Multiple serum biomarkers for predicting suicidal behaviours in depressive patients receiving pharmacotherapy.

BACKGROUND: Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders. METHODS: At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates. RESULTS: Increased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001). CONCLUSIONS: Application of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.

Psychological and Personality Characteristics Associated With COVID-19 Vaccination Behavior in Korean General Population.

BACKGROUND: This study characterized coronavirus disease 2019 (COVID-19) vaccination behavior in the Korean general population using cluster analysis and explored related psychological factors. METHODS: We categorized 1,500 individuals based on their attitudes toward COVID-19 vaccination using hierarchical clustering and identified their level of vaccine acceptance. We examined the associations between vaccine acceptance and behavioral and psychological characteristics. RESULTS: Clustering revealed three groups according to vaccine acceptance: 'totally accepting' (n = 354, 23.6%), 'somewhat accepting' (n = 523, 34.9%), and 'reluctant' (n = 623, 41.5%). Approximately 60% of all participants who belonged to the 'totally accepting' and 'somewhat accepting' groups were willing to receive a COVID-19 vaccine despite concerns about its side effects. High vaccine acceptance was associated with older age, regular influenza vaccination, and trust in formal sources of information. Participants with high vaccine acceptance had higher levels of gratitude, extraversion, agreeableness, and conscientiousness, and lower levels of depression, anxiety, and neuroticism. CONCLUSIONS: People weighed the benefits of COVID-19 vaccination against the risk of side effects when deciding to receive the COVID-19 vaccine. Our findings also indicate that this vaccination behavior may be affected by coping mechanisms and psychological factors.

Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy.

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3-12 week) phase (N = 1086), and in 3-month steps during the continuation (6-12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.

Interaction effect between childhood abuse and interleukin-1ß levels on suicidality in depressed patients.

INTRODUCTION: The roles of childhood abuse and interleukin (IL)-1ß levels, a representative pro-inflammatory cytokine, in suicidal behavior are unclear. This study investigated the main and interactive effects of childhood abuse and IL-1ß levels on suicidal behavior in patients with a depressive disorder before and after pharmacological treatment. METHODS: At baseline, exposure to self-reported childhood abuse, including emotional, physical, and sexual abuse, before the age of 16 years, and IL-1ß levels, were measured in 1,094 outpatients with a depressive disorder, 884 of whom were followed for 1 year. Suicidal behavior was evaluated, including previous suicide attempts (at baseline), suicidal ideation (at baseline and follow-up), and fatal/non-fatal suicide attempts (at follow-up). The main and interaction effects of self-reported childhood abuse and IL-1ß level on the four types of suicidal behavior were analyzed using logistic regression after adjusting for covariates. RESULTS: Individual associations of self-reported childhood abuse were significant only with previous suicidal attempt but not with other suicidal behaviors. There was no significant association of plasma IL-1ß level with any suicidal behavior. There were significant interactive associations of self-reported childhood abuse and a high IL-1ß level on previous suicide attempts, baseline suicidal ideation, and fatal/non-fatal suicidal attempts during follow-up. CONCLUSION: Suicidal behavior in patients with a depressive disorder could be influenced by considering the interactive effect of childhood abuse and IL-1ß levels. Our study suggests that childhood trauma and biochemical factors play roles in the pathology of suicide in depressed patients.

Modifying Effect of the Interleukin-18 Level on the Association between BDNF Methylation and Long-Term Cardiovascular Outcomes in Patients with Acute Coronary Syndrome.

This study investigated the potential modifying effects of the level of the serum interleukin-18 (IL-18) on the association between BDNF methylation status and long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Hospitalized ACS patients were recruited sequentially from 2006 to 2012. At baseline, the IL-18 level and BDNF methylation status were evaluated in 969 patients who were followed for major adverse cardiac events (MACEs) for 5-12 years, until 2017 or death. The time to first composite or individual MACE was compared between individuals with lower and higher average BDNF methylation levels (in the low- and high-IL-18 groups, respectively) using a Cox proportional hazards model. After adjusting for potential covariates, the modifying effects of IL-18 and average BDNF methylation levels on the initial composite and individual MACEs were examined. In the high-IL-18 group, but not in the low-IL-18 group, a higher average BDNF methylation level was associated with increases in composite MACEs (HR (95% CI) = 2.15 (1.42-3.26)), all-cause mortality (HR (95% CI) = 1.89 (1.11-3.22)), myocardial infarction (HR (95% CI) = 1.98 (1.07-3.67)), and percutaneous coronary intervention (HR (95% CI) = 1.81 (1.01-3.23)), independent of confounding variables. The interaction effect between the IL-18 and average BDNF methylation levels on composite MACEs (p = 0.019) and myocardial infarction (p = 0.027) was significant after adjusting for covariates. Analysis of BDNF methylation status and IL-18 levels may help identify ACS patients who are most likely to have adverse clinical outcomes.

Investigating associations of childhood abuse and serum brain-derived neurotrophic factor levels with suicidal behaviours in patients with depressive disorders.

BACKGROUND: The role of childhood abuse and serum brain-derived neurotrophic factor (BDNF) levels in suicidal behaviour is controversial. AIMS: We aimed to investigate the individual and interactive effects of the childhood abuse and serum BDNF on suicidal behaviour before and after pharmacologic treatment in patients with depressive disorders. METHOD: At baseline, reported childhood emotional, physical and sexual abuse were ascertained and serum BDNF levels were measured in 1094 patients with depressive disorder, 884 of whom were followed during a 1-year period of stepwise pharmacotherapy. Suicidal behaviours evaluated at baseline were previous suicide attempt and baseline suicide severity, and suicidal behaviours evaluated at follow-up were increased suicide severity and fatal/non-fatal suicide attempt. Individual and interactive associations of any childhood abuse and serum BDNF levels with four types of suicidal behaviours were analysed using logistic regression models, after adjusting relevant covariates. RESULTS: Individual associations of childhood abuse were significant only with previous suicide attempt, and no significant individual associations were found for serum BDNF with any suicide outcome. However, the presence of both childhood abuse and lower serum BDNF levels was associated with the highest prevalence/incidence of all four suicidal behaviours, with significant interactions for baseline suicide severity and fatal/non-fatal suicide attempt during follow-up. CONCLUSIONS: Synergistic interactive effects of child abuse and serum BDNF levels on suicidal behaviours were found before and after pharmacologic treatment in patients with depressive disorders. Information combining childhood abuse and serum BDNF levels could improve predictions of suicidal behaviour in patients with depressive disorders.

Long-term cardiac outcomes of depression screening, diagnosis and treatment in patients with acute coronary syndrome: the DEPACS study.

BACKGROUND: To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS). METHODS: Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5-12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M). RESULTS: Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63-2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline. CONCLUSIONS: Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.

Interactive effects of systemic inflammation and life stressors on treatment response of depressive disorders.

Inflammation is an important contributor in the pathophysiology of depression and recent evidence suggests that systemic inflammation and life stressors have interactive roles in depression onset. The aim of the present study was to investigate the individual and interactive effects of systemic inflammation and life stressors with short- and long-term treatment responses in outpatients with depressive disorders in a naturalistic one-year prospective design. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured and number of stressful life events (SLEs) during the last 3 months were ascertained from 1094 patients at baseline. These patients received initial antidepressant monotherapy, then, for patients with an insufficient response or uncomfortable side effects, next treatment with alternative strategies were administered at every 3 weeks in the acute treatment phase (3, 6, 9, and 12 weeks) and at every 3 months in the continuation treatment phase (6, 9, and 12 months). 12-week and 12-month remission was estimated, defined as a Hamilton Depression Rating Scale score of ≤ 7. In multivariable logistic regression analyses, individual effects were found only between higher baseline serum hsCRP levels (≥1.0 vs. < 1.0 mg/L) and 12-week non-remission. Significant interactive effects between higher hsCRP levels and higher number of SLEs (≥2 vs. < 2) on both 12-week and 12-month non-remission were observed. Combining serum hsCRP levels and number of SLEs might therefore be a useful predictor for short- and long-term treatment responses in patients with depressive disorders receiving pharmacotherapy.

Effects of acute and chronic depression on 12-year long-term outcomes after stroke.

OBJECTIVES: This study aimed to investigate whether acute and chronic poststroke depression (PSD) were associated with cardio-cerebrovascular events (CVEs). METHODS: A total of 423 patients with recent stroke were recruited from 2006 to 2009. They were diagnosed with major or minor depressive disorder during the acute phase (within 2 weeks) after stroke. Of these, 284 completed the same diagnostic evaluation during the chronic phase (1 year) after stroke. An average 12-year (range 8.7-14.1 years) follow-up was conducted to assess composite CVEs including recurrent stroke, myocardial infarction, and vascular death after the index stroke. During the follow-up, Kaplan-Meier event rates for outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates. RESULTS: The composite CVE incidence was higher in patients with acute or chronic PSD than in those without. Composite event incidence was highest in patients with PSD during both the acute and chronic phases. CONCLUSIONS: The presence of depression at acute and chronic phase of stroke predicted worse long-term cardio-cerebrovascular outcomes. Evaluation of PSD during both the acute and chronic phases is recommended.

Risk and protective factors of depression in the general population during the COVID-19 epidemic in Korea.

BACKGROUND: The risk of depression has risen in the general population during the COVID-19 epidemic. This study was conducted to explore risk and protective factors associated with depression among the general population uninfected by COVID-19. METHODS: A cross-sectional study was conducted with 1,500 representative South Korean citizens aged 19-65 years through an anonymous online survey. Depression was defined as a Patient Health Questionnaire-9 score of 10 or higher. Other questionnaires included one measuring psycho-behavioural and social changes, and stress, due to COVID-19, a six-item version of the Gratitude Questionnaire (GQ-6), and a three-item version of the UCLA loneliness scale. RESULTS: Of the 1492 participants not infected by COVID-19, 312 (20.9%) exhibited depression. Multiple logistic regression analysis revealed that depression was positively associated with COVID-19-related stress and psycho-behavioural variables such as disturbances in eating and sleeping, younger age, smoking, underlying mental illness, and loneliness scale scores. In contrast, exercise three or more times per week and GQ-6 scale scores were inversely associated with depression. CONCLUSION: During the COVID-19 pandemic, maintaining daily routines including eating, sleeping, and regular exercise and focusing on gratitude may be important for the prevention of depression. In addition, more attention should be paid to vulnerable populations, including young people, those with mental illnesses, and smokers, who might be more susceptible to depression.

The Relationships among Media Usage Regarding COVID-19, Knowledge about Infection, and Anxiety: Structural Model Analysis.

BACKGROUND: We examined the effects of mass media usage on people's level of knowledge about coronavirus disease 2019 (COVID-19), fear of infection, prejudice towards infected people, and anxiety level. In addition, we investigated whether knowledge about COVID-19 can reduce fear, prejudice, and anxiety. METHODS: We performed an anonymous online survey in 1,500 residents aged 19-65 years between April 24 and May 5 of 2020. Anxiety level was assessed using the generalized anxiety disorder-7 scale. We used a questionnaire to investigate COVID-19-related media use, knowledge about COVID-19, fear of infection, and prejudice towards infected people. We analyzed the relationships among the variables using the structural equation model. RESULTS: Media use had significant effects on fear of infection, prejudice against infected people, and anxiety. Knowledge about COVID-19 had a significant protective effect on fear of infection, prejudice against infected people, and anxiety. However, the effect of media use on knowledge about COVID-19 was not statistically significant. There was a partial mediating effect of prejudice against infected people and fear of infection on media usage and anxiety. CONCLUSION: Our study demonstrated significant effects of mass media coverage regarding COVID-19 on fear, prejudice, and anxiety. While knowledge about COVID-19 could decrease fear, prejudice, and anxiety, the use of mass media did not enhance this knowledge. Medical societies should guide mass media reporting of COVID-19 and provide appropriate public education.

Genetic Markers for Later Remission in Response to Early Improvement of Antidepressants.

Planning subsequent treatment strategies based on early responses rather than waiting for delayed antidepressant action can be helpful. We identified genetic markers for later non-remission in patients exhibiting poor early improvement using whole-exome sequencing data of depressive patients treated in a naturalistic manner. Among 1000 patients, early improvement at 2 weeks (reduction in Hamilton Depression Rating Scale [HAM-D] score ≥ 20%) and remission at 12 weeks (HAM-D score ≤ 7) were evaluated. Gene- and variant-level analyses were conducted to compare patients who did not exhibit early improvement and did not eventually achieve remission (n = 126) with those who exhibited early improvement and achieved remission (n = 385). Genes predicting final non-remission in patients who exhibited poor early improvement (COMT, PRNP, BRPF3, SLC25A40, and CGREF1 in males; PPFIBPI, LZTS3, MEPCE, MAP1A, and PFAS in females; ST3GAL5 in the total population) were determined. Among the significant genes, variants in the PRNP (rs1800014), COMT (rs6267), BRPF3 (rs200565609), and SLC25A40 genes (rs3213633) were identified. However, interpretations should be made cautiously, as complex pharmacotherapy involves various genes and pathways. Early detection of poor early improvement and final non-remission based on genetic risk would be helpful for decision-making in a clinical setting.

Modifying effects of depression on the association between BDNF methylation and prognosis of acute coronary syndrome.

AIMS: Brain-derived neurotrophic factor (BDNF) plays important roles in angiogenesis, inflammation, and neuronal plasticity. BDNF methylation has been extensively investigated in depression, but not in cardiac diseases. We asked whether BDNF methylation status is associated with a major adverse cardiac event (MACE), inflammation, and the association with depression comorbidity and its treatment in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A cross-sectional baseline study and nested 24 week double-blind escitalopram placebo-controlled trial (ClinicalTrial.gov identifier NCT00419471) were performed from 2006 to 2012, with 5-12 year follow-up for MACE. Patients with recent ACS (969 total) were divided into four groups according to depression comorbidity at baseline and treatment allocation: 591, absent depression; 127, depression on escitalopram; 128, depression on placebo; 123, depression on care as usual (CAU). BDNF methylation was measured in leucocyte DNA, and multiple demographic and clinical characteristics including interleukin 6 were evaluated as covariates at baseline. The primary outcome, time to first MACE (a composite of all-cause mortality, myocardial infarction and percutaneous coronary intervention), was investigated using Cox regression models after adjustment for covariates. Interleukin 6 level was significantly higher in patients with higher BDNF methylation values. Higher BDNF methylation was associated with increased MACE independent of confounding factors [HR (95% CI) = 1.45 (1.17-1.78)]. This association was significant in patients without depression [HR (95% CI) = 1.39 (1.01-1.90)] and depressive patients on placebo [HR (95% CI) = 1.72 (1.02-3.02)] or CAU [HR (95% CI) = 1.53 (1.01-2.61)], but not in those treated with escitalopram [HR (95% CI) = 1.00 (0.51-1.95)]. CONCLUSION: BDNF methylation was significantly associated with prognosis of ACS. Escitalopram may mitigate the deleterious effect of higher BDNF methylation in depressive patients with ACS. Further research is needed to elucidate the mechanistics and to assess the generalisability of these findings.

A longitudinal study of the associations of BDNF genotype and methylation with poststroke anxiety.

BACKGROUND: Although the precise etiology of poststroke anxiety (PSA) has yet to be fully elucidated, it is known that brain-derived neurotrophic factor (BDNF) is important for neural plasticity and long-term potentiation, associated with the pathophysiology of anxiety. The expression of BDNF is regulated by epigenetic and genetic profiles. Thus, we investigated the association between BDNF methylation status and PSA at 2 weeks and 1 year after stroke while accounting for interactions with the BDNF Val66Met polymorphism. METHODS: The baseline sample comprised 286 patients who were assessed at 2 weeks after stroke; of these patients, 222 (78%) were followed up with at 1 year after stroke. The presence of PSA was determined using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), and the effects of BDNF methylation status and polymorphisms on PSA status were assessed with multivariate logistic regression models. RESULTS: The prevalence of PSA was slightly lower (27 [9.4%]) at baseline, and 35 (15.8%) patients were identified as having PSA at the 1-year follow-up. Stroke patients with a higher average methylation status were more likely to have PSA at 1 year. The BDNF Val66Met polymorphism was not independently associated with PSA during either the acute or chronic phase after stroke, but there was a significant interactive effect between BDNF methylation and genotype on PSA at 2 weeks. CONCLUSIONS: In this study, BDNF methylation in combination with the met/met BDNF polymorphism (Val66Met polymorphism) was associated with PSA. These findings may help identify patients at higher risk for PSA.

Associations of white matter hyperintensities with poststroke depression: A 1-year longitudinal study.

BACKGROUND: Depression is common in stroke survivors and may lead to a poor prognosis and more severe functional impairment. Although subcortical white matter hyperintensities (WMHs) are associated with late-life depression, few studies have examined the association between depression and WMHs after a stroke. We investigated the associations of periventricular (PVWMH) and deep (DWMH) WMHs with poststroke depression (PSD) at two time points after stroke. METHODS: A total of 408 patients were evaluated 2 weeks after stroke (baseline), and of those, 284 (70%) were followed up 1 year later. Magnetic resonance images were obtained in all subjects at baseline. PVWMHs and DWMHs were rated using the four-point modified Fazekas scale and categorized as mild (grades 0 and 1) or severe (grades 2 and 3). Depression was diagnosed according to DSM-IV criteria, and subjects were divided into without PSD, any PSD, and major PSD groups at baseline, and follow-up examinations were conducted according to the severity of depression. Associations of PSD with PVWMHs and DWMHs were assessed using multivariate logistic regression analyses after adjusting for various demographic and clinical characteristics. RESULTS: The adjusted analyses revealed that severe PVWMHs were significantly associated with any PSD at baseline and severe DWMHs were significantly associated with major PSD at follow-up. CONCLUSION: The association between WMH and PSD varies according to type of WMH, and time after stroke, such that early depressive symptoms are associated with PVWMHs, and delayed severe depression is associated with DWMHs.

Social support deficit and depression treatment outcomes in patients with acute coronary syndrome: Findings from the EsDEPACS study.

OBJECTIVES: This study aimed to investigate whether social support deficit has moderating effects on depressive and cardiac outcomes in an antidepressant trial for depressed patients with acute coronary syndrome as a secondary analysis using Escitalopram for DEPression in acute coronary syndrome study (ClinicalTrial.gov registry number: NCT00419471). METHODS: In total, 217 acute coronary syndrome patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition depressive disorders were randomized into two groups that received escitalopram (N = 108) or placebo (N = 109) for 24 weeks. Social support deficit was evaluated by validated scales at study entry. Depressive outcomes were measured using the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the Beck Depression Inventory. Cardiac outcomes included echocardiography (left ventricular ejection fraction and wall motion scores), electrocardiography (heart rate, PR interval, QRS duration, and QTc duration), and laboratory test results (troponin I and creatine kinase-MB). RESULTS: A higher social support deficit at baseline was significantly associated with less improvement in Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, Beck Depression Inventory scores, and serum troponin I levels after adjustment for corresponding baseline scores, covariates associated with social support deficit at baseline, and treatment status. The strength of these associations was more prominent in the placebo group compared to the escitalopram group. CONCLUSIONS: Evaluation of social support deficit in depressed acute coronary syndrome is important, and particularly during the acute phase, depressed acute coronary syndrome patients with social support deficit should be treated more carefully to improve treatment outcomes, given that social support deficit was predictive of poorer depressive and cardiac outcomes during the 24-week treatment period. Acute coronary syndrome patients with social support deficit should be treated more carefully to improve treatment outcomes.

High sensitive and broad-range detection of cortisol in human saliva using a trap lateral flow immunoassay (trapLFI) sensor.

Cortisol, a steroid hormone, is a main biomarker of psychological stress. Early diagnosis and proper treatment of such stress is crucial to prevent the excessive secretion of cortisol. However, cortisol has a low molecular weight and cannot provide sufficient recognition sites for sandwich immunoreaction; it has previously been measured using a competitive immunoassay instead of a general sandwich immunoassay. The disadvantage of this approach is that quantitative measurements are limited because of the narrow measurable range that is key for biosensors. To overcome this limitation, we propose a new detection platform that enables small molecules such as cortisol to be quantified with high detection sensitivity. A trap lateral flow immunoassay (trapLFI) sensor has deletion and detection zones instead of the test and control zones in general lateral flow immunoassay (LFI) sensors. The conjugates used to minimize possible detection targets at low concentration are gold nanoparticles that include an antibody against cortisol and an enzyme for signal generation. Target-bound conjugates are captured in the detection zone, whereas conjugates not binding with targets are trapped in the deletion zone. Using this platform, enzyme-catalyzed color signals increase in the detection zone and decrease in the deletion zone with the concentration of cortisol. The ratio of signal from deletion zone and detection zone supplied a wide analytical range (0.01-100 ng mL-1) with high detection sensitivity (9.9 pg mL-1). Analysis of 15 human saliva samples showed a good correlation with conventional ELISA results (R2 = 0.9432).

The Impact of Tumor Necrosis Factor-α and Interleukin-1ß Levels and Polymorphisms on Long-Term Stroke Outcomes.

BACKGROUND: The accuracy of predictions regarding disability that sets in after stroke could be improved by using blood biomarker measurements. This study aimed to investigate the roles of serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß concentrations and polymorphisms in stroke outcomes. METHODS: In total, 286 patients were evaluated at the time of admission and at 2 weeks after stroke, and 222 of these patients (78%) were followed up for 1 year to evaluate the consequences of stroke during both the acute and chronic stages. Stroke outcomes were dichotomized into good and poor using the modified Rankin Scale. RESULTS: The association of TNF-α and IL-1ß concentrations and their corresponding genotypes with stroke outcomes was investigated using multivariate logistic regression. Higher TNF-α levels were associated with poor outcomes 1 year after stroke in the presence of the -850T and -308A alleles, and IL-1ß levels were associated with poor 1-year stroke outcomes in the presence of the -511T and +3953T alleles. No such associations were found at 2 weeks after stroke. CONCLUSIONS: These data provide evidence that serum TNF-α and IL-1ß concentrations are related to poor long-term outcomes after stroke in the presence of particular alleles.

Analysis of Design and Fabrication Parameters for Lensed Optical Fibers as Pertinent Probes for Sensing and Imaging.

A method for adjusting the working distance and spot size of a fiber probe while suppressing or enhancing the back-coupling to the lead-in fiber is presented. As the optical fiber probe, a lensed optical fiber (LOF) was made by splicing a short piece of coreless silica fiber (CSF) on a single-mode fiber and forming a lens at the end of the CSF. By controlling the length of the CSF and the radius of lens curvature, the optical properties of the LOF were adjusted. The evolution of the beam in the LOF was analyzed by using the Gaussian ABCD matrix method. To confirm the idea experimentally, 17 LOF samples were fabricated and analyzed theoretically and also experimentally. The results show that it is feasible in designing the LOF to be more suitable for specific or dedicated applications. Applications in physical sensing and biomedical imaging fields are expected.

Effect of Escitalopram vs Placebo Treatment for Depression on Long-term Cardiac Outcomes in Patients With Acute Coronary Syndrome: A Randomized Clinical Trial.

Importance: Depression has been associated with poorer medical outcomes in acute coronary syndrome (ACS), but there are few data on the effects of antidepressant treatment on long-term prognosis. Objective: To investigate the effect on long-term major adverse cardiac events (MACE) of escitalopram treatment of depression in patients with recent ACS. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted among 300 patients with recent ACS and depression enrolled from May 2007 to March 2013, with follow-up completed in June 2017, at Chonnam National University Hospital, Gwangju, South Korea. Interventions: Patients were randomly assigned to receive either escitalopram in flexible dosages of 5, 10, 15, or 20 mg/d (n = 149) or matched placebo (n = 151) for 24 weeks. Main Outcomes and Measures: The primary outcome was MACE, a composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI). Four secondary outcomes were the individual MACE components of all-cause mortality, cardiac death, MI, and PCI. Cox proportional hazards models were used to compare the escitalopram and placebo groups by time to first MACE. Results: Among 300 randomized patients (mean age, 60 years; 119 women [39.3%]), 100% completed a median of 8.1 (interquartile range, 7.5-9.0) years of follow-up. MACE occurred in 61 patients (40.9%) receiving escitalopram and in 81 (53.6%) receiving placebo (hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03). Comparing individual MACE outcomes between the escitalopram and placebo groups, respectively, incidences for all-cause mortality were 20.8% vs 24.5% (HR, 0.82; 95% CI, 0.51-1.33; P = .43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% CI, 0.41-1.52; P = .48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% CI, 0.27-0.96; P = .04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% CI, 0.33-1.04; P = .07). Conclusions and Relevance: Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT00419471.