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A novel series of tacrine based cyclopentapyranopyridine- and tetrahydropyranoquinoline-kojic acid derivatives were designed, synthesized, and evaluated as anti-cholinesterase agents. The chemical structures of all target compounds were characterized by 1 H-NMR, 13 C-NMR, and elemental analyses. The synthesized compounds mostly inhibited acetylcholinesterase enzyme (AChE) with IC50 values of 4.18-48.71 μM rather than butyrylcholinesterase enzyme (BChE) with IC50 values of >100 μM. Among them, cyclopentapyranopyridine-kojic acid derivatives showed slightly better AChE inhibitory activity compared to tetrahydropyranoquinoline-kojic acid. The compound 10-amino-2-(hydroxymethyl)-11-(4-isopropylphenyl)-7,8,9,11-tetrahydro-4H-cyclopenta[b]pyrano[2',3'  5,6]pyrano[3,2-e]pyridin-4-one (6f) bearing 4-isopropylphenyl moiety and cyclopentane ring exhibited the highest anti-AChE activity with IC50 value of 4.18 μM. The kinetic study indicated that the compound 6f acts as a mixed inhibitor and the molecular docking studies also illustrated that the compound 6f binds to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE. The compound 6f showed moderate neuroprotective properties against H2 O2 -induced cytotoxicity in PC12 cells. The theoretical ADME study also predicted good drug-likeness for the compound 6f. Based on these results, the compound 6f seems to be a very promising AChE inhibitor for the treatment of Alzheimer's disease.

Black Americans are disproportionately affected by cancer and chronic diseases. Black patients with cancer and their family caregivers may concurrently experience symptoms that influence their wellbeing. This study investigates the influence of mental and physical symptom distress on quality of life (QOL) among Black Americans with cancer and their family caregivers from a dyadic perspective.

One hundred and fifty-one dyads comprised of a Black American with breast, colorectal, lung or prostate cancer and a Black family caregiver were included in this secondary analysis of pooled baseline data from three studies. Self-reports of problems managing 13 symptoms were used to measure mental and physical symptom distress. Descriptive statistics and the actor-partner interdependence model were used to examine symptom prevalence and the influence of each person's symptom distress on their own and each other's QOL.

Fatigue, sleep problems, pain and mental distress were prevalent. Patients and caregivers reported similar levels of mental distress; however, patients reported higher physical distress. Increased patient mental distress was associated with decreased patient QOL (overall, emotional, social, functional). Increased patient physical distress was associated with decreased patient QOL (overall, physical, emotional, functional) and decreased caregiver emotional wellbeing. Increased caregiver mental distress was associated with decreased caregiver QOL (overall, emotional, social, functional) and decreased patient overall QOL. Increased caregiver physical distress was associated with decreased caregiver QOL (overall, physical, functional), decreased patient emotional wellbeing, and better patient social wellbeing.

Supporting symptom management in Black patient/caregiver dyads may improve their QOL.

Supporting symptom management in Black patient/caregiver dyads may improve their QOL.Liver fibrosis is a common feature of liver dysfunction during chronic liver diseases and is frequently associated with angiogenesis, a dynamic process that forms new blood vessels from preexisting vasculature. MicroRNAs (miRNAs), which act as posttranscriptional regulators of gene expression, have been shown to regulate liver fibrosis; however, how miRNAs regulate angiogenesis and its mechanism in fibrosis are not well understood. We aimed to elucidate the role and mechanism of miR-30c in attenuating liver fibrosis. Using miRNA profiling of fibrotic murine livers, we identified differentially regulated miRNAs and discovered that miR-30c is aberrantly expressed and targets endothelial delta-like ligand 4 (DLL4) in either carbon tetrachloride-treated or bile duct ligated fibrotic mice, as well as in patients with liver fibrosis. Using CCK-8, wound healing and Matrigel tube formation assays, we found that miR-30c inhibited liver sinusoidal endothelial cell (LSEC) proliferation, migration, and angiogenesis capacity by targeting DLL4 in vitro. Importantly, nanoparticle-based delivery of miR-30c to LSECs inhibited the DLL4/Notch pathway and angiogenesis, thereby ameliorating liver fibrosis in vivo. Collectively, our findings demonstrate a protective role of miR-30c in liver fibrosis by regulating DLL4/Notch signaling and angiogenesis. Thus, miR-30c may serve as a potential treatment for chronic liver diseases.

To estimate the aggregated effect sizes of reward-related decision-making deficits in internet gaming disorder (IGD) and to explore potential moderators on the variability of effect sizes across studies.

Review of peer-reviewed studies comparing reward-related decision-making performance between IGD and control participants identified via PubMed, Web of Science and ProQuest databases. Random-effects modeling was conducted using Hedge's g as the effect size (ES). The effects of decision-making situation, valence, sample type, testing environment, IGD severity and self-reported impulsivity on decision-making differences were examined by moderator analyses.

No restrictions on location.

Twenty-four studies (20 independent samples) were included in the meta-analysis, resulting in 604 IGD and 641 control participants and 35 ESs.

Reward-related decision-making differences between IGD and control groups.

The overall ES for decision-making deficits in IGD was small (g=-0.45, P<0.01). The effects were comparable across risky, ambiguous and inter-temporal decision-making. Larger aggregate ESs were identified for pure-gain and mixed compared with pure-loss decision-making. Studies based on clinical and community samples showed similar effects. No significant difference between behavioral studies and those with extra measurements was observed. Decision-making alterations were not closely associated with IGD severity or self-reported impulsivity differences at the study level.

Internet gaming disorder appears to be consistently associated with reward-related decision-making deficits.

Internet gaming disorder appears to be consistently associated with reward-related decision-making deficits.

The Brief Scale for Anxiety (BSA) and the State-Trait Anxiety Inventory Form Y-2 (STAI-Y-2) are self-report scales used to gauge anxiety symptoms in clinical settings. Co-occuring anxiety is common in alcohol use disorder (AUD); however, no studies have assessed the validity of the BSA and STAI-Y-2 compared with a clinical diagnostic tool of anxiety in alcohol treatment programs. We aimed to examine the validity of the BSA and STAI-Y-2 to predict a clinical diagnosis of an anxiety disorder (via the Structured Clinical Interview for DSM [SCID]) in AUD patients.

Participants were administered the BSA (n=1005) on day 2 and the STAI-Y-2 (n=483) between days 2 and 10 of the detoxification program. SCID-based clinical diagnoses of AUD and anxiety were made approximately on day 10.

Individuals seeking treatment for AUD admitted to an inpatient unit at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, USA (n=1010).

Inclusion criteria included a current diagnosis of alcohol dependence (Asorder among inpatients with alcohol use disorder. The BSA and STAI-Y-2 could serve as a screening tool to reject the presence of anxiety disorders rather than for detecting an anxiety disorder.

Use of the Brief Scale for Anxiety (BSA) and/or State-Trait Anxiety Inventory Form Y-2 (STAI-Y-2) does not appear to be a reliable substitute for clinical diagnoses of anxiety disorder among inpatients with alcohol use disorder. The BSA and STAI-Y-2 could serve as a screening tool to reject the presence of anxiety disorders rather than for detecting an anxiety disorder.A fifth of all known species are currently classified as threatened in the wild the rate of biodiversity loss is rapid, continuous, and mostly due to anthropogenic activities. To slow down this decline, the accurate estimation of demographic parameters for threatened species is critical. With this aim, zoo institutions play an important role, giving access to data on zoo-housed animals, which aids researchers working on species life-history traits and intrinsic factors influencing the fitness of both sexes, such as age. While tigers (Panthera tigris) are particularly threatened in their natural environment, few of their demographic parameters have been determined because of their solitary and elusive nature as well as low population density. Using individual-based information for more than 9200 tigers (from 1938 to 2018) recorded in the International Tiger Studbook 2018, we aimed to determine sub-species and sex-specific variability of survival and reproductive parameters with age. No significant sex-difference in actuarial senescence (i.e., decline of survival probabilities with age) was observed but males tended to have a higher juvenile mortality and a faster senescence than females. Reproductive senescence (i.e., decline of reproductive parameters with age) was more pronounced in females than males. Moreover, we observed sub-species-specific variation in mortality and reproductive patterns, pointing out the necessity to consider them independently for conservation goals. Our findings can provide meaningful improvements to the husbandry of zoo-housed tigers, emphasizing the importance of adult breeding females of 7-9 years-old to control zoo-housed population size, but also providing accurate demographic estimates, crucial to set up effective conservation plans.The study's objective was to compare the genomic prediction ability methods for the traits milk yield, milk composition and somatic cell count of Saanen Brazilian goats. Nine hundred forty goats, genotyped with an Axiom_OviCap (Caprine) panel, Affimetrix customized array with 62,557 single nucleotide polymorphisms (SNPs), were used for the genomic selection analyses. The genomic methods studied to estimate the effects of SNPs and direct genomic values (DGV) were as follows (a) genomic BLUP (GBLUP), (b) Bayes Cπ and (c) Bayesian Lasso (BLASSO). Estimated breeding values (EBV) and deregressed estimated breeding values (dEBV) were used as response variables for the genomic predictions. The prediction ability was assessed by Pearson's correlation between DGV and response variables (EBV and dEBV). Regression coefficients of the response variables on the DGV were obtained to verify if the genomic predictions were biased. In addition, the mean square error of prediction (MSE) was used as a measure of verification of model fit to the data. The means of prediction accuracy, when EBV was used as a response variable, were 0.68, 0.68 and 0.67 for GBLUP, Bayes Cπ and BLASSO, respectively. With dEBV, the mean prediction accuracy was 0.50 for all models. The averages of the EBV regression coefficients on DGV were 1.08 for all models (GBLUP, Bayes Cπ and BLASSO), higher than those obtained for the regression coefficient of dEBV on DGV, which presented values of 1.05, 1.05 and 1.08 for GBLUP, Bayes Cπ and BLASSO, respectively. None of the methods stood out in terms of prediction ability; however, the GBLUP method was the most appropriate for estimating the DGV, in a slightly more reliable and less biased way, besides presenting the lowest computational cost. learn more In the context of the present study, EBV was the preferred response variables considering the genomic prediction accuracy despite dEBV also presented lower bias.