Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

Once-for-All Sequence Compression for Self-Supervised Speech Models

The sequence length along the time axis is often the dominant factor of the computational cost of self-supervised speech models. Works have been proposed to reduce the sequence length for lowering the computational cost. However, different downstream tasks have different tolerance of sequence compressing, so a model that produces a fixed compressing rate may not fit all tasks. In this work, we introduce a once-for-all (OFA) sequence compression framework for self-supervised speech models that supports a continuous range of compressing rates. The framework is evaluated on various tasks, showing marginal degradation compared to the fixed compressing rate variants with a smooth performance-efficiency trade-off. We further explore adaptive compressing rate learning, demonstrating the ability to select task-specific preferred frame periods without needing a grid search.Comment: Submitted to ICASSP 202

Effect of pre-diabetes on future risk of stroke: meta-analysis

Objectives To assess the association between pre-diabetes and risk of stroke, and to evaluate whether this relation varies by diagnostic criteria for pre-diabetes

Generation of a Homozygous Knock-in Human Embryonic Stem Cell Line Expressing Meos4b-tagged Ctr1

Copper transporter 1 (CTR1) is the major membrane protein responsible for cellular copper (Cu) uptake and mediates cellular copper homeostasis. To elucidate CTR1\u27s behavior using imaging approaches, we generated a homozygous knock-in human embryonic stem cell (hESC) clone expressing photoconvertible fluorescence protein mEos4b-tagged endogenous CTR1 using CRISPR-Cas9 mediated homologous recombination. The engineered cells express functional CTR1-mEos4b fusion and have normal stem cell morphology. They remain pluripotent and can be differentiated into all three germ layers in vitro. This resource allows the study of CTR1 at an endogenous level in different cellular contexts using microscopy

Lung Epithelial TRPA1 Transduces the Extracellular ROS into Transcriptional Regulation of Lung Inflammation Induced by Cigarette Smoke: The Role of Influxed Ca 2+

The mechanism underlying the inflammatory role of TRPA1 in lung epithelial cells (LECs) remains unclear. Here, we show that cigarette smoke extract (CSE) sequentially induced several events in LECs. The Ca2+ influx was prevented by decreasing extracellular reactive oxygen species (ROS) with the scavenger N-acetyl-cysteine, removing extracellular Ca2+ with the chelator EGTA, or treating with the TRPA1 antagonist HC030031. NADPH oxidase activation was abolished by its inhibitor apocynin, EGTA, or HC030031. The increased intracellular ROS was halted by apocynin, N-acetyl-cysteine, or HC030031. The activation of the MAPKs/NF-κB signaling was suppressed by EGTA, N-acetyl-cysteine, or HC030031. IL-8 induction was inhibited by HC030031 or TRPA1 siRNA. Additionally, chronic cigarette smoke (CS) exposure in wild-type mice induced TRPA1 expression in LECs and lung tissues. In CS-exposure trpa1−/− mice, the increased BALF level of ROS was similar to that of CS-exposure wild-type mice; yet lung inflammation was lessened. Thus, in LECs, CSE may initially increase extracellular ROS, which activate TRPA1 leading to an increase in Ca2+ influx. The increased intracellular Ca2+ contributes to activation of NADPH oxidase, resulting in increased intracellular ROS, which activate the MAPKs/NF-κB signaling leading to IL-8 induction. This mechanism may possibly be at work in mice chronically exposed to CS

Low glomerular filtration rate and risk of stroke: meta-analysis

Objective To qualitatively and quantitatively investigate the link between a low estimated glomerular filtration rate (eGFR) at baseline and risk of future stroke

Comparison of outcome of unilateral locking plate and dual plating in the treatment of bicondylar tibial plateau fractures

BACKGROUND: Tibial plateau fracture (TPF) includes different fracture patterns with varied degrees of articular depression and displacement. Many kinds of fixators, including newly designed plate with locking screws, were applied to treat these complicated fractures. We intended to follow up the surgical outcomes of (1) unilateral locking plate, (2) classic dual plates, or (3) hybrid dual plates for TPF. MATERIALS AND METHODS: We retrospectively reviewed 76 patients with TPF, Schatzker types V and VI, who we operated from June 2006 to May 2009 in our institute. Excluding patients who expired due to other medical conditions and without complete follow-up, 45 patients were sorted out in this series. The scheme of surgical intervention was designed by visiting staff, and 15 patients, as group I, were treated with unilateral locking plate. The other 19 patients, as group II, were treated with classic dual plates. The residual 11 patients, as group III, were treated with hybrid dual plates (one lateral approach locking compression plate (LCP) + medial anti-gliding plate). All patients were under periodic F/U at about 6 weeks interval for at least 18 months postoperatively. RESULTS: In group I, 13 cases achieved solid bony union without obvious traumatic OA change, limitation of ROM, or malalignment. In groups II and III, 15 and 10 patients reached the same goal, respectively. By analysis of the recorded parameters with statistical software (SPSS 12.0), there were five parameters with significant difference, including Schatzker classification, operation time, staged treatment or not, hospitalization period, and hardware impingement. CONCLUSIONS: There was no significant statistical difference of union rate between these three groups in our series. Based on our clinical follow-up, several key points were emphasized: (1) Soft tissue problems should be kept in mind, and usage of locking plate can reduce the discomfort of hardware impingement effectively. (2) The single lateral approach technique for TPF with locking plate results in less operation time and shorter hospitalization period. (3) If the medial buttress cannot be established by reduction of the lateral fracture, then open reduction of the medial side is necessary and buttresses the medial fragment by dual plates

Paeonol Attenuates Cigarette Smoke-Induced Lung Inflammation by Inhibiting ROS-Sensitive Inflammatory Signaling

Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have previously reported that cigarette smoke (CS) activates reactive oxygen species- (ROS-) sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling leading to induction of lung inflammation. Paeonol, the main phenolic compound present in the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory properties. However, whether paeonol has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we showed that chronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration, increased lung vascular permeability, elevated lung levels of chemokines, cytokines, and 4-hydroxynonenal (an oxidative stress biomarker), and induced lung inflammation; all of these CS-induced events were suppressed by chronic treatment with paeonol. Using human bronchial epithelial cells (HBECs), we demonstrated that cigarette smoke extract (CSE) sequentially increased extracellular and intracellular levels of ROS, activated the MAPKs/NF-κB signaling, and induced interleukin-8 (IL-8); all these CSE-induced events were inhibited by paeonol pretreatment. Our findings suggest a novel role for paeonol in alleviating the oxidative stress and lung inflammation induced by chronic CS exposure in vivo and in suppressing CSE-induced IL-8 in vitro via its antioxidant function and an inhibition of the MAPKs/NF-κB signaling

Long-term follow-up of neurocognitive function in patients with citrin deficiency and cholestasis

Background Citrin deficiency is a rare metabolic disorder prevalent in East and Southeast Asia that affects liver or neurological function throughout various life stages. While early diagnosis and dietary management can improve prognosis for infant onset disease, data on long-term neurocognitive outcomes is scarce. Purpose This study aimed to clarify whether transient metabolic disturbances during early childhood have a lasting effect on the neurocognitive function of individuals with citrin deficiency. Methods Thirty patients diagnosed with citrin deficiency prior to 1 year of age underwent neuropsychological assessments including attention deficit/hyperactivity disorders (ADHD) and intelligence quotient (IQ). We compared the peak laboratory values during infancy between children who were versus were not later diagnosed with ADHD. Results Neurocognitive assessments of 30 individuals with citrin deficiency aged 3–25 years revealed that full-scale IQ scores were normally distributed. Of this cohort, 47% (14 of 30) were diagnosed with ADHD: 6, 6, and 2 with the combined, inattentive, and hyperactive-impulsive types, respectively. This prevalence was higher than that in the general population (1.7%–16%). Moreover, a one-unit increase in ammonia levels before 1 year of age was associated with a 1.023-fold increase in the likelihood of future hyperactivity-impulsivity symptoms (P=0.038; 95%confidence interval, 1.001–1.046). Despite these findings, this long-term follow-up of individuals with citrin deficiency indicated that it had minimal impact on neurocognitive function, allowing for a generally normal life. Conclusion Patients with a history of cholestasis caused by citrin deficiency during infancy have a greater incidence of ADHD than the general population, suggesting that metabolic disturbances during early childhood in individuals with citrin deficiency may have a long-term negative impact on their neurocognitive function

Discovery and Extensive Follow-up of SN 2024ggi, a Nearby Type IIP Supernova in NGC 3621

We present the discovery and early observations of the nearby Type II supernova (SN) 2024ggi in NGC 3621 at 6.64 ± 0.3 Mpc. The SN was caught 5.8−2.9+1.9 hr after its explosion by the ATLAS survey. Early-phase, high-cadence, and multiband photometric follow-up was performed by the Kilonova Finder (Kinder) project, collecting over 1000 photometric data points within 1 week. The combined o- and r-band light curves show a rapid rise of 3.3 mag in 13.7 hr, much faster than SN 2023ixf (another nearby and well-observed SN II). Between 13.8 and 18.8 hr after explosion, SN 2024ggi became bluer, with u − g color dropping from 0.53 to 0.15 mag. The rapid blueward evolution indicates a wind shock breakout (SBO) scenario. No hour-long brightening expected for the SBO from a bare stellar surface was detected during our observations. The classification spectrum, taken 17 hr after the SN explosion, shows flash features of high-ionization species such as Balmer lines, He i, C iii, and N iii. Detailed light-curve modeling provides critical insights into the circumstellar material (CSM). Our favored model has an explosion energy of 2 × 1051 erg, a mass-loss rate of 10−3 M⊙ yr−1 (with an assumed 10 km s−1 wind), and a confined CSM radius of 6 × 1014 cm. The corresponding CSM mass is 0.4 M⊙. Comparisons with SN 2023ixf highlight that SN 2024ggi has a less dense confined CSM, resulting in a faster rise and fainter UV flux. Citizen astronomer collaboration and extensive data are essential for SBO searches and detailed SN characterizations