Liquid Nitrogen Exfoliation and Nanodispersion of WS2 for Thermocatalysts.

The efficient and clean exfoliation of single and/or few-layer nanosheets of WS2, a two-dimensional transition metal dichalcogenides, remains a significant challenge. In this study, a simple exfoliation method was proposed to produce ultrathin WS2 nanosheets by combining the liquid nitrogen exfoliation and nanodispersion techniques. This approach efficiently exfoliated WS2 into several layers of nanosheets via rapid temperature changes and mechanical stress without inducing defects or contamination. After five cycles of heating/liquid nitrogen and nanodispersion, the resulting WS2 nanosheets (WS2-5N ND) were confirmed to have been successfully exfoliated into 1-4 layers. When applied as a promoter in a thermocatalyst for the selective catalytic reduction of NOX using NH3, 2V3WS2/Ti (WS2-5N ND) exhibited excellent NOX conversion and N2 selectivity, along with excellent durability even in the presence of SO2. This result was greater than 2V3WS2/Ti (WS2-5N) subjected to only liquid nitrogen exfoliation, proving the importance of the simultaneous action of both methods. This method is expected to be an important contribution to ongoing research on high-performance WS2-based catalysts, thereby opening up potential opportunities for a wide range of applications.

Factors affecting fat myringoplasty in elderly patients with chronic otitis media: A case control study.

BACKGROUND: We compared and analyzed the surgical results of fat myringoplasty between elderly and young adult patients with chronic otitis media. We also investigated whether underlying diseases and other factors impact the surgical outcome. METHODS: We retrospectively reviewed the data of 141 patients who underwent fat myringoplasty for chronic otitis media for five years. They were compared by age, sex, underlying disease, perforation size, pre- and postoperative pure tone audiometry, postoperative otorrhea, postoperative re-perforation, and cause of re-perforation. RESULT: Postoperative re-perforation was more common in the elderly group, albeit with no significant difference (p = 0.072). The factors affecting re-perforation were insufficient fat graft (44.4%), postoperative infection (33.3%), and nasal blowing (22.2%). Our findings revealed no significant association between preoperative perforation size and re-perforation (p = 0.391). Additionally, we found no significant relationship between hypertension and re-perforation (p > 0.99), nor between age group and postoperative infection (p = 0.488). Diabetes was also not significant (p = 0.640). Following surgery, both groups exhibited a significant improvement in hearing. CONCLUSION: Although age and underlying conditions play significant roles in the healing process, our results suggest that external factors such as infection, nasal blowing, cough, and insufficient grafted fat tissue have a similarly significant impact on surgical outcomes in elderly patients with COM as they do in adults. In conclusion, the decision to perform surgery in elderly patients with COM should be based on a comprehensive assessment of the patient's overall health status, hearing, use of hearing aids, and the indications for surgery.

Association of Adding Salt to Foods and Potassium Intake with Incident Atrial Fibrillation in the UK Biobank Study.

Background: High sodium and low potassium consumption are related to hypertension and cardiovascular disease. We aimed to determine the relationship between the frequency of salt addition and potassium consumption with the risk of new-onset atrial fibrillation (AF). Methods: Our study used the UK Biobank cohort, which included over 500,000 individuals enrolled from the United Kingdom between 2006 and 2010. This study involved 416,868 participants who filled out the dietary recall regarding the frequency of salt addition. Results: During follow-up, 19,164 (4.6%) developed AF. The incidence of new-onset AF was increased based on the frequency of salt addition (never/rarely 3.83; always 4.72 per 1000 person-years). Compared with the group that never/rarely added salt, those adding salt always were at significantly higher risk of incident AF after adjusting for multiple variables (hazard ratio (HR) 1.15; 95% confidence interval (CI) 1.06-1.24), and additional adjustment of dietary and total energy consumption (HR 1.37; 95% CI 1.08-1.73). In the subgroup analysis, the risk of AF incident according to the frequency of salt addition significantly increased in low urine potassium levels compared to high (p for interaction = 0.046). In the subgroup analysis for AF patients, higher salt addition frequency was related to increased all-cause mortality. Conclusions: Our study demonstrated that adding salt to foods more frequently increases the risk of incident AF, even after adjusting for dietary and total energy consumption. In the high urine potassium group, the impact of high sodium consumption on incident AF was attenuated.

Comparison of the risk of pneumothorax in COVID-19 and seasonal influenza.

Limited evidence exists regarding the link between coronavirus disease 2019 (COVID-19) and pneumothorax. Therefore, we aimed to evaluate the occurrence rate of pneumothorax in hospitalized patients with COVID-19 and compare the risk of pneumothorax between patients with COVID-19 and influenza. This retrospective cohort study used patient data from the National Health Insurance Service of South Korea. Patients diagnosed with COVID-19 (December 2019 to December 2021) and influenza (January 2019 to December 2021) who required hospitalization and respiratory support were included. We identified 46,460 patients with COVID-19 and 6,117 with influenza. The occurrence rate of pneumothorax was 0.74% in patients with COVID-19. In an inverse probability of treatment weighting matched cohort, the Cox proportional hazards regression model showed that COVID-19 was not associated with an increased risk of pneumothorax compared to influenza (hazard ratio, 1.22; 95% confidence interval, 0.75-1.99). However, the risk of pneumothorax associated with COVID-19 compared to influenza was significantly higher in patients without chronic lung disease than in those with (P for heterogeneity = 0.037). In conclusion, COVID-19, compared with influenza, is not associated with an increased risk of pneumothorax; however, it is associated with an increased risk in patients without chronic lung disease.

The impact of the Cochlear™ Osia® 2 System on patients with mixed or conductive hearing loss: A comparison with Cochlear™ Baha® Attract System outcomes.

OBJECTIVE: This prospective study assessed the efficacy of the Cochlear™ Osia® 2 System compared to the previous Baha® Attract System in patients with mixed or conductive hearing loss (MHL/CHL). METHODS: In this prospective case-control study, 10 patients (2 men and 8 women) with MHL/CHL were implanted with the Osia® 2 System. Their audiological outcomes were compared with 13 patients (2 men and 11 women) who had previously been implanted with the transcutaneous Baha® Attract system. We compared the complications and compliance of the two groups. Also, in the Osia 2 System group, subjective satisfaction was assessed using the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire and the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire. RESULTS: Complications such as poor magnetization, pain & infection, and abnormal noise were more common in the Baha Attract group, although not statistically significant. Also, the Osia 2 group exhibited better compliance. Subjective satisfaction was assessed using the K-IOI-HA and APHAB questionnaires with the Osia 2 group, revealing significantly improved scores in ease of communication, reverberation, background noise, and higher K-IOI-HA scores post-implantation. Postoperative-aided thresholds with both systems were significantly lower than preoperative-unaided thresholds, with the Osia 2 System demonstrating notably high satisfaction levels. Although both systems showed similar preoperative and postoperative word-recognition scores, the Osia 2 System provided greater audiological gain, especially at 2 kHz and 4 kHz frequencies. Additionally, the functional gain of both systems was comparable across all frequencies. CONCLUSIONS: The Osia 2 System demonstrated high subjective satisfaction and improved audiological outcomes compared to the Baha Attract system in patients with conductive or mixed hearing loss. Its superior audiological gain, particularly at critical frequencies, along with better compliance, suggests it as a favorable option for this patient population.

Invasive strategies for rhythm control of atrial fibrillation: a narrative review.

Atrial fibrillation (AF) is the most common sustained tachyarrhythmia and its increasing prevalence has resulted in a growing healthcare burden. A recent landmark randomized trial, the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial), highlighted the importance of early rhythm control in AF, which was previously underemphasized. Rhythm control therapy includes antiarrhythmic drugs, direct-current cardioversion, and catheter ablation. Currently, catheter ablation is indicated for patients with AF who are either refractory or intolerant to antiarrhythmic drugs or who exhibit decreased left ventricular systolic function. Catheter ablation can be categorized according to the energy source used, including radiofrequency ablation (RFA), cryoablation, laser ablation, and the recently emerging pulsed field ablation (PFA). Catheter ablation techniques can also be divided into the point-by-point ablation method, which ablates the pulmonary vein (PV) antrum one point at a time, and the single-shot technique, which uses a spherical catheter to ablate the PV antrum in a single application. PFA is known to be applicable to both point-by-point and single-shot techniques and is expected to be promising owing to its tissue specificity, resulting in less collateral damage than catheter ablation involving thermal energy, such as RFA and cryoablation. In this review, we aimed to outline catheter ablation for rhythm control in AF by reviewing previous studies.

A protein expression atlas on tissue samples and cell lines from cancer patients provides insights into tumor heterogeneity and dependencies.

The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) are foundational resources in cancer research, providing extensive molecular and phenotypic data. However, large-scale proteomic data across various cancer types for these cohorts remain limited. Here, we expand upon our previous work to generate high-quality protein expression data for approximately 8,000 TCGA patient samples and around 900 CCLE cell line samples, covering 447 clinically relevant proteins, using reverse-phase protein arrays. These protein expression profiles offer profound insights into intertumor heterogeneity and cancer dependency and serve as sensitive functional readouts for somatic alterations. We develop a systematic protein-centered strategy for identifying synthetic lethality pairs and experimentally validate an interaction between protein kinase A subunit α and epidermal growth factor receptor. We also identify metastasis-related protein markers with clinical relevance. This dataset represents a valuable resource for advancing our understanding of cancer mechanisms, discovering protein biomarkers and developing innovative therapeutic strategies.

Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men.

BACKGROUND: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics. METHODS: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort. RESULTS: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799). CONCLUSIONS: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.

Establishment and long-term expansion of adult hepatobiliary organoids co-cultured with liver endothelial cells.

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements.

Wearable Device-Based Intervention for Promoting Patient Physical Activity After Lung Cancer Surgery: A Nonrandomized Clinical Trial.

Importance: Emerging evidence suggests that wearable devices are feasible for monitoring physical activity among patients with lung cancer. However, the association between wearable devices and improvement in patient recovery after surgery remains underexplored. Objective: To evaluate the effects of a wearable device intervention on the recovery of physical activity, cardiopulmonary function, and health-related quality of life (HRQOL) after lung cancer surgery. Design, Setting, and Participants: This nonrandomized clinical trial with a historical control was conducted at a single tertiary cancer center (Samsung Comprehensive Cancer Center) in Seoul, South Korea, between October 18, 2018, and May 24, 2019. Patients were included if they had suspected or confirmed non-small cell lung cancer scheduled for curative surgery more extensive than lobectomy and had an Eastern Cooperative Oncology Group status of 0 or 1. Patients were compared with historical control participants from data collected between September 20, 2017, and September 10, 2018, as part of the Coordinated Approach to Cancer Patients' Health for Lung Cancer (CATCH-LUNG) prospective cohort study. Data analysis was performed between June 21 and July 16, 2020. Intervention: A personalized exercise regimen monitored via a wearable device was administered to intervention patients at home in 3 stages: preoperative (from diagnosis to surgery), immediate (from discharge to 2 months after surgery), and later postoperative (from 2 to 6 months after surgery). Control patients received usual care. Main Outcomes and Measures: The primary outcome was cardiopulmonary function, and the co-primary outcome was physical activity at 6 months after surgery, measured with 6-minute walking distance (6MWD) and number of daily steps, using a linear regression model. Secondary outcomes were changes in cardiopulmonary function, physical activity, and HRQOL, including function and symptoms from baseline to 2 weeks and 6 months after surgery. Additionally, cardiopulmonary function and physical activity (number of daily steps and time spent on moderate-to-vigorous physical activity [MVPA]) at 2 weeks after surgery, physical activity (time spent on MVPA) at 6 months after surgery, and HRQOL, including function and symptoms at 2 weeks and 6 months after surgery, were assessed as secondary outcomes. Results: This trial included 74 patients in the intervention group (mean [SD] age, 60.4 [8.7] years; 31 [41.9%] men and 43 [58.1%] women) and 120 in the control group (mean [SD] age, 60.2 [8.7] years; 65 [54.2%] men and 55 [45.8%] women). Daily steps, MVPA, and 6MWD decreased initially at 2 weeks after surgery but increased thereafter. The control group had a larger decrease in the number of daily steps from baseline compared with the intervention group (-4877 [95% CI, -5861 to -3893] steps vs -1753 [95% CI, -2968 to -539] steps) at 2 weeks after surgery. By 6 months after surgery, the intervention group increased their daily steps by 2220 (95% CI, 1006 to 3435) from baseline, whereas the control group did not return to their baseline number of steps. The intervention group had significantly more daily steps (12 321 [95% CI, 8749-15 761] vs 10 118 [95% CI, 7341-13 420]; P = .007) and had greater vigorous physical activity (33.6 [95% CI, 13.5 to 59.8] vs 18.5 [5.7 to 40.8] minutes; P = .003) at 6 months after surgery compared with the control group. No difference in 6MWD was found. However, the intervention group had better patient-reported physical function (mean [SD] score, 82.2 [17.3] vs 76.9 [17.5]; P = .04), less dyspnea (mean [SD] score, 24.8 [27.1] vs 34.5 [31.6]; P = .03), and less pain (mean [SD] score, 21.4 [20.2] vs 30.1 [26.8]; P = .01) at 2 weeks after surgery and less dyspnea (mean [SD] score, 5.4[12.4] vs 12[23.3]; P = .01) at 6 months after surgery compared with the control group. Conclusions and Relevance: In this nonrandomized clinical trial, integration of perioperative exercise interventions using wearable devices improved physical activity (especially MVPA) and dyspnea at 6 months after lung cancer surgery compared with usual care. This finding suggests a promising role for wearable devices in personalizing perioperative rehabilitation strategies. Trial Registration: ClinicalTrials.gov Identifier: NCT03215537.

Comparative analysis of body composition using torso CT from PET/CT with bioelectrical impedance and muscle strength in healthy adults.

The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia.

Liver-specific Coxsackievirus and adenovirus receptor deletion develop metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD.

Structural basis of lactate dehydrogenase A-gossypol complex.

Lactate dehydrogenase A (LDHA) is a key enzyme in Warburg's effect, a characteristic of cancer cells. LDHA is a target of anticancer agents that inhibit the metabolism of cancer cells. Gossypol is a known cancer therapeutic agent that inhibits LDHA by competitive inhibition. However, the mechanisms of inhibition of LDHA by gossypol is unknown. Here, we elucidate the binding of gossypol and LDHA using biochemical and biophysical methods. The crystal structure of the complex between LDHA and gossypol is presented. The binding of gossypol affects LDHA activity by a conformational change in the active-site loop. Our research contributes to the structural insight into LDHA with gossypol and approaches gossypol as a novel therapeutic candidate targeting the metabolic pathways for cancer cells.

Discovery of new acetamide derivatives of 5-indole-1,3,4-oxadiazol-2-thiol as inhibitors of HIV-1 Tat-mediated viral transcription.

Human immunodeficiency virus-1 (HIV-1) encodes a transcriptional factor called Tat, which is critical for viral transcription. Tat-mediated transcription is highly ordered apart from the cellular manner; therefore, it is considered a target for developing anti-HIV-1 drugs. However, drugs targeting Tat-mediated viral transcription are not yet available. Our high-throughput screen of a compound library employing a dual-reporter assay identified a 1,3,4-oxadiazole scaffold against Tat and HIV-1 infection. Furthermore, a serial structure-activity relation (SAR) study performed with biological assays found 1,3,4-oxadiazole derivatives (9 and 13) containing indole and acetamide that exhibited potent inhibitory effects on HIV-1 infectivity, with half-maximal effective concentrations (EC50) of 0.17 (9) and 0.24 µM (13), respectively. The prominent derivatives specifically interfered with the viral transcriptional step without targeting other infection step(s) and efficiently inhibited the HIV-1 replication cycle in the T cell lines and peripheral blood mononuclear cells infected with HIV-1. Additionally, compared to the wild type, the compounds exhibited similar potency against anti-retroviral drug-resistant HIV-1 strains. In a series of mode-of-action studies, the compounds inhibited the ejection of histone H3 for facilitating viral transcription on the long-terminal repeat (LTR) promoter. Furthermore, SAHA (a histone deacetylase inhibitor) treatment abolished the compound potency, revealing that the compounds can possibly target Tat-regulated epigenetic modulation of LTR to inhibit viral transcription. Overall, our screening identified novel 1,3,4-oxadiazole compounds that inhibited HIV-1 Tat, and subsequent SAR-based optimization led to the derivatives 9 and 13 development that could be a promising scaffold for developing a new class of therapeutic agents for HIV-1 infection.

Prescription of Oral Antibiotics and its Appropriateness for Outpatients in a Tertiary-Care Hospital in Korea.

OBJECTIVES: Antimicrobial stewardship programs (ASPs) have gained prominence with increased awareness regarding the importance of appropriate antibiotic use. However, ASP implementation for outpatient antibiotic prescriptions is uncommon, particularly in South Korea. This study aimed to analyse the patterns and appropriateness of outpatient antibiotic prescriptions at a tertiary care hospital in Korea. METHODS: We analysed the patterns of oral antibiotic prescription from June 1, 2018 to May 31, 2023, at the outpatient department of Seoul National University Bundang Hospital. Appropriateness was assessed for prescriptions issued between May 15 and May 19, 2023. The assessment criteria included: indications for antibiotic use, antibiotic choice, duration, dose, and frequency. Pharmacists and infectious diseases specialists performed evaluations. RESULTS: A total of 7,282,407 outpatient visits were recorded within the 5-year duration. Of these, 243,967 (3.4%) were prescribed oral antibiotics. The frequency of antibiotic prescription was highest in dentistry, dermatology, and urology departments. The most commonly prescribed antibiotics were cephalosporins, penicillins, and sulphonamides. Of the 423 prescriptions evaluated, 289 (68.3%) and 134 (31.7%) were for treatment and prophylaxis, respectively. Inappropriate prescriptions were identified in 28.4% (82/289) and 70.9% (95/134) of the treatment and prophylaxis cases, respectively. The primary reason for inadequacy in both treatment and prophylaxis was inappropriate indications, accounting for 46.3% (38/82) of treatment prescriptions and 96.8% (92/95) of prophylaxis prescriptions. CONCLUSIONS: Antibiotics were administered in 3.4% of all outpatient visits, with 28.4% of treatment and 70.9% of prophylactic antibiotics prescribed inappropriately. Proactive and expansive ASP activities by pharmacists should be considered in outpatient settings.

Development of human amniotic epithelial cell-derived extracellular vesicles as cell-free therapy for dry eye disease.

PURPOSE: This study aimed to investigate the therapeutic potential of extracellular vesicles (EVs) derived from human amniotic epithelial cells (hAEC-EVs) for Dry Eye Disease (DED) treatment. METHODS: Highly purified EVs were isolated from the culture supernatants of hAECs, which obtained from term placenta and characterized. Proteomic contents were analyzed for assessing its biological function related to the therapeutic potentials for DED. Subsequently, we examined the therapeutic efficacy of hAEC-EVs on human corneal epithelial cells exposed to hyperosmotic stress and in an experimental DED mouse model induced by desiccation stress. RESULTS: Proteomic analysis of hAEC-EVs revealed proteins linked to cell proliferation and anti-inflammatory responses. We demonstrated efficient uptake of hAEC-EVs by ocular surface cells. Under DED conditions, EV treatment increased corneal epithelial cell proliferation and migration, and concurrently reducing inflammatory cytokines. In the DED mouse model, hAEC-EVs showed significant improvements in corneal staining score, tear secretion, corneal irregularity, and conjunctival goblet cell density. Additionally, hAEC-EVs exhibited a mitigating effect on ocular surface inflammation induced by desiccation. CONCLUSIONS: These findings suggest that hAEC-EVs hold potential as a cell-free therapy for corneal epithelial defects and ocular surface diseases, presenting a promising treatment option for DED.

Effects of antiarrhythmic drug responsiveness and diagnosis-to-ablation time on outcomes after catheter ablation for persistent atrial fibrillation.

Background: The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods: We included data from 1038 AAD-resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD-partial responders; those maintaining PeAF on AAD were AAD-non-responders. We determined the DAT cutoff for best discriminating long-term rhythm outcomes using a maximum log-likelihood estimation method based on the Cox proportional hazard regression model. Results: Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD-non-responders. AAD-non-responders had a higher body mass index and a larger left atrial diameter than AAD-partial-responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33-2.30; log-rank p < .001) compared to AAD-partial-responders. The maximum log-likelihood estimation showed bimodal cutoffs at 22 and 40 months. The optimal DAT cutoff rhythm outcome was 22 months, which discriminated better in the AAD-partial-responders than in the AAD-non-responders. Conclusions: Both DAT and AAD responsiveness influenced AFCA rhythm outcomes. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF was changed to paroxysmal AF during AAD therapy.

Is There a Pathologic Running Motion Associated with Running-Related Injuries? A Methodological Study Using a Motion Analysis System Without Sensors.

(1) Background and objectives: Running-related injuries (RRIs) are commonly attributed to improper running posture and overuse. This study aims to analyze the running motions of individuals with and without RRIs using a sensor-free method, which offers a user-friendly and straightforward approach. (2) Materials and Methods: A total of 155 runners were divided into two groups: the normal runner group (runners who had never been injured, n = 50) and the RRI group (runners who had experience at least one injury while running, n = 105). The forward head posture (FHP), trunk lean, hip rotation, horizontal movement of the center of gravity (COG), vertical movement of the COG, pelvic rotation, hip hike, and type of strike were measured for posture analysis. (3) Results: We found that the left-right balance of the pelvis and the spinal posture during running were associated with RRIs. The difference in hip hike and FHP emerged as key predictors of running-related musculoskeletal injury occurrence from our logistic regression analysis. (4) Conclusions: Identifying pathological movements in runners through running motion analysis without the use of sensors can be instrumental in the prevention and treatment of RRIs.