Survey on caregiver competency and retraining needs.

OBJECTIVES: This study investigated caregivers' job image, abilities, and educational needs, which are rapidly increasing owing to an aging society. DESIGN: A self-administered written survey was conducted at 12 general hospitals in Korea from February 1, 2022 to March 15, 2023. SAMPLE: A total of 451 caregivers participated in the survey as subjects of analysis, and 560 nurses participated as external observers. MEASUREMENTS: The caregivers' self-assessment results regarding job performance, educational needs, and retraining needs were compared with those of external observers. RESULTS: Caregivers evaluated themselves significantly higher in all areas of job performance compared to the evaluations of external observers. In particular, the caregivers' self-evaluation of their abilities in "Recording and Reporting," "Basic Resuscitation," "Safety and Infection Control," and "Understanding Major Illnesses" was different from the evaluation of nurses. Both the caregivers and external observers agreed on the need for caregiver retraining, with 1-2 hours of supplementary training every 12 months being the most preferred amount of retraining. CONCLUSIONS: There was a significant difference between caregivers' self-evaluations of their capabilities and the external observers' evaluations. Therefore, systematic professional caregiver retraining is necessary.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-ß (Aß) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. Methods: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aß42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Results: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aß42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. Conclusion: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aß-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

Lumbar Extensor Muscle Strength and Physical Performance in Community-Dwelling Older Adults: Findings From SarcoSpine Cohort.

BACKGROUND: The lumbar extensor muscles (LEMs) play an important role in body posture and physical function in older adults. Because lumbar extensor strength decreases more rapidly than limb muscle strength with age, it should be evaluated to aid healthy aging. This study investigated the association between LEM strength and physical performance in community-dwelling older adults. METHODS: This prospective observational cohort study of spinal sarcopenia (SarcoSpine) was conducted at a single center. One hundred and ten consecutive individuals who completed the baseline survey, including conventional sarcopenic indices, lumbar spine three-dimensional magnetic resonance imaging, isokinetic lumbar extensor strength, and physical performance tests (Short Physical Performance Battery, Berg Balance Scale, and Back Performance Scale [BPS]), were enrolled. A multivariate linear regression analysis was performed to determine the variables for evaluating their association with LEM strength. RESULTS: Among the conventional sarcopenic indices, gait speed was significantly correlated with Short Physical Performance Battery results and Berg Balance Scale score in men and women. Handgrip strength was significantly correlated with the BPS score for both sexes. In the multivariable linear regression, age (ß = -2.12, p < .01) and BPS score (ß = -3.54, p = .01, R2 = .29) were independent indicators of LEM strength. CONCLUSIONS: Our findings reveal the substantial association between LEM strength and BPS score in older women. The targeted intervention aimed at improving the LEMs strength would be needed to enhance physical performance in the aging population.

Allergy Wheal and Erythema Segmentation Using Attention U-Net.

The skin prick test (SPT) is a key tool for identifying sensitized allergens associated with immunoglobulin E-mediated allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, urticaria, angioedema, and anaphylaxis. However, the SPT is labor-intensive and time-consuming due to the necessity of measuring the sizes of the erythema and wheals induced by allergens on the skin. In this study, we used an image preprocessing method and a deep learning model to segment wheals and erythema in SPT images captured by a smartphone camera. Subsequently, we assessed the deep learning model's performance by comparing the results with ground-truth data. Using contrast-limited adaptive histogram equalization (CLAHE), an image preprocessing technique designed to enhance image contrast, we augmented the chromatic contrast in 46 SPT images from 33 participants. We established a deep learning model for wheal and erythema segmentation using 144 and 150 training datasets, respectively. The wheal segmentation model achieved an accuracy of 0.9985, a sensitivity of 0.5621, a specificity of 0.9995, and a Dice similarity coefficient of 0.7079, whereas the erythema segmentation model achieved an accuracy of 0.9660, a sensitivity of 0.5787, a specificity of 0.97977, and a Dice similarity coefficient of 0.6636. The use of image preprocessing and deep learning technology in SPT is expected to have a significant positive impact on medical practice by ensuring the accurate segmentation of wheals and erythema, producing consistent evaluation results, and simplifying diagnostic processes.

Discovery of novel disease-causing mutation in SSBP1 and its correction using adenine base editor to improve mitochondrial function.

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.Arg91Gln) in single-stranded DNA-binding protein 1 (SSBP1), a crucial protein involved in mtDNA replisome. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy. This mutation impeded multimer formation and DNA-binding affinity, leading to reduced efficiency of mtDNA replication, altered mitochondria dynamics, and compromised mitochondrial function. To correct this mutation, we tested two adenine base editor (ABE) variants on patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), showed higher editing efficacy (≤30%) and enhanced mitochondrial replication and function, despite off-target editing frequencies; however, risks from bystander editing were limited due to silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (≤10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. Taken together, base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated with SSBP1 mutations.

The Visual Scene Network and Hippocampus Represent Spatial Boundary Structures for Temporal Episodic Memory Organization.

Crossing a spatial boundary such as a doorway plays an important role in the temporal organization of episodic memory. However, despite the wealth of evidence showing that visual boundary structures in scenes affect our representation of space, no studies have tested the possibility that they also function as event boundaries even without active navigation. In this study, we used a nonnavigational scene-based memory task that required participants to remember a sequence of objects moving to various baskets in a scene. In the boundary condition, there was a freestanding boundary in the middle of the room, low enough to see the rest of the room beyond it. We found that the additional boundary within the scene was sufficient to trigger a larger response in the cortical visual scene network, the hippocampus, and their coordinated activity. These results suggest that active navigation across a spatial boundary such as a doorway into another room is not necessary to form an event boundary and that a visual representation of boundaries is sufficient to influence the organization of a hippocampal episodic memory.

Clinical effects of a home care program for patients with peritoneal dialysis in a tertiary care hospital.

Background: Digital health technologies have been rapidly adopted during the coronavirus disease 2019 pandemic. In Korea, a home care program, including face-to-face educational consultation and remote patient monitoring, was initiated to improve patients' quality of life. This study focused on patients with end-stage renal disease undergoing peritoneal dialysis to verify the long-term clinical effectiveness of this home care program. Methods: This retrospective cohort study was designed as a pre-post study to analyze the clinical impact of a home care program for patients undergoing peritoneal dialysis in a single tertiary care hospital. A total of 186 patients were selected from June 2017 to May 2022 to identify clinical changes after program implementation by analyzing changes in peritonitis incidence and laboratory test results. Interrupted time series analyses with ordinary least squares linear regression and chi-square tests were used. Results: At baseline, the incidence of peritonitis continuously increased by 0.480 cases per 1,000 patient-months (p = 0.02). After program initiation, the trend significantly decreased by 0.886 cases per 1,000 patient-months (p = 0.02). In addition, the proportion of individuals reaching the clinical target range had increased calcium levels (4.9%p, p = 0.003), stable hemoglobin (1.2%p, p = 0.477), phosphorus (2.8%p, p = 0.09), potassium (-1.6%p, p = 0.22), while parathyroid hormone levels decreased (-6.6%p, p = 0.005). Conclusion: With a reduction in peritonitis incidence and overall improvement in laboratory test results, our study suggests that conducting a home care program for patients undergoing peritoneal dialysis is clinically effective.

Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease.

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

Malnutrition is associated with mortality in Sjögren's syndrome-associated interstitial lung disease.

The role of nutritional status as a prognostic factor in patients with Sjögren's syndrome-associated interstitial lung disease (SjS-ILD) is currently unclear. This study aimed to predict the prognosis of patients with SjS-ILD through their nutritional status assessment. In this retrospective observational study, nutritional status was evaluated at the time of diagnosis using body mass index (BMI) and nutritional markers such as controlling nutritional status (CONUT), the Glasgow prognostic score (GPS), and prognostic nutrition index (PNI) for all participants. Receiver operating characteristic (ROC) analyses were performed using BMI and each nutritional marker data to compare the area under the ROC curve (AUC) and find the cutoff value using the maximum Youden index. Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to predict the prognosis of SjS-ILD patients. A total of 112 SjS-ILD patients were enrolled in the study, and 8.9% died during the follow-up period. The median time from diagnosis to follow-up period was 4.2 years. The AUC for PNI was the highest among nutritional markers and BMI, and PNI cutoff value was used to distinguish between the PNI < 47.7 and PNI ≥ 47.7 groups. A statistical difference was observed in the Kaplan-Meier analysis and log-rank test (p = 0.005). In multivariable analyses, PNI < 47.7 (hazard ratio 9.40, 95% confidence interval 1.54-57.21) is associated with increased mortality, suggesting the importance of early nutritional intervention for malnutrition in SjS-ILD patients.

Understanding the metabolism of infants using whole-body metabolic models.

A whole-body model is a computational representation of sex-specific and organ-resolved whole-body metabolism. In this issue of Cell Metabolism, Zaunseder et al. report whole-body models of infants that represent metabolic, physiological, energetic, and nutritional features, accurately simulating the growth of infants and providing foundations for personalized medicine for infants.

Demographic Representation of Generative Artificial Intelligence Images of Physicians.

This cross-sectional study compares the race and ethnicity and gender of images of physicians generated by artificial intelligence (AI) with US physician demographic characteristics.

Immunostimulatory activity of the aqueous extract from the leaves of Sambucus racemosa subsp. pendula through TLR4­dependent JNK activation in RAW264.7 cells.

Sambucus racemosa subsp. pendula (SRP) is an endemic plant of Korea, exclusively found on Ulleungdo Island. SRP is widely used as both a traditional medicine and food source. However, there is a lack of research on the pharmacological activities of SRP. Therefore, the present study aimed to explore the potential use of SRP leaves (SRPL) as a natural immunostimulant by analyzing its macrophage activation properties and the underlying mechanisms of action. Among the various extraction conditions, SRPL (AE20-SRPL) extracted with 100% distilled water at 20˚C induced the highest nitric oxide (NO) production in RAW264.7 cells. Thus, the further studies were performed using AE20-SRPL. AE20-SRPL increased the production of immunostimulatory factors such as NO, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1ß and TNF-α and phagocytosis in a dose-dependent manner in RAW264.7 cells without exhibiting cytotoxicity. Among Toll-like receptor (TLR)2 and TLR4, inhibition of TLR4 significantly reduced AE20-SRPL-mediated increases in the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. Furthermore, in RAW264.7 cells, inhibition of JNK, one of the components of MAPK signaling along with ERK1/2 and p38, attenuated the AE20-SRPL-mediated increases in the production of immunostimulatory factors and phagocytosis. Additionally, AE20-SRPL induced the phosphorylation of JNK and inhibition of TLR4 reduced AE20-SRPL-mediated JNK phosphorylation. These results suggested that AE20-SRPL may enhance the production of immunostimulatory factors and phagocytosis through TLR4-dependent activation of JNK in macrophages. Although the present study is limited to in vitro research using a cell model, AE20-SRPL demonstrated potential as a natural material capable of inducing macrophage activation for immune enhancement.

Comparison of Midterm Outcomes between All-Inside Arthroscopic and Open Modified Broström Procedures as Treatment for Chronic Ankle Instability.

Background: Although the all-inside arthroscopic modified Broström operation (AMBO) and open modified Broström operation (OMBO) for chronic lateral ankle instability (CLAI) showed favorable outcomes up to 1-year short-term follow-up, concerns about the long-term stability of AMBO are still present. Therefore, we aimed to compare midterm outcomes between the 2 methods by extending the observation period. Methods: Fifty-four patients undergoing ankle surgery between August 2013 and July 2017 were included in the AMBO (n = 37) and OMBO (n = 17) groups. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale and a visual analog scale (VAS) were used to evaluate the clinical outcomes. Anterior drawer test and talar tilt angle were used to evaluate the radiological outcomes. The mean follow-up duration was 59.69 months. Results: The 2 groups both showed improved clinical and radiological results statistically. In addition, they did not differ in age, sex, or preoperative AOFAS ankle-hindfoot scale score, VAS score, anterior drawer test, or talar tilt angle. No significant difference in the final follow-up postoperative clinical scores or radiological outcomes was observed. Conclusions: AMBO and OMBO as treatments for CLAI did not yield differing clinical or radiological outcomes at a mean follow-up time point of 59.69 months.

Midterm Results after Tibiotalar or Tibiotalocalcaneal Fusion Using an Ilizarov External Fixator.

Background: Ankle fusion is considered a treatment of choice for end-stage ankle arthritis when a total ankle replacement procedure is not indicated. However, the potential risk of secondary arthritis in the adjacent joint after ankle fusion raises arguments on whether preserving the adjacent joint during an isolated tibiotalar (TT) fusion brings about any future benefits with regard to pain and gait discomfort. In this study, we intended to present midterm results following TT or tibiotalocalcaneal (TTC) fusion using an Ilizarov external fixator and to investigate whether spontaneous fusion occurred in the subtalar or midtarsal joint. Methods: This is a retrospective observational study. Medical records of patients who underwent TT or TTC fusion using an Ilizarov external fixator for substantial bone defects around the ankle joint between 1994 and 2018 were manually searched. Forty-one patients were included and the status of the joints adjacent to the fusion site was evaluated in radiographic examinations. Results: Of the 34 patients who underwent TT fusion, 30 patients (88.3%) had a spontaneous fusion in the adjacent joints. Specifically, 11 patients (29.4%) had subtalar joint fusion and 19 patients (55.9%) had both midtarsal joint and subtalar joint fusion. In TTC fusion, the midtarsal joint was spontaneously fused in all 7 patients. Conclusions: In this study, we observed spontaneous adjacent joint fusion following TT or TTC fusion using an Ilizarov external fixator for substantial bone defects around the ankle joint. Although a careful approach should be made since patients treated in this study may not represent typical candidates that need primary joint-sacrificing procedures, we believe that this study may draw attention from surgeons concerned about the fate of the adjacent joint status after TT or TTC fusion.

Can Pre-Transplant Psychometric Testing Predict Tacrolimus Intrapatient Variability After Living Kidney Transplantation?

OBJECTIVE: Tacrolimus intrapatient variability (Tac IPV) has been considered a marker for post-graft risk. We investigated pre-transplant psychometric testing to predict Tac IPV after living kidney transplantation. METHODS: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) examined during pre-transplant evaluation by 102 recipients were analyzed. Subjects were divided into two groups, low IPV (L-IPV) and high IPV (H-IPV), by cutoffs of Tac IPV: median of 24 and value of 30. T-scores of MMPI-2 scales were used to analyze difference between L-IPV and H-IPV using independent t-tests. Stepwise multiple logistic regression was used to test whether MMPI-2 scales affected Tac IPV. Confusion matrix of logistic regression was used to explain statistical power. Cutoff values of significant scales for H-IPV were analyzed by constructing receiver operating characteristic curves. RESULTS: Hysteria (Hy) and depression (D) scale scores and Tac IPV were associated in IPV 24 (odds ratio [OR]: 1.08, p<0.01 for Hy; OR: 0.93, p<0.01 for D) and IPV 30 models (OR: 1.09, p<0.01 for Hy; OR: 0.92, p<0.01 for D). Paranoia (Pa) scale scores were associated with Tac IPV in IPV 24 model (OR=1.10, p<0.01) and were significantly higher in H-IPV 24 (p<0.01). F1 scores of confusion matrix in IPV 24 and 30 models were 0.70 and 0.71, respectively. Cutoffs of Hy, D, and Pa scales were 51, 57, and 47, respectively. CONCLUSION: MMPI-2 profile is suggested as a predictor for high Tac IPV after living kidney transplantation.

Public Perception Towards Drug Abuse in South Korea: The Effects of Overconfidence and Affirmation.

OBJECTIVE: The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse. METHODS: Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse. RESULTS: In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569). CONCLUSION: The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

Effectiveness of the Korean-Patient Placement Criteria for Alcohol Use Disorders: A Prospective Exploratory Study.

OBJECTIVE: Various patient placement criteria (PPC) have been developed to address alcohol use disorder (AUD), which has a high relapse rate and imposes substantial socioeconomic costs. Although research has shown PPC to be an effective tool, evidence supporting the Korean-PPC (K-PPC) is insufficient. This paper investigated whether treatment matching with the K-PPC was effective, based on variables related to AUD. METHODS: In total, 524 participants were evaluated using the 6 dimensions of the K-PPC and levels of care (LoC) were recommended based on the results. Participants whose treatment matched with the recommended LoC were classified into the matched group, and those whose treatment did not match were classified into the mismatched group. Subsequently, treatment was planned according to the determined LoC, and a total of 3 follow-up evaluations were conducted at 1 month, 3 months, and 6 months. RESULTS: There was no significant difference in the follow-up rate between the K-PPC matched group and the mismatched group. Of the variables measured by the 6 dimensions of the K-PPC, alcohol-related variables, depression, insight, and biomedical outcomes showed the most significant results (especially alcohol-related variables) from the baseline evaluation to the 6-month follow-up. In addition, the average adherence to the treatment program in the 6-month period was found to be higher in the matched group than in the mismatched group. CONCLUSION: The K-PPC could be effective for placing patients and providing treatment by matching patient characteristics. Enhancing treatment program retention can also have a positive effect on clinical outcomes.

Drug-Coated Balloon Angioplasty in Patients Undergoing Complex Percutaneous Coronary Intervention.

Background: There are limited clinical data on drug-coated balloon (DCB)-based percutaneous coronary intervention (PCI) compared with drug-eluting stent (DES)-only PCI in patients with complex coronary artery lesions. Objectives: The goal of the current study was to investigate the efficacy of DCB in patients undergoing PCI for complex coronary artery lesions. Methods: From an institutional registry of patients with de novo complex coronary artery lesions, 126 patients treated with DCB-based PCI were compared with 234 propensity score-matched patients treated with DES-only PCI. Complex coronary artery lesions were defined as the presence of at least 1 of the following: bifurcation, chronic total occlusion, unprotected left main disease, long lesion ≥38 mm, multivessel disease, lesion requiring ≥3 devices, or severe calcification. The primary endpoint was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Results: Baseline characteristics were comparable between the 2 groups. DCB-based PCI showed a comparable risk of TVF vs DES-based PCI (7.6% vs 8.1%; HR: 0.81; 95% CI: 0.33-1.99; P = 0.638). The risks of cardiac death (5.0% vs 5.7%; HR: 0.78; 95% CI: 0.24-2.49), target vessel-related myocardial infarction (0.9% vs 1.3%; HR: 2.65; 95% CI: 0.26-27.06), and target vessel revascularization (3.5% vs 2.0%; HR: 1.30; 95% CI: 0.30-5.67) were also comparable between the 2 groups. Conclusions: DCB-based PCI showed comparable risks of TVF vs those of DES-only PCI in patients with complex coronary artery lesions. DCB might be considered as a suitable alternative device to DES in patients undergoing complex PCI. (Long-term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815).