Oxidized LDL Accelerates Cartilage Destruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway.

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

The impact of instrumented lumbar fusion surgery on psychiatric problems in elderly patients with degenerative spinal stenosis: The observational study.

This is a prospective cohort study to investigate the effects of instrumented lumbar fusion surgery on psychiatric problems, including anxiety, insomnia, and depression, in patients with degenerative spinal stenosis, as well as on pain and the activities of daily living. Surgery was performed in the patients with Schizas grade C or D spinal stenosis with; if a patient's quality of life was impaired for at least 3 months or if patient had neurologic deficits. Finally, 69 patients were reviewed. Beck anxiety inventory, insomnia severity index, geriatric depression scale short form-Korean, visual analog scale for back pain, visual analog scale for leg pain, and Oswestry disability index was measured on the day surgery was decided on (T1), the day before surgery (T2), the day before discharge (T3), and 6 months after surgery (T4). The patients had mild degrees of anxiety, insomnia, and depression at T1, and Beck anxiety inventory, insomnia severity index, visual analog scale for back pain, visual analog scale for leg pain, and Oswestry disability index improved significantly by T4. In elderly patients with degenerative spinal stenosis, instrumented lumbar fusion surgery improves not only pain and activities of daily living, but also anxiety and insomnia. However, there was no improvement in depression over the 6-month follow-up period.

Clinical features and outcomes of posterior reversible encephalopathy syndrome after heart transplantation: a case series.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease that may be associated with hypertension, autoregulatory failure, and the use of calcineurin inhibitors following heart transplantation (HT). In this article, we present a case series of PRES, discussing its potential causes and management strategies. Among the 126 HT recipients at our hospital, four were diagnosed with PRES. Three of these patients developed PRES within 7 days after HT. Prior to the onset of PRES, all patients experienced sustained hypertension, and strict blood pressure (BP) control was maintained. Three of the four patients recovered without PRES recurrence, while one patient died of sepsis after an episode of altered consciousness. Hypertension was observed in all patients prior to the onset of PRES, and the majority experienced symptom improvement with BP control. While most cases of PRES were reversible with conservative treatment, including the administration of antiepileptics, one irreversible case resulted in in-hospital mortality. Thus, PRES can have serious outcomes and is not invariably benign.

Investigating Factors Influencing the National Cancer Screening Program among Older Individuals in Republic of Korea-Data from the Korea National Health and Nutrition Examination Survey VIII.

This study aims to determine the influencing factors of the participation of older individuals aged 65 years and above in South Korea's National Cancer Screening Program (NCSP) using data from the eighth wave (2019-2021) of the Korea National Health and Nutrition Examination Survey (KNHANES VIII), and discuss potential problems and coping strategies. Variables were selected based on Andersen's healthcare utilization model. "Participation in the NSCP" was considered the dependent variable, with independent variables including sociodemographic characteristics (sex, marital status, residence, education level, income level, economic activity, medical coverage type, and private insurance), health conditions (subjective health status, hypertension, and diabetes), and health behaviors (physical activity, monthly alcohol consumption, and current smoking status). The analysis revealed that higher participation rates correlated with being married, having an education level beyond elementary school, being employed, subscribing to private insurance, perceiving oneself as having average or poor health, engaging in physical activity, and not smoking. Sex, residence, income, medical coverage type, hypertension, diabetes, and monthly alcohol consumption were found to be insignificantly correlated. These findings underscore the importance of tailored promotion and health education for older individuals to boost NCSP participation rates, which could ultimately elevate public health standards.

Sn-Doped Zinc Oxide as an Electron Transporting Layer for Enhanced Performance in PbS Quantum Dot Solar Cells.

Colloidal PbS quantum dot solar cells (QDSCs) have been primarily demonstrated in n-i-p structures by incorporating a solution-processed ZnO electron transporting layer (ETL). Nevertheless, the inherent energy barrier for the electron extraction at the ZnO/PbS junction along with the defective nature significantly diminishes the performance of the PbS QDSCs. In this study, by employing Sn-doped ZnO (ZTO) ETL, we have tuned the conduction band offset at the junction from spike-type to cliff-type so that the electron extraction barrier can be eliminated and the overall photovoltaic parameters can be enhanced (open-circuit voltage of 0.7 V, fill factor over 70%, and efficiency of 11.3%) as compared with the counterpart with the undoped ZnO ETL. The X-ray photoelectron spectroscopy (XPS) analysis revealed a mitigation of oxygen vacancies in the ZTO ETL of our PbS QDSCs. Our work signifies the importance of Sn doping into the conventional ZnO ETL for the superior electron extraction in PbS QDSCs.

Femoral anteversion linked to the inability to squat: Analysis of CT images in the patient and control groups.

Many patients who cannot squat well in a neutral toe position can only squat in an excessively out-toeing position. This excessive out-toeing squat is thought to be caused by rotational problems of the lower extremities. In this study, we aimed to identify the cause for the inability to squat by measuring and comparing femoral and tibial torsion between an excessive out-toeing squat patient group and a control group representing the general population. Between 2008 and 2022, a patient group comprising 50 lower extremities with excessive out-toeing squats was established. A control group representing the general population was selected from patients aged 0 to 29 years, who underwent lower-extremity CT angiography between 2012 and 2022, using the Clinical Data Warehouse with exclusion criteria applied. A total of 94 lower extremities were included in the control group. The femoral torsional angle (FTA) and tibial torsional angle (TTA) of both groups were measured and compared using Student t test. Additionally, 30 each of those with the highest and lowest 30 FTA values were selected from the patient and control groups, and the TTA was compared between the high- and low-FTA groups using Student t test. The mean FTA was 0.34° (SD, 11.11°) in the patient group and 10.14° (SD, 11.85°) in the control group, with a mean difference of 9.8° and P < .001. The mean TTA was 27.95° (SD, 7.82°) in the patient group and 32.67 ° (SD, 7.58°) in the control group, with a mean difference of 4.72° (P = .001). The mean TTA was 34.3° (SD, 7.72°) in the high-FTA group and 28.17° (SD, 8.35°) in the low-FTA group, with a mean difference of 6.13° (P = .005). Patients with excessive out-toeing squat showed lower FTA and TTA values than the general population. Furthermore, although a correlation between FTA and TTA was not established through Pearson correlation analysis, a tendency was observed where a decrease in FTA was associated with a decrease in TTA. Based on these results, decreased FTA was demonstrated to be one of the major causes of excessive out-toeing squats.

The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism.

N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Endoxifen Concentration is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dosage. However, the clinical significance of endoxifen on the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients, and tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% CI, 77.0-89.9%) and 88.3% (95% CI, 83.3-93.5%) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor affecting prognosis, which was adjusted with other clinical characteristics. Conclusion: Endoxifen could serve as a marker for appropriate tamoxifen treatment, and an endoxifen cutoff of 21.00 ng/mL could be advantageous in prognostication. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying a suboptimal concentration.

Mitigation of benzyl butyl phthalate toxicity in male germ cells with combined treatment of parthenolide, N-acetylcysteine, and 3-methyladenine.

Benzyl butyl phthalate (BBP) is a widely used plasticizer that poses various potential health hazards. Although BBP has been extensively studied, the direct mechanism underlying its toxicity in male germ cells remains unclear. Therefore, we investigated BBP-mediated male germ cell toxicity in GC-1 spermatogonia (spg), a differentiated mouse male germ cell line. This study investigated the impact of BBP on reactive oxygen species (ROS) generation, apoptosis, and autophagy regulation, as well as potential protective measures against BBP-induced toxicity. A marked dose-dependent decrease in GC-1 spg cell proliferation was observed following treatment with BBP at 12.5 µM. Exposure to 50 µM BBP, approximating the IC50 of 53.9 µM, markedly increased cellular ROS generation and instigated apoptosis, as evidenced by augmented protein levels of both intrinsic and extrinsic apoptosis-related markers. An amount of 50 µM BBP induced marked upregulation of autophagy regulator proteins, p38 MAPK, and extracellular signal-regulated kinase and substantially downregulated the phosphorylation of key kinases involved in regulating cell proliferation, including phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase. The triple combination of N-acetylcysteine, parthenolide, and 3-methyladenine markedly restored cell proliferation, decreased BBP-induced apoptosis and autophagy, and restored mTOR phosphorylation. This study provides new insights into BBP-induced male germ cell toxicity and highlights the therapeutic potential of the triple inhibitors in mitigating BBP toxicity.

Highly Permeable Mixed Matrix Membranes for Gas Separation via Dual Defect-Engineered Zeolitic Imidazolate Framework-8.

Defect engineering of metal-organic frameworks (MOFs) is a promising strategy for tailoring the interfacial characteristics between MOFs and polymers, aiming to create high-performance mixed matrix membranes (MMMs). This study introduces a new approach using dual defective alkylamine (AA)-modulated zeolitic imidazolate framework-8 (DAZIF-8), to develop high-flux MMMs. Tributylamine (TBA) and triethylamine (TEA) monodentate ligands coordinate with zinc ions in varying compositions. A mixture of Zn(CH3COO)2·2H2O:2-methylimidazole (Mim):AA in a 1:1.75:5 molar ratio facilitates high-yield coordination between Zn and multiple organic ligands, including Zn-Mim, Zn-TEA, and Zn-TBA (>80%). Remarkably, DAZIF-8 containing 3 mol% TBA and 2 mol% TEA exhibits exceptional characteristics, such as a Brunauer-Emmett-Teller surface area of 1745 m2 g-1 and enhanced framework rigidity. Furthermore, dual Zn-AA coordination sites on the framework's outer surface enhance compatibility with the polyimide (PI) matrix through electron donor-acceptor interactions, enabling the fabrication of high-loading MMMs with excellent mechanical durability. Importantly, the PI/DAZIF-8 (60/40 w/w) MMM demonstrates an unprecedented 759% enhancement in ethylene (C2H4) permeability (281 Barrer) with a moderate ethylene/ethane (C2H4/C2H6) selectivity of 2.95 compared to the PI, surpassing the polymeric upper limit for C2H4/C2H6 separation.

Correction: Hill et al. A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis. Nutrients 2023, 15, 3769.

In the original publication [...].

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

How is eyeball growth associated with optic nerve head shape and glaucoma? The Lamina cribrosa/Bruch's membrane opening offset theory.

The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma.

Micropropagation and Shoot Tip Cryopreservation of 'Sunny Gold' Freesia.

Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.

DNA Hypermethylation Inhibits the CD82 Metastasis Suppressor Gene in Gastric Cancer.

BACKGROUND/AIM: Gastric cancer, with its high global incidence and mortality rates, poses a significant challenge due to the rapid decline in patient survival upon metastasis. Understanding and combating metastasis are crucial in improving outcomes. The metastasis suppressor gene CD82 has demonstrated efficacy in inhibiting metastasis across various carcinomas but is frequently down-regulated. However, its role and regulatory mechanisms in gastric cancer remain elusive. MATERIALS AND METHODS: Utilizing public data, we assessed patient survival in relation to CD82 expression. CD82 expression in gastric cancer cell lines was evaluated via western blotting, and its impact on cell mobility was assessed through wound healing and Transwell assays. The demethylation of CD82 was induced using 5-aza-deoxycytidine, while methylation levels were detected via methylation-specific PCR. RESULTS: Low CD82 expression correlated with poor prognosis in patients, and down-regulation and over-expression of CD82 significantly affected cell mobility. Treatment with 5-aza-deoxycytidine restored CD82 expression in low-expressing cell lines, highlighting its methylation-dependent regulation. CONCLUSION: CD82 serves as a pivotal regulator of cell mobility in gastric cancer by suppressing metastasis. Its expression is attenuated in gastric cancer cells through promoter hypermethylation.

No Change in Complications Following Thyroidectomy Despite Increase in Thyroid Cancer Surgeries: A Meta-Regression Analysis.

PURPOSE: The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. MATERIALS AND METHODS: PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords "thyroidectomy" and "complication." A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. RESULTS: This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). CONCLUSION: Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase.

Changes in respiratory infection trends during the COVID-19 pandemic in patients with haematologic malignancy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in high-risk patients with haematological malignancies (HM) is uncertain. We aimed to examine how community-acquired pneumonia aetiology in patients with haematological malignancies changed during the COVID-19 pandemic. METHODS: This was a retrospective study that included 524 patients with haematological malignancies hospitalised with community-acquired pneumonia between March 2018 and February 2022. Patients who underwent bronchoscopy within 24 h of admission to identify community-acquired pneumonia aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and polymerase chain reaction tests were analysed and compared to identify changes and in-hospital mortality risk factors. RESULTS: Patients were divided into the 'pre-COVID-19 era' (44.5%) and 'COVID-19 era' (55.5%) groups. The incidence of viral community-acquired pneumonia significantly decreased in the COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (pre-COVID-19 era vs. COVID-19 era: 3.0% vs. 0.3%, P = 0.036; 6.5% vs. 0.7%, P = 0.001; 5.6% vs. 1.4%, P = 0.015; and 9.5% vs. 1.7%, P < 0.001, respectively), whereas that of bacterial, fungal, and unknown community-acquired pneumonia aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet counts correlated with in-hospital mortality after adjusting for potential confounding factors. CONCLUSIONS: In the COVID-19 era, the incidence of community-acquired pneumonia with viral aetiologies markedly decreased among patients with haematological malignancies, with no changes in the incidence of bacterial and fungal pneumonia. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with haematological malignancies and community-acquired pneumonia.

The Effects of National Insurance Coverage Expansion and Genetic Counseling's Role on BRCA1/2 Mutation Tests in Breast Cancer Patients.

PURPOSE: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. MATERIALS AND METHODS: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. RESULTS: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. CONCLUSION: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts.