Comparative Interrupted Time Series Analysis of Medical Expenses in Patients with Intertrochanteric Fracture Who Underwent Internal Fixation and Hemiarthroplasty.

Purpose: The objective of this study was to assess postoperative direct medical expenses and medical utilization of elderly patients who underwent either hemiarthroplasty (HA) or internal fixation (IF) for treatment of a femoral intertrochanteric fracture and to analyze differences according to surgical methods and age groups. Materials and Methods: Data from the 2011 to 2018 Korean National Health Insurance Review & Assessment Service database were used. Risk-set matching was performed for selection of controls representing patients with the same sex, age, and year of surgery. A comparative interrupted time series analysis was performed for evaluation of differences in medical expenses and utilization between the two groups. Results: A total of 10,405 patients who underwent IF surgery and 10,405 control patients who underwent HA surgery were included. Medical expenses were 18% lower in the IF group compared to the HA group during the first year after the fracture (difference-in-difference [DID] estimate ratio 0.82, 95% confidence interval [CI] 0.77-0.87, P<0.001), and 9% lower in the second year (DID estimate ratio 0.91, 95% CI 0.85-0.99, P=0.018). Length of hospital stay was significantly shorter in the IF group compared to the HA group during the first two years after time zero in the age ≥80 group. Conclusion: A noticeable increase in medical expenses was observed for patients who underwent HA for treatment of intertrochanteric fractures compared to those who underwent IF over a two-year period after surgery. Therefore, consideration of such findings is critical when designing healthcare policy support for management of intertrochanteric fractures.

miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner.

The circular RNA (circRNA) Cdr1as is conserved across mammals and highly expressed in neurons, where it directly interacts with microRNA miR-7. However, the biological function of this interaction is unknown. Here, using primary cortical murine neurons, we demonstrate that stimulating neurons by sustained depolarization rapidly induces two-fold transcriptional upregulation of Cdr1as and strong post-transcriptional stabilization of miR-7. Cdr1as loss causes doubling of glutamate release from stimulated synapses and increased frequency and duration of local neuronal bursts. Moreover, the periodicity of neuronal networks increases, and synchronicity is impaired. Strikingly, these effects are reverted by sustained expression of miR-7, which also clears Cdr1as molecules from neuronal projections. Consistently, without Cdr1as, transcriptomic changes caused by miR-7 overexpression are stronger (including miR-7-targets downregulation) and enriched in secretion/synaptic plasticity pathways. Altogether, our results suggest that in cortical neurons Cdr1as buffers miR-7 activity to control glutamatergic excitatory transmission and neuronal connectivity important for long-lasting synaptic adaptations.

Design Principles of Quinone Redox Systems for Advanced Sulfide Solid-State Organic Lithium Metal Batteries.

The emergence of solid-state battery technology presents a potential solution to the dissolution challenges of the high-capacity small molecule quinone redox systems. Among the various available solid-state electrolytes, the argyrodite-type Li6PS5Cl is regarded as one of the most promising system due to high room-temperature ionic conductivity and low-temperature processability. Nonetheless, the successful integration of Li6PS5Cl and quinone redox systems into solid-state organic lithium metal batteries remains elusive due to their inherent reactivity. Here, a library of quinone derivatives is selected as model electrode materials to ascertain the critical descriptors governing the (electro)chemical compatibility and subsequently the performances of Li6PS5Cl-based solid-state organic Li-metal cells. Compatibility is attained if the lowest unoccupied molecular orbital level of the quinone derivative is sufficiently higher than the highest occupied molecular orbital level of Li6PS5Cl. The energy difference is demonstrated to be critical in ensuring chemical compatibility during composite electrode preparation and enable high-efficiency operation of solid-state organic Li-metal cells. Considering these findings, a general principle is proposed for the selection of quinone derivatives to be integrated with Li6PS5Cl, and two solid-state organic Li-metal cells, based on 2,5-diamino-1,4-benzoquinone and 2,3,5,6-tetraamino-1,4-benzoquinone, are successfully developed and tested for the first time. Validating critical factors for the design of organic battery electrode materials is expected to pave the way for advancing the development of high-efficiency and long cycle life solid-state organic batteries based on sulfides electrolytes. This article is protected by copyright. All rights reserved.

Association between cerebral artery stenosis and depressive symptoms in elderly patients.

OBJECTIVE: To examine the association between cerebral artery stenosis and depressive symptoms in elderly patients. METHODS: The study participants were 365 patients aged ≥65 years who visited the psychiatric outpatient clinic, Samsung Medical Center between January 1, 2000, and December 31, 2019, and were diagnosed with depressive disorder. They had brain imaging tests including magnetic resonance angiography (MRA), psychological evaluations including the 15-item Geriatric Depression Scale (GDS-15), and lab tests. Individuals' cerebral artery stenosis was identified and the association with significant depressive symptoms was examined. RESULTS: Of the 365 subjects, 108 had at least one location of cerebral artery stenosis (29.6 %). The mean score of GDS-15 in the stenosis group was 8.1 (SD, 3.8), higher than the mean GDS-15 score of 6.5 (SD, 4.0) for the group without stenosis (p < 0.001). Compared to no middle cerebral artery (MCA) stenosis, having MCA stenosis was associated with significant depressive symptoms (p = 0.005). Compared to no posterior cerebral artery (PCA) stenosis, having left PCA stenosis was associated with significant depressive symptoms (p = 0.022). In the multivariable linear regression analysis, only bilateral MCA stenosis had a positive association with the score of GDS-15 (p = 0.013). CONCLUSION: Bilateral MCA stenosis and left PCA stenosis are associated with significant depressive symptoms among elderly patients, with bilateral MCA stenosis positively associated with the severity of depression.

Early Implementation of Exercise to Facilitate Recovery After Breast Cancer Surgery: A Randomized Clinical Trial.

Importance: Recovery of shoulder function following breast cancer surgery is crucial for physical functioning and quality of life. While early implementation of shoulder rehabilitation exercises may enhance recovery, the optimal timing and exercise program remain unclear. Objective: To investigate whether an early exercise intervention, initiated 1 day postsurgery and continued for 1 month through subsequent visits, could improve shoulder range of motion (ROM) and strength in patients with breast cancer. Design, Setting, and Participants: A parallel-group, 2-arm randomized clinical trial was conducted between June 2020 and October 2021 at the Breast Cancer Center in Seoul, South Korea. Fifty-six patients (of 119 screened) with early-stage breast cancer who were scheduled for partial or total mastectomy were randomized into a tailored resistance exercise group (n = 28) or a usual care group (n = 28). Data were analyzed from November 2021 to June 2022. Interventions: The exercise intervention commenced 1 day postsurgery and consisted of 4 supervised exercise education sessions corresponding with surgeon visits and daily home-based exercises for the first postoperative month. Tailored programs, including stretching and strength exercises, were adjusted based on individual shoulder function recovery status. Main Outcomes and Measures: Primary end points were shoulder ROM and strength at 1 and 6 months postsurgery. Physical activity, body composition, and quality of life were assessed at 6 months. Results: Of 56 patients randomized (mean [SD] age, 50.3 [6.6] years), 54 completed the trial (96%), with 100% and 97% compliance to supervised and home-based exercise sessions, respectively. At 1 month postsurgery, 19 (67.9%) in the exercise group had fully recovered shoulder strength compared to 1 (3.6%) in the usual care group (P < .001). At 6 months, 22 (78.6%) in the exercise group had fully recovered shoulder ROM and 24 (85.7%) had fully recovered strength compared to 6 (21.4%) and 5 (17.9%), respectively, in the usual care group (P < .001). The exercise group exhibited less loss in muscle mass and improved physical activity and quality of life compared to the usual care group. Conclusion and Relevance: In this trial, 1-month tailored exercise program, initiated immediately after breast cancer surgery and supplemented with supervised sessions coinciding with surgeon visits, significantly improved shoulder function in patients with breast cancer. Trial Registration: WHO International Clinical Trials Registry identifier: KCT0006997.

Physiological and metabolic analyses reveal the proline-mediated flowering delay mechanism in Prunus persica.

Peaches are susceptible to various environmental stresses. Particularly in late spring, freezing temperatures can damage peaches and consequently, affect their productivity. Therefore, flowering delay is a prominent strategy for avoiding spring frost damage. Our previous study confirmed that treatment with 5% sodium alginate and 100 mM CaCl2 (5AG) to avoid frost damage during the blooming stage delays flowering. To reveal the flowering delay mechanism of peaches, this study systematically analyzed the modification of amino acid profiles in control and 5AG-treated peach plants at different day intervals. Our findings indicate that arginine (Arg), glutamate (Glu), and proline (Pro) levels differed between the control and 5AG-treated peach shoots throughout the phenological development of flower buds. Furthermore, two amino acids (Arg and Glu) are involved in the Pro pathway. Thus, using a computational metabolomics method, Pro biosynthesis and its characteristics, gene ontology, gene synteny, cis-regulatory elements, and gene organizations were examined to decipher the involvement of Pro metabolism in peach flowering delay. In addition, qRT-PCR analysis revealed the transcriptional regulation of Pro-related and flowering-responsive genes and their role in flowering delay. Overall, this pilot study provides new insights into the role of Pro in the flowering delay mechanisms in Prunus persica through 5AG treatment.

Medium Chain Length Polyhydroxyalkanoate Production by Engineered Pseudomonas gessardii Using Acetate-formate as Carbon Sources.

Production of medium chain length polyhydroxyalkanoate (mcl-PHA) was attempted using Pseudomonas gessardii NIBRBAC000509957, which was isolated from Sunchang, Jeollabuk-do, Republic of Korea (35°24'27.7"N, 127°09'13.0"E) and effectively utilized acetate and formate as carbon sources. We first evaluated the utilization of acetate as a carbon source, revealing optimal growth at 5 g/L acetate. Then, formate was supplied to the acetate minimal medium as a carbon source to enhance cell growth. After overexpressing the acetate and formate assimilation pathway enzymes, this strain grew at a significantly higher rate in the medium. As this strain naturally produces PHA, it was further engineered metabolically to enhance mcl-PHA production. The engineered strain produced 0.40 g/L of mcl-PHA with a biomass content of 30.43% in fed-batch fermentation. Overall, this strain can be further developed to convert acetate and formate into valuable products.

Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.

Glioblastoma recruits various nontransformed cells from distant tissues. Although bone marrow-derived mesenchymal stem cells (MSCs) have been observed migrating to glioblastoma, the underlying mechanism driving MSC migration toward glioblastoma remains unclear. Tumor vascularity is critical in the context of recurrent glioblastoma and is closely linked to the expression of stromal cell-derived factor-1 (SDF-1). We demonstrated that cadherin-6 mediated MSC migration both toward SDF-1 and toward glioblastoma cells. Cadherin-6 knockdown resulted in the downregulation of MSCs capacity to migrate in response to SDF-1. Furthermore, MSCs with cadherin-6 knockdown exhibited impaired migration in response to conditioned media derived from glioblastoma cell lines (U87 and U373) expressing SDF-1, thus simulating the glioblastoma microenvironment. Moreover, MSCs enhanced the vasculogenic capacity of U87 cells without increasing the proliferation, cancer stem cell characteristics, or migration of U87. These results suggest that the current strategy of utilizing MSCs as carriers for antiglioblastoma drugs requires careful examination. Furthermore, cadherin-6 may represent a novel potential target for controlling the recruitment of MSCs toward glioblastoma.

The role of surgery for optic pathway gliomas in the era of precision medicine.

Optic pathway gliomas (OPGs) represent a unique subset of brain tumours that primarily affect the paediatric population. Traditionally, these tumours are managed conservatively due to their location to and association with vital structures. This article explores the evolving role of surgery in the management of OPGs, particularly in the context of advancements in precision medicine. The advent of targeted therapy, especially for tumours with specific genetic alterations, such as BRAF V600E mutations, has revolutionized the treatment landscape, offering new avenues for patient-specific therapy. However, surgery still plays a crucial role, especially for debulking in cases of hydrocephalus or when standard therapies are ineffective. Advances in surgical techniques, including neuronavigation, endoscopic approaches, and intraoperative neurophysiological monitoring, have enhanced the safety and efficacy of operative interventions. Despite these developments, the complexity of OPGs necessitates a multidisciplinary approach, focusing on long-term outcomes and quality of life. Future research is needed to further elucidate the role of surgery in an era increasingly dominated by molecular genetics and targeted therapies.

Outcome of Transarterial Radioembolization in the Treatment of Hepatocellular Carcinoma: Glass Versus Resin Microsphere.

PURPOSE: To compare the treatment outcomes of glass and resin microspheres for the treatment of hepatocellular carcinoma (HCC) and evaluate the prognostic factors that influence the outcomes. MATERIALS AND METHODS: We retrospectively reviewed 251 consecutive patients who underwent radioembolization for the treatment of HCC at a single tertiary center. Imaging responses after radioembolization were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors. RESULTS: A total of 195 patients were included in this study (glass microsphere, n = 75; resin microsphere, n = 120). The complete and objective response rates were 16.0% and 50.7% in the glass microsphere group and 17.5% and 58.3% in the resin microsphere group, respectively. Median PFS was 241 days in the glass microsphere group and 268 days in the resin microsphere group (p = 0.871). Median OS was 29 months in the glass microsphere group and 40 months in the resin microsphere group (p = 0.669). The only significant prognostic factor was bilobar tumor distribution, which favored resin microspheres (p = 0.023). Procedure-related adverse events occurred more frequently in the resin microsphere group (glass, 2.7% vs. resin, 5.0%; p < 0.001). CONCLUSION: Glass and resin microspheres for the treatment of HCC did not show a significant difference in survival, though major adverse events occurred more frequently with the use of resin microspheres.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

Paenarthrobacter aromaticivorans sp. nov., a paraoxon-degrading bacterium isolated from red pepper cultivation soil.

A bacterial strain designated MMS21-TAE1-1T, capable of degrading paraoxon, was isolated from red pepper soil (36° 25' 26.0″ N, 126° 25' 47.0″ E) and subjected to polyphasic taxonomic characterisation. MMS21-TAE1-1T was an aerobic, non-motile and Gram-stain-positive bacterium. MMS21-TAE1-1T showed growth at 10-37 °C (optimum, 30 °C), at pH 4-10 (optimum, pH 7) and in the presence of 0-6 % NaCl (optimum, 0 %). On the basis of the results of 16S rRNA gene sequence analysis, MMS21-TAE1-1T could be assigned to the genus Paenarthrobacter and shared the highest sequence similarities with Paenarthrobacter aurescens NBRC 12136T (99.72 %), then with Paenarthrobacter nitroguajacolicus G2-1T (99.65 %) and Paenarthrobacter ilicis DSM 20138T (99.17 %). However, the results of genome-based comparison using orthologous average nucleotide identity (orthoANI) and digital DNA-DNA hybridisation indicated that MMS21-TAE1-1T could be readily distinguished from all species of the genus with validly published names. The predominant menaquinone of MMS21-TAE1-1T was MK-9(H2). The diagnostic polar lipids were diphosphatidylglycerol and phosphatidylinositol, and unidentified glycolipids were also present. The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and iso-C15 : 0. The chemotaxonomic properties of MMS21-TAE1-1T were generally consistent with those of members of the genus Paenarthrobacter. The genome of MMS21-TAE1-1T contained genes related to degradation of aromatic compounds. It is evident from the results of this study that strain MMS21-TAE1-1T merits recognition as representing a novel species of the genus Paenarthrobacter, for which the name Paenarthrobacter aromaticivorans sp. nov. is proposed. The type strain is MMS21-TAE1-1T (=KCTC 49652T = LMG 32368T).

Association of the Type of Public Pension With Mental Health Among South Korean Older Adults: Longitudinal Observational Study.

BACKGROUND: As income and health are closely related, retirement is considered undesirable for health. Many studies have shown the association between pension and health, but no research has considered the association between contribution-based public pensions or their types and health. OBJECTIVE: This study investigates the association between the type of contributory public pension and depressive symptoms among older adults. METHODS: We analyzed the data of 4541 older adults who participated in the South Korea Welfare Panel Study (2014-2020). Depressive symptoms were measured using the 11-item Center for Epidemiologic Studies Depression scale. Public pensions in South Korea are classified into specific corporate pensions and national pensions. For subgroup analyses, pensioners were categorized according to the amount of pension received and the proportion of public pension over gross income. Analyses using generalized estimating equations were conducted for longitudinal data. RESULTS: Individuals receiving public pension, regardless of the pension type, demonstrated significantly decreased depressive symptoms (national pension: ß=-.734; P<.001; specific corporate pension: ß=-.775; P=.02). For both pension types, the higher the amount of benefits, the lower were the depression scores. However, this association was absent for those who received the smaller amount among the specific corporate pensioners. In low-income households, the decrease in the depressive symptoms based on the amount of public pension benefits was greater (fourth quartile of national pension: ß=-1.472; P<.001; second and third quartiles of specific corporate pension: ß=-3.646; P<.001). CONCLUSIONS: Our study shows that contributory public pension is significantly associated with lower depressive symptoms, and this association is prominent in low-income households. Thus, contributory public pensions may be good income sources for improving the mental health of older adults after retirement.

Demand and Requirements for a Digital Healthcare System to Manage Gestational Diabetes in Patients and Healthcare Professionals: A Cross-sectional Survey.

This study aimed to assess the current status of gestational diabetes mellitus (GDM) diagnosis and management, and the demand for a digital healthcare system, in order to develop an optimal digital-based management model for GDM. An anonymous online survey was conducted targeting pregnant/postpartum women (Group W), internal medicine physicians (Group P), and obstetricians (group O) from September 6, 2022 to December 31, 2022. The survey assessed the women's knowledge of GDM and gathered information about healthcare professionals' (HCPs) current GDM management practices. All groups were asked about their acceptance of and demands for a digital healthcare system for GDM. Statistical comparisons between groups were conducted using the chi-square test or Fisher's exact test where appropriate. A total of 168 participants were in Group W, 185 in Group P, and 256 in Group O. Participants from all groups recognized the need for a digital healthcare system for GDM (Group W: 95.8%, Group P: 85.9%, Group O: 60%). However, HCPs showed less willingness to integrate these systems into their clinics than pregnant/postpartum women. Essential features identified were recording blood glucose levels and insulin, along with automatic data linkage from self-monitoring devices. Group W showed a higher preference for lab test access, search functionality, and fetal weight assessment than groups P and O (all P < .0001), while Groups P and O had a greater preference for recording insulin and maternal body weight compared to Group W (P = .0141 and .0023, respectively). Both pregnant/postpartum women and HCPs acknowledged the benefits of utilizing a digital healthcare system for managing GDM. However, there were differences in perspectives among these groups.

Changes in ocular biometrics following cycloplegic refraction in strabismic and amblyopic children.

This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ±â€…0.33 vs 3.58 ±â€…0.29 mm, P < .05) and WTW (12.09 ±â€…0.42 vs 12.30 ±â€…0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ±â€…3.00 D to -0.06 ±â€…3.32 D (P < .05) in overall and a myopic shift from -6.97 ±â€…4.27 to -8.10 ±â€…2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study.

BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.

Integrative analysis of plasma and substantia nigra in Parkinson's disease: unraveling biomarkers and insights from the lncRNA-miRNA-mRNA ceRNA network.

Introduction: Parkinson's disease (PD) is a rapidly growing neurological disorder characterized by diverse movement symptoms. However, the underlying causes have not been clearly identified, and accurate diagnosis is challenging. This study aimed to identify potential biomarkers suitable for PD diagnosis and present an integrative perspective on the disease. Methods: We screened the GSE7621, GSE8397-GPL96, GSE8397-GPL97, GSE20163, and GSE20164 datasets in the NCBI GEO database to identify differentially expressed (DE) mRNAs in the substantia nigra (SN). We also screened the GSE160299 dataset from the NCBI GEO database to identify DE lncRNAs and miRNAs in plasma. We then constructed 2 lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory networks based on the ceRNA hypothesis. To understand the biological function, we performed Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses for each ceRNA network. The receiver operating characteristic analyses (ROC) was used to assess ceRNA results. Results: We identified 7 upregulated and 29 downregulated mRNAs as common DE mRNAs in the 5 SN datasets. In the blood dataset, we identified 31 DE miRNAs (9 upregulated and 22 downregulated) and 332 DE lncRNAs (69 upregulated and 263 downregulated). Based on the determined interactions, 5 genes (P2RX7, HSPA1, SLCO4A1, RAD52, and SIRT4) appeared to be upregulated as a result of 10 lncRNAs sponging 4 miRNAs (miR-411, miR-1193, miR-301b, and miR-514a-2/3). Competing with 9 genes (ANK1, CBLN1, RGS4, SLC6A3, SYNGR3, VSNL1, DDC, KCNJ6, and SV2C) for miR-671, a total of 26 lncRNAs seemed to function as ceRNAs, influencing genes to be downregulated. Discussion: In this study, we successfully constructed 2 novel ceRNA regulatory networks in patients with PD, including 36 lncRNAs, 5 miRNAs, and 14 mRNAs. Our results suggest that these plasma lncRNAs are involved in the pathogenesis of PD by sponging miRNAs and regulating gene expression in the SN of the brain. We propose that the upregulated and downregulated lncRNA-mediated ceRNA networks represent mechanisms of neuroinflammation and dopamine neurotransmission, respectively. Our ceRNA network, which was associated with PD, suggests the potential use of DE miRNAs and lncRNAs as body fluid diagnostic biomarkers. These findings provide an integrated view of the mechanisms underlying gene regulation and interactions in PD.

Efficacy and Safety of Bojungikgi-Tang for Persistent Allergic Rhinitis: A Randomized, Double-Blinded, Placebo-Controlled, Phase II Trial.

Conventional treatments for allergic rhinitis (AR) exhibit insufficiency and long-term use-related side effects. Considering the reported anti-inflammatory and immunoregulatory effects of Bojungikgi-tang (BJIGT), we aimed to assess its efficacy on persistent AR (PAR). Patients with PAR were randomly assigned in a 1:1:1 ratio into high-dose BJIGT, standard-dose BJIGT, and placebo groups, followed by 1-week run-in and 4-week treatment periods. The primary outcome included the mean change in Total Nasal Symptom Score (TNSS), with secondary outcomes encompassing the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, biomarkers, overall assessment, TNSS by AR pattern identification, and the Sasang constitution. The mean TNSS change was more improved in the BJIGT group than in the placebo group; however, no statistically significant differences were observed. Additional interaction effect analysis revealed a statistically significant improvement in the high-dose BJIGT group compared with the placebo group from weeks 1-2 to weeks 3-4. Regarding secondary outcomes, the BJIGT group exhibited similar or improved results compared with the placebo group, showing no statistically significant differences. No serious adverse effects or clinically significant changes in safety assessments were observed. Given that this study validated clinical improvement and safety, it serves as potential groundwork for pertinent future studies.

Quorum Quenching Potential of Reyranella sp. Isolated from Riverside Soil and Description of Reyranella humidisoli sp. nov.

Quorum quenching refers to any mechanism that inhibits quorum sensing processes. In this study, quorum quenching activity among bacteria inhabiting riverside soil was screened, and a novel Gram-stain-negative, rod shaped bacterial strain designated MMS21-HV4-11T, which showed the highest level of quorum quenching activity, was isolated and subjected to further analysis. Strain MMS21-HV4-11T could be assigned to the genus Reyranella of Alphaproteobacteria based on the 16S rRNA gene sequence, as the strain shared 98.74% sequence similarity with Reyranella aquatilis seoho-37T, and then 97.87% and 97.80% sequence similarity with Reyranella soli KIS14-15T and Reyranella massiliensis 521T, respectively. The decomposed N-acyl homoserine lactone was restored at high concentrations under acidic conditions, implying that lactonase and other enzyme(s) are responsible for quorum quenching. The genome analysis indicated that strain MMS21-HV4-11T had two candidate genes for lactonase and one for acylase, and expected protein structures were confirmed. In the quorum sensing inhibition assay using a plant pathogen Pectobacterium carotovorum KACC 14888, development of soft rot was significantly inhibited by strain MMS21-HV4-11T. Besides, the swarming motility by Pseudomonas aeruginosa PA14 was significantly inhibited in the presence of strain MMS21-HV4-11T. Since the isolate did not display direct antibacterial activity against either of these species, the inhibition was certainly due to quorum quenching activity. In an extended study with the type strains of all known species of Reyranella, all strains were capable of degrading N-acyl homoserine lactones (AHLs), thus showing quorum quenching potential at the genus level. This is the first study on the quorum quenching potential and enzymes responsible in Reyranella. In addition, MMS21-HV4-11T could be recognized as a new species through taxonomic characterization, for which the name Reyranella humidisoli sp. nov. is proposed (type strain = MMS21-HV4-11 T = KCTC 82780 T = LMG 32365T).