Effect of aerobic exercise and particulate matter exposure duration on the diversity of gut microbiota.

Inhalation of ambient particulate matter (PM) can disrupt the gut microbiome, while exercise independently influences the gut microbiome by promoting beneficial bacteria. In this study, we analyzed changes in gut microbial diversity and composition in response to combined interventions of PM exposure and aerobic exercise, extending up to 12 weeks. This investigation was conducted using mice, categorized into five groups: control group (Con), exercise group (EXE), exercise group followed by 3-day exposure to PM (EXE + 3-day PM), particulate matter exposure (PM), and PM exposure with concurrent treadmill exercise (PME). Notably, the PM group exhibited markedly lower alpha diversity and richness compared to the Con group and our analysis of beta diversity revealed significant variations among the intervention groups. Members of the Lachnospiraceae family showed significant enhancement in the exercise intervention groups (EXE and PME) compared to the Con and PM groups. The biomarker Lactobacillus, Coriobacteraceae, and Anaerofustis were enriched in the EXE group, while Desulfovibrionaceae, Mucispirillum schaedleri, Lactococcus and Anaeroplasma were highly enriched in the PM group. Differential abundance analysis revealed that Paraprevotella, Bacteroides, and Blautia were less abundant in the 12-week PM exposure group than in the 3-day PM exposure group. Moreover, both the 3-day and 12-week PM exposure groups exhibited a reduced relative abundance of Bacteroides uniformis, SMB53, and Staphylococcus compared to non-PM exposure groups. These findings will help delineate the possible roles and associations of altered microbiota resulting from the studied interventions, paving the way for future mechanistic research.

The Association Between Prenatal Food Insecurity and Breastfeeding Initiation and Exclusive Breastfeeding Duration: A Longitudinal Study Using Oregon PRAMS and PRAMS-2, 2008-2015.

Background: In the United States, 11.1% of households experience food insecurity; however, pregnant women are disproportionately affected. Maternal food insecurity may affect infant feeding practices, for example, through being a source of chronic stress that may alter the decision to initiate and continue breastfeeding. Thus, we sought to determine whether prenatal food insecurity was associated with breastfeeding (versus not) and exclusive breastfeeding duration among Oregon women. Method: The Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) data of live births from 2008 to 2015 and the Oregon PRAMS-2 follow-up survey were used (n = 3,624) in this study. Associations with breastfeeding initiation and duration were modeled with multivariable logistic regression and accelerated failure time (AFT), respectively. Models were adjusted for maternal sociodemographic and pre-pregnancy health characteristics. Results: Nearly 10% of women experienced prenatal food insecurity. For breastfeeding initiation, unadjusted models suggested non-significant decreased odds (odds ratio (OR) 0.88 [confidence intervals (CI): 0.39, 1.99]), whereas adjusted models revealed a non-significant increased odds (OR 1.41 [CI: 0.58, 3.47]). Unadjusted AFT models suggested that food-insecure mothers had a non-significant decrease in exclusive breastfeeding duration (OR 0.76 [CI: 0.50, 1.17]), but adjustment for covariates attenuated results (OR 0.89 [CI: 0.57, 1.39]). Conclusions: Findings suggest minimal differences in breastfeeding practices when exploring food security status in the prenatal period, though the persistence of food insecurity may affect exclusive breastfeeding duration. Lower breastfeeding initiation may be due to other explanatory factors correlated with food insecurity and breastfeeding, such as education and marital status.

Clinical benefits of surgical ablation during isolated aortic valve replacement: a nationwide study.

OBJECTIVES: To compare the early- and long-term clinical outcomes of concomitant surgical ablation (SA) for atrial fibrillation (AF) during isolated aortic valve replacement (AVR) using data from the Korean National Health Insurance Service Database. METHODS: Of 23,332 adult patients who underwent AVR between 2003 and 2019, those with underlying AF with or without concomitant SA were extracted, and propensity score matching analysis was performed. RESULTS: Overall, 1,741 patients with underlying AF with (n = 445, group A) or without (n = 1,296, group N) concomitant SA during isolated AVR were enrolled, from whom 435 pairs were matched in a 1:1 ratio using propensity score matching analysis. The operative mortality and early postoperative morbidities, including bleeding reoperation, stroke, permanent pacemaker implantation and acute kidney injury were comparable between the groups. The overall survival showed no differences between the groups. However, the cumulative incidence of new-onset late ischaemic stroke was significantly lower in group A than group N in propensity score-matched patients [2.3 vs 3.5 per 100 patient-years, adjusted hazard ratio (95% confidence interval) 0.64 (0.43-0.96), Group A versus Group N, respectively]. The cumulative incidence of other morbidities such as reoperation, permanent pacemaker implantation and progression to chronic renal failure showed no difference between groups. CONCLUSIONS: The incidence of late ischaemic stroke was significantly lower when concomitant SA was performed during isolated AVR in patients with underlying AF. Therefore, concomitant SA should be actively considered in patients with underlying AF undergoing isolated AVR to prevent the occurrence of late ischaemic stroke.

Asymmetric voltage amplification using a capacitive load energy management circuit in a triboelectric nanogenerator.

We investigated the polarity dependence of a capacitive energy management circuit in a triboelectric nanogenerator (TENG) power system. In a half-wave rectifying circuit, the Simulation Program with Integrated Circuit Emphasis and analytical models show that the charge dump to the load varied depending on the polarity of the rectifying circuit even with the same charge output from TENG. Depending on the polarity of the rectifying circuit, a fast saturation of the direct current (DC) output voltage or a high DC output voltage was obtained. Experiments with a half-wave rectifier and Bennet doubler confirmed our simulation and theoretical results. The charge dump from the minimum capacitance of the separated TENG to the load capacitance and the charge dump from the maximum capacitance of the contacted TENG to the load resulted in asymmetric charging behavior. We concluded that it is necessary to analyze the TENG and the capacitive energy management circuit as a single system rather than considering them as independent units in the rectifying circuit of the TENG. This work can provide insights for the design of triboelectric energy harvesting systems.

Temporal variations in the gut microbial diversity in response to high-fat diet and exercise.

High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p < 0.02), whereas diversity (Shannon, Faith's PD, and Fisher) and richness (ACE) was significantly reduced in the HFD (p < 0.005) and HFX (p < 0.03) groups over time. Beta diversity, based on the Jaccard, Bray-Curtis, and unweighted UniFrac distance metrics, was significant among the groups. Prevotella, Paraprevotella, Candidatus arthromitus, Lactobacillus salivarius, L. reuteri, Roseburia, Bacteroides uniformis, Sutterella, and Corynebacterium were differentially abundant in the chow-diet groups (CHD and EXE). Exercise significantly reduced the proportion of taxa characteristic of a high-fat diet, including Butyricimonas, Ruminococcus gnavus, and Mucispirillum schaedleri. Diet, age, and exercise significantly contributed to explaining the bacterial community structure and diversity in the gut microbiota. Modulating the gut microbiota and maintaining its stability can lead to targeted microbiome therapies to manage chronic and recurrent diseases and infections.

Distinct spatiotemporal patterns of cortical thinning in Alzheimer's disease-type cognitive impairment and subcortical vascular cognitive impairment.

Previous studies on Alzheimer's disease-type cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI) has rarely explored spatiotemporal heterogeneity. This study aims to identify distinct spatiotemporal cortical atrophy patterns in ADCI and SVCI. 1,338 participants (713 ADCI, 208 SVCI, and 417 cognitively unimpaired elders) underwent brain magnetic resonance imaging (MRI), amyloid positron emission tomography, and neuropsychological tests. Using MRI, this study measures cortical thickness in five brain regions (medial temporal, inferior temporal, posterior medial parietal, lateral parietal, and frontal areas) and utilizes the Subtype and Stage Inference (SuStaIn) model to predict the most probable subtype and stage for each participant. SuStaIn identifies two distinct cortical thinning patterns in ADCI (medial temporal: 65.8%, diffuse: 34.2%) and SVCI (frontotemporal: 47.1%, parietal: 52.9%) patients. The medial temporal subtype of ADCI shows a faster decline in attention, visuospatial, visual memory, and frontal/executive domains than the diffuse subtype (p-value < 0.01). However, there are no significant differences in longitudinal cognitive outcomes between the two subtypes of SVCI. Our study provides valuable insights into the distinct spatiotemporal patterns of cortical thinning in patients with ADCI and SVCI, suggesting the potential for individualized therapeutic and preventive strategies to improve clinical outcomes.

TGF-ß blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo.

HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing of anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirm the latency reversal properties of in vivo TGF-ß blockade, decrease viral reservoirs and stimulate immune responses. Treatment of eight female, SIV-infected macaques on ART with four 2-weeks cycles of galunisertib leads to viral reactivation as indicated by plasma viral load and immunoPET/CT with a 64Cu-DOTA-F(ab')2-p7D3-probe. Post-galunisertib, lymph nodes, gut and PBMC exhibit lower cell-associated (CA-)SIV DNA and lower intact pro-virus (PBMC). Galunisertib does not lead to systemic increase in inflammatory cytokines. High-dimensional cytometry, bulk, and single-cell (sc)RNAseq reveal a galunisertib-driven shift toward an effector phenotype in T and NK cells characterized by a progressive downregulation in TCF1. In summary, we demonstrate that galunisertib, a clinical stage TGF-ß inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in absence of toxicity.

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O2-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O2-GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2-GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O2-GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O2-GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2-GeMs. In vivo evaluation confirmed robust insertion and positioning of O2-GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage.

OBJECTIVE: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. METHODS: OA progression was examined in wild-type and Irf1-/- mice using histologic assessments and microcomputed tomography analysis of whole-joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase-accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ-H2AX foci and senescence-associated beta-galactosidase activity. RESULTS: Our genome-wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon-responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down-regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post-traumatic OA in mice. CONCLUSION: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development.

Identification of novel Nrf2-activating neuroprotective agents: Elucidation of structural congeners of (-)-galiellalactone and congener-based novel Nrf2 activators.

Herein, (-)-galiellalactone 1 congeners responsible for the nuclear factor erythroid 2-related factor 2 (Nrf2)-activating neuroprotective effects were elucidated. Additionally, novel congener-based Nrf2 activators were identified using a drug repositioning strategy. (-)-Galiellalactone, which comprises a tricyclic lactone skeleton, significantly activates antioxidant response element (ARE)-mediated transcription in neuroblastoma SH-SY5Y cells. Interestingly, two cyclohexene-truncated [3.3] bicyclic lactone analogs, which possess an exocyclic α-methylene-γ-butyrolactone moiety, exhibited higher Nrf2/ARE transcriptional activities than the parent (-)-galiellalactone. We confirmed that the cyclohexene moiety embedding the [3.3] bicyclic lactone congener does not play the essential role of (-)-galiellalactone for Nrf2/ARE activation. Nrf2/ARE activation by novel analogs resulted in the upregulation of downstream antioxidative and phase II detoxifying enzymes, heme oxygenase-1, and NAD(P)H quinone oxidoreductase 1, which are closely related to the cytoprotective effects on neurodegenerative diseases. (-)-Galiellalactone and its [3.3] bicyclic variants 3l and 3p increased the expression of antioxidant genes and exhibited neuroprotective effects against 6-hydroxydopamine-mediated neurotoxicity in the neuroblastoma SH-SY5Y cell line.

Association Between Baseline Gait Parameters and Future Fall Risk in Patients With De Novo Parkinson's Disease: Forward Versus Backward Gait.

BACKGROUND AND PURPOSE: Falls are not uncommon even in patients with early stages of Parkinson's disease (PD). The aims of this study were to determine the relationships between gait parameters and falls and identify crucial gait parameters for predicting future falls in patients with de novo PD. METHODS: We prospectively recruited patients with de novo PD, and evaluated their baseline demographics, global cognitive function on the Montreal Cognitive Assessment test, and parkinsonian motor symptoms including their subtypes. Both forward gait (FG) and backward gait (BG) were measured using the GAITRite system. The history of falls in consecutive patients with de novo PD was examined along with 1 year of follow-up data. RESULTS: Among the 76 patients with de novo PD finally included in the study, 16 (21.1%) were classified as fallers. Fallers had slower gait and shorter stride for FG and BG parameters than did non-fallers, while stride-time variability was greater in fallers but only for BG. Multivariable logistic regression analysis revealed that slow gait was an independent risk factor in BG. CONCLUSIONS: Among the patients with de novo PD, gait speed and stride length were more impaired for both FG and BG in fallers than in non-fallers. It was particularly notable that slow BG was significantly associated with future fall risk, indicating that BG speed is a potential biomarker for predicting future falls in patients with early-stage PD.

Comparison between remimazolam and propofol anaesthesia for interventional neuroradiology: a randomised controlled trial.

BACKGROUND: General anaesthesia can immobile patients during interventional neuroradiology to improve image quality. Remimazolam, an ultrashort-acting benzodiazepine, is advantageous for haemodynamic stability. This study compared remimazolam and propofol anaesthesia during neuroradiology procedures regarding intraoperative hypotensive events and rapid recovery. METHODS: This single-masked randomised-controlled study included 76 participants who underwent elective endovascular embolisation in a single centre. Patients were randomised between a continuous remimazolam infusion (n = 38) or a target-controlled propofol infusion group (n = 38). In the remimazolam group, flumazenil (0.2 mg) was administered at the end of the procedure. Phenylephrine was titrated to maintain the mean arterial pressure within ± 20% of the baseline value. The primary outcome was the total phenylephrine dose during the procedure. RESULTS: The total phenylephrine dose was 0.0 [0.0-30.0] µg in the remimazolam group and 30.0 [0.0-205.0] µg in the propofol group (p = 0.001). Hypotensive events were observed in 11 (28.9%) patients in the remimazolam group and 23 (60.5%) patients in the propofol group (p = 0.001). Recovery times to spontaneous breathing, eye-opening, extubation, and orientation were shorter in the remimazolam group than in the propofol group (all p < 0.001). CONCLUSIONS: Remimazolam anaesthesia showed superior haemodynamic stability compared with propofol anaesthesia during neuroradiology procedures. Systematic use of flumazenil enabled rapid recovery from remimazolam anaesthesia. REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry; Registration number: UMIN000047384; URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054046.

Sex-specific patterns of discomfort in patients with restless legs syndrome.

STUDY OBJECTIVES: Sex differences in the prevalence of restless legs syndrome (RLS) have been reported, with a higher prevalence in women than in men. However, sex differences in clinical presentation remain unclear. We aimed to investigate the phenotypic differences in patients with RLS between sexes by comparing clinical presentations, iron status, polysomnographic parameters, and treatment. METHODS: We retrospectively evaluated 614 patients (225 men, 389 women) diagnosed with RLS. To enhance the robustness of the study, an age-matched control group of 179 men and 286 women without sleep disorders was also included. Information on demographics and sleep-related questionnaires were collected. Iron status was evaluated using blood samples, and polysomnography was performed to evaluate periodic leg movements and comorbid sleep disorders. RESULTS: Our analysis revealed no sex difference in the severity of RLS but a difference in the pattern of symptoms. Women had more frequent symptoms of pain and awakening during sleep, while men had more common motor symptoms (both self-reported symptoms and periodic leg movement on polysomnography). Women with RLS also had lower iron parameters and received more frequent iron supplementation therapy than men. In contrast to women with RLS, who presented higher sleep disturbances and depressive mood, men with RLS had a higher risk of comorbidities such as hypertension and cardiovascular disease. These sex differences were notably more pronounced than in the control group. CONCLUSIONS: This study suggests that sex differences exist in RLS phenotypes, and clinicians should consider these differences for treatment. CITATION: Kim J, Kim JR, Park HR, Joo EY. Sex-specific patterns of discomfort in patients with restless legs syndrome. J Clin Sleep Med. 2024;20(2):253-259.

Incidence trend and epidemiology of tic disorders among youths and adults in Korea from 2003 to 2020: A national population-based study.

Tic disorder is a highly prevalent neurodevelopmental disorder; however, research on its incidence trends is still rare. We aimed to investigate its annual incidence rates and the characteristics of incident cases in the general Korean population using data from the National Health Insurance Service-National Health Information Database as a proxy measurement for true incidence in the community. The total number of incident cases and incidence rates of tic disorders from 2003 to 2020 were compared between youths and adults. Both the number of incident cases and the annual incidence rates of tic disorders significantly increased from 2003 to 2020. The overall increasing trend in the incidence rates was significantly greater in youths than in adults; however, the incidence rates in adults showed a relatively recent increase. The male predominance regarding the newly diagnosed case number in youths was no longer observed in adults. Tic disorders occurred more commonly in the low-income group than in the high-income group. Neurodevelopmental comorbidities in youths and mood or anxiety disorders and schizophrenia in adults were more frequently observed. Antipsychotic medication adherence was higher in youths than in adults. Efforts are required to raise awareness and promote expert education for adult patients with tic disorders.

Repeated intratracheal instillation of whole-cigarette smoke condensate to assess lung damage in a rat model.

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.

Antarctic Krill Oil from Euphausia superba Ameliorates Carrageenan-Induced Thrombosis in a Mouse Model.

FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, ß-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1ß, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.

Impact of an Emergency Department Isolation Policy for Patients With Suspected COVID-19 on Door-to-Electrocardiography Time and Clinical Outcomes in Patients With Acute Myocardial Infarction.

BACKGROUND: Rapid electrocardiography diagnosis within 10 minutes of presentation is critical for acute myocardial infarction (AMI) patients in the emergency department (ED). However, the coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the emergency care system. Screening for COVID-19 symptoms and implementing isolation policies in EDs may delay the door-to-electrocardiography (DTE) time. METHODS: We conducted a cross-sectional study of 1,458 AMI patients who presented to a single ED in South Korea from January 2019 to December 2021. We used multivariate logistic regression analysis to assess the impact of COVID-19 pandemic and ED isolation policies on DTE time and clinical outcomes. RESULTS: We found that the mean DTE time increased significantly from 5.5 to 11.9 minutes (P < 0.01) in ST segment elevation myocardial infarction (STEMI) patients and 22.3 to 26.7 minutes (P < 0.01) in non-ST segment elevation myocardial infarction (NSTEMI) patients. Isolated patients had a longer mean DTE time compared to non-isolated patients in both STEMI (9.2 vs. 24.4 minutes) and NSTEMI (22.4 vs. 61.7 minutes) groups (P < 0.01). The adjusted odds ratio (aOR) for the effect of COVID-19 duration on DTE ≥ 10 minutes was 1.93 (95% confidence interval [CI], 1.51-2.47), and the aOR for isolation status was 5.62 (95% CI, 3.54-8.93) in all patients. We did not find a significant association between in-hospital mortality and the duration of COVID-19 (aOR, 0.9; 95% CI, 0.52-1.56) or isolation status (aOR, 1.62; 95% CI, 0.71-3.68). CONCLUSION: Our study showed that ED screening or isolation policies in response to the COVID-19 pandemic could lead to delays in DTE time. Timely evaluation and treatment of emergency patients during pandemics are essential to prevent potential delays that may impact their clinical outcomes.

Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.

Development of a hospital frailty risk score for community-dwelling older adults using data from electronic hospital records in South Korea.

PURPOSE: We aimed to develop the Korean Hospital Frailty Risk Score (K-HFRS) by applying the International Classification of Diseases-10 codes to community-dwelling older adults' medical data. METHODS: We selected data from 2,761 people with no missing main variable values from the Korean Frailty and Aging Cohort Data (KFACD) and National Health Insurance Database (NHID) for analysis. Frailty was determined based on modified Fried's phenotype [MFP] and Korean Frailty Index for Primary Care [KFI-PC] in the KFACD. A previously established method calculated the K-HFRS, verified by the area under the receiver operating characteristic (ROC) curve. The calculated cutoff value predicted the medical use. RESULTS: The respective K-HFRSs of the frailty group using the MFP and KFI-PC criteria ranged from 3.64 (±3.03) to 8.15 (±5.72) and 4.07 (±3.42) to 9.10 (±6.28), with 7.67 (±5.40) and 8.59 (±6.03) when four diagnoses were included. The K-HFRS of the frailty group using the KFI-PC criteria was higher than that using the MFP criteria. With four diagnoses included using the MFP criteria, the adjusted odds ratio (OR) for medical expenditures in the frailty group compared to the non-frailty group was 3.01 (95% confidence interval [CI] 2.52-3.60, p < .001); for the number of emergency room (ER) visits was 2.19 (95% CI 1.77-2.70, p < .001); for inpatient days was 2.48 (95% CI 2.08-2.96, p < .001). With four diagnoses included using the KFI-PC criteria, the adjusted OR value for medical expenditures was 2.77 (95% CI 2.35-3.27, p < .001); for the number of ER visits was 1.87 (95% CI 1.51-2.32, p < .001); for inpatient days was 2.07 (95% CI 1.75-2.45, p < .001). CONCLUSION: This study substantiated that the K-HFRS can measure frailty efficiently at a lower cost. Follow-up studies are needed for additional validity.

Mobile Affinity Selection Chromatography Analysis of Therapeutic Monoclonal Antibodies.

Federal regulatory agencies require continuous verification of recombinant therapeutic monoclonal antibody (mAb) quality that is commonly achieved in a two-step process. First, the host-cell proteome and metabolome are removed from the production medium by protein A affinity chromatography. Second, following recovery from the affinity column with an acidic wash, mAb quality is assessed in multiple ways by liquid chromatography-mass spectrometry (LC-MS). However, lengthy sample preparation and the lack of higher-order structure analyses are limitations of this approach. To address these issues, this report presents an integrated approach for the analysis of two critical quality attributes of mAbs, namely titer and relative aggregate content. Integration of sample preparation and molecular-recognition-based analyses were achieved in a single step utilizing an isocratically eluted mobile affinity selection chromatography (MASC) column. MASC circumvents the protein A step, simplifying sample preparation. Within 10 min, (i) mAbs are fluorescently coded for specific detection, (ii) monomers and aggregates are resolved, (iii) the mAb titer is quantified, (iv) relative aggregate content is determined, (v) analytes are detected, and (vi) the column is ready for the next sample. It is suggested herein that this mode of rapid quality assessment will be of value at all stages of discovery (screening, clone selection, characterization), process R&D, and manufacturing. Rapid monitoring of variant formation is a critical element of quality evaluation.