The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia. METHODS: We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals. RESULTS: The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low. CONCLUSIONS: Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.

What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.

Association Between Depressed Mood Changes and Physical Activity Among Adolescents Post COVID-19 Pandemic.

Objectives: Following the coronavirus disease 2019 (COVID-19) pandemic, adolescents have experienced decreased physical activity and a decline in mental health. This study analyzed the association between changes in depressed mood after the COVID-19 pandemic and physical activity among adolescents. Methods: The analysis was based on the results of the 17th Youth Health Behavior Online Survey conducted in 2021, which included 54848 middle and high school students in South Korea. Information on physical activity included low-intensity physical activity lasting >60 min/day, high-intensity physical activity, and strength training exercises. A logistic regression analysis was performed to evaluate the association between physical activity and changes in depression after the COVID-19 pandemic. Results: After adjusting for sociodemographic characteristics and previous depression, adolescents who performed strength training exercises more than once per week had a 0.95-fold lower risk (odds ratio [OR]=0.948, 95% confidence interval [CI]=0.905-0.994, p= 0.027) of increasing depression after the COVID-19 pandemic, while the risk of decreasing depression increased by 1.22-fold (OR=1.215, 95% CI=1.131-1.305, p<0.001). The results were not significant for low-intensity physical activity for >60 min/day and high-intensity physical activity. Conclusion: Strength-training exercises are significantly associated with the prevention of depression among adolescents following the COVID-19 pandemic.

Dietary Carotene Intake and Suicidal Ideation in Korean Females: Analysis of Data From the Korea National Health and Nutrition Examination Survey (2012, 2013, and 2015).

OBJECTIVE: The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders. RESULTS: A total of 5,480 females aged 19-64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 µg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 µg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873-0.999). CONCLUSION: These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.

Shared Risk Factors for Depressive Disorder Among Older Adult Couples in Korea.

Importance: Although couples may share many risk factors for depressive disorders in their lifetime, whether these factors mediate the shared risk of depressive disorders has rarely been investigated. Objectives: To identify the shared risk factors for depressive disorder in couples and investigate their mediating roles in the shared risk of depressive disorders among older adult couples. Design, Setting, and Participants: This nationwide, multicenter, community-based cohort study assessed 956 older adults from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S) between January 1, 2019, to February 28, 2021. Exposures: Depressive disorders of the KLOSCAD participants. Main Outcomes and Measures: The mediating roles of shared factors in couples on the association between one spouse's depressive disorder and the other's risk of depressive disorders was examined using structural equation modeling. Results: A total of 956 KLOSCAD participants (385 women [40.3%] and 571 men [59.7%]; mean [SD] age, 75.1 [5.0] years) and their spouses (571 women [59.7%] and 385 men [40.3%]; mean [SD] age, 73.9 [6.1] years) were included. The depressive disorders of the KLOSCAD participants were associated with an almost 4-fold higher risk of depressive disorders in their spouses in the KLOSCAD-S cohort (odds ratio, 3.89; 95% CI, 2.06-7.19; P < .001). Social-emotional support mediated the association between depressive disorders in the KLOSCAD participants and their spouses' risk of depressive disorders by itself (ß = 0.012; 95% CI, 0.001-0.024; P = .04; mediation proportion [MP] = 6.1%) and through chronic illness burden (ß = 0.003; 95% CI, 0.000-0.006; P = .04; MP = 1.5%). Chronic medical illness burden (ß = 0.025; 95% CI, 0.001-0.050; P = .04; MP = 12.6%) and presence of a cognitive disorder (ß = 0.027; 95% CI, 0.003-0.051; P = .03; MP = 13.6%) mediated the association. Conclusions and Relevance: The risk factors shared by older adult couples may mediate approximately one-third of the spousal risk of depressive disorders. Identification of and intervention in the shared risk factors of depression among older adult couples may reduce the risk of depressive disorders in the spouses of older adults with depression.

Deep learning-based diagnosis of Alzheimer's disease using brain magnetic resonance images: an empirical study.

The limited accessibility of medical specialists for Alzheimer's disease (AD) can make obtaining an accurate diagnosis in a timely manner challenging and may influence prognosis. We investigated whether VUNO Med-DeepBrain AD (DBAD) using a deep learning algorithm can be employed as a decision support service for the diagnosis of AD. This study included 98 elderly participants aged 60 years or older who visited the Seoul Asan Medical Center and the Korea Veterans Health Service. We administered a standard diagnostic assessment for diagnosing AD. DBAD and three panels of medical experts (ME) diagnosed participants with normal cognition (NC) or AD using T1-weighted magnetic resonance imaging. The accuracy (87.1% for DBAD and 84.3% for ME), sensitivity (93.3% for DBAD and 80.0% for ME), and specificity (85.5% for DBAD and 85.5% for ME) of both DBAD and ME for diagnosing AD were comparable; however, DBAD showed a higher trend in every analysis than ME diagnosis. DBAD may support the clinical decisions of physicians who are not specialized in AD; this may enhance the accessibility of AD diagnosis and treatment.

Glioblastoma-educated mesenchymal stem-like cells promote glioblastoma infiltration via extracellular matrix remodelling in the tumour microenvironment.

BACKGROUND: The biological function of mesenchymal stem-like cells (MSLCs), a type of stromal cells, in the regulation of the tumour microenvironment is unclear. Here, we investigated the molecular mechanisms underlying extracellular matrix (ECM) remodelling and crosstalk between MSLCs and glioblastomas (GBMs) in tumour progression. METHODS: In vitro and in vivo co-culture systems were used to analyze ECM remodelling and GBM infiltration. In addition, clinical databases, samples from patients with GBM and a xenografted mouse model of GBM were used. RESULTS: Previous studies have shown that the survival of patients with GBM from whom MSLCs could be isolated is substantially shorter than that of patients from whom MSLCs could not be isolated. Therefore, we determined the correlation between changes in ECM-related gene expression in MSLC-isolatable patients with that in MSLC non-isolatable patients using gene set enrichment analysis (GSEA). We found that lysyl oxidase (LOX) and COL1A1 expressions increased in MSLCs via GBM-derived clusters of differentiation 40 ligand (CD40L). Mechanistically, MSLCs are reprogrammed by the CD40L/CD40/NFκB2 signalling axis to build a tumour infiltrative microenvironment involving collagen crosslinking. Importantly, blocking of CD40L by a neutralizing antibody-suppressed LOX expression and ECM remodelling, decreasing GBM infiltration in mouse xenograft models. Clinically, high expression of CD40L, clusters of differentiation 40 (CD40) and LOX correlated with poor survival in patients with glioma. This indicated that GBM-educated MSLCs promote GBM infiltration via ECM remodelling in the tumour microenvironment. CONCLUSION: Our findings provide mechanistic insights into the pro-infiltrative tumour microenvironment produced by GBM-educated MSLCs and highlight a potential therapeutic target that can be used for suppressing GBM infiltration.

ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer.

Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell-cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.

Mood disorders increase mortality mainly through dementia: A community-based prospective cohort study.

OBJECTIVE: The effects of mood disorders on mortality may be mediated by their effects on the risk of dementia, and interventions to reduce the occurrence of dementia may reduce their overall mortality. This study aimed to investigate the direct effects of depressive and bipolar disorders on the 6-year risk of mortality and also their indirect effects on mortality due to their effect on the risk of dementia. METHODS: A total of 5101 Koreans were selected from a community-based prospective cohort study, and 6-year risks of mortality and dementia in participants with depressive and bipolar disorders were estimated by Cox proportional hazard analysis. The direct and indirect effects of depressive and bipolar disorders on the risk of mortality were estimated using structural equation modeling. RESULTS: The depressive and bipolar disorder groups showed 51% and 85% higher 6-year mortality, and 82% and 127% higher risk of dementia, respectively, compared to euthymic controls. The effects of depressive and bipolar disorders on mortality were mainly mediated by their effects on the risk of dementia in a structural equation model. The direct effects of each mood disorder on mortality were not significant. CONCLUSION: Both depressive and bipolar disorders increased the risks of mortality and dementia, and the effects of mood disorders on mortality were mainly mediated through dementia. As dementia occurs later in life than mood disorders, measures to prevent it may effectively reduce mortality in individuals with a history of mood disorders, as well as being more feasible than attempting to control other causes of death.

Exploration of Cognitive Outcomes and Risk Factors for Cognitive Decline Shared by Couples.

Importance: Although couples could share many risk factors of cognitive disorders in their lifetime, whether shared risk factors mediate the shared risk of cognitive disorders has rarely been investigated. Objective: To identify the risk factors of cognitive decline shared within couples and investigate their mediating roles in the shared risk of cognitive disorders and cognitive functions within couples. Design, Setting, and Participants: A prospective cohort study was launched in November 1, 2010, and 784 participants were followed up every 2 years until December 31, 2020. This nationwide, multicenter, community-based study included older couples from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S). Exposures: The cognitive disorder of a spouse was defined as mild cognitive impairment or dementia. Main Outcomes and Measures: The mediating roles of factors shared within couples on the association between one spouse's cognitive disorder and the other's risk of cognitive disorders was examined with structural equation modeling. Results: Included were 784 KLOSCAD participants (307 women [39.2%] and 477 men [60.8%]; mean [SD] age, 74.8 [4.8] years) and their spouses (477 women [60.8%] and 307 men [39.2%]; mean [SD] age, 73.6 [6.2] years). The cognitive disorder of the KLOSCAD participants was associated with almost double the risk of cognitive disorder of their spouses in the KLOSCAD-S cohort (odds ratio, 1.74; 95% CI, 1.12-2.69; P = .01). History of head injury (ß = 0.50; 95% CI, 0.09-0.90; P = .02) and age (ß = 2.57; 95% CI, 1.37-3.76; P < .001) mediated the association between cognitive disorder in the KLOSCAD participants and their spouses' risk of cognitive disorder. Physical inactivity mediated the association through major depressive disorder (ß = 0.33, 95% CI, 0.09-0.57, P = .006 for physical inactivity; ß = 0.28, 95% CI, 0.13-0.44, P < .001 for major depressive disorder). These factors similarly mediated the association between spousal cognitive disorder and cognitive functions such as memory and executive function. Conclusions and Relevance: These findings suggest that the risk factors shared within couples may mediate approximately three-quarters of the spousal risk of cognitive disorders. Identification of and intervention in the shared risk factors of dementia within couples may reduce the risk of cognitive disorders in the spouses of people with dementia.

Association Between Suicide and Drinking Habits in Adolescents.

OBJECTIVES: Adolescent suicide is a serious social problem. Adolescent alcohol use is one of the most important risk factors for adolescent suicide. This study aimed to identify the relationship between drinking habits and suicide among Korean adolescents. METHODS: Data from the 14th and 15th Korean Youth Risk Behavior Web-based Survey, conducted in 2018 and 2019, were used for analysis. Multiple logistic regression analysis was used to identify the relationship between drinking habits-including the age of drinking initiation, frequency of drinking, average drinking amount, frequency of drunkenness-and suicidal ideation, plans, and attempts. RESULTS: Even after adjusting for age, sex, school grade, academic achievement, socioeconomic status, depression, stress, and drinking habits, the frequencies of drinking and drunkenness increased the risk of suicide attempts. Suicide attempts were associated with the frequency of drinking in girls and middle school students, and with the frequency of drunkenness in boys and high school students. CONCLUSION: This study identified associations between drinking habits (the age of drinking initiation, frequency of drinking, average amount of drinking, frequency of drunkenness) and suicidal behavior in adolescents. Our findings suggest that to prevent adolescent suicide, it might be necessary to investigate drinking habits, including the frequencies of drinking and drunkenness. Moreover, considering the differences in sex and school grade, it is important to include the individual group characteristics when evaluating drinking habits.

Association between Early Spermarche and Suicide Attempts in Boys: the Korea Youth Risk Behavior Web-based Survey.

BACKGROUND: Puberty is a biologically and psychologically unstable period, and pubertal changes differ by sex. However, most previous studies on pubertal timing and suicide have focused on girls. This study investigated the association between early spermarche and suicide attempts in boys. METHODS: We analyzed a nationally representative sample of Korean adolescents (The Korea Youth Risk Behavior Web-Based Survey, KYRBS) that included approximately 35,000 boys annually from 2011 to 2015. Pubertal timing in boys was defined by spermarche. Complex sampling logistic regression analyses were performed to evaluate the odds ratios (ORs) for suicide attempts between the early and average spermarche groups. RESULTS: The ORs for suicide attempts in boys with early spermarche were significantly higher than those in boys with average spermarche after adjustment for age, perceived stress, depressive symptoms, and suicidal ideation. The ORs from 2011 to 2015 were as follows: 1.782 (P < 0.001), 1.490 (P = 0.002), 1.693 (P < 0.001), 1.541 (P = 0.001), and 1.393 (1.024-1.895; P = 0.035), respectively. CONCLUSION: These findings suggest that early pubertal timing is a risk factor for suicide attempts in Korean boys after adjustment for depressive symptoms, perceived stress, and suicidal ideation, which have been previously reported as risk factors for suicide attempts. Therefore, careful attention should be paid to the prevention of suicide in boys who experience early spermarche in Korea.

Model-Based High-Definition Dynamic Contrast Enhanced MRI for Concurrent Estimation of Perfusion and Microvascular Permeability.

This work introduces a model-based, high-definition dynamic contrast enhanced (DCE) MRI for concurrent estimation of perfusion and microvascular permeability over the whole brain. A time series of reference-subtracted signals is decomposed into one component that reflects main contrast dynamics and the other one that includes residual contrast agents (CA) and background signals. The former is described by linear superposition of a finite number of basic vectors trained from an augmented set of data that consists of tracer-kinetic model driven signal vectors and patient-specific measured ones. Contrast dynamics is estimated by solving a constrained optimization problem that incorporates the linearized signal decomposition into the measurement model of DCE MRI and then combining the main component with the background-suppressed, residual CA signals. To the best of our knowledge, this is the first work that prospectively enables rapid temporal sampling with 1.5 s (3 ∼ 4 times higher than clinical routines) while simultaneously achieving high isotropic spatial resolution with 1.0 mm3 (4 ∼ 6 times higher than routines), enhancing estimation of both patient-specific inputs and outputs for quantification of microvascular functions. Simulations and experiments are performed to demonstrate the effectiveness of the proposed method in patients with brain cancer.

Induction of telomere shortening and cellular apoptosis by sodium meta-arsenite in human cancer cell lines.

The present study assessed the cytotoxicity of sodium meta-arsenite (SMA) on telomere shortening and cellular apoptosis in human A-549, MDA-MB-231 and U87-MG cancer cell lines. Following 2 weeks of 1 µM SMA treatment, population doubling time (PDT) was significantly (P < .05) increased by the inhibition of cell proliferation in all the cancer cell lines compared to that in untreated controls. Level of telomerase activity by relative-quantitative telomerase repeat amplification protocol was significantly (P < .05) downregulated by SMA treatment with significant (P < .05) decrease of both telomerase reverse transcriptase and telomerase RNA component transcripts, responsible for telomerase activity. A significant (P < .05) shortening of telomeric repeats by telomere restriction fragment analysis was consequently observed in SMA-treated cells. Moreover, high incidence of cells with senescence-associated ß-glucosidase activity was observed in SMA-treated cells and some cells were also differentiated into adipocytes probably due to the loss of tumorous characterizations. Cellular apoptosis proven by DNA fragmentation was observed, and intrinsic apoptotic transcripts (BAX, caspase 3 and caspase 9) and stress-related transcripts (p21, HSP70 and HSP90) were significantly (P < .05) increased in three cancer cell lines treated with SMA. Based on the present study, SMA treatment apparently induced a shortening of telomere length and cytotoxicity, such as induction of cell senescence, apoptosis and cell differentiation. Therefore, we conclude that SMA treatment at specific concentration can lead to gradual loss of tumorous characterizations and can be considered as a potential anti-cancer drug for chemotherapy treatment.

One-pot synthesis of magnetic particle-embedded porous carbon composites from metal-organic frameworks and their sorption properties.

Nano- and micro-composites comprised of porous carbon and magnetic particles are prepared by one-step pyrolysis of metal-organic frameworks (MOFs). The porosity and composition of resulting magnetic porous carbons are facilely regulated by altering the pyrolysis temperature and changing the organic building blocks incorporated within the initial MOFs.