A Prospective Sociocentric Study of 2 Entire Traditional Korean Villages: The Korean Social Life, Health, and Aging Project (KSHAP).

The Korean Social Life, Health, and Aging Project (KSHAP) was a multidisciplinary prospective study conducted in South Korea that measured various health biomarkers from blood, hair, and brain magnetic resonance imaging, and we examined their associations with sociocentric (global) social network data of older adults in 2 entire villages (or cohorts). Cohort K included participants aged 60 years or older, and cohort L included participants aged 65 years or older. We performed a baseline survey involving 814 of the 860 individuals (94.7% response rate) in cohort K in 2012 and 947 of the 1,043 individuals (90.8% response rate) in cohort L in 2017. We gathered longitudinal data for 5 waves in cohort K from 2011 to 2019 and 2 waves in cohort L from 2017 to 2022. Here, we describe for the first time the follow-up design of the KSHAP, the changes in social networks, and various biomarkers over a number of years. The data for cohort K are publicly available via the Korean Social Science Data Archive as well as the project website, and the data for cohort L will be shared soon.

Significant association of DRD2 enhancer variant rs12364283 with heroin addiction in a Pakistani population.

The dopamine D2 receptor encoded by DRD2 has been implicated in multiple psychiatric disorders, mediated at least in part by two intronic variants affecting mRNA splicing, rs1076560 and rs2283265, and a less frequent enhancer variant, rs12364283, which increases DRD2 mRNA expression. This study tests whether these functionally validated variants confer susceptibility toward heroin addiction in a Pakistani population. A total of 540 heroin addicts and 467 healthy controls were genotyped, basic allele and genotype tests were performed. Neither rs1076560 nor rs2283265 significantly associated with heroin addiction. The enhancer rs12364283 occurs more frequently in heroin-dependent cases than controls (MAF 13% vs. 7%, respectively), revealing significant association with heroin addiction (p = 3.0E-06, OR 2.1). This study identifies rs12364283 of DRD2 as a potential risk factor for heroin addiction in the Pakistani study population. This enhancer variant had been shown to increase DRD2 mRNA expression, a possible factor in increased vulnerability to heroin addiction. Further studies are needed to validate this association of rs12364283.

CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer.

BACKGROUND: Cervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated. METHODS: Three established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo. RESULTS: Treatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602. CONCLUSIONS: This is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies.

Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence.

BACKGROUND: The CHRNA5/A3/B4 gene locus is associated with nicotine dependence and other smoking related disorders. While the non-synonymous CHRNA5 variant rs16969968 appears to be the main risk factor, linkage disequilibrium (LD) bins in the gene cluster carry frequent variants that regulate expression. Pairwise LD and haplotype analyses had identified at least three haplotype tagging SNPs including rs16969968 as main genetic risk factors. Searching for variants with evidence of regulatory functions, we have reported interactions between CHRNA5 and CHRNA3 enhancer variants (tagged by rs880395 and rs1948, respectively) and rs16969968, forming 3-SNP haplotypes and diplotypes that may more accurately reflect the cluster's combined effects on nicotine dependence (Barrie et al., Hum Mutat 38:112-9, 2017). Here we address further contributions by variants affecting CHRNB4, a possibly limiting component of nicotinic receptors. RESULTS: We identify an LD bin (tagged by rs4887074) associated with expression of CHRNB4. Additive logistic regression models indicate that rs4887074 is associated with nicotine dependence and modulates the effect of rs16969968 in GWAS datasets (COGEND, UW-TTURC, SAGE). 4-SNP haplotype and diplotype analyses (rs880395-rs16969968-rs1948 -rs4887074) yield nicotine dependence risk values that further differentiate those obtained with the 3-SNP model. Moreover, both the main G allele of rs16969968 and the minor G allele of rs4887074 (associated with reduced expression of CHRNB4), residing predominantly on common haplotypes that are protective, represent significant allele-specific variance QTLs, indicating that they interact with each other. CONCLUSIONS: These results indicate rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. Assignable to individuals because of strong LD structures, 4-SNP haplotypes and diplotypes serve to assess the combined genetic influence of this multi-gene cluster on complex traits, accounting for complex LD relationships and tissue-specific genetic effects (CHRNA5/3) relevant to the traits analyzed. The 4-SNP haplotypes account at least in part for previous tagging SNPs, including the highly GWAS-significant rs6495308, located in a distinct pair-wise LD bin but included in protective 4-SNP haplotypes. Our approach refines and integrates the cluster's overall genetic influence, an important variable when integrating the genetics of multiple genomic loci.

The CHRNA5/CHRNA3/CHRNB4 Nicotinic Receptor Regulome: Genomic Architecture, Regulatory Variants, and Clinical Associations.

Functionally related genes often cluster into a genome region under coordinated regulation, forming a local regulome. To understand regulation of the CHRNA5/CHRNA3/CHRNB4 nicotinic receptor gene cluster, we integrate large-scale RNA expression data (brain and peripheral) from GTEx (Genotype Tissue Expression), clinical associations (GRASP), and linkage disequilibrium data (1000 Genomes) to find candidate SNPs representing independent regulatory variants. CHRNA3, CHRNA5, CHRNB4 mRNAs, and a well-expressed CHRNA5 antisense RNA (RP11-650L12.2) are co-expressed in many human tissues, suggesting common regulatory elements. The CHRNA5 enhancer haplotype tagged by rs880395 not only increases CHRNA5 mRNA expression in all tissues, but also enhances RP11-650L12.2 and CHRNA3 expression, suggesting DNA looping to multiple promoters. However, in nucleus accumbens and putamen, but not other brain regions, CHRNA3 expression associates uniquely with a haplotype tagged by rs1948 (located in the CHRNB4 3'UTR). Haplotype/diplotype analysis of rs880395 and rs1948 plus rs16969968 (a nonsynonymous CHRNA5 risk variant) in GWAS (COGEND, UW-TTURC, SAGE) yields a nicotine dependence risk profile only partially captured by rs16969968 alone. An example of local gene clusters, this nicotinic regulome is controlled by complex genetic variation, with broad implications for interpreting GWAS.

Longitudinal associations between gut microbiome diversity and emotional well-being.

OBJECTIVE: While a significant link between emotional well-being (EWB) and the gut microbiome has been reported recently, their temporal relationships remain elusive. This study aims to fill this gap by examining the longitudinal associations between EWB and the Shannon Index (SI), an indicator of gut microbiome diversity. METHOD: The analysis focused on a dataset that collected participants' current EWB and fecal samples in both 2019 and 2022 (N = 57, 56.1% female, Mage = 52.47 years, SD = 12.65). Gut microbiome profiles were generated by sequencing the 16S rRNA gene, from which SI was subsequently calculated. RESULTS: The cross-lagged panel analysis revealed significant positive cross-sectional associations between EWB and SI in both 2019 (ß = .296, SE = 0.121, p = .014) and 2022 (ß = .324, SE = 0.119, p = .006). However, no significant longitudinal associations were found between 2019 EWB and 2022 SI (ß = .068, SE = 0.138, p = .623), nor between 2019 SI and 2022 EWB (ß = -.016, SE = 0.13, p = .899). CONCLUSIONS: Our findings indicate that emotional happiness may be associated with gut microbiome profiles at a particular time point, but they may not serve as predictive factors for each other over time. Future research is needed to establish causal relationships between them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Social network position and the Conserved Transcriptional Response to Adversity in older Koreans.

BACKGROUND: Social connections are crucial to human health and well-being. Previous research on molecular mechanisms in health has focused primarily on the individual-level perception of social connections (e.g., loneliness). This study adopted socio-centric social network analysis that includes all social ties from the entire population of interest to examine the group-level social connections and their association with a molecular genomic measure of health. METHODS: Using socio-centric (global) social network data from an entire village in Korea, we investigated how social network characteristics are related to immune cell gene expression among older adults. Blood samples were collected (N = 53, 65-79 years) and mixed effect linear model analyses were performed to examine the association between social network characteristics and Conserved Transcriptional Response to Adversity (CTRA) RNA expression patterns. RESULTS: Social network positions measured by k-core score, the degree of cohesive core positions in an entire village, were significantly associated with CTRA downregulation. Such associations emerged above and beyond the effects of perceived social isolation (loneliness) and biobehavioral risk factors (smoking, alcohol, BMI, etc.). Social network size, defined as degree centrality, was also associated with reduced CTRA gene expression, but its association mimicked that of perceived social isolation (loneliness). CONCLUSIONS: The current findings implicate community-level social network characteristics in the regulation of individual human genome function above and beyond individual-level perceptions of connectedness.

Association of group-level segregation with cardiovascular health in older adults: an analysis of data from the Korean Social Life, Health, and Aging Project.

OBJECTIVES: The adverse health effects of individual-level social isolation (e.g., perceived loneliness) have been well documented in older adults. However, little is known about the impact of collective-level social isolation on health outcomes. We sought to examine the association of group-level segregation with cardiovascular health (CVH) in older adults. METHODS: From the prospective Korean Social Life, Health, and Aging Project database, we identified 528 community-dwelling older adults who were aged ≥60 years or were married to those aged ≥60 years. Participants who belonged to smaller social groups separate from the major social group were defined as group-level-segregated. The CVH score was calculated as the number of ideal non-dietary CVH metrics (0-6), as modified from the American Heart Association's Life's Simple 7. Using ordinal logistic regression models, we assessed cross-sectional and longitudinal associations between group-level segregation and CVH. RESULTS: Of the 528 participants (mean age, 71.7 years; 60.0% female), 108 (20.5%) were segregated at baseline. In the crosssectional analysis, group-level segregation was significantly associated with lower odds of having a higher CVH score at baseline after adjusting for socio-demographic factors and cognitive function (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43 to 0.95). Among 274 participants who completed an 8-year follow-up, group-level segregation at baseline was marginally associated with lower odds of having a higher CVH score at 8 years (OR, 0.49; 95% CI, 0.24 to 1.02). CONCLUSIONS: Group-level segregation was associated with worse CVH. These findings imply that the social network structure of a community may influence its members' health status.

Altered Urine Microbiome in Male Children and Adolescents with Attention-Deficit Hyperactivity Disorder.

While interest in developing the human microbiome as a biomarker for attention-deficit hyperactivity disorder (ADHD) is increasing, there has been limited exploration in utilizing urine samples. In this study, we analysed urine microbiome profiles by extracting 16S ribosomal DNA from purified bacteria-derived extracellular membrane vesicles obtained from urine samples. Sequencing libraries were constructed by amplifying V3-V4 hypervariable regions sequenced using Illumina MiSeq. Profiles of male Korean children and adolescents with ADHD (n = 33) were compared with healthy sex-matched controls (n = 39). Statistically controlling for age, we found decreased alpha diversity in the urine bacteria of the ADHD group, as evidenced by reduced Shannon and Simpson indices (p < 0.05), and significant differences in beta diversity between the two groups (p < 0.001). The phyla Firmicutes and Actinobacteriota, as well as the genera Ralstonia and Afipia, were relatively more abundant in the ADHD group. The phylum Proteobacteria and the genera Corynebacterium and Peptoniphilus were more abundant in the control group. Notably, the genus Afipia exhibited significant correlations with the Child Behavior Checklist Attention Problems score and DSM-oriented ADHD subscale. This study is the first to propose the urine microbiome as a potential biomarker for pediatric ADHD.

Psychological well-being and salivary markers of inflammation: The moderating effect of age.

Increasing evidence suggests a significant impact of higher psychological well-being (PWB) on health outcomes; however, such associations have been studied exclusively in middle-aged to older adults. This study examined the aging effect on PWB measures as well as the moderating effect of age on the link between PWB and inflammation, using salivary markers by comparing the younger adults (n = 127; Mage = 22.98 years) versus older adults (n = 75; Mage = 75.60 years). Older adults showed significantly lower levels of PWB, particularly regarding purpose in life and personal growth. Moreover, higher purpose in life was associated with lower salivary IL-1ß and IL-6 (b = 0.83, p < .001; b = 0.81, p < .01) only in the older adult group but not in younger adults. These findings highlight the potential buffering effect of the sense of living well on physiological pathways in later life.

Factors related to the success of smoking cessation: A retrospective cohort study in Korea.

INTRODUCTION: Every year, at least half of the smokers in South Korea attempt to quit smoking. However, the Korean smoking rate remains still high among OECD countries. This study aimed to identify the factors that influence the success of smoking cessation efforts. METHODS: The study included 1395 smokers, who participated in a 12-week program comprising doctor counseling and pharmacological treatment (i.e. varenicline), conducted at smoking cessation clinics in two general hospitals from 2015 to 2019. The participants responded to a survey questionnaire inquiring about their smoking behaviors at the first visit to the clinic. After completing the program, they were asked whether they succeeded in smoking cessation. Based on participants' reported success or failure, multivariable logistic regression analyses were conducted to obtain adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors related to smoking cessation success. RESULTS: Following the 12-week program, 39.6% of the participants (n=553) succeeded in smoking cessation. Lower rates of nicotine dependence (AOR=0.73; 95% Cl: 0.54-0.98) and lower total amounts of smoking (AOR=0.67; 95% Cl: 0.47-0.95) were significantly associated with higher success rates in smoking cessation. In addition, smokers who participated in the program for at least 8 weeks (AOR=7.16; 95% Cl: 5.57-9.20) and smokers who had hypertension (AOR=1.40; 95% Cl: 1.07-1.85) or a cardiovascular disease (AOR=1.68; 95% Cl: 1.03-2.75) achieved higher success rates. CONCLUSIONS: Smokers' success in smoking cessation was influenced by the period of visits to the smoking cessation clinic, the severity of nicotine dependence, and the presence of a cardiovascular disease including hypertension. Using these factors, smoking cessation strategy may be improved and personalized for individuals.

Social connectedness and hair cortisol in community-dwelling older adults.

Purpose: Hair cortisol is emerging as a reliable biomarker for measuring retrospective stress hormone levels. Given that social connectedness can buffer psychobiological stress reactivity, increasing attention is being paid to the specific types of social networks associated with the stress response. This study investigated the role played by two components of social life, emotional closeness and network size, to probe which aspects of social networks were related to stress measures. Methods: The scalp hair cortisol level was used to assess the cumulative cortisol production in 179 community-dwelling older adults, in the Korean Social Life, Health, and Aging Project (KSHAP). Multivariate regression approach was used to examine the link between the stress measures (cortisol and perceived stress scale) and social relationships (social network size and emotional closeness). Results: Emotional closeness (the average level of what one feels about one's relationship) was significantly associated with decreased levels of hair cortisol, whereas no such relationship was found with the network size. Conclusions: The current findings underscore the role of emotional support on reducing cumulative cortisol, thus providing potential resilience mechanisms for the psychobiological stress response.

Loneliness and immune gene expression in Korean adults: The moderating effect of social orientation.

OBJECTIVE: Loneliness, the distress experienced from a perceived lack of desired interpersonal relationship, is detrimental to mental and physical well-being. One of the physiological correlates of chronic loneliness is alteration of immune transcriptional profiles, characterized by up-regulation of proinflammatory response and down-regulation of antiviral response, called conserved transcriptional response to adversity (CTRA) gene expression. Here, we examined whether the loneliness-CTRA link would be moderated by individual differences in social orientation-that is, the degree to which individuals are collectivistic versus individualistic. METHOD: In a sample of 152 Korean adults (aged 20 to 69, mean age = 44.64, 50% female), we examined the relationship between loneliness and blood cell CTRA gene expression as moderated by individual levels of collectivism (vs. individualism). RESULTS: As predicted, social orientation significantly moderated the loneliness-CTRA link. Loneliness was associated with elevated CTRA expression among Koreans with high levels of collectivism (vs. individualism). In contrast, the loneliness-CTRA link was completely absent among those with lower levels of collectivism (vs. individualism). CONCLUSION: The current finding highlights the role that individual variation in social orientation plays in modulating the risk of loneliness on adverse health outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The relationship between smoking cigarettes and metabolic syndrome: A cross-sectional study with non-single residents of Seoul under 40 years old.

INTRODUCTION: Young adults receive health screenings at lower rates than other age groups, and it may be difficult to detect diseases in the early stages for this group. We examined differences in health status relative to smoking in a young age group using the results of health screenings conducted in engaged and newly married couples in a cross-sectional database. METHODS: The participants in this study were 808 young adults who visited a municipal hospital health screening center from July 2017 to March 2019. They completed a self-administered questionnaire, and physical measurements and a blood test were taken. They were classified into non-cigarette smokers, past cigarette smokers, and current cigarette smokers according to smoking behavior. In this study, we compared metabolic syndrome, the main components of which include obesity, high blood pressure, high blood triglycerides, low levels of HDL cholesterol and insulin resistance, with smoking behavior. RESULTS: The mean age of the participants was 30.9±3.3 years (males 32.0±3.2, females 29.8±3.1), and 13.9% were current cigarette smokers (males 22.8%, females 5.1%). The proportion of men in their 30s was 76.6% for male group and 50.0% for female group, indicating that the male group had a relatively higher proportion of older and current smokers. Significant differences were found in age, sex, blood pressure, metabolic abnormalities, and drinking status according to smoking status. Cigarette smokers had a 2.4-fold greater risk of metabolic syndrome (95% confidence interval [CI], 1.43-3.96) than non-cigarette smokers; in particular, they had a 2.6-fold (95% CI, 1.44-4.55) greater risk of hypertriglyceridemia and a three-fold (95% CI, 1.45-6.35) greater risk of low HDL cholesterol. CONCLUSIONS: In comparison with non-single, young and generally healthy city dwellers, the risk of metabolic syndrome was significantly higher in smokers than in non-smokers, and in particular, it was confirmed that the risk of hypertriglyceridemia and low HDL cholesterolemia was higher. Smoking cessation is necessary, even for the young, because smoking may cause changes in blood lipids even if the smoking duration is short.

Emotional well-being and gut microbiome profiles by enterotype.

With increasing attention being paid to improving emotional well-being, recent evidence points to gut microbiota as a key player in regulating mental and physical health via bidirectional communication between the brain and gut. Here, we examine the association between emotional well-being and gut microbiome profiles (i.e., gut microbiome composition, diversity, and the moderating role of the enterotypes) among healthy Korean adults (n = 83, mean age = 48.9, SD = 13.2). The research was performed using high-throughput 16S rRNA gene sequencing to obtain gut microbiome profiles, as well as a self-report survey that included the Positive Affect Negative Affect Schedule (PANAS). The cluster-based analysis identified two enterotypes dominated by the genera Bacteroides (n = 49) and Prevotella (n = 34). Generalized linear regression analysis reveals significant associations between positive emotion and gut microbiome diversity (Shannon Index) among participants in the Prevotella dominant group, whereas no such relationship emerged among participants in the Bacteroides group. Moreover, a novel genus from the family Lachnospiraceae is associated with emotional well-being scores, both positive and negative. Together, the current findings highlight the enterotype-specific links between the gut microbiota community and emotion in healthy adults and suggest the possible roles of the gut microbiome in promoting mental health.

Psychological well-being and gene expression in Korean adults: The role of age.

BACKGROUND: Happiness has traditionally been thought to comprise two parts - pleasure (hedonia) and meaning (eudaimonia). Even though the two types of happiness are correlated, genomics studies have found distinct transcriptional correlates of hedonia and eudaimonia, particularly in the Conserved Transcriptional Response to Adversity (CTRA) marked by up-regulation of proinflammatory genes and down-regulation of interferon-related genes. Eudaimonia has been associated with reduced CTRA gene expression in several studies, whereas hedonia shows no consistent association with the CTRA. However, most of these social genomics studies have been conducted in Western cultures with Caucasian samples, so it is unclear if these findings extended to non-Western cultures with other ethnic groups. Moreover, it is unknown whether age might modify the association between CTRA gene expression and eudaimonia. To this end, we examined in a sample of Koreans the relationship between CTRA profiles and measures of hedonia and eudaimonia, as well as the role of age in modulating the strength of those relationships. METHODS: Blood samples were collected from 152 healthy Korean adults (mean age = 44.64; 50 % female). Well-being was measured using the Mental Health Continuum short form (MHC-SF), Ryff Scales of Psychological Well-being (PWB), and subjective well-being (SWB) scales. RNA transcriptome profiles were obtained by RNA sequencing. Mixed effect linear model analyses examined the association between CTRA gene expression and measures of MHC-SF, SWB, PWB (total scores and six subscales) and additional analyses examined a possible moderating role of age. RESULTS: CTRA gene expression was significantly downregulated in association with the MHC-SF eudaimonic scores as well as the PWB total scores. Among the six domains of PWB, autonomy showed the strongest inverse correlation with CTRA profiles. Moreover, the inverse association between CTRA and PWB was stronger for older participants. CONCLUSION: Eudaimonia is associated with reduced CTRA gene expression in a Korean population, with particularly marked relationships for autonomy. Findings also suggest that aging with meaning may bring biological advantage in later life.

Estimating quality of life with biomarkers among older Korean adults: A machine-learning approach.

BACKGROUND: While health-related quality of life (HRQoL) has clinical value, its determinants, particularly objective health-related measurements, have not been fully explored. This study seeks to identify the biological indicators that relate to HRQoL among a group of older Korean adults using a machine-learning approach. METHODS: We used physical and mental scores from the 36-item Short Form Health Survey (SF-36) to measure HRQoL among older Korean adults who participated in the Korean Longitudinal Study of Aging (KLoSA) biomarker pilot study (N = 385). The variables for the multivariate penalized regression analysis included demographic factors, medical measurements, physical performance, and health-related behaviors. RESULTS: The multivariate profiles identified several significant biomarkers that relate to quality of life. Among the 20 variables, handgrip strength was the most powerful indicator in both men and women for the SF-36 physical scores, followed by walking speed. Age and total sleep duration exclusively were significantly associated with the SF-36 physical scores only in women, whereas body mass index, blood pressure, and sit-to-stand times were unique elements in men. CONCLUSIONS: The present study suggests significant physical indicators that explain quality of life in elderly populations, using a data-driven approach. Based on these findings, maintaining a good level of physical performance is considered a key element of successful aging.

Alpha-synuclein mRNA isoform formation and translation affected by polymorphism in the human SNCA 3'UTR.

BACKGROUND: Multiple variants in SNCA, encoding alpha-synuclein, a main component of Lewy bodies, are implicated in Parkinson's disease. METHODS: We searched for cis-acting SNCA variants using allelic mRNA ratios in human brain tissues. In a SNCA 3'UTR (2,520 bp) luciferase reporter gene assay, translation in SH-SY5Y cells in the presence of the rs17016074 G/A alleles was measured. To assess clinical impact, we queried neurocognitive genome-wide association studies. RESULTS: Allelic ratios deviated up to twofold, measured at a marker SNP in the middle of a long 3' untranslated region (3'UTR), but not at a marker at its start, suggesting regulation of 3'UTR processing. 3'UTR SNP rs17016074 G/A, minor allele frequency (MAF) <1% in Caucasians, 13% in Africans, strongly associates with large allelic mRNA expression imbalance (AEI), resulting in reduced expression of long 3'UTR isoforms. A second 3'UTR SNP (rs356165) associates with moderate AEI and enhances SNCA mRNA expression. The rs17016074 A allele reduces overall 3'UTR expression in luciferase reporter gene assays but supports more efficient translation, resolving previous contradictory results. We failed to detect significant genome-wide associations for rs17016074, possibly a result of low MAF in Caucasians or its absence from most genotyping panels. In the "Genome Wide Association Study of Yoruba in Nigeria," rs356165 was associated with reduced memory performance. CONCLUSIONS: Here, we identify two cis-acting regulatory variants affecting SNCA mRNA expression, measured by allelic ratios in the 3'UTR. The rs17016074 minor A allele is associated with higher expression of luciferase protein activity. Resolving the genetic influence of SNCA polymorphisms requires study of the interactions between multiple regulatory variants with distinct frequencies among populations.

Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users.

Substance dependent individuals (SDI) often exhibit decision-making deficits; however, it remains unclear whether the nature of the underlying decision-making processes is the same in users of different classes of drugs and whether these deficits persist after discontinuation of drug use. We used computational modeling to address these questions in a unique sample of relatively "pure" amphetamine-dependent (N = 38) and heroin-dependent individuals (N = 43) who were currently in protracted abstinence, and in 48 healthy controls (HC). A Bayesian model comparison technique, a simulation method, and parameter recovery tests were used to compare three cognitive models: (1) Prospect Valence Learning with decay reinforcement learning rule (PVL-DecayRI), (2) PVL with delta learning rule (PVL-Delta), and (3) Value-Plus-Perseverance (VPP) model based on Win-Stay-Lose-Switch (WSLS) strategy. The model comparison results indicated that the VPP model, a hybrid model of reinforcement learning (RL) and a heuristic strategy of perseverance had the best post-hoc model fit, but the two PVL models showed better simulation and parameter recovery performance. Computational modeling results suggested that overall all three groups relied more on RL than on a WSLS strategy. Heroin users displayed reduced loss aversion relative to HC across all three models, which suggests that their decision-making deficits are longstanding (or pre-existing) and may be driven by reduced sensitivity to loss. In contrast, amphetamine users showed comparable cognitive functions to HC with the VPP model, whereas the second best-fitting model with relatively good simulation performance (PVL-DecayRI) revealed increased reward sensitivity relative to HC. These results suggest that some decision-making deficits persist in protracted abstinence and may be mediated by different mechanisms in opiate and stimulant users.

A case of inguinal lymph node squamous cell carcinoma of unknown origin, accompanied with carcinoma in situ of cervix.

Metastatic Cancer of Unknown Primary Site (CUP) accounts for approximately 3-5% of all malignant neoplasms. CUP represents a heterogeneous group of metastatic tumors for which no primary site can be detected following a thorough medical history, careful clinical examination, and extensive diagnostic work-up. Several authors have reported poor prognosis of this malignancy, because there is no consensus on diagnostic guidelines and optimal therapy. Historically, chemotherapy has been the cornerstone of treatment for patients with CUP. We experienced a case of inguinal lymph node squamous cell carcinoma of unknown origin, accompanied with carcinoma in situ of the cervix. We report this case with a brief review of the literatures.