South Korean Nurse Residency Program for New Graduates: A Posttest Study.

BACKGROUND: Turnover rates among newly graduated nurses are high, increasing the workload for other nurses and hampering organizational productivity. This study investigates the effects of a nurse residency program (NRP), examining clinical competence, job satisfaction, organizational socialization, turnover intention, and turnover rates. METHOD: This study was conducted among newly employed graduate nurses in South Korea. Participants (N = 167) included nurses with less than 6 months of experience (NRP group, n = 52; control group, n = 115). The current results were measured 1 year after initiation of the NRP. RESULTS: The NRP group showed significantly lower turnover intention and turnover rates and substantially better clinical competence, job satisfaction, and organizational socialization. CONCLUSION: Even when applied in the unique South Korean cultural and medical context, the NRP improved job performance and satisfaction as well as organizational socialization and reduced turnover rates and turnover intention among new nurses. Therefore, a systematized NRP should be actively used when new nurses are onboarded. [J Contin Educ Nurs. 202x;5x(x):xx-xx.].

Posttranscriptional regulation of FAN1 by miR-124-3p at rs3512 underlies onset-delaying genetic modification in Huntington's disease.

Many Mendelian disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, arise from expansions of CAG trinucleotide repeats. Despite the clear genetic causes, additional genetic factors may influence the rate of those monogenic disorders. Notably, genome-wide association studies discovered somewhat expected modifiers, particularly mismatch repair genes involved in the CAG repeat instability, impacting age at onset of HD. Strikingly, FAN1, previously unrelated to repeat instability, produced the strongest HD modification signals. Diverse FAN1 haplotypes independently modify HD, with rare genetic variants diminishing DNA binding or nuclease activity of the FAN1 protein, hastening HD onset. However, the mechanism behind the frequent and the most significant onset-delaying FAN1 haplotype lacking missense variations has remained elusive. Here, we illustrated that a microRNA acting on 3'-UTR (untranslated region) SNP rs3512, rather than transcriptional regulation, is responsible for the significant FAN1 expression quantitative trait loci signal and allelic imbalance in FAN1 messenger ribonucleic acid (mRNA), accounting for the most significant and frequent onset-delaying modifier haplotype in HD. Specifically, miR-124-3p selectively targets the reference allele at rs3512, diminishing the stability of FAN1 mRNA harboring that allele and consequently reducing its levels. Subsequent validation analyses, including the use of antagomir and 3'-UTR reporter vectors with swapped alleles, confirmed the specificity of miR-124-3p at rs3512. Together, these findings indicate that the alternative allele at rs3512 renders the FAN1 mRNA less susceptible to miR-124-3p-mediated posttranscriptional regulation, resulting in increased FAN1 levels and a subsequent delay in HD onset by mitigating CAG repeat instability.

Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Digital Validation in Breast Cancer Needle Biopsies: Comparison of Histological Grade and Biomarker Expression Assessment Using Conventional Light Microscopy, Whole Slide Imaging, and Digital Image Analysis.

Given the widespread use of whole slide imaging (WSI) for primary pathological diagnosis, we evaluated its utility in assessing histological grade and biomarker expression (ER, PR, HER2, and Ki67) compared to conventional light microscopy (CLM). In addition, we explored the utility of digital image analysis (DIA) for assessing biomarker expression. Three breast pathologists assessed the Nottingham combined histological grade, its components, and biomarker expression through the immunohistochemistry of core needle biopsy samples obtained from 101 patients with breast cancer using CLM, WSI, and DIA. There was no significant difference in variance between the WSI and CLM agreement rates for the Nottingham grade and its components and biomarker expression. Nuclear pleomorphism emerged as the most variable histologic component in intra- and inter-observer agreement (kappa ≤ 0.577 and kappa ≤ 0.394, respectively). The assessment of biomarker expression using DIA achieved an enhanced kappa compared to the inter-observer agreement. Compared to each observer's assessment, DIA exhibited an improved kappa coefficient for the expression of most biomarkers with CLM and WSI. Using WSI to assess prognostic and predictive factors, including histological grade and biomarker expression in breast cancer, is acceptable. Furthermore, incorporating DIA to assess biomarker expression shows promise for substantially enhancing scoring reproducibility.

Conjunctival myxoma: A case report and review of a rare tumor.

RATIONALE: Conjunctival myxoma is a rare benign tumor, which can mimic more common conjunctival lesions such as a cyst, lymphangioma, amelanotic nevus, neurofibroma, amelanotic melanoma, or lipoma. We describe a patient with the conjunctival myxoma, who was initially misdiagnosed as a conjunctival cyst. This case report includes intraoperative photographs and various immunohistochemical staining images. PATIENTS CONCERNS: A 55-year-old woman presented with a painless mass in the superotemporal conjunctiva of the left eye, which she had noticed 1 month ago. The patient had no previous history of trauma or eye surgery. Slit-lamp examination revealed a well-circumscribed, freely movable, pinkish, semi-translucent mass on the temporal bulbar conjunctiva, suggestive of a conjunctival cyst. DIAGNOSES: Histopathological analysis showed stellate- and spindle-shaped cells within the loose myxoid stroma, confirming a diagnosis of conjunctival myxoma. INTERVENTIONS: The conjunctival lesion was completely excised under local anesthesia. OUTCOMES: After 4 months of follow-up, the patient remained in good health without recurrence of the conjunctival lesion and no evidence of any systemic abnormality. LESSONS: Myxoma is an extremely uncommon benign tumor derived from primitive mesenchyme. Considering the rarity of the tumor and its similarity to other conjunctival tumors, diagnosis can be challenging. Ophthalmologists should consider myxoma as a possible differential diagnosis when encountering conjunctival lesions. Surgical excision is essential to confirm the diagnosis and careful systemic evaluation is required to prevent potentially life-threatening underlying systemic conditions.

Personalized allele-specific CRISPR-Cas9 strategies for myofibrillar myopathy 6.

Myofibrillar myopathy 6 (MFM6) is a rare childhood-onset myopathy characterized by myofibrillar disintegration, muscle weakness, and cardiomyopathy. The genetic cause of MFM6 is p.Pro209Leu mutation (rs121918312-T) in the BAG3 gene, which generates the disease outcomes in a dominant fashion. Since the consequences of the BAG3 mutation are strong and rapidly progressing, most MFM6 patients are due to de novo mutation. There are no effective treatments for MFM6 despite its well-known genetic cause. Given p.Pro209Leu mutation is dominant, regenerative medicine approaches employing orthologous stem cells in which mutant BAG3 is inactivated offer a promising avenue. Here, we developed personalized allele-specific CRISPR-Cas9 strategies capitalizing on PAM-altering SNP and PAM-proximal SNP. In order to identify the disease chromosome carrying the de novo mutation in our two affected individuals, haplotype phasing through cloning-sequencing was performed. Based on the sequence differences between mutant and normal BAG3, we developed personalized allele-specific CRISPR-Cas9 strategies to selectively inactivate the mutant allele 1) by preventing the transcription of the mutant BAG3 and 2) by inducing nonsense-mediated decay (NMD) of mutant BAG3 mRNA. Subsequent experimental validation in patient-derived induced pluripotent stem cell (iPSC) lines showed complete allele specificities of our CRISPR-Cas9 strategies and molecular consequences attributable to inactivated mutant BAG3. In addition, mutant allele-specific CRISPR-Cas9 targeting did not alter the characteristics of iPSC or the capacity to differentiate into cardiomyocytes. Together, our data demonstrate the feasibility and potential of personalized allele-specific CRISPR-Cas9 approaches to selectively inactivate the mutant BAG3 to generate cell resources for regenerative medicine approaches for MFM6.

Metabolic syndrome awareness in the general Korean population: results from a nationwide survey.

BACKGROUND/AIMS: Metabolic syndrome (MetS) raises the risk of cardiovascular disease and type 2 diabetes. An awareness of MetS is vital for early detection and proactive management, which can mitigate the risks associated with MetS. Therefore, our study aimed to investigate the level of awareness of MetS among the Korean population. METHODS: We conducted a nationwide survey between January and February 2023 among a representative sample of the Korean population using an online survey. Information regarding the awareness of MetS and its risk, the importance of lifestyle modification, and health behavior were collected. The question about the awareness of MetS was "How much do you think you know about MetS?" and there were five answers: 1) I know very well, 2) I know well, 3) I know a little, 4) I do not know, and 5) I have no idea. The high-awareness group was defined as those who answered that they knew very well or well. RESULTS: Among 1,000 participants (mean age, 45.7 ± 13.2 yr), 29% were unaware of MetS, and only 20.8% had high awareness. The high-awareness group was significantly more knowledgeable about lifestyle modifications and demonstrated better health behaviors. After adjustment for possible confounding factors, younger age, low household income, and absence of comorbidity were independently associated with a lack of awareness regarding MetS. CONCLUSION: The high-awareness group showed greater knowledge of the importance of lifestyle modifications and better health behaviors regarding MetS. The findings highlight the need for improved public education and awareness programs regarding MetS.

Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Applicable Machine Learning Model for Predicting Contrast-induced Nephropathy Based on Pre-catheterization Variables.

Objective Contrast agents used for radiological examinations are an important cause of acute kidney injury (AKI). We developed and validated a machine learning and clinical scoring prediction model to stratify the risk of contrast-induced nephropathy, considering the limitations of current classical and machine learning models. Methods This retrospective study included 38,481 percutaneous coronary intervention cases from 23,703 patients in a tertiary hospital. We divided the cases into development and internal test sets (8:2). Using the development set, we trained a gradient boosting machine prediction model (complex model). We then developed a simple model using seven variables based on variable importance. We validated the performance of the models using an internal test set and tested them externally in two other hospitals. Results The complex model had the best area under the receiver operating characteristic (AUROC) curve at 0.885 [95% confidence interval (CI) 0.876-0.894] in the internal test set and 0.837 (95% CI 0.819-0.854) and 0.850 (95% CI 0.781-0.918) in two different external validation sets. The simple model showed an AUROC of 0.795 (95% CI 0.781-0.808) in the internal test set and 0.766 (95% CI 0.744-0.789) and 0.782 (95% CI 0.687-0.877) in the two different external validation sets. This was higher than the value in the well-known scoring system (Mehran criteria, AUROC=0.67). The seven precatheterization variables selected for the simple model were age, known chronic kidney disease, hematocrit, troponin I, blood urea nitrogen, base excess, and N-terminal pro-brain natriuretic peptide. The simple model is available at http://52.78.230.235:8081/Conclusions We developed an AKI prediction machine learning model with reliable performance. This can aid in bedside clinical decision making.

Self-care Behavior Based on Integrated Behavioral Model in Patients With Atrial Fibrillation: A Structural Equation Modeling Approach.

BACKGROUND: There is limited research exploring the behavioral intentions, beliefs, and application of theoretical models in relation to self-care in patients with atrial fibrillation (AF). OBJECTIVE: This study aimed to identify the factors that influence self-care behavior in patients with AF. METHODS: The study used an integrated behavioral model and collected data from 216 patients diagnosed with AF. Data were analyzed using SPSS 24.0 and AMOS/WIN 24.0 to verify the fit of the hypothesis model, confirm factor analysis, and the validity of the hypothesis itself. RESULTS: Self-care behavioral intention (ß = 0.433, p < .001) and habit (ß = 0.395, p = .005) had a significant direct effect, while instrumental attitude (ß = 0.077, p = .045), injunctive norm (ß = 0.084, p = .037), and self-efficacy (ß = 0.249, p = .011) had a significant indirect effect on self-care behavior, explaining 64.4% of the variance. CONCLUSION: The final model validated the factors that impact self-care behavior in patients with AF, highlighting the importance of fostering positive recognition of instrumental attitude, bolstering social influence and self-efficacy through significant individuals to improve self-care behavior. It is recommended to create an intervention program that encourages intentions and motivations for self-care behavior and incorporates tactics to make self-care behavior a habit. The study's path diagram can serve as a conceptual framework for designing strategies to enhance self-care behavior in patients with AF.

Optimizing the Hospital Blood Bank Stock in Korea: A Comparative Analysis of the Uniform 5-Day Stock Index and a Novel Blood Stock Index.

Background: Maintaining optimal blood inventory levels in hospitals is important to prevent blood shortage and wastage. We aimed to provide an efficient blood inventory management strategy for hospital blood banks nation-wide by comparing the current use of 5-day issuable stock (IS) with Lim's IS as a novel target IS. Methods: The average and CV of daily usage (DU) were calculated from information entered into Korea's Blood Management System by 194 participating hospitals in 2019 and 2020. Using these data, Lim's IS was calculated by determining the simulated annual average blood shortage day nearest to 1 for each blood group in each hospital. The 5-day IS (5IS) was estimated by multiplying the average DU in 2018 by five to count the shortage days in 2019. Results: The average DU (0.3-231.3 units) and corresponding CV (0.33-7.14) in the participating hospitals were inversely proportional (r=-0.699 to -0.695). The hypothetical averages of 5IS and Lim's IS were 27.0±41.2 and 24.7±20.8, respectively (P=0.006). The shortage days for 5IS and Lim's IS were 8.9±22.7 and 1.0±1.9, respectively (P<0.001). Conclusions: While 5IS was unacceptable for universal application, Lim's IS remained near one shortage day and is considered more efficient than 5IS. Hospitals should implement indicators that consider DU and its variations. This is the first study to introduce Lim's IS as an indicator of optimal blood inventory, and the data are expected to provide guidance for effective blood inventory management nationwide, particularly during blood shortages.

Increased CD16a (FcγRIIIA) Expression in The Tumor Microenvironment of Atypical Neurofibromatous Neoplasms of Uncertain Biologic Potential May Be Associated with Progression from Neurofibromas to Atypical Neurofibromas.

Neurofibroma (NF) is a benign tumor in the peripheral nervous system, but it can infiltrate around structures and cause functional impairment and disfigurement. We incidentally found that the expression of CD16a (Fc gamma receptor IIIA) was increased in NFs compared to in non-neoplastic nerves and hypothesized that CD16 could be relevant to NF progression. We evaluated the expressions of CD16a, CD16b, CD68, TREM2, Galectin-3, S-100, and SOX10 in 38 cases of neurogenic tumors (NF, n = 18; atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP), n = 14; and malignant peripheral nerve sheath tumor (MPNST), n = 6) by immunohistochemical staining. In the tumor microenvironment (TME) of the ANNUBPs, CD16a and CD16b expression levels had increased more than in the NFs or MPNSTs. CD68 and Galectin-3 expression levels in the ANNUBPs were higher than in the MPNSTs. Dual immunohistochemical staining showed an overlapping pattern for CD16a and CD68 in TME immune cells. Increased CD16a expression was detected in the ANNUBPs compared to the NFs but decreased with malignant progression. The CD16a overexpression with CD68 positivity in the ANNUBPs potentially reflects that the TME immune modulation could be associated with NF progression to an ANNUBP. Further studies should explore the role of CD16a in immunomodulation for accelerating NF growth.

Oncogenic KRAS mutation confers chemoresistance by upregulating SIRT1 in non-small cell lung cancer.

Kirsten rat sarcoma viral oncogene homologue (KRAS) is a frequent oncogenic driver of solid tumors, including non-small cell lung cancer (NSCLC). The treatment and outcomes of KRAS-mutant cancers have not been dramatically revolutionized by direct KRAS-targeted therapies because of the lack of deep binding pockets for specific small molecule inhibitors. Here, we demonstrated that the mRNA and protein levels of the class III histone deacetylase SIRT1 were upregulated by the KRASMut-Raf-MEK-c-Myc axis in KRASMut lung cancer cells and in lung tumors of a mouse model with spontaneous KrasG12D expression. KRASMut-induced SIRT1 bound to KRASMut and stably deacetylated KRASMut at lysine 104, which increased KRASMut activity. SIRT1 knockdown (K/D) or the SIRT1H363Y mutation increased KRASMut acetylation, which decreased KRASMut activity and sensitized tumors to the anticancer effects of cisplatin and erlotinib. Furthermore, in KrasG12D/+;Sirt1co/co mice, treatment with cisplatin and erlotinib robustly reduced the tumor burden and increased survival rates compared with those in spontaneous LSL-KrasG12D/+;Sirt1+/+ mice and mice in each single-drug treatment group. Then, we identified p300 as a KRASMut acetyltransferase that reinforced KRASMut lysine 104 acetylation and robustly decreased KRASMut activity. KRASMut lysine 104 acetylation by p300 and deacetylation by SIRT1 were confirmed by LC‒MS/MS. Consistent with this finding, the SIRT1 inhibitor EX527 suppressed KRASMut activity, which synergistically abolished cell proliferation and colony formation, as well as the tumor burden in KRASMut mice, when combined with cisplatin or erlotinib. Our data reveal a novel pathway critical for the regulation of KRASMut lung cancer progression and provide important evidence for the potential application of SIRT1 inhibitors and p300 activators for the combination treatment of KRASMut lung cancer patients.

Effects of Climate Change and Drought Tolerance on Maize Growth.

Climate change is affecting all regions of the world with different climates, and the scale of damage is increasing due to the occurrence of various natural disasters. In particular, maize production is highly affected by abnormal climate events such as heat waves and droughts. Increasing temperatures can accelerate growth and shorten the growing season, potentially reducing productivity. Additionally, enhanced temperatures during the ripening period can accelerate the process, reducing crop yields. In addition, drought stress due to water deficit can greatly affect seedling formation, early plant growth, photosynthesis, reproductive growth, and yield, so proper water management is critical to maize growth. Maize, in particular, is tall and broad-leaved, so extreme drought stress at planting can cause leaves to curl and stunt growth. It is important to understand that severe drought can have a detrimental effect on the growth and reproduction of maize. In addition, high temperatures caused by drought stress can inhibit the induction of flowering in male flowers and cause factors that interfere with pollen development. It is therefore important to increase the productivity of all food crops, including maize, while maintaining them in the face of persistent drought caused by climate change. This requires a strategy to develop genetically modified crops and drought-tolerant maize that can effectively respond to climate change. The aim of this paper is to investigate the effects of climate change and drought tolerance on maize growth. We also reviewed molecular breeding techniques to develop drought-tolerant maize varieties in response to climate change.

Nivolumab after Induction Chemotherapy in Previously Treated Non-Small-Cell Lung Cancer Patients with Low PD-L1 Expression.

This study aimed to investigate whether cyclophosphamide (C) and adriamycin (A) induction therapy (IT) prior to nivolumab could enhance the efficacy of nivolumab in previously treated patients with non-squamous (NSQ) non-small-cell lung cancer (NSCLC) with less than 10% programmed death-ligand 1 (PD-L1) expression. Twenty-two enrolled patients received four cycles of CA-IT every 3 weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle and 480 mg every 4 weeks after four cycles of CA-IT. The median progression-free survival (PFS) and overall survival (OS) were 2.4 months and 11.6 months, respectively. Fluorescence-activated cell sorting revealed the lowest ratio of myeloid-derived suppressor cells (MDSCs) to CD8+T-cells in the responders. Proteomic analysis identified a consistent upregulation of extracellular matrix-receptor interactions and phagosome pathways in the responders. Among the differentially expressed proteins, the transferrin receptor protein (TFRC) was higher in the responders before treatment (fold change > 1.2). TFRC validation with an independent cohort showed the prognostic significance of either OS or PFS in patients with low PD-L1 expression. In summary, CA-IT did not improve nivolumab efficacy in NSQ-NSCLCs with low PD-L1 expression; however, it induced decreasing MDSC, resulting in a durable response. Higher baseline TFRC levels predicted a favorable response to nivolumab in NSCLC with low PD-L1 expression.

Recent advances in understanding the role of the skin microbiome in the treatment of atopic dermatitis.

The skin is the largest organ in the human body, and histologically consists of the epidermis, dermis and subcutaneous tissue. Humans maintain a cooperative symbiotic relationship with their skin microbiota, a complex community of bacteria, fungi and viruses that live on the surface of the skin, and which act as a barrier to protect the body from the inside and outside. The skin is a 'habitat' and vast 'ecosystem' inhabited by countless microbes; as such, relationships have been forged through millions of years of coevolution. It is not surprising then that microbes are key participants in shaping and maintaining essential physiological processes. In addition to maintaining barrier function, the unique symbiotic microbiota that colonizes the skin increases the immune response and provides protection against pathogenic microbes. This review examines our current understanding of skin microbes in shaping and enhancing the skin barrier, as well as skin microbiome-host interactions and their roles in skin diseases, such as atopic dermatitis (AD). We also report on the current status of AD therapeutic drugs that target the skin microbiome, related research on current therapeutic strategies, and the limitations and future considerations of skin microbiome research. In particular, as a future strategy, we discuss the need for a skin-on-a-chip-based microphysiological system research model amenable to biomimetic in vitro studies and human skin equivalent models, including skin appendages.

Protection of c-Fos from autophagic degradation by PRMT1-mediated methylation fosters gastric tumorigenesis.

Both AP-1 and PRMT1 are vital molecules in variety of cellular progresssion, but the interaction between these proteins in the context of cellular functions is less clear. Gastric cancer (GC) is one of the pernicious diseases worldwide. An in-depth understanding of the molecular mode of action underlying gastric tumorigenesis is still elusive. In this study, we found that PRMT1 directly interacts with c-Fos and enhances AP-1 activation. PRMT1-mediated arginine methylation (mono- and dimethylation) of c-Fos synergistically enhances c-Fos-mediated AP-1 liveliness and consequently increases c-Fos protein stabilization. Consistent with this finding, PRMT1 knockdown decreases the protein level of c-Fos. We discovered that the c-Fos protein undergoes autophagic degradation and found that PRMT1-mediated methylation at R287 protects c-Fos from autophagosomal degradation and is linked to clinicopathologic variables as well as prognosis in stomach tumor. Together, our data demonstrate that PRMT1-mediated c-Fos protein stabilization promotes gastric tumorigenesis. We contend that targeting this modification could constitute a new therapeutic strategy in gastric cancer.

Analysis of Polymeric Immunoglobulin Receptor Expression in Olive Flounder (Paralichthys olivaceus) against Viral Hemorrhagic Septicemia Virus.

Polymeric immunoglobulin receptor (pIgR) mediates the transfer of polymeric immunoglobulin to protect organisms and is one of the most important mucosal effectors. In this study, the developmental stage- and tissue-specific expression of pIgR were observed before virus inoculation in olive flounder. pIgR was gradually expressed until the formation of immune tissue, exhibiting high expression in the late juvenile period; thereafter, pIgR expression gradually decreased and exhibited high expression in the spleen and skin. Moreover, pIgR expression after viral hemorrhagic septicemia virus infection was high in the kidney and spleen tissues at high density and low at low density. The results of this study can provide a basis for future studies on breeding density, virus expression, and immune system studies in fish.

How nursing students learn infection control education through undergraduate nursing programs: a phenomenographic research study.

BACKGROUND: Competency in infection control is crucial for implementing nursing best practices to ensure patient safety. However, research is lacking on the infection control education received by nursing students prior to entering clinical settings as nurses. This study aimed to explore how nursing students conceptualize infection control care in undergraduate nursing programs. METHODS: This study employed a qualitative research method using phenomenography. Universities providing undergraduate nursing programs in Korea. Thirty nursing students: 10 students each from the 2nd, 3rd, and 4th years of five undergraduate programs. Data were collected from May 2019 to February 2020 through semi-structured interviews and analyzed using a phenomenographic analysis procedure. RESULTS: Six descriptive categories were derived inductively for nursing students' frames of reference regarding infection control care and six descriptive categories of how nursing students learned about infection control care. The structural framework of the identified categories, about how nursing students learn about infection control care, was presented as an outcome space. CONCLUSIONS: Given that nursing students demonstrate diverse conceptualizations of infection control and are at varying levels of learning, professors and clinical mentors need to develop theoretical education and clinical practice opportunities that consider these differences.

Biosynthesis of kratom opioids.

Mitragynine, an analgesic alkaloid from the plant Mitragyna speciosa (kratom), offers a safer alternative to clinical opioids such as morphine, owing to its more favorable side effect profile. Although kratom has been traditionally used for stimulation and pain management in Southeast Asia, the mitragynine biosynthesis pathway has remained elusive. We embarked on a search for mitragynine biosynthetic genes from the transcriptomes of kratom and other members of the Rubiaceae family. We studied their functions in vitro and in vivo. Our investigations led to the identification of several reductases and an enol methyltransferase that forms a new clade within the SABATH methyltransferase family. Furthermore, we discovered a methyltransferase from Hamelia patens (firebush), which catalyzes the final step. With the tryptamine 4-hydroxylase from the psychedelic mushroom Psilocybe cubensis, we accomplished the four-step biosynthesis for mitragynine and its stereoisomer, speciogynine in both yeast and Escherichia coli when supplied with tryptamine and secologanin. Although we have yet to pinpoint the authentic hydroxylase and methyltransferase in kratom, our discovery completes the mitragynine biosynthesis. Through these breakthroughs, we achieved the microbial biosynthesis of kratom opioids for the first time. The remarkable enzyme promiscuity suggests the possibility of generating derivatives and analogs of kratom opioids in heterologous systems.