Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

Genomic analysis uncovers that cold-inducible RNA binding protein is associated with estrogen receptor in breast cancer.

BACKGROUND: RNA-binding proteins (RBPs) perform various biological functions in humans and are associated with several diseases, including cancer. Therefore, RBPs have emerged as novel therapeutic targets. Although recent investigations have shown that RBPs have crucial functions in breast cancer (BC), detailed research is underway to determine the RBPs that are closely related to cancers. OBJECTIVE: To provide an insight into estrogen receptor (ER) regulation by cold-inducible RNA binding protein (CIRBP) as a novel therapeutic target. RESULTS: By analyzing the genomic data, we identified a potential RBP in BC. We found that CIRBP is highly correlated with ER function and influences clinical outcomes, such as patient survival and endocrine therapy responsiveness. In addition, CIRBP influences the proliferation of BC cells by directly binding to ER-RNA. CONCLUSION: Our results suggest that CIRBP is a novel upstream regulator of ER and that the interplay between CIRBP and ER may be associated with the clinical relevance of BC.

Health-related quality of life instrument with 8 items to measure health-related quality of life among family caregivers of people with dementia: A pilot validation study.

BACKGROUND: The health-related quality of life instrument with 8 items (HINT-8) was developed to measure health-related quality of life (HRQoL) in Korea. However, the HINT-8 has not yet been validated among the family caregivers of people with dementia (PwD). DESIGN: A cross-sectional pilot study. OBJECTIVE: The study aimed to examine the convergent and discriminant validity of the HINT-8 among family caregivers of individuals with dementia. SAMPLE: Forty-seven family caregivers of PwD. MEASUREMENTS: HINT-8 was compared with the 5-level EQ-5D (EQ-5D-5L) to assess its convergent and discriminant validity. Additionally, the association between the two instruments assessing HRQoL was examined using the short-form Bédard-Zarit Burden Interview (SZBI). RESULTS: The HINT-8 was a promising and valid HRQoL instrument for family caregivers of PwD. There was a significantly high correlation between the overall HINT-8 and EQ-5D-5L indices (r = 0.85, p < .001). The HINT-8 had acceptable psychometric properties compared to the commonly used EQ-5D-5L, as indicated by the subdomains associated with family caregivers' burden measured by the SZBI. CONCLUSION: Future studies should compare the HINT-8 with existing dementia carer-specific QoL instruments among a larger study sample to enhance its statistical power and confirm its reliability and structural validity.

Interprofessional Educational Needs for Shared Governance of Integrated Care.

Introduction: This study investigated the educational needs of integrated care among professionals in the public sector of healthcare and social care services in South Korea. Methods: A cross-sectional secondary data analysis was performed. Original data were obtained from 10 metropolitan communities with a convenience sample of 210 integrated care professionals. The Borich Needs Assessment Model and the Locus for Focus Model were used to examine the priority educational needs of each integrated care professional. Results: This study analyzed the key details of educational needs in integrated care by focusing on the competencies of integrated care approaches for person-centered care, interprofessional collaboration, and community involvement. The core educational needs of community care administrators, care coordinators, healthcare and social care providers, and community health champions, which are common to all professionals, and the specific educational needs for each type of professional were demonstrated, which contained specific content to implement integrated care. Conclusion: This study provides an opportunity to comprehensively understand the educational needs of integrated care professionals based on their competencies. They want better interprofessional cooperation through networking and collaborative strategies. The results of this study may be utilized as fundamental data by future instructors to provide evidence-based education programs.

Integrative analysis of RNA-sequencing and microarray for the identification of adverse effects of UVB exposure on human skin.

Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.

Association between prevalence and severity of chronic kidney disease and employment status: a nationwide study in Korea.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing globally, and understanding the association between CKD and employment status is crucial. This cross-sectional study aimed to investigate the association of CKD with employment and occupation type among patients with CKD. METHODS: We analyzed data from 36,732 Korean adults aged ≥ 30 years, who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2021. CKD was detected based on the estimated glomerular filtration rate, and the employment status of the participants was classified into distinct categories: full-time permanent employment, unemployment, self-employment, and precarious employment. We analyzed the data using multiple logistic regression. RESULTS: We observed a significant association between CKD and a higher likelihood of unemployment compared to that in individuals without CKD (odds ratio, 1.70; 95% confidence interval, 1.47-1.96). This association was more prominent in patients with severe CKD. In the multivariable logistic analysis, patients with CKD had a higher likelihood for precarious employment (odds ratio, 1.29; 95% confidence interval, 0.92-1.88), self-employment (odds ratio, 1.3; 95% confidence interval, 0.90-1.88), and unemployment (odds ratio, 2.10; 95% confidence interval, 1.51-2.92) compared to individuals without CKD. CONCLUSIONS: Our study demonstrated that CKD is associated with a higher likelihood of unemployment and engagement in precarious employment. These findings highlight the challenges faced by patients with CKD in obtaining stable employment and emphasize the need for interventions to improve the employment outcomes of individuals with CKD.

Association of KIR Genes with Middle East Respiratory Syndrome Coronavirus Infection in South Koreans.

BACKGROUND: Middle East respiratory syndrome (MERS) is a lower respiratory tract disease caused by a beta coronavirus (CoV) called MERS-CoV, characterized by a high mortality rate. We aimed to evaluate the association between genetic variation in killer cell immunoglobulin-like receptors (KIRs) and the risk of MERS in South Koreans. METHODS: KIR genes were genotyped by multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP). A case-control study was performed to identify the odds ratios (OR) of KIR genes for MERS and the association of KIR genes and their ligands, human leukocyte antigens (HLA) genes. RESULTS: KIR2DS4D and KIR3DP1F showed higher frequencies in the group of all patients infected with MERS-CoV than in the control group (p = 0.023, OR = 2.4; p = 0.039, OR = 2.7). KIR2DL1, KIR2DP1, and KIR3DP1D were significantly associated with moderate/mild (Mo/Mi) cases. KIR2DL2, KIR2DS1, and KIR3DP1F were affected in severe cases. When we investigated the association between KIR genes and their ligands in MERS patient and control groups, KIR3DL1+/Bw4(80I)+, KIR3DL1+/Bw6+, KIR3DL1+/Bw6-, KIR2DS1+/C2+, and KIR3DS+/Bw4(80I)+ were associated with MERS. KIR3DL1+/Bw6- was found in Mo/Mi cases. KIR2DS1+/C2+ and KIR2DS2+/C1+ were found in severe cases. CONCLUSION: Further investigations are needed to prove the various immune responses of MERS-CoV-infected cells according to variations in the KIR gene and ligand gene. A treatment strategy based on current research on the KIR gene and MERS-CoV will suggest potential treatment targets.

Development of cost-effective and fast KIR genotyping by multiplex PCR-SSP.

Killer-cell immunoglobulin-like receptors (KIR) control natural killer (NK) cell functions by recognizing HLA molecules and modulating the activity of NK cells. The KIR gene cluster contains polymorphic and highly homologous genes. Diversity of the KIR region is achieved through differences in gene content, allelic polymorphism, and gene copy number, which result in unrelated individuals having different KIR genotypes and individualized immune responses that are relevant to multiple aspects of human health and disease. Therefore, KIR genotyping is increasingly used in epidemiological studies. Here, we developed multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP) to compensate for the shortcomings of the conventional PCR-SSP method, which is most commonly used for KIR analysis. Multiplex PCR-SSP method involves six multiplex reactions that detect 16 KIR genes and distinguish variant types of some KIR genes by adding two reactions. The assay was evaluated in a blind survey using a panel of 40 reference DNA standards from the UCLA KIR Exchange Program. The results are 100% concordant with the genotype determined using Luminex-based reverse sequence-specific oligonucleotide typing systems. Additionally, we investigated the currently known 16 KIR genes and their common variants in 120 unrelated Korean individuals. The results were consistent with the KIR genotype previously reported by Hwang et al. This multiplex PCR-SSP is an efficient method for analyzing KIR genotypes in both small- and large-scale studies with minimal labor, reagents, and DNA. Furthermore, by providing a better definition of KIR polymorphisms it can contribute to developments in immunogenetics.

A multi-channel collagen conduit with aligned Schwann cells and endothelial cells for enhanced neuronal regeneration in spinal cord injury.

Traumatic spinal cord injury (SCI) leads to Wallerian degeneration and the accompanying disruption of vasculature leads to ischemia, which damages motor and sensory function. Therefore, understanding the biological environment during regeneration is essential to promote neuronal regeneration and overcome this phenomenon. The band of Büngner is a structure of an aligned Schwann cell (SC) band that guides axon elongation providing a natural recovery environment. During axon elongation, SCs promote axon elongation while migrating along neovessels (endothelial cells [ECs]). To model this, we used extrusion 3D bioprinting to develop a multi-channel conduit (MCC) using collagen for the matrix region and sacrificial alginate to make the channel. The MCC was fabricated with a structure in which SCs and ECs were longitudinally aligned to mimic the sophisticated recovering SCI conditions. Also, we produced an MCC with different numbers of channels. The aligned SCs and ECs in the 9-channel conduit (9MCC-SE) were more biocompatible and led to more proliferation than the 5-channel conduit (5MCC-SE) in vitro. Also, the 9MCC-SE resulted in a greater healing effect than the 5MCC-SE with respect to neuronal regeneration, remyelination, inflammation, and angiogenesis in vivo. The above tissue recovery results led to motor function repair. Our results show that our 9MCC-SE model represents a new therapeutic strategy for SCI.

Translation, Cultural Adaptation, and Validation of a Korean Version of the Information Needs in Cardiac Rehabilitation Scale.

OBJECTIVE: : To translate and culturally adapt the Information Needs in Cardiac Rehabilitation (INCR) questionnaire into Korean and perform psychometric validation. METHODS: : The original English version of the INCR, in which patients are asked to rate the importance of 55 topics, was translated into Korean (INCR-K) and culturally adapted. The INCR-K was tested on 101 cardiac rehabilitation (CR) participants at Kangwon National University Hospital and Seoul National University Bundang Hospital in Korea. Structural validity was assessed using principal component analysis, and Cronbach's alpha of the areas was computed. Criterion validity was assessed by comparing information needs according to CR duration and knowledge sufficiency according to receipt of education. Half of the participants were randomly selected for 1 month of re-testing to assess their responsiveness. RESULTS: : Following cognitive debriefing, the number of items was reduced to 41 and ratings were added to assess participants' sufficient knowledge of each item. The INCR-K structure comprised eight areas, each with sufficient internal consistency (Cronbach's alpha>0.7). Criterion validity was supported by significant differences in mean INCR-K scores based on CR duration and knowledge sufficiency ratings according to receipt of education (p<0.05). Information needs and knowledge sufficiency ratings increased after 1 month of CR, thus supporting responsiveness (p<0.05). CONCLUSION: : The INCR-K demonstrated adequate face, content, cross-cultural, structural, and criterion validities, internal consistency, and responsiveness. Information needs changed with CR, such that multiple assessments of information needs may be warranted as rehabilitation progresses to facilitate patient-centered education.

Caregiving burden and healthcare utilization in family caregivers of people with dementia: Long term impact of the public family caregiver intervention.

Despite community-based interventions to decrease the caregiving burden on family caregivers of people with dementia (PwD), long-term assessment of community-based public programs is lacking. Therefore, the study aims to identify the long-term effects of community-based dementia caregiver intervention on the caregiving burden and healthcare utilization among family caregivers for PwD. Additionally, we investigated the predictors of caregiving burden and healthcare utilization. Of the participants, 32 (76%) intervention and 15 (38%) control groups responded to the one-year follow-up. We assessed caregiver burden using the short-form Zarit Burden Interview (sZBI) and collected healthcare utilization data using questionnaire at baseline and 12 months. Compared with the control group, the intervention group did not experience a reduction in caregiving burden and healthcare utilization. Predictors of caregivers' perceived burden were spouses as the primary caregiver and having multiple comorbidities. The predictors identified in this study should be considered when implementing public family support programs.

FeS2-incorporated 3D PCL scaffold improves new bone formation and neovascularization in a rat calvarial defect model.

199Three-dimensional (3D) scaffolds composed of various biomaterials, including metals, ceramics, and synthetic polymers, have been widely used to regenerate bone defects. However, these materials possess clear downsides, which prevent bone regeneration. Therefore, composite scaffolds have been developed to compensate these disadvantages and achieve synergetic effects. In this study, a naturally occurring biomineral, FeS2, was incorporated in PCL scaffolds to enhance the mechanical properties, which would in turn influence the biological characteristics. The composite scaffolds consisting of different weight fractions of FeS2 were 3D printed and compared to pure PCL scaffold. The surface roughness (5.77-fold) and the compressive strength (3.38-fold) of the PCL scaffold was remarkably enhanced in a dose-dependent manner. The in vivo results showed that the group with PCL/ FeS2 scaffold implanted had increased neovascularization and bone formation (2.9-fold). These results demonstrated that the FeS2 incorporated PCL scaffold might be an effective bioimplant for bone tissue regeneration.

Distributions of 11-loci HLA alleles typed by amplicon-based next-generation sequencing in South Koreans.

The range of HLA typing for successful hematopoietic stem cell transplantation (HSCT) is gradually expanding with the next-generation sequencing (NGS)-based improvement in its quality. However, it is influenced by the allocation of finances and laboratory conditions. HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 alleles were genotyped at the 3-field level by amplicon-based NGS using MiSeqDx system and compared to our previous study employing long-range PCR and NGS using TruSight HLA v2 kit, in healthy donors from South Korea. Exon 2, exons 2/3, exons 2/3/4 or 5 of 11-loci were amplified by multiplex PCR. The sequence reads of over 53 depth counts were consistently obtained in each sample exon, depending on the target exon determined to match the reference sequence contained in the IPD-IMGT/HLA Database. HLA alleles were investigated by combinations of the determined exons. A total of 18 alleles with a frequency over 10% were found at the 11 HLA loci. Three ambiguities of HLA-A, -C, and -DRB1 were resolved. We observed a total of 26 HLA-A ~ C ~ B and 6 HLA-DRB1 ~ DQA1 ~ DQB1 ~ DPA1 ~ DPB1 haplotypes having significant linkage disequilibrium between alleles at all neighboring HLA loci. This result was compatible with the previous one, using TruSight HLA v2 kit. Advantages are simple and short progress time because one plate is used for each PCR step in one PCR machine and 11-loci HLA typing is possible even if only eight samples. These data suggested that expanded 11-loci HLA typing data by amplicon-based NGS might help perform HSCT.

Gastric CD56-negative Extranodal Natural Killer/T-cell Lymphoma: A Case Report.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common subtype of Epstein-Barr virus-associated NK/T-cell lymphomas. ENKTCL-NT occurs infrequently in the gastrointestinal tract. In particular, reports of ENKTCL-on NT arising from the stomach are extremely rare. Several clusters of differentiation (CDs) have been useful in recognizing NK-cells, T-cells, and tumor cells of NK/T-cell lymphomas. Among them, the CD56 antigen is considered the most sensitive marker for ENKTCL-NT and is expressed in almost all cases of ENKTCL-NT. Thus, the development of CD56-negative ENKTCL-NT is highly atypical. This paper reports a case of a young Asian female who presented with gastric ulcer bleeding. The patient was histologically diagnosed with ENKTCL-NT. No tumor cells for CD56 were observed, whereas no monoclonality of the T-cell receptor gamma gene rearrangement was detected in the tumor cells. The patient was scheduled for systemic chemotherapy six times and achieved complete remission. Peripheral blood-hematopoietic stem cell transplantation was performed later.

The Mediating Effect of Inflammation between the Dietary and Health-Related Behaviors and Metabolic Syndrome in Adolescence.

Chronic diseases develop via complex pathways, depending on the degree of exposure to risk factors from early in life and childhood onward. Metabolic syndrome has multiple risk factors, including genetic factors, inappropriate diet, and insufficient physical activity. This study classified health-related behavior classes in childhood and adolescents and analyzed the direct and indirect effects of each class on the metabolic risk in inflammation-mediated pathways. We identified the health-related lifestyle classes based on health-related behavior indicators in subjects aged 3-15 years who participated in the Ewha Birth and Growth Cohort Study by using a latent class analysis. A mediation analysis was performed to access the direct and indirect effects of each class on the continuous metabolic syndrome score (cMetS), with the inflammatory index used as a mediating factor. Subjects were classified into inactive and positive lifestyle classes according to their characteristics. In the inactive lifestyle class, interleukin (IL)-6 and cMetS had a significant association. The study confirmed that IL-6 exerts a significant indirect effect between inactive lifestyle and cMetS. This result supports previous studies. Since the health behaviors of children and adolescents can affect the likelihood of subsequent metabolic syndrome, appropriate health behavior interventions for this period are needed.

The HLA-B*07:457 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*07:457 differs from HLA-B*07:02:01:01 in codon 117 in exon 3.

The HLA-DRB1*12:97 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-DRB1*12:97 differs from HLA-DRB1*12:02:01:01 in codon 63 in exon 2.

Association of HLA class I and II genes with Middle East respiratory syndrome coronavirus infection in Koreans.

INTRODUCTION: Middle East Respiratory Syndrome (MERS) caused by MERS-coronavirus (CoV) is a lower respiratory tract disease characterized by a high mortality rate. MERS-CoV spread from Saudi Arabia to other countries, including South Korea. Dysfunction of the human leukocyte antigen (HLA) system has many effects due to genetic complexity and its role in the adaptive immune response. We investigated the association of HLA class I and II alleles with MERS-CoV in 32 patients with MERS. METHODS: HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 were genotyped by polymerase chain reaction sequence-based typing. RESULTS: HLA-DQB1*03:02 are significantly associated with moderate/mild cases of MERS-CoV. Other alleles are no statistical significance. CONCLUSIONS: Treatment strategies based on current research on the HLA gene and MERS-CoV will provide potential therapeutic targets.

The HLA-B*51:353 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*51:353 differs from HLA-B*51:01:01:01 in codon 95 in exon 3.

Overcome the barriers of the skin: exosome therapy.

Exosomes are nano-sized cargos with a lipid bilayer structure carrying diverse biomolecules including lipids, proteins, and nucleic acids. These small vesicles are secreted by most types of cells to communicate with each other. Since exosomes circulate through bodily fluids, they can transfer information not only to local cells but also to remote cells. Therefore, exosomes are considered potential biomarkers for various treatments. Recently, studies have shown the efficacy of exosomes in skin defects such as aging, atopic dermatitis, and wounds. Also, exosomes are being studied to be used as ingredients in commercialized skin treatment products. In this review, we discussed the need for exosomes in skin therapy together with the current challenges. Moreover, the functional roles of exosomes in terms of skin treatment and regeneration are overviewed. Finally, we highlighted the major limitations and the future perspective in exosome engineering.