Presentation_1_Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study.pdf

ObjectivesThis study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries.MethodsPatients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group.ResultsEarly-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up.ConclusionDistinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.</p

Table_1_Modifying effect of the serum level of brain-derived neurotrophic factor (BDNF) on the association between BDNF methylation and long-term cardiovascular outcomes in patients with acute coronary syndrome.DOCX

IntroductionThis study investigated the potential modifying effects of the serum brain-derived neurotrophic factor (sBDNF) level on the association between BDNF methylation status and long-term cardiovascular outcomes in acute coronary syndrome (ACS) patients.MethodsFrom 2006 to 2012, hospitalized ACS patients were consecutively recruited. The sBDNF level and BDNF methylation status were assessed at baseline in 969 patients who were followed up for major adverse cardiac events (MACEs) over 5–12 years, until 2017 or death. Cox proportional hazards models were utilized to compare the time to first composite or individual MACEs between individuals with lower and those with higher average BDNF methylation levels in the low and high sBDNF groups, respectively. The modifying effects of the sBDNF and average BDNF methylation levels on first composite and individual MACEs were analyzed using Cox proportional hazards models after adjusting for potential covariates.ResultsIn the low sBDNF group, a higher average BDNF methylation level was linked to an increase in composite MACEs independent of confounding variables, but not in the high sBDNF group [HR (95 percent CI) = 1.04 (0.76–1.44)]. The interaction effect between the sBDNF and average BDNF methylation levels on composite MACEs was significant after adjusting for covariates (P = 0.008).ConclusionCombining the BDNF methylation status and sBDNF levels may help identify ACS patients who are likely to have unfavorable clinical outcomes.</p

Data_Sheet_1_Serotonin modifies the impact of sleep disturbance on suicidality in patients with acute coronary syndrome.DOCX

BackgroundThis study investigated the associations of sleep disturbance and serum serotonin levels with suicidal ideation, and evaluated the potential modifying effects of serotonin on these associations in patients with the acute coronary syndrome (ACS).MethodsIn total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of sleep disturbance (using the Leeds Sleep Evaluation Questionnaire), serum serotonin levels, and suicidal ideation (using the “suicidal thoughts” item of the Montgomery–Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of suicidal ideation. Logistic regression analysis was performed with adjustment for covariates.ResultsSleep disturbance was significantly associated with suicidal ideation at baseline and follow-up. Serum serotonin showed no such association but modified the association of sleep disturbance with suicidal ideation such that it was significant only in the lower serum serotonin group, with significant interaction terms obtained after adjustment for relevant covariates.ConclusionEvaluating sleep disturbance and serum serotonin levels could improve the accuracy of clinical predictions of suicidal ideation in the acute and chronic phases of ACS.</p

Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus

<div><p>Background</p><p>Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in <i>Orientia tsutsugamushi</i> infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels.</p><p>Methodology/Principal Findings</p><p>Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression.</p><p>Conclusions</p><p>This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.</p></div

Regression coefficients of MAIT cell percentages with respect to clinical and laboratory parameters in scrub typhus patients.

<p>Regression coefficients of MAIT cell percentages with respect to clinical and laboratory parameters in scrub typhus patients.</p

Expression of CD69 and PD-1 and apoptosis of MAIT cells after stimulation with IL-12 and IL-18.

<p>PBMCs (1 × 10⁶/well) were incubated for 24 hours in the presence of IL-12 (50 ng/mL) and IL-18 (50 ng/mL), and then stained with FITC-conjugated anti-CD3, FITC-conjugated annexin V, APC-conjugated anti-TCR Vα7.2, PE-conjugated anti-CD3, PE-conjugated anti-CD69, PE-conjugated anti-PD-1 and PE-Cy5-conjugated anti-CD161 monoclonal antibodies. Percentages of CD69-expressing cells (<u>panel A</u>), annexin V-positive cells (<u>panel C</u>), and PD-1-expressing cells (<u>panel E</u>) among MAIT cells were determined by flow cytometry. Data in <u>panels B, D and F</u> were obtained from 6 HCs. Values are expressed as the mean ± SEM. *p < 0.005 by paired t test.</p

Changes in MAIT cell levels and functions in scrub typhus patients.

<p>The percentages of MAIT cells (<u>panel A</u>) in the peripheral blood of 18 scrub typhus patients during active disease and remission were determined by flow cytometry. TNF-α expression (<u>panel B</u>) in the MAIT cell population after stimulation with PMA and IM was determined by intracellular flow cytometry. Data in <u>panel B</u> were obtained from 11 patients with scrub typhus. Symbols represent individual subjects. *p < 0.05 by the Wilcoxon matched-pairs signed rank test.</p

Clinical and laboratory characteristics of 38 scrub typhus patients.

<p>Clinical and laboratory characteristics of 38 scrub typhus patients.</p

Decreased circulating MAIT cell numbers in the peripheral blood of scrub typhus patients.

<p>Freshly isolated PBMCs from 53 HCs and 38 patients with scrub typhus were stained with APC-Alexa Fluor 750-conjugated anti-CD3, FITC-conjugated anti-TCR γδ, APC-conjugated anti-TCR Vα7.2 and PE-Cy5-conjugated anti-CD161 mAbs, and then analyzed by flow cytometry. Percentages of MAIT cells were calculated using a αβ T cell gate. <u>Panel A</u>: Representative MAIT cell percentages as determined by flow cytometry. <u>Panel B</u>: MAIT cell percentages among peripheral blood αβ T cells. <u>Panel C</u>: Absolute MAIT cell numbers (per microliter of blood). Symbols represent individual subjects and horizontal lines are median values. *p < 0.05, **p < 0.001 by the Mann-Whitney U test.</p

Expression of IFN-γ, IL-17 and TNF-α in MAIT cells from scrub typhus patients.

<p>Freshly isolated PBMCs (1 × 10⁶/well) were incubated for 4 hours in the presence of PMA (100 ng/ml) and IM (1 μM). Panel A: Representative IFN-γ, IL-17 and TNF-α expression in the MAIT cell population were determined by intracellular flow cytometry after stimulation with PMA and IM. Data in <u>panel B</u> were obtained from 14 HCs and 23 patients with scrub typhus. Symbols represent individual subjects and horizontal lines are median values. *p < 0.05 by the Mann-Whitney U test.</p