Assessing the Global Cognition of Community-Dwelling Older Adults Using Motor and Sensory Factors: A Cross-Sectional Feasibility Study.

Impairments in gait, postural stability, and sensory functions were proved to be strongly associated with severe cognitive impairment such as in dementia. However, to prevent dementia, it is necessary to detect cognitive deterioration early, which requires a deeper understanding of the connections between the aforementioned functions and global cognition. Therefore, the current study measured gait, postural, auditory, and visual functions and, using principal component analysis, explored their individual and cumulative association with global cognition. The global cognitive function of 82 older Korean males was determined using the Montreal Cognitive Assessment. The motor and sensory functions were summarized into seven independent factors using factor analysis, followed by age and education-level-adjusted linear regression model analysis. The seven factors obtained using factor analysis were gait speed, gait stability, midstance, general auditory ability, auditory recognition, overall visual ability, and postural stability. The linear regression model included years of education, gait stability, postural stability, and auditory recognition, and was able to explain more than half of the variability in cognitive score. This shows that motor and sensory parameters, which are obtainable through wearable sensors and mobile applications, could be utilized in detecting cognitive fluctuations even in the early stages of cognitive deterioration.

Molecular Docking Assessment of Cathinones as 5-HT2AR Ligands: Developing of Predictive Structure-Based Bioactive Conformations and Three-Dimensional Structure-Activity Relationships Models for Future Recognition of Abuse Drugs.

Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HT2AR, the enclosed study summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure-activity relationship (3-D QSAR) studies. The bioactive conformations of cathinones were modeled by AutoDock Vina and were used to build structure-based (SB) 3-D QSAR models using the Open3DQSAR engine. Graphical inspection of the results led to the depiction of a 3-D structure analysis-activity relationship (SAR) scheme that could be used as a guideline for molecular determinants by which any untested cathinone molecule can be predicted as a potential 5-HT2AR binder prior to experimental evaluation. The obtained models, which showed a good agreement with the chemical properties of co-crystallized 5-HT2AR ligands, proved to be valuable for future virtual screening campaigns to recognize unused cathinones and similar compounds, such as 5-HT2AR ligands, minimizing both time and financial resources for the characterization of their psychedelic effects.

Changes in sensory, postural stability and gait functions depending on cognitive decline, and possible markers for detection of cognitive status.

BACKGROUND: Numerous people never receive a formal dementia diagnosis. This issue can be addressed by early detection systems that utilize alternative forms of classification, such as gait, balance, and sensory function parameters. In the present study, said functions were compared between older adults with healthy cognition, older adults with low executive function, and older adults with cognitive impairment, to determine which parameters can be used to distinguish these groups. RESULTS: A group of cognitively healthy older men was found to have a significantly greater gait cadence than both the low executive function group (113.1 ± 6.8 vs. 108.0 ± 6.3 steps/min, p = 0.032) and the cognitively impaired group (113.1 ± 6.8 vs. 107.1 ± 7.4 steps/min, p = 0.009). The group with low executive function was found to have more gait stability than the impaired cognition group, represented by the single limb support phase (39.7 ± 1.2 vs. 38.6 ± 1.3%, p = 0.027). Additionally, the healthy cognition group had significantly greater overall postural stability than the impaired cognition group (0.6 ± 0.1 vs. 1.1 ± 0.1, p = 0.003), and the low executive function group had significantly greater mediolateral postural stability than the impaired cognition group (0.2 ± 0.1 vs. 0.6 ± 0.6, p = 0.012). The low executive function group had fewer mistakes on the sentence recognition test than the cognitively impaired (2.2 ± 3.6 vs. 5.9 ± 6.4, p = 0.005). There were no significant differences in visual capacity, however, the low executive function group displayed an overall greatest ability. CONCLUSIONS: Older adults with low executive function showcased a lower walking pace, but their postural stability and sensory functions did not differ from those of the older adults with healthy cognition. The variables concluded as good cognitive status markers were (1) gait cadence for dividing cognitively healthy from the rest and (2) single limb support portion, mediolateral stability index, and the number of mistakes on the sentence recognition test for discerning between the low executive function and cognitive impairment groups.

Computational Studies on Selected Macrolides Active against Escherichia coli Combined with the NMR Study of Tylosin A in Deuterated Chloroform.

Although many antibiotics are active against Gram-positive bacteria, fewer also show activity against Gram-negative bacteria. Here, we present a combination of in silico (electron ion-interaction potential, molecular docking, ADMET), NMR, and microbiological investigations of selected macrolides (14-membered, 15-membered, and 16-membered), aiming to discover the pattern of design for macrolides active against Gram-negative bacteria. Although the conformational studies of 14-membered and 15-membered macrolides are abundant in the literature, 16-membered macrolides, and their most prominent representative tylosin A, have received relatively little research attention. We therefore report the complete 1H and 13C NMR assignment of tylosin A in deuterated chloroform, as well as its 3D solution structure determined through molecular modelling (conformational search) and 2D ROESY NMR. Additionally, due to the degradation of tylosin A in deuterated chloroform, other species were also detected in 1D and 2D NMR spectra. We additionally studied the anti-bacterial activity of tylosin A and B against selected Gram-positive and Gram-negative bacteria.

Titanium Dioxide and Zinc Oxide Nanoparticles in Sunscreens: A Review of Toxicological Data.

The positive effects of sunlight have been known for many years, and the negative ones, too. Sunscreens are physical and chemical UV absorbers. Nanotechnology has developed nanoparticles of physical blockers: titanium dioxide (TiO2) and zinc oxide (ZnO). Their smaller diameter and increased bioreactivity are the focus of many toxicological studies. The usage of sunscreens has increased around the world, so all toxicological aspects should be carefully considered. There are in vitro and in vivo studies: studies on animal and human skin; investigations of potential genotoxicity and cytotoxicity; generation of reactive oxygen species; penetration; skin irritation; acute, subchronic, and chronic toxicity; and carcinogenesis. The experimental conditions of these studies differ from study to study, but most authors agree that there is no penetration of nanoparticles into viable skin layers. Risk-benefit analysis of TiO2 and ZnO nanoparticles (NPs) usage in sunscreens strongly indicates that potential risks are vastly outweighed over the benefits. Because of the results of some authors indicating possible penetration through damaged skin, further studies should be conducted, primarily addressed on skin penetration mechanisms.

Gait variability-based classification of the stages of the cognitive decline using partial least squares-discriminant analysis.

The purpose of the present study was to examine the differences in gait variability in terms of spatiotemporal, sub-gait cycle, ground reaction force, and the joint profiles of kinematics and kinetics between older individuals with and without risk of potential cognitive impairment, and to derive the crucial features to discriminating the older adults with future risk cognitive decline by using partial least squares-discriminant analysis. A total of 90 community-dwelling older adults aged over 65 years underwent cognitive function assessment and were divided into three groups depending on cognitive assessment score. The participants' level-walking was analyzed by using three-dimensional instrumented gait analysis. The coefficient of variation was extracted and then comparatively analyzed depending on the stages of the cognitive decline. To identify the most important contributor when differentiating the older adults with a risk of future cognitive decline, partial least squares-discriminant analysis was applied, and the discriminative power of the coefficients confirmed as features of great importance were investigated via the receiver operating characteristic area under the curve. The differences in gait variability were found mainly between the suspected dementia groups and other groups, especially in joint dynamics variables. Through the partial least squares-discriminant analysis, the discriminative features were found as follows: the mid-stance, the moments, and the power in the hip, knee, and ankle joints. In addition, the discrimination model was found to differentiate well between the three groups. The classification accuracy of intact cognition, diminished cognition, and suspected dementia was 0.857, 0.710, and 0.857, respectively. These findings mean that gait variability changes according to continuous cognitive decline, especially in sub-gait cycles and joint biomechanics, and suggest that measures of variation can be used as predictors to identify older individuals with a risk of potential cognitive impairment.