HLA-DPB1*05:01 and HLA-A*11:01 Is Associated with Adverse Drug Reactions to Isoniazid and Rifampin for Treatment of Latent Tuberculosis Infection in South Korea.

Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H-) compared to the control group (DHS-/H-) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415-59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493-21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110-92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity.

Effect of atractylenolide III on zearalenone-induced Snail1-mediated epithelial-mesenchymal transition in porcine intestinal epithelium.

BACKGROUND: The intestinal epithelium performs essential physiological functions, such as nutrient absorption, and acts as a barrier to prevent the entry of harmful substances. Mycotoxins are prevalent contaminants found in animal feed that exert harmful effects on the health of livestock. Zearalenone (ZEA) is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals. Here, we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium. RESULTS: Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin, which induced Snail1-mediated epithelial-to-mesenchymal transition (EMT). In addition, ZEA induces Snail-mediated EMT through the activation of TGF-ß signaling. The treatment of IPEC-J2 cells with atractylenolide III, which were exposed to ZEA, alleviated EMT. CONCLUSIONS: Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epithelial cells and ways to mitigate it.

Effect of Auriculotherapy on Stress: A Systematic Review and Meta-Analysis.

Background: Auriculotherapy, a form of therapy that involves stimulating specific points on the ear auricle, has garnered attention for its potential in holistic stress management in adults, aligning with broader patient-centered therapeutic approaches. Objective: The aim of this study was to evaluate the effectiveness of auriculotherapy for stress relief in adults. Methods: A comprehensive search of nine databases (PubMed, Scopus, CINAHL, Web of Science, Ovid Medline, Cochrane Library, RISS, KMbase, and KISS) was performed, yielding 553 studies. Of these, 12 were selected for meta-analysis based on the inclusion criteria, which considered demographic data, types of auriculotherapy, intervention characteristics, auricular points, and stress-related outcomes. The risk of bias was also evaluated for each selected study. Results: The meta-analysis results (n = 12) indicated that auriculotherapy was significantly superior to the control group in terms of subjective stress index, blood pressure, heart rate variability, and pulse rate, as well as improving low-frequency (LF) and high-frequency (HF) heart rate components and their ratio (LF/HF) in adults. Additionally, the subgroup analysis indicated a trend where the effect size of acupressure may be larger than that of acupuncture. Conclusions: Our findings underscore auriculotherapy's efficacy in reducing stress in adults, advocating for its integration into nursing curriculums as a viable clinical intervention for stress management. Promoting its application in clinical environments could complement holistic, patient-centric care paradigms.

Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3ß inhibitor enhances antitumor immune response against bladder cancer.

Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3ß inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder cancer.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Auricular Acupressure on Breast Pain Among Breastfeeding Mothers Receiving Gentle Hand Techniques: A Randomized, Single-Blind, Sham-Controlled Trial.

BACKGROUND: Auricular acupressure influences pain reduction in patients with diseases. However, study results on its influence on breast pain, common among breastfeeding mothers, are insufficient. RESEARCH AIM: This study aimed to explore the effectiveness of auricular acupressure on breast pain among breastfeeding mothers who also received a standard gentle hand technique. METHODS: This was a placebo-controlled study wherein auricular acupressure was provided for 4 weeks to 52 breastfeeding mothers consulting a local breastfeeding clinic. In the intervention group, auricular acupressure was applied to specific acupoints, including Shenmen, central rim, breast, and endocrine, which are related to breast pain and postpartum lactation. For the placebo control group, auricular acupressure was applied to acupoints not related to breast pain. The degree of breast pain was assessed using a numeric rating scale and a pressure algometer. RESULTS: After 4 weeks of auricular acupressure, numeric rating scale pain scores did not show a significant change. However, the pressure pain threshold for the upper left (Z = -2.202, p = .028) and upper right (t = 2.613, p = .012) areas of the right breast increased significantly in the intervention group. CONCLUSION: This study employed subjective and objective measurements to evaluate the efficacy of auricular acupressure in alleviating breast pain. The intervention shows potential as a nursing measure. Further research is required to determine the optimal intervention duration and frequency, particularly for breastfeeding parents with severe pain, and to evaluate long-term outcomes.

Human papillomavirus infection and cardiovascular mortality: a cohort study.

BACKGROUND AND AIMS: High-risk human papillomavirus (HR-HPV) infection-a well-established risk factor for cervical cancer-has associations with cardiovascular disease (CVD). However, its relationship with CVD mortality remains uncertain. This study examined the associations between HR-HPV infection and CVD mortality. METHODS: As part of a health examination, 163 250 CVD-free Korean women (mean age: 40.2 years) underwent HR-HPV screening and were tracked for up to 17 years (median: 8.6 years). National death records identified the CVD mortality cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard regression analyses. RESULTS: During 1 380 953 person-years of follow-up, 134 CVD deaths occurred, with a mortality rate of 9.1 per 105 person-years for HR-HPV(-) women and 14.9 per 105 person-years for HR-HPV(+) women. After adjustment for traditional CVD risk factors and confounders, the HRs (95% CI) for atherosclerotic CVD (ASCVD), ischaemic heart disease (IHD), and stroke mortality in women with HR-HPV infection compared with those without infection were 3.91 (1.85-8.26), 3.74 (1.53-9.14), and 5.86 (0.86-40.11), respectively. The association between HR-HPV infection and ASCVD mortality was stronger in women with obesity than in those without (P for interaction = .006), with corresponding HRs (95% CI) of 4.81 (1.55-14.93) for obese women and 2.86 (1.04-7.88) for non-obese women. CONCLUSIONS: In this cohort study of young and middle-aged Korean women, at low risks for CVD mortality, those with HR-HPV infection had higher death rates from CVD, specifically ASCVD and IHD, with a more pronounced trend in obese individuals.

The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy.

The development of first-generation immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. Although immune-checkpoint blockade therapies have shown clinical success, a substantial number of patients yet fail to benefit. Many studies are under way to discover next-generation immunotherapeutic targets. Immunoglobulin superfamily member 1 (IGSF1) is a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role for IGSF1, in immune response, remains unknown. Here, our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1low non-small cell lung cancer (NSCLC) cells as compared with PD-L1high cells. Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promoted antitumor immunity and overcame the limitations of first-generation immune-checkpoint inhibitors, likely via a distinct mechanism of action. We further demonstrated high WM-A1 efficacy in humanized peripheral blood mononuclear cells (PBMC), and syngeneic mouse models, finding additive efficacy in combination with an anti-PD-1 (a well-characterized checkpoint inhibitor). These findings support IGSF1 as an immune target that might complement existing cancer immunotherapeutics.

A holistic approach to implementing artificial intelligence in radiology.

OBJECTIVE: Despite the widespread recognition of the importance of artificial intelligence (AI) in healthcare, its implementation is often limited. This article aims to address this implementation gap by presenting insights from an in-depth case study of an organisation that approached AI implementation with a holistic approach. MATERIALS AND METHODS: We conducted a longitudinal, qualitative case study of the implementation of AI in radiology at a large academic medical centre in the Netherlands for three years. Collected data consists of 43 days of work observations, 30 meeting observations, 18 interviews and 41 relevant documents. Abductive reasoning was used for systematic data analysis, which revealed three change initiative themes responding to specific AI implementation challenges. RESULTS: This study identifies challenges of implementing AI in radiology at different levels and proposes a holistic approach to tackle those challenges. At the technology level, there is the issue of multiple narrow AI applications with no standard use interface; at the workflow level, AI results allow limited interaction with radiologists; at the people and organisational level, there are divergent expectations and limited experience with AI. The case of Southern illustrates that organisations can reap more benefits from AI implementation by investing in long-term initiatives that holistically align both social and technological aspects of clinical practice. CONCLUSION: This study highlights the importance of a holistic approach to AI implementation that addresses challenges spanning technology, workflow, and organisational levels. Aligning change initiatives between these different levels has proven to be important to facilitate wide-scale implementation of AI in clinical practice. CRITICAL RELEVANCE STATEMENT: Adoption of artificial intelligence is crucial for future-ready radiological care. This case study highlights the importance of a holistic approach that addresses technological, workflow, and organisational aspects, offering practical insights and solutions to facilitate successful AI adoption in clinical practice. KEY POINTS: 1. Practical and actionable insights into successful AI implementation in radiology are lacking. 2. Aligning technology, workflow, organisational aspects is crucial for a successful AI implementation 3. Holistic approach aids organisations to create sustainable value through AI implementation.

The Effects of Auricular Acupressure on Menopausal Symptoms, Stress, and Sleep in Postmenopausal Middle-Aged Women: A Randomized Single-Blind Sham-Controlled Trial.

INTRODUCTION: Middle-aged women in the postmenopausal period experience menopause symptoms, stress, and poor sleep quality due to hormonal changes. Nonetheless, most of them recognize such symptoms as an aging process without receiving proper treatment, and there are few nonpharmacologic interventions available. METHODS: This was a randomized single-masked, sham-controlled trial. For the intervention group, a vaccaria seed was applied to the auricular points of Shenmen, anterior lobe, adrenal glands, central rim, and endocrine that are related to the menopause symptoms, stress, and sleep while applying a seed to the auricular points not related to the forementioned symptoms to the control group. The Menopause Rating Scale (MRS), Perceived Stress Scale (PSS), heart rate variability, and electroencephalogram (EEG) were measured before the intervention, 4 weeks after the intervention, and 8 weeks after the intervention. Actigraphy was measured with a Fitbit, and the Pittsburgh Sleep Quality Index (PSQI) was measured before and after the intervention. The study was registered with the World Health Organization International Clinical Trials Registry Platform (KCT0007364). RESULTS: The MRS showed significant differences over time in the intervention group (F, 22.057; P < .001). There was a significant difference over time in the PSS (F, 22.576; P < .001), stress index measured by heart rate variability (F, 14.027; P = .001), and antistress quotient of the right brain measured by EEG (F, 4.865; P = .033). Sleep quality, measured by the PSQI (t = -4.050, P < .001), and sleep efficiency measured by actigraphy (t = 5.996, P < .001) were found to be significantly different over time in the intervention group. DISCUSSION: This study demonstrated that auricular acupressure is effective in improving menopause symptoms, stress, and sleep in postmenopausal middle-aged women. Therefore, auricular acupressure may be a useful nonpharmacologic intervention for alleviating these symptoms in this population.

Human gut microbiota from hepatitis B virus-infected individuals is associated with reduced triglyceride level in mice: faecal transplantation study.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is associated with a reduced risk of dyslipidaemia. Using a human faecal microbiota transplantation (FMT), we compared changes in gut microbiota and lipid profiles in mice transplanted with human faeces from HBV-infected and non-infected individuals. APPROACH AND RESULTS: A total of 19 mice received human FMT from four HBV-infected individuals and were categorised into the HBV-positive mice group, while 20 mice received FMT from four HBV-non-infected individuals into the HBV-negative one. In the analysis of gut microbiota in FMT mice, we observed a robust increase in alpha diversity and abundance of Akkermansia muciniphila in HBV-positive mice, compared to that in HBV-negative. Functional inference analysis revealed that the pathways involved in glycerolipid metabolism were more enriched in HBV-positive mice. At 5 weeks of FMT, the reduced triglyceride (TG) level was predominantly observed in HBV-positive mice. CONCLUSIONS: Altered gut microbiota accompanied by HBV infection was associated with a robust increase in alpha diversity and butyrate producers, which resulted in a reduced level of TG at 5 weeks post-FMT. This indicates that the reduced risk of dyslipidaemia in chronic HBV infection may be due to the altered gut microbiota accompanied by HBV infection.

Effect of lyophilized gelatin-norbornene cryogel size on calvarial bone regeneration.

Molding processes with molds containing topographical structures have been used for fabrication of hydrogel and cryogel particles. However, they can involve difficulties in separation of fabricated particles with complex shape from the molds or repeated fabrication of the particles although the overall processes do not require much skill and equipment. In this study, molds with etched superhydrophobic patterns have been developed by etching polytetrafluoroethylene (PTFE) blocks in user-defined designs with a femtosecond (FS) laser-based etching system. Lyophilized cryogel particles with various designs and sizes were fabricated by molding precursors with these PTFE molds. Additionally, the clean and easy separation of particles from the molds allowed repeated fabrication of the particles. For an application, relatively 'big' gelatin-norbornene (GelNB) cryogel particles prepared via molding with polydimethylsiloxane (PDMS) molds, swelling in phosphate buffered saline (PBS) and slicing height in half and 'small' GelNB cryogel particles fabricated with the PTFE molds were fabricated. Then, they were used to study scaffold size effect on calvarial bone regeneration. The molds generated with the FS laser-based etching system can be useful for various applications that require the mass production of cryogel particles in various geometries.

Administering Antibiotics for Less Than Four Weeks Increases the Risk of Relapse in Culture-Positive Septic Arthritis of Native Joints.

(1) Objectives: This study investigated the optimal duration of antibiotic therapy and determined the risk factors associated with relapse in patients with culture-proven septic arthritis of native joints. (2) Methods: A retrospective review was conducted on patients aged ≥18 years diagnosed with native joint septic arthritis, with bacteria isolated from joints and/or blood. The exclusion criteria were prosthetic joint infections and cases with no identified microorganisms. The outcomes were assessed in the remission and relapse groups. (3) Results: Among 479 patients with native joint septic arthritis, 137 met the inclusion criteria, with a median follow-up duration of 2.7 years. The relapse rate was 9.5%, which mainly occurred within 30 days after antibiotic treatment completion. Compared with the remission group, the relapse group showed a significantly higher proportion of cases that received antibiotic therapy for ≤ 4 weeks (4.8% vs. 46.2%, p < 0.001), synovial fluid white blood cell (WBC) counts ≥150 × 103/mm3 (25.3% vs. 60.0%, p = 0.030), acute kidney injury (19.2% vs. 50%, p = 0.024), and extended-spectrum beta-lactamases-producing Enterobacteriaceae (0.8 vs. 15.4%, p = 0.024). Independent risk factors for relapse were determined as antibiotic therapy duration of ≤ 4 weeks (odds ratio (OR), 25.47; 95% confidence interval (CI), 1.57-412.33; p = 0.023) and synovial fluid WBC counts ≥150 × 103/mm3 (OR, 17.46; 95% CI, 1.74-175.62; p = 0.015). (4) Conclusions: Patients with native joint septic arthritis require vigilant monitoring for relapse, particularly when treated with antibiotic regimens administered for less than four weeks or when synovial aspirates exhibit elevated WBC counts at diagnosis.

Methicillin Resistance Increased the Risk of Treatment Failure in Native Joint Septic Arthritis Caused by Staphylococcus aureus.

This study aimed to compare clinical characteristics and outcomes in patients with native joint septic arthritis (NJSA) due to methicillin-resistant Staphylococcus aureus (MRSA) in comparison to methicillin-sensitive S. aureus (MSSA) and identify treatment failure risk factors. We conducted a multi-center retrospective study on adult NJSA patients at three teaching hospitals in South Korea from 2005 to 2017. Among 101 patients diagnosed with S. aureus NJSA, 39 (38.6%) had MRSA strains. Compared to MSSA, patients with MRSA had a higher prevalence of nosocomial infections (17.9% vs. 1.6%; p = 0.005) and received inappropriate antibiotics within 48 h more frequently (74.4% vs. 0%; p < 0.001). In total, twenty patients (19.8%) experienced treatment failure, which encompassed five patients (5.0%) who passed away, nine (8.9%) requiring repeated surgical drainage after 30 days of antibiotic therapy, and seven (6.9%) with relapse. The MRSA group showed a higher rate of overall treatment failure (33.3% vs. 11.3%; p = 0.007) with a notably increased frequency of requiring repeated surgical interventions after 30 days of antibiotic therapy (17.9% vs. 3.2%, p = 0.026), in contrast to the MSSA group. Independent risk factors for treatment failure included Charlson comorbidity score, elevated CRP levels, and methicillin resistance. Methicillin resistance is an independent risk factor for treatment failure, emphasizing the need for vigilant monitoring and targeted interventions in MRSA-related NJSA cases.

Detoxification of arsenite by iodide in frozen solution.

The oxidation of arsenite (As(III)) to arsenate (As(V)) has received significant attention because it helps mitigate the hazardous and adverse effects of As(III) and subsequently improves the effectiveness of arsenic removal. This study developed an efficient freezing technology for the oxidative transformation of As(III) based on iodide (I-). For a sample containing a very low concentration of 20 µM As(III) and 200 µM I- frozen at -20 °C, approximately 19 µM As(V) was formed after reaction for 0.5 h at pH 3. This rapid conversion has never been achieved in previous studies. However, As(V) was not generated in water at 25 °C. The acceleration of the oxidation of As(III) by I- in ice may be attributed to the freeze-concentration effect. During freezing, all components (i.e., As(III), I-, and protons) are highly concentrated in the ice grain boundary regions, resulting in thermodynamically and kinetically favorable conditions for the redox reaction between As(III) and I-. The efficiency of the oxidation of As(III) using I- increased at high I- concentrations and low pH values. The low freezing temperature (below -20 °C) hindered the oxidative transformation of As(III) by I-. The efficiency of the oxidation of As(III) significantly increased using a fixed initial concentration of I- by subjecting the system to six freezing-melting cycles. The outcomes of this study suggest the possibility of the self-detoxification of As(III) in the natural environment, indicating the potential for developing an eco-friendly method for the treatment of As(III)-contaminated areas in regions with a cold climate. It also demonstrates radical remediation to almost completely remove a very small amount of As(III) that was input in As(III)-contaminated wastewater detoxification, a benchmark that existing methods have been unable to achieve.

Classical Hodgkin lymphoma following follicular lymphoma: a case report.

The simultaneous, composite, or sequential occurrence of follicular lymphoma (FL) and classical Hodgkin lymphoma (HL), both of which originate from germinal center B-cell, is rare. Questions have been raised with regard to the type of tests that pathologists should perform when observing the presence of a "large-cell lymphoma" following an FL and what are the most critical pathological points for diagnosis. Here, we present a case of a classical HL following an FL after administering rituximab-bendamustine (R-Benda) chemotherapy. Furthermore, we also summarized the literature and compared this case with other HLs that followed FLs. A 55-year-old woman was diagnosed with a grade 3A FL of the breast and axillary lymph node masses. She completed six R-Benda chemotherapy cycles for stage IV FL. Twenty-three months after the diagnosis, follow-up image studies showed an increase in the size and number of the lesions. Biopsies of the neck lymph node and liver were performed, and the diagnosis was classical HL. Sequential or composite FL and HL may sometimes develop from the same clone because they share the same genetic alterations, such as B-cell lymphoma (Bcl)-2 or Bcl-6 translocation. When a large-cell lymphoma is found after the treatment of FL, classical HL should be considered a pathological differential diagnosis, and histological, immunohistochemical, or molecular investigations must be considered during the diagnostic process.

Nursing Interventions for Children with Atopic Dermatitis and Their Families: A Scoping Review.

PURPOSE: The purpose of this scoping review was to summarize and synthesis studies about nursing interventions for children and adolescents with atopic dermatitis and their families. METHODS: A scoping review was conducted and described as per PRISMA-ScR via four electronic databases, PubMed, Web of science, Scopus, and EBSCOhost, evaluating research on nursing interventions for children diagnosed with atopic dermatitis and their families. RESULTS: Eleven articles were included in the review. Nursing interventions were conducted for children, parents, or both and primarily focused on education, consultation, and management of complications. Outcomes of the interventions showed improvements in atopic dermatitis severity for children and enhanced quality of life for children and their families. CLINICAL IMPLICATIONS: Nursing interventions targeting children and parents have been found to be effective in alleviating the severity of atopic dermatitis in children and improving their quality of life. Despite the increasing prevalence of atopic dermatitis in children, studies on nursing interventions are insufficient and outdated. Future research should focus on providing comprehensive and age-appropriate interventions for children with atopic dermatitis and their families to improve their well-being and overall quality of life.

Heterologous protein production using Psychrobacter sp. PAMC 21119 analyzed with a green fluorescent protein-based reporter system.

Insolubility and low expression are typical bottlenecks in the production of proteins for studying their function and structure using X-ray crystallography or nuclear magnetic resonance spectroscopy. Cold-active enzymes from polar microorganisms have unique structural features that render them unstable and thermolabile, and are responsible for decreased protein yield in heterologous expression systems. To address these challenges, we developed a heterologous protein expression system using a psychrophilic organism, Psychrobacter sp. PAMC 21119, as a protein expression host with its own promoter. We screened 11 promoters and evaluated their strength using quantitative real-time polymerase chain reaction and a reporter system harboring the SfGFP gene. The highest expression was achieved using promoters RH96_RS13655 (P21119_20930) and RH96_RS15090 (P21119_23410), regardless of the temperature used. The p20930 strain exhibited a maximum expression level 19.6-fold higher than that of its control at 20 °C and produced approximately 0.5 mg of protein per gram of dry cell weight. To our knowledge, this is the first report of a low-temperature recombinant protein expression system developed using Psychrobacter sp. that can be used to express various difficult-to-express and cold-active proteins.

Clinical Characteristics and Risk Factors for Mortality in Critical COVID-19 Patients Aged 50 Years or Younger During Omicron Wave in Korea: Comparison With Patients Older Than 50 Years of Age.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. METHODS: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. RESULTS: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m² or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043-1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584-14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042-8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691-98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294-10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. CONCLUSION: Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.

Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis.

Background: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for 'planned' dose modification, and the 'actually administered' dose varied more. Objective: To map a 10-year trend for 'planned' and 'actual' doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly 'planned' versus 'actual' dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program (www.RDI-map.com). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of 'planned' dose modification in FOLFIRINOX ranging 75-100% oxaliplatin, 75-100% irinotecan, 0-100% 5-fluorouracil (5-FU) bolus, and 75-133% 5-FU continuous injection. The 'actual' dose further decreased to 54-96%, 61-88%, 0-92%, and 63-98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5-33.9%) and 33.8% (95% CI: 30.3-37.3%), respectively (p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0-16.0%) and 5.5% (95% CI: 0-8.9%), respectively (p = 0.030). Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the 'planned' and 'actual' doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.