Novel insight into astrocyte-mediated gliotransmission modulates the synaptic plasticity in major depressive disorder.

Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.

Naringenin counteracts LPS-induced inflammation and immune deficits in chicken thymus by alleviating mtROS/ferroptosis levels.

Naringenin is a flavonoid with significant anti-inflammatory and antioxidant properties. Mitochondrial dynamics, the mitochondrial respiratory chain, and mtROS are closely related to each other and regulate various biological processes. Ferroptosis is closely related to inflammatory responses and immune function in multiple tissues and organs. However, whether naringenin can alleviate LPS-induced inflammation and immune disorders in the chicken thymus via mtROS/ferroptosis has not been reported. Therefore, in this study, we constructed chicken thymus and MSB-1 cell models of LPS and naringenin based on screening for naringenin concentrations that have positive effects on inflammation and immune function to further investigate the anti-inflammatory, antiferroptosis, and maintenance of the immune function of naringenin. The results showed that 40 mg/kg naringenin alleviated LPS-induced tissue damage, elevated serum inflammatory factors, and decreased serum immune factors. The mechanism by which naringenin attenuates mtROS release by alleviating the imbalance of mitochondrial dynamics and the blockage of the respiratory chain. The effect of naringenin on alleviating LPS-induced lipid peroxidation, disruption of the GSH/GSSG system, iron overload, and GPx4 inactivation, thereby attenuating ferroptosis in thymus tissue, was inhibited by the addition of mtROS activators. In conclusion, naringenin alleviates LPS-induced ferroptosis in chicken thymus by attenuating mtROS release.

A Novel Scaffold of Icariin/Porous Magnesium Alloy-Repaired Knee Cartilage Defect in Rat by Wnt/ß-Catenin Signaling Pathway.

Cartilage defects caused by joint diseases are difficult to treat clinically. Tissue engineering materials provide a new means to promote the repair of cartilage defects. The purpose of this study is to design a novel scaffold of porous magnesium alloy loaded with icariin and sustained release in order to explore the effect and possible mechanism of this scaffold in repairing SD rat knee articular cartilage defect. We constructed a novel type of icariin/porous magnesium alloy scaffold, observed the structure of the scaffold by electron microscope, detected the drug release of icariin in the scaffold and the biological safety, and established an animal model of cartilage defect in the femoral intercondylar fossa of the knee joint in rats; the scaffold was placed in the defect. After 12 weeks of repair, the rat knee articular cartilage repair was evaluated by gross specimens and micro-CT, HE, safranin O-fast green, and toluidine blue staining combined with the modified Mankin's score. The protein expressions of the Wnt/ß-catenin signaling pathway-related factors (ß-catenin, Wnt5a, Wnt1, sFRP1) and chondrogenic differentiation-related factors (Sox9, Aggrecan, Col2α1) were detected by immunohistochemical staining. We found that the novel scaffold of icariin/porous magnesium alloy can release icariin slowly and has biosafety in rats. Compared with other groups, icariin/porous magnesium alloy can significantly promote the repair of cartilage defects and the expressions of ß-catenin, Wnt5a, Wnt1, Sox9, Aggrecan, and Col2α1 (P < 0.05). This novel scaffold can promote the repair of rat knee cartilage defects, and this process may be achieved by activating the Wnt/ß-catenin signaling pathway.

A nonparametric point-by-point method to measure time-dependent frequency in wavelength modulation spectroscopy.

A nonparametric point-by-point (NPP) method is presented for high-accuracy measurement of the time-dependent frequency (laser frequency) in tunable laser absorption spectroscopy, crucial for ensuring ultimate measurement accuracy. In wavelength modulation spectroscopy in particular, the parametric methods in current use for time-dependent frequency measurement are insufficiently accurate and are difficult to apply to complex modulation scenarios. Based on a multi-scale viewpoint, point-by-point measurement of the frequency is realized by linear superposition of the frequency information mapped from the interferometric signal on a unit scale and on a local scale. Validation experiments indicate that the measurement accuracy of the proposed NPP method is three times that of the existing parametric methods, while effectively immunizing against non-ideal tuning effects. Additionally, the NPP method is suitable for use with arbitrarily complex modulations such as square wave modulation, for which parametric methods are inapplicable.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Well Leg Compartment Syndrome in the Thigh and Calf Caused by a Forced Prone Position after Syncope.

An 80-year-old male patient was admitted to the hospital due to swelling in the right lower limb with local blisters caused by a forced prone position for 9 hours after syncope. The patient got up in the middle of the night and fainted beside the bed due to a transient cerebral ischemia attack. The front of the right thigh and calf contacted the bed edge, presenting a forced prone position for 9 hours. The physical examination revealed swelling of the right lower limb, accompanied by local tension blisters, and the tension of the thigh and calf was increased. The patient had a history of diabetes, and no lower limb artery or vein thrombosis was found on B-ultrasound. Based on these findings, the patient was diagnosed with well leg compartment syndrome in the right thigh and calf. When the patient was admitted, the creatine phosphokinase level was 62,300 u/L, and the creatinine level was 2.66 mg/dL. Besides, the urea level of this patient was 11 mmol/L. He developed anuria with a high creatinine level, indicating acute kidney injury. Subsequently, temporary hemodialysis was performed for treatment. The patient underwent fasciotomy of the right thigh and calf, and the vacuum-assisted closure device was adopted for wound treatment. After 2 weeks of decompression, the wound was directly sutured under tension. After renal replacement therapy, the creatine phosphokinase level of this patient was 102 u/L, and the creatinine level was 95 mol/L, which tended to be normal.

ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41.

HIV-1 envelope glycoprotein gp41 mediates fusion between HIV-1 and host cell membranes, making inhibitors of gp41 attractive anti-HIV drugs. We previously reported an efficient HIV-1 fusion inhibitor, ADS-J1, with a Y-shaped structure. Here, we discovered a new compound, ADS-J21, with a Y-shaped structure similar to that of ADS-J1 but with a lower molecular weight. Moreover, ADS-J21 exhibited effective anti-HIV-1 activity against divergent HIV-1 strains in vitro, including several HIV-1 laboratory-adapted strains and primary isolates with different subtypes (clades A to F) and tropisms (X4 or R5). Mechanistic studies have demonstrated that ADS-J21 blocks the formation of the gp41 six-helix bundle (6-HB) by targeting conserved amino acids Lys35 and Trp32. These findings suggest that ADS-J21 can be used as a new lead compound for further optimization in the development of a small-molecule fusion inhibitor.

Aristolochic acids-hijacked p53 promotes liver cancer cell growth by inhibiting ferroptosis.

Aristolochic acids (AAs) have been identified as a significant risk factor for hepatocellular carcinoma (HCC). Ferroptosis is a type of regulated cell death involved in the tumor development. In this study, we investigated the molecular mechanisms by which AAs enhanced the growth of HCC. By conducting bioinformatics and RNA-Seq analyses, we found that AAs were closely correlated with ferroptosis. The physical interaction between p53 and AAs in HepG2 cells was validated by bioinformatics analysis and SPR assays with the binding pocket sites containing Pro92, Arg174, Asp207, Phe212, and His214 of p53. Based on the binding pocket that interacts with AAs, we designed a mutant and performed RNA-Seq profiling. Interestingly, we found that the binding pocket was responsible for ferroptosis, GADD45A, NRF2, and SLC7A11. Functionally, the interaction disturbed the binding of p53 to the promoter of GADD45A or NRF2, attenuating the role of p53 in enhancing GADD45A and suppressing NRF2; the mutant did not exhibit the same effects. Consequently, this event down-regulated GADD45A and up-regulated NRF2, ultimately inhibiting ferroptosis, suggesting that AAs hijacked p53 to down-regulate GADD45A and up-regulate NRF2 in HepG2 cells. Thus, AAs treatment resulted in the inhibition of ferroptosis via the p53/GADD45A/NRF2/SLC7A11 axis, which led to the enhancement of tumor growth. In conclusion, AAs-hijacked p53 restrains ferroptosis through the GADD45A/NRF2/SLC7A11 axis to enhance tumor growth. Our findings provide an underlying mechanism by which AAs enhance HCC and new insights into p53 in liver cancer. Therapeutically, the oncogene NRF2 is a promising target for liver cancer.

Evaluation of a nomogram model for predicting in-hospital mortality risk in patients with acute ST-elevation myocardial infarction and acute heart failure post-PCI.

OBJECTIVES: This study aims to identify the risk factors contributing to in-hospital mortality in patients with acute ST-elevation myocardial infarction (STEMI) who develop acute heart failure (AHF) post-percutaneous coronary intervention (PCI). Based on these factors, we constructed a nomogram to effectively identify high-risk patients. METHODS: In the study, a collective of 280 individuals experiencing an acute STEMI who then developed AHF following PCI were evaluated. These subjects were split into groups for training and validation purposes. Utilizing lasso regression in conjunction with logistic regression analysis, researchers sought to pinpoint factors predictive of mortality and to create a corresponding nomogram for forecasting purposes. To evaluate the model's accuracy and usefulness in clinical settings, metrics such as the concordance index (C-index), calibration curves, and decision curve analysis (DCA) were employed. RESULTS: Key risk factors identified included blood lactate, D-dimer levels, gender, left ventricular ejection fraction (LVEF), and Killip class IV. The nomogram demonstrated high accuracy (C-index: training set 0.838, validation set 0.853) and good fit (Hosmer-Lemeshow test: χ2 = 0.545, p = 0.762), confirming its clinical utility. CONCLUSION: The developed clinical prediction model is effective in accurately forecasting mortality among patients with acute STEMI who develop AHF after PCI.

An acidophilic fungus promotes prey digestion in a carnivorous plant.

Leaves of the carnivorous sundew plants (Drosera spp.) secrete mucilage that hosts microorganisms, but whether this microbiota contributes to prey digestion is unclear. We identified the acidophilic fungus Acrodontium crateriforme as the dominant species in the mucilage microbial communities, thriving in multiple sundew species across the global range. The fungus grows and sporulates on sundew glands as its preferred acidic environment, and its presence in traps increased the prey digestion process. A. crateriforme has a reduced genome similar to other symbiotic fungi. During A. crateriforme-Drosera spatulata coexistence and digestion of prey insects, transcriptomes revealed significant gene co-option in both partners. Holobiont expression patterns during prey digestion further revealed synergistic effects in several gene families including fungal aspartic and sedolisin peptidases, facilitating prey digestion in leaves, as well as nutrient assimilation and jasmonate signalling pathway expression. This study establishes that botanical carnivory is defined by adaptations involving microbial partners and interspecies interactions.

Improved A* Algorithm for Mobile Robots under Rough Terrain Based on Ground Trafficability Model and Ground Ruggedness Model.

Considering that the existing path planning algorithms for mobile robots under rugged terrain do not consider the ground flatness and the lack of optimality, which leads to the instability of the center of mass of the mobile robot, this paper proposes an improved A* algorithm for mobile robots under rugged terrain based on the ground accessibility model and the ground ruggedness model. Firstly, the ground accessibility and ruggedness models are established based on the elevation map, expressing the ground flatness. Secondly, the elevation cost function that can obtain the optimal path is designed based on the two types of models combined with the characteristics of the A* algorithm, and the continuous cost function is established by connecting with the original distance cost function, which avoids the center-of-mass instability caused by the non-optimal path. Finally, the effectiveness of the improved algorithm is verified by simulation and experiment. The results show that compared with the existing commonly used path planning algorithms under rugged terrain, the enhanced algorithm improves the smoothness of paths and the optimization degree of paths in the path planning process under rough terrain.

Research on the mechanism of Ursolic acid for treating Parkinson's disease by network pharmacology and experimental verification.

The objective of this study was to investigate the potential targets and mechanisms of UA in the treatment of PD. The efficacy of UA in PD was assessed through network pharmacology, molecular docking, and experimental methods. Common target protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape. As a result, 9 key genes, namely CASP3, IL6, IL1B, PTGS2, CREB1, TNF, MAPK3, JUN, and CASP8, were selected. Molecular docking simulations were performed using Discovery Studio 2019 to validate the correlation between UA and the core targets. The results demonstrated a favorable binding affinity between UA and CASP8, IL1B, CASP3, TNF, MAPK3 and IL6. In vivo studies showed UA ameliorated motor dysfunction, and UA can significantly increase the protein expression of tyrosine hydroxylase (TH) in PD mice model. In addition, in vitro experiments confirmed that UA effectively reduced the protein expression of CASP8, CASP3 and MAPK3 in PD cell models and suppressed the gene expression of TNF-α, IL-6, and IL-1ß. These findings indicate that the therapeutic effects of UA on PD could be due to its influence on various targets within both the apoptosis and neuroinflammatory signaling pathways. Consequently, this study provides a methodological and theoretical foundation for further elucidating the pharmacological mechanism of UA.

The effects of sleep quality on loneliness among older adults: cohort analysis from the life course perspective.

BACKGROUND: Using cohort analysis to examine the effects of sleep quality on loneliness among older adults from the life course perspective. METHODS: The hierarchical age-period-cohort growth curve model was used to analyze the data from the 2005-2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). RESULTS: (1) Loneliness has a 'U' curve relationship with age, but with the rate of increase gradually slowing down. (2) There were significant differences in loneliness across birth cohorts, with younger cohorts having higher predicted loneliness than older cohorts at the same age. (3) The influence of different sleep quality on loneliness showed a trend of increasing with age. (4) There were no significant differences in the impact of sleep quality on loneliness in different cohorts. CONCLUSIONS: This study has identified heterogeneity in loneliness, emphasising the need for a diversified intervention approach. Sleep quality has a protective effect on loneliness and is easy to assess, making it an important intervention tool. In addition, it is imperative to account for the influences of age and cohort effects when formulating intervention strategies.

Associations between Statin Use and Glaucoma in the All of Us Research Program.

PURPOSE: To investigate associations between statin use and glaucoma in the 2017-2022 All of Us (AoU) Research Program. DESIGN: Cross-sectional, population-based. PARTICIPANTS: 79,742 adult participants aged ≥ 40 years with hyperlipidemia and with electronic health record (EHR) data in the AoU database. METHODS: Hyperlipidemia, glaucoma status, and statin use were defined by diagnoses and medication information in EHR data collected by AoU. Logistic regression analysis was performed to evaluate the association between statin use and glaucoma likelihood. Logistic regression modeling was used to examine associations between glaucoma and all covariates included in adjusted analysis. Serum low-density lipoprotein cholesterol (LDL-C) was used to assess hyperlipidemia severity. Analyses stratified by LDL-C level and age were performed. MAIN OUTCOME MEASURES: Any glaucoma as defined by International Classification of Diseases (ICD) codes found in EHR data. RESULTS: Of 79,742 individuals with hyperlipidemia in AoU, there were 6,365 (8.0%) statin users. Statin use was associated with increased glaucoma prevalence when compared with statin non-use (adjusted odds ratio [aOR]: 1.13, 95% confidence interval [CI]: 1.01-1.26). Higher serum levels of LDL-C were associated with increased odds of glaucoma (aOR: 1.003, 95% CI: 1.003, 1.004). Statin users had significantly higher LDL-C levels compared to nonusers (144.9 mg/dL versus 136.3 mg/dL, p-value < 0.001). Analysis stratified by LDL-C identified positive associations between statin use and prevalence of glaucoma among those with optimal (aOR = 1.39, 95% CI = 1.05-1.82) and high (aOR = 1.37, 95% CI = 1.09-1.70) LDL-C levels. Age-stratified analysis showed a positive association between statin use and prevalence of glaucoma in individuals aged 60-69 years (aOR = 1.28, 95% CI = 1.05-1.56). CONCLUSIONS: Statin use was associated with increased glaucoma likelihood in the overall adult AoU population with hyperlipidemia, in individuals with optimal or high LDL-C levels, and in individuals 60-69 years old. Findings suggest that statin use may be an independent risk factor for glaucoma, which may furthermore be affected by one's lipid profile and age.

Polyphenol (-)-Epigallocatechin Gallate (EGCG) mitigated kidney injury by regulating metabolic homeostasis and mitochondrial dynamics involvement with Drp1-mediated mitochondrial fission in mice.

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury.

Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Microscale Normal Compression Behaviors of Clay Aggregates: A Coarse-Grained Molecular Dynamics Study.

Given the limitations of micromechanical experiments and molecular dynamics simulations, the normal compression process of clay aggregates was simulated under different vertical pressures (P), numbers of particles, loading methods, and environments by a Gay-Berne potential model. On the basis of the variations of particle orientation and the distribution of stacks, the evolution of deformation and stresses was elucidated. The results showed that the effects of the pressure level and loading environment on the deformation were significant. In the range of 0.1-10 MPa, the changes in the void ratio were essentially the evolution of the distribution of stacks determined by attractive short-range van der Waals interactions. The deformation under constant pressure was larger than that under step loading. Because the interactions between clay particles were mainly controlled by mechanical force when in the range of 40-100 MPa, the void ratios under various loading conditions were consistent. It was also found that changes in three-dimensional stresses during compression were dependent on those of the distribution of stacks. In the vacuum environment, owing to the lateral movement of interlocked small stacks, the horizontal stress decreased. The lateral pressure coefficients (k) were greater in an atmospheric environment because the anisotropic particle orientation was relatively less obvious. In the range of 10-100 MPa, when the loading path became longer, k was similar in vacuum but became smaller in an atmosphere. If the initial loading pressure was increased, the number of large stacks sharply increased and the anisotropy was significant in a vacuum environment, which was less prone to lateral expansion. In contrast, more consistent particle arrangements were maintained in an atmosphere. This work will be conducive to explaining experimental observations of long-term ripening.

Implications of lncRNAs in Helicobacter pylori-associated gastrointestinal cancers: underlying mechanisms and future perspectives.

Helicobacter pylori (H. pylori) is a harmful bacterium that is difficult to conveniently diagnose and effectively eradicate. Chronic H. pylori infection increases the risk of gastrointestinal diseases, even cancers. Despite the known findings, more underlying mechanisms are to be deeply explored to facilitate the development of novel prevention and treatment strategies of H. pylori infection. Long noncoding RNAs (lncRNAs) are RNAs with more than 200 nucleotides. They may be implicated in cell proliferation, inflammation and many other signaling pathways of gastrointestinal cancer progression. The dynamic expression of lncRNAs indicates their potential to be diagnostic or prognostic biomarkers. In this paper, we comprehensively summarize the processes of H. pylori infection and the treatment methods, review the known findings of lncRNA classification and functional mechanisms, elucidate the roles of lncRNAs in H. pylori-related gastrointestinal cancer, and discuss the clinical perspectives of lncRNAs.

Racial and ethnic differences in the prevalence and treatment patterns for neovascular glaucoma in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).

PURPOSE: To examine racial and ethnic differences in the prevalence and treatment patterns for neovascular glaucoma (NVG) in at-risk individuals in the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight). PARTICIPANTS: Eyes in the IRIS Registry with a retinal ischemia based on a history of proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO), and/or ocular ischemic syndrome (OIS). METHODS: Race and ethnicity was defined as Asian, Black, Hispanic/Latino, Non-Hispanic White, and Other/Unknown. In eyes with retinal ischemia, the outcome was neovascular glaucoma (NVG). In eyes with NVG, outcomes included treatment of retinal ischemia with pan-retinal photocoagulation (PRP), and surgery to lower intraocular pressure (IOP) with trabeculectomy, tube shunt, and cyclophotocoagulation (CPC). Covariates included age, sex, region of residence, insurance type, smoking status, and systemic and ocular comorbidities. Cox proportional hazards regression was used to examine adjusted associations between race and ethnicity and NVG and each type of NVG treatment. MAIN OUTCOME MEASURES: Incidence of NVG, PRP, trabeculectomy, tube shunt, CPC, and any IOP-lowering surgery RESULTS: Of 312,106 eyes with retinal ischemia, there were 5,885 (1.9%) with NVG. Compared to eyes of individuals who identified as Non-Hispanic White, eyes of individuals who were Black and Hispanic/Latino had higher hazards of NVG in adjusted analyses (hazards ratio [HR]=1.28, 95% confidence interval [CI]=1.15, 1.43 for Black; HR=1.32, 95% CI=1.17, 1.47 for Hispanic/Latino). Compared to eyes of individuals who were Non-Hispanic White, there was higher hazards of trabeculectomy in eyes of individuals who were Hispanic/Latino (adjusted HR=1.91, 95% CI=1.08, 3.39) and higher hazards of tube shunt (adjusted HR=1.35, 95% CI=1.07, 1.69) and of any IOP-lowering surgery (adjusted HR=1.29, 95% CI=1.09, 1.53) in eyes of individuals who were Black. There were no statistically significant differences in the hazards of PRP or CPC. CONCLUSIONS: Eyes of Black and Hispanic/Latino individuals with retinal ischemia in the IRIS Registry had higher likelihood of NVG and of IOP-lowering surgery for NVG. Further study is needed to examine the medical and social factors that preclude optimal management of diabetic eye disease, in order to prevent its blinding complications.

Association of Open-Angle Glaucoma with Dementia in California Medicare Beneficiaries.

PURPOSE: To examine the associations between open-angle glaucoma (OAG) subtypes and dementia in 2019 California (CA) Medicare beneficiaries. DESIGN: Retrospective cross-sectional study. METHODS: OAG diagnosis was determined by the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes in Part B claims, including the following OAG subtypes: primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), pseudoexfoliative glaucoma (PXG), and pigmentary glaucoma (PG). Diagnoses of any dementia, Alzheimer's dementia (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD) were identified by ICD-10 diagnosis codes. Covariates included: demographics, systemic diseases, depression, hearing loss, obesity, smoking and alcohol-related disorders, and long-term aspirin, anticoagulant, and antithrombotic or antiplatelet use. Univariate and multivariable logistic regression models were used to assess the associations between OAG and dementia, adjusting for all covariates. Age-stratified analysis was also performed for beneficiaries aged 65-74 years, 75-84 years, and 85+ years. RESULTS: Among 2,431,150 CA Medicare beneficiaries included in this study, 104,873 (4.3%) had POAG, 9,199 (0.4%) had NTG, 4,045 (0.2%) had PXG and 1,267 (0.05%) had PG. The overall prevalence of any dementia was 3.2% (n=79,009). In adjusted analyses, the odds of any dementia were lower for beneficiaries with all OAG subtypes compared to beneficiaries without glaucoma (odds ratio [OR]=0.74 for POAG, OR=0.74 for PXG, OR=0.60 for NTG, and OR=0.38 for PG; p<0.01). In age-stratified analyses, beneficiaries with PXG had greater odds of VD (OR: 2.84, p=0.006, [aOR]: 2.18, p=0.04) in the youngest age stratum (65-74 years) compared to patients with no glaucoma. The odds for any dementia were lower for beneficiaries with all OAG subtypes compared to beneficiaries without glaucoma in the oldest, but not in the youngest age stratum. CONCLUSIONS: In the 2019 CA Medicare population, PXG is associated with an increased likelihood of VD in beneficiaries 65-74 years old, while other subtypes of POAG are associated with a decreased likelihood of any dementia. These findings may suggest selection bias since older adults who continue to follow up with glaucoma care may be more cognitively intact. Further studies are needed to better understand the complex relationship between glaucoma, dementia, and their subtypes.