Prevalence of motor neuron diseases in gout patients: a nationwide population-based cohort study.

BACKGROUND: Increased uric acid may have a protective effect in motor neuron diseases (MNDs). The association between gout, characterized by hyperuricemia, and MNDs was not investigated previously. To estimate the prevalence of MNDs in gout patients using the Health Insurance and Review Assessment (HIRA) database, a nationwide database of South Korea. METHODS: The current descriptive study was conducted using the HIRA database. Subjects diagnosed with gout from 2011 to 2018 were included in this study. Among them, the annual prevalence of MNDs was analyzed, stratified by age and sex. Comorbidities including the Charlson Comorbidity Index score and type of prescribed gout-related drug were also demonstrated. RESULTS: The age-adjusted prevalence of MNDs per 105 persons ranged from 0.598 (95% confidence interval (CI): - 0.231-1.426) to 2.534 (95% CI: 1.100-3.968) between 2011 and 2018. Compared to previous reports, the prevalence of MNDs, especially amyotrophic lateral sclerosis (ALS), in gout patients was significantly lower than in the general population. None of the female gout patients were diagnosed with MNDs. Cerebrovascular accidents, vascular risk factors including hypertension, dyslipidemia, and diabetic complications, and the use of uric acid-lowering agents were more common in gout patients with MNDs than in those without MNDs. CONCLUSION: This study adds to the evidence of MND prevalence in gout patients. Gout might have a protective effect against the risk of MNDs.

Gout and the Prevalence of Dementia: A Nationwide Population-Based Study.

BACKGROUND: Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported. OBJECTIVE: To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population. METHODS: Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout. RESULTS: Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7-60.2) to 69.9 (95% confidence interval: 65.3-74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia. CONCLUSIONS: This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia.

Applications of deep learning methods in digital biomarker research using noninvasive sensing data.

Introduction: Noninvasive digital biomarkers are critical elements in digital healthcare in terms of not only the ease of measurement but also their use of raw data. In recent years, deep learning methods have been put to use to analyze these diverse heterogeneous data; these methods include representation learning for feature extraction and supervised learning for the prediction of these biomarkers. Methods: We introduce clinical cases of digital biomarkers and various deep-learning methods applied according to each data type. In addition, deep learning methods for the integrated analysis of multidimensional heterogeneous data are introduced, and the utility of these data as an integrated digital biomarker is presented. The current status of digital biomarker research is examined by surveying research cases applied to various types of data as well as modeling methods. Results: We present a future research direction for using data from heterogeneous sources together by introducing deep learning methods for dimensionality reduction and mode integration from multimodal digital biomarker studies covering related domains. The integration of multimodality has led to advances in research through the improvement of performance and complementarity between modes. Discussion: The integrative digital biomarker will be more useful for research on diseases that require data from multiple sources to be treated together. Since delicate signals from patients are not missed and the interaction effects between signals are also considered, it will be helpful for immediate detection and more accurate prediction of symptoms.

Intracardiac Echocardiogram: Feasibility, Efficacy, and Safety for Guidance of Transcatheter Multiple Atrial Septal Defects Closure.

We aimed to determine the feasibility, efficacy, success, and safety of intracardiac echocardiography (ICE) in transcatheter multiple atrial septal defect (ASD) closure. Of 185 patients with multiple ASDs who underwent transcatheter closure, 140 (76%) patients who weighed <30kg with a narrow distance between defects or in whom single device closure was anticipated were guided by ICE and 45 patients were guided by three-dimensional (3D) transesophageal echocardiography (TEE) with or without ICE. Patients in the ICE group were relatively younger and weighed less than those in the 3D TEE group (p < 0.0001). The ratio of the distance between defects >7 mm was high, and more cases required ≥2 devices in the 3D TEE group than those in the ICE group (p < 0.0001). All patients in the 3D TEE group and seven patients (5%) in the ICE group were operated on under general anesthesia (p < 0.0001). The fluoroscopic time was shorter in the ICE group (13.98 ± 6.24 min vs. 24.86 ± 16.47 min, p = 0.0005). No difference in the complete closure rate and complications was observed. ICE-guided transcatheter and 3D TEE were feasible, safe, and effective in successful multiple ASD device closures, especially for young children and patients at high risk under general anesthesia.

Decontamination of chokeberries (Aronia melanocarpa L.) by cold plasma treatment and its effects on biochemical composition and storage quality of their corresponding juices.

To improve the microbiological quality of chokeberries, corona discharge plasma jet (CDPJ) was employed as a decontaminating agent. The mean levels of aerobic bacteria and yeast and molds contaminants in chokeberries were 4.78 and 4.87 log CFU/g, respectively; the viable counts were decreased by 2.09 and 1.83 log units following CDPJ treatment for 3 min, respectively. A first-order kinetic model was well-suited for explaining the inactivations. The concentration of total polyphenols of chokeberries was unaffected (up to 3 min treatment), whereas DPPH radical scavenging activity was significantly decreased by CDPJ treatment (2 min and more). CDPJ treatment (all tested times) of chokeberries led to a significant decrease of monomeric anthocyanin content of their corresponding juices, whereas soluble solids content (Brix) and pH were unaffected. After storage at 4 °C for 72 h, juices obtained from CDPJ-treated berries possessed relatively low levels of contaminants with no significant alterations in pH and soluble solids content when compared with controls. In conclusion, CDPJ treatment for 2 min was optimal to improve the microbiological quality of the berries without negatively affecting biochemical qualities of their corresponding juices.

Is Tumor Cell Specificity Distinct from Tumor Selectivity In Vivo?: A Quantitative NIR Molecular Imaging Analysis of Nanoliposome Targeting.

The significance and ability for receptor targeted nanoliposomes (tNLs) to bind to their molecular targets in solid tumors in vivo has been questioned, particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity. This study presents, for the first time, in situ NIR molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors, as opposed to tumor selectivity, which includes influences of enhanced tumor permeability and retention. Results show that neither tumor delivery nor selectivity (tumor-to-normal ratio) of cetuximab and IRDye conjugated tNLs correlate with EGFR expression in U251, U87 and 9L tumors, and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%. Conversely, their in vivo specificity, which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging, correlates positively with EGFR expression levels in vitro and ex vivo (Pearson's r= 0.92 and 0.96, respectively). This study provides a unique opportunity to address the problematic disconnect between tNL synthesis and in vivo specificity. The findings encourage their continued adoption as platforms for precision medicine, and facilitates intelligent synthesis and patient customization in order to improve safety profiles and therapeutic outcomes.

Paired-agent imaging for detection of head and neck cancers.

Head and neck cancers overwhelmingly overexpress epidermal growth factor receptor (EGFR). This overexpression has been utilized for head and neck cancers using molecular targeted agents for therapy and cancer cell detection. Significant progress has been made in using EGFR-targeted fluorescent antibody and Affibody molecule agents for fluorescent guided surgery in head and neck cancers. Although success in achieving tumor-to-background ratio of 3-5 have been achieved, the field is limited by the non-specific fluorescence in normal tissues as well as EGFR specific fluorescence in the oral cavity. We propose that paired-agent imaging (PAI) could improve the contrast between tumor and normal tissue by removing the fluorescent signal arising from non-specific binding. Here, ABY-029 - an anti-EGFR Affibody molecule labeled with IRDye 800CW - and IRDye 680RD conjugated to Affibody Control Imaging Agent molecule (IR680-Affctrl) are used as targeted and untargeted control agents, respectively, in a panel of head and neck squamous cell carcinomas (HNSCC) to test the ability of PAI to increase tumor detection. Initial results demonstrate that binding potential, a value proportional to receptor concentration, correlates well to EGFR expression but experimental limitations prevented pixel-by-pixel analysis that was desired. Although promising, a more rigorous and well-defined experimental protocol is required to align ex vivo EGFR immunohistochemistry with in vivo binding potential and fluorescence intensity. Additionally, a new set of paired-agents, ABY-029 and IRDye 700DX, are successfully tested in naïve mice and will be carried forward for clinical translation.