Biomarker-driven phase 2 umbrella trial: Clinical efficacy of olaparib monotherapy and combination with ceralasertib (AZD6738) in small cell lung cancer.

BACKGROUND: Based on a high incidence of genomic alteration in the cell cycle and DNA damage and response (DDR)-related pathways in small cell lung cancer (SCLC), the clinical efficacy of the DDR-targeting agent olaparib (PARP inhibitor) as monotherapy and in combination with ceralasertib (ATR inhibitor) in relapsed or refractory SCLC was evaluated. METHODS: As part of a phase 2 biomarker driven umbrella study, patients with SCLC and predefined DDR gene alterations who failed to benefit from prior platinum-based regimens were allocated to the olaparib monotherapy arm and nonbiomarker-selected patients were allocated to the olaparib and ceralasertib combination arm. RESULTS: In the olaparib monotherapy arm (n = 15), the objective response rate was 6.7% (one partial response), and the disease control rate was 33.3%, including three patients with stable disease. The median progression-free survival was 1.3 months (95% CI, 1.2-NA). In the combination arm (n = 26), the objective response rate and disease control rate were 3.8% and 42.3%, respectively, with one partial response and 10 patients with stable disease. The median progression-free survival was 2.8 months (95% CI, 1.8-5.4). Treatment was generally well tolerated except for one fatal case of neutropenic fever in the combination arm. CONCLUSIONS: Targeting DDR pathways with olaparib as a single agent or in combination with ceralasertib did not meet the predefined efficacy end point. However, disease stabilization was more evident in the combination arm. Further investigation of the combination of olaparib in SCLC should be performed with diverse combinations and patient selection strategies to maximize efficacy.

Influence of frailty status on the health-related quality of life in older patients with chronic low back pain: a retrospective observational study.

PURPOSE: Understanding the influence of frailty on health-related quality of life (HRQoL) in older individuals experiencing chronic low back pain can provide valuable insights into the impact of frailty. Therefore, the aim of our study is to assess how different frailty statuses among older outpatients with chronic low back pain affect their HRQoL. METHODS: Patients aged 60 and above with chronic low back pain were recruited from March 2022 to February 2023. Frailty was assessed via the frailty phenotype questionnaire, and HRQoL was evaluated using the EQ-5D-5L. Multiple regression models were used to explore the influence of frailty status on the EQ-5D-5L index and EQ-VAS. Logistic regression was used to determine odds ratios for the impact of frailty status on belonging to the lowest EQ-5D-5L index quartile. RESULTS: A total of 1,054 participants were classified into robust (29.8%), pre-frail (47.7%), and frail (22.5%) groups. Frailty was significantly associated with declining HRQoL. Pre-frail and frail statuses were inversely linked to the EQ-5D-5L index, with significantly higher odds of scoring in the lowest quartile compared to robust individuals. Stratification analysis identified sex as an effect modifier, emphasizing a more substantial association between frailty and the lowest EQ-5D-5L index quartile in female patients. CONCLUSIONS: A significant association exists between frailty and reduced HRQoL in patients with chronic low back pain. This association was predominant in female patients. Furthermore, considering the dynamic nature of frailty, early detection and effective interventions targeting pre-frailty are essential to delaying the transition to full frailty and improving HRQoL.

Performance of calf circumference in identifying sarcopenia in older patients with chronic low back pain: a retrospective cross-sectional study.

BACKGROUND: Calf circumference is currently recommended as a case-finding marker for sarcopenia, but its usefulness has not been determined in chronic pain conditions. Therefore, the present study aimed to evaluate the predictive performance of calf circumference in diagnosing sarcopenia in older patients with chronic low back pain. METHODS: Ambulatory adult patients aged ≥ 65 years with chronic low back pain were enrolled. A diagnosis of sarcopenia was established based on the criteria outlined by the Asian Working Group for Sarcopenia in 2019. Patient demographics, pain-related factors, clinical factors, and sarcopenia-related measurements were compared between non-sarcopenic and sarcopenic patients. Linear regression analysis was used to evaluate the correlation of calf circumference with muscle mass, strength, and physical performance. Also, a receiver operating characteristic curve analysis for calf circumference in predicting sarcopenia was conducted; and area under the curve (AUC) values, along with their corresponding 95% confidence intervals (CI), were calculated. RESULTS: Data from 592 patients were included in the analysis. Eighty-five patients were diagnosed with sarcopenia (14.3%), 71 of whom had severe sarcopenia (11.9%). A higher prevalence of sarcopenia was observed in female patients (9.0% vs. 16.7%, p = 0.016). After adjusting for age, BMI, and comorbidities, calf circumference correlated positively with muscle mass but not with muscle strength and physical performance. The AUC values for sarcopenia were 0.754 (95% CI = 0.636-0.871, p = 0.001) in males and 0.721 (95% CI = 0.657-0.786, p < 0.001) in females. The cut-offs for calf circumference in predicting sarcopenia were 34 cm (sensitivity 67.1%, specificity 70.6%) in males, and 31 cm (sensitivity 82.5%, specificity 51.5%) in females. CONCLUSIONS: Even though sex differences in its predictive value for sarcopenia should be considered, our findings suggest that calf circumference can be used as an indicator for predicting muscle mass and may serve as a potential marker for identifying sarcopenia in older patients with chronic low back pain.

Exposure to Radiofrequency Induces Synaptic Dysfunction in Cortical Neurons Causing Learning and Memory Alteration in Early Postnatal Mice.

The widespread use of wireless communication devices has necessitated unavoidable exposure to radiofrequency electromagnetic fields (RF-EMF). In particular, increasing RF-EMF exposure among children is primarily driven by mobile phone use. Therefore, this study investigated the effects of 1850 MHz RF-EMF exposure at a specific absorption rate of 4.0 W/kg on cortical neurons in mice at postnatal day 28. The results indicated a significant reduction in the number of mushroom-shaped dendritic spines in the prefrontal cortex after daily exposure for 4 weeks. Additionally, prolonged RF-EMF exposure over 9 days led to a gradual decrease in postsynaptic density 95 puncta and inhibited neurite outgrowth in developing cortical neurons. Moreover, the expression levels of genes associated with synapse formation, such as synaptic cell adhesion molecules and cyclin-dependent kinase 5, were reduced in the cerebral cortexes of RF-EMF-exposed mice. Behavioral assessments using the Morris water maze revealed altered spatial learning and memory after the 4-week exposure period. These findings underscore the potential of RF-EMF exposure during childhood to disrupt synaptic function in the cerebral cortex, thereby affecting the developmental stages of the nervous system and potentially influencing later cognitive function.

IL-6 Inhibitory Compounds from the Aerial Parts of Piper attenuatum and Their Anticancer Activities on Ovarian Cancer Cell Lines.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

NecroX Improves Polyhexamethylene Guanidine-induced Lung Injury by Regulating Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress.

Various environmental compounds are inducers of lung injury. Mitochondria are crucial organelles that can be affected by many lung diseases. NecroX is an indole-derived antioxidant that specifically targets mitochondria. We aimed to evaluate the therapeutic potential and related molecular mechanisms of NecroX in preclinical models of fatal lung injury. We investigated the therapeutic effects of NecroX on two different experimental models of lung injury induced by polyhexamethylene guanidine (PHMG) and bleomycin, respectively. We also performed transcriptome analysis of lung tissues from PHMG-exposed mice and compared the expression profiles with those from dozens of bleomycin-induced fibrosis public data sets. Respiratory exposure to PHMG and bleomycin led to fatal lung injury manifesting extensive inflammation followed by fibrosis. These specifically affected mitochondria regarding biogenesis, mitochondrial DNA integrity, and the generation of mitochondrial reactive oxygen species in various cell types. NecroX significantly improved the pathobiologic features of the PHMG- and bleomycin-induced lung injuries through regulation of mitochondrial oxidative stress. Endoplasmic reticulum stress was also implicated in PHMG-associated lung injuries of mice and humans, and NecroX alleviated PHMG-induced lung injury and the subsequent fibrosis, in part, via regulation of endoplasmic reticulum stress in mice. Gene expression profiles of PHMG-exposed mice were highly consistent with public data sets of bleomycin-induced lung injury models. Pathways related to mitochondrial activities, including oxidative stress, oxidative phosphorylation, and mitochondrial translation, were upregulated, and these patterns were significantly reversed by NecroX. These findings demonstrate that NecroX possesses therapeutic potential for fatal lung injury in humans.

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).

BACKGROUND: Loss of PTEN function leads to increased PI3Kß signaling. AZD8186, a selective PI3Kß/δ inhibitor, has shown anti-tumor activity in PTEN-deficient preclinical models. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed in advanced gastric cancer with PTEN loss. METHODS: In the phase Ib dose-escalation, subjects with advanced solid tumors received oral AZD8186 (60 mg or 120 mg; twice daily (BID); 5 days on/2 days off) plus intravenous paclitaxel (70 mg/m2 or 80 mg/m2; days 1, 8, and 15) every 4 weeks. In the phase II part, MRGC patients with PTEN loss or PTEN/PIK3CB gene abnormality were enrolled and received recommended phase II dose (RP2D) of AZD8186 plus paclitaxel. Primary endpoints were to determine maximum tolerated dose (MTD) and RP2D in phase Ib and 4-month progression-free survival (PFS) rate in phase II. RESULTS: In phase Ib, both MTD and RP2D were determined at paclitaxel 80 mg/m2 and AZD8186 120 mg BID. In phase II, 18 patients were enrolled [PTEN loss (n = 18) and PIK3CB mutation (n = 1)]. The 4-month PFS rate was 18.8% (3 of 16 evaluable patients) and further enrollment stopped due to futility. CONCLUSION: Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.ClinicalTrials.gov Identifier: NCT04001569.

Developing Hemodynamic Valve Deterioration and Mortality in Aortic Valve Replacement.

BACKGROUND: As life span increases, in patients having a bioprosthetic valve, the development of hemodynamic valve deterioration (HVD) is an important concern. We evaluated the association of developing HVD to survival in patients undergoing surgical aortic valve replacement (SAVR). METHODS: The individuals undergoing isolated SAVR and serial echocardiography exams (interval >30 d) were included in this study. HVD was defined as mean pressure gradient ≥ 20 mmHg, mean pressure gradient ≥10 mmHg higher than in the baseline exam, or more than moderate regurgitation on Doppler echocardiography (moderate and severe grade). A time-dependent Cox proportional hazard model was used for this study. RESULTS: A total of 631 patients were included. The mean age was 71.8 ± 6.1 y old (female: 53.6%). HVD was found in 259 patients (41%) during echocardiographic follow-up (mean 3.3 ± 3.0 y). Patient-prosthetic mismatch was found in 174 patients. One hundred and twenty-six patients died during follow-up (median 62.1 mo, interquartile range 31.1-96.8). The development of HVD was an independent risk factor for death during follow-up (P = 0.038, hazard ratio 1.46, 95% confidential interval: 1.02-2.08). CONCLUSIONS: HVD was common after bioprosthetic SAVR during mid-term follow-up. Developing HVD, including moderate and severe grades, was associated with a poor survival rate compared with patients without HVD.

Perioperative Red Blood Cell Transfusion Is Associated With Adverse Cardiovascular Outcomes in Heart Valve Surgery.

BACKGROUND: We examined the relationship between blood transfusion and long-term adverse events to evaluate the clinical impact of red blood cell (RBC) transfusion on patients undergoing cardiac valve surgery. METHODS: From the National Health Insurance Service database, individuals undergoing heart valve surgery were verified, including aortic valve (AV), mitral valve (MV), tricuspid valve (TV), and complex valves (more than 2 valve surgeries). The interested outcomes were incidence of death, ischemic stroke, hemorrhagic stroke, and admission for myocardial infarction during follow-up. Associations between perioperative RBC transfusion and long-term cardiovascular events were analyzed with Cox-proportional hazard model. RESULTS: Perioperative RBC transfusion (±2 days from the day of surgery) was categorized into 0, 1, 2, and >3 units based on the number of packs transfused. From 2003 to 2019, the data of 58,299 individuals were retrieved (51.6% were male and 58% were aged above 60 years). The median follow-up duration was 5.53 years. Of the total cohort, 86.5% received at least 1 transfusion. In multivariable analysis, adverse cardiovascular event risk proportionally increased with transfusion in a dose-dependent manner. The adjusted hazard ratios and 95% confidence intervals of outcomes after the transfusion of 1, 2, and ≥3 units compared to those with no transfusion were as follows: death, 1.53 (1.41-1.66), 1.97 (1.81-2.14), and 3.03 (2.79-3.29); ischemic stroke, 1.27 (1.16-1.39), 1.31 (1.19-1.44), and 1.51 (1.38-1.66); hemorrhagic stroke, 1.38 (1.16-1.66), 1.71 (1.43-2.05), and 2.31 (1.94-2.76); and myocardial infarction 1.35 (1.13-1.62), 1.60 (1.33-1.91), and 1.99 (1.66-2.38), respectively (all P < .01). CONCLUSIONS: In the analysis of the national cohort, perioperative RBC transfusion during heart valve surgery was associated with adverse cardiovascular outcomes correlated with the volume of RBC transfusion.

Influence of Biogenetic Explanations of Mental Disorders on Stigma and Help-Seeking Behavior: A Systematic Review and Meta-Analysis.

BACKGROUND: Biogenetic causal explanations of mental disorders are commonly used for public education and campaigns. However, the influence of biogenetic explanations on the ideas about and attitudes toward mental illness is unclear. We examined the influence of biogenetic explanations on attitudes toward mental disorders using a meta-analytic method accompanied by subgroup analyses. METHODS: The protocol for this meta-analysis was registered in PROSPERO (CRD42020158656) in March 2020. Experimental and correlational studies were analyzed separately. Five outcome measures related to attitudes toward mental disorders were included: 'attitude toward help-seeking,' 'blame,' 'perceived dangerousness,' 'prognostic pessimism,' and 'social distance.' Subgroup analyses were performed for the type of mental disorder, population, and geographic region for which a biogenetic explanation was provided. RESULTS: A total of 44 studies were included, of which 24 were experimental and 20 were correlational. A positive attitude toward help-seeking was associated with having a biogenetic concept (d = 0.43; 95% confidence interval [CI], 0.18 to 0.67; P < 0.001) in general population and in Eastern countries in particular. Although a biogenetic explanation was associated with a decreased level of blame (d = -0.20; 95% CI, -0.38 to -0.02; P = 0.029) in the general population, it was also associated with significantly higher levels of perceived dangerousness (d = 0.13; 95% CI, 0.03 to 0.23; P = 0.008). A tendency toward a higher level of prognostic pessimism and social distance was associated with a biogenetic concept of mental disorders although there was no statistical significance. CONCLUSION: Having a biogenetic concept of the cause of mental disorders was related with a positive attitude toward help-seeking, particularly in the general population and individuals living in Eastern countries. Providing a biogenetic explanation decreased blame toward individuals with mental illness but was associated with increased perceived dangerousness and prognostic pessimism. Therefore, although a biogenetic explanation promotes public use of mental health services, it should be carefully applied to avoid an increase in negative thoughts, such as that mental illness is biologically irreversible and untreatable.

Butein Inhibits Cell Growth by Blocking the IL-6/IL-6Rα Interaction in Human Ovarian Cancer and by Regulation of the IL-6/STAT3/FoxO3a Pathway.

Butea monosperma (Fabaceae) has been used in traditional Indian medicine to treat a variety of ailments, including abdominal tumors. We aimed to investigate the anti-IL-6 activity of butein in ovarian cancer and elucidate the underlying molecular mechanisms. Butein was isolated and identified from B. monosperma flowers, and the inhibition of IL-6 signaling was investigated using the HEK-Blue™ IL-6 cell line. The surface plasmon resonance assay was used to estimate the binding of butein to IL-6, IL-6Rα, and gp130. After treatment with butein, ovarian cancer cell migration, apoptosis, and tumor growth inhibition were evaluated in vitro and in vivo. Furthermore, we used STAT3 siRNA to identify the mechanistic effects of butein on the IL-6/STAT3/FoxO3a pathway. Butein suppressed downstream signal transduction through higher binding affinity to IL-6. In ovarian cancer, butein inhibited cell proliferation, migration, and invasion, and induced cell cycle arrest and apoptosis. In addition, it decreased the growth of ovarian cancer cells in xenograft tumor models. Butein inhibited STAT3 phosphorylation and induced FoxO3a accumulation in the nucleus by inhibiting IL-6 signaling. The anticancer activity of butein was mediated by blocking the IL-6/IL-6Rα interaction and suppressing IL-6 bioactivity via interfering with the IL-6/STAT3/FoxO3a pathway.

Evaluation of Paraspinal Muscle Degeneration on Pain Relief after Percutaneous Epidural Adhesiolysis in Patients with Degenerative Lumbar Spinal Disease.

Background and Objectives: The analgesic effectiveness of epidural adhesiolysis may be influenced by morphological changes in the paraspinal muscles, particularly in elderly patients. The objective of this study was to assess whether the cross-sectional area or fatty infiltration of the paraspinal muscles impacts the treatment outcomes of epidural adhesiolysis. Materials and Methods: The analysis included a total of 183 patients with degenerative lumbar disease who underwent epidural adhesiolysis. Good analgesia was defined as a reduction in pain score of ≥30% at the 6-month follow up. We measured the cross-sectional area and fatty infiltration rate of the paraspinal muscles and divided the study population into age groups (≥65 years and <65 years). Variables were compared between the good and poor analgesia groups. Results: The results revealed that elderly patients experienced poorer analgesic outcomes as the rate of fatty infiltration in the paraspinal muscles increased (p = 0.029), predominantly in female patients. However, there was no correlation between the cross-sectional area and the analgesic outcome in patients younger than or older than 65 years (p = 0.397 and p = 0.349, respectively). Multivariable logistic regression analysis indicated that baseline pain scores < 7 (Odds Ratio (OR) = 4.039, 95% Confidence Interval (CI) = 1.594-10.233, p = 0.003), spondylolisthesis (OR = 4.074, 95% CI = 1.144-14.511, p = 0.030), and ≥ 50% fatty infiltration of the paraspinal muscles (OR = 6.576, 95% CI = 1.300-33.268, p = 0.023) were significantly associated with poor outcomes after adhesiolysis in elderly patients. Conclusions: Fatty degeneration of paraspinal muscles is correlated with inferior analgesic outcomes following epidural adhesiolysis in elderly patients, but not in young and middle-aged patients. The cross-sectional area of the paraspinal muscles is not associated with pain relief after the procedure.

Neuropathic pain component and its association with time elapsed since pain onset in patients with low back pain.

BACKGROUND: Time elapsed since pain onset might affect the likelihood of neuropathic component in low back pain. The aim of this study was to investigate the relationship between neuropathic pain component and pain duration in patients with low back pain and to identify factors associated with neuropathic pain component. METHODS: Patients with low back pain who received treatment at our clinic were enrolled. Neuropathic component was assessed using the painDETECT questionnaire at the initial visit. PainDETECT scores and the results for each item were compared according to pain duration category (< 3 months, 3 months to 1 year, 1 year to 3 years, 3 years to 10 years, and ≥ 10 years). A multivariate analysis was used to identify factors associated with neuropathic pain component (painDETECT score ≥ 13) in low back pain. RESULTS: A total of 1957 patients, including 255 patients who reported neuropathic-like pain symptoms (13.0%), fully satisfied the study criteria for analysis. No significant correlation between painDETECT score and pain duration was observed (ρ = -0.025, p = 0.272), and there were no significant differences between median painDETECT score or trend of change in the proportion of patients with neuropathic component and the pain duration category (p = 0.307, p = 0.427, respectively). The electric shock-like pain symptom was frequently reported in patients with acute low back pain, and the persistent pain pattern with slight fluctuations was predominant in chronic low back pain. The pattern of attacks with pain between them was much less common in patients with pain for 10 years or longer. Multivariate analysis revealed that a history of lumbar surgery, severe maximum pain, opioid use, lumbosacral radiculopathy, and sleep disturbance were significantly associated with a neuropathic component in low back pain. CONCLUSION: Time elapsed since current pain onset did not correlate with neuropathic pain component in patients with low back pain. Therefore, diagnostic and therapeutic approaches for this condition should be based on a multidimensional evaluation at assessment and not on pain duration alone.

Spinal Versus General Anesthesia for Cesarean Delivery in Pregnant Women With Moyamoya Disease: A Retrospective Observational Study.

BACKGROUND: Moyamoya disease, a rare chronic cerebrovascular disease with a fragile vascular network at the base of the brain, can cause ischemic or hemorrhagic strokes or seizures. Precise blood pressure control and adequate analgesia are important for patients with moyamoya disease to prevent neurological events such as ischemia and hemorrhage. This study aimed to compare the intraoperative mean arterial pressure of pregnant women with moyamoya disease according to the mode of anesthesia (general anesthesia versus spinal anesthesia) used during cesarean delivery. METHODS: We retrospectively reviewed the medical records of 87 cesarean deliveries in 74 patients who had been diagnosed with moyamoya disease before cesarean delivery. The primary outcome, intraoperative maximum mean arterial pressure during anesthesia, was compared according to the type of anesthesia administered (general versus spinal anesthesia). Other perioperative hemodynamic data (lowest mean arterial pressure, incidence of hypotension, vasopressor use, and antihypertensive agent use), maternal neurologic symptoms, neonatal outcomes (Apgar scores <7, ventilatory support, and intensive care unit admission), maternal and neonatal length of stay, postoperative pain scores, and rescue analgesic use were assessed as secondary outcomes. RESULTS: While the lowest blood pressure during anesthesia and incidence of hypotension did not differ between the 2 groups, the maximum mean arterial pressure during anesthesia was lower in the spinal anesthesia group than that in the general anesthesia group (104.8 ± 2.5 vs 122.0 ± 4.6; P = .002). Study data did not support the claim that maternal neurologic symptoms differ according to the type of anesthesia used (5.6% vs 9.3%; P = .628); all patients recovered without any sequelae. The postoperative pain scores were lower, and fewer rescue analgesics were used in the spinal anesthesia group than in the general anesthesia group. Other maternal and neonatal outcomes were not different between the 2 groups. CONCLUSIONS: Compared with general anesthesia, spinal anesthesia mitigated the maximum arterial blood pressure during cesarean delivery and improved postoperative pain in patients with moyamoya disease.

Perceived barriers to psychiatric help-seeking in South Korea by age groups: text mining analyses of social media big data.

BACKGROUND: The psychiatric treatment gap is substantial in Korea, implying barriers in seeking help. OBJECTIVES: This study aims to explore barriers of seeing psychiatrists, expressed on the internet by age groups. METHODS: A corpus of data was garnered extensively from internet communities, blogs and social network services from 1 January 2016 to 31 July 2019. Among the texts collected, texts containing words linked to psychiatry were selected. Then the corpus was dismantled into words by using natural language processing. Words linked to barriers to seeking help were identified and classified. Then the words from web communities that we were able to identify the age groups were additionally organized by age groups. RESULTS: 97,730,360 articles were identified and 6,097,369 were included in the analysis. Words implying the barriers were selected and classified into four groups of structural discrimination, public prejudice, low accessibility, and adverse drug effects. Structural discrimination was the greatest barrier occupying 34%, followed by public prejudice (27.8%), adverse drug effects (18.6%), and cost/low accessibility (16.1%). In the analysis by age groups, structural discrimination caused teenagers (51%), job seekers (64%) and mothers with children (43%) the most concern. In contrast, the public prejudice (49%) was the greatest barriers in the senior group. CONCLUSIONS: Although structural discrimination may most contribute to barriers to visiting psychiatrists in Korea, variation by generations may exist. Along with the general attempt to tackle the discrimination, customized approach might be needed.

Compressed Deep Learning to Classify Arrhythmia in an Embedded Wearable Device.

The importance of an embedded wearable device with automatic detection and alarming cannot be overstated, given that 15-30% of patients with atrial fibrillation are reported to be asymptomatic. These asymptomatic patients do not seek medical care, hence traditional diagnostic tools including Holter are not effective for the further prevention of associated stroke or heart failure. This is likely to be more so in the era of COVID-19, in which patients become more reluctant on hospitalization and checkups. However, little literature is available on this important topic. For this reason, this study developed efficient deep learning with model compression, which is designed to use ECG data and classify arrhythmia in an embedded wearable device. ECG-signal data came from Korea University Anam Hospital in Seoul, Korea, with 28,308 unique patients (15,412 normal and 12,896 arrhythmia). Resnets and Mobilenets with model compression (TensorFlow Lite) were applied and compared for the diagnosis of arrhythmia in an embedded wearable device. The weight size of the compressed model registered a remarkable decrease from 743 MB to 76 KB (1/10000), whereas its performance was almost the same as its original counterpart. Resnet and Mobilenet were similar in terms of accuracy, i.e., Resnet-50 Hz (97.3) vs. Mo-bilenet-50 Hz (97.2), Resnet-100 Hz (98.2) vs. Mobilenet-100 Hz (97.9). Here, 50 Hz/100 Hz denotes the down-sampling rate. However, Resnets took more flash memory and longer inference time than did Mobilenets. In conclusion, Mobilenet would be a more efficient model than Resnet to classify arrhythmia in an embedded wearable device.

Bioactive Phytochemicals from Salix pseudolasiogyne Twigs: Anti-Adipogenic Effect of 2'-O-Acetylsalicortin in 3T3-L1 Cells.

Salix pseudolasiogyne (Salicaceae) is a willow tree and has been used as a medicinal herb in Korea to treat pain and fever. As a part of an ongoing study to identify bioactive natural products, potential anti-adipogenic compounds were investigated using the ethanol (EtOH) extract of S. pseudolasiogyne twigs. Phytochemical investigation of the EtOH extracts using liquid chromatography-mass spectrometry (LC/MS) led to the separation of two compounds, oregonin (1) and 2'-O-acetylsalicortin (2). The structures of the isolates were identified using nuclear magnetic resonance spectroscopy and LC/MS analysis. To the best of our knowledge, it is the first report identifying oregonin (1) in twigs of S. pseudolasiogyne. Here, we found that the isolated compounds, oregonin (1) and 2'-O-acetylsalicortin (2), showed anti-adipogenic effects during 3T3-L1 cell differentiation. Notably, 2'-O-acetylsalicortin (2), at a concentration of 50 µM, significantly suppressed lipid accumulation. Moreover, the mRNA and protein levels of lipogenic and adipogenic transcription factors were reduced in 2'-O-acetylsalicortin (2)-treated 3T3-L1 cells. Taken together, these results indicate that 2'-O-acetylsalicortin (2), isolated from S. pseudolasiogyne twigs, has the potential to be applied as a therapeutic agent to effectively control adipocyte differentiation, a critical stage in the progression of obesity.

Anti-Adipogenic Effects of Salicortin from the Twigs of Weeping Willow (Salix pseudolasiogyne) in 3T3-L1 Cells.

Salix pseudolasiogyne (Salicaceae), the "weeping willow," has been used in traditional Korean medicine to treat pain and fever due to its high concentrations of salicylic acid and salicin. The present study investigated bioactive compounds from S. pseudolasiogyne twigs to discover bioactive natural products. Phytochemical investigation of the ethanol (EtOH) extract of S. pseudolasiogyne twigs followed by liquid chromatography-mass spectrometry (LC/MS)-based analysis led to the isolation of two salicin derivatives, salicortinol and salicortin, the structures of which were determined by interpretation of their NMR spectra and data from the LC/MS analysis. To the best of our knowledge, this is the first report of salicortinol isolated from S. pseudolasiogyne. The isolated compounds were evaluated for their anti-adipogenic effects in 3T3-L1 cells. Both salicortinol and salicortin were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, salicortin exhibited a strong inhibitory effect on lipid accumulation. Furthermore, salicortin inhibited the expression of lipogenic and adipogenic transcription factors, including FASN, FABP4, C/EBPα, C/EBPß, and PPARγ, without inducing cytotoxicity. These results suggest that salicortin could be a potential therapeutic compound for the prevention or treatment of metabolic disorders such as obesity.

Characterization and Health-Related Quality of Life in Older Adults With Disabilities According to Timing of Disability Onset.

The current study examined characteristics of early-onset and late-onset disability in older adults and identified predictors of health-related quality of life (HRQoL). This is a secondary data analysis of the 2017 national survey in South Korea. Participants were 4,014 older adults with disabilities, who were divided into an early-onset group (n = 2,229) and late-onset group (n = 1,785). Data were analyzed using complex sample analyses. Difficulties during outdoor activity and transportation use, self-rated health, and stress were common predictors in both groups. Comorbidity was a significant predictor only in the early-onset group. Use of information technology devices, household income, and perceived social discrimination were significant predictors in the late-onset group. Characteristics and predictors of HRQoL were different between groups, despite sharing common characteristics. It is necessary to improve support systems and health care services for older adults with disabilities. [Journal of Gerontological Nursing, 48(3), 37-47.].

Attitudes toward Alzheimer's disease and dementia caregiving and health outcomes: Racial and ethnic differences.

This study aimed to explore racial/ethnic differences in the attitudes toward Alzheimer's Disease (AD) and dementia caregiving among midlife women who were family caregivers of persons living with AD (MWPLAD) in the U.S. and examine the associations of the attitudes to their health outcomes. This was a cross-sectional online survey study among 172 MWPLAD. The instruments included: the Attitude toward AD and Related Dementias Scale, the Questions on Attitudes toward AD Caregiving, the Social Readjustment Rating Scale, the EQ-5D-5L and the Midlife Women's Symptom Index. Multiple linear regression analyses were conducted. There were significant racial/ethnic differences in caregivers' attitudes toward dementia caregiving, health-related quality of life, and total severity scores of symptoms (p < .01). Controlling for covariates including race/ethnicity, caregivers' positive attitudes toward dementia caregiving were significantly associated with their health outcomes (p ≤ .05). Interventions for MWPLAD need to consider racial/ethnical differences in their attitudes toward dementia caregiving.