Extracellular fluid excess linked to reduced choroidal vascularity index in patients with chronic kidney disease.

Extracellular fluid (ECF) excess is common in patients with chronic kidney disease (CKD). This study (involving 284 patients with CKD) explored the association between choroidal vascularity index (CVI) and ECF excess. We categorised patients into three groups based on extracellular water/total body water: normal, mildly overhydrated, and severely overhydrated. The more severe ECF status was associated with a lower CVI after adjustment (B = - 0.902, p = 0.001). In non-diabetic patients, both vascular luminal (LA, p < 0.001) and stromal areas (SA, p = 0.003) were significantly reduced in patients with severe ECF excess compared to others, whereas diabetic patients showed no significant differences in LA (p = 0.96) and SA (p = 0.86) based on ECF excess status. These findings suggest that ECF status may influence CVI in patients with CKD, underscoring the need for further research to clarify its direct impact on choroidal changes.

Long-Term Prognostic Value of Infarct Transmurality Determined by Contrast-Enhanced Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction.

The long-term prognostic significance of maximal infarct transmurality evaluated by contrast-enhanced cardiac magnetic resonance (CE-CMR) in ST-segment elevation myocardial infarction (STEMI) patients has yet to be determined. This study aimed to see if maximal infarct transmurality has any additional long-term prognostic value over other CE-CMR predictors in STEMI patients, such as microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). The study included 112 consecutive patients who underwent CE-CMR after STEMI to assess established parameters of myocardial injury as well as the maximal infarct transmurality. The primary clinical endpoint was the occurrence of major adverse cardiac events (MACE), which included all-cause death, non-fatal reinfarction, and new heart failure hospitalization. The MACE occurred in 10 patients over a median follow-up of 7.9 years (IQR, 5.8 to 9.2 years) (2 deaths, 3 nonfatal MI, and 5 heart failure hospitalization). Patients with MACE had significantly higher rates of transmural extent of infarction, infarct size >5.4 percent, MVO, and IMH compared to patients without MACE. In stepwise multivariable Cox regression analysis, the transmural extent of infarction defined as 75 percent or more of infarct transmurality was an independent predictor of the MACE after correction for MVO and IMH (hazard ratio 8.7, 95% confidence intervals [CIs] 1.1-71; p=0.043). In revascularized STEMI patients, post-infarction CE-CMR-based maximal infarct transmurality is an independent long-term prognosticator. Adding maximal infarct transmurality to CE-CMR parameters like MVO and IMH could thus identify patients at high risk of long-term adverse outcomes in STEMI.

Expression of ChAT, Iba-1, and nNOS in the Central Nervous System following Facial Nerve Injury.

Facial nerve injury can cause significant functional impairment, impacting both the peripheral and central nervous systems. The present study evaluated changes in facial motor function, numbers of cholinergic neurons and microglia, and nNOS levels in the facial nucleus of the central nervous system (CNS) following peripheral facial nerve injury. Facial nerve function, as determined by eyeblink and whisker-movement reflexes, was evaluated at baseline and 1, 2, 3, 4, 8, and 12 weeks after inducing facial nerve injury through compression or axotomy. The expression of choline acetyltransferase (ChAT), ionized calcium-binding adaptor molecule 1 (Iba-1), and neuronal nitric oxide synthase (nNOS) in the facial nucleus of the CNS was analyzed 2, 4, and 12 weeks after peripheral facial nerve injury. Compression-induced facial nerve injury was found to lead to temporary facial motor impairment, whereas axotomy resulted in persistent impairment. Moreover, both compression and axotomy reduced ChAT expression and increased Iba-1 and nNOS expression in the facial nucleus, indicating upregulation of an inflammatory response and neurodegeneration. These results indicate that, compared with compression-induced injury, axotomy-induced facial nerve injury results in greater facial motor dysfunction and more persistent microglial and nitric oxide activation in the facial nucleus of the CNS.

Molecular Chaperonin HSP60: Current Understanding and Future Prospects.

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.

Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases.

Importance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD. Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea. Design, Setting, and Participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023. Main Outcomes and Measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis. Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis. Conclusions and Relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.

Factors predicting redislocation or suture-break in eyes after scleral-fixated intraocular lens.

PURPOSE: To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation following secondary scleral-fixated IOL (SFIOL) surgery. SETTING: Two tertiary referral hospitals. DESIGN: Retrospective case series. METHODS: Patients undergoing SFIOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SFIOL surgery between June 2014 and December 2019 at two tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded. RESULTS: We included 237 eyes of 225 patients (169 [75.1%] men). The redislocation group was more likely to have a younger mean age at the initial SFIOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P=0.008), have a prior history of a previous suture-break (23 eyes, 52.3% vs 1 eye, 0.5%; P<0.001), and have undergone the initial SFIOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P=0.002) than was the no-redislocation group. Additionally, the redislocation group had a higher occurrence of complications (P<0.001). Multivariable regression revealed that younger age, left eye involvement, aphakic status prior to the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P<0.05) associated with redislocation. CONCLUSION: Younger age, left eye involvement, postoperative complications like ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.

Long-term Outcomes of Surgeries for Retinal Detachment Secondary to Parasitic or Viral Infectious Retinitis.

Purpose: This study sought to compare the long-term outcomes of surgeries for retinal detachment (RD) secondary to viral or parasitic infectious retinitis. Methods: 47 eyes that received pars plana vitrectomy with or without scleral buckling due to RD secondary to polymerase chain reaction-proven viral (Cytomegalovirus, Varicella zoster virus, and Herpes zoster virus) or parasitic (toxoplasma and toxocara) retinitis from October 1st, 2006 to June 30th, 2023 in a single medical center were retrospectively enrolled. Results: Mean follow-up period was 59.03 ± 55.24 months in viral retinitis and 34.80 ± 33.78 months in parasitic retinitis after primary reattachment surgery. During follow-up, 9 eyes (24.3%) with viral retinitis and 5 eyes (50.0%) with parasitic retinitis developed retinal redetachment. Visual acuity success at final follow-up was achieved in 19 eyes (51.4%) with viral retinitis and 6 eyes (60.0%) with parasitic retinitis (p = 0.64). The incidence of retinal redetachment during the first postoperative year was significantly higher in parasitic retinitis compared with viral retinitis (crude incidence 0.21 vs 0.85 in viral and parasitic retinitis, respectively; p = 0.02). Hazard ratio analysis adjusted for age and sex showed 4.58-fold (95% confidence interval 1.22-17.27, p = 0.03) increased risk of retinal redetachment in parasitic retinitis compared with viral retinitis during the first postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis. Conclusions: Compared with RD secondary to viral retinitis, RD secondary to parasitic retinitis showed higher incidence of retinal redetachment during the first postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis.

Prognostic potentials of AI in ophthalmology: systemic disease forecasting via retinal imaging.

BACKGROUND: Artificial intelligence (AI) that utilizes deep learning (DL) has potential for systemic disease prediction using retinal imaging. The retina's unique features enable non-invasive visualization of the central nervous system and microvascular circulation, aiding early detection and personalized treatment plans for personalized care. This review explores the value of retinal assessment, AI-based retinal biomarkers, and the importance of longitudinal prediction models in personalized care. MAIN TEXT: This narrative review extensively surveys the literature for relevant studies in PubMed and Google Scholar, investigating the application of AI-based retina biomarkers in predicting systemic diseases using retinal fundus photography. The study settings, sample sizes, utilized AI models and corresponding results were extracted and analysed. This review highlights the substantial potential of AI-based retinal biomarkers in predicting neurodegenerative, cardiovascular, and chronic kidney diseases. Notably, DL algorithms have demonstrated effectiveness in identifying retinal image features associated with cognitive decline, dementia, Parkinson's disease, and cardiovascular risk factors. Furthermore, longitudinal prediction models leveraging retinal images have shown potential in continuous disease risk assessment and early detection. AI-based retinal biomarkers are non-invasive, accurate, and efficient for disease forecasting and personalized care. CONCLUSION: AI-based retinal imaging hold promise in transforming primary care and systemic disease management. Together, the retina's unique features and the power of AI enable early detection, risk stratification, and help revolutionizing disease management plans. However, to fully realize the potential of AI in this domain, further research and validation in real-world settings are essential.

Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.

The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases.

Gynostemma pentaphyllum Hydrodistillate and Its Major Component Damulin B Promote Hair Growth-Inducing Properties In Vivo and In Vitro via the Wnt/ß-Catenin Pathway in Dermal Papilla Cells.

Alopecia, a prevalent yet challenging condition with limited FDA-approved treatments which is accompanied by notable side effects, necessitates the exploration of natural alternatives. This study elucidated the hair growth properties of Gynostemma pentaphyllum leaf hydrodistillate (GPHD) both in vitro and in vivo. Furthermore, damulin B, a major component of GPHD, demonstrated hair growth-promoting properties in vitro. Beyond its established anti-diabetic, anti-obesity, and anti-inflammatory attributes, GPHD exhibited hair growth induction in mice parallel to minoxidil. Moreover, it upregulated the expression of autocrine factors associated with hair growth, including VEGF, IGF-1, KGF, and HGF. Biochemical assays revealed that minoxidil, GPHD, and damulin B induced hair growth via the Wnt/ß-catenin pathway through AKT signaling, aligning with in vivo experiments demonstrating improved expression of growth factors. These findings suggest that GPHD and damulin B contribute to the hair growth-inducing properties of dermal papilla cells through the AKT/ß-catenin signaling pathway.

Seven-year follow-up of endovascular treatment of iatrogenic brachioradial artery injury complicating percutaneous coronary intervention: a case report.

The radial artery has been used increasingly for percutaneous coronary intervention because of its safety and feasible access route. Nevertheless, transradial complications are possible because of the variation in radial artery anatomy. We experienced a case of the brachioradial artery injury secondary to catheterization, presenting as hypovolemic shock. A 76-year-old woman presented at our emergency department complaining of effort-induced angina. Coronary angiography via the right radial artery showed critical stenosis in the middle of the left anterior descending coronary artery. After wiring into this vessel, balloon angioplasty using a 6-Fr Judkin left guiding catheter was performed with the deployment of the zotarolimus-eluting stent. There was difficulty in negotiating the guidewire and balloons in that resistance was experienced while passing the catheter in the upper arm. Therefore, retrograde radial arteriography was performed to determine any injury to radial artery. This showed contrast extravasation in the brachioradial artery. Initially, manual compression was tried. However, 2 hours later, the patient developed cold sweating and went into a stupor. Laboratory findings showed a decline in hemoglobin, leading to suspicion of hemorrhagic shock. We applied over 30 minutes of balloon inflation, but this was ineffective. While surgical repair was not available, a 6.0 × 50 mm Viabahn stent was placed over the axillary artery. Subsequent angiography showed no further leakage or occlusion of the brachioradial artery. The postprocedural period was uneventful, and the patient was discharged with dual antiplatelet agents. At a 7-year clinical follow-up, the patient was free from limb ischemia symptoms.

Autophagy Genes and Otitis Media Outcomes.

Otitis media (OM) is a common cause of hearing loss in children that requires corrective surgery. Various studies have investigated the pathomechanisms and treatment of OM. Autophagy, an essential cellular recycling and elimination mechanism implicated in various diseases, is known to play an important role in the pathogenesis of OM. Here, we conducted a literature review on autophagy in OM, highlighting the relationship between expression patterns of autophagy-related factors and pathophysiological and clinical aspects of OM. We summarized the existing research results on the expression of autophagy-related factors in acute OM (AOM), OM with effusion (OME), chronic OM (COM) with cholesteatoma, and COM without cholesteatoma (CholeOM) in animals and humans. Autophagy-related factors are expressed in the middle ear mucosa or fluid of AOM, effusion of OME, granulation tissue of COM, and cholesteatoma of CholeOM. Among ATGs and other autophagy-related factors, the most extensively studied in relation to the pathogenesis of OM are mTOR, LC3II/I, PI3K, Beclin-1, FLIP, Akt, and Rubicon. Expression of autophagy-related factors is associated with AOM, OME, COM, and CholeOM. Inadequate expression of these factors or a decrease/increase in autophagy responses can result in OM, underscoring the critical role of ATGs and related factors in the pathogenesis of OM.

Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study.

PURPOSE: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history. DESIGN: Retrospective matched cohort and crossover case series study. METHODS: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis. RESULTS: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively. CONCLUSIONS: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history.

Multitask Deep Learning for Joint Detection of Necrotizing Viral and Noninfectious Retinitis From Common Blood and Serology Test Data.

Purpose: Necrotizing viral retinitis is a serious eye infection that requires immediate treatment to prevent permanent vision loss. Uncertain clinical suspicion can result in delayed diagnosis, inappropriate administration of corticosteroids, or repeated intraocular sampling. To quickly and accurately distinguish between viral and noninfectious retinitis, we aimed to develop deep learning (DL) models solely using noninvasive blood test data. Methods: This cross-sectional study trained DL models using common blood and serology test data from 3080 patients (noninfectious uveitis of the posterior segment [NIU-PS] = 2858, acute retinal necrosis [ARN] = 66, cytomegalovirus [CMV], retinitis = 156). Following the development of separate base DL models for ARN and CMV retinitis, multitask learning (MTL) was employed to enable simultaneous discrimination. Advanced MTL models incorporating adversarial training were used to enhance DL feature extraction from the small, imbalanced data. We evaluated model performance, disease-specific important features, and the causal relationship between DL features and detection results. Results: The presented models all achieved excellent detection performances, with the adversarial MTL model achieving the highest receiver operating characteristic curves (0.932 for ARN and 0.982 for CMV retinitis). Significant features for ARN detection included varicella-zoster virus (VZV) immunoglobulin M (IgM), herpes simplex virus immunoglobulin G, and neutrophil count, while for CMV retinitis, they encompassed VZV IgM, CMV IgM, and lymphocyte count. The adversarial MTL model exhibited substantial changes in detection outcomes when the key features were contaminated, indicating stronger causality between DL features and detection results. Conclusions: The adversarial MTL model, using blood test data, may serve as a reliable adjunct for the expedited diagnosis of ARN, CMV retinitis, and NIU-PS simultaneously in real clinical settings.

Quantification of the Carbon-Coating Effect on the Interfacial Behavior of Graphite Single Particles.

The effect of carbon coating on the interfacial charge transfer resistance of natural graphite (NG) was investigated by a single-particle measurement. The microscale carbon-coated natural graphite (NG@C) particles were synthesized by the simple wet-chemical mixing method using a phenolic resin as the carbon source. The electrochemical test results of NG@C using the conventional composite electrodes demonstrated desirable rate capability, cycle stability, and enhanced kinetic property. Moreover, the improvements in the composite electrodes were confirmed with the electrochemical parameters (i.e., charge transfer resistance, exchange current density, and solid phase diffusion coefficient) analyzed by a single-particle measurement. The surface carbon coating on the NG particles reduced the interfacial charge transfer resistance (Rct) and increased the exchange current density (i0). The Rct decreased from 81-101 (NG) to 49-67 Ω cm2 (NG@C), while i0 increased from 0.25-0.32 (NG) to 0.38-0.52 mA cm-2 (NG@C) after the coating process. The results suggested both electrochemically and quantitatively that the outer uniformly coated surface carbon layer on the graphite particles can improve the solid-liquid interface and other kinetic parameters, therefore enhancing the rate capabilities to obtain the high-power anode materials.