Cardiac and kidney outcomes after sacubitril-valsartan therapy: recovery of cardiac function relative to kidney function decline.

BACKGROUND: Sacubitril-valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction (HFrEF). However, its long-term protective effects on cardiac function with concurrent acute kidney injury (AKI) remain unclear. This study investigated the recovery of cardiac function relative to kidney function decline. METHODS: A total of 512 patients with HFrEF who started sacubitril-valsartan or valsartan treatment were enrolled in cohort 1. Additionally, patients who experienced AKI and underwent follow-up transthoracic echocardiography were enrolled in cohort 2. In cohort 1, short- and long-term kidney outcomes were analyzed. For cohort 2, changes in cardiac function in relation to changes in kidney function after drug initiation were analyzed. RESULTS: The mean age of the patients was 68.3 ± 15.1 years, and 57.4% of the patients were male. AKI occurred in 15.9% of the sacubitril-valsartan group and 12.5% of the valsartan group. After AKI, 78.4% of patients in the sacubitril-valsartan group and 71.4% of those in the valsartan group underwent recovery. Furthermore, cardiovascular outcomes in patients who developed AKI after drug initiation were analyzed in cohort 2. The sacubitril-valsartan group showed a greater improvement in cardiac function compared with the valsartan group (12.4% ± 15.4% vs. 1.4% ± 5.7%, p = 0.046). The ratio of deltas of cardiac and kidney function in the sacubitril-valsartan and valsartan groups were -1.76 ± 2.58 and -0.20 ± 0.58, respectively (p = 0.03). CONCLUSION: Patients with HFrEF treated with sacubitril-valsartan exhibited significant improvements in cardiovascular outcomes despite AKI.

Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes.

Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19+ B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.

Piezo1 mediates mechanical signals in TRPV1-positive nociceptors in mice.

AIM: This investigation addresses Piezo1's expression and mechanistic role in dorsal root ganglion (DRG) neurons and delineates its participation in mechanical and inflammatory pain modulation. METHODS: We analyzed Piezo1's expression patterns in DRG neurons and utilized Piezo1-specific shRNA to modulate its activity. Electrophysiological assessments of mechanically activated (MA) currents in DRG neurons and behavioral analyses in mouse models of inflammatory pain were conducted to elucidate Piezo1's functional implications. Additionally, we investigated the excitability of TRPV1-expressing DRG neurons, particularly under inflammatory conditions. RESULTS: Piezo1 was preferentially expressed in DRG neurons co-expressing the TRPV1 nociceptor marker. Knockdown of Piezo1 attenuated intermediately adapting MA currents and lessened tactile pain hypersensitivity in models of inflammatory pain. Additionally, silencing Piezo1 modified the excitability of TRPV1-expressing neurons under inflammatory stress. CONCLUSION: Piezo1 emerges as a key mediator in the transmission of mechanical and inflammatory pain, indicating its potential as a novel target for pain management therapies. Our finding not only advances the understanding of nociceptive signaling but also emphasizes the therapeutic potential of modulating Piezo1 in the treatment of pain.

Organophosphate Detection in Animal-Derived Foods Using a Modified Quick, Easy, Cheap, Effective, Rugged, and Safe Method with Liquid Chromatography-Mass Spectrometry.

Organophosphates are widely used in the livestock industry. In this study, we developed a method for detecting 27 organophosphate insecticides in animal-derived foods, including beef, pork, chicken, milk, and eggs, using liquid chromatography-tandem mass spectrometry. A modified QuEChERS method was optimized for sample pretreatment. A mixture of acetonitrile and acetone was used as the extraction solvent, and MgSO4 and NaCl were used as salts. Among the five different dispersive solid-phase extraction systems, MgSO4, primary secondary amines, and C18 were selected for purification because they had the highest recovery rates and least matrix effects. The matrix-dependent limit of quantitation was 0.0005-0.005 mg/kg, and the correlation coefficient of the matrix-matched calibration curve was >0.99, which was acceptable for quantifying residues below 0.01 mg/kg-the default maximum residue limit in a positive list system. The recovery efficiencies ranged from 71.9 to 110.5%, with standard deviations ranging from 0.2% to 12.5%, satisfying the SANTE guidelines. The established analytical method was used to monitor organophosphates in animal-derived foods obtained from a local market, and no pesticides were detected. With respect to industry standards, our proposed method is recommended for practical organophosphate detection in animal-derived foods.

Opioid-Free Using Ketamine versus Opioid-Sparing Anesthesia during the Intraoperative Period in Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial.

Opioids effectively manage perioperative pain but have numerous adverse effects. Opioid-free anesthesia (OFA) eliminates intraoperative opioid use; however, evidence for its use in video-assisted thoracoscopic surgery (VATS) is limited. This study assessed the effect of OFA using ketamine in VATS patients compared to opioid-sparing anesthesia (OSA). A total of 91 patients undergoing VATS lobectomy or segmentectomy were randomized to either the OFA group (ketamine) or the OSA group (remifentanil). The primary outcome was the quality of recovery (QoR) on postoperative day (POD) 1, measured with the QoR-40 questionnaire. Secondary outcomes included postoperative pain scores and adverse events. Both groups had comparable baseline and surgical characteristics. On POD 1, the QoR-40 score was higher in the OFA group than in the OSA group (164.3 ± 10.8 vs. 158.7 ± 10.6; mean difference: 5.6, 95% CI: 1.1, 10.0; p = 0.015), though this did not meet the pre-specified minimal clinically important difference of 6.3. The visual analog scale score was lower in the OFA group as compared to the OSA group at 0-1 h (4.2 ± 2.3 vs. 6.2 ± 2.1; p < 0.001) and 1-4 h after surgery (3.4 ± 1.8 vs. 4.6 ± 1.9; p = 0.003). The OFA group had a lower incidence of PONV (2 [4.4%] vs. 9 [19.6%]; p = 0.049) and postoperative shivering (4 [8.9%] vs. 13 [28.3%]; p = 0.030) than the OSA group at 0-1 h after surgery. Using OFA with ketamine proved feasible, as indicated by the stable intraoperative hemodynamics and absence of intraoperative awareness. Patients undergoing VATS with OFA using ketamine showed a statistically significant, but clinically insignificant, QoR improvement compared to those receiving OSA with remifentanil.

Change in Iridotrabecular Contact and Intraocular Pressure after Phacoemulsification in Primary Angle Closure Disease Spectrum.

Purpose: To compare changes in the swept-source anterior segment optical coherence tomography (SS AS-OCT) parameters and intraocular pressure (IOP) control after lens extraction in various spectra of primary angle closure disease (PACD). Methods: A total 92 eyes from 92 patients with PACD who underwent lens extraction were included in the study. All patients underwent IOP measurement preoperatively and postoperatively at 1 day, 1 week, 1 month, 3 months, and 6 months. SS AS-OCT was performed in all subjects preoperatively and 1 month postoperatively. All participants were divided into two groups depending on the presence of glaucomatous optic disc or visual field damage (group A: primary angle closure suspect or primary angle closure; group B: primary angle closure glaucoma). The changes in IOP and anterior chamber angle (ACA) parameters of SS AS-OCT of each group were compared. Regression analysis was performed to find factors associated with the degree of IOP reduction after lens extraction. Results: Preoperatively, there was no significant difference in IOP (16.3 ± 2.5 vs 16.9 ± 3.2 mmHg, P=0.297) between the two groups, but the number of glaucoma medications used (0.6 ± 1.0 vs 2.0 ± 0.9, P<0.001) was greater in group B. Postoperatively, IOP was not significantly different, but the number of medications used was greater in group B (0.2 ± 0.7, 0.9 ± 0.8, P<0.001). ACA parameters including angle opening distance and trabecular-iris angle had a greater increase in group B after lens extraction. However, the residual iridotrabecular contact (ITC) index (5.6 ± 7.0 vs 10.7 ± 12.1, P=0.014) was significantly greater in group B. A greater change in the ITC index was related to a greater degree of IOP reduction (beta coefficient = 0.429, P<0.001). Conclusions: Eyes with PACG had a greater residual ITC index after lens extraction compared with eyes of other PACD spectrum, and required a greater number of glaucoma medications to maintain a similar level of IOP.

Is Posterior Cervical Foraminotomy Better Than Fusion for Warfighters?: A Biomechanical Study.

INTRODUCTION: Cervical spondylosis in the warfighter is a common musculoskeletal problem and can be career-ending especially if it requires fusion. Head-mounted equipment and increased biomechanical forces on the cervical spine have resulted in accelerated cervical spine degeneration. Current surgical gold standard is anterior cervical discectomy and fusion (ACDF). Posterior cervical foraminotomy (PCF) is a nonfusion surgical alternative, and this can be effective in alleviating radiculopathy from foraminal stenosis caused by disc-osteophyte complex. Biomechanical studies have not been done to analyze motion associated with military aircrew personnel following PCF. The aim of this study was to compare the biomechanical responses of the effects of ACDF and PCF with different grades of facet resection under simulated military aircrew conditions using range of motion, disc pressure, and facet loads at the index and adjacent levels. MATERIALS AND METHODS: A validated 3D finite element model of the human cervical spinal column was used to simulate various graded PCF and ACDF. All surgical simulations were performed at the most commonly operated level (C5-C6) in warfighters. Pure moment loading under flexion, extension, and lateral bending, and in vivo follower force of 75 N were applied to the intact spine. Hybrid loading protocol was used to achieve 134 degrees of combined flexion-extension and 83 degrees of lateral bending in intact and surgical models to reflect military loading conditions. Segmental motions, disc pressure, and facet load were obtained and normalized with respect to the intact model to quantify the biomechanical effect. RESULTS: Anterior cervical discectomy and fusion decreased range of motion at the index and increased motion at the adjacent levels, while all graded PCF responses had an opposite trend: increased motion at the index and decreased motion at adjacent levels. The magnitude of changes depended on the level of resection, spinal level, and loading mode. Disc pressure increased at the index level and decreased at the adjacent levels after PCF. These changes were exaggerated with increasing extent of facet resection. Facet load increased at the index level after PCF especially with extension and right (contralateral) lateral bending. Complete facetectomy led to facet load increases greater than ACDF at the adjacent levels in both flexion and extension. CONCLUSIONS: Posterior cervical foraminotomy is a motion-preserving implant-free surgical alternative to ACDF for warfighters with cervical radiculopathy after failure of conservative management. The treating surgeon must pay close attention to the extent of facet resection to avoid potential spinal instability and future disc and facet degeneration after PCF. Posterior cervical foraminotomy can be more advantageous than ACDF in terms of adjacent segment degeneration, motion preservation, reoperation rate, surgical cost, and retention of warfighters.

Intraplantar aminoglutethimide, a P450scc inhibitor, reduced the induction of mechanical allodynia in a rat model of thrombus-induced ischemic pain.

Neuroactive steroids (NASs) directly affect neuronal excitability. Despite their role in the nervous system is intimately linked to pain control, knowledge is currently limited. This study investigates the peripheral involvement of NASs in chronic ischemic pain by targeting the cytochrome P450 side-chain cleavage enzyme (P450scc). Using a rat model of hind limb thrombus-induced ischemic pain (TIIP), we observed an increase in P450scc expression in the ischemic hind paw skin. Inhibiting P450scc with intraplantar aminoglutethimide (AMG) administration from post-operative day 0 to 3 significantly reduced the development of mechanical allodynia. However, AMG administration from post-operative day 3 to 6 did not affect established mechanical allodynia. In addition, we explored the role of the peripheral sigma-1 receptor (Sig-1R) by co-administering PRE-084 (PRE), a Sig-1R agonist, with AMG. PRE reversed the analgesic effects of AMG during the induction phase. These findings indicate that inhibiting steroidogenesis with AMG alleviates peripheral ischemic pain during the induction phase via Sig-1Rs.

Cumulative Blood Pressure Load and Incident CKD.

RATIONALE & OBJECTIVE: The association of long-term cumulative blood pressure (BP) loads with the risk of incident chronic kidney disease (CKD) remains a matter of debate. This study investigated this association among healthy Korean adults with normal kidney function. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We analyzed 5,221 participants without CKD in the Korean Genome and Epidemiology Study. Cumulative systolic and diastolic BP (SBP and DBP) loads were calculated as the ratios of the areas under the curve (AUC) for SBP≥120mm Hg or≥80mm Hg for DBP divided by the AUC for all SBP or DBP measurements during the exposure period. These AUCs were categorized into 4 groups: group 0 (reference), cumulative BP load of 0 and groups 1-3, tertiles of cumulative BP loads. OUTCOME: Primary end point was incident CKD defined as a composite of an estimated glomerular filtration rate (eGFR) below 60mL/min/1.73m2 or proteinuria greater than 1+on dipstick examination for at least 2 consecutive measurements≥90 days apart. ANALYTICAL APPROACH: Multivariable Cox proportional hazards regression to estimate the independent association of cumulative BP loads with incident CKD. RESULTS: Higher cumulative SBP and DBP loads were associated with an increased risk of incident CKD (HR, 1.23 [95% CI, 1.12-1.35] for SBP; and HR, 1.14 [95% CI, 1.04-1.26] for DBP loads for each 1.0-unit greater load). Compared with SBP group 0, groups 2 and 3 were associated with 1.94- and 1.89-fold greater risk of incident CKD. Compared with DBP group 0, groups 2 and 3 were associated with 1.42- and 1.54-fold greater risks. These associations of high cumulative BP loads with an increased risk of incident CKD remained consistent even in the subgroups not taking antihypertensive agents or without prior hypertension diagnosis. LIMITATIONS: The assessment of CKD outcomes relied on eGFR and spot urine tests. CONCLUSIONS: These findings highlight the association between high cumulative SBP and DBP loads and the occurrence of CKD, even in individuals with normal BP levels. PLAIN-LANGUAGE SUMMARY: Although hypertension is a major risk factor for chronic kidney disease (CKD), most studies have focused on single-point blood pressure (BP) measurements. To explore the association between long-term cumulative BP load and the development of CKD, 5,221 Korean adults with normal kidney function were included in this study. Cumulative systolic BP and diastolic BP load both exhibited a significant association with an increased risk of incident CKD. Notably, the association of cumulative BP loads with elevated risk of incident CKD was evident also in individuals who were not taking antihypertensive agents or who had no previous history of hypertension. These findings underscore the importance of managing long-term exposure to high BP, even in individuals with normal BP levels.

Insecticides chlorantraniliprole and flubendiamide in Aster scaber: Dissipation kinetics, processing effects, and risk assessment.

The residue characteristics, processing effects of washing and drying, and dietary risks of chlorantraniliprole (CAP) and flubendiamide (FBD) to Koreans were investigated using Aster scaber in a greenhouse. Following foliar application, the initial FBD residues were 3-10 times higher than those of CAP. However, the biological half-lives were similar at 6.0-8.3 and 6.8-9.9 days for CAP and FBD, respectively. The pre-harvest residue limits (PHRLs) 7 days before harvest, derived from the dissipation rates and maximum residue limits, were 12.2 and 33.2 mg/kg for CAP and FBD, respectively. For the removal of CAP and FBD from A. scaber, washing with a neutral detergent was more effective than running under or dipping in tap water (86.5 % and 66.2 %, respectively). Processing factors in fields I and II were 2.6 and 5.1 for CAP and 2.0 and 5.7 for FBD, respectively. Drying removal efficiencies in fields I and II averaged 46.4 % and 52.3 % for CAP and 48.4 % and 49.2 % for FBD, respectively. Chronic health risk assessments indicated that dietary exposure to CAP and FBD is acceptable for Korean health.

Correlation between environmental pollutant exposure and cardiopulmonary health by serum biomarker analysis in the Swedish elderly population.

Persistent organic pollutants (POPs) affect human health through the aryl hydrocarbon receptor (AhR) pathway and are implicated in mitochondrial dysfunction. Using data from the PIVUS study, we investigated the associations of serum AhR ligand (POP)-mediated luciferase activity (AhRL), mitochondrial ATP production inhibiting substances (MIS-ATP), and those affecting reactive oxygen species (MIS-ROS) with several metabolic syndrome (MetS) and cardiopulmonary function parameters. These include insulin resistance (HOMA-IR), inflammation, oxidative stress, and cardiopulmonary variables (FVC, FEV1, LV-EF, CCA distensibility). MIS-ATP showed significant correlations with HOMA-IR and pulmonary functions, indicating its direct impact of MIS-ATP on metabolic and pulmonary health. MIS-ROS correlated with oxidative stress markers and CCA distensibility, suggesting a role in systemic inflammatory responses. This study highlights the intricate relationships between environmental pollutant mixture and cardiopulmonary health in MetS as indicated by biomarkers of POP exposure in the elderly population, suggesting POP exposure may influence MetS onset and progression through mitochondrial dysfunction.

Comparison of Nefopam-Based Patient-Controlled Analgesia with Opioid-Based Patient-Controlled Analgesia for Postoperative Pain Management in Immediate Breast Reconstruction Surgery: A Randomized Controlled Trial.

Background/Objectives: Immediate breast reconstruction surgery (BRS) often leads to significant postoperative pain, necessitating effective analgesia. This study aimed to compare the analgesic efficacy of patient-controlled analgesia (PCA) containing nefopam with that of PCA containing opioids alone in patients undergoing BRS. Methods: A prospective, double-blind, randomized controlled trial was conducted on 120 patients undergoing immediate BRS after mastectomy. Patients were randomly allocated to receive PCA with fentanyl alone (Group F: fentanyl 10 mcg/kg), fentanyl and nefopam (Group FN: fentanyl 5 mcg/kg + nefopam 1 mg/kg), or nefopam alone (Group N: nefopam 2 mg/kg). Pain intensity (expressed in VASr and VASm), opioid consumption, and opioid-related complications were assessed. Results: PCA with nefopam, either alone or in combination with opioids, demonstrated non-inferior analgesic efficacy compared to PCA with fentanyl alone. At 24 h postoperatively, the VASr scores were 2.9 ± 1.0 in Group F, 3.1 ± 1.2 in Group FN, and 2.8 ± 0.9 in Group N (p = 0.501). At the same timepoint, the VASm scores were 4.1 ± 1.2 in Group F, 4.5 ± 1.5 in Group FN, and 3.8 ± 1.4 in Group N (p = 0.129). Significant differences among the three groups were observed at all timepoints except for PACU in terms of the total opioid consumption (p < 0.0001). However, there were no significant differences in opioid-related complications among the three groups. Conclusions: PCA with nefopam, whether alone or in combination with opioids, offers non-inferior analgesic efficacy compared to PCA with fentanyl alone in patients undergoing immediate BRS.

Effect of Preoperative Clear Liquid Consumption on Postoperative Recovery in Pediatric Patients Undergoing Minimally Invasive Repair of Pectus Excavatum: A Prospective Randomized Controlled Study.

Background/Objectives: Preoperative fasting guidelines traditionally aim to reduce pulmonary aspiration risk. However, concerns over the adverse effects of prolonged fasting have led to exploring alternatives. This study aimed to investigate the impact of preoperative clear liquid intake on postoperative outcomes in children undergoing minimally invasive repair of pectus excavatum (MIRPE). Methods: A prospective randomized controlled study was conducted on children aged 3-6 years scheduled for elective MIRPE. Patients were randomized into either a routine overnight fasting group (NPO) or a clear liquid group. The incidence and severity of emergence delirium (ED) were assessed using Pediatric Anesthesia Emergence Delirium (PAED) and Watcha scales at recovery room. Postoperative pain scores and opioid requirements were evaluated at intervals of 1-6 h, 6-12 h, and 12-24 h after surgery. Results: Fasting time was 178.6 ± 149.5 min and 608.9 ± 148.4 min in the clear liquid group compared and NPO group, respectively. The incidence of ED, measured by PAED and Watcha scales, was lower in the clear liquid group (PAED score ≥ 12: 55.6% vs. 85.2%, p = 0.037; Watcha score ≥ 3: 51.9% vs. 85.2%, p = 0.019). The highest PAED score recorded in the recovery room was significantly lower in the clear liquid group (11.4 ± 2.8 vs. 14.6 ± 2.8, p < 0.001). Clear liquid group showed significantly lower pain scores at 1-6, 6-12, and 12-24 h postoperatively. Additionally, clear liquid group had lower opioid requirement at 1-6 and 6-12 h postoperatively. Conclusions: Preoperative clear liquid consumption was associated with a lower incidence of ED in pediatric patients undergoing MIRPE.

Comparative Biological Half-Life of Penthiopyrad and Tebufenpyrad in Angelica Leaves and Establishment of Pre-Harvest Residue Limits (PHRLs).

To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.

Loss of Ninjurin1 alleviates acetaminophen-induced liver injury via enhancing AMPKα-NRF2 pathway.

Acetaminophen (APAP), a widely used pain and fever reliever, is a major contributor to drug-induced liver injury, as its toxic metabolites such as NAPQI induce oxidative stress and hepatic necrosis. While N-acetylcysteine serves as the primary treatment for APAP-induced liver injury (AILI), its efficacy is confined to a narrow window of 8-24 h post-APAP overdose. Beyond this window, liver transplantation emerges as the final recourse, prompting ongoing research to pinpoint novel therapeutic targets aimed at enhancing AILI treatment outcomes. Nerve injury-induced protein 1 (Ninjurin1; Ninj1), initially recognized as an adhesion molecule, has been implicated in liver damage stemming from factors like TNFα and ischemia-reperfusion. Nonetheless, its role in oxidative stress-related liver diseases, including AILI, remains unexplored. In this study, we observed up-regulation of Ninj1 expression in the livers of both human DILI patients and the AILI mouse model. Through the utilization of Ninj1 null mice, hepatocyte-specific Ninj1 KO mice, and myeloid-specific Ninj1 KO mice, we unveiled that the loss of Ninj1 in hepatocytes, rather than myeloid cells, exerts alleviative effects on AILI irrespective of sex dependency. Further in vitro experiments demonstrated that Ninj1 deficiency shields hepatocytes from APAP-induced oxidative stress, mitochondrial dysfunctions, and cell death by bolstering NRF2 stability via activation of AMPKα. In summary, our findings imply that Ninj1 likely plays a role in AILI, and its deficiency confers protection against APAP-induced hepatotoxicity through the AMPKα-NRF2 pathway.

Analysis of intraocular lens decentration and tilt after femtosecond laser-assisted cataract surgery using swept-source anterior optical coherence tomography.

Objective: To evaluate and compare the magnitude of intraocular lens (IOL) decentration and tilt following conventional and femtosecond laser-assisted cataract surgery (FLACS) using swept-source anterior optical coherence tomography (SS-OCT). Methods: In this retrospective observational study, we enrolled patients who underwent conventional cataract surgery or FLACS with the implantation of hydrophobic 1-piece monofocal IOL. The magnitude of IOL decentration and tilt were measured using SS-OCT. Visual acuity, intraocular pressure, spherical equivalent, axial length, contrast sensitivity, and satisfaction questionnaire were evaluated before and one-month post-surgery. Additionally, postoperative internal cylinder measurements were obtained using a wavefront aberrometer. Correlation factors between each parameter and IOL decentration or tilt were analyzed. Results: This study included 100 eyes from 100 patients. Mean IOL decentration and tilt were 0.21 ± 0.13 mm and 5.01 ± 1.49°, respectively. Conventional cataract surgery (versus FLACS, P = 0.001) and male sex (versus female, P = 0.047) were significantly correlated with higher postoperative decentration. Preoperative lens diameter (P < 0.001), preoperative lens tilt (P = 0.007), and preoperative intraocular pressure (P = 0.027) were correlated with higher postoperative tilt. Fifty eyes that underwent FLACS demonstrated mean postoperative decentration of 0.21 ± 0.13 mm and tilt of 4.64 ± 1.48°. Compared with the conventional surgery group, the FLACS group significantly differed in postoperative decentration (0.30 ± 0.12 mm, P < 0.001) but not in tilt (5.03 ± 1.35°, P = 0.173). Postoperative visual acuity did not significantly differ between the two groups. Conclusion: Patients who underwent FLACS demonstrated better IOL decentration and tilt than those who underwent conventional cataract surgery one-month post-surgery. However, differences in IOL decentration and tilt did not affect postoperative visual acuity.

Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

Cumulative sum analysis of the learning curve for retrograde intrarenal stone surgery in newbie surgeons.

INTRODUCTION: This study investigated the learning curve of retrograde intrarenal surgery (RIRS) in patients with medium-sized stones using cumulative sum analysis (CUSUM) to evaluate the competence and proficiency of three new surgeons during their first RIRS procedures. MATERIALS AND METHODS: We conducted a retrospective review of 227 patients from 2019 to 2022 at a single institution. The patients were divided into four groups based on the operating surgeon: tutor surgeon (85 patients), newbie surgeon A (21 patients), newbie surgeon B (85 patients), and newbie surgeon C (36 patients). Patients had one or multiple stones with the largest stone diameter fell within the range of 10-30 mm. Fragmentation efficacy was calculated as "removed stone volume (mm3) divided by operative time (minutes)." CUSUM analysis monitored changes in fragmentation efficacy and validated surgical outcomes. RESULTS: No statistically significant differences were observed in the total stone volume, maximum stone size, or total operation time between the three newbie surgeons and the tutor surgeon. The mean fragmentation efficacy value was comparable among the newbie surgeons, but significantly different from that of the tutor surgeon. The minimum acceptable fragmentation efficacy level was set at 25.12 mL/min, based on the tutor's average value. The CUSUM curves for the three surgeons initially remained relatively flat until Cases 12-15, after which they increased and eventually plateaued. Stone-free rates and postoperative complications did not differ significantly among the surgeons. CONCLUSION: Learning curve analysis for the three newbie surgeons indicated that approximately 12-15 cases were required to reach a plateau.

Specificity of tilt illusion reduction through perceptual learning.

Human perceptual ability can be improved by perceptual learning through repeated exposure or training. Perceptual learning studies have focused on achieving accurate perception of stimuli by improving perceptual sensitivity. However, eliminating illusions can also be one of the ways of accurate perception. To determine whether the illusion can be attenuated by perceptual learning, the current study used a tilt illusion where the orientation of the grating presented in the center (central grating) was misperceived because of the orientation of the grating presented in the periphery (surrounding grating). In Experiment 1, participants were trained either in the illusion training condition, in which they trained with illusory stimuli presenting both surrounding and central gratings together, or in the control training condition, where only the central grating was presented. The results confirmed that the tilt illusion was reduced only in the illusion training condition. Experiment 2 tested the transfer effect of learning, which is not often observed in perceptual learning. During training, the orientation of the surrounding grating was fixed to see whether the elimination of the illusion also occurred in the surrounding grating with an orientation that was not used during training. A decrease in the illusion was found only in the case of a surrounding grating with trained orientations, and not in the case of surrounding gratings with untrained orientations. These results suggest that the reduction in tilt illusion through training is due to perceptual learning.