Case-case genome-wide association analysis identifying genetic loci with divergent effects on Crohn's disease and ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.

Domain-Selective Enzymatic Cross-linking and Etching for Shape-Morphing DNA-Linked Nanoparticle Films.

The highly programmable and responsive molecular recognition properties of DNA provide unparalleled opportunities for fabricating dynamic nanostructures capable of structural transformation in response to various external stimuli. However, they typically operate in tightly controlled environments because certain conditions (ionic strength, pH, temperature, etc.) must be met for DNA duplex formation. In this study, we adopted site-specific enzymatic ligation and DNA-based layer-by-layer thin film fabrication to build shape-morphing DNA-linked nanoparticle films operational in a broad range of environments. The ligated films remained intact in unusual conditions such as pure water and high temperature causing dissociation of DNA duplexes and showed predictable and reversible shape morphing in response to various environmental changes and DNA exchange reactions. Furthermore, domain-selective ligation combined with photoinduced interlayer mixing allowed for the fabrication of unusual edge-sealed double-layered films through midlayer etching, which is difficult to realize by other methods.

Diversity, Equity, and Inclusion Lessons From Developing Stroke Education Programs for West Michigan Asian Communities.

BACKGROUND: Asians in the United States, facing health care disparities, have increased stroke risk. Multiple subgroups, with distinct cultures and languages, add complexity to caring for Asian American (AsA) communities. We developed a tailored stroke education program for underserved West Michigan AsA communities. Methodology, lessons learned, and diversity, equity, and inclusion insights are described. METHODS: Neurology residents and faculty, in collaboration with trained community-specific navigators, developed culturally resonant stroke education that was tailored to meet the needs of specific self-identified West Michigan AsA communities. Educational and debriefing sessions were delivered over 6 months, following the Plan-Do-Study-Act model, to elucidate diversity, equity, and inclusion insights and improve materials and delivery methods. RESULTS: Eighty-six non-English-speaking participants from 5 self-identified AsA communities (Burmese, Buddhist Vietnamese, Catholic Vietnamese, Chinese, and Nepali) attended educational stroke sessions. The average age of attendees was 57.6±13.2 years; most were females (70%). Diversity, equity, and inclusion insights included identification of Asian cultural beliefs about acute stroke treatment (eg, bloodletting), investigator insights (eg, need for kitchen-table programs), systemic barriers (eg, language), and mitigation strategies. CONCLUSIONS: Institutions should consider the integration of equity-focused, trainee-influenced quality improvement projects, such as this culturally resonant stroke educational program for AsA, to enhance stroke care in these vulnerable communities.

High-throughput drug screening using a library of antibiotics targeting cancer cell lines that are resistant and sensitive to gemcitabine.

Gemcitabine is a nucleoside analog widely used as an anticancer agent against several types of cancer. Although gemcitabine sometimes shows excellent effectiveness, cancer cells are often poorly responsive to or resistant to the drug. Recently, specific strains or dysbiosis of the human microbiome were correlated with drug reactivity and resistance acquisition. Therefore, we aimed to identify antibiotic compounds that can modulate the microbiome to enhance the responsiveness to gemcitabine. To achieve this, we confirmed the gemcitabine responsiveness based on public data and conducted drug screening on a set of 250 antibiotics compounds. Subsequently, we performed experiments to investigate whether the selected compounds could enhance the responsiveness to gemcitabine. First, we grouped a total of seven tumor cell lines into resistant and sensitive group based on the IC50 value (1 µM) of gemcitabine obtained from the public data. Second, we performed high-throughput screening with compound treatments, identifying seven compounds from the resistant group and five from the sensitive group based on dose dependency. Finally, the combination of the selected compound, puromycin dihydrochloride, with gemcitabine in gemcitabine-resistant cell lines resulted in extensive cell death and a significant increase in cytotoxic efficacy. Additionally, mRNA levels associated with cell viability and stemness were reduced. Through this study, we screened antibiotics to further improve the efficacy of existing anticancer drugs and overcome resistance. By combining existing anticancer agents and antibiotic substances, we hope to establish various drug combination therapies and ultimately improve cancer treatment efficacy.

Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Multidimensional profiles of head start preschoolers' moral self-concept predict subsequent, but not concurrent, aggression.

The moral self-concept (MSC) describes how children view themselves as moral agents. Research suggests that the MSC may relate to moral behavior, yet little is known about how MSC relates to moral behavior in preschoolers. One hundred six low-income children (M age = 52.78 months, SD = 6.61 months) and their teachers participated in this study. In the fall, children completed a MSC puppet task measure. In the fall and spring, teachers reported via children's survey prosocial behavior and aggressive behavior. We used a person-centered approach to identify profiles of MSC, which revealed two profiles of behavior: comforting prosocials and helpful aggressors. Comforting prosocials showed a moderate preference for comforting, a slight preference for helping, and a slight preference for avoiding aggression. Helpful aggressors had a moderate aversion to comforting, a strong preference for helping, and a slight preference for aggressive behavior. Subsequent analysis of covariance analysis revealed that MSC profiles did not differ in concurrent behavior but did differ in behavior 6 months later. The comforting prosocial group participated in more aggression than the helpful aggressors. Additionally, analysis of covariance analysis of change in aggression scores over time showed that comforting prosocials aggression increased, while helpful aggressors aggression decreased. Both groups over time decreased in prosocial behavior, but to different degrees. Overall, findings reveal that the MSC in preschoolers may relate to future not concurrent moral behavior.

Isolated respiratory tract microorganisms and clinical characteristics in asthma exacerbation of obese patients: a multicenter study.

BACKGROUND: Viral infection is a risk factor for asthma exacerbation (AE). However, bacterial infections related to AE in adults are poorly known. On the other hand, obese patients with asthma have their own clinical and biological characteristics compared with non-obese patients. METHODS: We investigated the differences in isolated pathogens for AE between obese and non-obese patients with asthma. We included 407 patients with AE from 24 medical centers in Korea. Microorganisms isolated from culture, RT-PCR or serologic tests using lower respiratory tract specimens were retrospectively investigated. RESULTS: A total of 171 obese and 236 non-obese patients with asthma were included for analysis. Compared to non-obese patients, obese patients were associated with women (77.2% vs. 63.6%), never smoker (82.5% vs. 73.9%), shorter duration of asthma (7.9 ± 8.4 vs. 10.5 ± 10.1 years), less history of pulmonary tuberculosis (8.8% vs. 17.4%), and more comorbidity of allergic rhinitis (48.5% vs. 0.8%). Viral and/or bacterial infections were detected in 205 patients (50.4%) with AE. The numbers of patients with viral only, bacterial only, or both infections were 119, 49, and 37, respectively. The most commonly isolated bacterium was Streptococcus pneumoniae, followed by Pseudomonas aeruginosa and Chlamydia pneumoniae. Obese patients showed a lower incidence of Chlamydia pneumoniae infection. In the non-obese group, bacterial infection, especially Chlamydia pneumoniae infection, was significantly associated with the duration of systemic corticosteroid use (13.6 ± 19.8 vs. 9.7 ± 6.7 days, p = 0.049). CONCLUSION: Bacterial infection was associated with a longer period of corticosteroid use in the non-obese group. Acute Chlamydia pneumoniae infection was less associated with obese patients with AE. Further well-designed studies are needed to evaluate microorganisms and the efficacy of antibiotics in patients with AE.

Decreased aggressive care at the end of life among advanced cancer patients in the Republic of Korea: a nationwide study from 2012 to 2018.

BACKGROUND: This study aimed to investigate the trends of aggressive care at the end-of-life (EoL) for patients with advanced cancer in Korea and to identify factors affecting such care analyzing nationwide data between 2012 to 2018. METHODS: This was a population-based, retrospective nationwide study. We used administrative data from the National Health Insurance Service and the Korea Central Cancer Registry to analyze 125,350 patients aged 20 years and above who died within one year of a stage IV cancer diagnosis between 2012 and 2018. RESULTS: The overall aggressiveness of EoL care decreased between 2012 and 2018. In patients' last month of life, chemotherapy use (37.1% to 32.3%; p < 0.05), cardiopulmonary resuscitation (13.2% to 10.4%; p < 0.05), and intensive care unit admission (15.2% to 11.1%; p < 0.05) decreased during the study period, although no significant trend was noted in the number of emergency room visits. A steep increase was seen in inpatient hospice use in the last month of life (8.6% to 26.6%; p < 0.05), while downward trends were observed for hospice admission within three days prior to death (13.9% to 11%; p < 0.05). Patients were more likely to receive aggressive EoL care if they were younger, women, had treatment in tertiary hospitals, or had hematologic malignancies. In the subgroup analysis, the overall trend of aggressive EoL care decreased for all five major cancer types. CONCLUSION: The aggressiveness of EoL care in stage IV cancer patients showed an overall decrease during 2012-2018 in Korea.

Prognostic Factors for Predicting Post-COVID-19 Condition in Patients With COVID-19 in an Outpatient Setting.

BACKGROUND: Although data on post-coronavirus disease 2019 (COVID-19) conditions are extensive, the prognostic factors affecting symptom duration in non-hospitalized patients with COVID-19 are currently not well known. We aimed to investigate the various prognostic factors affecting symptom duration among outpatients with COVID-19. METHODS: Data were analyzed from 257 patients who were diagnosed with mild COVID-19 and visited the 'post-COVID-19 outpatient clinic' between April and December 2022 after a mandatory isolation period. The symptom duration was measured from diagnosis to symptom resolution. Laboratory and pulmonary function test results from their first visit were collected. RESULTS: The mean age of patients was 55.7 years, and the median symptom duration was 57 days. The development of post-COVID-19 conditions (> 12 weeks) were significantly correlated with not using antiviral drugs, leukocytosis (white blood cell > 10,000/µL), lower 25(OH)D3 levels, forced vital capacity (FVC) < 90% predicted, and presence of dyspnea and anxiety/depression. Additionally, in multivariable Cox regression analysis, not using antiviral drugs, lower 25(OH)D3 levels, and having dyspnea were poor prognostic factors for longer symptom duration. Particularly, vitamin D deficiency (< 20 ng/mL) and not using antivirals during the acute phase were independent poor prognostic factors for both post-COVID-19 condition and longer symptom duration. CONCLUSION: The non-use of antivirals, lower 25(OH)D3 levels, leukocytosis, FVC < 90% predicted, and the presence of dyspnea and anxiety/depression symptoms could be useful prognostic factors for predicting post-COVID-19 condition in outpatients with COVID-19. We suggest that the use of antiviral agents during the acute phase and vitamin D supplements might help reduce COVID-19 symptom duration.

Loneliness Among Low-Income Older Immigrants Living in Subsidized Senior Housing: Does Perceived Social Cohesion Matter?

This study compared the level of loneliness among older immigrants residing in subsidized senior housing with that of non-immigrant residents. The study also sought to examine the differential influence of perceived social cohesion on loneliness among these groups. 231 study participants were recruited from subsidized senior housing in St. Louis and the Chicago area. Multiple regression analyses showed that there was a significant difference in loneliness between immigrants and non-immigrants (b = .3, SE = 0.150, p < .05). Also, perceived social cohesion was negatively associated with loneliness (b=-.102, SE = .022, p < .001). Furthermore, immigration status moderated the relationship (b=-.147, SE = .043, p < .01), showing immigrants may benefit more from higher perceived social cohesion in terms of loneliness. The results suggest that perceived social cohesion may act as an important community-level protective factor against loneliness, particularly for older immigrants residing in subsidized senior housing. Creating socially cohesive environments, particularly for this subgroup, could be a crucial strategy for mitigating loneliness. .

Long-Term Health Effects of Work Trajectories Among Middle-Aged and Older Adults: The Mediating Role of Work, Material, and Social Environments.

Using data from 14 waves (2003-2016) of the Korean Labor and Income Panel Study (KLIPS) (N = 1,627 individuals aged 45-64; 22778 observations), in this study, we conducted sequence analysis and a multi-categorical variable mediation analysis (1) to examine to what extent long-term work histories exhibit varying degrees of de-standardization and precariousness using sequence analysis (2) to explore the potential mediating effects of work, material, and social environments in the association between multiple work sequences and self-rated health. We found the coexistence of a relatively stable long-term employment pattern and a high prevalence of precariousness. The health and economic risks of precarious work fall disproportionately on older workers. Future researchers should continue to analyze whether the COVID-19 pandemic will lead to long-term changes in the workforce to improve our understanding of and response to working in later life and its health effects.

Transplanting Gold Active Sites into Non-Precious-Metal Nanoclusters for Efficient CO2-to-CO Electroreduction.

Electrocatalytic CO2 reduction reaction (CO2RR) is greatly facilitated by Au surfaces. However, large fractions of underlying Au atoms are generally unused during the catalytic reaction, which limits mass activity. Herein, we report a strategy for preparing efficient electrocatalysts with high mass activities by the atomic-level transplantation of Au active sites into a Ni4 nanocluster (NC). While the Ni4 NC exclusively produces H2, the Au-transplanted NC selectively produces CO over H2. The origin of the contrasting selectivity observed for this NC is investigated by combining operando and theoretical studies, which reveal that while the Ni sites are almost completely blocked by the CO intermediate in both NCs, the Au sites act as active sites for CO2-to-CO electroreduction. The Au-transplanted NC exhibits a remarkable turnover frequency and mass activity for CO production (206 molCO/molNC/s and 25,228 A/gAu, respectively, at an overpotential of 0.32 V) and high durability toward the CO2RR over 25 h.

Conjugated Block Copolymers for Functional Nanostructures.

Conjugated polymers have been actively studied as an alternative to inorganic semiconductors for their unique optical and electrical properties and low-cost solution processability. However, typical conjugated polymer films contain numerous defects that negatively affect their transport properties, which remains a major issue despite much effort to develop ways to improve the molecular packing structure. In principle, conjugated block copolymers (BCPs) composed of a rod-type conjugated polymer and a coil-type insulating polymer can assemble into various types of ordered nanostructures based on the microphase segregation of two polymer blocks. However, such assembly typically requires a relatively large volume fraction of the coil block or modification of the rod block, both of which tend to impede charge transport. As an alternative, we and others have fabricated nanoscale assemblies of conjugated BCPs via solution-phase self-assembly, which can be used as building blocks for construction of extended nanoarrays of conjugated polymers. In particular, BCPs containing poly(3-hexylthiophene) (P3HT), a conjugated polymer widely used for its high hole mobility, form highly ordered and technologically relevant one-dimensional (1D) nanowires with controlled lengths. A range of well-defined assembly structures such as square plates, ribbons, vesicles, and helices have been prepared from various conjugated BCPs, resembling those of peptide self-assembly, forming diverse nanostructures through combinations of π-π stacking, hydrogen bonding, and hydrophobic interactions.When the self-assembly of P3HT BCPs takes place at an air-water interface, the initially formed polymer nanowires further assemble into hierarchical two-dimensional (2D) nanoarrays with solvent evaporation. The fluidic nature of the water subphase allows fabrication of highly ordered assembly structures from P3HT BCPs with high P3HT content. The ultrathin free-standing film integrated in a field effect transistor (FET) showed orders of magnitude higher current and hole mobility compared to that fabricated by conventional spin-coating. Furthermore, binary self-assembly of a P3HT BCP and quantum dots (QDs) at the air-water interface generates well-ordered 2D films of alternating P3HT nanowires and 1D QD arrays. Unlike coil-coil BCP systems, QDs reside at the interface between P3HT and coil blocks for a broad range of QD sizes due to the strong P3HT packing interactions and the flexible water subphase, forming tight p-n junctions for enhanced photocurrent. Incorporation of magnetic nanoparticles can further improve the degree of order, enabling fabrication of long-range order and direction-controlled P3HT nanoarrays through magnetic-field induced self-assembly.The conjugated BCP approach is highly modular and can be combined with various types of functional molecules, polymers, and nanoparticles, offering a powerful platform for fabrication of functional polymer nanostructures with desired morphologies and properties. This Account introduces recent advances in the self-assembly of π-conjugated BCPs, describes how they differ from prototypical coil-coil type BCPs, and discusses current issues and future outlooks.

Oligonucleotides as Inhibitors of Ice Recrystallization.

Oligonucleotides of adenine (A20), guanine (G20), cytosine (C20), thymine (T20), cytosine-guanine ((CG)20), and adenine-thymine ((AT)20) were investigated as model compounds for ice recrystallization inhibition (IRI). Dehydroxy uracil (dU20), U20, and T20 were also compared to investigate the effect of minute changes in the hydrophobicity of the oligonucleotides on the IRI activity. Among the oligonucleotides considered in this study, T20 exhibited the best performance for IRI. In addition, the degree of polymerization of oligothymines varied over 5, 10, 20, 30, 50, and 100, and T20 was found to be the most effective for IRI. The IRI mechanism was investigated by comparing U20 and T20, which exhibited the lowest and highest IRI activity, respectively, among the oligonucleotides for their dynamic ice-shaping, thermal hysteresis, and ice nucleation inhibition. Little or no dynamic ice-shaping activity and small thermal hysteresis were observed for both nucleotides. All of the findings suggest that not the ice-polymer adhesion but the hydrophobic interactions of T20 in the interface layer might interfere with the water deposition on the ice crystal surfaces and contribute to the IRI activity of the T20 oligonucleotide.

Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing.

CRISPR-based base editors (BEs) are widely used to induce nucleotide substitutions in living cells and organisms without causing the damaging DNA double-strand breaks and DNA donor templates. Cytosine BEs that induce C:G to T:A conversion and adenine BEs that induce A:T to G:C conversion have been developed. Various attempts have been made to increase the efficiency of both BEs; however, their activities need to be improved for further applications. Here, we describe a fluorescent reporter-based drug screening platform to identify novel chemicals with the goal of improving adenine base editing efficiency. The reporter system revealed that histone deacetylase inhibitors, particularly romidepsin, enhanced base editing efficiencies by up to 4.9-fold by increasing the expression levels of proteins and target accessibility. The results support the use of romidepsin as a viable option to improve base editing efficiency in biomedical research and therapeutic genome engineering.

Stratifying non-small cell lung cancer patients using an inverse of the treatment decision rules: validation using electronic health records with application to an administrative database.

BACKGROUND: To validate a stratification method using an inverse of treatment decision rules that can classify non-small cell lung cancer (NSCLC) patients in real-world treatment records. METHODS: (1) To validate the index classifier against the TNM 7th edition, we analyzed electronic health records of NSCLC patients diagnosed from 2011 to 2015 in a tertiary referral hospital in Seoul, Korea. Predictive accuracy, stage-specific sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and c-statistic were measured. (2) To apply the index classifier in an administrative database, we analyzed NSCLC patients in Korean National Health Insurance Database, 2002-2013. Differential survival rates among the classes were examined with the log-rank test, and class-specific survival rates were compared with the reference survival rates. RESULTS: (1) In the validation study (N = 1375), the overall accuracy was 93.8% (95% CI: 92.5-95.0%). Stage-specific c-statistic was the highest for stage I (0.97, 95% CI: 0.96-0.98) and the lowest for stage III (0.82, 95% CI: 0.77-0.87). (2) In the application study (N = 71,593), the index classifier showed a tendency for differentiating survival probabilities among classes. Compared to the reference TNM survival rates, the index classification under-estimated the survival probability for stages IA, IIIB, and IV, and over-estimated it for stages IIA and IIB. CONCLUSION: The inverse of the treatment decision rules has a potential to supplement a routinely collected database with information encoded in the treatment decision rules to classify NSCLC patients. It requires further validation and replication in multiple clinical settings.

Preference to Age in Place in Low-Income Senior Housing.

Low-income senior housing provided through the Section 202 Supportive Housing for the Elderly program is a critical site for aging in place, and many of these properties have hired service coordinators to monitor residents' quality of life, provide access to services, and promote their ability to age in place. To address gaps in the limited literature on Section 202 buildings, this study examined the association between service coordination and low-income senior housing residents' preference to age in place with particular attention to the most economically vulnerable. We analyzed data from 255 older adults living in eight Section 202 buildings in Southeastern Michigan using logistic regression. Self-perceived economic vulnerability moderated the relationship between service coordination and preference to age in place. Among those who had not received service coordination, the high economic vulnerability group was more likely to prefer to age in place compared to more economically secure residents. Among those who received assistance from a service coordinator, economically vulnerable residents were less likely to express a preference to age in place compared to other residents. Findings indicate a complex relationship between service coordination, economic resources, and preference to age in place in senior housing, and suggest areas for future research.

Deaths of Despair and Population Aging in Missouri.

Recent declines in life expectancy in the US, especially for middle-aged White persons, have called attention to mortality from deaths of despair - deaths due to alcohol, drugs, and suicide. Using data from the Centers for Disease Control and the U.S. Census Bureau, this paper examined deaths of despair by race/ethnicity, age, cause of death, birth cohort, and sex in Missouri. We focused on Area Agencies on Aging as geographic units of interest to increase usefulness of our findings to public administrators. Deaths of despair began trending up for all age groups beginning in 2007-2009, with the sharpest increases occurring for Black or African American non-Hispanics beginning in 2013-2015. The most dramatic increases occurred for the population age 50-59 in St. Louis City and Area Agency on Aging regions in southern Missouri. For older adults, considerable variation in rates, trends, and cause of deaths of despair is evident across the state.

The Association Between Patterns of Social Engagement and Conversion From Mild Cognitive Impairment to Dementia: Evidence From the Health and Retirement Study.

OBJECTIVES: This study examined the association between patterns of social engagement and conversion from cognitive impairment, no dementia (CIND) to dementia. It also tested whether social engagement is associated with conversion independently from physical and cognitive engagements. METHOD: Data from 2 waves (2010 and 2014) of the Health and Retirement Study (HRS) were used. The sample consisted of 1227 people who had CIND in 2010. To identify the heterogeneity of social engagement, latent class analysis was utilized. Multinomial logistic regression analysis was utilized to investigate the association between patterns of social engagement and probability of conversion to dementia and death or dropout. RESULTS: The result showed that patterns of social engagement that represent higher level and more variety of social engagement were associated with lower probabilities of conversion to dementia in 4 years but not with probabilities of death or dropout. The relationship held after controlling for physical and cognitive engagements. DISCUSSION: Findings implied that promoting social engagement may be protective against developing dementia even for the high-risk group of people with CIND. Future studies should investigate the mechanism behind the relationship between patterns of social engagement and lower probabilities of conversion to dementia.

Multiple pathways linking early socioeconomic circumstances and depressive symptoms in late Middle age in the U.S.

Objectives: A growing number of life course studies are examining the influence of earlier life experiences on morbidity, disability, and mortality in mid-old age.Method: Drawing from the social pathway model, this study expands the life course literature by utilizing data collected over 35 years from the National Longitudinal Survey of Youth, 1979 Cohort, spanning four life course phases (childhood, young adulthood, middle adulthood, and late-middle adulthood). Through structural equation analyses with a phantom model, we estimated depressive symptoms in late middle age as a result of pathway effects starting with childhood socio-economic status (SES) which effect young adulthood and middle adulthood. The multi-pathway life course model includes three potential mediators of middle adulthood: health risk behaviors, social activity, and negative life events.Results: We found limited support for a direct effect of childhood SES disadvantage on depressive symptoms in middle age. Instead, much of the effects of childhood SES on later-year depressive symptoms appear to be mediated by SES in young adulthood. Further, the long-term pathway is mediated through the influence of health risk behaviors and negative life events in middle adulthood.Conclusion: Our findings do not propose this chain is permanent and irreversible; rather, this study highlights the possibility that interventions focused on promoting health behaviors and improving living conditions for people from socioeconomically disadvantaged backgrounds could help reduce the instance of depression in middle age and health outcomes along the life course could be improved.