Repositioned versus exchanged flanged intraocular lens fixation for intraocular lens dislocation.

This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.

Case report: Management of recurrent pupillary optic capture with sutureless surgical technique using 7-0 polypropylene flange.

Background: To report a novel surgical technique for recurrent pupillary optic capture after flanged intraocular lens (IOL) fixation. Methods: In this retrospective case series, we detail our use of two parallel 7-0 polypropylene sutures passed between the iris plane and the optic of scleral-fixated IOL to address pupillary optic capture. Flanges were created using ophthalmic cautery to secure it to the sclera without suture. Results: Two eyes with pupillary optic capture underwent a sutureless surgical technique using 7-0 polypropylene flanges. No recurrences of pupillary optic capture were observed during the 1-year follow-up. Conclusion: Our sutureless surgical technique using a 7-0 polypropylene flange was an effective, efficient, and less invasive approach for treating recurrent pupillary optic capture.

Effects of physical activity participation on cognitive impairment in older adults population with disabilities.

Background: Existing research on the association between cognitive function and physical activity in the older adults population with disabilities is limited. Additionally, there is a need to explore avenues for enhancing the longevity and quality of life among these individuals. Objective: This study aimed to investigate the independent and joint associations between cognitive function and levels of physical activity in the older adults population with disabilities. Methods: A total of 315 older adults adults (men = 182, women = 133), identified with disabilities based on medical evaluation, were recruited from the first survey of the Korean Longitudinal Study of Aging (KLoSA). Participants underwent assessments for cognitive function, physical activity (PA), activities of daily living (ADLs), instrumental activities of daily living (IADLs), and grip strength. Results: ADLs (p < 0.001) and IADLs (p < 0.001) scores were significantly higher in the male normal cognitive group compared to both the male and female cognitive impairment groups. In an unadjusted model, disabled older adults individuals who did not meet the recommended PA guidelines showed an increased odds ratio for cognitive dysfunction (OR = 2.29, 95% CI = 1.32-3.97). Those participating in PA at least 1 day per week also demonstrated an elevated odds ratio (OR = 1.22, 95% CI = 1.08-1.38) for cognitive dysfunction compared to those who engaged in regular PA. A negative correlation was observed between K-MMSE scores and grip strength (r = 0.448, p < 0.001). Conclusion: This study provides robust evidence that disabled older adults individuals who do not meet the recommended guidelines for PA or who do not participate in PA at least once a week have an increased likelihood of cognitive impairment compared to those who are regularly active.

Airway leakage due to malpositioning of esophageal temperature probe during robot-assisted radical prostatectomy: a case report.

Measuring patients' core body temperature during surgery is essential and commonly performed with an esophageal temperature probe. The probe must be placed in the lower third of the esophagus for accurate measurement. In this case report, we describe our experience of discovering an inadvertently malpositioned esophageal temperature probe in the right inferior lobar bronchus, which led to ventilation-related problems in a patient undergoing prostate surgery.

Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy.

Activation of hypoxia-inducible factor 1α (HIF1α) contributes to blood-retinal barrier (BRB) breakdown and pathological neovascularization responsible for vision loss in ischemic retinal diseases. During disease progression, mitochondrial biology is altered to adapt to the ischemic environment created by initial vascular dysfunction, but the mitochondrial adaptive mechanisms, which ultimately contribute to the pathogenesis of ischemic retinopathy, remain incompletely understood. In the present study, it is identified that expression of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) is essential for BRB breakdown and pathologic retinal neovascularization in mouse models mimicking ischemic retinopathies. Genetic Trap1 ablation or treatment with small molecule TRAP1 inhibitors, such as mitoquinone (MitoQ) and SB-U015, alleviate retinal pathologies via proteolytic HIF1α degradation, which is mediated by opening of the mitochondrial permeability transition pore and activation of calcium-dependent protease calpain-1. These findings suggest that TRAP1 can be a promising target for the development of new treatments against ischemic retinopathy, such as retinopathy of prematurity and proliferative diabetic retinopathy.

Effect of external subretinal fluid drainage on persistent subretinal fluid after scleral buckle surgery in macula-involving rhegmatogenous retinal detachment.

This study aimed to analyze the duration and causes of persistent subretinal fluid (PSF) after scleral buckle (SB) surgery in patients with macula-involving rhegmatogenous retinal detachment (RRD). Sixty-one eyes of 61 patients with macula-involving RRD who underwent SB surgery between 2016 and 2022 were reviewed retrospectively. PSF was confirmed on optical coherence tomography. The PSF duration after surgery and the analysis of relevant ocular and systemic factors were conducted according to the PSF duration. The mean duration of PSF was 5.9 ± 4.6 months in all eyes and 8.1 ± 5.0 months in eyes not treated with external subretinal fluid (SRF) drainage, which was significantly longer than 4.5 ± 3.7 months in those subjected to external SRF drainage. The mean best-corrected visual acuity improved significantly 3 months after surgery. There were significant visual improvements in the external SRF drainage group compared to the non-drainage group during all follow-up periods. Longstanding shallow RRD was significantly associated with longer PSF duration after SB surgery. External SRF drainage during SB surgery can effectively reduce SRF, shorten the duration of PSF, and accelerate visual improvement.

Effect of cholesterol variability on the incidence of cataract, dementia, and osteoporosis: A study using a common data model.

The effects of cholesterol variability on cataracts, dementia, and osteoporosis remain controversial. Using a common data model, we investigated the effects of variations in cholesterol levels on the development of cataracts, dementia, and osteoporosis. Patients who received statin therapy between 2011 and 2020 and those with 3 or more tests for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were included. The patients were divided into those with a coefficient of variation (CV) of TC higher than the mean (high-CV group) and those with a lower CV of TC (low-CV group). Moreover, 1:1 propensity score matching was conducted based on demographic variables. Cataract, dementia, or osteoporosis was defined as having a diagnostic, drug, or surgical code based on the cohort definition. Of the 12,882 patients, cataracts, dementia, and osteoporosis were developed in 525 (4.1%), 198 (1.5%), and 438 (3.4%) patients, respectively. The stratified Cox proportional hazards model showed that the incidences of cataracts and osteoporosis were 1.38 and 1.45 times greater in the high-CV group than in the low-CV group, respectively. Our study revealed that TC variability is associated with developing cataracts and osteoporosis.

Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.

Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.

Spontaneous pneumothorax after shoulder arthroscopy under general anesthesia: a case report.

A woman in her early 70s presented with a right fifth rib fracture along with left scapular body and glenoid fractures resulting from a traffic accident. She had no history of lung disease. The patient underwent multi-incisional video-guided arthroscopic fracture reduction and screw fixation in the right lateral decubitus position under general anesthesia, and surgery was followed by chest tube insertion. Left-sided pneumothorax was found during routine postoperative radiography despite the absence of relevant symptoms or signs such as hypoxia, chest pain, or respiratory difficulty. We herein report this unusual case with a brief literature review.

Protective Effects of Cirsilineol against Lipopolysaccharide-Induced Inflammation; Insights into HO-1, COX-2, and iNOS Modulation.

In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in Artemisia vestita, were examined on lipopolysaccharide (LPS)-induced inflammatory responses. CSL was found to have antioxidant, anticancer, and antibacterial properties, and was lethal to many cancer cells. We assessed the effects of CSL on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). We also examined the effects of CSL on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in the pulmonary histological status of LPS-injected mice. The results showed that CSL increased HO-1 production, inhibited luciferase-NF-κB interaction, and reduced COX-2/PGE2 and iNOS/NO levels, leading to a decrease in signal transducer and activator of transcription (STAT)-1 phosphorylation. CSL also enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and reduced IL-1ß expression in LPS-treated HUVECs. We found that CSL's suppression of iNOS/NO synthesis was restored by inhibiting HO-1 through RNAi. In the animal model, CSL significantly decreased iNOS expression in the pulmonary biostructure, and TNF-α level in the bronchoalveolar lavage fluid. These findings indicate that CSL has anti-inflammatory properties by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, CSL may have potential as a candidate for developing new clinical substances to treat pathological inflammation.

Procyanidin B2 Attenuates Sepsis-Induced Acute Lung Injury via Regulating Hippo/Rho/PI3K/NF-κB Signaling Pathway.

Acute lung injury (ALI) is a frequent and challenging aspect of sepsis that currently lacks effective treatments. Procyanidin B2 (PB2) has anti-inflammatory and antioxidant properties. The aim of this study was to determine the effectiveness and mechanism of action of PB2 in treating sepsis-induced ALI using animal experiments. A sepsis-induced ALI mouse model was used by administering lipopolysaccharide (LPS) and then evaluating the levels of inflammatory cytokines and lung injury through measurements of cytokine levels using enzyme-linked immunosorbent assay (ELISA), Western blot and real-time PCR, as well as by the examination of relevant signaling pathways. The animal experiments showed that PB2 protected the lungs from injury caused by LPS and reduced the levels of various inflammatory cytokines in both the serum and lung tissue. Western blot analysis showed that PB2 reduced the expression of TLR4/NF-κB and increased the expression of PI3K/Akt, and also inhibited the Hippo and Rho signaling pathways. The results of the study showed that PB2 helps to treat sepsis-induced ALI by controlling cytokine storms and reducing inflammation by altering the expressions of the TLR4/NF-κB, PI3K/Akt, Hippo and Rho signaling pathways. This research provides a foundation for the further investigation of PB2's mechanism and its potential use in treating sepsis.

Melatonin and Exercise Counteract Sarcopenic Obesity through Preservation of Satellite Cell Function.

Sarcopenic obesity (SO) is characterized by atrophic skeletal muscle impairment (sarcopenia) and obesity, which is associated with adverse outcomes of morbidity and mortality in elderly people. We investigated the effects of melatonin and exercise training on SO in 32-week-old senescence-accelerated mouse-prone-8 (SAMP8) mice fed a normal diet or a high-fat diet for 16 weeks. Melatonin, exercise, or melatonin and exercise for 8 weeks displayed reductions in the SO-induced impairment of skeletal muscle function and atrophy. Specifically, a decrease in mitochondrial calcium retention capacity in skeletal muscles observed in the HFD-con group was attenuated in melatonin and/or exercise intervention groups. More importantly, HFD-con mice displayed a lower number of Pax7+ satellite cells (SCs) and higher expression of p16ink than P8ND mice, which were attenuated by melatonin and/or exercise interventions. The cellular senescence in SC-derived primary myoblasts from HFD-con mice was significantly attenuated in myoblasts from the melatonin and/or exercise groups, which was reproduced in a senescence model of H2O2-treated C2C12 myoblasts. Our results suggest that melatonin and exercise training attenuate SO-induced skeletal muscle dysfunction, at least in part, through preserving the SC pool by inhibiting cellular senescence and attenuating mitochondrial dysfunction.

Antiplatelet Aggregation Properties of Cirsilineol: A Novel Inhibitor of Blood Coagulation Factor Xa.

A small natural substance called cirsilineol (CSL), which was discovered in the plant Artemisia vestita, is lethal to many cancer cells and has antioxidant, anticancer, and antibacterial properties. Here, we investigated the underlying mechanisms of the antithrombotic action of CSL. We demonstrated that CSL has antithrombotic efficacy comparable to rivaroxaban, a direct blood coagulation factor Xa (FXa) inhibitor employed as a positive control, in inhibiting the enzymatic activity of FXa and the platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a thromboxane A2 analog. The expression of P-selectin, the phosphorylation of myristoylated alanine-rich C kinase substrate by U46619 or ADP, and the activation of PAC-1 in platelets were inhibited by CSL. Nitric oxide production was increased by CSL in ADP- or U46619-treated human umbilical vein endothelial cells (HUVECs), although excessive endothelin-1 secretion was suppressed. CSL demonstrated strong anticoagulant and antithrombotic effects in a mouse model of arterial and pulmonary thrombosis. Our findings suggest that CSL is a potential pharmacological candidate for a novel class of anti-FXa and antiplatelet medications.

A multiplexed siRNA screen identifies key kinase signaling networks of brain glia.

The dynamic behaviors of brain glial cells in various neuroinflammatory conditions and neurological disorders have been reported; however, little is known about the underlying intracellular signaling pathways. Here, we developed a multiplexed kinome-wide siRNA screen to identify the kinases regulating several inflammatory phenotypes of mouse glial cells in culture, including inflammatory activation, migration, and phagocytosis of glia. Subsequent proof-of-concept experiments involving genetic and pharmacological inhibitions indicated the importance of T-cell receptor signaling components in microglial activation and a metabolic shift from glycolysis to oxidative phosphorylation in astrocyte migration. This time- and cost-effective multiplexed kinome siRNA screen efficiently provides exploitable drug targets and novel insight into the mechanisms underlying the phenotypic regulation of glial cells and neuroinflammation. Moreover, the kinases identified in this screen may be relevant in other inflammatory diseases and cancer, wherein kinases play a critical role in disease signaling pathways.

Therapeutic Effects of Cornuside on Particulate Matter-Induced Lung Injury.

Particulate matter (PM) is a mixture comprising both organic and inorganic particles, both of which are hazardous to health. The inhalation of airborne PM with a diameter of ≤2.5 µm (PM2.5) can cause considerable lung damage. Cornuside (CN), a natural bisiridoid glucoside derived from the fruit of Cornus officinalis Sieb, exerts protective properties against tissue damage via controlling the immunological response and reducing inflammation. However, information regarding the therapeutic potential of CN in patients with PM2.5-induced lung injury is limited. Thus, herein, we examined the protective properties of CN against PM2.5-induced lung damage. Mice were categorized into eight groups (n = 10): a mock control group, a CN control group (0.8 mg/kg mouse body weight), four PM2.5+CN groups (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight), and a PM2.5+CN group (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight). The mice were administered with CN 30 min following intratracheal tail vein injection of PM2.5. In mice exposed to PM2.5, different parameters including changes in lung tissue wet/dry (W/D) lung weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were examined. Our findings revealed that CN reduced lung damage, the W/D weight ratio, and hyperpermeability caused by PM2.5. Moreover, CN reduced the plasma levels of inflammatory cytokines produced because of PM2.5 exposure, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and nitric oxide, as well as the total protein concentration in the BALF, and successfully attenuated PM2.5-associated lymphocytosis. In addition, CN substantially reduced the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1, and increased protein phosphorylation of the mammalian target of rapamycin (mTOR). Thus, the anti-inflammatory property of CN renders it a potential therapeutic agent for treating PM2.5-induced lung injury by controlling the TLR4-MyD88 and mTOR-autophagy pathways.

Contribution of High-Intensity Interval Exercise in the Fasted State to Fat Browning: Potential Roles of Lactate and ß-Hydroxybutyrate.

PURPOSE: Fat browning contributes to energy consumption and may have metabolic benefits against obesity; however, the potential roles of lactate and ß-hydroxybutyrate (ß-HB) in fat browning remain unclear. We investigated the roles of a single bout of aerobic exercise that increases lactate and ß-HB levels in the fasted state on the regulation of fat browning in rats and humans. METHODS: Male Sprague-Dawley rats were exposed to 24-h fasting and/or a single bout moderate-intensity aerobic exercise (40 min): sedentary (CON), exercise (ND-EX), fasting (FAST), and exercise + fasting (F-EX). Adult men ( n = 13) were randomly assigned into control with food intake (CON), exercise with intensity at onset of blood lactate accumulation in the fasted state (F-OBLA), and high-intensity interval exercise in the fasted state (F-HIIE) until each participant expended 350 kcal of energy. For evaluating the effects of exercise intensity in rats, we conducted another set of animal experiment, including groups of sedentary fed control, fasting control, and exercise with moderate-intensity or HIIE for 40 min after a 24-h fasting. RESULTS: Regardless of fasting, single bout of exercise increases the concentration of lactate and ß-HB in rats, but the exercise in the fasted state increases the ß-HB level more significantly in rats and humans. F-EX-activated fat browning (AMPK-SirT1-PGC1α pathway and PRDM16) and thermogenic factor (UCP1) in white fat of rats. In rats and humans, exercise in the fasted state increased the blood levels of fat browning-related adipomyokines. In particular, compared with F-OBLA, F-HIIE more efficiently increases free fatty acid as well as blood levels of fat browning adipomyokines in humans, which was correlated with blood levels of lactate and ß-HB. In rats that performed exercise with different intensity, the higher plasma lactate and ß-HB levels, and higher expression of p-AMPK, UCP1, and PRDM16 in white adipose tissue of HIIE group than those of moderate-intensity group, were observed. CONCLUSIONS: A single bout of aerobic exercise in the fasted state significantly induced fat browning-related pathways, free fatty acid, and adipomyokines, particularly F-HIIE in human. Although further evidence for supporting our results is required in humans, aerobic exercise in the fasted state with high intensity that increase lactate and ß-HB may be a modality of fat browning.

Comparison of the Estimation Methods from Acute to Chronic Biotic Ligand Model-Based Predicted No-Effect Concentrations for Nickel in Freshwater Species.

Biotic ligand models (BLMs) and the sensitivities of indigenous species are used to assess the environmental risk considering the bioavailability of metals, such as nickel. However, the BLM-based acute-to-chronic ratio (ACR) is required if the predicted no-effect concentration (PNEC) cannot be derived from the chronic species sensitivity distribution (SSD). The applicability of the ACR approach for estimating BLM-based PNEC for nickel from acute toxicity data was evaluated in the present study. The BLM-based acute SSD for nickel was built using the sensitivities of 21 indigenous species and different taxon-specific BLMs for each taxonomic group. To predict the acute sensitivity of invertebrates, the chronic crustacean nickel BLM with pH effect term, which can account for nickel toxicity at high pH levels, was used. This was used instead of the existing acute BLM for crustacean, which has too narrow a pH range to cover the pH dependency of toxicity. The final BLM-based ACR of nickel, determined within a factor of 1.53 from the species-specific acute and chronic sensitivities of the six species, was more reliable than the typical ACR estimated within a factor of 1.84. A linear relationship (r2 = 0.95) was observed between the PNECs using BLM-based ACR and the PNECs derived from the BLM-based chronic SSD of the European Union Risk Assessment Reports. In conclusion, the BLM-based PNEC for nickel could be derived using the ACR approach, unlike when copper BLM was applied. The BLM-based ACR for nickel is the first result calculated by directly comparing acute and chronic species sensitivities, and will contribute to the application of BLM-based risk assessment in broader ecoregions. Environ Toxicol Chem 2023;42:914-927. © 2023 SETAC.