Detection of a Human Adenovirus Outbreak, Including Some Critical Infections, Using Multipathogen Testing at a Large University, September 2022-January 2023.

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

Highly visible-light-active sulfur and carbon co-doped TiO2 (SC-TiO2) heterogeneous photocatalysts prepared by underwater discharge plasma.

To promptly and simply create highly crystalline S/C co-doped TiO2 (SC-TiO2) photocatalysts at room temperature and atmospheric pressure, we suggest a novel plasma-assisted sol-gel synthesis method. This method is a simultaneous synthetic process, in which an underwater plasma undergoes continuous reactions to generate high-energy atomic and molecular species that enable TiO2 to achieve crystallinity, a large surface area, and a heterogeneous structure within a few minutes. In particular, it was demonstrated that the heterogeneously structured TiO2 was formed by doping that sulfur and carbon replace O or Ti atoms in the TiO2 lattice depending on the composition of the synthesis solution during underwater plasma treatment. The resultant SC-TiO2 photocatalysts had narrowed bandgap energies and extended optical absorption scope into the visible range by inducing the intermediate states within bandgap due to generation of oxygen vacancies on the surface of TiO2 through synthesis, crystallization, and doping. Correspondingly, SC-TiO2 showed a significant degradation efficiency ([k] = 6.91 h-1) of tetracycline (TC, antibiotics) under solar light irradiation, up to approximately 4 times higher compared to commercial TiO2 ([k] = 1.68 h-1), resulting in great water purification. Therefore, we anticipate that this underwater discharge plasma system will prove to be an advantageous technique for producing heterostructural TiO2 photocatalysts with superior photocatalytic efficiency for environmental applications.

Prediction of neovascular age-related macular degeneration recurrence using optical coherence tomography images with a deep neural network.

Neovascular age-related macular degeneration (nAMD) can result in blindness if left untreated, and patients often require repeated anti-vascular endothelial growth factor injections. Although, the treat-and-extend method is becoming popular to reduce vision loss attributed to recurrence, it may pose a risk of overtreatment. This study aimed to develop a deep learning model based on DenseNet201 to predict nAMD recurrence within 3 months after confirming dry-up 1 month following three loading injections in treatment-naïve patients. A dataset of 1076 spectral domain optical coherence tomography (OCT) images from 269 patients diagnosed with nAMD was used. The performance of the model was compared with that of 6 ophthalmologists, using 100 randomly selected samples. The DenseNet201-based model achieved 53.0% accuracy in predicting nAMD recurrence using a single pre-injection image and 60.2% accuracy after viewing all the images immediately after the 1st, 2nd, and 3rd injections. The model outperformed experienced ophthalmologists, with an average accuracy of 52.17% using a single pre-injection image and 53.3% after examining four images before and after three loading injections. In conclusion, the artificial intelligence model demonstrated a promising ability to predict nAMD recurrence using OCT images and outperformed experienced ophthalmologists. These findings suggest that deep learning models can assist in nAMD recurrence prediction, thus improving patient outcomes and optimizing treatment strategies.

Light emitting diode (LED) irradiation of liposomes enhances drug encapsulation and delivery for improved cancer eradication.

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.

Comparison of vancomycin area under the curve calculated based on Bayesian approach versus equation-based approach.

OBJECTIVE: Area under the curve (AUC)-based vancomycin dose adjustment is recommended to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. AUC estimation methods include Bayesian software programs and simple analytical equations. This study compared the AUC obtained using the Bayesian approach with that obtained using an equation-based approach. MATERIALS AND METHODS: Patients receiving intravenous vancomycin for MRSA infection were included. Peak and trough levels were measured for each patient on days 3, 7, and 10 post vancomycin dosing (day 1). AUC was calculated using software based on the Bayesian method (MwPharm Online) and an equation-based calculator, Stanford Health Care (SHC) calculator. RESULTS: The AUC estimated using MwPharm Online was similar to that estimated using the SHC calculator. The geometric mean ratio (GMR) and their 90% confidence intervals (90% CI) were 1.08 (1.05 - 1.11), 1.03 (0.99 - 1.07), and 0.99 (0.94 - 1.05) at days 3, 7, and 10, respectively. Furthermore, according to the software used, there were no significant differences in the proportions of patients in the categories "within" and "below or above" the AUC target range. Additionally, trough levels predicted by both software programs were lower than the observed ones. Still, there was no significant difference between the predicted and observed peak levels for both software programs on day 10. CONCLUSION: AUC calculated using the Bayesian software allows for calculation with samples at a non-steady state, can integrate covariates, and is interconvertible with that estimated using an equation-based calculator, which is simpler and relies on fewer assumptions. Therefore, either method can be used, considering each method's strengths and limitations.

Comparison of the Effect of Landmark-Based Midline and Paramedian Approaches on Spinal Anesthesia-Related Complications in Adult Patients: A Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Spinal anesthesia is widely used in various types of surgery. However, several complications can occur afterward. This study aimed to identify differences in the incidence of anesthesia-related complications according to the approach methods (midline versus paramedian) for landmark-based spinal anesthesia. Materials and Methods: We searched electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, for eligible randomized controlled trials. The primary outcome was post-dural puncture headache (PDPH) incidence, and secondary outcomes were low back pain (LBP) incidence and success rate in the first trial of spinal anesthesia. We estimated the odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. Results: In total, 2280 patients from 13 randomized controlled trials were included in the final analysis. The incidence rates of PDPH were 5.9% and 10.4% in the paramedian and midline approach groups, respectively. The pooled effect size revealed that the incidence of PDPH (OR: 0.43, 95% CI [0.22-0.83]; p = 0.01; I2 = 53%) and LBP (OR: 0.27, 95% CI [0.16-0.44]; p < 0.001; I2 = 16%) decreased, and the success rate in the first attempt was higher (OR: 2.30, 95% CI [1.36-3.87]; p = 0.002; I2 = 35%) with the paramedian than with the midline approach. Conclusions: Paramedian spinal anesthesia reduced PDPH and LBP and increased the success rate of the first attempt.

Upconverting-photon quenching-mediated perforation influx as an intracellular delivery method using posAuNP@UCNPs nanocomposites for osteoarthritis treatment.

Photoporation techniques based on plasmonic nanoparticles such as gold nanoparticles have been extensively studied for the intracellular delivery of substances via cell membrane disruption. However, the clinical application of AuNP is challenging due to its absorption in the 500 nm region of the light spectrum. To overcome this challenge, upconversion nanoparticles were employed to stimulate AuNP at NIR wavelengths. posAuNP@UCNPs nanocomposites were produced by coating 30 nm UCNPs on 80 nm AuNPs using DOPA-PEI, which were then irradiated with 980 nm NIR light to facilitate their intracellular delivery. TEM and DLS confirmed that posAuNP and UCNP combine to form nanocomposites. Additionally, multiphysics simulation was used to analyze the distribution of the posAuNP electric field based on morphological differences that change as the UCNP ratio increases. Next, effective LED irradiation conditions were established by applying upconverting-photon quenching-mediated perforation influx to C28/I2 cells as suspensions or spheroids. posAuNP@UCNP nanocomposites were confirmed to be effective for the delivery of baricitinib as a treatment for osteoarthritis in a three-dimensional osteoarthritis model. Finally, chondrocyte differentiation was induced through intracellular delivery of baricitinib using posAuNP@UCNPs. The findings suggest that posAuNP@UCNPs have great potential as a tool for non-invasive drug delivery via UCPPin.

Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.

OBJECTIVE: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS: Meal intervention statistically significantly stabilized serum phosphorus level (ß = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.

Questionnaire-Based Survey of Diabetes Self-Care Activities and Barriers among Young Korean Adults with Early-Onset Diabetes.

PURPOSE: Self-management of diabetes is a significant challenge. This study aimed to assess diabetes self-care activities and barriers among Korean young adults with diabetes mellitus. MATERIALS AND METHODS: This study recruited 209 Korean adults with diabetes, with an onset age of 20-39 years, from four university hospitals. Demographic characteristics and the Summary of Diabetes Self-Care Activities (SDSCA) measure and Diabetes Self-Care Barriers Assessment Scale for Older Adults (DSCB-OA) scores were assessed using questionnaires. RESULTS: The average age of study participants was 32.9±6.1 years. Their self-care activities, including adherence to recommended diabetes medication (5.6±2.4) and number of diabetes pills (5.5±2.3) in the SDSCA measure, were the most well-performed activities among all domains. Responses to inspection of the inside of shoes in the foot care activity (0.8±1.5) and specific exercise sessions in the exercise activity (1.6±1.9) reflected poor levels of compliance. According to the DSCB-OA questionnaire, the mean diabetes self-care barrier of DSCB-OA was 20.6±5.0 of total score 45. The greater perceived barriers to self-care on the DSCB-OA were having difficulty exercising regularly (1.9±0.7) and eating three meals and snacks leading to weight gain (1.9±0.8). CONCLUSION: Young adults with early-onset diabetes showed a greater barrier to regular exercise and poor compliance with foot care and blood sugar testing. Healthcare providers must strengthen their relationship with young adults with diabetes to provide more education and guidelines for lifestyle modification focused on exercise and to promote higher compliance with diabetic self-care activities for improving clinical outcomes.

Unmet Needs of Patients With Chronic Urticaria: A Survey in Korea.

Chronic urticaria (CU) is a common problem with a high disease burden that has a significant negative impact on quality of life. Many patients are undertreated, and awareness of management strategies is low among clinicians. The present study aimed to improve understanding of CU from the patients' perspective, including the disease burden and current healthcare system use. Adult patients who presented to our referral hospital for CU treatment completed self-report questionnaires about demographics, clinical characteristics of CU, the impact of CU on daily life, unmet needs, and the history of medical service usage. This self-report survey included 127 participants (females, 57.0%; mean age, 42.0 ± 13.6 years; mean CU duration, 1.8 ± 3.4 years); 51.6% reported frequent discomfort with CU in daily life, including 44.1% of those who reported a good response to medication. More than half of the respondents reported a depressed mood and anxiety. Although 46.4% of the respondents reported that urticaria completely disappeared while on medication, only 10% were satisfied with the CU management provided by primary care hospitals. The principal cause of dissatisfaction was that they did not know the cause of CU (68.4% of patients). In total, 55% of the patients visited 2 or more hospitals before presenting to our referral hospital and 6.3% had tried folk remedies. In conclusion, most patients report that CU is not adequately controlled. Therefore, in addition to appropriate medication, information on the cause of CU, long-term treatment plan, medication safety, and expected prognosis is required to meet patients' needs.

Developing and Evaluating an AI-Based Computer-Aided Diagnosis System for Retinal Disease: Diagnostic Study for Central Serous Chorioretinopathy.

BACKGROUND: Although previous research has made substantial progress in developing high-performance artificial intelligence (AI)-based computer-aided diagnosis (AI-CAD) systems in various medical domains, little attention has been paid to developing and evaluating AI-CAD system in ophthalmology, particularly for diagnosing retinal diseases using optical coherence tomography (OCT) images. OBJECTIVE: This diagnostic study aimed to determine the usefulness of a proposed AI-CAD system in assisting ophthalmologists with the diagnosis of central serous chorioretinopathy (CSC), which is known to be difficult to diagnose, using OCT images. METHODS: For the training and evaluation of the proposed deep learning model, 1693 OCT images were collected and annotated. The data set included 929 and 764 cases of acute and chronic CSC, respectively. In total, 66 ophthalmologists (2 groups: 36 retina and 30 nonretina specialists) participated in the observer performance test. To evaluate the deep learning algorithm used in the proposed AI-CAD system, the training, validation, and test sets were split in an 8:1:1 ratio. Further, 100 randomly sampled OCT images from the test set were used for the observer performance test, and the participants were instructed to select a CSC subtype for each of these images. Each image was provided under different conditions: (1) without AI assistance, (2) with AI assistance with a probability score, and (3) with AI assistance with a probability score and visual evidence heatmap. The sensitivity, specificity, and area under the receiver operating characteristic curve were used to measure the diagnostic performance of the model and ophthalmologists. RESULTS: The proposed system achieved a high detection performance (99% of the area under the curve) for CSC, outperforming the 66 ophthalmologists who participated in the observer performance test. In both groups, ophthalmologists with the support of AI assistance with a probability score and visual evidence heatmap achieved the highest mean diagnostic performance compared with that of those subjected to other conditions (without AI assistance or with AI assistance with a probability score). Nonretina specialists achieved expert-level diagnostic performance with the support of the proposed AI-CAD system. CONCLUSIONS: Our proposed AI-CAD system improved the diagnosis of CSC by ophthalmologists, which may support decision-making regarding retinal disease detection and alleviate the workload of ophthalmologists.

Fusogenic liposomes encapsulating mitochondria as a promising delivery system for osteoarthritis therapy.

Many attempts have been made to use mitochondria (MT) to treat human diseases; however, MT are large, making them difficult to deliver effectively. Therefore, a transfer strategy based on membrane fusion was established. Fusogenic mitochondrial capsules (FMCs) comprising a neutral lipid (PE), a cationic lipid (DOTAP), an aromatic lipid (Liss Rhod PE), and three types of liposome (FMC0, FMC1, and FMC2), were designed and synthesized. The amount of DOTAP, which affects membrane fusion efficiency, differed between FMC preparations. The characteristics of these FMCs were analyzed by DLS, TEM, and AFM, and the encapsulation and fusion efficiency between FMC-MT and FMC-chondrocytes were confirmed by FRET, mtDNA copy number, and CLSM, respectively. Compared with naked MT, delivery of FMCs to chondrocytes was faster and more efficient. Moreover, fusion was a more stable delivery method than endocytosis, as evidenced by reduced induction of mitophagy. In vitro and in vivo experiments revealed that FMCs reduced expression of inflammatory cytokines and MMP13, increased expression of extracellular matrix components, and promoted cartilage regeneration. These findings suggest that FMCs are a highly effective and promising strategy for delivery of MT to promote cartilage regeneration, and highlight their potential as a novel platform for MT transfer therapy.

Prediction of Visual Acuity in Pathologic Myopia with Myopic Choroidal Neovascularization Treated with Anti-Vascular Endothelial Growth Factor Using a Deep Neural Network Based on Optical Coherence Tomography Images.

Myopic choroidal neovascularization (mCNV) is a common cause of vision loss in patients with pathological myopia. However, predicting the visual prognosis of patients with mCNV remains challenging. This study aimed to develop an artificial intelligence (AI) model to predict visual acuity (VA) in patients with mCNV. This study included 279 patients with mCNV at baseline; patient data were collected, including optical coherence tomography (OCT) images, VA, and demographic information. Two models were developed: one comprising horizontal/vertical OCT images (H/V cuts) and the second comprising 25 volume scan images. The coefficient of determination (R2) and root mean square error (RMSE) were computed to evaluate the performance of the trained network. The models achieved high performance in predicting VA after 1 (R2 = 0.911, RMSE = 0.151), 2 (R2 = 0.894, RMSE = 0.254), and 3 (R2 = 0.891, RMSE = 0.227) years. Using multiple-volume scanning, OCT images enhanced the performance of the models relative to using only H/V cuts. This study proposes AI models to predict VA in patients with mCNV. The models achieved high performance by incorporating the baseline VA, OCT images, and post-injection data. This model could assist in predicting the visual prognosis and evaluating treatment outcomes in patients with mCNV undergoing intravitreal anti-vascular endothelial growth factor therapy.

Microbiome maps: Hilbert curve visualizations of metagenomic profiles.

Abundance profiles from metagenomic sequencing data synthesize information from billions of sequenced reads coming from thousands of microbial genomes. Analyzing and understanding these profiles can be a challenge since the data they represent are complex. Particularly challenging is their visualization, as existing techniques are inadequate when the taxa number is in the thousands. We present a technique, and accompanying software, for the visualization of metagenomic abundance profiles using a space-filling curve that transforms a profile into an interactive 2D image. We created Jasper, an easy to use tool for the visualization and exploration of metagenomic profiles from DNA sequencing data. It orders taxa using a space-filling Hilbert curve, and creates a "Microbiome Map", where each position in the image represents the abundance of a single taxon from a reference collection. Jasper can order taxa in multiple ways, and the resulting microbiome maps can highlight "hot spots" of microbes that are dominant in taxonomic clades or biological conditions. We use Jasper to visualize samples from a variety of microbiome studies, and discuss ways in which microbiome maps can be an invaluable tool to visualize spatial, temporal, disease, and differential profiles. Our approach can create detailed microbiome maps involving hundreds of thousands of microbial reference genomes with the potential to unravel latent relationships (taxonomic, spatio-temporal, functional, and other) that could remain hidden using traditional visualization techniques. The maps can also be converted into animated movies that bring to life the dynamicity of microbiomes.

Comparison of the Analgesic Efficacy between Arthroscopically Placed Continuous Suprascapular Nerve Block and Ultrasound-guided Continuous Superior Trunk Block: A Double-blinded Randomized Controlled Trial.

BACKGROUND: Single-shot suprascapular nerve block and superior trunk block have been reported to provide a noninferior analgesic effect after shoulder surgery with a lesser incidence of hemidiaphragmatic paresis compared with interscalene brachial plexus block. This study hypothesized that continuous suprascapular nerve block provides noninferior analgesia with minimal effects on diaphragmatic movement compared with continuous superior trunk block in patients undergoing arthroscopic shoulder surgery. METHODS: 100 patients were randomized undergoing arthroscopic shoulder surgery between December 2020 and October 2021 into continuous suprascapular nerve block and continuous superior trunk block groups. Before the surgery, patients received either a single-shot superior trunk block or subomohyoid suprascapular nerve block. Thereafter, a superior trunk catheter was inserted by anesthesiologists in patients in the continuous superior trunk block group, and a posterior suprascapular nerve catheter was inserted with arthroscopic assistance during the surgery by surgeon in the continuous suprascapular nerve block group. The primary outcome was the postoperative pain score at postoperative 24 h, and the incidence of hemidiaphragmatic paresis was also compared. RESULTS: Overall, 98 patients were included in the final analysis. The worst and resting pain scores at postoperative 24 h in the continuous suprascapular nerve block group were inferior compared with those in the continuous superior trunk block group in the test with a noninferiority margin of 1 (worst pain score: mean difference, 0.9; 95% CI, 0.1 to 1.7; resting pain score: mean difference, 0.5; 95% CI, 0.0 to 1.0). However, the continuous suprascapular nerve block group had a significantly lower incidence of hemidiaphragmatic paresis at postoperative 24 h than the continuous superior trunk block group. CONCLUSIONS: Continuous suprascapular nerve block provides statistically inferior analgesia compared to the continuous superior trunk block; however, the continuous suprascapular nerve block had a minimal effect on the phrenic nerve function.

Assessing Quality of Life in Patients With Chronic Urticaria Through Comparisons With Patients Having Other Common Chronic Diseases.

BACKGROUND: Chronic urticaria (CU) is a common chronic inflammatory disease, but the burden on quality of life (QOL) has been underestimated. OBJECTIVE: To compare QOL among patients with CU and those with other chronic diseases. METHODS: Adult patients who visited a referral hospital for CU were enrolled. Patients completed self-reported questionnaires including clinical characteristics of chronic urticaria and the short form 36 health survey. As a comparative group, patients with rheumatoid arthritis, patients with diabetes treated with insulin, patients on maintenance hemodialysis, and healthy controls were enrolled and completed the short form 36 health survey. RESULTS: In all, 119 patients with CU were enrolled and their short form 36 scores were not significantly different from those of healthy controls. However, patients with CU with poor responses to treatment showed impaired QOL to a degree similar to that of patients with rheumatoid arthritis or insulin-treated diabetes. The patients with CU showed various clinical characteristics with respect to treatment response, accompanying symptoms, and aggravating factors. Among these factors, pain at the urticarial lesion and symptom aggravation during exercise and after the consumption of certain foods were related with lower QOL. CONCLUSIONS: Patients with CU with an incomplete response to treatment had significantly low QOL, comparable to that of patients with rheumatoid arthritis or insulin-treated diabetes. To minimize this effect, clinicians should aim to control symptoms and aggravating factors.

Gut Microbial Genes and Metabolism for Methionine and Branched-Chain Amino Acids in Diabetic Nephropathy.

Diabetic mellitus nephropathy (DMN) is a serious complication of diabetes and a major health concern. Although the pathophysiology of diabetes mellitus (DM) leading to DMN is uncertain, recent evidence suggests the involvement of the gut microbiome. This study aimed to determine the relationships among gut microbial species, genes, and metabolites in DMN through an integrated clinical, taxonomic, genomic, and metabolomic analysis. Whole-metagenome shotgun sequencing and nuclear magnetic resonance metabolomic analyses were performed on stool samples from 15 patients with DMN and 22 healthy controls. Six bacterial species were identified to be significantly elevated in the DMN patients after adjusting for age, sex, body mass index, and estimated glomerular filtration rate (eGFR). Multivariate analysis found 216 microbial genes and 6 metabolites (higher valine, isoleucine, methionine, valerate, and phenylacetate levels in the DMN group and higher acetate levels in the control group) that were differentially present between the DMN and control groups. Integrated analysis of all of these parameters and clinical data using the random-forest model showed that methionine and branched-chain amino acids (BCAAs) were among the most significant features, next to the eGFR and proteinuria, in differentiating the DMN group from the control group. Metabolic pathway gene analysis of BCAAs and methionine also revealed that many genes involved in the biosynthesis of these metabolites were elevated in the six species that were more abundant in the DMN group. The suggested correlation among taxonomic, genetic, and metabolic features of the gut microbiome would expand our understanding of gut microbial involvement in the pathogenesis of DMN and may provide potential therapeutic targets for DMN. IMPORTANCE Whole metagenomic sequencing uncovered specific members of the gut microbiota associated with DMN. The gene families derived from the discovered species are involved in the metabolic pathways of methionine and branched-chain amino acids. Metabolomic analysis using stool samples showed increased methionine and branched-chain amino acids in DMN. These integrative omics results provide evidence of the gut microbiota-associated pathophysiology of DMN, which can be further studied for disease-modulating effects via prebiotics or probiotics.

Incidence of Retinal Artery Occlusion and Related Mortality in Korea, 2005 to 2018.

Importance: It remains unclear whether comorbidities in patients with retinal artery occlusion (RAO), a rare retinal vascular disorder, differ by subtype and whether mortality is higher. Objective: To examine the nationwide incidence of clinically diagnosed, nonarteritic RAO, causes of death, and mortality rate in patients with RAO compared with that in the general population in Korea. Design, Setting, and Participants: This retrospective, population-based cohort study examined National Health Insurance Service claims data from 2002 to 2018. The population of South Korea was 49 705 663, according to the 2015 census. Data were analyzed from February 9, 2021, to July 30, 2022. Main Outcomes and Measures: The nationwide incidence of any RAO, including central RAO (CRAO; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code, H34.1) and noncentral RAO (other RAO; ICD-10 code, H34.2) was estimated using National Health Insurance Service claims data from 2002 to 2018, with 2002 to 2004 as the washout period. Furthermore, the causes of death were evaluated and the standardized mortality ratio was estimated. The primary outcomes were the incidence of RAO per 100 000 person-years and the standardized mortality ratio (SMR). Results: A total of 51 326 patients with RAO were identified (28 857 [56.2%] men; mean [SD] age at index date: 63.6 [14.1] years). The nationwide incidence of any RAO was 7.38 (95% CI, 7.32-7.44) per 100 000 person-years. The incidence rate of noncentral RAO was 5.12 (95% CI, 5.07-5.18), more than twice that of CRAO (2.25 [95% CI, 2.22-2.29]). Mortality was higher in patients with any RAO than in the general population (SMR, 7.33 [95% CI, 7.15-7.50]). The SMR for CRAO (9.95 [95% CI, 9.61-10.29]) and for noncentral RAO (5.97 [95% CI, 5.78-6.16]) showed a tendency toward a gradual decrease with increasing age. The top 3 causes of death in patients with RAO were diseases of the circulatory system (28.8%), neoplasms (25.1%), and diseases of the respiratory system (10.2%). Conclusions and Relevance: This cohort study found that the incidence rate of noncentral RAO was higher than that of CRAO, whereas SMR was higher for CRAO than noncentral RAO. Patients with RAO show higher mortality than the general population, with circulatory system disease as the leading cause of death. These findings suggest that it is necessary to investigate the risk of cardiovascular or cerebrovascular disease in patients newly diagnosed with RAO.

Melatonin loaded PLGA nanoparticles effectively ameliorate the in vitro maturation of deteriorated oocytes and the cryoprotective abilities during vitrification process.

Almost all cells can be exposed to stress, but oocytes, which are female germ cells, are particularly vulnerable to damage. In this study, melatonin, a well-known antioxidant, was loaded into biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and delivered to damaged oocytes in order to improve their quality and restoration. Etoposide (ETP)-induced deteriorated oocytes show poor maturity, mitochondrial aggregation, and DNA damage. Treatment of NPs not only reduced DNA damage but also improved mitochondrial stability, as evidenced by increased ATP levels and mitochondrial homogeneity. When melatonin was added to the culture medium at the same concentration as that present in NPs, DNA and mitochondrial repair was insignificant due to the half-life of melatonin, whereas DNA repair in damaged oocytes upon multiple treatments with melatonin was similar to that observed with melatonin-loaded NPs. Next, we evaluated whether the oocytes treated with NPs could have cryoprotective abilities during vitrification/thawing. Vitrified-oocytes were stored at -196 °C for 0.25 h (T1) or 0.5 h (T2). After thawing, live oocytes were subjected to in vitro maturation. The NP-treated group showed maturity similar to the control group (77.8% in T1, 72.7% in T2) and the degree of DNA damage was reduced compared to the ETP-induced group (p < 0.05).

Detecting Macular Disease Based on Optical Coherence Tomography Using a Deep Convolutional Network.

Neovascular age-related macular degeneration (nAMD) and central serous chorioretinopathy (CSC) are two of the most common macular diseases. This study proposes a convolutional neural network (CNN)-based deep learning model for classifying the subtypes of nAMD (polypoidal choroidal vasculopathy, retinal angiomatous proliferation, and typical nAMD) and CSC (chronic CSC and acute CSC) and healthy individuals using single spectral-domain optical coherence tomography (SD-OCT) images. The proposed model was trained and tested using 6063 SD-OCT images from 521 patients and 47 healthy participants. We used three well-known CNN architectures (VGG-16, VGG-19, and ResNet) and two customized classification layers. Additionally, transfer learning and mix-up-based data augmentation were applied to improve robustness and accuracy. Our model demonstrated high accuracies of 99.7% and 91.1% in the nAMD and CSC classification and retinopathy (nAMD and CSC) subtype classification, including normal participants, respectively. Furthermore, we performed an external test to compare the classification accuracy with that of eight ophthalmologists, and our model showed the highest accuracy. The region determined to be important for classification by the model was confirmed using gradient-weighted class activation mapping. The model's clinical criteria were similar to that of the ophthalmologists.