Total Sedentary Time and Cognitive Function in Middle-Aged and Older Adults: A Systematic Review and Meta-analysis

Background: An estimated 47 million people have dementia globally, and around 10 million new cases are diagnosed each year. Many lifestyle factors have been linked to cognitive impairment; one emerging modifiable lifestyle factor is sedentary time. Objective: To conduct a systematic review and meta-analysis of peer-reviewed literature examining the association between total sedentary time with cognitive function in middle-aged and older adults under the moderating conditions of (a) type of sedentary time measurement; (b) the cognitive domain being assessed; (c) looking at sedentary time using categorical variables (i.e., high versus low sedentary time); and (d) the pattern of sedentary time accumulation (e.g., longer versus shorter bouts). We also aimed to examine the prevalence of sedentary time in healthy versus cognitively impaired populations and to explore how experimental studies reducing or breaking up sedentary time affect cognitive function. Lastly, we aimed to conduct a quantitative pooled analysis of all individual studies through meta-analysis procedures to derive conclusions about these relationships. Methods: Eight electronic databases (EMBASE; Web of Science; PsycINFO; CINAHL; SciELO; SPORTDiscus; PubMed; and Scopus) were searched from inception to February 2021. Our search included terms related to the exposure (i.e., sedentary time), the population (i.e., middle-aged and older adults), and the outcome of interest (i.e., cognitive function). PICOS framework used middle-aged and older adults where there was an intervention or exposure of any sedentary time compared to any or no comparison, where cognitive function and/or cognitive impairment was measured, and all types of quantitative, empirical, observational data published in any year were included that were published in English. Risk of bias was assessed using QualSyst. Results: Fifty-three studies including 83,137 participants met the inclusion criteria of which 23 studies had appropriate data for inclusion in the main meta-analysis. The overall meta-analysis suggested that total sedentary time has no association with cognitive function (r = −0.012 [95% CI − 0.035, 0.011], p = 0.296) with marked heterogeneity (I2 = 89%). Subgroup analyses demonstrated a significant negative association for studies using a device to capture sedentary time r = −0.035 [95% CI − 0.063, − 0.008], p = 0.012). Specifically, the domains of global cognitive function (r = −0.061 [95% CI − 0.100, − 0.022], p = 0.002) and processing speed (r = −0.067, [95% CI − 0.103, − 0.030], p < 0.001). A significant positive association was found for studies using self-report (r = 0.037 [95% CI − 0.019, 0.054], p < 0.001). Specifically, the domain of processing speed showed a significant positive association (r = 0.057 [95% CI 0.045, 0.069], p < 0.001). For prevalence, populations diagnosed with cognitive impairment spent significantly more time sedentary compared to populations with no known cognitive impairments (standard difference in mean = −0.219 [95% CI − 0.310, − 0.128], p < 0.001). Conclusions: The association of total sedentary time with cognitive function is weak and varies based on measurement of sedentary time and domain being assessed. Future research is needed to better categorize domains of sedentary behaviour with both a validated self-report and device-based measure in order to improve the strength of this relationship

Monotone and near-monotone biochemical networks

Monotone subsystems have appealing properties as components of larger networks, since they exhibit robust dynamical stability and predictability of responses to perturbations. This suggests that natural biological systems may have evolved to be, if not monotone, at least close to monotone in the sense of being decomposable into a “small” number of monotone components, In addition, recent research has shown that much insight can be attained from decomposing networks into monotone subsystems and the analysis of the resulting interconnections using tools from control theory. This paper provides an expository introduction to monotone systems and their interconnections, describing the basic concepts and some of the main mathematical results in a largely informal fashion

Variable Selection and Interpretation in Structure-Affinity Correlation Modeling of Estrogen Receptor Binders

A computational approach for the identification and investigation of correlations between a chemical structure and a selected biological property is described. It. is based on a set of 132 compounds of known chemical structures, which were tested for their binding affinities to the estrogen receptor. Different multivariate modeling methods, i.e., partial least-squares regression, counterpropagation neural network, and error-back-propagation neural network, were applied, and the prediction ability of each model was tested in order to compare the results of the obtained models. To reduce the extensive set of calculated structural descriptors, two types of variable selection methods were applied, depending on the modeling approach used. In particular, the final partial least-squares regression model was built using the "variable importance in projection" variable selection method, while genetic algorithms were applied in neural network modeling to select the optimal set of descriptors. A thorough statistical study of the variables selected by genetic algorithms is shown. The results were assessed with the aim to get insight to the mechanisms involved in the binding of estrogenic compounds to the receptor. The variable selection oil the basis of genetic algorithm wits controlled with the test set of compounds, extracted from the data set available. To compare the predictive ability of all the optimized models, a leave-one-out cross-validation procedure was applied, the best model being the nonlinear neural network model based on error back-propagation algorithm, which resulted in R-2 = 92.2% and Q(2) = 70.8%

Impact of Mercury(II) on proteinase K catalytic center: investigations via classical and Born-Oppenheimer molecular dynamics

Mercury(II) has a strong affinity for the thiol groups in proteins often resulting in the disruption of their biological functions. In this study we present classical and first-principles, DFT-based molecular dynamics (MD) simulations of a complex of Hg(II) and proteinase K, a well-known serine protease with a very broad and diverse enzymatic activity. It contains a catalytic triad formed by Asp39, His69, and Ser224, which is responsible for its biological activity. It was found previously by X-ray diffraction experiments that the presence of Hg(II) inhibits the enzymatic action of proteinase K by affecting the stereochemistry of the triad. Our simulations predict that (i) the overall structure as well as the protein backbone dynamics are only slightly affected by the mercury cation, (ii) depending on the occupied mercury site, the hydrogen bonds of the catalytic triad are either severely disrupted (both bonds for mercury at site 1, and the His69-Ser224 contact for mercury at site 2) or slightly strengthened (the Asp39-His69 bond when mercury is at site 2), (iii) the network of hydrogen bonds of the catalytic triad is not static but undergoes constant fluctuations, which are significantly modified by the presence of the Hg(II) cation, influencing in turn the triad's ability to carry out the enzymatic function-these facts explain the experimental findings on the inhibition of proteinase K by Hg(II)

Properties of flavonoids influencing the binding to bilitranslocase investigated by neural network modelling

Bilitranslocase is a plasma membrane carrier firstly identified on the sinusoidal (vascular) domain of liver cells and later on also in the gastric epithelium. It transports diverse organic anions, such as bilirubin, some phthaleins and many dietary anthocyanins, suggesting that it could play a role both in the absorption of flavonoids from dietary sources and in their hepatic metabolism. This work was aimed at characterising the interaction of bilitranslocase with flavonols, a flavonoid sub-class. The results obtained show that, contrary to anthocyanins, flavonol glycosides do not interact with the carrier, whereas just some of the corresponding aglycones act as relatively poor ligands to bilitranslocase. These data point to a clear-cut discrimination between anthocyanins and flavonols occurring at the level of the bilitranslocase transport site. A quantitative structure-activity relationship based on counter propagation artificial neural network modelling was undertaken in order to shed light on the nature of flavonoid interaction with bilitranslocase. It was found that binding relies on the ability to establish hydrogen bonds, ruling out the involvement of charge interactions. This requisite might be at the basis of the discrimination between anthocyanins and flavonols by bilitranslocase and could lie behind some aspects of the distinct pharmacokinetic properties of anthocyanins and flavonols in mammals

Armenian Cultural Properties and Cultural Heritage: What Protection under International Law One Hundred Years Later?

"Cultural genocide" is not per se covered by the 1948 UN Convention. However, it was very carefully taken into consideration in works of the most prominenmt scholars immediately after the Armenian massacres of 1915-17. The fact that violent acts of cultural destruction and other similar actions directed at annihilating the distinctive culture of a group are usual precursors of massive killings and of other serious violations of human rights was evident before and during WWII and is even more evident today. Consequently the few limited, albeit significant, international legal rules concerning the protection of cultural heritage that were in force in 1915 have considerably developed and are still evolving, within the protection of human rights and peace. Today, States are under the duty to protect cultural heritage whatever its origin, both in time of peace and in time of war, and the UN Security Council itself endorses UNESCO's efforts, addressing not only the unlawful destruction and looting and smuggling in the event of armed conflicts, but also "the attempt to deny historical roots and cultural diversity" because it "can fuel and exacerbate conflict and hamper post-conflict national reconciliation". In this context, the recent attention paid by Turkey to the protection of certain specific Armenian sites is an undoubtedly positive sign, and it is essential that involvement of all relevant stakeholders in the management of the properties is ensured