian RMT constant, i.e., words, faces, and buildings. Multiple regression analysis revealed significant effects of age and educational level on performance but no effect of sex. Inferential cutoffs have been determined and equivalent scores computed. The availability of equivalent scores for the Recognition Memory Test will prove useful in the clinical evaluation of patients' memory profiles.

Emotional Awareness and Cognitive Performance in Borderline Intellectual Functioning Young Adolescents.

According to DSM-5 and ICD-10, borderline intellectual functioning (BIF) should not be classified properly as a disorder. However, BIF people may present relevant problems of adaptive functioning in several areas of daily activities, and they seem to be more vulnerable to mental diseases. Young adolescence may be considered a particular period for emotional information processing. The "own and others' emotions" awareness can play a crucial role in many daily life situations, such as decision making, interpersonal relationships, and decoding of facial expressions. On this background, a BIF young adolescents group underwent a neuropsychological assessment including emotional and cognitive domains, and was compared with a healthy young adolescents control group (HC). In the overall sample, a significant negative correlation between general intellectual abilities and emotional awareness was found. The BIF group showed a significantly greater level of alexithymia and a poorer performance in higher cognitive tasks than HC group. As hypothesized, a border cognitive functioning influences mentalization processes as ability to discriminate and monitor emotions, as well as higher domains of cognition.

Structure-Based Virtual Screening Allows the Identification of Efficient Modulators of E-Cadherin-Mediated Cell-Cell Adhesion.

Cadherins are a large family of transmembrane calcium-dependent cell adhesion proteins that orchestrate adherens junction formation and are crucially involved in tissue morphogenesis. Due to their important role in cancer development and metastasis, cadherins can be considered attractive targets for drug discovery. A recent crystal structure of the complex of a cadherin extracellular portion and a small molecule inhibitor allowed the identification of a druggable interface, thus providing a viable strategy for the design of cadherin dimerization modulators. Here, we report on a structure-based virtual screening approach that led to the identification of efficient and selective modulators of E-cadherin-mediated cell-cell adhesion. Of all the putative inhibitors that were identified and experimentally tested by cell adhesion assays using human pancreatic tumor BxPC-3 cells expressing both E-cadherin and P-cadherin, two compounds turned out to be effective in inhibiting stable cell-cell adhesion at micromolar concentrations. Moreover, at the same concentrations, one of them also showed anti-invasive properties in cell invasion assays. These results will allow further development of novel and selective cadherin-mediated cell-cell adhesion modulators for the treatment of a variety of cadherin-expressing solid tumors and for improving the efficiency of drug delivery across biological barriers.

Benton visual form discrimination test in healthy children: normative data and qualitative analysis.

The attention evaluation may be considered a crucial phase in neuropsychological assessment. It must take into account the systemic nature of the attentional functions and must use different reliable tests in relation to the neurological and attentional problems to be addressed. The aim of the study was to offer the clinician an effective tool for attention assessment and provide the normative data and performance analysis on the Benton Visual Form Discrimination Test on an Italian sample (number 323) of healthy school children, from ages 5 to 11. Performance on Visual Form Discrimination Test (VFDT) significantly increased with growing age. Performances were significantly different when the test was divided into four sets. All groups, especially the younger ones, showed some difficulty in maintenance and sustained attention. The correct answers were significantly more numerous when they were placed at the top quadrants. This effect was more marked in the younger groups. Sex was never a significantly influencing performance. Our data seem to indicate that the higher attentional frontoparietal network becomes more functionally organized around 9-10 years. VFDT appears as a discriminative task. In clinical practice, our normative data can be used both on complex visual attention skill evaluation in children and on the ability to maintain visual attention in time.

Standardization and validation of a parallel form of the verbal and non-verbal recognition memory test in an Italian population sample.

In the neuropsychological assessment of several neurological conditions, recognition memory evaluation is requested. Recognition seems to be more appropriate than recall to study verbal and non-verbal memory, because interferences of psychological and emotional disorders are less relevant in the recognition than they are in recall memory paradigms. In many neurological disorders, longitudinal repeated assessments are needed to monitor the effectiveness of rehabilitation programs or pharmacological treatments on the recovery of memory. In order to contain the practice effect in repeated neuropsychological evaluations, it is necessary the use of parallel forms of the tests. Having two parallel forms of the same test, that kept administration procedures and scoring constant, is a great advantage in both clinical practice, for the monitoring of memory disorder, and in experimental practice, to allow the repeated evaluation of memory on healthy and neurological subjects. First aim of the present study was to provide normative values in an Italian sample (n = 160) for a parallel form of a verbal and non-verbal recognition memory battery. Multiple regression analysis revealed significant effects of age and education on recognition memory performance, whereas sex did not reach a significant probability level. Inferential cutoffs have been determined and equivalent scores computed. Secondly, the study aimed to validate the equivalence of the two parallel forms of the Recognition Memory Test. The correlations analyses between the total scores of the two versions of the test and correlation between the three subtasks revealed that the two forms are parallel and the subtasks are equivalent for difficulty.

Mechanistic insights into Pin1 peptidyl-prolyl cis-trans isomerization from umbrella sampling simulations.

The peptidyl-proyl isomerase Pin1 plays a key role in the regulation of phospho(p)-Ser/Thr-Pro proteins, acting as a molecular timer of the cell cycle. After recognition of these motifs, Pin1 catalyzes the rapid cis-trans isomerization of proline amide bonds of substrates, contributing to maintain the equilibrium between the two conformations. Although a great interest has arisen on this enzyme, its catalytic mechanism has long been debated. Here, the cis-trans isomerization of a model peptide system was investigated by means of umbrella sampling simulations in the Pin1-bound and unbound states. We obtained free energy barriers consistent with experimental data, and identified several enzymatic features directly linked to the acceleration of the prolyl bond isomerization. In particular, an enhanced autocatalysis, the stabilization of perturbed ground state conformations, and the substrate binding in a procatalytic conformation were found as main contributions to explain the lowering of the isomerization free energy barrier.

An automated docking protocol for hERG channel blockers.

A docking protocol aimed at obtaining a consistent qualitative and quantitative picture of binding for a series of hERG channel blockers is presented. To overcome the limitations experienced by standard procedures when docking blockers at hERG binding site, we designed a strategy that explicitly takes into account the conformations of the channel, their possible intrinsic symmetry, and the role played by the configurational entropy of ligands. The protocol was developed on a series of congeneric sertindole derivatives, allowing us to satisfactorily explain the structure-activity relationships for this set of blockers. In addition, we show that the performance of structure-based models relying on multiple-receptor conformations statistically increases when the protein conformations are chosen in such a way as to capture relevant structural features at the binding site. The protocol was then successfully applied to a series of structurally unrelated blockers.

Multiscale Simulations of a Two-Pore Potassium Channel.

Two-pore domain channels control cell excitability by modulating background potassium currents in response to several physicochemical stimuli. Thanks to the many crystal structures available, the TRAAK channel is one of the most studied, but little is known about its functional dynamics. Here, we explore TRAAK functionality complementing molecular dynamics with Brownian dynamics in a multiscale-modeling framework. We identify potential states of the channel that can prevent ion conduction, and we demonstrate that the suppression of currents is consistent with the presence of lipids inside the cavity.