The flowering time regulator FLK controls pathogen defense in Arabidopsis thaliana.

Plant disease resistance is a complex process that is maintained in an intricate balance with development. Increasing evidence indicates the importance of posttranscriptional regulation of plant defense by RNA binding proteins. In a genetic screen for suppressors of Arabidopsis (Arabidopsis thaliana) accelerated cell death 6-1 (acd6-1), a small constitutive defense mutant whose defense level is grossly in a reverse proportion to plant size, we identified an allele of the canonical flowering regulatory gene FLOWERING LOCUS K HOMOLOGY DOMAIN (FLK) encoding a putative protein with triple K homology (KH) repeats. The KH repeat is an ancient RNA binding motif found in proteins from diverse organisms. The relevance of KH-domain proteins in pathogen resistance is largely unexplored. In addition to late flowering, the flk mutants exhibited decreased resistance to the bacterial pathogen Pseudomonas syringae and increased resistance to the necrotrophic fungal pathogen Botrytis cinerea. We further found that the flk mutations compromised basal defense and defense signaling mediated by salicylic acid (SA). Mutant analysis revealed complex genetic interactions between FLK and several major SA pathway genes. RNA-seq data showed that FLK regulates expression abundance of some major defense- and development-related genes as well as alternative splicing of a number of genes. Among the genes affected by FLK is ACD6, whose transcripts had increased intron retentions influenced by the flk mutations. Thus, this study provides mechanistic support for flk suppression of acd6-1 and establishes that FLK is a multifunctional gene involved in regulating pathogen defense and development of plants.

Development of an End-of-Life Nursing Care Protocol for Intensive Care Units: Delphi Survey Method.

Because of the lack of guidelines and standardized protocols for end-of-life nursing care in intensive care units in Korea, many nurses have reported facing difficulties when providing care for patients. This study attempted to develop a standardized end-of-life nursing protocol for use in intensive care units. A draft of the end-of-life nursing care protocol was developed after a literature review. A Delphi survey was carried out twice with 30 experts, and the content validity ratio of the items was investigated. The draft end-of-life nursing care protocol was divided into 3 separate stages with 24 items: 8 initial end-of-life care assessment items, 5 ongoing end-of-life care items, and 11 post-end-of-life care items. The content validity ratios of the first and second rounds were 0.33 or greater in each category, demonstrating the validity of the proposed draft as a standardized protocol. Furthermore, at the suggestion of the experts, an extra item was added in the last stage, resulting in 25 items. The results of this study are expected to help leading hospitals in South Korea outline the roles and range of tasks for end-of-life care in an intensive care unit and thereby resolve difficulties for nurses. Furthermore, this will improve the medical services that family members receive during end-of-life care.

Impact of the definition of bronchopulmonary dysplasia on neurodevelopmental outcomes.

Understanding the short and long-term pulmonary and neurologic outcomes of neonates with bronchopulmonary dysplasia (BPD) is important in neonatal care for low-birth-weight infants. Different criteria for BPD may have different associations with long-term outcomes. Currently, two criteria for diagnosing BPD have been proposed by the NIH (2001) and NRN (2019) for preterm infants at a postmenstrual age (PMA) of 36 weeks. We investigated which BPD definition best predicts long-term outcomes. Korean nationwide data for preterm infants born between 24+0 and < 32+0 weeks gestation from January 2013 to December 2015 were collected. For long-term outcomes, severity based on the NRN criteria was significantly related to neurodevelopmental impairment (NDI) in a univariate analysis after other risk factors were controlled. For the admission rate for respiratory disorder, grade 3 BPD of the NRN criteria had the highest specificity (96%), negative predictive value (86%), and accuracy (83%). For predicting NDI at the 18-24 month follow-up, grade 3 BPD of the NRN criteria had the best specificity (98%), positive (64%) and negative (79%) predictive values, and accuracy (78%) while NIH severe BPD had the highest sensitivity (60%). The NRN definition was more strongly associated with poor 2-year developmental outcomes. BPD diagnosed by NRN definitions might better identify infants at high risk for NDI.

Risk factors that affect the degree of bronchopulmonary dysplasia: Comparison by severity in the same gestational age.

OBJECTIVE: To investigate the risk factors for BPD severity by gestational age (GA) and identify a way to reduce the incidence of moderate-to-severe BPD. STUDY DESIGN: This was a retrospective cohort study of very-low-birth-weight-infants (VLBWIs) delivered at 24 to 28 weeks GA from Korean Neonatal Network registry between 2013 and 2016. BPD was defined using the National Institutes of Health criteria. Study populations were divided by GA and subdivided into no/mild BPD and moderate/severe BPD. The initial statuses of all infants, including those who died before BPD diagnosis and the maternal and neonatal factors of the live infants were compared. Statistical methods included descriptive statistics, comparative tests, and logistic regression. RESULTS: Of 3,976 infants, 3,717 were included (24weeks, n = 456; 25 weeks, n = 650, 26 weeks, n = 742; 27 weeks, n = 836; 28 weeks, n = 1,033). The overall mortality rate was 18% and the rates by GA were 43%, 29%, 11%, and 6% in the 24-, 25-, 26-, 27-, 28-GA groups, respectively. Small for GA (SGA), treated patent ductus arteriosus (PDA), hypotension, and late-onset sepsis were significant risk factors for developing moderate/severe BPD in the 25 to 28-week GA groups in the multivariate analyses. However, for infants born at 24 weeks GA, there were no significant risk factors apart from initial resuscitation. CONCLUSIONS: Effective initial resuscitation was the most important factor for infants delivered at 24 weeks GA determining the severity of BPD. For infants delivered between 25 and 28 weeks, judicious care of SGA infants, aggressive treatment for PDA and hypotension, and intense efforts to decrease the sepsis rate are needed to reduce the development of moderate-to-severe BPD.

Effect of antenatal azithromycin for Ureaplasma spp. on neonatal outcome at ≤30 weeks' gestational age.

BACKGROUND: Ureaplasma spp. in the maternal genitourinary tract has come to attention as a cause of preterm labor, spontaneous abortion, chorioamnionitis and adverse outcomes. A few controversies, however, still remain, namely, whether it should be treated aggressively or not. The aim of this study was to evaluate the effect of maternal azithromycin (AZ) treatment for Ureaplasma colonization on neonatal morbidities including bronchopulmonary dysplasia (BPD). METHODS: A retrospective case-control study of preterm babies delivered at ≤30 weeks of gestational age (GA) from 2012 to 2016 was conducted. Infants whose mothers had confirmed Ureaplasma colonization and treatment with AZ (m-AZ, cases) were matched by GA to control subjects whose mothers did not have Ureaplasma colonization. A subgroup analysis (nUU(+), infants with neonatal respiratory Ureaplasma colonization; nUU(-), infants without colonization) was also performed. RESULTS: Fifty-five control subjects were matched to 110 m-AZ subjects. The incidence of preterm premature rupture of membranes (P = 0.003) and of moderate-severe BPD (P = 0.010) was significantly higher in the m-AZ group. On subgroup analysis with post-hoc analysis (m-AZ + nUU(+) [I, n = 55] vs m-AZ + nUU(-) [II, n = 55] vs controls [n = 55]), the incidence of moderate-severe BPD was significantly different: 26% (I) vs 22% (II) vs 7% (controls), P = 0.033. CONCLUSIONS: Maternal Ureaplasma colonization was associated with moderate-severe BPD despite the use of AZ treatment. In addition, if the neonatal respiratory tract was colonized, then moderate-severe BPD developed even with maternal AZ treatment. Hence, selective antenatal and postnatal treatment of Ureaplasma colonization would be needed to control BPD development.

Organized hematoma of the sphenoid sinus causing acute visual loss.

Sinonasal organized hematoma, which has locally aggressive characteristics, is a non-neoplastic disease. We report a rare case of sphenoid sinus organized hematoma causing acute visual loss. A 35-year-old male presented with progressive headaches, retro-orbital pain, and frequent epistaxis. He had a medical history of aplastic anemia and of taking warfarin for a valvular heart disease. On image studies, an expansive soft tissue density lesion with bony destruction was found in his left sphenoid sinus. While waiting for elective surgery, acute visual loss occurred. Emergent endoscopic surgery was performed after correction of abnormal hematological profiles, but his visual disturbance did not improve. Although sphenoid sinus organized hematoma is a rare disease, organized hematoma should be considered in the differential diagnosis for sphenoid sinus lesion with acute visual loss. Rapid and correct diagnosis and timely treatment are essential to prevent permanent sequela.

The role of B cell Activating Factor (BAFF) expression on pathogenesis of nasal polyp in chronic rhinosinusitis with nasal polyposis.

BACKGROUND: B cells, plasma cells, and local immunoglobulins, are important as a mucosal immune barrier function, and tend to increase in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). However, their association with eosinophils' aggregation has not been fully understood. The objectives of this study was to explore whether BAFF expression in the subepithelial area in nasal polyp tissues of CRSwNP was associated with eosinophils' accumulation, and also to evaluate cells which cells produce BAFF. METHODOLOGY: Immunohistochemical and immunofluorescence staining were used to analyse expression of BAFF, CD20, immunoglobulin A (IgA) and a proliferation inducing ligand (APRIL) on nasal tissues from CRSwNP patients to control subjects. To identify the relationship between BAFF and tissue eosinophilia, CRSwNP subjects were divided into eosinophilic polyp and non-eosinophilic groups. Double immunofluorescence analysis for BAFF and CD11c or CD11b was performed to identify cells producing BAFF. RESULTS: The numbers of BAFF, CD20, and IgA-positive cells in the subepithelial area were significantly higher in the CRSwNP group (both eosinophilic polyps and non-eosinophilic polyps. There were statistically significant correlations between the number of BAFF and CD20-positive cells, CD20 and IgA-positive cells, and BAFF and IgA-positive cells. CD11b-positive were co-localized with BAFF positive cells. CONCLUSION: The subepithelial expression of BAFF was associated with increased number of B cells and plasma cells, and increased production of IgA in the patients with CRSwNP, especially eosinophilic nasal polyps. Therefore, BAFF-induced IgA production may be associated with eosinophils' aggregation and degranulation, which cause aggravation of tissue inflammation and finally polyp formation. The expression of BAFF in the subepithelial area may be associated with innate inflammatory cells (CD11b+ cells), such as monocytes, granulocytes, macrophages, and natural killer cells.

Role of staphylococcal enterotoxin B on the differentiation of regulatory T cells in nasal polyposis.

BACKGROUND: The pathogenesis of nasal polyposis has not been fully understood. Recent studies indicate that there is a subset of CD4(+)CD25(high)FoxP3(+)T cells (regulatory T cells [Tregs]) that express retinoic acid receptor related orphan receptor C (RORC) or IL-17, and these cells might be new proinflammatory cells because of the expression of IL-17 with loss of their suppressive function. The goals of this study were to localize Th17-like Tregs (Th17-like Tregs or RORC(+)Tregs) in nasal polyps and to investigate the role of staphylococcal enterotoxin B (SEB) on the differentiation of Tregs to RORC(+)Tregs in vitro. METHODS: A total of 60 patients were enrolled in this study. Of the 60 patients, 40 had chronic rhinosinusitis with nasal polyps (CRSwNPs), and 20 subjects who were undergoing septoplasty were enrolled as control subjects. The nasal polyps of CRSwNP patients were subclassified as either eosinophilic polyp (EP) and noneosinophilic polyp (NEP) according to the result of hematoxylin and eosin stain. Tissues and whole blood were collected from all subjects. Double immunofluorescent staining and reverse-transcription polymerase chain reaction for RORC and FOXP3 were conducted on the tissues. RORC expressions of Tregs were measured in the tissue using flow cytometry. The proportions of RORC(+)Tregs subsets and cytokines profiles from the supernatant were measured using flow cytometry after stimulation with SEB. RESULTS: The cells that express both RORC and FOXP3 and RORC(+)Tregs were significantly higher in the nasal polyps, especially in EPs compared with NEPs, and control mucosa. RORC(+)Tregs in peripheral blood mononuclear cells significantly increased in patients with EPs 24 hours after SEB stimulation in vitro. CONCLUSION: The results indicate that SEB may be involved in the differentiation of Tregs to RORC(+)Tregs, and these cells may be involved in the pathogenesis of eosinophilic nasal polyposis.

Upregulation of HGF and c-MET is associated with subclinical central lymph node metastasis in papillary thyroid microcarcinoma.

BACKGROUND: Identification of a novel biomarker of subclinical lymph node metastasis (SLNM) in papillary thyroid microcarcinoma (PTMC) could provide important clues regarding SLNM in PTMC. We evaluated the significance of HGF and c-Met expression in surgically removed tumor tissue from PTMC patients as a predictive marker of SLNM. METHODS: We analyzed the immunohistochemical relationship between HGF and c-Met expression and SLNM in 113 surgically treated PTMC patients with clinically negative nodes presurgery. In addition, we explored whether HGF/c-Met pathway activation enhanced the in vitro migration and invasion of PTC cells. RESULTS: Positive immunohistochemical HGF and c-Met staining was found in 107 (95 %) and 103 (91 %) cases, respectively. The HGF staining distribution was as follows: no staining in 6 cases, weak staining in 43, moderate staining in 55, and strong staining in 9. Of the nine cases with strong HGF staining, eight (89 %) had SLNM. The c-Met staining distribution was as follows: no staining in 10 cases, weak staining in 39, moderate staining in 59, and strong staining in 5. Of the five cases with strong c-Met staining, three (60 %) had SLNM. The presence of SLNM was strongly correlated with HGF and c-Met expression in PTMC in a univariate analysis (P < 0.05). HGF overexpression was also associated with SLNM in a multivariate analysis (P < 0.05). Stimulation with exogenous HGF and constitutive activation of c-Met enhanced the migration and invasion of PTC cells in vitro by enhancing VEGF-A expression. CONCLUSIONS: HGF/c-Met pathway activation is associated with SLNM of the central neck in PTMC.

Role of hypoxia-inducible factor-1α expression in regulatory T cells on nasal polypogenesis.

OBJECTIVES/HYPOTHESIS: Hypoxia-inducible factor-1α (HIF-1α) is considered as a key molecule in regulating Th17:regulatory T-cells (Tregs) balance. The aims of this study were to investigate whether HIF-1α is associated with the RORγ (RAR-related orphan receptor gamma) expression of Tregs in nasal polyps and to verify whether Staphylococcus enterotoxin B (SEB) is involved in this process. STUDY DESIGN: Clinical experimental study. METHODS: Forty patients with chronic rhinosinusitis with nasal polyposis were enrolled and divided into eosinophilic nasal polyps (EPs) and noneosinophilic nasal polyps (NEPs) according to the proportion of eosinophils. Fifteen subjects who were undergoing septoplasty were enrolled as control subjects. Expression of HIF-1α in the tissue was measured using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and flow cytometry. The mRNA expression of RORC (RAR-related orphan receptor C) and HIF-1α in Tregs separated from tissues were measured by RT-PCR. Double immunofluorescent staining for RORC/FOXP3 and HIF-1α/FOXP3 were conducted on the tissues. Expression of RORC and HIF-1α in Tregs from peripheral blood mononuclear cells (PBMCs) was measured using flow cytometry after stimulation with SEB. RESULTS: Expression of RORC and HIF-1α in Tregs was significantly higher in EPs and NEPs compared with control mucosa, and there was a significant correlation between RORC and HIF-1α expression in Tregs. Expression of RORC and HIF-1α mRNA in Tregs separated from the tissues was also significantly higher in nasal polyps compared with control mucosa. Expression of RORC and HIF-1α in Tregs were increased after 24-hour stimulation with SEB in the PBMCs. CONCLUSIONS: HIF-1α-induced RORC expression in Tregs may play a key role in the pathogenesis of nasal polyps.

Acupuncture and spontaneous regression of a radiculopathic cervical herniated disc.

The spontaneous regression of herniated cervical discs is not a well-established phenomenon. However, we encountered a case of a spontaneous regression of a severe radiculopathic herniated cervical disc that was treated with acupuncture, pharmacopuncture, and herb medicine. The symptoms were improved within 12 months of treatment. Magnetic resonance imaging (MRI) conducted at that time revealed marked regression of the herniated disc. This case provides an additional example of spontaneous regression of a herniated cervical disc documented by MRI following non-surgical treatment.