Background: Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators. Methods: This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms. Results: Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017). Conclusion Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: This study aimed to assess the severity of postoperative delirium (PD) in elderly patients who underwent reverse total shoulder arthroplasty (rTSA) for irreparable massive rotator cuff tears (mRCTs) under general anesthesia (GA) compared to those under interscalene block (IB). Methods: Forty elderly patients aged 65 years or older diagnosed with an irreparable mRCT who underwent rTSA were included in the prospective case-controlled study. Of these, 20 patients were operated under GA and the other 20 under IB. The average age was 77.1 years (range, 65–95 years). The severity of delirious symptoms was evaluated by the Delirium Rating Scale–revised–98 (DRS) score from the patients or guardians before the surgery and at 0, 3, and 7 days and 1, 3, and 6 months after the surgery and compared between the 2 groups. Results: Immediately after surgery, the visual analog scale score difference between the groups was statistically significant, with the GA group at 6.25 (standard deviation, ± 0.85) and the IB group at 3.80 (± 0.62) (p < 0.001). On the day of operation, the mean DRS score in the GA and IB groups were 9.10 (± 5.63) and 6.60 (± 5.33), respectively (p = 0.157). On day 3 of surgery, the mean DRS score in the GA group peaked to 9.95 (± 8.73), while in the IB group, it declined to 6.40 (±5.81) (p = 0.138). After 3 days, DRS scores showed a decreasing trend in both groups. When comparing the mean change (∆) from the preoperative baseline scores to the postoperative values, the ∆DRS score was significantly higher with 4.15 (± 4.53) points in the GA group as compared to 1.30 (± 1.92) in the IB group (p = 0.014). Conclusions IB can be an attractive and efficient anesthetic choice in preventing PD for elderly patients undergoing rTSA for irreparable mRCTs. The IB group showed lower DRS scores and a peak on day 0 compared to the higher DRS scores and peak on day 3 in the GA group. Additionally, IB showed less pain than GA.

Background: The purpose of our study was to analyze the effects of hospital volume and region on in-hospital and long-term mortality, direct medical costs (DMCs), and length of hospital stay (LOS) in elderly patients following hip fracture, utilizing nationwide claims data. Methods: This retrospective nationwide study sourced its subjects from the Korean National Health Insurance Review and Assessment Service database spanning from January 2011 to December 2018. A generalized estimating equation model with a Poisson distribution and logarithmic link function was used to estimate adjusted odds ratios (aORs) and 95% CIs to assess the association of hospital volume with in-hospital and 1-year mortality, DMCs, and LOS . Results: A total of 172,144 patients were included. Comparing the risk of in-hospital death between high-volume and low-volume hospitals, the risk of in-hospital death was 1.2 times higher at low-volume hospitals (aOR, 1.20; 95% CI, 1.07–1.33; p = 0.002).Additionally, the risk of death at 1 year was 1.05 times higher at low-volume hospitals (aOR, 1.05; 95% CI, 1.01–1.09; p = 0.008) compared to high-volume hospitals. DMCs were 0.84 times lower at low-volume hospitals for in-hospital period (aOR, 0.84; 95% CI, 0.84–0.85; p < 0.001) and 0.87 times lower for 1 year (aOR, 0.87; 95% CI, 0.86–0.88; p < 0.001) compared to high-volume hospitals. In-hospital LOS was 1.21 times longer at low-volume hospitals (aOR, 1.21; 95% CI, 1.20–1.22; p < 0.001) than at high-volume hospitals. In addition, the risk of in-hospital death was 1.22 times higher (aOR, 1.22; 95% CI, 1.12–1.33; p < 0.001) and the risk of 1-year death was 1.07 times higher (aOR, 1.07; 95% CI, 1.04–1.10; p < 0.001) at rural hospitals compared to urban hospitals. Conclusions Clinicians should focus on improving clinical outcomes for hip fracture patients in low-volume and rural hospital settings, with a specific emphasis on reducing mortality rates.

Background: Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations. Methods: This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID. Results: Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001). Conclusion Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Background: The 16S rRNA-targeted next-generation sequencing (NGS) has been widely used as the primary tool for microbiome analysis. However, whether the sequenced microbial diversity absolutely represents the original sample composition remains unclear. This study aimed to evaluate whether 16S rRNA gene-targeted NGS accurately captures bacterial community composition. Methods: Mock communities were constructed using equal amounts of DNA from 18 bacterial strains in three formats: genomic DNA, recombinant plasmids, and polymerase chain reaction (PCR) templates. The V3V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq. Results: Data regression analysis revealed that the recombinant plasmid produced more accurate and precise correlation curve than that by the gDNA and PCR products, with a slope closest to 1 (1.0082) and the highest R² value (0.9975). Despite the same input amount of bacterial DNA, the NGS read distribution varied across all three mock communities. Using multiple regression analysis, we found that the guanine-cytosine (GC) content of the V3V4 region, 16S rRNA gene, size of gDNA, and copy number of 16S rRNA were significantly associated with the NGS output of each bacterial species. Conclusion This study demonstrated that recombinant plasmids are the preferred option for quality control and that NGS output is biased owing to certain bacterial characteristics, such as %GC content, gDNA size, and 16S rRNA gene copy number. Further research is required to develop a system that compensates for NGS process biases using mock communities.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Background: Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators. Methods: This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms. Results: Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017). Conclusion Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.