Separating Risk Prediction: Myocardial Infarction vs. Ischemic Stroke in 6.2M Screenings.

BACKGROUND: Traditional cardiovascular disease risk prediction models generate a combined risk assessment for myocardial infarction (MI) and ischemic stroke (IS), which may inadequately reflect the distinct etiologies and disparate risk factors of MI and IS. We aim to develop prediction models that separately estimate the risks of MI and IS. METHODS: Our analysis included 6,242,404 individuals over 40 years old who participated in a cardiovascular health screening examination in 2009. Potential predictors were selected based on a literature review and the available data. Cox proportional hazards models were used to construct 5-year risk prediction models for MI, and IS. Model performance was assessed through discrimination and calibration. RESULTS: During a follow-up of 39,322,434.39 person-years, 89,140 individuals were diagnosed with MI and 116,259 with IS. Both models included age, sex, body mass index, smoking, alcohol consumption, physical activity, diabetes, hypertension, dyslipidemia, chronic kidney disease, and family history. Statin use was factored into the classification of dyslipidemia. The c-indices for the prediction models were 0.709 (0.707-0.712) for MI, and 0.770 (0.768-0.772) for IS. Age and hypertension exhibited a more pronounced effect on IS risk prediction than MI, whereas smoking, body mass index, dyslipidemia, and chronic kidney disease showed the opposite effect. The models calibrated well for low-risk individuals. CONCLUSIONS: Our findings underscore the necessity of tailored risk assessments for MI and IS to facilitate the early detection and accurate identification of heterogeneous at-risk populations for atherosclerotic cardiovascular disease.

Study of Weight Quantization Associations over a Weight Range for Application in Memristor Devices.

The development of hardware-based cognitive computing systems critically hinges upon the integration of memristor devices capable of versatile weight expression across a spectrum of resistance levels while preserving consistent electrical properties. This investigation aims to explore the practical implementation of a digit recognition system utilizing memristor devices with minimized weighting levels. Through the process of weight quantization for digits represented by 25 or 49 input signals, the study endeavors to ascertain the feasibility of digit recognition via neural network computation. The integration of memristor devices into the system architecture is poised to streamline the representation of the resistors required for weight expression, thereby facilitating the realization of neural-network-based cognitive systems. To minimize the information corruption in the system caused by weight quantization, we introduce the concept of "weight range" in this work. The weight range is the range between the maximum and minimum values of the weights in the neural network. We found that this has a direct impact on weight quantization, which reduces the number of digits represented by a weight below a certain level. This was found to help maintain the information integrity of the entire system despite the reduction in weight levels. Moreover, to validate the efficacy of the proposed methodology, quantized weights are systematically applied to an array of double-layer neural networks. This validation process involves the construction of cross-point array circuits with dimensions of 25 × 10 and 10 × 10, followed by a meticulous examination of the resultant changes in the recognition rate of randomly generated numbers through device simulations. Such endeavors contribute to advancing the understanding and practical implementation of hardware-based cognitive computing systems leveraging memristor devices and weight quantization techniques.

Distorted time perception in patients with neurocognitive impairment.

Background: Time perception is known to be distorted in patients with neuropsychiatric disorders. Therefore, this study aims to investigate the correlation between cognitive decline and time distortion by examining time perception in participants with neurocognitive impairment (Alzheimer's disease [AD], vascular dementia [VD], and Parkinson's disease dementia [PDD]) compared to those with subjective cognitive impairment (SCI). Methods: Overall, 569 participants with cognitive decline complaints between 2013 and 2022 were investigated. Participants were subjected to a verbal estimation task, time production task, time comparison task, and neuropsychological assessments. Results: Time perception abilities were distorted in patients with neurocognitive impairment compared to those with SCI. Despite similar educational backgrounds, the vascular cognitive impairment (VCI)/VD group demonstrated the lowest MMSE scores (22.4 ± 4.2, p-value <0.001) and larger time-estimation errors. Patients with VCI/VD significantly underestimated time in the 35-s (19.6 ± 12.6s) and 60-s (28.7 ± 19.9s) tasks. In the time production task, patients with VCI/VD produced shorter times in their 15-s (12.7 ± 4.3; p-value = 0.001), 30-s (23.6 ± 8.3; p value < 0.001), and 60-s (43.8 ± 18.9; p-value <0.001) trials. In the time comparison task, the VCI/VD group had significantly fewer correct answers than that in the SCI groups (6.0 ± 1.3 vs. 7.1 ± 0.9, p-value <0.001). Correlation analysis revealed that multiple cognitive functions are involved in the time perception tasks. Conclusions: Patients with VCI/VD had the poorest time perception. These findings may provide a modest contribution to understanding the underlying pathophysiology and psychological connections related to temporal abilities in time perception.

"Straw in the Clay Soil" Strategy: Anticarbon Corrosive Fluorine-Decorated Graphene Nanoribbons@CNT Composite for Long-Term PEMFC.

Carbon corrosion poses a significant challenge in polymer exchange membrane fuel cells (PEMFCs), leading to reduced cell performance due to catalyst layer degradation and catalyst detachment from electrodes. A promising approach to address this issue involves incorporating an anticorrosive carbon material into the oxygen reduction reaction (ORR) electrode, even in small quantities (≈3 wt% in electrode). Herein, the successful synthesis of fluorine-doped graphene nanoribbons (F-GNR) incorporated with graphitic carbon nanotubes (F-GNR@CNT), demonstrating robust resistance to carbon corrosion is reported. By controlling the synthesis conditions using an exfoliation method, the properties of the composite are tailored. Electronic structural studies, employing density functional theory (DFT) calculations, to elucidate the roles of fluorine dopants and graphitic carbon nanotubes (CNTs) in mitigating carbon corrosion are conducted. Physicochemical and electrochemical characterization of F-GNR@CNT reveal its effectiveness as a cathode additive at the single-cell scale. The addition of F-GNR@CNT to the Pt/C cathode improves durability by enhancing carbon corrosion resistance and water management, thus mitigating the flooding effect through tailored surface properties. Furthermore, advanced impedance analysis using a transmission line model is performed to gain insights into the internal resistance and capacitive properties of electrode structure.

Impact of Systolic Blood Viscosity on Deep White Matter Hyperintensities in Patients With Acute Ischemic Stroke.

BACKGROUND: Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. METHODS AND RESULTS: We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). CONCLUSIONS: Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

BACKGROUND: This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). METHODS: We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. RESULTS: Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. CONCLUSION: AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

Vacuum-Processed Propylene Urea Additive: A Novel Approach for Controlling the Growth of CH3NH3PbI3 Crystals in All Vacuum-Processed Perovskite Solar Cells.

In this study, we present a novel method for controlling the growth of perovskite crystals in the vacuum thermal evaporation process by utilizing a vacuum-processable additive, propylene urea (PU). By coevaporation of perovskite precursors with PU to form the perovskite layer, PU, acting as a Lewis base additive, retards the direct reaction between the perovskite precursors. This facilitates a larger domain size and reduced defect density. Following the removal of the residual additive, the perovskite layer, exhibiting improved crystallinity, demonstrates reduced charge recombination, as confirmed by a time-resolved microwave conductivity analysis. Consequently, there is a notable enhancement in open-circuit voltage and power conversion efficiency, increasing from 1.05 to 1.15 V and from 17.17 to 18.31%, respectively. The incorporation of a vacuum-processable and removable Lewis base additive into the fabrication of vacuum-processed perovskite solar cells offers new avenues for optimizing these devices.

Effects of Prior Metformin Use on Stroke Outcomes in Diabetes Patients with Acute Ischemic Stroke Receiving Endovascular Treatment.

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET- groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12-0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14-0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0-2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.

Association between pre-diagnostic serum uric acid levels in patients with newly diagnosed epilepsy and conversion rate to drug-resistant epilepsy within 5 years: A common data model analysis.

PURPOSE: Drug-resistant epilepsy (DRE) poses a significant challenge in epilepsy management, and reliable biomarkers for identifying patients at risk of DRE are lacking. This study aimed to investigate the association between serum uric acid (UA) levels and the conversion rate to DRE. METHODS: A retrospective cohort study was conducted using a common data model database. The study included patients newly diagnosed with epilepsy, with prediagnostic serum UA levels within a six-month window. Patients were categorized into hyperUA (≥7.0 mg/dL), normoUA (<7.0 and >2.0 mg/dL), and hypoUA (≤2.0 mg/dL) groups based on their prediagnostic UA levels. The outcome was the conversion rate to DRE within five years of epilepsy diagnosis. RESULTS: The study included 5,672 patients with epilepsy and overall conversion rate to DRE was 19.4%. The hyperUA group had a lower DRE conversion rate compared to the normoUA group (HR: 0.81 [95% CI: 0.69-0.96]), while the hypoUA group had a higher conversion rate (HR: 1.88 [95% CI: 1.38-2.55]). CONCLUSIONS: Serum UA levels have the potential to serve as a biomarker for identifying patients at risk of DRE, indicating a potential avenue for novel therapeutic strategies aimed at preventing DRE conversion.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.

Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

Effect of pre-stroke antiplatelet use on stroke outcomes in acute small vessel occlusion stroke with moderate to severe white matter burden.

BACKGROUND: Cerebral small vessel disease is characterized by white matter hyperintensities (WMH) and acute small vessel occlusion (SVO) stroke. We investigated the effect of prior antiplatelet use (APU) on stroke outcome in 1151 patients with acute SVO stroke patients and moderate to severe WMH. METHODS: Using a multicenter database, this retrospective study used quantitative WMH volume measurements and propensity score matching (PSM) for comparisons between patients with prior APU and without APU. Primary outcomes were stroke progression and poor functional outcome (modified Rankin Scale>2) at 3 months. Logistic regression analyses assessed associations between prior APU, WMH burden, and stroke outcomes. RESULTS: Stroke progression was lower in the prior APU group in both the total cohort (14.8% vs. 6.9%, p < 0.001) and the PSM cohort (16.3% vs. 6.9%, p < 0.001). The proportion of poor functional outcomes at 3 months was not significantly different in the total cohort, but the PSM cohort showed a lower proportion in the prior APU group (30.8% vs. 20.2%, p = 0.002). Logistic regression analysis confirmed that prior APU was associated with a reduced risk of stroke progression (OR, 0.39; 95% CI, 0.22-0.70; p = 0.001) and poor functional outcome at 3 months (OR, 0.37; 95% CI, 0.23-0.59; p < 0.001). CONCLUSION: Prior APU is associated with reduced stroke progression and improved functional outcome at 3 months in acute SVO stroke patients with moderate to severe WMH. Early treatment of WMH and acute SVO stroke may have potential benefits in improving stroke outcomes.

Brain-wide circuit-specific targeting of astrocytes.

Astrocytes are integral components of brain circuitry. They enwrap synapses, react to neuronal activity, and regulate synaptic transmission. Astrocytes are heterogeneous and exhibit distinct features and functions in different circuits. Selectively targeting the astrocytes associated with a given neuronal circuit would enable elucidation of their circuit-specific functions but has been technically challenging to date. Recently, we constructed anterograde transneuronal viral vectors based on yellow fever vaccine YFV-17D. Among them, the replication-incompetent YFVΔNS1-Cre can selectively turn on reporter genes in postsynaptic neurons if the viral gene NS1 is expressed in postsynaptic neurons. Here we show that without exogenous expression of NS1 at the postsynaptic sites, locally injected YFVΔNS1-Cre selectively turns on reporter genes in astrocytes in downstream brain regions. The targeting of astrocytes can occur across the whole brain but is specific for the neuronal circuits traced. Therefore, YFVΔNS1-Cre provides a tool for selective genetic targeting of astrocytes to reveal their circuit-specific roles.

Proton pump inhibitors and chronic kidney disease risk: a comparative study with histamine-2 receptor antagonists.

This observational study explored the association between proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use and the risk of chronic kidney disease (CKD). Using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) and six-hospital electronic health record (EHR) databases, CKD incidence was analyzed among PPI and H2RA users. Propensity score matching was used to balance baseline characteristics, with 1,869 subjects each in the PPI and H2RA groups from the NHIS-NSC, and 5,967 in EHR databases. CKD incidence was similar for both groups (5.72/1000 person-years vs. 7.57/1000 person-years; HR = 0.68; 95% CI, 0.35-1.30). A meta-analysis of the EHR databases showed no significant increased CKD risk associated with PPI use (HR = 1.03, 95% CI: 0.87-1.23). These results suggest PPI use may not increase CKD risk compared to H2RA use, but the potential role of PPI-induced CKD needs further research. Clinicians should consider this when prescribing long-term PPI therapy.

Effect of Cerebral Small Vessel Disease Burden on Infarct Growth Rate and Stroke Outcomes in Large Vessel Occlusion Stroke Receiving Endovascular Treatment.

This study aimed to investigate the association between cerebral small vessel disease (CSVD) burden and infarct growth rate (IGR) in patients with large vessel occlusion (LVO) stroke who underwent endovascular treatment (EVT). A retrospective analysis was conducted on a cohort of 495 patients with anterior circulation stroke who received EVT. CSVD burden was assessed using a CSVD score based on neuroimaging features. IGR was calculated from diffusion-weighted imaging (DWI) lesion volumes divided by the time from stroke onset to imaging. Clinical outcomes included stroke progression and functional outcomes at 3 months. Multivariate analyses were performed to assess the relationship between CSVD burden, IGR, and clinical outcomes. The fast IGR group had a higher proportion of high CSVD scores than the slow IGR group (24.4% vs. 0.8%, p < 0.001). High CSVD burden was significantly associated with a faster IGR (odds ratio [95% confidence interval], 26.26 [6.26-110.14], p < 0.001) after adjusting for confounding factors. High CSVD burden also independently predicted stroke progression and poor functional outcomes. This study highlights a significant relationship between CSVD burden and IGR in LVO stroke patients undergoing EVT. High CSVD burden was associated with faster infarct growth and worse clinical outcomes.

High ApoB/ApoA-I Ratio Predicts Post-Stroke Cognitive Impairment in Acute Ischemic Stroke Patients with Large Artery Atherosclerosis.

BACKGROUND: We aimed to investigate the association between the ApoB/ApoA-I ratio and post-stroke cognitive impairment (PSCI) in patients with acute stroke of large artery atherosclerosis etiology. METHODS: Prospective stroke registry data were used to consecutively enroll patients with acute ischemic stroke due to large artery atherosclerosis. Cognitive function assessments were conducted 3 to 6 months after stroke. PSCI was defined as a z-score of less than -2 standard deviations from age, sex, and education-adjusted means in at least one cognitive domain. The ApoB/ApoA-I ratio was calculated, and patients were categorized into five groups according to quintiles of the ratio. Logistic regression analyses were performed to assess the association between quintiles of the ApoB/ApoA-I ratio and PSCI. RESULTS: A total of 263 patients were included, with a mean age of 65.9 ± 11.6 years. The median NIHSS score and ApoB/ApoA-I ratio upon admission were 2 (IQR, 1-5) and 0.81 (IQR, 0.76-0.88), respectively. PSCI was observed in 91 (34.6%) patients. The highest quintile (Q5) of the ApoB/ApoA-I ratio was a significant predictor of PSCI compared to the lowest quintile (Q1) (adjusted OR, 3.16; 95% CI, 1.19-8.41; p-value = 0.021) after adjusting for relevant confounders. Patients in the Q5 group exhibited significantly worse performance in the frontal domain. CONCLUSIONS: The ApoB/ApoA-I ratio in the acute stage of stroke independently predicted the development of PSCI at 3-6 months after stroke due to large artery atherosclerosis. Further, a high ApoB/ApoA-I ratio was specifically associated with frontal domain dysfunction.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Recurrent Stroke and Myocardial Infarction.

BACKGROUND/AIMS: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). METHODS: This study used two databases for two different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS data base converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study based on large-scale propensity score matching. RESULTS: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1216 patients with history of MI within1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 (95% confidence interval (CI); 1.83-2.38); the RR showed an increasing trend parallel to the time from the beginning of PPI co-prescription. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group (Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, p = 0.04). The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, p = 0.23). The impact of individual PPIs on stroke and MI showed different patterns. CONCLUSIONS: A PPI co-prescription >4 weeks with clopidogrel was associated with hospitalization of recurrent stroke within 1 year of initial diagnosis; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.

Impact of symptomatic menopausal transition on the occurrence of depression, anxiety, and sleep disorders: A real-world multi-site study.

BACKGROUND: The menopause transition is a vulnerable period that can be associated with changes in mood and cognition. The present study aimed to investigate whether a symptomatic menopausal transition increases the risks of depression, anxiety, and sleep disorders. METHODS: This population-based, retrospective cohort study analysed data from five electronic health record databases in South Korea. Women aged 45-64 years with and without symptomatic menopausal transition were matched 1:1 using propensity-score matching. Subgroup analyses were conducted according to age and use of hormone replacement therapy (HRT). A primary analysis of 5-year follow-up data was conducted, and an intention-to-treat analysis was performed to identify different risk windows over 5 or 10 years. The primary outcome was first-time diagnosis of depression, anxiety, and sleep disorder. We used Cox proportional hazard models and a meta-analysis to calculate the summary hazard ratio (HR) estimates across the databases. RESULTS: Propensity-score matching resulted in a sample of 17,098 women. Summary HRs for depression (2.10; 95% confidence interval [CI] 1.63-2.71), anxiety (1.64; 95% CI 1.01-2.66), and sleep disorders (1.47; 95% CI 1.16-1.88) were higher in the symptomatic menopausal transition group. In the subgroup analysis, the use of HRT was associated with an increased risk of depression (2.21; 95% CI 1.07-4.55) and sleep disorders (2.51; 95% CI 1.25-5.04) when compared with non-use of HRT. CONCLUSIONS: Our findings suggest that women with symptomatic menopausal transition exhibit an increased risk of developing depression, anxiety, and sleep disorders. Therefore, women experiencing a symptomatic menopausal transition should be monitored closely so that interventions can be applied early.

Impact of Osteoporosis Pharmacotherapy on Functional Outcomes after Ischemic Stroke.

This study evaluated whether osteoporosis pharmacotherapy (OPT) affected functional outcomes in acute ischemic stroke patients with osteoporosis. Using a single-center registry database, we consecutively registered acute ischemic stroke patients between May 2016 and December 2020. All patients older than 55 years underwent routine bone densitometry within 7 days of stroke onset. OPT prescription was confirmed by reviewing medical records. We classified the patients into OPT and no OPT groups. We performed propensity score matching (PSM) to overcome the imbalance in multiple covariates between the two groups. We investigated whether OPT affected 1-year functional outcomes by multivariate analysis using a PSM cohort. Among 1307 consecutively registered acute ischemic stroke patients, 381 patients were enrolled in this study, of whom 134 (35.2%) were prescribed OPT at discharge, which was maintained for 1 year. In a multivariate analysis using a PSM cohort, the OPT group had a lower risk of dependency (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.27-0.996) and poor functional outcome at 1 year (OR, 0.24; 95% CI, 0.10-0.57). The OPT group also had increased chance of late functional improvement (OR, 6.16; 95% CI, 1.12-33.79). This study showed that OPT could reduce dependency and poor functional outcomes and increase the chance of improving functional outcomes at 3 months and 1 year after ischemic stroke onset, and these findings could be helpful for improving functional outcomes and bone health after ischemic stroke.