FragGrow: A Web Server for Structure-Based Drug Design by Fragment Growing within Constraints.

Fragment growing is an important ligand design strategy in drug discovery. In this study, we present FragGrow, a web server that facilitates structure-based drug design by fragment growing. FragGrow offers two working modes: one for growing molecules through the direct replacement of hydrogen atoms or substructures and the other for growing via virtual synthesis. FragGrow works by searching for suitable fragments that meet a set of constraints from an indexed 3D fragment database and using them to create new compounds in 3D space. The users can set a range of constraints when searching for their desired fragment, including the fragment's ability to interact with specific protein sites; its size, topology, and physicochemical properties; and the presence of particular heteroatoms and functional groups within the fragment. We hope that FragGrow will serve as a useful tool for medicinal chemists in ligand design. The FragGrow server is freely available to researchers and can be accessed at https://fraggrow.xundrug.cn.

Analyzing the process of achieving common wealth for different groups in China based on the opportunity advantage perspective of income distribution.

Realizing the common wealth of all people is the essential requirement of socialism with Chinese characteristics. Measuring the process of realizing common wealth and the differences between groups is one of the important issues that need to be addressed urgently. In order to reasonably measure the process of realizing common wealth in China, on the premise of horizontal comparability and vertical consistency, the principles of comparability and consistency are introduced, and a comparative method of opportunity advantage based on income distribution is proposed from the perspective of opportunity equity. Using the 2012-2020 CFPS data to measure and test the opportunity advantages and their differences across regions and groups in China. The study found, firstly, that the opportunity advantage persists but tends to diminish across groups, with the more educated group having a more pronounced opportunity advantage, but that this advantage is diminishing over time. Secondly, the doctoral degree group has a greater probability of earning higher incomes, followed by the master's and bachelor's degree groups, but this opportunity advantage, i.e., the probability of earning higher incomes, is diminishing, i.e., the education dividend is diminishing. Third, the difference in opportunity advantage between urban and rural areas still exists, as evidenced by the greater probability of higher incomes in towns than in rural areas, but this advantage has narrowed further over time, with a clear process of urban-rural integration. Fourthly, in terms of gender, men have a certain opportunity advantage over women, but this difference is not significant. Fifthly, in the context of education levels, gender and urban/rural subgroups, under the framework proposed in this paper, China has achieved some success in the process of realizing the common wealth, and is showing a steady upward trend.

MOCNN: A Multiscale Deep Convolutional Neural Network for ERP-Based Brain-Computer Interfaces.

Event-related potentials (ERPs) reflect neurophysiological changes of the brain in response to external events and their associated underlying complex spatiotemporal feature information is governed by ongoing oscillatory activity within the brain. Deep learning methods have been increasingly adopted for ERP-based brain-computer interfaces (BCIs) due to their excellent feature representation abilities, which allow for deep analysis of oscillatory activity within the brain. Features with higher spatiotemporal frequencies usually represent detailed and localized information, while features with lower spatiotemporal frequencies usually represent global structures. Mining EEG features from multiple spatiotemporal frequencies is conducive to obtaining more discriminative information. A multiscale feature fusion octave convolution neural network (MOCNN) is proposed in this article. MOCNN divides the ERP signals into high-, medium-and low-frequency components corresponding to different resolutions and processes them in different branches. By adding mid-and low-frequency components, the feature information used by MOCNN can be enriched, and the required amount of calculations can be reduced. After successive feature mapping using temporal and spatial convolutions, MOCNN realizes interactive learning among different components through the exchange of feature information among branches. Classification is accomplished by feeding the fused deep spatiotemporal features from various components into a fully connected layer. The results, obtained on two public datasets and a self-collected ERP dataset, show that MOCNN can achieve state-of-the-art ERP classification performance. In this study, the generalized concept of octave convolution is introduced into the field of ERP-BCI research, which allows effective spatiotemporal features to be extracted from multiscale networks through branch width optimization and information interaction at various scales.

Effect of transcutaneous electrical nerve stimulation (TENS) on the electromyographic activity of human masticatory muscles in young people with normal occlusion.

STATEMENT OF PROBLEM: Transcutaneous electrical nerve stimulation (TENS) has been used in several clinical areas. However, the effect of TENS on the masticatory muscles of young individuals with normal occlusion remains unclear. PURPOSE: The purpose of the study was to assess the effect of TENS on the surface electromyographic (sEMG) activity of masticatory muscles in a young population with normal occlusion. MATERIAL AND METHODS: Twenty residents (5 men and 15 women, mean 24.27 ±2.59 years) of Dalian Stomatological Hospital were enrolled as the study participants. A trained operator collected the required information from the participants. The experiment was divided into 3 stages: pre-TENS acquisition, TENS application, and post-TENS acquisition. The pre-TENS stage was performed using surface electromyography (sEMG) (Myotronics Inc) to acquire the potential values of masticatory muscles in the following 3 states 5 times each: resting, intercuspal occlusion (ICO), and maximum voluntary clench (clenching). The potential values of the anterior of temporalis (TA), the masseter (MM), the sternocleidomastoid (SCM), and the anterior digastric (DA) muscles were collected in the resting state, and TA and MM were collected in the ICO and clenching states. During the TENS application phase, a TENS Unit device (J5 Myomonitor) (J5) was used on each participant for 45 minutes. The post-TENS acquisition phase involved the same procedure as the pre-TENS phase. The experimental data were recorded, and the normality of each group was analyzed using the Shapiro-Wilk test in a statistical software program (IBM SPSS Statistics, v26.0). The paired-sample t test was used to compare the differences in the mean values of sEMG and the asymmetry index (As); the independent-sample t test was used to compare the activity index (Ac) and torque index (To) (α=.05). RESULTS: Significant differences were observed in the mean potential values of TA, MM, LSCM, and RDA before and after TENS in the resting state and RTA, LMM, and RMM before and after TENS in the clenching state (P<.05). Moreover, although AsDA values showed a significant difference (P=.027) before and after TENS in the resting state, the differences in As values for the other muscles in the resting state were statistically similar. Furthermore, in each state, the mean values of Ac and To after TENS showed no significant differences before and after TENS (P>.05). CONCLUSIONS: The resting EMG values of the TA and MM differed significantly before and after TENS. After TENS, the resting EMG activity decreased, whereas the functional EMG activity tended to increase.

Dietary Oat ß-Glucan Alleviates High-Fat Induced Insulin Resistance through Regulating Circadian Clock and Gut Microbiome.

SCOPE: High-fat diet induced circadian rhythm disorders (CRD) are associated with metabolic diseases. As the main functional bioactive component in oat, ß-glucan (GLU) can improve metabolic disorders, however its regulatory effect on CRD remains unclear. In this research, the effects of GLU on high-fat diet induced insulin resistance and its mechanisms are investigated, especially focusing on circadian rhythm-related process. METHODS AND RESULTS: Male C57BL/6 mice are fed a low fat diet, a high-fat diet (HFD), and HFD supplemented 3% GLU for 13 weeks. The results show that GLU treatment alleviates HFD-induced insulin resistance and intestinal barrier dysfunction in obese mice. The rhythmic expressions of circadian clock genes (Bmal1, Clock, and Cry1) in the colon impaired by HFD diet are also restored by GLU. Further analysis shows that GLU treatment restores the oscillatory nature of gut microbiome, which can enhance glucagon-like peptide (GLP-1) secretion via short-chain fatty acids (SCFAs) mediated activation of G protein-coupled receptors (GPCRs). Meanwhile, GLU consumption significantly relieves colonic inflammation and insulin resistance through modulating HDAC3/NF-κB signaling pathway. CONCLUSION: GLU can ameliorate insulin resistance due to its regulation of colonic circadian clock and gut microbiome.

Comprehensive review on lipid metabolism and RNA methylation: Biological mechanisms, perspectives and challenges.

Adipose tissue plays a crucial role in maintaining energy balance, regulating hormones, and promoting metabolic health. To address disorders related to obesity and develop effective therapies, it is essential to have a deep understanding of adipose tissue biology. In recent years, RNA methylation has emerged as a significant epigenetic modification involved in various cellular functions and metabolic pathways. Particularly in the realm of adipogenesis and lipid metabolism, extensive research is ongoing to uncover the mechanisms and functional importance of RNA methylation. Increasing evidence suggests that RNA methylation plays a regulatory role in adipocyte development, metabolism, and lipid utilization across different organs. This comprehensive review aims to provide an overview of common RNA methylation modifications, their occurrences, and regulatory mechanisms, focusing specifically on their intricate connections to fat metabolism. Additionally, we discuss the research methodologies used in studying RNA methylation and highlight relevant databases that can aid researchers in this rapidly advancing field.

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

BACKGROUND AND PURPOSE: Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS: INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS: Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION: Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study.

Objective: The association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. Methods: People who had participated in health check-ups in 2006-2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). Results: During 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01-1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01-1.13). Besides, the HR was 1.10 (95 % CI=1.06-1.15), 1.13 (95 % CI=1.08-1.18), and 1.22 (95 % CI=1.16-1.30) (P for trend <0.001) in (10-20], (20-30], and (30-40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. Conclusion: People with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Acceptability and experience of a smartphone symptom monitoring app for people with psychosis in China (YouXin): a qualitative study.

BACKGROUND: Access to high-quality mental healthcare remains challenging for people with psychosis globally, including China. Smartphone-based symptom monitoring has the potential to support scalable mental healthcare. However, no such tool, until now, has been developed and evaluated for people with psychosis in China. This study investigated the acceptability and the experience of using a symptom self-monitoring smartphone app (YouXin) specifically developed for people with psychosis in China. METHODS: Semi-structured interviews were conducted with 10 participants with psychosis to explore the acceptability of YouXin. Participants were recruited from the non-randomised feasibility study that tested the validity, feasibility, acceptability and safety of the YouXin app. Data analysis was guided by the theoretical framework of acceptability. RESULTS: Most participants felt the app was acceptable and easy to use, and no unbearable burdens or opportunity costs were reported. Participants found completing the self-monitoring app rewarding and experienced a sense of achievement. Privacy and data security were not major concerns for participants, largely due to trust in their treating hospital around data protection. Participants found the app easy to use and attributed this to the training provided at the beginning of the study. A few participants said they had built some form of relationship with the app and would miss the app when the study finished. CONCLUSIONS: The YouXin app is acceptable for symptom self-monitoring in people with experience of psychosis in China. Participants gained greater insights about their symptoms by using the YouXin app. As we only collected retrospective acceptability in this study, future studies are warranted to assess hypothetical acceptability before the commencement of study to provide a more comprehensive understanding of implementation.

Does voice endorsement by supervisors enhance or constrain voicer's personal initiative? Countervailing effects via feeling pride and feeling envied.

While the previous research has examined antecedents of supervisors' voice endorsement, it has generally overlooked its effects on voicers' affective and behavioral reactions, probably because of the underlying assumption that supervisors' voice endorsement is inherently beneficial and likely to encourage more proactive behaviors in the future. In this research, we offer a theoretical model of the double-edged effects of supervisors' voice endorsement on voicers' subsequent personal initiative. Drawing on cognitive appraisal theory and related research, we proposed that supervisors' voice endorsement prompts two different cognitive appraisal processes in voicers that evoke two distinct emotional experiences-feeling pride and feeling envied-with countervailing effects on voicers' subsequent personal initiative. Specifically, voice endorsement results in voicers not only feeling pride, which enhances their subsequent personal initiative, but also in their feeling envied, which reduces their later personal initiative. Moreover, we extend the cognitive appraisal theory of emotion from a social constructionist approach by incorporating coworker support-an important relational context-as a contingent factor shaping the effects of voice endorsement on feeling pride and feeling envied and on voicers' subsequent personal initiative. The results from two field studies-a weekly experience sampling study with 574 observations from 119 employees and an event-based daily experience sampling study with 787 observations from 180 employees-largely support our theoretical model. This research suggests the importance of considering the perspectives of all the stakeholders in the proactivity triad (i.e., the focal employee, the supervisor, and coworkers) in order to sustain employee proactivity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cation doping and oxygen vacancies in the orthorhombic FeNbO4 material for solid oxide fuel cell applications: A density functional theory study.

The orthorhombic phase of FeNbO4, a promising anode material for solid oxide fuel cells (SOFCs), exhibits good catalytic activity toward hydrogen oxidation. However, the low electronic conductivity of the material specifically in the pure structure without defects or dopants limits its practical applications as an SOFC anode. In this study, we have employed density functional theory (DFT + U) calculations to explore the bulk and electronic properties of two types of doped structures, Fe0.9375A0.0625NbO4 and FeNb0.9375B0.0625O4 (A, B = Ti, V, Cr, Mn, Co, Ni) and the oxygen-deficient structures Fe0.9375A0.0625NbO3.9375 and FeNb0.9375B0.0625O3.9375, where the dopant is positioned in the first nearest neighbor site to the oxygen vacancy. Our DFT simulations have revealed that doping in the Fe sites is energetically favorable compared to doping in the Nb site, resulting in significant volume expansion. The doping process generally requires less energy when the O-vacancy is surrounded by one Fe and two Nb ions. The simulated projected density of states of the oxygen-deficient structures indicates that doping in the Fe site, particularly with Ti and V, considerably narrows the bandgap to ∼0.5 eV, whereas doping with Co at the Nb sites generates acceptor levels close to 0 eV. Both doping schemes, therefore, enhance electron conduction during SOFC operation.

A Time-Local Weighted Transformation Recognition Framework for Steady State Visual Evoked Potentials Based Brain-Computer Interfaces.

Canonical correlation analysis (CCA), Multivariate synchronization index (MSI), and their extended methods have been widely used for target recognition in Brain-computer interfaces (BCIs) based on Steady State Visual Evoked Potentials (SSVEP), and covariance calculation is an important process for these algorithms. Some studies have proved that embedding time-local information into the covariance can optimize the recognition effect of the above algorithms. However, the optimization effect can only be observed from the recognition results and the improvement principle of time-local information cannot be explained. Therefore, we propose a time-local weighted transformation (TT) recognition framework that directly embeds the time-local information into the electroencephalography signal through weighted transformation. The influence mechanism of time-local information on the SSVEP signal can then be observed in the frequency domain. Low-frequency noise is suppressed on the premise of sacrificing part of the SSVEP fundamental frequency energy, the harmonic energy of SSVEP is enhanced at the cost of introducing a small amount of high-frequency noise. The experimental results show that the TT recognition framework can significantly improve the recognition ability of the algorithms and the separability of extracted features. Its enhancement effect is significantly better than the traditional time-local covariance extraction method, which has enormous application potential.

Cation-Loaded Porous Mg2+-Zeolite Layer Direct Dendrite-Free Deposition toward Long-Life Lithium Metal Anodes.

Lithium metal, with ultrahigh theoretical specific capacity, is considered as an ideal anode material for the lithium-ion batteries. However, its practical application is severely plagued by the uncontrolled formation of dendritic Li. Here, a cation-loaded porous Mg2+-Zeolite layer is proposed to enable the dendrite-free deposition on the surface of Li metal anode. The skeleton channels of zeolite provide the low coordinated Li+-solvation groups, leading to the faster desolvation process at the interface. Meanwhile, anions-involved solvation sheath induces a stable, inorganic-rich SEI, contributing to the uniform Li+ flux through the interface. Furthermore, the co-deposition of sustained release Mg2+ realizes a new faster migration pathway, which proactively facilitates the uniform diffusion of Li on the lithium substrate. The synergistic modulation of these kinetic processes facilitates the homogeneous Li plating/stripping behavior. Based on this synergistic mechanism, the high-efficiency deposition with cyclic longevity exceeding 2100 h is observed in the symmetric Li/Li cell with Mg2+-Zeolite modified anode at 1 mA cm-2. The pouch cell matched with LiFePO4 cathode fulfills a capacity retention of 88.4% after 100 cycles at a severe current density of 1 C charge/discharge. This synergistic protective mechanism can give new guidance for realizing the safe and high-performance Li metal batteries.

The role of mitochondrial dynamics and mitophagy in skeletal muscle atrophy: from molecular mechanisms to therapeutic insights.

Skeletal muscle is the largest metabolic organ of the human body. Maintaining the best quality control and functional integrity of mitochondria is essential for the health of skeletal muscle. However, mitochondrial dysfunction characterized by mitochondrial dynamic imbalance and mitophagy disruption can lead to varying degrees of muscle atrophy, but the underlying mechanism of action is still unclear. Although mitochondrial dynamics and mitophagy are two different mitochondrial quality control mechanisms, a large amount of evidence has indicated that they are interrelated and mutually regulated. The former maintains the balance of the mitochondrial network, eliminates damaged or aged mitochondria, and enables cells to survive normally. The latter degrades damaged or aged mitochondria through the lysosomal pathway, ensuring cellular functional health and metabolic homeostasis. Skeletal muscle atrophy is considered an urgent global health issue. Understanding and gaining knowledge about muscle atrophy caused by mitochondrial dysfunction, particularly focusing on mitochondrial dynamics and mitochondrial autophagy, can greatly contribute to the prevention and treatment of muscle atrophy. In this review, we critically summarize the recent research progress on mitochondrial dynamics and mitophagy in skeletal muscle atrophy, and expound on the intrinsic molecular mechanism of skeletal muscle atrophy caused by mitochondrial dynamics and mitophagy. Importantly, we emphasize the potential of targeting mitochondrial dynamics and mitophagy as therapeutic strategies for the prevention and treatment of muscle atrophy, including pharmacological treatment and exercise therapy, and summarize effective methods for the treatment of skeletal muscle atrophy.

Effectiveness of a standardized quality control management procedure for COVID-19 RT-PCR testing: a large-scale diagnostic accuracy study in China.

BACKGROUND: The study aimed to construct a standardized quality control management procedure (QCMP) and access its accuracy in the quality control of COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: Considering the initial RT-PCR results without applying QCMP as the gold standard, a large-scale diagnostic accuracy study including 4,385,925 participants at three COVID-19 RT-PCR testing sites in China, Foshan (as a pilot test), Guangzhou and Shenyang (as validation sites), was conducted from May 21, 2021, to December 15, 2022. RESULTS: In the pilot test, the RT-PCR with QCMP had a high accuracy of 99.18% with 100% specificity, 100% positive predictive value (PPV), and 99.17% negative predictive value (NPV). The rate of retesting was reduced from 1.98% to 1.16%. Its accuracy was then consistently validated in Guangzhou and Shenyang. CONCLUSIONS: The RT-PCR with QCMP showed excellent accuracy in identifying true negative COVID-19 and relieved the labor and time spent on retesting.

Injectable hydrogel harnessing foreskin mesenchymal stem cell-derived extracellular vesicles for treatment of chronic diabetic skin wounds.

Chronic skin wounds are a serious complication of diabetes with a high incidence rate, which can lead to disability or even death. Previous studies have shown that mesenchymal stem cells derived extracellular vesicles (EVs) have beneficial effects on wound healing. However, the human foreskin mesenchymal stem cell (FSMSCs)-derived extracellular vesicle (FM-EV) has not yet been isolated and characterized. Furthermore, the limited supply and short lifespan of EVs also hinder their practical use. In this study, we developed an injectable dual-physical cross-linking hydrogel (PSiW) with self-healing, adhesive, and antibacterial properties, using polyvinylpyrrolidone and silicotungstic acid to load FM-EV. The EVs were evenly distributed in the hydrogel and continuously released. In vivo and vitro tests demonstrated that the synergistic effect of EVs and hydrogel could significantly promote the repair of diabetic wounds by regulating macrophage polarization, promoting angiogenesis, and improving the microenvironment. Overall, the obtained EVs-loaded hydrogels developed in this work exhibited promising applicability for the repair of chronic skin wounds in diabetes patients.

Strongly-Confined CsPbBr3 Perovskite Quantum Dots with Ultralow Trap Density and Narrow Size Distribution for Efficient Pure-Blue Light-Emitting Diodes.

The development of pure-blue perovskite light-emitting diodes (PeLEDs) faces challenges of spectral stability and low external quantum efficiency (EQE) due to phase separation in mixed halide compositions. Perovskite quantum dots (QDs) with strong confinement effects are promising alternatives to achieve high-quality pure-blue PeLEDs, yet their performance is often hindered by the poor size distribution and high trap density. A strategy combining thermodynamic control with a polishing-driven ligand exchange process to produce high-quality QDs is developed. The strongly-confined pure-blue (≈470 nm) CsPbBr3 QDs exhibit narrow size distribution (12% dispersion) and are achieved in Br-rich ion environment based on growth thermodynamic control. Subsequent polishing-driven ligand exchange process removes imperfect surface sites and replaces initial long-chain organic ligands with short-chain benzene ligands. The resulting QDs exhibit high photoluminescence quantum yield (PLQY) to near-unity. The resulting PeLEDs exhibit a pure-blue electroluminescence (EL) emission at 472 nm with narrow full-width at half-maximum (FWHM) of 25 nm, achieving a maximum EQE of 10.7% and a bright maximum luminance of 7697 cd m-2. The pure-blue PeLEDs show ultrahigh spectral stability under high voltage, a low roll-off of EQE, and an operational half-lifetime (T50) of 127 min at an initial luminance of 103 cd m-2 under continuous operation.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Pre-morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study.

BACKGROUND AND PURPOSE: Whilst sleep disturbances are associated with stroke, their association with stroke severity is less certain. In the INTERSTROKE study, the association of pre-morbid sleep disturbance with stroke severity and functional outcome following stroke was evaluated. METHODS: INTERSTROKE is an international case-control study of first acute stroke. This analysis included cases who completed a standardized questionnaire concerning nine symptoms of sleep disturbance (sleep onset latency, duration, quality, nocturnal awakening, napping duration, whether a nap was planned, snoring, snorting and breathing cessation) in the month prior to stroke (n = 2361). Two indices were derived representing sleep disturbance (range 0-9) and obstructive sleep apnoea (range 0-3) symptoms. Logistic regression was used to estimate the magnitude of association between symptoms and stroke severity defined by the modified Rankin Score. RESULTS: The mean age of participants was 62.9 years, and 42% were female. On multivariable analysis, there was a graded association between increasing number of sleep disturbance symptoms and initially severe stroke (2-3, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.94; 4-5, OR 1.66, 95% CI 1.23-2.25; >5, OR 2.58, 95% CI 1.83-3.66). Having >5 sleep disturbance symptoms was associated with significantly increased odds of functional deterioration at 1 month (OR 1.54, 95% CI 1.01-2.34). A higher obstructive sleep apnoea score was also associated with significantly increased odds of initially severe stroke (2-3, OR 1.48; 95% CI 1.20-1.83) but not functional deterioration at 1 month (OR 1.19, 95% CI 0.93-1.52). CONCLUSIONS: Sleep disturbance symptoms were common and associated with an increased odds of severe stroke and functional deterioration. Interventions to modify sleep disturbance may help prevent disabling stroke/improve functional outcomes and should be the subject of future research.