Association of the protective effect of telmisartan on hearing loss among patients with hypertension.

Aim: Hearing loss, affecting a significant portion of the global population, is prevented with peroxisome proliferator-activated receptor γ agonism. Understanding potential protective treatments is crucial for public health. We examine the effect of telmisartan, an antihypertensive drug and partial peroxisome proliferator-activated receptor γ agonist, on hearing loss in patients with hypertension. Method and results: This retrospective cohort analysis used data from the OMOP Common Data Model database, encompassing information from three tertiary institutions in South Korea. The study included a substantial sample size of 860,103 people diagnosed with hypertension. The study included individuals who had been medically diagnosed with hypertension and had been prescribed antihypertensive drugs, including telmisartan. The study design was established to evaluate the comparative effects of telmisartan and other hypertension medications on hearing loss. We used propensity score matching (PSM) to create a balanced cohort, reducing potential biases between the telmisartan and non-telmisartan groups. From the initial 860,103 patients with hypertension, a propensity score matched cohort was derived from 20,010 patients, with 2,193 in the telmisartan group. After PSM, lower incidence of total hearing loss was observed in the telmisartan group compared to the non-telmisartan group during the 3-year follow-up (0.5% vs. 1.5%, log-rank p = 0.005). In subgroup analysis, this study showed consistent results that lower incidence of total hearing loss was higher in the telmisartan group than in the non-telmisartan group. Conclusion: Telmisartan was associated with reducing certain types of hearing loss in patients with hypertension. Further research is needed to confirm these findings and understand the mechanisms.

Nitrosamine formation driven by electrochemical chlorination of urine-containing source waters: Effects of operational conditions.

We investigated the formation of nitrosamines from urine during electrochemical chlorination (EC) using dimensionally stable anodes. Short-term electrolysis (< 1 h) of urine at 25 mA cm-2 generated seven nitrosamines (0.1-7.4 µg L-1), where N-nitrosodimethylamine, N-nitrosomethylethylamine, and N-nitrosodiethylamine were predominant with concentrations ranging from 1.2 to 7.4 µg L-1. Mechanistic studies showed that the formation kinetics of nitrosamines was influenced by urine aging and composition, with fresh urine generating the highest levels (0.9-5.8 µg L-1) compared with aged, centrifuged, or filtered urine (0.2-4.1 µg L-1). Concurrently, studies on urine pretreatment through filtration and centrifugation underscored the significance of nitrogenous metabolites (such as protein-like products and urinary amino acids) and particle-associated humic fractions in nitrosamine formation during EC of urine. This finding was confirmed through chromatographic and spectroscopic studies utilizing LCOCD, Raman spectra, and 3DEEM fluorescence spectra. Parametric studies demonstrated that the ultimate [nitrosamines] increased at a pH range of 4.5-6.2, and with increasing [bromide], [ammonium], and current density. Conversely, sulfate and carbonate ions inhibited nitrosamine formation. Moreover, the implications of EC in urine-containing source waters were evaluated. The results indicate that regardless of the urine source (individual volunteers, septic tank, swimming pool, untreated municipal wastewater), high levels of nitrosamines (0.1-17.6 µg L-1) were generated, surpassing the potable reuse guideline of 10 ng L-1. Overall, this study provides insights to elucidate the mechanisms underlying nitrosamine formation and optimize the operating conditions. Such insights facilitate suppressing the generation of nitrosamine byproducts during electrochemical treatment of urine-containing wastewater.

Autonomous real-time control for membrane capacitive deionization.

Artificial intelligence has been employed to simulate and optimize the performance of membrane capacitive deionization (MCDI), an emerging ion separation process. However, a real-time control for optimal MCDI operation has not been investigated yet. In this study, we aimed to develop a reinforcement learning (RL)-based control model and investigate the model to find an energy-efficient MCDI operation strategy. To fulfill the objectives, we established three long-short term memory models to predict applied voltage, outflow pH, and outflow electrical conductivity. Also, four RL agents were trained to minimize outflow concentration and energy consumption simultaneously. Consequently, actor-critic (A2C) and proximal policy optimization (PPO2) achieved the ion separation goal (<0.8 mS/cm) as they determined the electrical current and pump speed to be low. Particularly, A2C kept the parameters consistent in charging MCDI, which caused lower energy consumption (0.0128 kWh/m3) than PPO2 (0.0363 kWh/m3). To understand the decision-making process of A2C, the Shapley additive explanation based on the decision tree model estimated the influence of input parameters on the control parameters. The results of this study demonstrate the feasibility of RL-based controls in MCDI operations. Thus, we expect that the RL-based control model can improve further and enhance the efficiency of water treatment technologies.

Comprehensive single cell transcriptomics analysis of murine osteosarcoma uncovers Skp2 function in metastasis, genomic instability and immune activation and reveals additional target pathways.

Osteosarcoma (OS) is the most common primary pediatric bone malignancy. One promising new therapeutic target is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase responsible for ubiquitination and proteasome degradation of substrate p27, thus driving cellular proliferation. We have shown previously that knockout of Skp2 in an immunocompetent transgenic mouse model of OS improved survival, drove apoptosis, and induced tumor inflammation. Here, we applied single-cell RNA-sequencing (scRNA-seq) to study primary OS tumors derived from Osx-Cre driven conditional knockout of Rb1 and Trp53. We showed that murine OS models recapitulate the tumor heterogeneity and microenvironment complexity observed in patient tumors. We further compared this model with OS models with functional disruption of Skp2: one with Skp2 knockout and the other with the Skp2-p27 interaction disrupted (resulting in p27 overexpression). We found reduction of T cell exhaustion and upregulation of interferon activation, along with evidence of replicative and endoplasmic reticulum-related stress in the Skp2 disruption models, and showed that interferon induction was correlated with improved survival in OS patients. Additionally, our scRNA-seq analysis uncovered decreased activities of metastasis-related gene signatures in the Skp2-disrupted OS, which we validated by observation of a strong reduction in lung metastasis in the Skp2 knockout mice. Finally, we report several potential mechanisms of escape from targeting Skp2 in OS, including upregulation of Myc targets, DNA copy number amplification and overexpression of alternative E3 ligase genes, and potential alternative lineage activation. These mechanistic insights into OS tumor biology and Skp2 function suggest novel targets for new, synergistic therapies, while the data and our comprehensive analysis may serve as a public resource for further big data-driven OS research.

Antiepileptic and Neuroprotective Effects of Rheum tanguticum Root Extract on Trimethyltin-Induced Epilepsy and Neurodegeneration: In Vivo and in Silico Analyses.

BACKGROUND: Rheum tanguticum root, cataloged as "Daehwang" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5). CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.

Occurrence, removal, and prioritization of organic micropollutants in four full-scale wastewater treatment plants in Korea.

This study investigated the occurrence, removal rate, and potential risks of 43 organic micropollutants (OMPs) in four municipal wastewater treatment plants (WWTPs) in Korea. Results from two-year intensive monitoring confirmed the presence of various OMPs in the influents, including pharmaceuticals such as acetaminophen (pain relief), caffeine (stimulants), cimetidine (H2-blockers), ibuprofen (non-steroidal anti-inflammatory drugs- NSAIDs), metformin (antidiabetics), and naproxen (NSAIDs) with median concentrations of >1 µg/L. Some pharmaceuticals (carbamazepine-anticonvulsants, diclofenac-NSAIDs, propranolol-ß-blockers), corrosion inhibitors (1H-benzotriazole-BTR, 4-methyl-1H-benzotriazole-4-TTR), and perfluorinated compounds (PFCs) were negligibly removed during WWTP treatment. The OMP concentrations in the influents and effluents were mostly lower in August than those of other months (p-value <0.05) possibly due to wastewater dilution by high precipitation or enhanced biodegradation under high-temperature conditions. The anaerobic-anoxic-oxic process (A2O) with a membrane bioreactor exhibited higher OMP removal than other processes, such as A2O with sedimentation or the conventional activated sludge process (p-value <0.05). Pesticides (DEET and atrazine), corrosion inhibitors (4-TTR and BTR), and metformin were selected as priority OMPs in toxicity-driven prioritization, whereas PFCs were determined as priority OMPs given their persistence and bioaccumulation properties. Overall, our results contribute to an important database on the occurrence, removal, and potential risks of OMPs in Korean WWTPs.

Loss of micropollutants on syringe filters during sample filtration: Machine learning approach for selecting appropriate filters.

Prefiltration before chromatographic analysis is critical in the monitoring of environmental micropollutants (MPs). However, in an aqueous matrix, such monitoring often leads to out-of-specification results owing to the loss of MPs on syringe filters. Therefore, this study investigated the loss of seventy MPs on eight different syringe filters by employing Random Forest, a machine learning algorithm. The results indicate that the loss of MPs during filtration is filter specific, with glass microfiber and polytetrafluoroethylene filters being the most effective (<20%) compared with nylon (>90%) and others (regenerated-cellulose, polyethersulfone, polyvinylidene difluoride, cellulose acetate, and polypropylene). The Random Forest classifier showed outstanding performance (accuracy range 0.81-0.95) for determining whether the loss of MPs on filters exceeded 20%. Important factors in this classification were analyzed using the SHapley Additive exPlanation value and Kruskal-Wallis test. The results show that the physicochemical properties (LogKow/LogD, pKa, functional groups, and charges) of MPs are more important than the operational parameters (sample volume, filter pore size, diameter, and flow rate) in determining the loss of most MPs on syringe filters. However, other important factors such as the implications of the roles of pH for nylon and pre-rinsing for PTFE syringe filters should not be ignored. Overall, this study provides a systematic framework for understanding the behavior of various MP classes and their potential losses on syringe filters.

Loranthus tanakae Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust.

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD.

An Integrative Study of Scrophularia takesimensis Nakai in an Ovalbumin-Induced Murine Model of Asthma: The Effect on T Helper 2 Cell Activation.

Scrophularia have traditionally been used as herbal medicines to treat neuritis, sore throats, and laryngitis. In particular, S. takesimensis, a Korean endemic species with restricted distribution on Ulleung Island, holds significant resource and genetic value. However, its pharmacological properties have not been thoroughly evaluated. Thus, we provide detailed morphological characteristics and genomic information for S. takesimensis in this study. Moreover, its pharmacological activity was evaluated in an ovalbumin-induced asthma rat model, using extracts of S. takesimensis roots (100 or 200 mg/kg). The distinguishing features of S. takesimensis from related species include the presence or absence of stem wings, leaf shape, and habitat. The chloroplast (cp) genome of this species is 152,420 bp long and exhibits a conserved quadripartite structure. A total of 114 genes were identified, which included 80 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the S. takesimensis cp genome was highly conserved and consistent with the general structure observed in S. buergeriana and S. ningpoensis cp genomes. Confirming the anti-inflammatory effects of S. takesimensis extract (STE) using an established mouse model of ovalbumin-induced asthma, we observed reduced asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and suppression of T helper 2 (Th2) cell. Furthermore, STE treatment reduced Th2 cell activation and differentiation. This study underscores the medicinal value of S. takesimensis. The importance of preserving S. takesimensis was revealed and crucial insights were provided for further research on its utilization as a medicinal resource.

Multitemporal analysis of land subsidence induced by open-pit mining activity using improved combined scatterer interferometry with deep learning algorithm optimization.

Mine operational safety is an important aspect of maintaining the operational continuity of a mining area. In this study, we used the InSAR time series to analyze land surface changes using the ICOPS (improved combined scatterers with optimized point scatters) method. This ICOPS method combines persistent scatterers (PS) with distributed scatterers (DS) to increase surface deformation analysis's spatial coverage and quality. One of the improvements of this study is the use of machine learning in postprocessing, based on convolutional neural networks, to increase the reliability of results. This study used data from the Sentinel-1 SAR C-band satellite during the 2016-2022 observation period at the Musan mine, North Korea. In the InSAR surface deformation time analysis, the maximum average rate of land subsidence was approximately > 15.00 cm per year, with total surface deformation of 170 cm and 70 cm for the eastern dumping area and the western dumping area, respectively. Analyzing the mechanism of land surface changes also involved evaluating the geological conditions in the Musan mining area. Our research findings show that combining machine learning and statistical methods has great potential to enhance the understanding of mine surface deformation.

The posterior tibial slope affects the measurement reliability regarding the radiographic parameter of the knee.

BACKGROUND: Posterior tibial slope (PTS) exhibits considerable variability among individuals and is anticipated to influence the accuracy of radiographic measurements related to the knee. Despite this potential impact, there is a lack of prior research investigating how PTS affects the accuracy of these measurements. Therefore, this study aimed to investigate the effect of PTS on the measurement reliability regarding the radiographic parameter of the knee. METHODS: The medical records of patients who took full-length anteroposterior radiographs of the lower limb between January 2020 and June 2022 were evaluated retrospectively. Radiographic parameters related to the knee joint characteristics such as osteoarthritis grade, hip-knee-ankle angle, weight-bearing line ratio, medial proximal tibial angle (MPTA), lateral distal femoral angle, joint-line convergence angle (JLCA), and PTS were measured. Subjects were classified into 3 groups according to PTS (group A, PTS < 4°; group B, PTS ≥ 4° and < 8°; group C, PTS ≥ 8°), and the measurement reliability for the radiographic variables was compared between groups. The intra- and inter-observer agreements were assessed using the kappa coefficients, intra-class correlation coefficients (ICC), and Bland-Altman plots. RESULTS: A total of 175 limbs (86 patients) were included in this study. As the intra- and inter-observer reliability for PTS ranged over 0.9, grouping was performed based on the average of the measured PTSs. The inter-observer reliability of the MPTA and JLCA decreased as the PTS increased (ICCs for MPTA in Groups A, B, and C: 0.889, 0.796, and 0.790, respectively; ICCs for JLCA in Groups A, B and C: 0.916, 0.859, and 0.843, respectively), whereas there were no remarkable differences in other variables. Similar trends were observed in the comparisons of intra-observer reliability and Bland-Altman plots also showed consistent results. CONCLUSION: The larger the PTS, the lower the measurement reliability regarding the radiographic parameters of the knee that includes the joint line, such as MPTA and JLCA. Given the occasional challenge in accurately identifying the knee joint line in patients with a relatively large PTS, careful measurement of radiographic parameters is crucial and utilizing repetitive measurements for verification may contribute to minimizing measurement errors.

Association between body mass index and three-year outcome of acute myocardial infarction.

Body mass index (BMI), as an important risk factor related to metabolic disease. However, in some studies higher BMI was emphasized as a beneficial factor in the clinical course of patients after acute myocardial infarction (AMI) in a concept known as the "BMI paradox." The purpose of this study was to investigate how clinical outcomes of patients treated for AMI differed according to BMI levels. A total of 10,566 patients in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) from May 2010 to June 2015 were divided into three BMI groups (group 1: BMI < 22 kg/m2, group 2: ≥ 22 and < 26 kg/m2, and group 3: ≥ 26 kg/m2). The primary outcome was major adverse cardiac and cerebrovascular event (MACCE) at 3 years of follow-up. At 1 year of follow-up, the incidence of MACCE in group 1 was 10.1% of that in group 3, with a hazard ratio (HR) of 2.27, and 6.5% in group 2, with an HR of 1.415. This tendency continued up to 3 years of follow-up. The study demonstrated that lower incidence of MACCE in the high BMI group of Asians during the 3-year follow-up period compared to the low BMI group. The results implied higher BMI could exert a positive effect on the long-term clinical outcomes of patients with AMI undergoing percutaneous coronary intervention (PCI).

Adsorption of uranyl ion on hexagonal boron nitride for remediation of real U-contaminated soil and its interpretation using random forest.

Acid leaching has been widely applied to treat contaminated soil, however, it contains several inorganic pollutants. The decommissioning of nuclear power plants introduces radioactive and soluble U(VI), a substance posing chemical toxicity to humans. Our investigation sought to ascertain the efficacy of hexagonal boron nitride (h-BN), an highly efficient adsorbent, in treating U(VI) in wastewater. The adsorption equilibrium of U(VI) by h-BN reached saturation within a mere 2 h. The adsorption of U(VI) by h-BN appears to be facilitated through electrostatic attraction, as evidenced by the observed impact of pH variations, acidic agents (i.e., HCl or H2SO4), and the presence of background ions on the adsorption performance. A reusability test demonstrated the successful completion of five cycles of adsorption/desorption, relying on the surface characteristics of h-BN as influenced by solution pH. Based on the experimental variables of initial U(VI) concentration, exposure time, temperature, pH, and the presence of background ions/organic matter, a feature importance analysis using random forest (RF) was carried out to evaluate the correlation between performances and conditions. To the best of our knowledge, this study is the first attempt to conduct the adsorption of U(VI) generated from real contaminated soil by h-BN, followed by interpretation of the correlation between performance and conditions using RF. Lastly, a. plausible adsorption mechanism between U(VI) and h-BN was explained based on the experimental results, characterizations, and a. comparison with previous adsorption studies on the removal of heavy metals by h-BN.

Changes in Otitis Media During COVID-19.

OBJECTIVES: During the COVID-19 pandemic, various non-pharmaceutical interventions such as individual hygiene practices like hand washing, social distancing, and mandates for the use of masks in public spaces were implemented to reduce the spread of the disease. Otitis media (OM) is a common infectious disease. How the changed environment due to the COVID-19 pandemic has influenced the prevalence of infectious diseases like OM is not known. This study aimed to investigate how OM prevalence and trends changed during COVID-19 in Korea. METHODS: OM patient data from 2017 to 2021 were extracted from the Health Insurance Review and Assessment Service database. Patients diagnosed with disease code H66 (suppurative and unspecified otitis media) were selected for analysis. Data on OM prevalence, gender, region, medical institution, and number of ventilating-tube prescriptions were analyzed. All age groups were included, and ages were categorized into 5-year ranges. RESULTS: The number of patients diagnosed with the OM disease code decreased continuously from 2017 to 2021 (1 598 205, 1 560 178, 1 520 948, 983 701, and 734 901). The average OM prevalence per 1000 persons decreased by 45.0% from 30.2 in 2017 to 2019 to 16.6 in 2020 to 2021. The change of OM prevalence was greater for the 0 to 5 age group than other age groups. The decrease in average prevalence per 1000 persons was greatest in the 0 to 5 age group (48.6% decrease from 358.2 in 2017-2019 to 184.1 in 2020-2021). The impact of environmental changes on ventilation-tube insertion was smaller than on OM prevalence. The average number of ventilating-tube insertions decreased by 28.1% from 27 311 in 2017 to 2019 to 19 650 in 2020 to 2021. CONCLUSIONS: OM prevalence decreased by 45.0%, and the number of ventilating-tube insertions decreased by 28.1% in Korea during COVID-19.

Mucosa-associated Lymphoid Tissue Misdiagnosis as Glomus Tympanicum.

Middle ear tumors are diverse, but relatively uncommon. The most frequent tumor in the middle ear is glomus tumor, followed by others such as schwannoma and cholesteatoma. We experienced a case of Mucosa-associated lymphoid tissue hyperplasia as a middle ear tumor. The mass behind tympanic membrane appeared a hypervascular tumor, mimicking a glomus tumor, but the form of multiple separate masses in middle ear and mastoid cavity was the distinguishing feature that set it apart from a glomus tumor. Additionally, another characteristic was its tendency to easily shrink under pressure. This characteristic should be considered when encounter a hypervascular looking middle ear mass. Laryngoscope, 134:1894-1896, 2024.

Camellia sinensis (L.) Kuntze Extract Attenuates Ovalbumin-Induced Allergic Asthma by Regulating Airway Inflammation and Mucus Hypersecretion.

Asthma is a pulmonary disease induced by the inhalation of aeroallergens and subsequent inappropriate immune responses. Camellia sinensis (L.) Kuntze has been evaluated as an effective antioxidant supplement produced from bioactive compounds, including flavonoids. In this study, we aimed to determine the effects of Camellia sinensis (L.) Kuntze extract (CE) on ovalbumin-induced allergic asthma. The components of CE were analyzed using high-performance liquid chromatography (HPLC) chromatogram patterns, and asthmatic animal models were induced via ovalbumin treatment. The antioxidant and anti-inflammatory effects of CE were evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), and nitric oxide (NO) assays. Seven compounds were detected in the CE chromatogram. In the ovalbumin-induced mouse model, CE treatment significantly decreased the inflammation index in the lung tissue. CE also significantly decreased eosinophilia and the production of inflammatory cytokines and OVA-specific IgE in animals with asthma. Collectively, our results indicate that CE has anti-inflammatory and antioxidant activities, and that CE treatment suppresses asthmatic progression, including mucin accumulation, inflammation, and OVA-specific IgE production.

Predicting micropollutant fate during wastewater treatment using refined classical kinetic model based on quantitative monitoring in multi-metropolitan regions of South Korea.

This study aimed to implement an extensive prediction model for the fate of micropollutants (MPs) in wastewater treatment plants (WWTPs). Five WWTPs equipped with seven different biological treatment processes were monitored from 2020 to 2022 with three to four sampling events in each year, and 27 datasets for 20 MPs were collected. Among these datasets, 12 were used to investigate the behavior and fate of MPs in WWTPs in South Korea. Metformin, acetaminophen, caffeine, naproxen, and ibuprofen were the MPs with the highest influent concentrations (ranging from 3,933.3-187,637.0 ng L-1) at all WWTPs. More than 90% of MPs were removed by biological treatment processes in all WWTPs. The Kruskal-Wallis test verified that their efficacy did not differ statistically (p-value > 0.05). Meanwhile, to refine the performance of the prediction model, this study optimized the biodegradation rate constants (kbio) of each MP according to the variation of seasonal water temperature. As a result, compared to the original prediction model, the mean difference between the actual data and predicted results (MEAN) decreased by 6.77%, while the Nash-Sutcliffe efficiency (NSE) increased by 0.226. The final MEAN and NSE for the refined prediction model were calculated to be 5.09% and 0.964, respectively. The prediction model made accurate predictions, even for MPs exhibiting behaviors different from other cases, such as estriol and atrazine. Consequently, the optimization strategy proposed in this study was determined to be effective because the overall removal efficiencies of MPs were successfully predicted even with limited reference datasets.

Hydrophilic and lipophilic statin use and risk of hearing loss in hyperlipidemia using a Common Data Model: multicenter cohort study.

Hearing impairment, the third largest health burden worldwide, currently lacks definitive treatments or preventive drugs. This study compared the effects of hydrophilic and lipophilic statin on hearing loss using a common database model. This retrospective multicenter study was conducted in three hospitals in South Korea (Anam, Guro, Ansan). We enrolled patients with hyperlipidemia with an initial hearing loss diagnosis. Data were collected during January 1, 2022-December 31, 2021 using the Observational Health Data Science and Informatics open-source software and Common Data Model database. The primary outcome was the occurrence of first-time hearing loss following a hyperlipidemia diagnosis, as documented in the Common Data Model cohort database. The measures of interest were hearing loss risk between hydrophilic and lipophilic statin use. Variables were compared using propensity score matching, Cox proportional regression, and meta-analysis. Among 37,322 patients with hyperlipidemia, 13,751 (7669 men and 6082 women) and 23,631 (11,390 men and 12,241 women) were treated with hydrophilic and lipophilic statins, respectively. After propensity score matching, according to the Kaplan-Meier curve, hearing loss risk did not significantly differ among the hospitals. The hazard ratio (HR) of the male patients from Anam (0.29, [95% confidence interval (CI), 0.05-1.51]), Guro (HR, 0.56, [95% CI 0.18-1.71]), and Ansan (hazard ratio, 0.29, [95% CI 0.05-1.51]) hospitals were analyzed using Cox proportional regression. Overall effect size (HR, 0.40, [95% CI 0.18-0.91]) was estimated using meta-analysis, which indicated that hearing loss risk among hydrophilic statin users was less than that among lipophilic statin users and was statistically significant. Men in the hydrophilic statin group had a lower risk of hearing impairment than those in the lipophilic statin group.

Safety and tolerability of agalsidase beta infusions shorter than 90 min in patients with Fabry disease: post-hoc analysis of a Japanese post-marketing study.

BACKGROUND: Agalsidase beta, an enzyme replacement therapy for Fabry disease, is dosed biweekly at 1 mg/kg body weight, with increasing infusion rates based on tolerability. The US label specifies ≥ 90-min infusions for all patients; the US and EU labels require ≤ 15 mg/hr infusions in patients < 30 kg. The Japanese label allows infusions up to 30 mg/hr, allowing < 90-min dosing for some patients weighing < 45 kg. Japanese post-marketing data were analyzed for rate of infusion-associated reactions (IARs), adverse events (AEs), and serious AEs (SAEs) based on infusion rate and patient attributes (weight, antibody status). RESULTS: Data were available for 436 reduced-duration infusions (< 90 min) and 2242 standard infusions (≥ 90 min). SAEs were rare (0.6%), and the frequency of all safety events decreased over the treatment course. Little impact of infusion duration on safety outcomes was observed: IARs and AEs were numerically more common when infusion duration was ≥ 90 min compared to < 90 min (IARs: 2.0% vs 0.9%; AEs: 2.9% vs 1.4%), while the rate of SAEs was similar (0.4% vs 0.5%). IAR, AE, and SAE frequencies decreased significantly with increasing infusion rates, and this trend was consistent in patients < 30 kg. Safety events tended to be less frequent in patients < 30 kg vs those ≥ 30 kg (IARs: 1.8% vs 2.1%; AEs: 2.3% vs 3.6%; SAEs: 0.0% vs 0.6%), although the differences were not statistically significant. IARs occurred in < 1% of all infusions in the < 30 kg group, 84% of which were < 90 min. More anti-agalsidase beta antibody-positive patients experienced IARs (41.9% vs 30.7%; P = 0.0445) and AEs (61.1% vs 49.3%; P = 0.0497) vs antibody-negative patients; however, there was no significant difference in the frequency of SAEs. In patients with available data, no changes in antibody status were observed after infusion durations were reduced to < 90 min. CONCLUSIONS: The results of this post-hoc analysis demonstrated no significant impact of infusion duration on safety outcomes, and no significant difference in outcomes between patients of different weights. These findings suggest that infusion times in patients who are tolerating treatment can, with careful monitoring, be gradually decreased.

Regenerative capacity of trophoblast stem cell-derived extracellular vesicles on mesenchymal stem cells.

BACKGROUND: Human mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs. METHODS: We employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs. RESULTS: TSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway. CONCLUSION: The results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.