Optimizing polystyrene degradation, microbial community and metabolite analysis of intestinal flora of yellow mealworms, Tenebrio molitor.

This study explored a direct feeding of expanded polystyrene as the sole diet for breeding Tenebrio molitor larvae. Temperature and relative humidity were manipulated to evaluate polystyrene biodegradation efficiency, survival rate, and formation of micro-polystyrene residue. Efficient conditions were at temperature of 25 °C with a humidity of 65 ± 5 %. Comparative metabolomic and metabolic-metabolic network analyses was performed for visualizing detailed pathway. Possibility of forming 4 (p)-hydroxyphenylacetic acid from phenylacetic acid with further conversion to 4-methylphenol, 4-hydroxybenzaldehyde, and 4-hydroxybenzoate could be seen as a side chain route for further biodegrading process. Key species identified in the gut of T. molitor larvae included Citrobacter sp., Serratia marcescens, Klebsiella aerogenes, and Klebsiella oxytoca. Pseudomonas aeruginosa was detected only under an anaerobic condition whereas Acinetobacter sp. was present only under an aerobic condition. These results demonstrate the potential to decrease micro-polystyrene by optimizing breeding conditions and biodegradation process of polystyrene.

Values, challenges, and responses associated with high-priced potential cures: perspectives of diverse stakeholders in South Korea.

BACKGROUND: The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies. METHODS: From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online surveys to effectively capture and synthesise stakeholder perspectives. RESULTS: Affordability was identified as a critical concern by 84% of stakeholders, followed by clinical uncertainty (76%) and limited value for money (72%). Stakeholders expressed a preference for both financial-based controls and outcome-based pricing strategies to mitigate these challenges. Despite the support for outcome-based refunds, payers raised concerns about the feasibility of instalment payment models, whether linked to outcomes or not, due to the specific challenges of the Korean reimbursement system and the potential risk of 'cumulative liabilities' from ongoing payments for previously administered treatments. In addition, the FGIs highlighted the need for clear budgetary limits for drugs with high uncertainties, with mixed opinions on the creation of special silo funds (64.0% agreement). Less than half (48%) endorsed the use of external reference pricing, currently applied to such essential drugs in South Korea. A significant majority (84%), predominantly non-pharma stakeholders, advocated for addressing cost-effectiveness uncertainty through re-assessment once long-term clinical data become available. CONCLUSIONS: This study uncovers a broad agreement among stakeholders on the need for more effective value assessment methodologies for high-priced potential cures, stressing the importance of more robust and comprehensive re-assessment supported by long-term data collection, rather than primarily relying on external reference pricing. Each type of stakeholders exhibited a cautious approach to their specific uncertainties, suggesting that new funding strategies should accommodate these uncertainties with predefined guidelines and agreements prior to the initiation of managed entry agreements.

Plant-Produced Therapeutic Crizanlizumab Monoclonal Antibody Binds P-Selectin to Alleviate Vaso-occlusive Pain Crises in Sickle Cell Disease.

Sickle Cell Disease (SCD) is a severe genetic disorder causing vascular occlusion and pain by upregulating the adhesion molecule P-selectin on endothelial cells and platelets. It primarily affects infants and children, causing chronic pain, circulatory problems, organ damage, and complications. Thus, effective treatment and management are crucial to reduce SCD-related risks. Anti-P-selectin antibody Crizanlizumab (Crimab) has been used to treat SCD. In this study, the heavy and light chain (HC and LC) genes of anti-P-Selectin antibody Crimab were cloned into a plant expression binary vector. The HC gene was under control of the duplicated 35S promoter and nopaline synthase (NOS) terminator, whereas the LC gene was under control of the potato proteinase inhibitor II (PIN2) promoter and PIN2 terminator. Agrobacterium tumefaciens LBA4404 was used to transfer the genes into the tobacco (Nicotiana tabacum cv. Xanthi) plant. In plants the genomic PCR and western blot confirmed gene presence and expression of HC and LC Crimab proteins in the plant, respectively. Crimab was successfully purified from transgenic plant leaf using protein A affinity chromatography. In ELISA, plant-derived Crimab (CrimabP) had similar binding activity to P-selectin compared to mammalian-derived Crimab (CrimabM). In surface plasmon resonance, the KD (dissociation binding constant) and response unit values were lower and higher than CrimabP, respectively. Taken together, these results demonstrate that the transgenic plant can be applied to produce biofunctional therapeutic monoclonal antibody.

miR-616-3p alleviates inflammatory response by targeting C-X-C motif chemokine ligand 5.

C/EBP homologous protein (CHOP) is a key regulator in ER stress-mediated signaling pathway via PERK-dependent unfolded protein response. It has been known that microRNA-616 (miR-616) is produced from the intron of the human DDIT3 gene encoding CHOP and increased by ER stress. However, the role of miR-616 and its targets are not fully addressed yet. Here we try to identify a novel target of miR-616 in human lung epithelial cells. Microarray analysis showed that CXCL5 is the most downregulated gene by miR-616 overexpression in A549 cells. We also found that CXCL5 mRNA and protein levels were significantly reduced by miR-616 mimic in the presence or absence of TNFα, while anti-miR-616 enhanced CXCL5 expression. In addition, miR-616-3p targeting sequence in 3'UTR of CXCL5 was confirmed by luciferase reporter assay suggesting that miR-616-3p directly binds to 3'UTR of CXCL5 and inhibits CXCL5 expression. Finally, we confirmed that conditioned medium from A549 cells treated with TNFα or Streptococcus pneumoniae lysates increased intra-alveolar neutrophil infiltration in a mouse model of pulmonary inflammation, while this induction was significantly reduced in a conditioned medium from cells transfected with miR-616-3p. These results suggest that miR-616-3p can alleviate CXCL5-induced pulmonary inflammatory response via targeting 3'UTR of CXCL5 gene.

The road to recovery: impact of COVID-19 on healthcare utilization in South Korea in 2016-2022 using an interrupted time-series analysis.

Background: The COVID-19 pandemic substantially disrupted healthcare utilization patterns, globally. South Korea had been praised widely in its efforts to contain the spread of the pandemic, which may have contributed to a significantly smaller reduction in healthcare utilization compared to neighboring countries. However, it remains unknown how the COVID-19 pandemic impacted utilization patterns across population sub-groups, particularly vulnerable patient groups in South Korea. This paper quantifies the changes in healthcare utilization attributable to COVID-19 and the COVID-19 vaccination by sub-groups. Methods: An interrupted time series analysis was conducted to examine the impact of COVID-19 on healthcare utilization in South Korea from January 2016 to December 2022 using aggregated patient-level data from the national health insurance system that accounts for 99% of all healthcare services in South Korea. We applied negative binomial models adjusting for seasonality and serial correlation. Falsification tests were conducted to test the validity of breakpoints. Stratified analyses by type of healthcare services, age, sex, income level, health facility type, and avoidable/non-avoidable hospitalizations was performed, and we assessed differences in utilization trends between population groups across three phases of the pandemic. Findings: In early 2020, the COVID-19 pandemic caused a reduction in monthly volume of outpatient utilization by 15.7% [95% CI 13.3%-18.1%, p < 0.001] and inpatient utilization by 11.6% [10.1%-13.0%, p < 0.001]. Most utilization recovered and rebounded to pre-COVID-19 levels as of December 2022 although variations existed. We observed heterogeneity in the magnitude of relative changes in utilization across types of services, varying from a 42.7% [36.8%-48.0%, p < 0.001] decrease for pediatrics, a 23.4% [20.1%-26.5%%, p < 0.001] reduction in utilization of public health centers, and a 24.2% [21.2%-27.0%, p < 0.001] reduction in avoidable hospitalizations compared to the pre-pandemic period. Contrary to global trends, health utilization among the elderly population (65 and older) in South Korea saw only marginal reductions compared to other age groups. Similarly, Medicaid patients and lower income groups experienced a smaller reduction compared to higher income groups. Interpretation: The impact of the COVID-19 pandemic on healthcare utilization in South Korea was less pronounced compared to the global average. Utilization of vulnerable populations, including adults over 65 years old and lowest-income groups reduced less than other type of patients. Funding: No funding.

Suppression of TBCK enhances TRAIL-mediated apoptosis by causing the inactivation of the akt signaling pathway in human renal carcinoma Caki-1 cells.

BACKGROUND: TBC1 domain-containing kinase (TBCK) protein functions as a growth suppressor in certain cell types and as a tumor promoter in others. Although TBCK knockdown increases the responsiveness of cancer cells to anticancer drugs, the detailed mechanisms by which TBCK knockdown increases susceptibility to anticancer drugs remain unknown. OBJECTIVE: This study analyzed the role of TBCK in sensitivities to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and doxorubicin in human renal cancer cells. METHODS: Flow cytometry was employed to evaluate the extent of apoptosis. Western blotting, transient transfection, and lentiviral infection techniques were conducted to investigate the impact of TBCK on apoptosis-related protein expression and mitogen-activated protein kinase (MAPK). RESULTS: TBCK knockdown in renal cancer cells inhibits ERK and Akt signaling pathways and increases TRAIL and doxorubicin sensitivity. In TBCK-knockdown Caki-1 cells, ERK and Akt phosphorylation was suppressed compared to control cell lines, and TRAIL and doxorubicin sensitivities were increased in these cells. In addition, the phosphorylation of PDK1 was suppressed in TBCK-suppressed cells, indicating that TBCK may be involved in the PDK1 and Akt signaling pathways. The introduction of dominantly active Akt into TBCK-suppressed cells restored their sensitivity to TRAIL. In addition, TBCK downregulation enhanced TRAIL sensitivity in different renal cancer cell lines. CONCLUSIONS: These data suggest that TBCK could potentially have a crucial function in influencing the effects of anti-cancer drugs including TRAIL by modulating the signaling pathway involving Akt and PDK1 in human renal cancer cells.

Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study.

Background: The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease-Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI). Objectives: The goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy. Methods: A Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country. Results: From the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively. Conclusions: Based on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Mechanisms of Phytochemicals in Anti-Inflammatory and Anti-Cancer.

Phytochemicals are chemical compounds that exist in plants and serve various functions such as protecting against pests, UV radiation, and diseases [...].

Acoustic and Magnetic Stimuli-Based Three-Dimensional Cell Culture Platform for Tissue Engineering.

In a conventional two-dimensional (2D) culture method, cells are attached to the bottom of the culture dish and grow into a monolayer. These 2D culture methods are easy to handle, cost-effective, reproducible, and adaptable to growing many different types of cells. However, monolayer 2D cell culture conditions are far from those of natural tissue, indicating the need for a three-dimensional (3D) culture system. Various methods, such as hanging drop, scaffolds, hydrogels, microfluid systems, and bioreactor systems, have been utilized for 3D cell culture. Recently, external physical stimulation-based 3D cell culture platforms, such as acoustic and magnetic forces, were introduced. Acoustic waves can establish acoustic radiation force, which can induce suspended objects to gather in the pressure node region and aggregate to form clusters. Magnetic targeting consists of two components, a magnetically responsive carrier and a magnetic field gradient source. In a magnetic-based 3D cell culture platform, cells are aggregated by changing the magnetic force. Magnetic fields can manipulate cells through two different methods: positive magnetophoresis and negative magnetophoresis. Positive magnetophoresis is a way of imparting magnetic properties to cells by labeling them with magnetic nanoparticles. Negative magnetophoresis is a label-free principle-based method. 3D cell structures, such as spheroids, 3D network structures, and cell sheets, have been successfully fabricated using this acoustic and magnetic stimuli-based 3D cell culture platform. Additionally, fabricated 3D cell structures showed enhanced cell behavior, such as differentiation potential and tissue regeneration. Therefore, physical stimuli-based 3D cell culture platforms could be promising tools for tissue engineering.

Posterior Preventive Foraminotomy before Laminectomy Combined with Pedicle Screw Fixation May Decrease the Incidence of C5 Palsy in Complex Cervical Spine Surgery in Patients with Severe Myeloradiculopathy.

C5 palsy is a frequent sequela of cervical decompression surgeries for cervical myeloradiculopathy. Although many researchers have suggested various risk factors, such as cord shifting and the correction of lordotic angles, the tethering of the C5 root beneath the narrow foramen is an independent risk factor for C5 palsy. In this study, we tried to investigate different techniques for foramen decompression with posterior cervical fusion and assess the incidence of C5 palsy with each technique depending on the order of foraminal decompression. A combined 540° approach with LMS and uncovertebrectomy was used in group 1. Group 2 combined a 540° approach with pedicle screws and posterior foraminotomy, while posterior approach only with pedicle screws and foraminotomy was used in group 3. For groups 2 and 3, prophylactic posterior foraminotomy was performed before laminectomy. Motor manual testing to assess C5 palsy, the Neck Disability Index (NDI) and the Japanese Orthopedic Association (JOA) scores were determined before and after surgery. Simple radiographs, MRI and CT scans, were obtained to assess radiologic parameters preoperatively and postoperatively. A total of 362 patients were enrolled in this study: 208 in group 1, 72 in group 2, and 82 in group 3. The mean age was 63.2, 65.5, and 66.6 years in groups 1, 2, and 3, respectively. The median for fused levels was 4 for the three groups. There was no significant difference between groups regarding the number of fused levels. Weight, height, comorbidities, and diagnosis were not significantly different between groups. Preoperative JOA scores were similar between groups (p = 0.256), whereas the preoperative NDI score was significantly higher in group 3 than in group 2 (p = 0.040). Mean JOA score at 12-month follow-up was 15.5 ± 1.89, 16.1 ± 1.48, and 16.1 ± 1.48 for groups 1, 2, and 3, respectively; it was higher in group 3 compared with group 1 (p = 0.008) and in group 2 compared with group 1 (p = 0.024). NDI score at 12 months was 13, 12, and 13 in groups 1, 2, and 3, respectively; it was significantly better in group 3 than in group 1 (p = 0.040), but there were no other significant differences between groups. The incidence of C5 palsy was significantly lower in posterior foraminotomy groups with pedicle screws (groups 2 and 3) than in LMS with uncovertebrectomy (group 1) (p < 0.001). Thus, preventive expansive foraminotomy before decompressive laminectomy is able to significantly decrease the root tethering by stenotic lesion, and subsequently, decrease the incidence of C5 palsy associated with posterior only or combined posterior and anterior cervical fusion surgeries. Additionally, such expansive foraminotomy might be appropriate with pedicle screw insertion based on biomechanical considerations.

A Huge Gastric Angiolipoma Presenting with Acute Upper Gastrointestinal Hemorrhage: A Case Report.

BACKGROUND: Angiolipoma is a benign neoplasm mainly composed of adipose tissue and proliferating blood vessels and is relatively rare in the gastrointestinal tract. And among them, gastric angiolipomas are extremely rare and tend to be small. CASE PRESENTATION: We report the clinical and imaging features of a patient with a huge angiolipoma in the stomach and an episode of hematemesis and melena, caused by the ulceration of the gastric mucosa overlying the gastric subepithelial angiolipoma revealed by the endoscopic evaluation. The patient was anemic, and the anemia resolved after local surgical resection of the tumor. We also reviewed the imaging and histological features of the presenting gastric angiolipoma. CONCLUSION: Radiologists should be aware of this rare benign gastric tumor that may present with gastrointestinal hemorrhage.

L-carnosine Attenuates Bleomycin-Induced Oxidative Stress via NFκB Pathway in the Pathogenesis of Pulmonary Fibrosis.

Idiopathic Pulmonary fibrosis (IPF), a chronic interstitial lung disease, has pulmonary manifestations clinically characterized by collagen deposition, epithelial cell injury, and a decline in lung function. L-carnosine, a dipeptide consisting of ß-alanine and L-histidine, has demonstrated a therapeutic effect on various diseases because of its pivotal function. Despite the effect of L-carnosine in experimental IPF mice, its anti-oxidative effect and associated intercellular pathway, particularly alveolar epithelial cells, remain unknown. Therefore, we demonstrated the anti-fibrotic and anti-inflammatory effects of L-carnosine via Reactive oxygen species (ROS) regulation in bleomycin (BLM)-induced IPF mice. The mice were intratracheally injected with BLM (3 mg/kg) and L-carnosine (150 mg/kg) was orally administrated for 2 weeks. BLM exposure increased the protein level of Nox2, Nox4, p53, and Caspase-3, whereas L-carnosine treatment suppressed the protein level of Nox2, Nox4, p53, and Caspase-3 cleavage in mice. In addition, the total SOD activity and mRNA level of Sod2, catalase, and Nqo1 increased in mice treated with L-carnosine. At the cellular level, a human fibroblast (MRC-5) and mouse alveolar epithelial cell (MLE-12) were exposed to TGFß1 following L-carnosine treatment to induce fibrogenesis. Moreover, MLE-12 cells were exposed to cigarette smoke extract (CSE). Consequently, L-carnosine treatment ameliorated fibrogenesis in fibroblasts and alveolar epithelial cells, and inflammation induced by ROS and CSE exposure was ameliorated. These results were associated with the inhibition of the NFκB pathway. Collectively, our data indicate that L-carnosine induces anti-inflammatory and anti-fibrotic effects on alveolar epithelial cells against the pathogenesis of IPF.

Renomedullary Interstitial Cell Tumor Mimicking Renal Cell Carcinoma: A Case Report.

Renomedullary interstitial cell tumors are often incidentally identified either upon autopsy or kidney resection for other reasons. However, rare renomedullary interstitial cell tumor cases resulting in a clinical symptomatic mass have been reported. We present a case of renomedullary interstitial cell tumor that was manifested as an incidentally detected renal mass and mimicked renal cell carcinoma on the imaging features.

Health improvements of older adults based on benefit duration: Lessons from Korean social pension policies.

The social pension, introduced in 2008 in Korea, has now become the most prominent old age income for most older adults. As of May 2022, it paid a monthly benefit of around USD 275 for 6.0 million older persons aged 65 and over who belong to the bottom 70% of the income and asset distribution. Although social pension's objectives focus on alleviating old age poverty and increasing income levels, it also encompasses a clear implication on health: social pension benefit can be spent on items or activities that improve the beneficiary's health. Using the Korean Longitudinal Study on Ageing data, between 2006 and 2018, and the Propensity Score Matching combined with Generalized Difference-In-Differences based on event study design, this study investigates the effects of receiving the social pension on objective measures of health that are representative of health and well-being in old age, by benefit duration. Study results showed that continually receiving social pension significantly improved beneficiaries' grip strength and cognitive ability. Grip strength was improved by 2.3-kg in the fifth year of receiving social pension. Additionally, the cognitive ability (K-MMSE score) was improved by 1.309 points in the first year. Results of descriptive analysis suggested that the social pension may have benefitted the health of the beneficiaries by improving their nutrition, health care utilization, and physical activities, and reducing financial strain and associated stress level. To the best of our knowledge, this is the first study to investigate the cumulative effects of nation-wide social pension programs on older adults' objective health measures by benefit duration up to five years, in a high-income country setting where old age income security systems are under-developed.

Effect of Severe Plastic Deformation and Post-Deformation Heat Treatment on the Microstructure and Superelastic Properties of Ti-50.8 at.% Ni Alloy.

Severe plastic deformation via high-ratio differential speed rolling (HRDSR) was applied to the Ni-rich Ti-50.8Ni alloy. Application of HRDSR and a short annealing time of 5 min at 873 K leads to the production of a partially recrystallized microstructure with a small grain size of 5.1 µm. During the aging process for the annealed HRDSR sample at 523 K for 16 h, a high density of Ni3Ti4 particles was uniformly precipitated over the matrix, resulting in the formation of an R phase as the major phase at room temperature. The aged HRDSR sample exhibits excellent superelasticity and superelastic cyclability. This achievement can be attributed to an increase in strength through effective grain refinement and particle strengthening by Ni3Ti4 and a decrease in the critical stress for stress-induced martensite (B19') due to the presence of the R-phase instead of B2 as a major phase at room temperature. The currently proposed method for using HRDSR and post-deformation heat treatment allows for the production of Ni-rich NiTi alloys with excellent superelasticity in sheet form.

The Primary Process and Key Concepts of Economic Evaluation in Healthcare.

Economic evaluations in the healthcare are used to assess economic efficiency of pharmaceuticals and medical interventions such as diagnoses and medical procedures. This study introduces the main concepts of economic evaluation across its key steps: planning, outcome and cost calculation, modeling, cost-effectiveness results, uncertainty analysis, and decision-making. When planning an economic evaluation, we determine the study population, intervention, comparators, perspectives, time horizon, discount rates, and type of economic evaluation. In healthcare economic evaluations, outcomes include changes in mortality, the survival rate, life years, and quality-adjusted life years, while costs include medical, non-medical, and productivity costs. Model-based economic evaluations, including decision tree and Markov models, are mainly used to calculate the total costs and total effects. In cost-effectiveness or costutility analyses, cost-effectiveness is evaluated using the incremental cost-effectiveness ratio, which is the additional cost per one additional unit of effectiveness gained by an intervention compared with a comparator. All outcomes have uncertainties owing to limited evidence, diverse methodologies, and unexplained variation. Thus, researchers should review these uncertainties and confirm their robustness. We hope to contribute to the establishment and dissemination of economic evaluation methodologies that reflect Korean clinical and research environment and ultimately improve the rationality of healthcare policies.

Dapagliflozin induces apoptosis by downregulating cFILPL and increasing cFILPS instability in Caki-1 cells.

Dapagliflozin is a sodium/glucose cotransporter 2 inhibitor used recently to treat patients with type 2 diabetes. A recent study has demonstrated that dapagliflozin induces apoptosis in human renal and breast tumor cells. However, to the best of our knowledge, the molecular mechanism underlying dapagliflozin-mediated apoptosis in Caki-1 human renal carcinoma cells has not been elucidated. The present study demonstrated that the dapagliflozin treatment dose-dependently increased cell death in Caki-1 cells. Dapagliflozin treatment also induced apoptosis as confirmed by FITC-conjugated Annexin V/PI staining. Additionally, treatment with dapagliflozin reduced the expression levels of anti-apoptotic proteins, cellular Fas-associated death domain-like interleukin-1-converting enzyme-inhibitory protein (cFLIP)L and cFLIPS in Caki-1 cells. Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone inhibited dapagliflozin-induced apoptosis, implying that dapagliflozin-induced apoptosis is regulated by a caspase-dependent pathway. By contrast, N-acetylcysteine had no effect on dapagliflozin-induced apoptosis and downregulation of cFLIPL and cFLIPS expression. Furthermore, overexpression of cFLIPL, but not cFLIPS, partially inhibited apoptosis induced by dapagliflozin. cFLIPL and cFLIPS mRNA levels remained constant in Caki-1 cells after treatment with 0, 20, 40, 60, 80 and 100 µM dapagliflozin. Notably, it was confirmed that cFLIPS protein levels were reduced due to the increased cFLIPS instability in dapagliflozin-treated Caki-1 cells. The present study also demonstrated that dapagliflozin had no effect on HK-2 normal human kidney cells. Taken together, the present study revealed that dapagliflozin induced apoptosis via the downregulation of cFLIPL and an increase in cFLIPS instability, suggesting that dapagliflozin may be a feasible drug candidate for the treatment of human renal cancer.

A Tale of Two Social Insurance Systems in South Korea and Taiwan: A Financial Risk Protection Perspective.

Universal Health Coverage (UHC) is a widespread policy goal in the 21st century. The aim is to protect people from financial risk while promoting their access to good-quality care. This study examined the social insurance systems of South Korea and Taiwan to explore the critical challenges of achieving effective UHC. By assessing the impact of UHC on financial risk protection (measured by out-of-pocket payment share and catastrophic payment headcount), we found that when South Korea inaugurated its National Health Insurance (NHI) program with a limited benefits package and high cost sharing, it did not reduce the financial burden. Meanwhile, we observed a drop of 5 to 6 percentage points in the catastrophic payment headcount in Taiwan, which offered a universal and rather comprehensive benefits package with a modest cost-sharing design under its single-payer NHI system. The political-economic context of the UHC policy evolution was further explored through an in-depth discussion. We conclude that to provide sufficient financial risk protection against unexpected medical expenses, the design of the insurance scheme, in particular the risk-sharing mechanism, not only matters but is also the key to success.

Adjustable-Loop Cortical Suspensory Fixation Results in Greater Tibial Tunnel Widening Compared to Interference Screw Fixation in Primary Anterior Cruciate Ligament Reconstruction.

Background: Although the use of adjustable-loop suspensory fixation has increased in recent years, the influence of the shortcomings of suspensory fixation, such as the bungee-cord or windshield-wiper effects, on tunnel widening remains to be clarified. Hypothesis/Purpose: The purpose of this study was to compare adjustable-loop femoral cortical suspensory fixation and interference screw fixation in terms of tunnel widening and clinical outcomes after anterior cruciate ligament reconstruction (ACLR). We hypothesized that tunnel widening in the adjustable-loop femoral cortical suspensory fixation (AL) group would be comparable to that in the interference screw fixation (IF) group. Methods: This study evaluated patients who underwent primary ACLR at our institution between March 2015 and June 2019. The femoral and tibial tunnel diameters were measured using plain radiographs in the immediate postoperative period and 2 years after ACLR. Tunnel widening and clinical outcomes (Lysholm score, 2000 International Knee Documentation Committee subjective score, and Tegner activity level) were compared between the two groups. Results: There were 48 patients (mean age, 29.8 ± 12.0 years) in the AL group and 44 patients (mean age, 26.0 ± 9.5 years) in the IF group. Tunnel widening was significantly greater in the AL group than that in the IF group at the tibia anteroposterior (AP) middle (2.03 mm vs. 1.32 mm, p = 0.017), tibia AP distal (1.52 mm vs. 0.84 mm, p = 0.012), tibia lateral proximal (1.85 mm vs. 1.00 mm, p = 0.001), tibia lateral middle (2.36 mm vs. 1.03 mm, p < 0.001), and tibia lateral distal (2.34 mm vs. 0.85 mm, p < 0.001) levels. There were no significant differences between the two groups with respect to femoral tunnel widening and clinical outcomes. Conclusions: Tibial tunnel widening was significantly greater in the AL group than in the IF group at 2 years after primary ACLR. However, the clinical outcomes in the two groups were comparable at 2 years.

Interleukin-10 Protects against Ureteral Obstruction-Induced Kidney Fibrosis by Suppressing Endoplasmic Reticulum Stress and Apoptosis.

Fibrosis is a common final pathway of chronic kidney disease, which is a major incurable disease. Although fibrosis has an irreversible pathophysiology, the molecular and cellular mechanisms responsible remain unclear and no specific treatment is available to halt the progress of renal fibrosis. Thus, an improved understanding of the cellular mechanism involved and a novel therapeutic approach are urgently required for end-stage renal disease (ESRD). We investigated the role played by interleukin-10 (IL-10, a potent anti-inflammatory cytokine) in kidney fibrosis and the mechanisms involved using IL-10-/- mice and TCMK-1 cells (mouse kidney tubular epithelial cell line). Endoplasmic reticulum stress (ERS), apoptosis, and fibrosis in IL-10-/- mice were more severe than in IL-10+/+ mice after unilateral ureteral obstruction (UUO). The 4-Phenylbutyrate (an ERS inhibitor) treatment induced dramatic reductions in ERS, apoptosis, and fibrosis-associated factors in the renal tissues of IL-10-/- mice, compared to wild-type controls after UUO. On the other hand, in cultured TCMK-1 cells, the ERS inducers (tunicamycin, thapsigargin, or brefeldin A) enhanced the expressions of proapoptotic and profibrotic factors, though these effects were mitigated by IL-10. These results were supported by the observation that IL-10 siRNA transfection aggravated tunicamycin-induced CHOP and a-SMA expressions in TCMK-1 cells. We conclude that the anti-fibrotic effects of IL-10 were attributable to the inhibition of ERS-mediated apoptosis and believe that the results of this study improve the understanding of the cellular mechanism responsible for fibrosis and aid in the development of novel therapeutic approaches.