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Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10−6). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.

Background: Bisphosphonates can adversely affect fracture-healing because they inhibit osteoclastic bone resorption. It is unclear whether bisphosphonates can be initiated safely for patients who have sustained an acute distal radial fracture. The purpose of this randomized study was to determine whether the early use of bisphosphonate affects healing and outcomes of osteoporotic distal radial fractures treated with volar locking plate fixation.Methods: Fifty women older than fifty years of age who had undergone volar locking plate fixation of a distal radial fracture and had been diagnosed with osteoporosis were randomized to Group I (n = 24, initiation of bisphosphonate treatment at two weeks after the operation) or Group II (n = 26, initiation of bisphosphonate treatment at three months). Patients were assessed for radiographic union and other radiographic parameters (radial inclination, radial length, and volar tilt) at two, six, ten, sixteen, and twenty-four weeks, and for clinical outcomes that included Disabilities of the Arm, Shoulder and Hand (DASH) scores, wrist motion, and grip strength at twenty-four weeks. The two groups were compared with regard to the time to radiographic union, the radiographic parameters, and the clinical outcomes.Results: No significant differences were observed between the two groups with respect to radiographic or clinical outcomes after volar locking plate fixation. All patients obtained fracture union, and the mean times to radiographic union in Groups I and II were similar (6.7 and 6.8 weeks, respectively; p = 0.65). Furthermore, the time to radiographic union was not related to osteoporosis severity or fracture type.Conclusions: In patients with an osteoporotic distal radial fracture treated with volar locking plate fixation, the early initiation of bisphosphonate treatment did not affect fracture-healing or clinical outcomes.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Previous studies of minimal medial epicondylectomy for cubital tunnel syndrome included patients with mild disease, making it difficult to determine how much this procedure improved sensory and motor impairments in patients with moderate to severe disease.Questions/purposes: We asked if minimal epicondylectomy improved sensory and motor impairments in patients with moderate to severe cubital tunnel syndrome.Methods: We retrospectively reviewed 25 patients treated with minimal medial epicondylectomy for advanced cubital tunnel syndrome involving motor weakness between January 2003 and February 2009. Preoperatively, five patients had Medical Research Council (MRC) Grade 4 motor strength without atrophy (McGowan Grade IIA), nine had MRC Grade 3 motor strength with detectable atrophy (McGowan Grade IIB), and 11 had MRC Grade 3 or less motor strength with severe atrophy (McGowan Grade III). Postoperatively we obtained DASH scores and evaluated improvement of sensory impairment and motor impairment: excellent with minimal sensory deficit and motor deficit, good with mild deficits, fair with improved but persistent deficit(s), and poor with no improvement. The minimum followup was 13 months (mean, 46 months; range, 13-86 months).Results: The mean DASH score was 14 points (range, 2-47 points). Of the 25 patients, sensory improvement and motor improvement were excellent in 16 patients, good in five, fair in two, and poor in two. Twenty-three of the 25 patients improved at least one McGowan grade. There were no complications, such as medial elbow instability.Conclusions: Minimal medial epicondylectomy can improve sensory and motor impairments for patients with moderate to severe cubital tunnel syndrome.Level Of Evidence: Level IV, therapeutic study. See the guidelines for authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Abstract Introduction Locked knee caused by inferior patellar dislocation is considered rare in elderly patients. It was originally thought that, in the osteoarthritic knee, osteophytes on the pole of the patella become entrapped in the inter-condylar notch, which is managed by performing closed reduction and immobilization in a knee splint for three to four weeks. We present an unusual case of a locked knee with an impaction fracture. To the best of our knowledge, there have been no previous reports of such impaction fractures managed with arthroscopy. Case presentation We present an unusual case of an 88-year-old Caucasian woman with moderate arthritis who had a locked knee caused by an impaction fracture of the patella into the lateral femoral condyle. In this case report, we describe the need for arthroscopic surgery to prevent relocking of the knee in these patients. Conclusions This case report emphasizes the need for careful assessment of locked knees in elderly patients. Impaction fractures should be considered in all rare cases of patellar dislocation, and we advocate arthroscopic assessment of the articular cartilage in these patients. This is an important consideration, as the population demographics change and such impaction fractures may become more common in patients with degeneration in the knees.

Objective: Item response theory analyses were used to examine alcohol abuse and dependence symptoms and diagnoses in adolescents. Previous research suggests that the DSM-IV alcohol use disorder (AUD) symptoms in adolescents may be characterized by a single dimension. The present study extends prior research with a larger and more comprehensive sample and an examination of an alternative diagnostic algorithm for AUDs.Method: Approximately 5,587 adolescents between the ages of 12 and 18 years from adjudicated, clinical, and community samples were administered structured clinical interviews. Analyses were conducted to examine the severity of alcohol abuse and dependence symptoms and the severity of alcohol use problems (AUDs) within the diagnostic categories created by the DSM-IV.Results: Although the DSM-IV diagnostic categories differ in severity of AUDs, there is substantial overlap and inconsistency in AUD severity of persons across these categories. Item Response Theory-based AUD severity estimates suggest that many persons diagnosed with abuse have AUD severity greater than persons with dependence. Similarly, many persons who endorse some symptoms but do not qualify for a diagnosis (i.e., diagnostic orphans) have more severe AUDs than persons with an abuse diagnosis. Additionally, two dependence items, "tolerance" and "larger/longer," show differences in severity between samples.Conclusions: The distinction between DSM-IV abuse and dependence based on severity can be improved using an alternative diagnostic algorithm that considers all of the alcohol abuse and dependence symptoms conjointly. [ABSTRACT FROM AUTHOR]

This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838). [ABSTRACT FROM AUTHOR]

We present data on the lifetime prevalence of substance use, abuse and dependence in adolescents obtained through structured psychiatric interviews and self-report questionnaires. Most notably, we evaluate symptom profiles based on DSM-IV abuse and dependence criteria for tobacco, alcohol and marijuana, including a gender comparison. Participants are 3,072 adolescents (12-18 years) drawn from three community-based family samples in Colorado. Age trends suggest that substance use is a developmental phenomenon, which increases almost linearly from early to late adolescence. Substance use disorders are less common than experimentation in adolescence, but approximately 1 in 4 adolescents in the oldest cohorts meets criteria for abuse for at least one substance, and 1 in 5 meets criteria for substance dependence. By age 18 nearly 1 in 3 adolescents report daily smoking and 8.6% meet criteria for tobacco dependence. Although alcohol is the most commonly abused substance (10%), a slightly larger proportion of adolescents meet criteria for dependence on marijuana (4.3%) than alcohol (3.5%). Gender differences in prevalence of use more often show greater use in males than females. Males more frequently meet criteria for dependence on alcohol and marijuana in late adolescence, while females are more often nicotine dependent. A comparison of abuse and dependence symptom profiles shows some interesting variability across substances, and suggests that manifestations of a subset of symptoms are gender specific. [ABSTRACT FROM AUTHOR]

Objective: Pediatric loss-of-control (LOC) eating is associated with high BMI and predicts binge-eating disorder and obesity onset with age. Research on the etiology of this common comorbidity has not explored the potential for shared genetic risk. This study examined genetic and environmental influences on LOC eating and its shared influence with BMI., Method: Participants were 499 monozygotic and 398 same-sex dizygotic twins (age = 17.38 years ± 0.67, BMIz = 0.03 ± 1.03, 54% female) from the Colorado Center for Antisocial Drug Dependence Study. LOC eating was assessed dichotomously. Self-reported height and weight were converted to BMIz. Univariate and bivariate twin models estimated genetic and environmental influences on LOC eating and BMIz., Results: More girls (21%) than boys (9%, p < 0.001) reported LOC eating. The phenotypic correlation with BMIz was 0.03 in girls and 0.18 in boys. Due to the nonsignificant phenotypic correlation in girls, bivariate twin models were fit in boys only. Across all models, the best-fitting model included genetic and unique environmental effects. Genetic factors accounted for 0.51 (95% CI: 0.23, 0.73) of the variance of LOC eating in girls and 0.54 (0.18, 0.90) in boys. The genetic correlation between LOC eating and BMIz in boys was 0.45 (0.15, 0.75)., Discussion: Findings indicate moderate heritability of LOC eating in adolescence, while emphasizing the role of unique environmental factors. In boys, LOC eating and BMIz share a proportion of their genetic influences., (© 2024 Wiley Periodicals LLC.)

The internalizing construct captures shared variance underlying risk for mood and anxiety disorders. Internalizing factors based on diagnoses (or symptoms) of major depressive disorder (MDD) and generalized anxiety disorder (GAD) are well established. Studies have also integrated self-reported measures of associated traits (e.g., questionnaires assessing neuroticism, worry, and rumination) onto these factors, despite having not tested the assumption that these measures truly capture the same sets of risk factors. This study examined the overlap among both sets of measures using converging approaches. First, using genomic structural equation modeling, we constructed internalizing factors based on genome-wide association studies (GWASs) of internalizing diagnoses (e.g., MDD) and traits associated with internalizing (neuroticism, loneliness, and reverse-scored subjective well-being). Results indicated the two factors were highly ( r g = .79) but not perfectly genetically correlated ( r g < 1.0, p < .001). Second, we constructed similar latent factors in a combined twin/adoption sample of adults from the Colorado Adoption/Twin Study of Lifespan Behavioral Development and Cognitive Aging. Again, both factors demonstrated strong overlap at the level of genetic ( r g = .76, 95% confidence interval [CI] [0.40, 0.97]) and nonshared environmental influences ( r e = .80, 95% CI [0.53, 1.0]). Shared environmental influences were estimated near zero for both factors. Our findings are consistent with current frameworks of psychopathology, though they suggest there are some unique genetic influences captured by internalizing diagnosis compared to trait measures, with potentially more nonadditive genetic influences on trait measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The present study examined early socioeconomic status (SES) and neighborhood disadvantage (ND) as independent predictors of antisocial behavior (ASB) and addressed the etiology of the associations (i.e., genes versus the environment) using a longitudinal adoption design. Prospective data from the Colorado Adoption Project (435 adoptees, 598 nonadopted children, 526 biological grandparents of adoptees, 481 adoptive parents, and 617 nonadoptive parents including biological parents of unrelated siblings of adoptees) were examined. SES and ND were assessed during infancy and ASB was evaluated from ages four through 16 using parent and teacher report. Associations between predictors and ASB were compared across adoptive and nonadoptive families and sex. Early SES was a nominally significant, independent predictor of antisocial ASB, such that lower SES predicted higher levels of ASB in nonadoptive families only. ND was not associated with ASB. Associations were consistent across aggression and delinquency, and neither SES nor ND was associated with change in ASB over time. Nominally significant associations did not remain significant after controlling for multiple testing. As such, despite nonsignificant differences in associations across sex or adoptive status, we were unable to make definitive conclusions regarding the genetic versus environmental etiology of or sex differences in the influence of SES and ND on ASB. Despite inconclusive findings, in nonadoptees, results were consistent-in effect size and direction-with previous studies in the literature indicating that lower SES is associated with increased risk for ASB., Competing Interests: The authors have declared that competing interests exist., (Copyright: © 2024 Gresko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although psychological symptoms are broadly considered to be risk factors for substance use, internalizing symptoms may be associated with lower risk for adolescent substance use after controlling for co-occurring externalizing symptoms. The present study explored two potential mediators of this protective association between internalizing symptoms and adolescent substance use: popularity and harm avoidance. The study used data from the Colorado Longitudinal Twin Study (LTS) and Colorado Adoption Project (CAP). Annual assessments of internalizing and externalizing symptoms and social competence were completed by parents and teachers at participant ages 7 to 16. Harm avoidance and substance use were assessed at age 17. In this sample, internalizing symptoms were associated with less frequent substance use, controlling for externalizing symptoms. We did not find evidence that popularity or harm avoidance accounts for the protective association of internalizing symptoms with adolescent substance use. Teacher-reported popularity was associated with less frequent substance use, suggesting that social connectedness in the school context may be a protective factor for adolescent substance use. Harm avoidance was not associated with substance use after accounting for internalizing and externalizing symptoms.

Background: This study investigated a safe and effective bolus dose and lockout time for patient-controlled sedation (PCS) with dexmedetomidine for dental treatments. The depth of sedation, vital signs, and patient satisfaction were investigated to demonstrate safety., Methods: Thirty patients requiring dental scaling were enrolled and randomly divided into three groups based on bolus doses and lockout times: group 1 (low dose group, bolus dose 0.05 µg/kg, 1-minute lockout time), group 2 (middle dose group, 0.1 µg/kg, 1-minute), and group 3 (high dose group, 0.2 µg/kg, 3-minute) (n = 10 each). ECG, pulse, oxygen saturation, blood pressure, end-tidal CO 2 , respiratory rate, and bispectral index scores (BIS) were measured and recorded. The study was conducted in two stages: the first involved sedation without dental treatment and the second included sedation with dental scaling. Patients were instructed to press the drug demand button every 10 s, and the process of falling asleep and waking up was repeated 1-5 times. In the second stage, during dental scaling, patients were instructed to press the drug demand button. Loss of responsiveness (LOR) was defined as failure to respond to auditory stimuli six times, determining sleep onset. Patient and dentist satisfaction were assessed before and after experimentation., Results: Thirty patients (22 males) participated in the study. Scaling was performed in 29 patients after excluding one who experienced dizziness during the first stage. The average number of drug administrations until first LOR was significantly lower in group 3 (2.8 times) than groups 1 and 2 (8.0 and 6.5 times, respectively). The time taken to reach the LOR showed no difference between groups. During the second stage, the average time required to reach the LOR during scaling was 583.4 seconds. The effect site concentrations (Ce) was significantly lower in group 1 than groups 2 and 3. In the participant survey on PCS, 8/10 in group 3 reported partial memory loss, whereas 17/20 in groups 1 and 2 recalled the procedure fully or partially., Conclusion: PCS with dexmedetomidine can provide a rapid onset of sedation, safe vital sign management, and minimal side effects, thus facilitating smooth dental sedation., Competing Interests: DECLARATIONS OF INTEREST: The authors declare no conflicts of interest., (Copyright © 2024 Journal of Dental Anesthesia and Pain Medicine.)

Externalizing psychopathology is a strong risk factor for substance use, whereas the role of internalizing manifestations of distress, and anxiety in particular, in predicting substance use remains unclear. Studies have suggested that anxiety may be either a protective or risk factor for substance use. The present study aimed to clarify evidence for anxiety-specific associations with substance use, examining sex and developmental period (adolescence vs. adulthood) as potential moderators that may help explain conflicting results in the literature. In a longitudinal twin sample, cross-sectional associations of anxiety with substance use differed in adolescents and adults and in girls/women and boys/men. Controlling for externalizing psychopathology and depression, anxiety was associated with reduced substance use in adolescent girls and increased substance use in adult women. In contrast, anxiety-specific associations with substance use were not significant in boys and men. Possible explanations for these contrasting results across development and sex are discussed.

Background: The literature on the association between subjective effects (SEs; i.e., how an individual perceives their physiological and psychological reactions to a drug) and substance use disorders (SUDs) is largely limited to community samples. The present study addressed the following aims in a clinical sample: whether SEs predict general versus substance-specific SUD in adolescence and adulthood after controlling for conduct disorder symptoms (CDsymp); whether SEs predict SUDs across drug classes; whether SEs predict change in SUD from adolescence to adulthood; and whether there are racial/ethnic differences in associations., Methods: Longitudinal analyses were conducted using data from a sample of 744 clinical probands recruited from residential and outpatient SUD treatment facilities in CO during adolescence (M age = 16.26) and re-assessed twice in adulthood (M ages = 22.56 and 28.96), approximately seven and twelve years after first assessment. SEs and CDsymp were assessed in adolescence. SUD severity was assessed at adolescence and twice during adulthood., Results: SEs assessed in adolescence robustly predicted general SUD for legal and illegal substances in adolescence and adulthood, whereas CDsymp predicted SUD primarily in adolescence. Higher positive and negative SEs in adolescence were associated with greater SUD severity after controlling for CDsymp, with similar magnitudes. Results indicated cross-substance effects of SEs on SUD. We found no evidence for racial/ethnic differences in associations., Conclusions: We investigated the progression of SUD in a high-risk sample with greater odds of sustained SUD. In contrast to CDsymp, both positive and negative SEs consistently predicted general SUD across substances in adolescence and adulthood., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This issue of the Journal of Child Psychology and Psychiatry includes a systematic review on the emergence of problem gambling from childhood to emerging adulthood (Richard & King, 2023). The importance of understanding the risks for problem gambling earlier in development is clear, given the increasing availability of gambling to minors, especially online gambling., (© 2023 Association for Child and Adolescent Mental Health.)

Lactobacillus plantarum ( L. plantarum ) is a probiotic that has emerged as novel therapeutic agents for managing various diseases, such as cancer, atopic dermatitis, inflammatory bowel disease, and infections. In this study, we investigated the potential mechanisms underlying the anticancer effect of the metabolites of L. plantarum . We cultured L. plantarum cells to obtain their metabolites, created several dilutions, and used these solutions to treat human colonic Caco-2 cells. Our results showed a 10% dilution of L. plantarum metabolites decreased cell viability and reduced the expression of autophagy-related proteins. Moreover, we found co-treatment with L. plantarum metabolites and chloroquine, a known autophagy inhibitor, had a synergistic effect on cytotoxicity and downregulation of autophagy-related protein expression. In conclusion, we showed the metabolites from the probiotic, L. plantarum , work synergistically with chloroquine in killing Caco-2 cells and downregulating the expression of autophagy-related proteins, suggesting the involvement of autophagy, rather than apoptosis, in their cytotoxic effect. Hence, this study provides new insights into new therapeutic methods via inhibiting autophagy.

Atractylodin is a major compound in the rhizome of Atractylodes lancea, an oriental herbal medicine used for the treatment of gastrointestinal diseases, including dyspepsia, nausea, and diarrhea. Recent studies have shown that atractylodin exerts anti-inflammatory effects in various inflammatory diseases. Herein, we investigated the anti-colitis effects of atractylodin and its molecular targets. We determined the non-cytotoxic concentration of atractylodin (50 μM) using a cell proliferation assay in colonic epithelial cells. We found that pretreatment with atractylodin significantly inhibits tumor necrosis factor-α-induced phosphorylation of nuclear factor-κ-light-chain-enhancer of activated B in HCT116 cells. Through docking simulation analysis, luciferase assays, and in vitro binding assays, we found that atractylodin has an affinity for peroxisome proliferator-activated receptor alpha (PPARα). Daily administration of atractylodin (40 mg/kg) increased the survival rate of mice in a dextran sodium sulfate-induced colitis mouse model. Thus, atractylodin can be a good strategy for colitis therapy through inducing PPARα-dependent pathways.

This study aimed to investigate in vitro biologic properties of mineral trioxide aggregate (MTA) mixed with 3% PVA (MTA-3% PVA) and in vivo dental pulp responses to direct capping in comparison with MTA mixed with distilled water (MTA-DW). Cell proliferation and osteogenic differentiation in culture of human dental pulp cells (hDPCs), and pH changes were evaluated. Pulps in 24 mandibular premolars of four 9-month-old beagle dogs were mechanically exposed and direct pulp capping was performed. Histological specimens were scored according to the degree of mineralization. MTA-3% PVA showed similar cell proliferation and similar or superior osteogenic differentiation of hDPCs compared with MTA-DW. All specimens were associated with calcified bridge formation and there were no significant differences in mineralization scores between the groups (p>0.05). The results suggested that MTA-3% PVA exhibited favorable biocompatibility and osteogenic differentiation in vitro compared with MTA-DW. Furthermore, both groups demonstrated similar results when used as pulp-capping agents in vivo.

The present study examined putative environmental predictors of adolescent substance use, using a prospective adoption design to distinguish between environmental mediation (i.e., parenting influencing adolescent substance use), passive gene-environment correlation (i.e., parental genetic predisposition influencing the association between parenting characteristics and adolescent substance use), and evocative gene-environment correlation (i.e., children's genetic predisposition influencing parenting). Longitudinal data from the Colorado Adoption Project (395 adoptees, 491 nonadoptees, 485 adoptive parents, and 490 biological parents) were examined. Children (48% girls) were assessed at ages 1 to 17 years. Over 90% of the sample were non-Hispanic White. Associations between parenting and adolescent substance use were compared between adoptive and nonadoptive families. Positive, negative, and inconsistent parenting measures in early childhood through adolescence were not consistently associated with adolescent substance use, with only 6% of correlations being statistically significant ( r = -0.152 to .207). However, parent-child relationship quality assessed from childhood to adolescence and orientation to parents assessed during adolescence were significantly, negatively associated with adolescent substance use, with 71% of correlations being statistically significant ( r = -0.88 to -0.11). There was little evidence of sex differences in the associations. Environmental mediation, rather than passive or evocative gene-environment correlation, explained most associations.

Medical and recreational cannabis legalization lead to increased cannabis use among adults. There is concern that legalization has negative implications for minors via effects on parents. We conducted a systematic review of studies examining legalization in the United States. Web of Science, PsycInfo, and PubMed were searched through May 2021, studies examining effects of legalization on maternal cannabis and other substance use during pregnancy and postpartum, perinatal outcomes, parental cannabis and other substance use and attitudes, parenting, and child outcomes were identified, and two independent reviewers extracted information on study designs, samples, and outcomes, and assessed classification of evidence and risk of bias. Forty-one studies met inclusion criteria; only 6 (15%) used the most causally informative study design (difference in differences). It is likely legalization increases maternal cannabis use during pregnancy and postpartum, parental cannabis use, and approval of adult cannabis use. Legalization may increase some adverse perinatal outcomes, though findings were inconsistent. It is likely legalization increases unintentional pediatric cannabis exposure. There is insufficient evidence for effects of legalization on child abuse and neglect, and there have been no studies examining effects of legalization on other aspects of parenting or on child adjustment. There is a critical lack of causally informative epidemiological studies examining effects of legalization on parenting and young children. Additional causally informative research is needed. Studies of parental cannabis use in a legal context are particularly needed. Commonsense guidelines must recognize the shifting national landscape around legalization while seeking to minimize potential harm to minors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Chronic gut inflammation such as inflammatory bowel disease is believed to be associated with neurodegenerative diseases in humans. However, the direct evidence for and the underlying mechanism of this brain-gut interaction remain elusive. In this study, manganese-enhanced magnetic resonance imaging was used to assess functional brain activity from awake and freely moving mice with chronic colitis. Manganese ion uptake (indicative of Ca 2+ influx into neuronal cells) and accumulation were reduced in the hippocampus of chronic colitis mice compared with control mice. Long-term memory declined and neuroinflammatory signals, including IL-1β production and activation of caspase-1, caspase-11, and gasdermin, were induced. High-mobility group box 1 (HMGB1) levels were elevated both in the serum and in the hippocampus; however, lipopolysaccharide (LPS) levels remained at low levels without significant changes in these samples. The blood-brain barrier permeability was increased in chronic colitis mice. In the presence of LPS, HMGB1 treatment induced the activation of caspase-11 and gasdermin in the mouse microglial cell line SIM-A9. These findings suggest that HMGB1 released from the inflamed intestine may move to the brain through the blood circulatory system; in conjunction with a low level of endogenous LPS, elevated HMGB1 can subsequently activate caspase-mediated inflammatory responses in the brain., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: Prior research has found a positive association between the quality or adjustment of an individual's intimate relationship, such as marriage, and their physical health. However, it is possible that this association may be due, at least in part, to confounding variables (i.e., variables that are causally associated both with relationship adjustment and health and could account for their covariation), including genetically influenced confounds. This study was conducted using a genetically informative sample of twins to examine the association between intimate relationship adjustment and self-rated health, accounting for unmeasured genetic and environmental confounds., Method: A Swedish sample of 539 monozygotic and dizygotic twins (321 male twin pairs and 218 female twin pairs) and their spouse or long-term partner completed self-report measures of relationship adjustment and health., Results: Relationship adjustment was positively associated with self-rated health in male and female twins. For male twins, nonshared environmental influences largely accounted for the association between relationship adjustment and health; for female twins, this association was generally explained by shared and nonshared environmental influences. For male twins, results obtained from partners' reports of relationship adjustment were largely consistent with those obtained from twins' reports., Conclusions: Results suggest that the association between relationship adjustment and self-rated health remains after accounting for shared genetic influences, and that nonshared environmental influences, such as partners' characteristics, account for the association between relationship adjustment and self-rated health in men. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Meta-analytic findings suggest that antisocial behavior, broadly defined, may relate to a Common Executive Function (EF) factor that captures covariance across response inhibition, working memory updating, and mental set shifting tasks. However, it is unclear whether this common factor, which is isomorphic with individual differences in response inhibition, accounts for all of the EF variance in antisocial behavior and psychopathy, or if they also relate to updating- and shifting-specific abilities. Moreover, findings that antisocial behavior and lower cognitive ability are particularly associated with the psychopathy dimension reflecting impulsivity and irresponsibility, compared to the dimension reflecting affective-interpersonal functioning, raise the possibility that EF relates to the variance shared between the impulsive-irresponsible psychopathy dimension and antisocial personality disorder. We examined these questions in a young adult twin sample (N = 765) with measures of multiple EF latent variables, Levenson Self-Report Psychopathy (LSRP) Primary (affective-interpersonal) and Secondary (impulsive-irresponsible) scales, and antisocial personality disorder symptoms (ASPDsx). Phenotypically, higher ASPDsx and LSRP Secondary psychopathy, but not LSRP Primary psychopathy, were associated with lower Common EF. Moreover, both psychopathy dimensions were negatively correlated with Updating-Specific ability, which was unrelated to ASPDsx. Results from twin models indicated that the association between LSRP Secondary psychopathy and ASPDsx was due to both genetic and nonshared environmental influences; however, Common EF's association with ASPDsx was primarily genetic, whereas its association with LSRP Secondary psychopathy had a significant environmental component. Thus, the interrelations among these constructs may reflect heterogeneous etiological pathways., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hydroxyapatite, an essential mineral in human bones composed mainly of calcium and phosphorus, is widely used to coat bone graft and implant surfaces for enhanced biocompatibility and bone formation. For a strong implant-bone bond, the bone-forming cells must not only adhere to the implant surface but also move to the surface requiring bone formation. However, strong adhesion tends to inhibit cell migration on the surface of hydroxyapatite. Herein, a cell migration highway pattern that can promote cell migration was prepared using a nanosecond laser on hydroxyapatite coating. The developed surface promoted bone-forming cell movement compared with the unpatterned hydroxyapatite surface, and the cell adhesion and movement speed could be controlled by adjusting the pattern width. Live-cell microscopy, cell tracking, and serum protein analysis revealed the fundamental principle of this phenomenon. These findings are applicable to hydroxyapatite-coated biomaterials and can be implemented easily by laser patterning without complicated processes. The cell migration highway can promote and control cell movement while maintaining the existing advantages of hydroxyapatite coatings. Furthermore, it can be applied to the surface treatment of not only implant materials directly bonded to bone but also various implanted biomaterials implanted that require cell movement control., (© 2021 The Authors.)

The present study examined empathy deficits in toddlerhood (age 14 to 36 months) as predictors of antisocial personality disorder (ASPD) symptoms and psychopathy measured by the Levenson Self-Report Psychopathy scale (Levenson, Kiehl, & Fitzpatrick, 1995) in adulthood (age 23 years) in 956 individuals from the Colorado Longitudinal Twin Study. Consistent with the hypothesis that antisocial behavior is associated with "active" rather than "passive" empathy deficits, early disregard for others, not lack of concern for others, predicted later ASPD symptoms. Early disregard for others was also significantly associated with factor 1 of the Levenson Self-Report Psychopathy Scale, which includes items assessing interpersonal and affective deficits, but not with factor 2, which includes items assessing impulsivity and poor behavioral control. The association between early disregard for others and psychopathy factor 2 was near zero after controlling for the shared variance between psychopathy factors 1 and 2. These results suggest that there is a propensity toward adulthood ASPD symptoms and psychopathy factor 1 that can be assessed early in development, which may help identify individuals most at risk for stable antisocial outcomes.

Background: Orthognathic surgery requires red blood cell (RBC) transfusions more frequently than other oral and maxillofacial surgeries. The purpose of this study was to identify reliable predictors for RBC transfusion during bimaxillary orthognathic surgery (BOS). Methods: This retrospective study reviewed 1,616 electronic medical records of patients who underwent BOS during a 5-year period at Seoul National University Dental Hospital. The perioperative variable data were collected from electronic medical records and analyzed by dividing patients into the two groups (non-transfusion and transfusion group). Results: Of the 1,616 patients, 1,311 patients were excluded. The remaining 305 patients were divided into non-transfusion (NTF, n = 256) and transfusion (TF, n = 49) groups. Univariate logistic regression analysis revealed that age, body mass index, the presence of several adjunctive surgeries (including genioplasty, extraction, and mandibular angle reduction), preoperative hemoglobin (Hb) and prothrombin time, surgical time, amount of fluid infusion and blood loss, and mean pulse rate during surgery were significant factors predicting RBC transfusion. Multivariate logistic regression analysis revealed that preoperative Hb and blood loss amount during surgery were significantly related to RBC transfusion in BOS patients. Conclusion: Since blood loss amounts could not be measured preoperatively, we found that the independent predictor associated with RBC transfusion during BOS was a low preoperative Hb level., Competing Interests: Competing Interests: The authors have no funding and conflicts of interest to disclose., (© The author(s).)

The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.

Background : Public acceptance of cannabis continues to increase across the US, yet there has been little research on how cannabis legalization affects young children. The present study compared knowledge of cannabis and other substances among children living in states with different cannabis laws and examined whether the association between such substance knowledge and externalizing behavior varies by state cannabis regulations. Methods : Participants were from the Adolescent Brain Cognitive Development SM Study (ABCD Study®) at the baseline assessment ( N  = 11,875, ages 9-11, collected from 2016 to 2018). Chi-square difference tests were used to compare nested models testing group differences in knowledge of substances and the association between externalizing disorder/behavior and substance knowledge as a function of state legality of cannabis use (recreational, medical, low THC/CBD, none). Results : Children living in states with more permissive cannabis laws had a greater knowledge of cannabis and reported more alcohol experimentation. In contrast, knowledge regarding alcohol, tobacco, and other illicit drugs was not greater in children from states with more permissive cannabis laws. Externalizing disorder/behavior was not significantly associated with cannabis knowledge in any group and not significantly different across groups. The association between externalizing disorder/behavior and illicit drug knowledge was significant only in states with the recreational and medical use laws but did not differ significantly across groups. Conclusion : Children living in environments with more permissive cannabis regulations have greater knowledge of cannabis, but not other substances, and report more experimentation with alcohol.

Although stress is frequently considered an environmental factor, dependent stressful life events (SLEs)--stressors that result from one's actions or behaviors--may in fact be evoked by a genetic liability. It has been suggested that dependent SLEs may be partially caused by poor executive function (EFs), higher-level cognitive abilities that enable individuals to implement goal-directed behavior. We investigated the possibility of genetic and environmental overlap between SLEs and EFs in a longitudinal twin study. We found high genetic stability in the number of dependent SLEs from age 23 to age 29, suggesting that the number of dependent stressors show persistence across time due to their genetic etiology. In addition, there was a nominally significant negative genetic correlation between a Common EF latent factor and dependent SLEs at age 23. The genetic stability of dependent SLEs and association with Common EF provides insight into how some behaviors may lead to persistent stress.

Protease-activated receptor 2 (PAR2) regulates inflammatory responses and lipid metabolism. However, its precise role in colitis remains unclear. In this study, we aimed to investigate the function of PAR2 in high-fat diet-fed mice with colitis and its potential role in autophagy. PAR2 +/+ and PAR2 -/- mice were fed a high-fat diet (HFD) for 7 days before colitis induction with dextran sodium sulfate. Deletion of PAR2 and an HFD significantly exacerbated colitis, as shown by increased mortality, body weight loss, diarrhea or bloody stools, colon length shortening, and mucosal damage. Proinflammatory cytokine levels were elevated in HFD-fed PAR2 -/- mice and in cells treated with the PAR2 antagonist GB83, palmitic acid (PA), and a cytokine cocktail (CC). Damaging effects of PAR2 blockage were associated with autophagy regulation by reducing the levels of YAP1, SIRT1, PGC-1α, Atg5, and LC3A/B-I/II. In addition, mitochondrial dysfunction was demonstrated only in cells treated with GB83, PA, and CC. Reduced cell viability and greater induction of apoptosis, as shown by increased levels of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP), were observed in cells treated with GB83, PA, and CC but not in those treated with only PA and CC. Collectively, protective effects of PAR2 were elucidated during inflammation accompanied by a high-fat environment by promoting autophagy and inhibiting apoptosis, suggesting PAR2 as a therapeutic target for inflammatory bowel disease co-occurring with metabolic syndrome. NEW & NOTEWORTHY Deletion of PAR2 with high-fat diet feeding exacerbates colitis in a murine colitis model. Proinflammatory effects of PAR2 blockage in a high-fat environment were associated with an altered balance between autophagy and apoptosis. Increased colonic levels of PAR2 represent as a therapeutic strategy for IBD co-occurring with metabolic syndrome.

Autotaxin (ATX) converts lysophosphatidylcholine and sphingosyl-phosphorylcholine into lysophosphatidic acid and sphingosine 1-phosphate, respectively. Despite the pivotal function of ATX in lipid metabolism, mechanisms by which ATX regulates immune and inflammatory disorders remain elusive. Here, using myeloid cell lineage-restricted Atx knockout mice, we show that Atx deficiency disrupts membrane microdomains and lipid rafts, resulting in the inhibition of Toll-like receptor 4 (TLR4) complex formation and the suppression of adaptor recruitment, thereby inhibiting TLR4-mediated responses in macrophages. Accordingly, TLR4-induced innate immune functions, including phagocytosis and iNOS expression, are attenuated in Atx-deficient macrophages. Consequently, Atx -/- mice exhibit a higher bacterial prevalence in the intestinal mucosa compared to controls. When combined with global Il10 -/- mice, which show spontaneous colitis due to the translocation of luminal commensal microbes into the mucosa, myeloid cell lineage-restricted Atx knockout accelerates colitis development compared to control littermates. Collectively, our data reveal that Atx deficiency compromises innate immune responses, thereby promoting microbe-associated gut inflammation., (© 2020 The Authors.)

Background: The success rate of intubation under direct laryngoscopy is greatly influenced by laryngoscopic grade using the Cormack-Lehane classification. However, it is not known whether grade under direct laryngoscopy can also affects the success rate of nasotracheal intubation using a fiberoptic bronchoscpe, so this study investigated the same. In addition, we investigated other factors that influence the success rate of fiberoptic nasotracheal intubation (FNI)., Methods: FNI was performed by 18 anesthesiology residents under general anesthesia in patients over 15 years of age who underwent elective oral and maxillofacial operations. In all patients, the Mallampati grade was measured. Laryngeal view grade under direct laryngoscopy, and the degree of secretion and bleeding in the oral cavity was measured and divided into 3 grades. The time required for successful FNI was measured. If the intubation time was > 5 minutes, it was evaluated as a failure and the airway was managed by another method. The failure rate was evaluated using appropriate statistical method. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were also measured., Results: A total of 650 patients were included in the study, and the failure rate of FNI was 4.5%. The patient's sex, age, height, weight, Mallampati, and laryngoscopic view grade did not affect the success rate of FNI (P > 0.05). BMI, the number of FNI performed by residents (P = 0.03), secretion (P < 0.001), and bleeding (P < 0.001) grades influenced the success rate. The AUCs of bleeding and secretion were 0.864 and 0.798, respectively, but the AUC of BMI, the number of FNI performed by residents, Mallampati, and laryngoscopic view grade were 0.527, 0.616, 0.614, and 0.544, respectively., Conclusion: Unlike in intubation under direct laryngoscopy, in the case of FNI, oral secretion and nasal bleeding had a significant effect on FNI difficulty than Mallampati grade or Laryngeal view grade., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Journal of Dental Anesthesia and Pain Medicine.)

MicroRNAs (miRNAs) have emerged as key players in tumor angiogenesis. Interleukin-17C (IL-17C) was identified to promote colorectal cancer (CRC) progression. Therefore, we aimed to investigate the effect of IL-17C on tumor angiogenesis, the involvement of miR-23a-3p in IL-17C signaling, and the direct target gene of miR-23a-3p in CRC. In vitro and ex vivo angiogenesis, a mouse xenograft experiment, and immunostaining were performed to test the effect of IL-17C on tumor angiogenesis. ELISA, quantitative real time PCR, and gene silencing were used to uncover the underlying mechanism. IL-17C induced angiogenesis of intestinal endothelial cells, subsequently enhancing cell invasion and migration of DLD-1 cells. IL-17C-stimulated DLD-1 cells produced vascular endothelial growth factor (VEGF) to enhance angiogenesis. Moreover, IL-17C markedly accelerated xenograft tumor growth, which was manifested by substantially reduced tumor growth when treated with the VEGF receptor 2 inhibitor Ki8751. Accordingly, Ki8751 suppressed the expression of IL-17C-stimulated PECAM and VE-cadherin in xenografts. Furthermore, IL-17C activated STAT3 to increase the expression of miR-23a-3p that suppressed semaphorin 6D (SEMA6D) expression, thereby permitting VEGF production. Taken together, our study demonstrates that IL-17C promotes tumor angiogenesis through VEGF production via a STAT3/miR-23a-3p/SEMA6D axis, suggesting its potential as a novel target for anti-CRC therapy.

Peri-implantitis is an inflammatory disease that results in bone destruction around dental implants. A preclinical study using beagle models is frequently performed prior to clinical application in dentistry. Previously, we proposed an immediate peri-implantitis experimental model with a shorter experimental duration and less expense than the conventional experimental model. However, the differences in the regenerative outcomes between the immediate and conventional models were not fully revealed. In this study, we aimed to compare the regenerative outcomes between both models when ex vivo BMP2 gene therapy using autologous periodontal ligament stem cells (B2/PDLSCs) was applied to peri-implantitis defects. The results showed that the defect depths were significantly different between both models. New bone formation occurred in both models, but there were significant differences between the models. More than 70% of the defects were filled with newly formed bone in the conventional model, whereas 30-40% of the defects were filled in the immediate model. However, after adjustment for the differences in the defect depths between the models, the statistically significant differences in the regenerative outcomes between the models were lost. In conclusion, the inferior regenerative outcome of an immediate peri-implantitis model at B2/PDLSCs transplantation resulted from the defect depths, not the model itself.

Although prior theory suggests that rumination contributes to cognitive impairments associated with depression, recent work suggests that rumination is associated with higher levels of intelligence. The present study examined the relations between two ruminative subtypes (brooding and reflective pondering) and multiple measures and types of intelligence (verbal and performance) after controlling for rumination's overlapping variance with depression. Participants were 751 individuals from the Colorado Longitudinal Twin Study who completed the Ruminative Response Scale; the Center for Epidemiological Studies-Depression Scale and a fully structured clinical interview as measures of depression; and verbal and performance intelligence tasks at age 16 and the Raven's Advanced Progressive Matrices at age 23. Reflective pondering was positively associated with all measures of intelligence, whereas brooding was not associated with intelligence. Our findings indicate that any negative associations between rumination and intelligence are attributable to shared variance with depression, and that examination of rumination as a multifaceted construct may provide new insights into the relations between rumination and cognition., Competing Interests: Conflicts of interest: None.

Background: It is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect. Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study., Methods: We first examined the phenotypic associations between cannabis initiation, frequency, and use disorder with cognitive abilities, while also controlling for pre-use general cognitive ability and other substance involvement. We tested the concurrent association between the cannabis use variables and cognitive abilities in late adolescence and young adulthood and the longitudinal association between cannabis use variables during adolescence and young adulthood cognitive abilities. Next, we used multilevel models to test whether these relations reflect between- and/or within-twin pair associations., Results: Phenotypically, cannabis use was related to poorer cognitive functioning, although most associations were negligible after accounting for other substance use. Nevertheless, there were few significant within-family twin-specific associations, except that age 17 cannabis frequency was associated with worse age 23 Common EF and general cognitive ability., Conclusions: We found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The effect of grain size of dental zirconia on the shear bond strength of composite resin cement was newly studied. Disc-shaped dental zirconia with small (sample S) and large (sample L) grains were made by sintering of pre-sintered dental zirconia at 1450°C for 0.5 h and 40 h, respectively. After the sintering, the average grain size of sample S was 1.37 ± 0.15 µm, while that of sample L was 3.74 ± 0.50 µm. The sintered discs were successively polished with different grades of diamond and alumina slurries. The interfacial free energies were 63.5 ± 4.2 dyne/cm for sample S and 52.1 ± 5.5 dyne/cm for sample L. Stainless steel cylinders, previously sandblasted with 50 µm alumina powder, were bonded to the zirconia discs using composite resin cement. Next, samples were kept in an oven for 7 d at 36.5°C. The shear bond strength of sample S was 23.0 ± 4.5 MPa while that of sample L was 17.5 ± 4.6 MPa. After the fracture, the areal % values of composite resin cement remaining on the zirconia surfaces were 89.7 ± 5.9% for sample S and 61.6 ± 5.5% for sample L. The results suggest that grain size reduction has a potential to enhance the degree of bonding between a composite resin cement and a dental zirconia due to the increase of interfacial free energy.

The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = -0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although phosphatase and tensin homolog (PTEN) is typically considered a tumor-suppressor gene, it was recently suggested that PTEN regulates TLR5-induced immune and inflammatory responses in intestinal epithelial cells (IECs), suggesting an immunomodulatory function of PTEN in the gut. However, this alternative function of PTEN has not yet been evaluated in an in vivo context of protection against enteropathogenic bacteria. To address this, we utilized IEC-restricted Pten knockout (Pten ΔIEC/ΔIEC ) and littermate Pten +/+ mice. These mice were subjected to the streptomycin-pre-treated mouse model of Salmonella infection, and subsequently given an oral gavage of a low inoculum (2 × 10 4 CFU) of Salmonella enterica serovar Typhimurium (S. Typhimurium). This bacterial infection not only increased the mortality of Pten ΔIEC/ΔIEC mice compared to Pten +/+ mice, but also induced deleterious gastrointestinal inflammation in Pten ΔIEC/ΔIEC mice manifested by massive histological damage to the intestinal mucosa. S. Typhimurium infection up-regulated pro-inflammatory cytokine production in the intestine of Pten ΔIEC/ΔIEC mice compared to controls. Furthermore, bacterial loads were greatly increased in the liver, mesenteric lymph node, and spleen of Pten ΔIEC/ΔIEC mice compared to controls. Together, these results suggest that IEC-restricted Pten deficiency renders the host greatly susceptible to Salmonella infection and support an immune-regulatory role of PTEN in the gut.

Developing self-restraint, or the inhibition of behavior in response to a prohibition, is an important process during toddlerhood. The objective of this study was to gain a better understanding of individual differences in the development of self-restraint during toddlerhood by examining stable elements and growth of temperament (i.e., attentional control, behavioral inhibition, negative emotionality), general intelligence, and self-restraint. Participants were 412 same-sex twin pairs (approximately 90% European American) from predominately middle-class households in Colorado. Data were collected at 14, 20, 24, and 36 months. Results indicated that higher behavioral inhibition, attentional control, and intelligence were independently associated with better self-restraint, whereas higher negative emotionality was an independent predictor of lower self-restraint. The associations between temperament and self-restraint generally appeared to be stable from 14 to 36 months., (© 2018 Society for Research in Child Development.)

Ginseng ( Panax ginseng ) has long been used as a traditional medicine for the prevention and treatment of various diseases. Generally, the harvest time and age of ginseng have been regarded as important factors determining the efficacy of ginseng. However, most studies have mainly focused on the root of ginseng, while studies on other parts of ginseng such as its berry have been relatively limited. Thus, the aim of this study iss to determine effects of harvest time on yields, phenolics/ginsenosides contents, and the antioxidant/anti-elastase activities of ethanol extracts of three- and four-year-old ginseng berry. In both three- and fourfour-year-old ginseng berry extracts, antioxidant and anti-elastase activities tended to increase as berries ripen from the first week to the last week of July. Liquid chromatography-tandem mass spectrometry analysis has revealed that contents of ginsenosides except Rg1 tend to be the highest in fourfour-year-old ginseng berries harvested in early July. These results indicate that biological activities and ginsenoside profiles of ginseng berry extracts depend on their age and harvest time in July, suggesting the importance of harvest time in the development of functional foods and medicinal products containing ginseng berry extracts. To the best of our knowledge, this is the first report on the influence of harvest time on the biological activity and ginsenoside contents of ginseng berry extracts.

In the present study, various extracts of C . tricuspidata fruit were prepared with varying ethanol contents and evaluated for their biomarker and biological properties. The 80% ethanolic extract showed the best tyrosinase inhibitory activity, while the 100% ethanolic extract showed the best total phenolics and flavonoids contents. The HPLC method was applied to analyze the chlorogenic acid in C . tricuspidata fruit extracts. The results suggest that the observed antioxidant and tyrosinase inhibitory activity of C . tricuspidata fruit extract could partially be attributed to the presence of marker compounds in the extract. In this study, we present an analytical method for standardization and optimization of C. tricuspidata fruit preparations. Further investigations are warranted to confirm the in vivo pharmacological activity of C . tricuspidata fruit extract and its active constituents and assess the safe use of the plant for the potential development of the extract as a skin depigmentation agent., Competing Interests: The authors declare no conflict of interest.

Introduction: Both rumination, a pattern of repetitive, self-focused thought in response to distress, and deficits in executive functions (EFs), a set of cognitive abilities that facilitate higher-order thinking, have transdiagnostic associations with psychopathology. Although empirical studies suggest associations between EFs and rumination, this literature has not examined subtypes of rumination and different components of EFs. It also has not examined whether rumination and EFs explain overlapping variance in psychopathology, which is relevant to theoretical models suggesting that rumination might mediate the EF-psychopathology association., Methods: We used structural equation modeling to examine the association between latent factors for two types of rumination (anger and depressive) and three components of EF (a Common EF factor, and factors specific to updating working memory and shifting mental sets) and whether they independently relate to internalizing and externalizing psychopathology in a population sample of 764 young adults (mean age 23 years) from the Colorado Longitudinal Twin Study., Results: Depressive and Anger Rumination showed small correlations with a Common EF factor (rs = -.09 to -.11). Anger Rumination and Common EF ability were associated with independent variance in externalizing psychopathology, whereas Depressive Rumination, but not Common EF, was associated with internalizing psychopathology., Limitations: Examination of cross-sectional relations in a population sample led to low symptom endorsement for psychopathology and necessitated examination of lifetime, rather than past-year, psychopathology., Conclusions: Inconsistent with mediation hypotheses, Common EF abilities and rumination are correlated yet largely independent constructs that both predict psychopathology., (Published by Elsevier B.V.)